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January 2018

Some interesting topics I learned from the abstracts of the Archives of Pathology and laboratory medicine, Jan 2018,  Vol 142, No 1.More in:http://www.archivesofpathology.org

-MSI status has been recognized as good px indicator and is predictive of poor response to 5 fluorouracil based chemo. MSI commonly shows a medullary type nested growth, mucinous adenoCa with signet rings  and prominent lymphocytic infiltration. Be careful in younger than 50 y/o, syncronicus or metacronicus or > 2 first degree or second degree relatives with Lynch.
-anti PD-1/PDL1 checkpoint block appears to be useful in MSI-high colon tumors, not in MSI stable tumors.
-Celiac disease in duodenum shows excess of 25 lymphos/100 epithelial cells. Adolescents with anti tTG antibodies greater than 10 times upper limit, positive endomysial antibodies and HLA-DQ2/DQ8 probably have Celiac disease but should be confirmed with duodenal bx.
-Follicular lymphomas duodenal type are positive for CD20, CD10 and and BCL2
-Do not use frozen to evaluate presence of tumor spread through alveolar spaces of lung cancer.
-Full thickness CK20 and strong p53 in the urothelium favor Carcinoma in situ of the bladder rather than reactive changes.
-Nuclear BAP1 immunostain lost may happen in malignant mesothelioma. Dx is supported by diffuse and strong nuclear and cytoplasmic calretinin,  nuclear WT1 stain, strong membranous podoplanin (D2-40). Claudin 4 strong membranous staining favor Carcinomas.  Focal MOC31 staining is possible in some mesotheliomas.
-Pax 8, a great marker for dx of metatatic RCC.
-In hypersensitivity pneumonitis peribronchiolar centrilobular fibrosis may bridge to another bronchiole or pleura, something uncommon in UIP/IPF. Vague not well formed granulomas are not always present. Overlying metaplastic bronchiolar epithelium is common.
-CD30 transformed cells in mycosis fungoides are also CD43+, a T cell process, important feature in differentiation of Hodgkin.  EBV+ and PAX5+ favor Hodgkin.

Some interesting topics I learned  in the Cancer Journal, Jan 2018, Vol 124 , Issues 1. More in http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0142;jsessionid=44C411B0BEC05F1C5FF49CFD3B63E98E.f02t01

-Recent studies adds to the evidence that chronic inflammation or proinflammatory diets are associated with CRC
-Althoug most HPV cancers are preventable, 5 years survival rate for penile and vulvar Ca is still high in USA, 47% for penile Ca and 66% in vulvar cancer.
-FOX2 transcription factor is commonly  somatically mutated in uterine Carcinosarcomas and likely a pathogenic driver gene in this tumor.
-HIV related HNSCC revealed a distinct patter of mutations compared with non HIV mutation, especially for TP53.
-Smoking does appear to be significantly associated with all major salivary gland cancers,  with the exception of mucoepidermoid Ca.
-5 years survival for HPV  related Ca in all locations is significantly superior in whites than black patients.

Some interesting topics in Human Pathology, Jan 2018, Vol 71. More in http://www.humanpathol.com/issues

-CD166 (ALCAM) is a type I transmembrane protin, a member of the Ig superfamily that regulate angiogenesis and immune response in normal cells. In cancer, this molecule is associated with neoplastic progression, invasion and mets. The expression of CD166 in malignant mesothelioma preditcts shorter survival.
-Kras mutation is common in invasive mucinous adenoca of the lung
-Hepatic small vessel neoplasm (HSVN) is a recently described vascular neo of adult liver, positive for CD31 and 34, distinctive in morphology of cavernous hemangioma, showing low to absent mitosis and low proliferation index (different to higher index in epithelioid hemangioendothelioma and angiosarc).

Some interesting topics in Modern Pathology, Jan 2018, Vol 31, Issue 1. More in
https://www.nature.com/modpathol/

-50% of advance melanomas harbor BRAF mutation. Targeted therapy is available. Molecular testing for BRAF is a priority. Discordance in BRAF mutation status between primary and metastatic lesion is known to occur. Resistance fo BRAF inhibitors is another known obstacle.
-Activating mutations of estrogen receptor alpha gene (ESR1) can cause endocrine resistance in metastatic breast tumor cells. Mutated cancers display strong estrogen receptor expression
-Neuroendocrine breast Carcinomas are a distinct subtype of luminal Carcinoma with low rate of PIK3CA mutations and aggressive clinical behavior.
-SOX2 silenced SCC of the esophagus are a minor but distinct malignancy with poor px. The SOX2 silencing is probably due to epigenetic hypermethylation.
-High PD-L1 expression is associated with adverse px in pulmonary SCC. Mediastinal lymph node mets are adequate for immunohistochemical assessment of PD-L1.
-Napsin A positive LCNEC of the lung is possible in adeno like LCNEC, a separate entity from adenocarcinoma with expression of neuroendocrine markers and more aggressive behavior.
-Young patients with pleural mesothelioma have likely history of mantle radiation, family history of breast Ca and lower rates of CDKN2a deletion than older patients. It is probably a distinc clinical entity.
-A FISH assay can be easily implemented to detect BRAF fusions in acinar type neoplasms of the pancreas. Good test  to identify patients suitable for targeted therapy to inhibit MAPK pathway activity.
-FISH for PRKACA rearrangement is a useful tool to confirm the dx of fibrolamellar Ca of the liver.

