Dr.Prashant Jani
  Literature Update

Literature Update - Surgical Pathology

For updates in oncopathology, 

August 2009

American Journal of Clinical Pathology, Vol. 132, No. 2, August 2009
-   Page 211: A double sequential immunostain (CK5/6 and AMACR) for problem prostate biopsies demonstrated a 100% (CK5/6) and 97% (AMACR) specificity for cancer, respectively.
-  Page 221: The importance/role of the autopsy is once again demonstrated in this study showing the varying prevalences/trends of opportunistic invasive fungal infections in AIDS patients. During the period 1984-2002, a decrease in Pneumocystis/cryptococcus and an increase in candida/zygomycosis with aspergillus/histoplasmosis remaining stable.
-   Page 237: The role of circulating (in blood) and disseminated (in bone marrow) tumor cells in breast cancer is slowly gaining a threshold in management/prognosis. This paper reviews the current methodologies for the detection of these cells, including immunomagnetic capture (with epithelial targeted antibodies) and molecular methods (RT-PCR for amplification).
Journal of Clinical Pathology, Vol. 62, No. 8, August 2009
-   Page 673:  Criteria for screening colonic tumors in HNPCC (Lynch syndrome) are well established (see Bethesda guidelines) with no equivalent guidelines for endometrial cancers. This paper reviews criteria (tumor infiltrating lymphocytes, dedifferentiated/undifferentiated carcinoma, lower segment origin and synchronous clear cell carcinoma of the ovary) and proposes a more formal guideline structure to be formulated.
-  Page 699: This author (KC) has long campaigned the shift from ABC immunodetection systems to the polymer dextran system, due to the dangers/pitfalls of endogenous biotin/avidin cross reacting with the former system. The present study underscores this need by demonstrating that biotin-free systems provide a stronger IHC signal for the evaluation of estrogen receptor in breast cancers. So, if you have not yet taken the plunge…
-   Page 760: Phosphaturic mesenchymal tumors typically present with osteomalacia. These rare morphologically heterogeneous lesions are well established in the literature (see AJSP 2004; 28:1). This study presents two cases of PMT without oncogenic osteomalacia.
Human Pathology, Vol. 40, No. 8, August 2009
-   Page 1057: For those of you planning to engage in, or are currently practicing telepathology, these series of papers cover all aspects, including virtual microscopy and whole slide imaging referable to both education and diagnostic services (the latter including frozen sections, both on-site and distant). With most medical schools using digital images for laboratory teaching, a breed of students are being produced who would prefer digital images for diagnostic purposes (similar to radiology). This therefore demands that required standards and quality assurance be implemented.
Histopathology, Vol. 55, No. 2, August 2009
-   Page 145: The IHC and genetic profile of acquired cystic disease associated renal cell carcinomas show a proximal nephron phenotype (CD10+, RCC+, p504+) with CGH/FISH gains on chr 3&4 (and 7/17 similar to papillary carcinoma).
-   page 174: Alas, the sentinel lymph node (SLN) has arrived in GYN tract cancers! This study explores the detection of micrometastases/single tumor cell deposits being typical of LS-associated vulvar squamous cell carcinoma. Regrettably, serial sections and IHC were required to detect positive SLN!

American Journal of Surgical Pathology, Vol. 33, No. 8, August 2009
-   Page 1113: Basaloid carcinomas are well described in the upper aerodigestive tract and salivary glands. This study presents 12 cases in the thymus, exploring the relationship to adenoid cystic carcinoma. Thymic basaloid carcinomas are aggressive with 75% presenting with lymph node involvement and 35-50% with distant metastases. 
-   Page 1125: Prophylactic salpingo-oophorectomy specimens (from BRCA+ patients) may rarely harbor occult primary or secondary (breast) cancers. This study explores a cohort with an in-depth study of mimics of occult cancer (e.g. hyperthecosis, adrenal rests, hilus cell nodules/hyperplasia, etc.). 
-   Page 1137: Salivary gland carcinomas with high grade transformation (previously AKA dedifferentiated carcinoma) have been recognized in adenoid cystic carcinoma, PLGA, mucoepidermoid and, in the present series, acinic cell carcinoma. Nuclear pleomorphism, increased mitoses, solid or glandular and necrosis characterize the high grade transformation.
-   Page 1146: The dermies are now FISHing! A set of four probes targeting 6p25, 6 centromere, 6q23 and 11q13 aberrations provide the highest diagnostic discrimination for melanomas (~87% sensitivity and ~95% specificity) (see Mod Pathol 2008; 22:989).
-   Page 1157: It would appear that ovarian endometrioid carcinoma may have a dualistic pathology: 
     Low grade: β-catenin+, MSI, KRAS mutation
     High grade: p53 overexpression (without any of the above)
-   Page 1173: Sarcomatous transformation in teratomatous germ cell tumors is well recognized. This study examines a cohort of primary testicular tumors (rhabdomyosarcoma commonest, followed by high grade unclassified) and demonstrates that such tumors confined to the testis carry the same mortality as testicular germ cell tumors without sarcomatous components (for comparable stage). However, tumors with metastasis had increased mortality. 
-   Page 1179: A small series of SETTLE (spindled epithelial tumors with thymus-like elements) involving the thyroid (11 cases) is revisited. This study demonstrates the absence of tx;18 helping discriminate from synovial sarcoma – the crucial differential diagnosis.
-   Page 1206: UTROSCT (uterine tumor resembling ovarian sex-cord-like tumor) may occur as a focal component of endometrial stromal tumors (EST type I, t7;14) or as a predominant component (type II). This study demonstrates the absence of t7;14, affirming the latter distinct from type I. Note that the genes involved in type I EST are JAZF1-JJAZF1 and have been demonstrated in about 50% of EST with a variety of morphological features (smooth muscle, myxoid and fibrous differentiation).
-   Page 1220: Intermediate grade II nuclear features (between low grade I and high grade III) carry the molecular profile of the latter (p53+) and not the former (BRAF, KRAS, ERBB2).
-   Page 1225: Clusterin is a follicular dendritic cell glycoprotein involved in lipid recycling and apoptosis, and is positive in the large mononuclear cells of tenosynovial giant cell tumors (TSGCT) (and normal synoviocytes), attesting to synovial differentiation; and is negative in the smaller histiocytoid cells (CD68, CD163 +). 
     Note that these tumors are recognized as a neoplastic process due to consistent chromosomal abnormalities(gains chromosomes 5&7, rearrangement 1p11).
-   Page 1249: Following the introduction of several manifestations of the systemic IgG4-related lymphoplasmacytic sclerosing disease, please welcome the new kid on the block: IgG4-related sclerosing PACYMENINGITIS!
-   Page 1253: Similarly, NUT midline carcinoma, also previously reviewed in these pages (AJSP 2009; 33:484) is now described in the parotid gland. Primarily thymic/upper aerodigestive tract (midline), these undifferentiated basaloid carcinomas with focal squamoid differentiation are aggressive and uniformly fatal (afflicting young adults) and carry t15;19 involving the NUT gene (nuclear protein in testis).
Modern Pathology, Vol. 22, No. 8, August 2009
-   Page 985: The case for routine examination for occult carcinomas (serous and endometrioid) is presented with the SEE-FIM (serial sectioning and entire examination of fimbrial end) sampling method of fallopian tubes. Presently, this is only done in patients with prophylactic salpingo-oophorectomy for hereditary breast cancer (BRCA+).
-   Page 989: The dermies are FISHing again! The same group (see AJSP 2009; 33:1146), using the same system of targeting four genes, is discriminatory in distinguishing benign from malignant melanocytes in melanomas arising from nevi. This becomes critical when microstaging and determining the deeper dermal component.
-   Page 1049: Small intestinal inflammatory fibroid polyps also harbor PDGFRA gain of function mutations in about 55% of cases (majority exon 12) (see previous gastric IFP with similar finding).   Hence the contention is that these should be regarded as PDGFRA-driven benign neoplasms. Note that the majority (95%) express PDGFRA protein. 



July 2009

Human Pathology, Vol. 40, No. 7, July 2009
-   Page 909: A nice review on GvHD (GIT) with an overview of both histopathology and recommendations for reporting.
-   Page 942: An interesting HPV profile of cervical HSILs from Belize City. HPV16 comprised less than 50%, whilst HPV18 was absent! HPV35 and 58 comprised about 20% each and HPV31 about 15%. Important stats for HPV vaccine efficacy in developing countries, given that only HPV16/18 (HR) is covered by the vaccine.
-   Page 957: Another study comparing the value of p16, MIB-1 (Ki-67) and ProExC in cervical SILs. p16 proved to be most sensitive and specific, whilst two concordant results (using all three markers) improved the diagnostic accuracy. Beware of the p16 aberrant patterns with LSIL: about 50% are negative and about 10% are strongly positive. Hence, p16 is not useful to distinguish between low and high SILs.
Journal of Pathology, Vol. 218, No. 3, July 2009
-   Page 301: Micropapillary carcinoma (MPC) of the breast (utilizing a combination of genomic and IHC) is a distinct aggressive subset (ER+) of invasive ductal carcinoma (IDC). Although often demonstrating a mixed phenotype of MPC and IDC, it is more closely related to pure MPC than pure IDC. 
Modern Pathology, Vol. 22, No. 7, July 2009
-   Page 887: Good old morphological clinico-pathological correlation: psammoma bodies in papillary thyroid carcinoma correlate with lymph node metastases and stage (poorer disease-free survival). 
Archives of Pathology & Laboratory Medicine, Vol. 133, No. 7, July 2009
Another useful series of updates on surgical pathology, this time from the University of Chicago. Some highlights include:
-   INI-1 negative in medullary renal tumors (page 1026, renal tumors).
-   A useful review of pathologic evaluation of GYN specimens in selected genetic diseases (page 1041).
-   The chemotherapeutic effects on GBM (page 1062).
-   FNH of the liver renamed as telangiectatic adenoma (page 1078).
-   Pleomorphic LCIS of the breast reviewed (page 1116).
-  A useful paper on practical points for frozen sections in surgical pathology (page 1135), which I personally recommend.
International Journal of Gynecological Pathology, Vol. 28, No. 4, July 2009
-   Page 301: TTF-1 (a useful marker of thyroid and lung adenocarcinomas) is not useful for pulmonary neuroendocrine tumors (since extrapulmonary N/E tumors may also demonstrate immunoreactivity). This study demonstrates TTF-1 immunoreactivity in normal GYN tract tissue. Note that recent publications have demonstrated 15-30% immunoreactivity in GYN adenocarcinomas.
-   Page 308: Intraepithelial serous carcinoma (ISC) of the endometrium may co-exist with tubal intraepithelial carcinoma (TIC) in about 50% of cases. Hence, the SEE-FIM grossing of fallopian tubes is recommended in all patients with ISC. 


-   Page 334: Stromal cellular atypia has been observed in the oral, bladder, cervical, vulva and GIT mucosae. This study illustrates similar atypia in endometrial stroma.
-   Page 356: A unique feature of ovarian fibroma is the heavy deposition of hyaline globules, hence the need to rule out Krukenberg and YST which could pose potential diagnostic pitfalls.
-   Page 389: Glassy cell carcinoma of the cervix is thought to originate from reserve or uncommitted cells and represents a variant of adenosquamous carcinoma. This study proposes a predominant commitment to squamous lineage with 6/9 (66%) being HPV positive (predominant HPV18 and 32).
Journal of Clinical Pathology, Vol. 62, No. 7, July 2009
-   Page 597:  The enigmatic concept of intraductal carcinoma of the prostate (IDCP) (NOT to confuse with HGPIN or invasive ductal/endometrioid carcinoma). This review reaffirms IDCP as a distinct entity and provides precise Gleason reporting grades when identified. IDCP fills and expands ducts (as opposed to HGPIN), basal cells are intact with marked pleomorphism, cribriform/solid I comedonecrosis. The importance of recognizing IDCP in prostatectomy specimens is its association with aggressive cancers. When found in isolation on biopsy then a comment that unsampled aggressive disease may be present is essential to ensure a rebiopsy.
-  Page 617: A 3-D reconstruction of SLN with metastatic breast cancer reveals three patterns of growth: sinusoidal, nodular and diffuse. The significance of these growth patterns awaits evaluation for prognosis/biological significance.
-   Page 629: Recently tissue microassay (TMA) has been questioned with respect to IHC evaluation, given that only a small sample is represented. This study (using MPNST and
     S-100) shows good agreement between TMA and whole sections.
Advances in Anatomic Pathology, Vol. 16, No. 4, July 2009
-   Page 183: A nice review of the radiology, clinical and pathological correlation of non-malignant lesions on core needle biopsy of the breast.
-   Page 196: Many of our clinical oncology colleagues have requested EGFR IHC in colorectal cancers in order to execute EGFR inhibitor treatment, which has been shown to be effective in a subset of colon cancers. However, this therapy has been shown to be ineffective in tumors with mutations of codon 12/13 on exon 2 of the KRAS gene. Hence, the FDA now requires all potential candidates for anti-EGFR therapy to undergo/determine the KRAS mutation status prior to treatment. 
-   Page 236: Remember Castleman’s disease (hyaline-vascular, plasma-cell and multicentric types). This paper reviews the clinical, pathological and pathogenesis of these subtypes. The hyaline vascular (unicentric, follicular dendritic cell abnormality with associated FDC tumors evolving in a subset), plasma cell (IL6 abnormality, POEMS associated), HHV8-associated (microlymphomas, plasmablastic lymphomas) and multicentric (plasma cell, IL6) types are reviewed.
-   Page 247: Goblet cell carcinoid tumors of the appendix are now divided into three subgroups:
     A: Typical GCC
     B: Adenocarcinoma, ex GCC, signet ring type
     C: Adenocarcinoma, ex GCC, poorly differentiated Ca


