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September 2017


Great review of Immunostains in Archives of Pathology with many important markers. Some interesting things I learned:

-Strong and diffuse STAB2 expression in colorectal adenoCa vs patchy and weak expressions in small intestine. Mucinous cystadenoma of the ovary shows negative SATB2 staining.
-Her2 for gastric Ca: 0 (negative), 1+ (faintly perceptible membranous), 2+ (weak complete, basolateral or lateral membranous reactivity), 3+ (strong complete, basolateral or lateral membranous).
-This issue has and excellent interpretation of all combinations for MLH1, PMS2, MSH2 and MSH6 with all recommendations including MLH1 methylation test, germ line testing and other genetic testing.
-HCC: Glypican-3+, Glutamine synthetase strong and diffuse, diffuse sinusoidal pattern of CD34, enhanced canalicular pattern of clusterin.
-Pax8 in GI tract indicates possible origin in pancreas, duodenum or rectum.
-Ki67 in pancreatic neuroendocrine: Low grade <3%, Intermediate grade 2-20% and High grade > 20%
-TFE3+ in MiT family present in translocation RCC.
-Oncocytoma is focally positive for CK7, important differential with chromophobic RCC (negative). Papillary RCC shows strong CK7+ and Racemase+
-Ca in situ of the bladder: full thickness CK20 positivity
-Bladder Urothelial Ca positive for high molecular weight keratin, p63 and GATA3
-OCT4 positive in embryonal Ca, negative in yolk sac. Glypican 3 opposite staining pattern (positive in Yolk sac, negative in embryonal Ca).
-p40, more specific than p63 for lung SCC.
-ALK, ROS1 and EGFR can be evaluated by immunohistochemistry
-Profile for lung sclerosing pneumocytoma: AE1/AE3 positive, TTF1+, neg CK7
-Mammary analogue secretory Ca in parotid is looks like low grade breast Ca with focal areas resembling low grade DCIS. IHC profile is CK7+, STAT5a+. Confirm with ETV6-NTRK3 by FISH.
-Mantle Cell Lymphoma is SOX11 positive

Archives of Pathology and Laboratory Medicine, Sept 2017, Vol 141, No 9


Some interesting concepts I learned in the American Journal of Clinical Pathology issue, Sept 2017:

-A study in California shows higher positivity in Her2 with higher tumor stage or grade, larger tumor size, ER negative, younger patients or lower socioeconomic
-PD-1 and PD-L1 are highly expressed in small intestine Adenoca. PD-1 pathway should be evaluated for the treatment.
-Most IgG4 monoclonal plasma cell proliferations are unrelated with IgG4-RD
-CD200 is a new sensitive marker  for neuroendocrine neoplasms.
-Aberrant muclear B catenin and absent staining for CD34 are usuful studies to diagnose breast fibromatosis. Lesional cells are CD34 negative, adjacent normal stromal cells are CD34 positive.
-Thyroid tumors with signet ring cells: most are benign (follicular adenomas), some NIFTPs, rarely secretory carcinomas of the thyroid (signet ring cells with eosinophilic inclusions)
-With NFITPs, reducing the threshold for adequacy from 60 to 10 benign follicle cells without atypia or Hurthle cells change lead to a nonsignificant decrease in the risk of malignancy of a benign aspirate.
-CK17 is a powerful specific and sensitive marker  for HGSIL, also expressed in most cases of invasive endocervical and in situ endocervical adenoca. In benign glands, CK17 cells only present in  subcolumnar reserve cells. In Adenoca epithelial cells are CK17+

American Journal of Clinical Pathology, Sept 2017, Vol 148, No 3.


Two interesting concepts I learned in the issues of Cancer, Sept 2017:

-MLH is a syndrome of severe persistent immune activation due to dysregulation secondary to reumathologic, infectious or malignant conditions (may occur in 1% of patients with hematologic malignancy). It is associated to poor, less than 2 months survival. If early detected may be treated with immunosuppressive agents.
-TAF1 is a novel gene candidate for clear cell endometrial Cancer.

Cancer, Sept 2017. Vol 123, Issue 17 and 18


Some interesting concepts I learned in the issue of Cancer Cytopathology, Sept 2017:
-Parathyroid nodules may be challenging in the differentiation of thyroid lesions. They may present with oncocytic pattern, like follicular lesion of undetermined significance or with nonspecific endocrine clusters. PTH immunoassays aid in distinguishing as well as molecular studies or sestamibi scans.
-Reclassification of NIFTP decreases the PPV of the Afirma Gen expression classifier. It raises concerns over reliance on suspicious Afirma Gen results by clinicians to justify total thyroidectomy.
-The category of NIFTP category does not appear to affect significantly the rate of Malignancy for  the positive for malignancy cytology category
-The Aperio whole slide scanner and the Panoptiq imaging system are both suitable for cytopath screening and interpretation.
-Digital image analysis supports a nuclear to cytoplasmic ratio cutoff value of 0.5 for atypical urothelial cells.
-EUS guided thranbronchial needle aspiration may pic additional malignant lymph nodes missed by PET.