Interesting topics in the American Journal of Surgical Pathology, Vol 42, Issue 1. Jan 2018.  More in:
http://journals.lww.com/ajsp/Pages/default.aspx

In the urothelial Ca T1, involving the lamina propria on biopsy or thransurethral resection, the cutoff of > 2.3 mm is the best predictor of progression to muscularis prorpia.
-Gastric pathology of gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) involving gastric body/fundus and sparing the antrum are reported to be primarily fundic gland polyps and progress to adenoca of intestinal type. It is associated with proliferation of oxyntic glands high up in the mucosa involving the attenuated foveolar region around the gastric pits (hyperpoliferative aberrant pits). Dysplasia and adenocarcinoma in these lesions may follow the gastric pathway.
-Seromucinous hamartoma or epithelial adenomatoid hamartoma of sinunasal region contain some olfactory receptor cells in the seromucinous glands expressing CD56, neurofilaments and synaptophysin.
-A molecular study concludes that most Epithelial myoepithelial Carcinomas arose from ex PA. Progression to higher grade Epithelial myoepithelial Ca with intact PLAG1 and HMGA2 corrlate with presence of TP53, FBXW7 mutations, or SMARCB1 deletion.
-Most IFS show ETV6-NTRK3 gene fusions. Some cases lacking the fusion show BRAF rearrangements, possible in children and adolescents in axial locations.
-Study shows that WSI is noninferior to microscopy for primary dx in surgical pathology, including biopsies, resection, immunostains and special stains
-study shows that digital image reading times  compare favorably to glass slides for different organs and specimens with mean increase of 4 seconds/case.
-Tumor budding (small clusters of cells in the tumor stroma) 

and pTstage are the best predictors of disease free survival in colorectal Cancer
-Many cysts reported as hepatobiliary cystadenoma/cystadenocarcinoma are not MCN (do not show diffuse ovarian stroma type). MCN are uncommon  among resected hepatic cysts, occur more in females, left lobe
-Even unusual variants of mucoepidermoid (like Warthin like or ciliated with macrocystic spaces and tubulopapillary proliferations) harbor MAML2 fusions, clear link to the conventional MEC

Interesting topics of the American Journal of Clinical Pathology. Jan 2018, Vol 149, No 1. More in:https://academic.oup.com/ajcp

-CD163+ tumor associated macrophages infiltrating the epithelium are higher in high grade laryngeal dysplasia than low grade. The over-expression of Ki67 and cyclin D1 favor high grade dysplasia.
-11q gain/loss is not specific for Burkitt like lymphoma. It occurs in MYC positive Burkitt Lymphoma and Myc + HGBL
-Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (NEFVPTC) has been reclassified as Non Invasive Follicular thyroid Neoplasm with papillary like nuclear features. It is a lesion with extremely low metastatic potential and recurrence that probably requires only lobectomy.
-Nuclear SOX11 and TTF3 can be potentially used as dx markers in distinguishing indeterminate Solid Pseudopapillary Neo from their histologic mimickers.

Interesting topics in Cancer Cytopathology, Jan 2018,Vol 26, Issue 1. More in:
http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1934-6638

-PDL1 (programmed death cell ligand) is expressesed in macrophages, dendritic cells, fibroblasts and tumoral cells. PD1 (programmed cell death) binds PDL1 and is expressed in lymphocytes. Pembrolizumab is an inhibitor of PD-1. Avelumab is a PD-L1 blocking antibody.
-Immunohistochemistry for STAT6 is valuable in fine needle aspiration diagnosis of Solitary Fibrous Tumor.
-Well differentiated neuroendocrine neoplasm in the pancreas with elevated Ki67 proliferation rate > 20% have been shown to have and overlapping histology with poorly differentiated neuroendocrine carcinomas. Necrosis is a good indicator of poorly differentiated cases.
-Homozygous deletion of 9p21 by FISH and loss of BRCA1 associated protein 1 (BAP1) by immunohistochemistry are useful differentiating mesotheliomas from reactive mesothelial hyperplasia. Both markers combined yield a sensitivity of 77.8%
-Malignant urothelial cells in urine cytology with jet black chromatin (dark black)  are common and they can be diagnosed as positive for malignancy based also on irregular nuclear outline, increase cellularity (> 50 abnormal cells) and frequent necrosis.