American Journal of Surgical Pathology, Vol. 33, No. 7, July 2009
-   Page 963: SIRT (selective internal radiation therapy) comprising glass or resin microspheres labelled with Yttrium-90, has been introduced via hepatic vasculature for primary or metastatic hepatic tumors. It has a tissue penetrance of 2.4 mm and is introduced directly into the tumors with the reduced potential for adjacent/surrounding tissue damage. This paper demonstrates the microspheres in gastritis (3) and cholecystitis (as well as hepatic tumors). See Histopathol, V55, N1, July 2009.
-   Page 976: Previously introduced as “ossifying stromal-epithelial tumors” (3) and “desmoplastic-nested spindle cell tumors” (6) of the liver, this present series (9) refers to this “new kid on the block” as calcifying nested stromal-epithelial tumors. Approximately 5-20 cm, the nests/islands of spindled/epithelioid cells are embedded in a cellular desmoplastic stroma with focal psammoma-like calcification. Focal cytokeratin, with a potential for recurrence, places these tumors in the low grade malignant category.
-   Page 1037: The primary site of metastatic micropapillary carcinoma can easily be determined with uroplakin (bladder), TTF-1 (lung), mammoglobin (breast) and WT1 (ovary).
-   Page 1058: Another new member of the IgG4 lymphoplasmacytic sclerosing disease: IgG4 sclerosing mastitis presents with a painless mass and comprises 50-85% IgG-4 plasma cells. As with other organs, outcome is favorable.
-   Page 1085: Epithelioid cell myofibroblastoma adds to the expanding morphological spectrum of this enigmatic breast tumor: cellular, fibrous, lipomatous, infiltrative and myxoid. The epithelioid variant reflects the same IHC immunoprofile: CD34, desmin,
     α-SMA and ER/PR positive, and presents with a variety of patterns: alveolar, single file/cell, solid, fascicular.
American Journal of Clinical Pathology, Vol. 132, No. 1, July 2009
-   Page 86: The role of frozen section is addressed in this study with the importance of recognition of fungal hyphae (acute fungal sinusitis) in necrotic debris, viz mucor/aspergillus.  These sections should also be reviewed for vascular and perineurial invasion.
 - Page 94: A subset of well-defined criteria in high grade dysplasia in Barrett esophagus is predictive of associated carcinoma:
     - cribriform/solid pattern
     - dilated tubules/necrotic debris
     - ulcerated HGD
     - neutrophils in dysplasia
     - invasion into squamous epithelium.
     When one of these criteria is present in the esophageal biopsy, then carcinoma was present in about 40% of the resected specimen. When two (~80%), three (~85%) and four (~90%) criteria were present, the incidence of carcinoma increased exponentially.
June 2009
Human Pathology, Vol. 40, No. 6, June 2009
-   Page 757: The Weiss System is the standard for assessment and categorization of adrenal cortical tumors (after 25 years of the seminal publication). This review revisits the original criteria (1989): high nuclear grade, >5/50 HPF mitoses, atypical mitoses, <25% clear cells, >1/3 diffuse architecture, necrosis and invasion (capsular, venous, sinusoidal), with 3 or more corresponding to malignant behavior. The modified Weiss criteria published in 2002 permitted greater reproducibility: mitoses >5/50 H PF, clear cells <25%, abnormal mitoses, necrosis, capsular invasion. Note that both pediatric tumors (>400g, >10 cm, >15/20 mitoses) and oncocytic tumor (>10 cm, >200g) require a slightly modified approach.
-   Page 807: An in-depth study of 16 cases of primary cutaneous NK/T cell lymphomas: CD3 positive, CD48 negative, CD56 positive, γ/β TCR negative, EBER positive, angiocentric with epidermotropism.
-   Page 904: A comparison of p16 vs ProExC for cervical SILs reveals the following: p16 is more sensitive/specific for HSIL (see Human Pathol 2009 40:942) and ProExC is more sensitive/specific for LSIL (more diffuse/stronger than p16 and MIB-1). However, combined p16/ProExC provides the highest diagnostic value for both HSIL and LSIL.
Journal of Clinical Pathology, Vol. 62, No. 6, June 2009
A triplet of superb review papers addresses drug-induced injury in liver (481), skin (493) and kidney (505) written by specialists experienced in their art. A common thread that evolves from a humble generalist’s purview is that all three organs may mimic ANY pattern of disease following drug-induced injury and that awareness of this possibility should always enter the differential diagnosis when reviewing biopsies from these organs with diseases of unknown etiologies. Further, a single drug may elicit a range of disease/injury patterns with no pattern specific for a particular drug (hence the overlapping histological pattern being a useful clue to potential drug-induced injury).
-   Page 530:  The frequently overlooked/underdiagnosed entity of peritoneal stromal endometriosis  comprising superficial plaques/nodules of endometrioid-type stroma (without glands) is highlighted in this manuscript. Although typically associated with endometriosis (at other concurrent sites), the superficial location in a sub-mesothelial distribution incites these authors to hypothesize a metaplastic origin from mesothelial cells. 
American Journal of Surgical Pathology, Vol. 33, No. 6, June 2009
-   Page 805: A study reaffirming and validating the role of p57 IHC (with molecular genotyping confirmation) for the diagnosis of complete hydatidiform molar (CHM) pregnancy. Remember that p57 is negative in both the stroma and cytotrophoblast of CHM in the majority of cases (androgenetic diploidy). In contrast, p57 is positive in partial HM (diandric triploid), biparental diploid non-molar pregnancy and the rare CHM with trisomy 11 (with retained maternal allele).
-   Page 835: As with mucoepidermoid carcinoma of the salivary glands, this investigation reveals a similar t11;19 in similar tumors of the uterine cervix (with aberration of at least one loci)! Importantly, adenosquamous carcinomas were negative.
-   Page 844: Subdividing clear cell carcinoma of the ovary into cystic and adenofibromatous reveals that the latter presents more often in an advanced stage, less frequently with associated endometriosis and a poorer five year survival.

-   Page 925: The clinical, gross and morphological features of MSI-H colon cancers are well described. This study provides selection criteria for identifying endometrial cancers from MMR IHC to identify patients with the Lynch/HNPCC Syndrome: <50 years, infiltrating lymphocytes (emphasizing intraepithelial lymphocytes), dedifferentiated carcinoma, and synchronous clear cell carcinoma.
-   Page 934: In contrast, all sebaceous neoplasms should be routinely subjected to MMR IHC (regardless of age or clinical features) to identify patients with Muir-Torre Syndrome.
-   Page 945: Some years ago, the cervical lesion of SMILE (stratified mucin-producing intraepithelial lesion: AJSP 2000; 24:1414-1419) was described and thought to arise from reserve cells with both squamous (p63 positive) and glandular (CEA positive) differentiation. This study describes a similar phenomenon in VIN with mucinous differentiation.
Histopathology, Vol. 54, No. 7, June 2009
-   Page 783: Recent advances in refractory celiac disease (RCD) have revealed two cell population types: a polyclonal intraepithelial lymphocytes (IEL) population with a normal immunophenotype and a monoclonal IEL. The latter comprises an aberrant immunophenotype and may represent an early stage lymphoma (EATL). This paper reviews the clinical, IHC and molecular features of RCD. 
-  Page 796: The volume of metastatic melanoma in SLN is a strong predictor of disease recurrence and survival. These authors recommend step sectioning of LN with stereological assessment of the metastatic volume of tumor.
-   Page 814:   Much emphasis is placed (correctly so!) on the diagnosis of dysplasia in Barrett esophagus. What then is the natural history of low grade dysplasia (LGD) in BE? A study of 283 patients reveals that 20% persist, ~18% convert to indefinite status, and about 50% revert to non-dysplastic. Only 2.2% progress to high grade dysplasia/adenocarcinoma and only 1.4% to adenocarcinoma. Overall, LGD has a 3x risk of progression to cancer compared to non-dysplastic epithelia.
-   Page 854: We are all familiar with the “tankards” of blood sinus washings that are filtered and processed for microscopy. The majority of fungal rhinosinusitis (FR) are non-invasive (~60%) with about 55% being allergic FR and approximately 5% a fungal ball. The remaining 35% of invasive FR are distributed equally between chronic invasive granulomatous inflammation and acute fulminant FR. Hence, the exact histopathological categorization of FR is an important component to patient treatment. Note that invasive FR is listed as a so-called “critical value” in surgical pathology, indicating an immediate call to the patient’s physician. 
Modern Pathology, Vol. 22, No. 6, June 2009
-   Page 737: Complying with the theme of drug-induced injury in the GIT (see JCP 2009; 62:481), mycophenolate mofetil (an immunosuppressive agent for bone marrow and solid transplanted patients) shows that a third comprises IBD-like injury and a third GVH-like changes. Almost 3% show ischemic-like and 16% self-limited colitis-like changes.
-   Page 824: GPC3 (glypican 3) is a heparan sulfate proteoglycan that regulates cellular growth and apoptosis in the embryo, but is silenced in adult tissue, and is expressed as an oncofetal protein in HCC, melanoma and YST. This study adds clear cell carcinoma (44%) of the ovary to this list.

American Journal of Clinical Pathology, Vol. 131, No. 6, June 2009
-   Page 768/770:  A clear, concise, convenient summary of the clinical indications for HPV DNA test utilization in the management of SIL of the uterine cervix. An appropriate commentary accompanies the indications, allowing physicians/pathologists and all health care professionals involved in the management of these lesions/pre-neoplastic dysplasias to make the best choice for their patients, emphasizing benefit and minimizing harm: reminding us all of the Hippocratic oath “First do not harm”!
-   Page 788: A review of eosinophilic esophagitis (EE) in adults between 1992-2004 reveals an increasing prevalence with pathologists providing an accurate diagnosis in the face of changing criteria. These authors used >15 E/HPF plus confirmatory clinical evidence to make a diagnosis of EE. Note that eosinophilic GE (EGE) is distinct from EE. Some interesting facets of EE are that the degranulating eosinophilic elicits fibrosis and that eosinophils are recruited by EOTAXIN (a gene that is highly induced in children with EE).
-   Page 802:   Deeper/multiple levels (3-4) of flat epithelial atypia (FEA) on needle core biopsy (NCB) of the breast frequently evolves into atypical ductal hyperplasia (ADH) (at the same site). Another illustration of the “power of deeper sections” in surgical pathology.
Archives of Pathology & Laboratory Medicine, Vol. 133, No. 5, May 2009
-   Page 950: New variants of epithelial-myoepithelial carcinomas of the salivary gland: oncocytic-sebaceous and apocrine variants.
-   Page 973: We have all assumed that most “floaters” on our glass slides in surgical pathology emanated from the water baths. This study surprisingly reveals that by far the majority of contaminants are in the staining baths and that the first set of xylenes and alcohols are most heavily contaminated. 