Cancer Cytopathology Sept 17, Vol 125, Issue 9


Some interesting concepts I learned in the issue of Diagnostic Cytopathology, Sept 2017:

-Metastatic tumors diagnosed by CT guided biopsies or EUS guided (with ROSE) are most commonly from lung, followed by renal and GI malignancies.
-Rhabdo is the most common sarcoma metastasing to lymph nodes followed by Synovial Sarcoma. Rarely mets are leiomyosarcoma, epithelioid sarcoma, liposarcoma, MFH, Ewing/PNET.
-Intraoperative frozen section is not supported for FNA Bethesda II, III, IV and VI. It is of value for nodules with Bethesda I and V interpretation.
-Urinary tract washings with atypical urothelial tissue fragments are significantly associated with urothelial Ca.
-Cystic major salivary gland lesions are rare and challenging to diagnose on FNA due to low cellularity. Specificity is high but sensitivity low, making clinical and radiologic correlation imperative.
-Mylan classification for Salivary gland cytopath include following categories: non diagnositic, non neoplastic, benign neoplasm, Neoplasm of undetermined malignant potential, suspicious of rmalignanty or malingnant.

Vol 45, Issue 9, September 2017


Some interesting concepts I learned in the issue of International Journal of Gyn Path, Sept 2017:

-Endometrial carcinomas with AR expression showed increase survival and late disease recurrence.
-Expression of  p16, p53 and PAX8 in both epithelial and stromal component of Carcinosarcomas (MMMT)  support the monoclonal theory of tumorigenesis.
-AR, ER and PR are more commonly expressed in Low grade ESS than high grade.
-Extraovarian unclassifiable malignant sex cord stromal tumor are rare poorly diff tumors involving pelvis, peritoneum and omentum.
-Degree of epithelial proliferation, autoimplants, adenofibroma pattern and eosinophilic cells are important features to report in the ovarian serous borderline tumors.
-Micropapillary pattern in Endocervical adenocarcinoma related with high rate of mets. Survival also worse in diffuse destructive tumors.
-Expression of p16 may not be a predictor of HSIL risk in vulvar LSIL. Vulvar LSIL appears to behave different from othe LSIL in other lower anogenital sites.

International Journal of Gyn Pathology, Vol 36 , Issue 5.


Some interesting concepts I learned in the issue of Journal of Clinical Pathology, Sept 2017:

-Use of Gleason grade Groups (GG) described by Epstein is of px value in Asian men: 1 (GS < 6), 2 (3+4), 3 (4+3), 4 (4+4 or 5+3 or 3+5) and 5 (9 or 10 score).
-Microvessel density (MVD) is and independent px factor in HER2 subtype of breast Ca.
-Distinciton between plasmablastic lymphoma and plasmablastic myeloma is difficult. Important factors to support Lymphoma are the positive EBV in situ hybridization, presence of lymphadenopathy, oral mass and absence of myeloma in clinical, lab and radilogic findings.
-Accelerated methods with brief fixation enable same day breast Ca dx with reliable ER, PR, Her2 and E Cadherin.

Journal of Clinical Pathology Vol 70, Issue 9


Some interesting concepts I learned in the issue of Modern Pathology, Sept 2017:
-High risk HPV related oropharyngeal SCC have a more favorable px than HPV negative cases. The recommended cut off is 50% of the staining.
-Oligomonocytic CMML represent probably the early dysplastic phase of CMML. They both appear to be the same entity expressing mutations in ASXL1, TET2 and SRSF2 mutation
-3/11 of the following predictors  improve the pathology performance detecting malignancy in bile duct brushings: 3 dimensional clusters, pleomorphism, high N/C ratio, nuclear irregularity, hypercellularity, discohesion, chromatin changes, vacuoles, prominent nucleoli, molding and 2 cell population.
-in Colorectal cancer tumor budding is assess in the invasive front of the tumor with the presence or single tumor cell or cell cluster (4 cells or less). It is an independent predictor of lymph node mets in pT1 Ca and survival in Stage II
-PAX 7 immnostain in Ewing sarcoma is a useful marker. EWSR1 fusion proteins mediate the PAX7 expression.

Modern Pathology, Sept 17, Vol 30, Issue 9


Some interesting concepts I learned in the issue of American Journal of Surgical Pathology, Sept 2017:
-Double or triple hit large B cell lymphomas involve rearrangements in Myc2, BCL2 and BCL6. Amoung the double or triple hit Large B cell lymphomas, MYC+BCL2 + double expresors had the worse px.
-Malfunction in the main pancreatic duct and common bile duct allow reflux or pancreatic juice to the gallbladder creating a cholecystopaghy with mucosal hyperplasia, elongated folds and villoglandular proliferations pushing into muscle (Rookitansky-Aschoff). This may create a chemical (rather than inflammatory) model of Carcinogenesis in the gallbladder.
-WNT pathway gene mutations are involved in the development of dysplasia in SSA/Ps (sessile serrated adenoma/polyps). MLH-1 deficient and MLH1 retained SSA/Ps with dysplasia exhibit distinct mutation profiles of WNT pathway genes.
-Strong diffuse GATA3 favors a dx of sarcomatoid/desmoplastic mesothelioma over metastatic sarcomatoid carcinoma of the lung. Complete absence of GATA-3 staining is evidence against a dx of sarcomatoid/desmoplastic mesothelioma.
-Spindle cell lipoma is common in young women in unconventional locations. They show  bland spindled cells, ropey collagen, myxoid matrix and adipocytes. All are CD34+, desmin neg, commonly ER positive and exhibit loss of p16 epression. Many show RB1 loss by FISH
-Residual pure intralymphatic breast Ca following neoadjuvant chemotherapy is a feature indicative of poor outcome.

American Journal of Surgical Pathology. Vol 41, Issue 9