Disclosures I have nothing to disclose Practical Gastrointestinal - PowerPoint PPT Presentation

5/24/2013 � Disclosures I have nothing to disclose Practical Gastrointestinal (and Liver) Pathology Noon Slide Session Ryan M. Gill ryan.gill@ucsf.edu 415-476-3212 Colonic Adenomas – Summary Diagnostic Issues � Colonic Adenomas � “Intramucosal adenocarcinoma” confusion � Epithelial misplacement/pseudoinvasion vs pT1 � Hepatocellular Adenomas � Lymphovascular invasion � Risk stratification � Unusual cell clusters � IBD dysplasia 1 �

5/24/2013 � “intramucosal “intramucosal adenocarcinoma” adenocarcinoma” � Tumor cells extend through BM into lamina propria, but not through muscularis mucosa � Single cells, abortive gland formation, marked sheet like growth � No metastatic risk 2012 Recommendations for Pseudoinvasion Screening No polyps 10 years � Misplaced (herniated) epithelium in submucoa � Small (<10 mm) HPs in rectum or sigmoid 10 years � Most often in pedunculated polyps in sigmoid (~ 86%) � 1–2 small (<10 mm) tubular adenomas 5–10 years � � Usually > 1 cm 3–10 tubular adenomas 3 years � � Well circumscribed crypts, lobular architecture >10 adenomas <3 years � � Surrounding rim of lamina propria One or more tubular adenomas ≥ 10 mm 3 years � One or more villous adenomas 3 years � No desmoplasia � Adenoma with HGD 3 years � Hemorrhage/hemosiderin deposition in stroma � Invasion in a pedunculated adenoma 0.5-1 year � Differential diagnosis – Invasive adenocarcinoma, Inadequately removed or large sessile adenoma � mucinous adenocarcinoma, localized colitis cystica 2-6 months profunda/prolapse 2 �

5/24/2013 � Colectomy? Risk for pT1 tumors Traditional pT1 treatment decisions: � Residual local disease (20% in R1 cases) � Colectomy for unfavorable histology � Lymph node metastasis (10-15% in high risk cases) (pedunculated), invasion in sessile polyp, invasion � Distant metastasis (? Increased risk in poorly beyond stalk into bowel wall differentiated tumors) � Unfavorable histology (poorly differentiated, LVI, � Risk is balanced against operative morbidity (age, <1-2 mm from margin), 20-43% recurrence +/- LN site, comorbidities) and mortality mets Risk Parameter Table ( adapted, USCAP 2013, Prof Risk IBD associated dysplasia CRC Kieran Sheahan ) Risk Depth of tumor invasion from muscularis mucosa = 0.8 Low Sporadic Adenoma/ Adenoma-like DALM Low mm Non-adenoma DALM >40% Tumor width = 2.8 mm Low Low grade flat dysplasia 20%* Kikuchi level = Sm2 Low High grade flat dysplasia 20-50% Radial margins = uninvolved Low Indefinite for dysplasia 9% (in 5 Deep margin = negative, >1 mm Low yrs) Tumor budding level is low Low PRELIMINARY DATA Lymphovascular invasion present (1 vein only by elastic High SSA-like changes (n=29) 0% stain) Site = rectum High ? TSA-like changes (n=30) 77% Morphology = Sessile Lesion High ? “Hyperplastic polyp with cytologic atypia” (n=19) 53% 3 �

5/24/2013 � Low grade dysplasia in Hepatic Adenomas – Crohns Diagnostic Issues � HCA vs FNH � Subtyping of HCA � Risk of HCC Well Differentiated Lesion Adenoma (HCA) Variants Algorithm History of a mass -> 1 H&E, 1 reticulin, and 8 unstained HNF1 α -inactivated HCA � on first cut � Hallmark: Fatty change Portal tracts? � � Yes β -catenin mutated HCA � Atypia/reticulin abnormalities � Hallmark: Increased risk for HCC • Yes � early HCC vs partial sampling of HCA -> GS, SAA, BC, LFABP, CD34, GPC3 Inflammatory adenoma • No � Mass not sampled or FNH-like lesion -> GS � No � Hallmark: Obesity/metabolic syndrome association � Well differentiated hepatocellular lesion • FNH features present, no atypia/reticulin abnormalities (Variant 4 + ?) – Yes – FNH vs Inflammatory variant HCA -> GS, SAA, BC � Hallmark: No specific trait – No – HCA, requires stains for further subclassificaiton -> GS, SAA, BC, LFABP – If atypia/reticulin abnormalities, w/u early HCC as above 4 �

5/24/2013 � Linda Ferrell MD Ryan Gill MD, PhD Sanjay Kakar MD Grace Kim MD Rageshree Ramachandran MD, PhD Hepatocellular Adenoma diagnosis � Cases: � HCA, inflammatory variant � Focal nodular hyperplasia � HCA, HNF1 alpha inactivated variant � HCA, beta catenin mutated variant � HCC arising in HCA 5 �

5/24/2013 � Current Risk Stratification Current Risk Stratification � Low risk (no resection needed) – 40% of cases � “High risk”/”unfavorable histology” (… it depends) – 60% of cases � No LVI � LVI present, poorly differentiated and tumor � Moderately to well differentiated budding present warrants immediate surgery if � No tumor budding possible � One or two risk factors present = uncertainty! � In high risk cases that go to surgery ~80% of patients will have no residual tumor or metastasis Risk Factor Quantitation Pseudoinvasion � Semi-quantitative � Haggitt level (0-4) - pedunculated � Kikuchi level (sm1-3) – non-polypoid � Quantitative � Depth of tumor invasion � Tumor width � Distance from resection margin 6 �

5/24/2013 � Pseudoinvasion? Colonic Adenoma Sinusoidal Infiltrates � Cases � Case � Tubular adenoma with pseudoinvasion � Primary DLBCL, sinusoidal predominant � Localized Colitis Cystica Profunda/prolapse � Tubular adenoma with invasive adenocarcinoma � Colorectal dysplasia (IBD associated) 7 �

5/24/2013 � Sinusoidal Infiltrate Differential Diagnosis Lymphoid neoplasms Reactive infiltrate Sinusoidal distention/cells pile up Single mature lymphoid cells Cytologic atypia Mixed acute and chronic inflammation Aberrant T-cell antigen loss Viral type injury Hemophagocytosis EBER in rare B-cells EBER positive tumor cells Other liver disease findings Geographic necrosis TCR PCR negative Primary Hepatic Lymphoma Sinusoidal Involvement Mature B-cell neoplasms Mature T- and NK-cell neoplasms � Rare diagnosis (0.06% of NHL) Burkitt lymphoma Adult T-cell leukemia/lymphoma � Wide age range, M:F (2:1) B-cell prolymphocytic leukemia Aggressive NK cell leukemia � Hepatomegaly is common CLL/SLL Anaplastic large cell lymphoma � Mild transaminitis may be present, jaundice rare Diffuse large B-cell lymphoma Angioimmunoblastic T-cell lymphoma � Solitary mass, multinodular, or diffuse Follicular lymphoma EBV positive LPD of childhood Hairy cell leukemia Hepatosplenic T-cell lymphoma � DLBCL, Burkitt lymphoma, MALT lymphoma, LPL, Lymphomatoid granulomatosis Other γ / δ T-cell lymphomas Follicular lymphoma, and PTCL most common Lymphoplasmacytic lymphoma Mycosis fungoides/Sezary syndrome Mantle cell lymphoma Peripheral T-cell lymphoma, NOS Marginal zone lymphoma (MALT) PTLD PTLD T-cell LGL leukemia 8 �

5/24/2013 � CD20 Atypical Sinusoidal Infiltrate Atypical Sinusoidal Infiltrate? Pitfalls � Ductopenia due to lymphoma � EBV hepatitis � Atypical lymphoid infiltrates in a hepatocellular lesion 9 �

5/24/2013 � Hepatocellular Adenoma Key Points Inflammatory Variant � Reactive infiltrates are common in the liver, most are benign � Correlate with background GI and liver disease findings � Cytologic atypia an important clue � Immunohistochemical evaluation � Molecular testing as needed 10 �

5/24/2013 � Duodenum Benign MALT CD20 CD3 11 �

5/24/2013 � CD10 BCL6 CD21 BCL2 12 �

5/24/2013 � Small Intestine Follicular CD20 lymphoma CD3 CD10 13 �

5/24/2013 � BCL6 CD21 CD43 BCL2 14 �

5/24/2013 � Low grade (grade 2, scale 1-3) 15 �

5/24/2013 � Approach to Sinusoidal Infiltrates � Sinusoidal infiltrate cell type? � Out of proportion to primary liver disease? � Cytologic atypia? � Immunophenotype? � Molecular testing if still uncertain. Sinusoidal Infiltrate – Cell Sinusoidal Infiltrate – Cell Type Type � Granulocytes/ immature myeloid � Granulocytes/ immature myeloid � MPN � Macrophages � Leukemoid reaction � Surgical effect � Blasts � Macrophages � Mature lymphoid cells � Blasts � Mature lymphoid cells 16 �

5/24/2013 � Myeloid Proliferation related to Down Syndrome Extramedullary Hematopoiesis in Transient Abnormal Myelopoiesis Polycythemia Vera MPN/MDS Extramedullary Hematopoiesis in Polycythemia Vera Megakaryocyte Erythroid Precursors 17 �

5/24/2013 � Sinusoidal Infiltrate – Cell CD163 Type � Granulocytes/myeloid � Macrophages � Immunologic (HLH) � Infectious ( Histoplasmosis, Cryptococcus , visceral leishmaniasis) � Storage disorders (Gaucher disease, Niemann- Pick disease, etc) � Blasts � Mature lymphoid cells Gill RM et al. Macrophage Infiltrate, Ch 18 Liver Pathology, eds Linda Ferrell and Sanjay Kakar, Demos 2011 Organisms Niemann-Pick Disease Gill RM et al. Macrophage Infiltrate, Ch 18 Liver Pathology, eds Linda Ferrell and Sanjay Kakar, Gill RM et al. Macrophage Infiltrate, Ch 18 Liver Pathology, eds Linda Ferrell and Sanjay Kakar, Demos 2011 Demos 2011 18 �

5/24/2013 � Sinusoidal Infiltrate – Cell Amastigotes of Visceral Leishmaniasis Type � Granulocytes/myeloid � Macrophages � Blasts � ALL � AML � CML blast crisis � Mature lymphoid cells Gill RM et al. Macrophage Infiltrate, Ch 18 Liver Pathology, eds Linda Ferrell and Sanjay Kakar, Demos 2011 Suspicious Sinusoidal Infiltrate Lymphoblasts 19 