May 2009
Journal of Pathology, Vol. 218, No. 1, May 2009
-   Page 7: For the traditional autopsy pathologists interested in the micropathogenesis of plaque rupture/thrombus formation in atherogenesis, this review explores the role of angiogenesis and hypoxia (secondary to inflammation creating an increased oxygen demand) followed by microvessel endothelial destruction, intraplaque hemorrhage and ultimate rupture. Hence, clinically both angiogenesis and hypoxia present novel targets for non-invasive imaging of plaques at risk for rupture.
-   Page 48: The last few months has seen the literature present a viral oncogenetic role for the pathogenesis of (most unlikely!) Merkel cell carcinoma. This study explores 10 cases demonstrating the so-called Merkel cell virus in an integrated physical state with no alteration of the adjacent cellular genes and a clonal pattern of the MCV integration pattern, further evidence supporting a causative role for MCV in the tumor process.
Human Pathology, Vol. 40, No. 5, May 2009
-   Page 624: Not entirely new to those of us who have spent hours searching for spirochetes on mucocutaneous lesion of syphilis is this study demonstrating an epitheliotropic (lower epidermis/mucosa) intercellular distribution of Treponema pallidum in secondary syphilis. Primary syphilitic lesions, in contrast, demonstrated a mixed epitheliotropic and vasculotropic (treponemes surrounding vascular wall) distribution. This study also showed that IHC was superior to Warthin-Starry silver for the detection of these spiral organisms.
-   Page 662: An interesting survey revealing that residents found virtual microscopy acceptable as a learning aid but not for diagnostic testing (even though there was no difference in their diagnostic ability with either tool), and preferred glass microscopy for the latter!
 - Page 678: Another study (from Japan) exploring minute pulmonary meningothelial-like nodules attesting to the power of common thought seen not too infrequently in the literature. The previous study was from the USA (see Am J Surg Path, April 2009).
Histopathology, Vol. 54, No. 6, May 2009
-   Page 768: We have all encountered the frustrating call from our surgeons demanding 12-15 lymph nodes (?magical number) dissection from colo-rectal carcinoma specimens. This study throws light on the subject with the following: (a) the “second search” for lymph nodes in mesorectal cancer excision does not influence staging nor management; (b) an average of 5 lymph nodes were found on second search; (c) there were no upgrades in lymph node status with any second search, especially in cases that had negative lymph nodes the first time around; (d) those lymph nodes that were positive were usually found in the first search (naturally, since pathologists practice due diligence to avoid the surgeon’s call!); (e) finally, however, the second search does bring the total number of lymph nodes to the magical figure of 12 (hurrah for all concerned!). These findings were similar for patients with and without preoperative adjuvant chemo-radiation.
-   Page 763: Serous carcinomas of the ovary typically follow a binary pathway based on morphology (low grade vs high grade) and molecular analysis (k-ras/BRAF vs p53 mutations), respectively. This case report documents a case of low grade transforming to high grade serous carcinoma. To date, six cases were previously published in the literature (see Am J Surg Path 2007; 31:1007).

Advances in Anatomic Pathology, Vol. 16, No. 2, May 2009
-   Page 135: If you have missed the recent literature on the viral etiology of Merkel cell carcinoma, this review does an excellent job of bringing us up to date (includes etiology, differential diagnosis and IHC).
-   Page 161: Esophageal biopsies comprise a major part of our daily practice. This timely review explores the pathologists’ perspective regarding criteria (with great photographs) for GERD.
Journal of Clinical Pathology, Vol. 62, No. 5, May 2009
-   Page 385:  This excellent review in the “My Approach” series is also an “Editor’s Choice”. The subject is interstitial lung disease and superbly outlines the authors’ pattern approach to interstitial lung disease. Great photographs too!! This can be downloaded free of charge – so strongly recommended.
International Journal of Gynecological Pathology, Vol. 28, No. 3, May 2009
-   Page 239: This excellent overview provides a wonderful framework for GYN pathologists (and generalists too!) with respect to microsatellite instability (MSI) in endometrial carcinomas (EC). MMR (mismatch gene repair), carcinogenesis, testing and the morphology of MSI endometrial cancers are reviewed. Basically, 20-30% of EC are MSI, being detected by IHC or PCR. It appears to be an early event in both sporadic and HNPCC-associated endometrial carcinomas. The sporadic cases are exclusively type I (endometrioid), whilst 40-50% of the HNPCC patients present with higher grade/ lymphocytes+++ morphology.
-   Page 286: A neat report of two cases of epithelial-myoepithelial carcinoma of Bartholin’s gland – a distinctive neoplasm arising in the vulvovaginal region.
American Journal of Surgical Pathology, Vol. 33, No. 5, May 2009
-   Page 645: A review of liposarcomas (LS) in young patients (82 cases) under 22 years. Myxoid LS appears to be the commonest with two novel subtypes (spindle cell and pleomorphic) described, probably representing low and high grade variants of MLS.
-   Page 659: Urachal carcinomas (24 cases) arise in the dome and form the epicenter in the bladder wall. A wide variety of morphological types of carcinoma arise in this setting (adeno-, enteric type-, LEL-like, urothelial and signet ring).
-   Page 669: The differential diagnosis of chordoid meningioma is reviewed in this well-illustrated/investigated series (chordoma, ES myxoid CS, chordoid glioma of III V, skeletal myxoid CS, low grade chondrosarcoma and enchondroma). A novel finding is that ESMCS are D2-40 positive!
-   Page 775: The PAX gene family encodes a group of transcription factors crucial to organogenesis. PAX-5 is expressed in normal B-cells and a subset of neuroendocrine, urothelial and Merkel cell carcinoma, glioblastomas. This study demonstrates that B-lymphoblastic lymphomas and 67% of alveolar rhabdomyosarcomas (ARMS) may react with PAX-5. The latter is not surprising given that the PAX gene family is involved in ARMS translocation, resulting in possible immuno-crossreactivity. These authors further contend that PAX-5 immunoreactivity may be specific for the (t1;13) and (t2;13).

American Journal of Clinical Pathology, Vol. 131, No. 5, May 2009
-   Page 683: Many of us have saved ribbons between sections of prostate biopsies. This study nicely demonstrates that IHC on these saved interval sections (vs new recut sections) is of greater benefit, due to frequent loss of pertinent foci in recut sections.
-   Page 694: The link between morphological observation and molecular anomalies continues to fascinate. This study demonstrates that lung adenocarcinomas with a micropapillary pattern are more likely to harbor (t=73%) k-ras (33%), EGFR (20%) and BRAF (20%) mutations. Most of these patients were smokers and Caucasian (Western).
Archives of Pathology & Laboratory Medicine, Vol. 133, No. 5, May 2009
This edition carries the Memorial Sloan-Kettering surgical pathology course:
-   Page 683: Problems and controversies in thyroid follicular carcinoma explores the importance of accurate assessment of vascular invasion, the role of proliferative grading (mitoses/necrosis) being of high prognostic value (previously neglected) and the usefulness of molecular data to reassess the follicular variant of PTC.
-   Page 692: Necrotizing sialometaplasia of minor salivary glands may be a manifestation of bulaemia. Morphologically, these enigmatic lesions (not to be confused with invasive squamous cell carcinomas of the palate) comprise pseudoepitheliomatous hyperplasia, squamous metaplasia of ducts/acini with preservation of lobular architecture (which shows lobular infarction and mucin spillage).
-   Page 699: The major diagnostic challenge of undifferentiated malignant neoplasm of sinonasal tract is visited in the context of its differential diagnoses: olfactory neuroblastoma, melanoma, small cell carcinoma, NK/T-cell lymphoma, rhabdomyosarcoma and poorly differentiated carcinoma. Great write-up with excellent photomicrographs.
-   Page 713: Fibroepithelial tumors of breast.
 - Page 722: Mimics of mammary neoplasia.

-           Page 729: Current concepts in cervical pathology.

April 2009


Journal of Clinical Pathology, Vol. 62, No. 4, April 2009

-   Page 289: This paper on stromal tumors in the “My diagnostic approach…” series reiterates the role of alk rearrangements in up to 70% of inflammatory myofibroblastic tumors (vs pseudosarcomatous myofibroblastic proliferations). These authors emphasize the role of FISH to accomplish this distinction… to be a “modern updated pathologist”.

-   Page 380: At long last, some competition in the “Snippets” series, begging the question: Should this be called “Snippets in Surgical Pathology” or “Snippets in Hematopathology”? Perhaps the readership should decide! Anyway, a warm welcome to these contributors.


Human Pathology, Vol. 40, No. 4, April 2009

-   Page 471: Prostate carcinoma with glomeruloid features (dilated glands with intraluminal cribriform structures) are associated with concurrent Gleason grade 4 or higher, justifying that this pattern is best regarded as Gleason grade 4. At the recent USCAP, Dr. Jonathan Epstein proposed that all cribriform patterns be regarded as Gleason grade 4.

-   Page 478: A small series of oncocytic rectal adenocarcinomas recognizing true oncocytes, especially at the infiltrative edge of these cancers (either as single cells or glands). Recognition is important since these tumors have an aggressive outcome (rapid recurrence or shorter interval to distant metastases).

-   Page 538: We have all see intraprostatic adipose tissue in occasional radical prostatectomy, but what exactly is the incidence of this phenomenon? This study demonstrates a 4% incidence (out of a series of 427 cases) and defines the observation as the presence of adipocytes intermingled with peripheral glands and internal to the most peripheral glands. (Note that skeletal muscle may also be present within prostate tissue). The importance of these observations is to caution pathologists not to diagnose extra-prostatic extension (especially on core biopsy) when tumor is observed amidst fat cells.


American Journal of Surgical Pathology, Vol. 33, No. 4, April 2009

-   Page 487: Previously known as pulmonary chemodectoma (due to its predominantly perivenular location), these curious interstitial cellular proliferations are now known as pulmonary meningothelial-like nodules. They are negative with neuroendocrine markers, but positive with EMA, PR and CD56. They are not that uncommon, being observed in about 48% of lobectomies with a mean age of 62 years (but not in the pediatric age group). Further, they are randomly distributed in the interstitium (without a definite predilection for blood vessel distribution).

-   Page 496: Microglandular adenosis (MGA) of the breast is characterized by single layered round glands that infiltrate collagen and fat. They are recognized by their distinctive intra-luminal eosinophilic secretion with a prominent basement membrane. They also have a distinctive IHC profile (EMA/S-100+). Atypical MGA is characterized by cell expansion, prominent nucleoli and vesicular nuclei. CIS (DCIS) retains the alveolar pattern of adenosis/solid nests, whilst the invasive carcinoma (arising from MGA) demonstrates a coalescent growth pattern with expanding alveolar CIS elements. Molecular analysis supports the progression of MGA → atypical → CIS → IDC.

-   Page 505: A small series of CD3+ DLBCL warns us against the pitfall.

-   Page 513: HPV typing (either by PCR or ISH) is a useful tool to discriminate between primary and metastatic SCC to the lung (the latter primarily from the cervix or oropharynx).


-   Page 526: We have all seen (or read about) the occasional rare primary retroperitoneal mucinous tumors. This series reiterates its exclusivity in women and the similarity in classification (benign, BL, malignant) to ovarian tumors. Note that in this context both borderline and malignant mucinous tumors are more common (hence, extensive sampling is mandatory – at least 2 blocks/cm of tumor!).

-   Page 534: Matrix-producing breast carcinomas are regarded as an aggressive subtype of metaplastic carcinoma, with an abrupt transition to osteoid or cartilaginous matrix (without spindle cells). Note that the term metaplastic carcinoma (in the breast) encompasses a morphologically heterogeneous group of tumors viz sarcomatoid or spindle cell carcinoma, squamous cell carcinoma, adenosquamous carcinoma, carcinosarcoma, metaplastic carcinoma with osteoclastic giant cells, and the innocuous-looking low grade fibromatosis-like carcinoma (the only type with a relatively good prognosis).

-   Page 542: It is now well established that the loss of INI-1 immunoexpression is characteristic of both conventional and proximal epithelioid sarcoma (in >90%). This study also warns that 50% epithelioid MPNST and occasional myoepithelial carcinomas (of soft tissue) may also demonstrate this profile.

-   Page 583:  Originally (in 1996) described as Gleason 3+3, foamy gland prostate carcinoma may also demonstrate a higher grade (7 or greater) with cribriform or fused glands, cords and sheets. Prominent nucleoli and mitotic figures may also be observed.


Archives of Pathology & Laboratory Medicine, Vol. 133, No. 4, April 2009

-   Page 512: The “Futurescope of Pathology 2008” proceedings held in Chicago are presented in this issue. Dealing with a wide range of futuristic innovations in pathology, some of the presentations certainly are interesting to read and contemplate upon.

-   Page 648: A nice “resident review” of perivascular epithelioid tumors (PEComas).


Modern Pathology, Vol. 22, No. 4, April 2009

-   Page 489: This review deals with novel endoscopic therapeutic modalities of mucosal resection and photodynamic treatment of superficial neoplasms of the esophagus.

-  Page 516: Even Merkel cell carcinomas harbor a virus (polyomavirus). This study demonstrates a 76% incidence by PCR in paraffin tissue. Would be interesting to determine the status of other neuroendocrine tumors/carcinomas.


American Journal of Clinical Pathology, Vol. 131, No. 4, April 2009

-   Page 468: Following the institution of the LEAN process in their laboratory, Henry Ford Pathology now presents their improvement/reduction in slide misidentification (by 62%) with the use of bar-coded labels. The throughput at the histology microtomy station improved by 125%.

-   Page 461/463: Two editorials for mandatory reading: Quality in Pathology and Disclosing Harmful Errors to Patients.


Histopathology, 2009

Two reviews on line as pre-publication reviews are “Squamous intraepithelial lesions of the larynx” (dealing with the controversial diagnosis/classification issues as well as the etiology and carcinogenesis of laryngeal cancer) and an update/review of “Recent developments/entities in pediatric renal tumors” (the latter including the role of molecular investigation as an adjunct to morphological diagnosis on needle core biopsy.


Journal of Pathology, Vol. 217, No. 5, April 2009

-   Page 716: A single case of hemosiderotic fibrolipomatous tumor demonstrating the t(1:10) that has been found in myxoinflammatory fibroblastic sarcoma.

March 2009

 Journal of Clinical Pathology, Vol. 62, No. 3, March 2009

-   Page 201: An often difficult diagnosis that we should only resort to in colectomy specimens (NOT biopsies) is that of “indeterminate colitis”. This paper reviews the current controversies related to this diagnosis with the role of the pathologist outlined. This review also provides an algorithm for the diagnosis of colitis with a focus on indeterminate colitis.

 - Page 226/219: For the rare (dare we say dying) breed of cardiac pathologists (traditionally autopsy pathologists), a treatise on dilated cardiomyopathy (an often abused diagnosis in our experience) and hypertrophic cardiomyopathy (HCM). Both papers review the current diagnostic criteria and management principles. 

-   Page 236: An excellent review of myofibroblasts and its tumors.


American Journal of Clinical Pathology, Vol. 131, No. 1, January 2009

-   Page 7: The volume of prostate cancer on core needle biopsy (CNB) or TURP is of clinical significance since it predicts response to surgery and radiation treatment (based on devised nomograms that clinicians use to predict/determine management criteria in individual patients). Hence, the numbers of positive cores/total cores is critical to our reports. Also critical is the volume (either the percentage of cancer in each core AND/OR linear (in mm) measurement of the cancer per positive core) must be included in the report. This useful editorial also concludes that tumor volume in radical prostatectomy has NOT been established as being clinically helpful and is not embedded in the nomograms. 

-   Page 112: ADH on >2 foci on CNB of breast is a strong predictor of DCIS. Micropapillary ADH also has similar predictive value. ADH <3 foci, especially with associated microcalcification and completely removed by CNB, carries a much lower risk of DCIS on excision and may perhaps not require surgery.


American Journal of Clinical Pathology, Vol. 131, No. 2, February 2009

-   Page 206: The lung pathologists have the entity of neuroendocrine carcinoma nicely sewn up in their minds (with great clarity!). This review explores current nomenclature, classification and IHC criteria. Note that carcinoid tumor (well differentiated NE carcinoma), atypical carcinoid (moderately differentiated NE endocrine carcinoma) and small cell/large cell neuroendocrine carcinoma (poorly differentiated) are clearly identified and demarcated in the lung. GI/pancreatic pathologists take note!

-   Page 222: Epithelioid sarcomas (both conventional and proximal types) have been shown to demonstrate loss of INI1 in about 80% of tumors. However, (as this study shows) the absent IHC expression of INI1 is not mirrored by INI1 gene deletion (which is the hallmark of malignant rhabdoid tumors and atypical teratoid tumors). (See Hum Path 2009; 40(3):349)


American Journal of Surgical Pathology, Vol. 33, No. 3, March 2009

-   Page 325: Malignant peripheral nerve sheath tumors (MPNST) of cranial and intracranial origin occur in the setting of NF1, post-radiation and rarely following schwannoma/plexiform neurofibroma. The majority are high grade with heterologous elements. Note that S-100 immunoreactivity is focal and scattered (if diffusely positive, then tumor is more likely a benign nerve sheath tumor). Prognosis is poor (as with spinal nerve root tumors).

-   Page 354: A superb update on IHC of ovarian sex-cord stromal tumors: inhibin (and calretinin) is still the best overall marker. Fibroma/thecomas are least beneficial from IHC. Steroidogenic factor 1 (SF-1) appears to be the most sensitive marker overall.

-   Page 367: Microcystic stromal tumor (16 cases) is a newly described morphological entity (mean age 45 yrs; mean size 9 cm) that may be solid or cystic (or mixed). Microscopically it comprises lobulated cellular masses of cells with a microcystic pattern and intervening fibrous stroma.   The uniform bland cells have round to ovoid nuclei (no mitoses). 

     CD10+/EMA-    An average 5 year follow-up showed no recurrence. 

-   Page 384: Tubulocystic carcinoma (31 cases) of the kidney (grossly spongy/”bubble wrap”) variably cystic dilated tubules, closely spaced with intervening fibrotic stroma (PAX-2 positive, distal nephron differentiation), low but definite metastatic potential.

-   Page 393: Thyroid-like follicular carcinoma of the kidney mimics metastatic well differentiated thyroid follicular carcinoma. Encapsulated, microfollicular, inspissated colloid-like material, TG/TTF-1 negative. Approximately 48 mth follow-up, low malignant potential; must distinguish from secondary thyroid carcinoma.

-   Page 401: The majority of sinonasal adenocarcinomas are of salivary gland origin. The intestinal type (high grade, CDX-2+, CK20+) dominates in woodworkers and males. The non-intestinal comprises high grade (mitoses/necrosis ++, CK7+, males) and low grade, which is exophytic, papillary (S-100, CK7+) with no basal/myoepithelial cells with an excellent prognosis.

-   Page 417: Plasmacytoid urothelial carcinoma is a subtype comprising cords, nests, sheets in non-cohesive pattern with eccentric nuclei, abundant amphophilic cytoplasm, low-intermediate grade nuclei and minimal pleomorphism resembling plasma cells. The population with a plasmacytoid appearance may comprise 15-100% and is frequently (~75%) associated with high grade urothelial carcinomas. 

     IHC: CK7+, CK20+ and CD138+ (beware major pitfall)

-   Page 437: DOG1.1 shows a higher sensitivity than c-kit (CD117) in the diagnosis of GIST. A third of KIT negative GIST were demonstrated to be positive with DOG1.1. Hence, tumors negative for both KIT and DOG1 would require mutational screening to confirm the diagnosis of GIST.


Human Pathology, Vol. 40, No. 3, March 2009

-   Page 323: Amazingly, c-kit (CD117) highlights Giardia lamblia! Both paired nuclei with partial membrane staining is recorded.

-   Page 341: Alveolar rhabdomyosarcoma is rare in >45 yr. This study of cases with confirmed t2;13 and t1;13 also shows CD56/synaptophysin immunoreactivity (hence potentially a pitfall if myogenic markers are not applied concurrently in this age group). (See also Mod Path 2008; 21:795-806)

-   Page 349: INI1 gene alteration in epithelioid sarcomas is rare, although absent INI1 protein expression is a useful adjunctive component to the diagnosis. (see above: Am J Clin Path 2009; 133:22).


International Journal of Gynecological Pathology, Vol. 28, No. 2, March 2009

-   Page 107: About 45% of microglandular hyperplasia of the cervix is p16 IHC positive. It is mostly patchy but occasionally strong (HPV negative). Beware of this pitfall!

 - Page 114: ProExC (MCM-2 and TOPα2A) shows a strong intensity of staining in AIS and adenocarcinoma of the cervix (as opposed to benign mimics). Hence, it is useful in the setting of small biopsies of AIS (vs benign mimics).

-   Page 179: p16 is expressed in both high grade serous and undifferentiated carcinomas of the ovary (in contrast to clear, endometrioid and mucinous carcinomas).

Archives of Pathology & Laboratory Medicine, Vol. 133, No. 3, March 2009

-   Page 349: A new series entitled “Insights & Controversies” in this instance of pancreatic pathology, reviews endocrine (350), familial cancer (365), PanIN (375), autoimmune pancreatitis (383), molecular (405), cysts (423) and mimics (439). A nice paper rounds off with an algorithmic approach to the diagnosis of pancreatic tumors (454).



February 2009




Histopathology, Vol. 54, No. 1, January 2009

-   Page 1: This entire issue is dedicated to a review of pulmonary pathology. Topics which are all covered by subspecialty experts in the field included the 2009 TNM staging/classification of lung tumors, subclassifying poorly differentiated carcinoma, problems in mesothelial diagnosis, thymic tumors (other than thymomas), classification of idiopathic interstitial pneumonias, pulmonary hypertension, pathology of small airways disease, and industrial post-mortems.


Human Pathology, Vol. 40, No. 2, February 2009

-   Page 166: p5045/AMACR has previously been recommended as a useful marker for dysplasia in Barrett esophagus (see AJSP 2006:30; 871 and Hum Path 200:37; 1601). The present study reports a co-expression of AMACR with p53 in approximately 76% of neoplasias (low/high grade dysplasia and carcinoma) in inflammatory bowel disease. Caution, however is advised since 0.6% (<1%) of non-neoplastic (inflammatory) tissue and a third of “indefinite for dysplasias” also expressed these markers. The latter, according to the authors, may reflect neoplastic transformation.


Histopathology, Vol. 54, No. 2, February 2009

-   A superb update/review on recent developments in vulvovaginal pathology. The challenging spindle cell/myxoid tumors are reviewed with some of the highlights including the use of HMGA2 (nuclear transcription factor) expressed as a useful diagnostic marker of “aggressive” deep angiomyxoma. Cellular angiofibroma (not surprising given the similar morphological and IHC features) shares similar genetic/chromosomal abnormalities, involving loss of chromosome 13q, with spindle cell lipoma and myofibroblastoma. The recently described prepubertal (3-13 yrs) vulval fibroma is reviewed and the diagnostic pitfall of massive vulval edema (similar to lymphedema) is reiterated. We are also reminded that GIST may present as vulvovaginal tumors and that prolapsed fallopian tubes following hysterectomy may present as a vaginal nodule presenting a diagnostic pitfall to the unwary. The dualistic carcinogenetic/pathogenetic pathway of VIN/squamous carcinomas of the vulva is also reviewed. The controversial proposal by the ISSVD to drop VIN I (replaced with condyloma/HPV) with classic VIN (II and III) and differentiated VIN (regarded as high grade) being the only terms for (high grade) vulval dysplasia. The other recently described vaginal Tubulosquamous polyp (presumably originating from periurethral Skene’s glands – same origin for ectopic prostate tissue in the cervix) is also reviewed.


Journal of Clinical Pathology, Vol. 62, No. 2, February 2009

-   Page 97: The next time the urge to complain about aspects of our surgical practice in the West, be it volume issues, staffing, salary, teaching, infra-structure (including administration), quality control, or even the autopsy, please read the sobering and humbling experiences of our pathologist colleagues at the Aga Khan University Hospital in Pakistan. To those of us who trained and worked (including those who presently practice) in developing countries, this account of “laboratory battlefields” began long before the turn of this century. “Friends of Africa”, USCAP-led initiative, and Association of Indian Pathologists of North America (AIPNA) are two bodies that presently provide continuing medical education to pathologists in the developing world. Contact details for Friends of Africa Initiative: Adekunle Adesina (aadesina@bcm.tmc.edu) and AIPNA Megha Joshi (meghascarff@yahoo.com).

-   Page 104: Another excellent overview of iatrogenic lesions and artifacts in GYN pathology. These include mechanical displacements of neoplastic tissue in lymphovascular spaces (see later), thermal artifacts (e.g. post-ablation of endometrium or cautery granulomas following endometriosis), chemotherapy-induced tissue changes, and leiomyomata changes secondary to GnRH agonists, to name a few.

-   Page 113: We encounter on occasional pill fragments in upper GIT biopsies (e.g. iron pills). This review covered medication-induced upper GIT injury.


Archives of Pathology & Laboratory Medicine, Vol. 133, No. 2, February 2009

-   Page 176: An anecdotal report of CD117 in an anorectal primary malignant melanoma, reminding us that epithelioid GIST should be subjected to the full immunohistochemical panel targeting the appropriate differential diagnosis.

-   Page 289: The enigmatic and controversial eosinophilic cystitis (EC) (food allergens, infections and drugs) is characterized by eosinophils (acute) and fibrosis (chronic) and is predominantly in women. This study explores a study of eight males with EC.

-   Page 295: This highly specialized laboratory, whose gross specimens comprise approximately 85% of prostate biopsies, inks sequential gross specimens with five colors to maintain specimen identity and reduce errors.


Modern Pathology, Vol. 22, No. 1, January 2009

-   Page 167: Squamous morules in premalignant endometrial neoplasia (atypical hyperplasia) are a functionally inert (ER negative hormonally incompetent) subpopulation of the glandular lesions (ER positive). Note, however, that the presence of isolated morules in an endometrial biopsy demand a broader sampling (curettage) to rule out atypical complex hyperplasia or endometrial intraepithelial neoplasia.

-   Page 175: A nice review of ectopic adrenal tissue (renal-adrenal fusion). Note that these can infiltrate renal parenchyma mimicking low grade clear renal cell carcinoma.

 - Page 223: An important study demonstrating that myxoid/round cell liposarcoma probably does not exist in the retroperitoneum and that they are all well-differentiated/dedifferentiated liposarcomas. These investigators used both IHC (MDM2 and CDK4) and FISH molecular analysis to substantiate their hypothesis. Hence, their contention that the finding of a retroperitoneal t12;16 myxoid/round cell liposarcoma should alert the clinician to rule out a metastasis.


American Journal of Surgical Pathology, Vol. 33, No. 2, February 2009

-   Page 218: It is now evident that the majority of inoperable/metastatic GIST treated with TKI (tyrosine kinase inhibitor) progress at around two years due to drug resistance. These tumors have been demonstrated to develop secondary KIT gene mutation accounting for the clinical progression (whilst being on TKI imatinib). Some studies have claimed that second line TKI, like sunitinib, is of value in such situations. This study documents five cases of metastatic GIST (treated with TKI) with loss of CD117 expression, but retained KIT mutation of precursor GIST (and no secondary mutation associated with drug resistance) develop rhabdomyosarcomatous differentiation. Awareness of this phenomenon is critical to avoid diagnostic pitfalls.

-   Page 227: An interesting important study showing that myoepithelial cells (MEC) alter their immunophenotypic character in DCIS. 85% of DCIS-associated MEC showed reduced expression of one or more MEC markers. Rather disappointingly, SMMHC showed reduced expression more frequently in HG-DCIS than non-HG-DCIS. In contrast, both p63 and Calponin were more frequently preserved. This study underscores the need to target the

     epitope with more than one antibody. We routinely use both p63 (nuclear)and SMMHC (cytoplasmic) to demonstrate basal/myoepithelial cells in breast tissue. It may be worth considering Calponin as a routine third line (personal opinion) in light of this study.

-   Page 241: PAX2 is expressed in metanephric mesenchyme, which is vital for renal tubule formation and development. A large study (using tissue sections rather than tissue microarray) demonstrates that PAX2 is useful in the following distinction:

              Oncocytoma (+) vs chromophobe carcinoma (-)

              Clear cell/papillary (+) vs translocation Xp11 tumors (-)

              High-grade clear cell (+) vs urothelial (-)

     Note: There are exceptions to the above and only about 50% of papillary carcinomas are PAX2 positive.

-   Page 248: Recent reviews of appendiceal mucinous neoplasms (AMN) have been covered in these series (see Ad Anat Path. 2005:12;291-311 and 2008:15;1-17). This paper deals with the somewhat controversial subject of periappendiceal mucinous deposition in the background of AMN. With reasonable follow-up, these investigators purport that acellular periappendiceal mucin is unlikely to develop recurrent disease, whilst lesions with tumor cells are more likely to develop disseminated disease (pseudomyxomatous peritonei, disseminated peritoneal adenomucinosis (DPAM), or low grade mucinous carcinoma). However, importantly, as pointed out by the authors, the entire appendix should always be submitted in these settings.

-   Page 256: Have you ever seen a pure intralymphatic carcinoma, whether on core needle biopsy or excision following adjuvant therapy of breast cancers? D2-40 is useful in this setting to highlight the lymphatic spaces. However, the staging criteria need to be clarified to incorporate the tumor stage assignment.

-   Page 264: Angiosarcomas in viscera and soft tissue (majority mediastinum) in childhood and young adults is covered in this small series.

-   Page 270: Epithelioid hemangioma of bone is reviewed in this series of 50 cases (previously AKA angiolymphoid hyperplasia with eosinophilia and histiocytoid hemangioma). Note that distinction from epithelioid hemangioendothelioma (EHE) is critical given the unpredictable behaviors of EHE.

-   Page 278: A review of uterine adenosarcomas questioning whether adenofibromas (<2 mitoses/10 HPF) exist, since two cases with the latter features (with mild nuclear atypia and absent necrosis) resulted in disease progression.

-   Page 289: Renal epithelioid angiomyolipoma (EAML) is present as a potentially malignant mesenchymal neoplasm in the WHO series. This study, in contrast, shows that typical AML with areas of epithelioid differentiation (even with mitoses, necrosis and atypia) purport a good prognosis. Further, AML with epithelial cysts, epithelioid areas and microscopic foci of AML outside main tumor mass is strongly associated with tuberous sclerosis complex (TSC).

-  Page 298: Vascular pseudoinvasion in laparoscopic hysterectomy in low risk endometrial carcinoma has been reviewed in this series (see AJSP 2008; 32:560-565). This study adds further proof of the existence of this phenomenon and contends that mechanical displacement during grossing may contribute to this aberration. 



December 2008


Human Pathology, Vol. 39, No. 12, December 2008

-   Page 1823: This study recommends that the presence of an appendicular diverticulosis should result in a meticulous examination of the appendix to rule out an underlying neoplasm (e.g. carcinoid, adenoma or carcinoma), especially in the proximal end.


Journal of Pathology, Vol. 216, No. 4, December 2008

-   Page 394: A neat review/commentary of the molecular characteristics and microarray-based expression profiles and its impact on the understanding of breast cancer. A few vignettes: secretory carcinoma is “triple negative” and carries a balanced t12;15; medullary carcinoma is very likely to harbor germline BRCA1 mutation and metaplastic carcinoma appears to demonstrate inactivation of BRCA1 and p53.


Modern Pathology, Vol. 21, No. 12, December 2008

-   Page 1461: Distinguishing chordoma (especially the chondroid chordoma) from chondrosarcoma of the skull base can be challenging. This study concludes that cytokeratin/brachyury (a transcription factor involved in notochordal regulation/formation) immunoreactivity is 98-100% (sensitive/specific) in this distinction. In contrast, D240 (the sialoglycoprotein podoplanin) is positive in chondrosarcoma, but with less sensitivity.

-       Page 1490: Cd4 diffuse peritubular capillary immunoreactivity is essential for the recognition of humoral rejection in renal allografts. Most laboratories perform this test with a monoclonal antibody on frozen sections (with fluorescent microscopy). This study demonstrates the role of a polyclonal antibody on paraffin-embedded tissue sections with focal/less than diffuse immunoreactivity.

-       Page 1517: Borrelia burgdorferi has been touted as the antigenic driving force behind primary cutaneous marginal zone lymphomas in Asia and Europe (but less so in the US). This study reviews data from all three continents, indicating a less significant association (including t11;18 [API2-MALT1]). Eosinophilic infiltrate appeared to be a significant finding in Asia.

-       Page 1533:  Signet ring cells in colorectal mucinous adenocarcinomas are associated with a worse prognosis and poor survival. This study recommends that the percentage of signet ring cells be included in the final report of mucinous carcinomas.


Histopathology, Vol. 53, No. 6, December 2008

-   Page 621: A review of the morphological classification of neoplastic lesions of the urinary bladder. A comparison of the 1973 and 2004 WHO classification systems is also reviewed. (Please also see the “My Approach” series in J Clin Pathol 2008; 61:3-10).

-   Page 650: Follow-up excision of atypical ductal hyperplasia/radial scar/complex sclerosing lesions diagnosis on needle core biopsy reveals that about 20% reveal an underlying malignancy (DCIS or invasive cancer, 106 cases) and the remainder (about 80%, 417 cases) are benign.

-   Page 676: A comparative morphological analysis of eosinophilic esophagitis (EE) vs GERD (gastroesophageal reflux disease) using combined morphology, immunohistochemistry (IHC) and histochemistry indicates absolute counts on morphology (55 vs 9) and IHC (77 vs 24) respectively (per HPF). Further, secondary qualitative squamous epithelial changes were more robust in EE than GERD.

-   Page 728: A wonderful review with a unique approach to the “ten trapdoors” in testicular germ-cell tumor pathology. This is a gem of a review strongly recommended for all surgical pathologists who sign out testicular tumors. Much of the “treats” are derived from the authors’ experience and include recommendations on staging (vascular invasion), classification, morphological differential diagnosis, metastases and transformation.


American Journal of Surgical Pathology, Vol. 32, No. 12, December 2008

-   Page 1751: A review of pulmonary artery (intimal) sarcomas from the AFIP. Not surprisingly, the majority are pleomorphic, ranging from myxofibrosarcoma-like to undifferentiated round cell morphology. Interestingly, three cases of intravascular low grade myofibroblastic sarcomas with a good prognosis (following complete excision) are described for the first time at this site.

-   Page 1762/1770: Two studies highlighting the importance of early diagnosis of autoimmune pancreatitis (AIP) (IgG4 lymphoplasmacytic sclerosing disease) to avoid unnecessary surgery, given that these lesions are responsive to steroids. The first study (page 1762) emphasizes that a patchy distribution of the lesions may result in a falsely negative biopsy, whilst the second (page 1770) proposed that IgG4:IgG plasma cell ratio on ampullary biopsy material may help differentiate AIP from other pancreatic lesions.

-   Page 1780: Do not ignore a renal cell carcinoma with clear cells and papillary configuration, as it may harbor trisomy 7, 17 or loss of Y chromosome and be p504S (AMACR)/CK7 positive, indicative of papillary carcinoma. In this study of 14 such cases, 9 demonstrated the above genotype/phenotype, whilst only 3 turned out to be clear/conventional type. (See also AJSP 2008; 32:1239)

-   Page 1807: A superb study asserts that lobular endocervical glandular hyperplasia (LEGH) may be a precursor lesion to some minimal derivation adenocarcinomas (MDA) by demonstrating that 3/14 LEGH (with atypia) harbor 3q gains/1p loss (similar to that found in MDA). (See also AJSP 1999; 23:886 for the seminal paper on LEGH and Histopath 2001; 39:364 for pyloric metaplasia in LEGH).

-   Page 1822: The largest series of chromophobe renal cell carcinomas (145 cases) reviews the morphology (pale or eosinophilic cells either >80%) (10% vs 40%, respectively) (mixed 45%) and reiterates the lower malignant potential than clear cell, and similar or better than papillary. Noticeably, a subset may show areas similar to oncocytoma (which tend to be bilateral and multifocal). Hence, sampling is critical (and a cautious interpretation of needle core biopsies!). The majority of chromophobe carcinomas (CC) were Fuhrman nuclear grade 3 (although previously studies have suggested that Fuhrman grading is inappropriate for CC; AJSP 2007; 31:957).

-  Page 1854: Parathyroid intraoperative consultations can be quite the challenge. The knowledge of parathyroid lipoadenomas (LA) and lipohyperplasias (LH) stand at odds with typical parathyroid adenomas/hyperplasia which are characterized by a reduced fat content. Hence, knowledge/awareness of the weight (although partial submission may preclude this value) and nodular expansions would help distinguish LA/LH from normal parathyroid glands.

-  Page 1877: Hyalinizing trabecular tumors of the thyroid are almost all benign, according to this study, and can therefore be called adenomas.

-   Page 1890: Note that focal 34βE12 (high MW cytokeratin) may be positive in prostate carcinoma cells in 0.3% of needle core biopsies. Hence, concurrent use of p63 for basal cells is present as being more specific (although p63 may rarely stain prostate cancers – see AJSP 2008; 32(3):461-467).

-   Page 1896: A review of primary angiosarcomas of the breast reaffirms the notion that there is no correlation between histologic grade and patient outcome, since well/poorly differentiated tumors are not predictive.


American Journal of Clinical Pathology, Vol. 130, No. 6, December 2008

-   Page 905: A focused rather than random review of surgical pathology cases for detection of errors is presented in this study of 7444 cases with a higher proportion of errors (3.2%) being detected over random review (0.36%).


Journal of Clinical Pathology, Vol. 61, No. 12, December 2008

-   Page 1303: Another review paper in the “My Approach” series. This manuscript presents the clinical, pathological and diagnostic approaches to intraductal papillary mucinous neoplasms of the pancreas. 



November 2008


Human Pathology, Vol. 39, No. 11, November 2008

-   Page 1656: Galectin-3 plays an important role in pathogenesis/progression of differentiated thyroid carcinomas. This study demonstrated an expression of 82% (>5% cells) in both differentiated papillary and follicular thyroid carcinoma. 


Journal of Pathology, Vol. 216, No. 3, November 2008

-   Page 286: Patients with hereditary diffuse gastric cancer carry a germline E-cad (CDH1) mutation. Endoscopic surveillance is best targeted toward positive foci in the fundus. The yield of detection is proportional to the number of endoscopic biopsies, with E-cad protein expression absent or decreased in the foci of collections of signet ring cells in the lamina propria, with a low proliferative index.


Modern Pathology, Vol. 21, No. 11, November 2008

-   Page 1303: Extraskeletal chondrosarcoma is a multinodular tumor with myxoid, reticular/cord-like, polygonal spindled/epithelioid cells arranged in a cribriform/solid pattern. The cellular variant comprises epithelioid cell sheets, mitoses, hemorrhage and necrosis. FISH analysis (with break apart probes t9;22) is useful to distinguish this neoplasm from its differential diagnosis (e.g. soft tissue myoepithelioma and chordoma).

-       Page 1311: Soft tissue myoepithelium (STM) demonstrates a heterogeneous genetic profile, however minimal deleted 19p13 CDKN2A (inactivation of a tumor suppressor gene) is common to all STM.

-       Page 1345: Pilomyxoid astrocytoma (PMA) (recognized in the 2006 WHO) is seen in young patients (especially hypothalamus/optic chiasma) and comprises monophasic, monomorphic, elongated pilocytic cells in a prominent myxoid stroma with a peculiar angiocentric arrangement. In this site, it is more aggressive (than traditional pilocytic astrocytoma (PCA)) with a propensity for CSF spread. Genomic evidence suggests that PMA is an aggressive variant of PCA.

-       Page 1403: Mismatch repair (MMR) deficient colon cancers demonstrate a high tumor grade with increased lymphocytes. Importantly, they often express a CK20/CDX2 negative phenotype more frequently than MMR-proficient cancers. 


Lab Investigations, Vol. 88, No. 11, November 2008

-     Page 1143: Medulloblastomas comprise about 15% of pediatric CNS tumors and spread via the CSF pathways (about 30%) of the brain and spine. This study demonstrates α9/β1 integrin mediated adhesion in leptomeningeal metastases, presenting potential design of future therapies to target this process.

-     Page 1227: In his seminal work, Robin Warren (Nobel laureate) showed that Helicobacter pylori induces epithelial apoptosis. This study demonstrates a regulation of this environment with an expression of bcl-X2 and bcl-2 in chief cells (both strongly inhibit apoptosis) and, in contrast, BAD (pro-apoptotic protein) detected in parietal cells.


Archives of Pathology & Laboratory Medicine, Vol. 132, No. 10, October 2008

-     Page 1586: An excellent practical approach to the diagnosis of gastritis includes the following sequence with an assessment of: chronicity, activity, Helicobacter pylori, topography, gland atrophy/intestinal metaplasia, and finally special features (e.g. viral, granulomas, etc.).

-     Page 1608: This QA paper outlines the reporting guidelines for surgical pathology reporting. It delineates all the components that should be included in a surgical pathology report: required, preferred and optional elements. Mandatory reading for all surgical pathology and QA directors.


Histopathology, Vol. 53, No. 5, November 2008

-   Page 533: Pediatric Xp11.2 translocation renal cell carcinomas show a wide heterogeneous morphology with high nuclear grade, abundant cytoplasm (clear to granular) and a solid/papillary architecture. TFE3 nuclear immunoreactivity confirms the diagnosis. Presentation is usually advanced stage with an unfavorable outcome.

-   Page 545: Neovascularization of mucin in mucinous DCIS of the breast (on needle core biopsy) does not discriminate between invasive and in-situ carcinoma. These authors hypothesize that the mucin promotes neovascularization followed by tumor invasion into richly vascularized mucinous stroma.

-   Page 578: Morphology predicts 1p/19q loss in oligodendroglial tumors in about 80%: round, uniform nuclei, perinuclear halos, calcification and absent gemistocytic cells in a non-temporal/non-insular location.


Journal of Clinical Pathology, Vol. 61, No. 11, November 2008

-   Page 1153: In this “My Approach” series, clear clarification of the IHC of solid pseudopapillary tumor of the pancreas:

  • β-catenin – nuclear and cytoplasmic (as a result of β-catenin mutation)
  • E-cad – extracellular domain antibody: loss of membranous staining.

                 – cytoplasmic antibody: nuclear expression.

      (CDH1 gene mutation uncommon)

  • CD10 and progesterone immunoreactivity adds to diagnosis

-   Page 1203: GEWF (glacial acetic acid, ethanol, distilled water and formalin) solution increases the lymph node harvest in colon cancer. First published in 2001, this method requires a 16-24 hour fixation in 10% buffered formalin, followed by 12-18 hours in GEWF solution, to reveal lymph nodes as white nodules. This study increased harvest from 9-10 to 16-17 lymph nodes per pericolic fat dissection.

-   Page 1193: LEAN quality improvements have been used in industry (e.g. Toyota). This process addresses immediate problem solving reorganization of processes/workflow with a view to improving quality, decreasing inefficiency and reducing waste/cost. This laboratory in Pittsburgh applied this system to their surgical pathology laboratory and significantly improved their work units/FTE and reduced specimen turnaround time. In Vermont, we have also tested and applied this system to surgical pathology with overwhelming positive improvements (unpublished).

-   Page 1184: An important review of all the technical pitfalls in IHC. These authors systematically explore all steps from fixation, tissue processing, embedding, decalcification and antigen retrieval, revealing potential areas of errors. Endogenous enzymes/biotin and correct antibody/immunodetection choices are also outlined, along with emphasis on correct interpretation.


Advances in Anatomic Pathology, Vol. 15, No. 6, November 2008

-   Page 309: An excellent review of the etiology of hepatic granulomas with an emphasis on infectious causes.

-   Page 332: The non-medullary familial thyroid carcinomas are reviewed in this presentation: FAP, PTEN syndrome, Carney’s syndrome, Werner’s, etc. A diagnostic algorithm is also nicely tabulated.

-   Page 350: The second part of the Ackerman pattern-based approach to non-neoplastic dermatopathology. The first was presented in Ad Anat Path 2008; 15:76-96. The first part dealt with spongiotic, psoriasiform, interface and bullous dermatoses. This paper completes the picture with perivascular, vasculitis, panniculitis and nodular/diffuse dermatitic patterns.

-   Page 370: Do occult axillary lymph nodes metastases in breast cancer have a prognostic significance? This commentary on a paper published in JCO 2008; 26:1803-1809 shows that it does carry prognostic significance. The study also demonstrates that SLN protocol (serial sectioning), combined with IHC, is more sensitive for the detection of micrometastases (<2.0 mm) and isolated tumor cells (<0.2 mm). Larger studies are awaited, so watch this space!


American Journal of Surgical Pathology, Vol. 32, No. 11, November 2008

-   Page 1608: As with many antibodies on the market, the specificity decreases inversely as we become more familiar with its application. In this study, CDX2 is shown to be positive in up to 30% of uterine cervical adenocarcinomas.

-   Page 1620: The ever-expanding “new disease” syndrome! IgG4-related lymphoplasmacytic vasculitis and interstitial fibrosis in the lung.

-   Page 1661: Colorectal adenomas infiltrated by lymphocytes with reduced apoptotic bodies may be a potential marker for HNPCC.

-   Page 1675: Extracapsular penetration of hepatocellular carcinoma is associated with a poor disease free survival.

-   Page 1683: A nice summary of metastatic carcinoma to the testis:  prostate, renal, colon, urinary tract, lung (in descending order of frequency). They are usually solitary and unilateral and may simulate primary testicular tumors including rete adenocarcinomas and Sertoli cell tumors.


Archives of Pathology & Laboratory Medicine, Vol. 132, No. 11, November 2008

-   Page 1723: Yet another paper reaffirming the role of Glypican-3 in positively identifying hepatocellular carcinomas (75% cytoplasmic, membranous and canalicular) and negative in adenoma, FNH, large regenerative nodules.

-   Page 1729: Prostatic stromal hyperplasia with atypia are ill-defined nodules of bizarre giant cells with smudged chromatin which may represent degenerate myocytes (in some instances), that are largely benign and rarely recur. They should not be confused with phyllodes tumors or sarcomas of the prostate gland. Importantly, these authors advise not to use the stromal tumor of uncertain malignant potential for these lesions.

-   Page 1767: C-cell hyperplasia (CCH) (>50 c-cells/LPF) and medullary microcarcinomas (MMC) (<1 cm) are concisely explored in this study of prophylactic thyroidectomies for familial medullary carcinoma of the thyroid.

-   Page 1813: A superb review of mammary myofibroblastoma (MM) by an authoritative author who has spent much time studying these tumors. The variants (cellular, infiltrative, lipomatous, epithelioid, myoid and deciduoid) and differential diagnosis (nodular fasciitis, desmoid fibromatosis, low grade spindle cell (fibromatosis-like) carcinoma, nerve sheath tumors, spindle cell lipoma (shares the same cytogenetic 13q14 deletion as MM), inflammatory myofibroblastic tumor and myoepithelioma) are presented.

September 2008


Human Pathology, Vol. 39, No. 9, September 2008

-   Page 1275: UIP (idiopathic pulmonary fibrosis) is a life threatening diagnosis with a high mortality and, as such, should be made with great caution. This excellent review revisits the criteria for diagnosis with great photographs (spatial/temporal heterogeneity with architectural distortion and fibroblastic foci), and distinguishes UIP fro NSIP (both cellular and fibrosing phases), chronic hypersensitivity pneumonitis and LCH (both acute and chronic phases). Remember also that chemoradiation, collagen vascular diseases and smokers lung must always be ruled out before a diagnosis of UIP is made. Lastly, there is no role for transbronchial biopsies (R/O sarcoid, infection, malignancy) in the diagnosis of UIP.

-   Page 1295: Always wondered what TOKER cells of the nipple are? This paper describes the morphology (bland, benign, basal zones of nipple epidermis that disappear on deeper sections), along with hyperplasia (even atypia!) and, of course, the IHC (ER/PR positive, CD138 negative, p63 negative). In contrast, Paget’s disease is ER/PR negative, CD138 positive and p63 positive. Both are CK7/EMA positive.

-   Page 1350:  Collecting duct carcinomas of the kidney are rare (in my experience) and are usually medullary based with adjacent in-situ changes in collecting ducts (useful to make a diagnosis). Ulex (if you still keep this antibody), c-kit (also positive in chromophobe) and E-cad confirm the diagnosis of CDC, which must be distinguished from urothelial (because of location) and papillary carcinomas (which are p504S positive). 


Advances in Anatomic Pathology, Vol. 15, No. 5, September 2008

-   Page 263: A great exposé of anal pathology (a rarely visited area) sees a revision of the normal anatomy (anal canal [intra-canal] versus anal margin [5 cm of anal opening] versus perianal skin [>5 cm form anal opening]), risk factors predisposing to pathology in this area (HIV+, immunosuppression, organ transplants) and the related pathological entities that surgical pathologists are called upon to preside over (SILs [AIN], carcinomas and their differential diagnoses). The role of p16 and ProEx C is also nicely summarized (largely similar to the cervix), along with the HPV-associated basaloid/cloacogenic/transitional carcinomas and verrucous carcinomas (remember giant condyloma of Buschke and Lowenstein!).

-  Page 277: Early bladder cancer detection on cytology and FISH (Urovysion) analysis are now state of the art tools for screening of high risk patients. This review explores both the technique and chromosomal abnormalities with great photographs using pericentromeric probes to chromosome 3 (red), 7 (green), 17 (aqua) and 9p21 band (gold). 

-   Page 287: Another review (see Arch Pathol 2008; 132:993-1007) of the “gray zones” of brain tumor classification largely based on recent changes in the new WHO classification.


Journal of Clinical Pathology, Vol. 61, No. 9, September 2008

-   Page 1041: HPV does not play a role in the pathogenesis of Mullerian adenosarcomas of the uterine cervix. Note that these tumors are seen more often in the uterus/endometrial cavity with prolapse into the cervical os.

-  Page 1029: Intestinal spirochetosis is not uncommonly seen (or missed), in my experience. This study explores the clinical significance of this infection with no correlation between symptoms and persistence/eradication. Hence the recommendation is to adopt a “wait and see” approach towards treatment, with a trial of treatment if symptoms are severe/persistent. Useful for the next phone call you receive from a perplexed GI physician inquiring about your (much prized) diagnosis!


Histopathology, Vol. 53, No. 2, August 2008

-   Page 245: A timely review reiterating the role of mutational analysis in the management of GIST:

  • Secondary mutations detected during treatment may cause resistance to drugs.
  • Exon 11KIT mutation is most common; gastric GIST with del is more aggressive than substitution. Overall good response to imatinib.
  • Less common exon 9 mutation aggregate in intestinal GIST; also less sensitive to imatinib therapy.
  • Exon 18 substitution most common PDGFRA mutation may be resistant to imatinib.
  • PDGFRA mutation usually associated with c-kit negative gastric GIST, is epithelioid in morphology and follows a less aggressive course of disease.
  • GISTs in neurofibromatosis and Carney’s triad (both rare) lack KIT/PDGFRA mutation.
  • Secondary KIT mutation usually involves exon 13-17 and is sensitive (especially 13-14) to sunitinib.
  • Therefore KIT/PDGFRA genotyping is important for assessment of GIST sensitivity to tyrosine kinase inhibitors. 

-  Page 299:  Careful examination of splenic red pulp to separate SANT (sclerosing angiomatoid nodular transformation) from inflammatory pseudotumor since both lesions may demonstrate areas resembling each other.

-   Page 311: Iron-induced mucosal pathology of esophagus and gastric mucosa is a common finding in patients on oral iron therapy, usually associated with erosion and reactive gastritis. Iron is seen in the macrophages in villous tips. 


American Journal of Surgical Pathology, Vol. 32, No. 9, September 2008

-   Page 1273: Luteinized thecoma associated with sclerosing peritonitis was first described by Scully in the 70s. The ovarian lesions are α-inhibin/calretinin positive with entrapped follicles and variable edema, with no recorded spread beyond the ovary. The peritoneal lesions are AE1/3 positive and may cause morbidity. These authors propose the term “thecomatosis” at least as a parenthetic alternative to luteinized thecoma. 

-   Page 1299: For those lymphomaniacs fixated on the breast: a nice review of 106 cases. Not surprisingly, DLBCL is the commonest (64%), presenting with a localized mass. Disseminated lymphomas are headed by FL and other B, T and HL in lower frequencies. Localized disease carries a better prognosis than disseminated disease.

-   Page 1360: Diffuse adenosis of the peripheral zone of the prostate gland (first presented at USCAP 2008) occurs in younger patients, comprising multiple foci of small non-lobular crowded glands with bland acini. Interestingly, 57% of those cases rebiopsied within a 15 month period revealed carcinoma, raising the question whether these lesions are a risk factor for developing carcinoma. For now, close follow-up and rebiopsy are the authors’ recommendation. 

-   Page 1396: Angiotropism or migration of melanoma cells along the external surface of blood vessels was previously proposed as a mechanism for metastases of cutaneous melanoma. This study re-affirms the features as an independent predictor of local recurrence. So Dermies out there, keep your eye on the blood vessels!


American Journal of Clinical Pathology, Vol. 130, No. 2, August 2008

-   Page 162: An excellent and convincing editorial purporting the need for mandatory consensus (second opinion) on all CIN2 diagnoses (since these usually young patients are subjected to LEEP), supported by the (judicious) use of immunostains (p16, ProEx C,

     MIB-1) that are predictive of persistence and/or progression to determine those lesions that merit ablation.

-   Page 219: Yet another study on Glypican-3 IHC for the detection of HCC. This study shows ~50% immunoreactivity in needle core biopsies.

-   Page 224: Another useful role for Glypican-3 (from the same group above) purporting the role of this heparan sulfate proteoglycan for the diagnosis of yolk sac tumors and choriocarcinoma, not surprising since this protein is essential for embryonic development. Fortunately, GPC-3 is negative in embryonal carcinoma (CD30, OCT 3/4 positive) and seminoma (c-kit, OCT 3/4, D2-40 positive).


American Journal of Clinical Pathology, Vol. 130, No. 3, September 2008

-   Page 375: Put your rulers away since this study demonstrated that the quantitative assessment of the collagen table does NOT increase the accuracy of diagnosing collagenous colitis. A constellation of features including distorted (degenerative) superficial epithelial cell arrangement, epithelial denudation (not often cited but seen often, in my experience) and both surface epithelial and lamina propria inflammation (along with the clinical picture) captures the diagnosis. Note that acute inflammation may be superimposed on the above picture, raising the erroneous possibility of acute self-limiting colitis (as I recently learned rather embarrassingly!).

-   Page 389: Concurrent uterine cervical glandular preneoplasias and SILs are clonally mutually exclusive, indicating separate HPV-associated pathways. Further, the glandular dysplasia/AIS carcinogenetic evolution appears to mirror that of SIL, i.e. early lower grade lesions (episomal HPV/polyclonal) versus late higher grade lesions (integrated HPV/monoclonal). In contrast, the squamous and glandular component in adenosquamous carcinoma evolve from the same clone with an identical HPV type/physical state.

-   Page 401: The cross-reactivity of the Hybrid Capture II System (purported to detect 13 HR HPV types) with LR HPV types is further challenged by a new HPV detection system (Invader) in this manuscript.


Archives of Pathology & Laboratory Medicine, Vol. 132, No. 9, September 2008

-   Page 1388: Continuing the series entitled “Best Practices in Diagnostic IHC”, this paper highlights the role/application of immunoreagents in both the diagnosis of prostate cancer and the ability to rule out mimics. An excellent overview!

-   Page 1417: Remember that AMACR (P504S), whilst this immunoreagent is useful in the diagnosis of prostate cancer, is not specific nor confined to this organ. It is also expressed in high levels in papillary RCC (useful for the exclusion of the other RCC types) and colon cancer. This study highlights the over-expression of this enzyme (involved in β-oxidation of lipids) in clear cell adenocarcinoma of the bladder and urethra. 


Modern Pathology, Vol. 21, No. 9, September 2008

-   Page 1067: TOP IIα and MCM proteins (associated aberrant S-phase induction and packaged as ProEx C) is a useful alternative to p16. This study demonstrates that combined ProEx C/p16 is more predictive of SIL versus NO SIL than p16/MIB-1. Further, ProEx C has an equivalent sensitivity and higher specificity for HSIL. However, the principal value of this marker is in the reduction of false-positive rates for SIL relative to MIB-1. 

-   Page 1084: A nice lovely morphological study reminding us that sarcomatoid mesothelioma has the capability of demonstrating heterologous differentiation (chondro, osteo and rhabdomyo- sarcomatous) and that biopsies of pertinent sites (pleural or mediastinal based tumors) with such features should always raise this possibility.

-       Page 1095: Perineural invasion (even in the presence of extraprostatic nerves) is not a significant prognostic indicator in prostate cancer.




August 2008


American Journal of Surgical Pathology, Vol. 32, No. 8, August 2008

-   Page 1159: IgG-4 related systemic sclerosing diseases have featured frequently in these updates (autoimmune pancreatitis, chronic sclerosing sialadenitis, so-called Kuttner tumor, and chronic sclerosing dacryoadenitis, to name a few). This paper describes the further evolution of this process to ocular adnexal lymphoma associated/arising in IgG-4 chronic sclerosing dacryoadenitis.

-   Page 1175: Recent morphological variants of seminoma have been highlighted in the literature (interstitial, tubular, and intratubular). This study demonstrates another potential pitfall – conspicuous signet ring cells, not surprisingly containing glycogen (as do all seminomas). Oct 3/4 and CD117 immunoreactivity rapidly removes any doubts of metastatic adenocarcinoma!

-   Page 1201: The modern robotic technology of prostatectomy has introduced a higher degree of capsular incision (in my own experience). These resection planes (devoid of capsule) may be benign or malignant transections. The present study demonstrates that the latter recurs more often than prostates with focal extra-prostatic extension but with negative margins, and less often than prostates with non-focal extra-prostatic extensions with positive margins. Remember the extra-prostatic extension (EPE) bumps up the stage, but a positive margin with capsular incision does not unless concurrent EPE is also demonstrated.

-   Page 1239: Clear cell papillary renal cell carcinoma (CK7+, p504-, CD10-), negative trisomy 7, negative loss chromosome Y, and absent deletion of chr 3, i.e. neither clear NOR papillary, warrants a distinctive entity?

-   Page 1246: Some of us are called upon to interpret mismatch repair protein IHC. This study explores interpretative issues and clearly declares that experience is required to identify

     MSI-H +ve tumors.


Modern Pathology, Vol. 21, No. 8, August 2008

-   Page 925: Endometrial carcinomas associated with tamoxifen therapy demonstrate a higher β-catenin expression (than the classic type 1 pathway: hyperestrogens, MSI-H, PTEN, β-catenin and k-ras mutations). 

-   Page 937:   This study proposes that p53 IHC is still the best discriminator between uterine papillary serous carcinoma (p53 +++) and high grade endometrioid adenocarcinoma (which can also be p53+ with IHC!).

-   Page 961: p504 (AMACR) immunoreactivity highlights 90% of LG dysplasia, 95% of HG dysplasia with early adenocarcinoma but only 25% of indefinite for dysplasia in Barrett esophagus. Potentially a useful marker in difficult cases?

-   Page 973: Approximately 10-20% follicular lymphoma lack a bcl2 gene rearrangement. These cases may harbor bcl-6 gene amplificiation/3q27 gain according to this paper.

-   Page 992: The micropapillary pattern of adenocarcinoma has now been well documented (and recognized) with an aggressive outcome (salivary gland, lung, colon, bladder, breast). This study of lung cancers demonstrates intact E-cad and β-cat IHC indicating preservation of tight adhesion molecules, but loss of laminin/basement membrane (EM) inferring an anchorage independent growth.

-   Page 1011: Glypican-3 expression in HCC (well diff 50%, moderate diff 80%, poorly differentiation 90%) is not surprising considering that this heparin sulfate proteoglycan is expressed in fetal liver. As with previous studies (rather comforting), hepatic adenoma and macroregenerative nodules are negative. However, focal positivity has been noticed in regenerative/dysplastic cirrhotic nodules as well (pitfall in needle core biopsies). Note that only 60% of the fibrolamellar variant is GPC-3 positive.


Histopathology, Vol. 53, No. 2, August 2008

-   Page 127: Another review of tubal and ovarian pathways to pelvic epithelial carcinomas. Pathological perspectives, cell/site and origin (Mullerian inclusions, endometriosis vs endosalpinx) are all nicely reviewed.

-  Page 218: The saga of classification of thymic tumors continues: this study examining the interobserver variation of the WHO classification. Overall a moderate degree of reproducibility was demonstrated with the best agreement being in A and AB. Difficulties still persist with B1 vs B2 and B2 vs B3. 


Human Pathology, Vol. 39, No. 8, August 2008

-   Page 1239: A powerful paper exploring the role of tumor cell type vs grade in prognosticating ovarian cancers. Serous carcinomas (40% in this series) commonly present as advanced stage III, whilst non-serous (clear 25%, endometrioid 24%, mucinous 6%) usually present as stage I or II in over 90% of cases. The Silverberg grading was found to be a more powerful prognosticator than FIGO. Conclusion: Stage is still the most powerful indicator of prognosis, followed by tumor type. Grading is NOT  of independent significance. 


Archives of Pathology & Laboratory Medicine, Vol. 132, No. 8, August 2008

-   Page 1228: A review of practical and molecular approaches to endocrine pathology. Some highlights are illustrated. The reticulin stain is preserved with an acinar architecture in pituitary hyperplasia vs a disruption in pituitary adenoma (1231). Thyroid Hurthle cell neoplasms (1241) are now classified as adenoma and carcinoma based on the absence/presence of vascular and capsular invasion (minimal vs extensive). Criteria for distinguishing oncocytic variant of PTC (nuclear features) from Hurthle cell neoplasms (HCN) vs tall cell variant of PTC (2-3x tall than width) are also highlighted. We are reminded that the oncocytic variant of medullary carcinoma of the thyroid has small uniform nuclei (salt and pepper chromatin) vs the large prominent nucleoli and pleomorphic nuclei of HCN. A rare cause of primary hyperparathyroid (1251) is parathyroid carcinoma (densely adherent and invading surrounding structures, with fibrous bands, trabecular growth, mitotic activity). Only one of the latter three features may constitute a diagnosis of atypical adenoma. The WEISS criteria for distinguishing adrenal cortical adenoma from carcinoma (1263) has stood the test of time. We now refer to adrenal medullary pheochromocytoma (1272) as opposed to extra-adrenal paraganglioma (sympathetic/parasympathetic). None of the traditional identifiers of potential risk for metastases (capsular/vascular invasion, cytologic atypia) help in these tumors. Hence, the behavior is unpredictable and long term follow-up is essential. We should follow the WHO classification for gastroenteropancreatic neuroendocrine tumor (1285), where CK19 is an independent marker of aggressive behavior.

-   Page 1313: How often have you had to return to the bucket/pot to submit all TURP curettings after you have discovered cancer in the first six blocks? This study demonstrates that the Gleason score and tumor volume does NOT change with the additional submission (1 block/5g NOR complete submission).


Journal of Clinical Pathology, Vol. 61, No. 8, August 2008

-   Page 881/914: Neither mitoses/Ki-67 index (nor morphological pattern, age, size, etc.) can predict the prognosis of granulosa cell tumors (GCT). Stage I (unruptured tumors) is still the best indicator of good prognosis, although all GCT should be followed up for long periods (10-20 years). The juvenile GCT carries an excellent prognosis, whilst the adult GCT should be regarded as LG malignant potential. Stage II-IV should receive adjuvant therapy.


 International Journal of Gynecological Pathology, Vol. 27, No. 3, July 2008

-   Page 318: We still do very poorly at reproducing endometrial hyperplasia on biopsy. This study proposed a two-tier grading system (simple/complex vs atypical/carcinoma).

-       Page 326: p16, p53 and MIB-1 are useful to distinguish between leiomyosarcoma (LMS) and leiomyoma (including cellular variety) of the uterus. However, considerable overlap between LMS and bizarre/symplastic leiomyoma and STUMP (where it is most crucially needed!) presents a limited role for IHC.

-       Page 353: An excellent review of a practical approach to intraoperative consultation to GYN pathology (copy and share with your GYN surgeons). Mucinous tumors (the complex problem) of the ovary are reviewed. 

-       Page 366: A nice expose of extrahepatic bile duct and gallbladder carcinoma metastatic to the ovary is presented. The usual criteria (bilateral, <10 cm, multinodular, surface involvement, heterogeneity of pattern, “dirty” necrosis, infiltration and signet ring cells) are ubiquitous to these metastases to the ovary.

-       Page 418: Surprise! Mammaglobin is NOT specific to breast primary and shows variable immunoreactivity with endocervical (less often) and endometrial (more often) carcinomas.

-       Page 447: An important diagnostic pitfall: massive vulval edema secondary to obesity and immobility mimicking aggressive angiomyxoma!


July 2008


Journal of Pathology, Vol. 215, No. 3, July 2008

-   Page 231: Pleomorphic lobular carcinoma (in our institution at least) is treated as ductal carcinoma. However, this paper demonstrates that the molecular profiling of PLC is similar to classic lobular carcinoma: frequent ER/PR+; E-cad neg; 1q+, 11q-, 16p+, 16q-.


Histopathology, Vol. 53, No. 8, July 2008

-   Page 91: The polypoid changes of mucosal prolapse at the anorectal junction (so-called inflammatory cloacogenic polyp) is well known to most. This study alerts us to the possibility of anorectal adenomas superimposed with secondary polypoid mucosal prolapse changes. If any doubt, p53/MIB-1 immunoreactive will highlight the former.


Human Pathology, Vol. 39, No. 7, July 2008

-   Page 1072: CDX2- expression in the morules (squamous differentiation) of endometria is demonstrated in this study, corresponding to β-catenin expression. This phenomenon is predominant in hyperplasia and carcinoma.

-  Page 1080: A study of 300 cases of thyroid hyperplasia demonstrating that papillary hyperplasia (13%), nuclear clearing (15%), nuclear grooves (8%), nuclear atypia (7%), and mitoses (6%) should not be confused with a neoplastic process.


Modern Pathology, Vol. 21, No. 7, July 2008

-   Page 795:   An important observation demonstrating epithelial (pan-keratin 50%, CAM 5.2 52%) and neuroendocrine (syn 32%, chromogranin 22%) in alveolar rhabdomyosarcoma. This could potentially be a major diagnostic pitfall in adults (especially) if small cell carcinoma is pursued in a head/neck primitive small round blue cell tumor. Therefore a panel including desmin and myogenin is recommended.

-   Page 817: As with most (if not all!) immunomarkers initially marketed with high degree of specificity, Glypican-3 (HCC +ve) is also expressed in squamous cell carcinoma (55%) of the lung.


American Journal of Surgical Pathology, Vol. 32, No. 7, July 2008

-   Page 955: High grade ovarian carcinomas often pose diagnostic difficulties in typing (in my experience anyway!). This study presents the mixed ovarian epithelial carcinoma (serous WT1, ER, p53+) and (clear), claiming that this represents a variant of serous carcinomas. Remember also that serous carcinomas often present as high stage (III or IV), whilst pure clear cell carcinomas present with lower stage (I or II).

-   Page 996: Ossifying fibromyxoid tumors revisited in this 104 case series from AFIP. The majority are S-100+, whilst desmin is only occasional and focal. Only about 20% recur (especially with mitoses >2/50 HPF), but no metastases were documented.

-   Page 1022: A study of rhabdomyosarcoma in the urinary bladder in adults also (see above) highlights the problem of small cell carcinoma as a diagnostic pitfall with focal synaptophysin immunoreactivity.

-   Page 1038: A nice paper form Durban highlighting otic pneumocystosis. Recognizing the foamy exudates in an unconventional location is key to applying the methenamine silver stain to demonstrate the trophozoites and cysts.

-   Page 1044: The HPV status in basaloid squamous cell carcinoma of the head and neck is again highlighted in this paper. Remember that HPV positivity is now firmly established as a powerful indicator of improved patient survival (even though lymph node metastases).

-   Page 1080: An unusual variant of schwannoma (microcystic/reticular) presenting in GIT and subcutaneous is presented in this study of 10 cases. Only a third showed conventional schwannoma-like area. This variant is recognized with anastamosing/intersecting strands of eosinophilic spindle cells distributed around islands of myxoid/collagenous/hyalinized stroma. In the GIT, this variant should be distinguished from mucinous/signet ring cell carcinoma, and outside GIT from reticular perineurioma, myoepithelioma and extraskeletal myxoid chondrosarcoma.

-   Page 1088: A nice “conclusive” paper proposing that fibroblastic polyps and perineuriomas of the colon are one and the same entity: both being EMA, claudin and glut-1 +ve.


Journal of Clinical Pathology, Vol. 61, No. 7, July 2008

-   Page 785: For all the cytopathologists among our readers: An excellent review of FNA of the thyroid – with almost 30 years of experience for good measure!

-   Page 787: An update on the pathological and molecular features of adrenocortical carcinoma, especially with respect to the Weiss criteria (which appears to still be superior to the molecular data). I like their approach to the Weiss criteria:

           3 structural (dark cytoplasm, diffuse architecture, necrosis)

           3 cytological (atypia, mitoses, and atypical mitoses)

           3 invasion (sinusoidal, veins, capsule)

-   Page 802: An excellent overview of the HIV+ skin biopsy from Master Wayne Grayson.


Advances in Anatomic Pathology, Vol. 15, No. 4, July 2008

-   Page 211: An important review of identifying cross contaminants and specimen mix-ups in surgical pathology. This is written by one of the leading molecular pathologists with the approach being: clinical and laboratory correlation, IHC work-up, and finally an excellent overview of DNA-based molecular identity testing (DNA fingerprinting) to identify mixed specimens/tissues in surgical pathology.

-       Page 218: An update on the recent variants of urothelial carcinomas (with both the micropapillary and nest variants included).

-       Page 234: For those of us still grappling with E-cad IHC (nuclear vs membranous expression) and the molecular/cellular explanations, this paper is the answer with nice graphic illustrations of the pathways. The value of E-cad in PST, RCC and Merkel cell tumors is also addressed.


Archives of Pathology & Laboratory Medicine, Vol. 132, No. 7, July 2008

-         Pages 1055-1149:   An excellent symposia of a review of pulmonary neoplasias: neuroendocrine, IHC, preneoplasias, pediatric, sarcomatous, pleural tumors, and histologic disorder are presented separately with excellent photomicrographs. An a superb overview of under-, over- and mis-diagnosis of lung tumor (by our Kelly Butnor) is also present.

-   Page 1182: Protocol for colorectal cancer examination: A must review for all of us who sign out colorectal carcinomas.


June 2008



American Journal of Surgical Pathology, Vol. 32, No. 6, June 2008

-   Page 799:  Previously visited by the Mayo, small pockets of families with germline E-cadherin (CDH1) mutation are the focus of this study (from Stanford).  These authors grossed in the entire gastrectomy specimens removed prophylactically to better understand the precursor lesions of signet ring cell carcinoma in this setting.  Not surprisingly, superficial intramucosal signet ring carcinoma was demonstrated.  Interestingly, and more importantly, the majority of these foci were in the proximal third of the stomach, encouraging GI physicians to sample these areas when screening families with E-cad germline mutations.  Both E-cad and β-catenin were negative in tumor cells.

-   Page 835:  For the Dermies:  A nice clinicopathologic distinction between subungual melanoma and lentigo. 

-   Page 851:  Partial atrophy (PA) of the prostate gland is probably overcalled as ASAP in general practice.  This study highlights the important morphologic distinctions between partial atrophy (pale cytoplasm, ruffled cytoplasmic border, minimal nuclear enlargement, small nucleoli and patchy/fragmented basal cells on IHC, which may even be absent) and adenocarcinoma (basophilic cytoplasm, straight luminal borders, large nuclei/nucleoli and negative basal cells).  Note that PA may have weak-moderate p504 immunoreaction.  Hence, morphology trumps!

-   Page 858:   The morphologic distinction between metastatic melanoma to the GIT and primary clear cell sarcoma may be almost impossible given the potential considerable overlap.  Hence, the history of previous melanoma elsewhere and resorting to FISH analysis for t(12;22) EWS/ATF1 may be the only way to go!

-   Page 867:  We have previously observed in these series that asymptomatic microscopic GISTs may be present in about 10-30% of GEJ resection specimens.  In fact, up to 20% of proximal stomach specimens from autopsy have demonstrated minute sclerosing GISTs (<5 mm).  Outside of GEJ (the present study), they appear to be uncommon, harbor mutation at exon 11, and predominate in the muscularis propria.

-   Page 891:  Intravascular (angiotrophic) lymphomas are predominantly B-cell.  This study explores a series of large T-cell or NK-cell lymphoma with a unique intravascular pattern.

-   Page 899:  Due to recent law suits, the usual supply of p16 is rapidly dwindling and will soon (very soon) only be available in kit form.  Alternative ProExC (comprising TOP2A and MCM2; topoisomerase II alpha and minichromosome maintenance protein; unbundling of DNA before replication and a cell proliferation maker, respectively) appears to deliver similar nuclear distribution patterns to LSIL and HSIL as p16/MIB1.

-   Page 913:  Epithelial-myoepithelial carcinoma of the salivary gland is rare (although I saw several in Africa).  This small series of six cases from Asia shows these tumors with sebaceous differentiation. 

-   Page 924:  Epithelioid hemangioendothelioma (EHE) of soft tissue (so-called intermediate grade) may still metastasize.  This study of 49 cases provides risk stratification criteria: >3 mitoses/50 hpf and tumors >3 cm offer the worst prognosis (~60% 5 yr survival).  The site, necrosis, spindling of tumor cells and cytologic atypia do not correspond with adverse effects.



-   Page 943:  With the advances in neoadjuvant treatment with breast sparing surgery, there is an increase in dermal/subcutis vascular proliferations (mean size 8 mm) averaging about six years out.  This study (revisits) the criteria (anastamosing lymphatic-type channels in dermis or vascular-type small irregular capillaries with invested pericytes) for diagnosis.  Endothelial atypia (large nuclei/nucleoli) appear to be prone to recurrence or rarely be precursor to angiosarcoma.





Modern Pathology, Vol. 21, No. 6, June 2008

-   Page 647:  Renal medullary carcinoma with rhabdoid features show loss of INI1 expression, akin to pediatric rhabdoid tumor, atypical teratoid/rhabdoid tumor and epithelioid sarcoma. 

-   Page 756:  Nuclear β-catenin immunoreactivity in endometrial stromal sarcoma/undifferentiated endometrial sarcomas helps to distinguish these tumors from uterine cellular leiomyomata.



American Journal of Clinical Pathology, Vol. 129, No. 6, June 2008

-   Page 886:  D2-40 (podoplanin) is diffusely positive in schwannoma (including the cellular variety) and epithelioid MPNST but negative in spindled MPNST, neurofibroma and spindle cell melanoma.  The ever expanding “specificity” of D2-40 (lymphatics, seminoma, mesothelioma, DF, hemangioblastoma, EHE of the liver, adrenal cortical tumors…)!

-   Page 894:  Another study demonstrating that TdT is immunoreactive in Merkel cell carcinoma (Mona, I always believed you!)

-   Page 899:  The ever expanding “specificity” of GPC-3 expression in neoplasms:  still useful for HCC (~65% positive), but about 10% of non-neoplastic liver and 16% of preneoplastic liver may also be positive.  Further, approximately 50% squamous cell carcinomas of the lung, 50% non-seminomatous germ cell tumors (especially YST) and 50% liposarcomas also react with GPC-3!



Journal of Pathology, Vol. 215, No. 2, June 2008

-   Page 145:  An exquisite study demonstrating that multifocal papillary thyroid carcinoma follows an intraglandular spread of a primary clone, rather than multi-clonal origin.  Subsequent acquisition of genetic defects may result in morphologic diversity.



Journal of Clinical Pathology, Vol. 61, No. 6, June 2008

-       Page 689:  ER continues to remain the most reliable predictive marker of breast cancer.

-       Page 707:  Loss of basal cell CK14 confers an increased risk of recurrence in sinonasal inverted papillomas.

-       Page 713:  How do you gross in radical prostatectomy specimens?



Histopathology, Vol. 52, No. 7, June 2008

-   Page 816:  CD117 expression in GI Kaposi’s sarcoma may lead to a potential misdiagnosis as GIST.  Remember that CD34 is positive in both tumors, whilst HHV8 does distinguish.



Human Pathology, Vol. 39, No. 6, June 2008

-   Page 846:  A timeous exploration highlighting the morphological and immunohistochemical distinguishing features between inflammatory myofibroblastic tumor (heterogeneous architecture and cytology, 40% ALK positive/FISH ALK gene rearrangement, and importantly a third being cytokeratin positive) and low grade myofibroblastic sarcoma (homogeneous increased cellularity with nuclear hyperchromasia and wide infiltrative growth pattern).  Both IMT and LGMS are α-SMA, MSA, Calponin and desmin (low level, 40%) immunoreactive.

-   Page 954:  Ureteral endometriosis usually presents with hydroureter and hydronephrosis involving the distal one-third of the ureter.



Archives of Pathology & Laboratory Medicine, Vol. 132, No. 6, June 2008

Neuropathology Update

-   Page 907:  Protocol for examination of CNS/spinal tumors.

-   Page 993:  A review of grading changes, new entities/variants/patterns in the updated WHO 2007 CNS tumors.  A must read for all who sign out neuropathology tumors. 









Dr. Kumarasen Cooper, MBChB

Department of Pathology

University of Vermont,USA


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