Case #1 Unforced Error 50 year old woman s/p renal transplant, with - PowerPoint PPT Presentation

5/26/2017 • Unforced error (LWL) Pitfalls in Gastrointestinal and Hepatic – A player makes an error that is not the result of an action by his/her opponent – The player has full control of his/her actions, but still makes a mistake Pathology • Forced error (LWL plus clinician) – The opponent hits a difficult shot and causes the player to miss – Succumbing to an impossible ball that can’t be returned • Errors from the stands Laura W. Lamps M.D. – Errors that I did not actually commit, but watched happen, and had good seats Godfrey D. Stobbe Professor of Gastrointestinal Pathology University of Michigan Department of Pathology Patient Safety Officer, Michigan Medicine Ann Arbor, MI Duodenal biopsy Case #1 Unforced Error 50 year old woman s/p renal transplant, with diarrhea 1

5/26/2017 Next day…………. • Clinician called and asked for CMV immunostain because he was sure patient had CMV (of note, this was on the requisition, but it’s on 98% of his requisitions, so I ignored it) • CMV immunostain grudgingly ordered CMV immunostain 2

5/26/2017 Mistakes Made Mistakes Made • Looked at cases too quickly • Looked at cases too quickly • Violated own rules of when to order special stains • Violated own rules of when to order special stains • Allowed irritability to cloud judgment • Corollary: Just because the person asking drives you nuts, doesn‘t mean what they are asking for is crazy 3

5/26/2017 Essentially Normal Bx in Immunocompromised Patient Don ’ t overlook Increased Are they severely apoptotic immunocompromised? epithelial cells spirochetosis, Is there another reason coccidians, or to worry? Giardia! No Yes CMV Adenovirus Get history, Done! consider GMS, CMV Utility of Special Stains in Evaluation of Big unexplained ulcer Biopsies for GI Infections • Monkemuller et al, AJCP 2000 Immunocompromised • HIV patients Patient • 28 months ? Elderly Patient • Sensitivity and specificity for CMV diagnosis on H&E were 97% Yes and 100% • AFB/GMS stains did not identify previously diagnoses infection in Yes No any patient • Long-term follow-up revealed no missed infections on H&E CMV CMV • Stains doubled cost ?HSV Get history, tailor workup to that GMS ?AFB 4

5/26/2017 Utility of CMV Stains in Evaluation of Biopsies from UC Flares • Kambham et al, AJSP 2004 • Case control study of UC patient with refractory disease • 25% of patients with refractory UC had CMV inclusions on immunostain • 60% of these had been missed on H&E • Recommend using CMV IHC in evaluation of biopsies in these patients CMV-poorly formed inclusions 5

5/26/2017 Lessons Learned Whatever it was, I didn’t do it. • Slow down • Don ’ t break own your own rules; you made them for a reason • Don ’ t allow irritability to cloud judgment/good patient care Case #2 Unforced Error 56 year old woman with abdominal pain, gastritis 6

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5/26/2017 Pseudo-Signet Ring Cells •Benign cells with signet ring morphology •Degenerative change associated with: • Ulceration/reactive gastropathy • Ischemia • C. difficile -associated pseudomembranous colitis Partial gastrectomy 8

5/26/2017 Autoimmune gastritis Pseudo signet ring cells in C. difficile infection- courtesy Dr. Wendy Frankel 9

5/26/2017 Real signet ring cells Can Stains Help? Mistakes Made • Didn ’ t put enough weight on the fact that all the atypical cells were • Cytokeratin • Both benign and malignant signet ring cells will be positive detached • Didn ’ t put enough weight on the fact that the largest nuclei were not • Exception: muciphages • Mucin that much larger than normal nuclei • Helpful if negative, not so if positive • Correlation with macroscopic appearance (doesn ’ t always help with • Reticulin • Maybe gastric cancer, though) 10

5/26/2017 Can Stains Help? • Proliferation markers • Maybe • Reactive processes can also be very proliferative • E-cadherin • Maybe • E-cadherin often decreased in signet ring cell carcinomas Muciphages Reticulin stain highlights basement membrane of glands From Hughes, Greywoode, and Chetty: Virchows Arch 2011;459:347-9 11

5/26/2017 Courtesy Dr. Wendy Frankel E-cadherin Pseudomembranous colitis Signet ring cell carcinoma Ki-67 Pseudomembranous colitis Chemical gastropathy E-cadherin-signet ring cell carcinoma Courtesy Dr. Wendy Frankel 12

5/26/2017 Is that a real Lessons Learned signet ring cell or a fake one? • Location of signet ring cells of paramount importance • Lamina propria vs. discohesive, detached • Four fine pathologists can all be wrong • Proliferation markers, reticulin, E-cadherin might have helped but not necessarily Case #3 Unforced Error 65 year old man with poorly defined gastric mass 13

5/26/2017 Diagnosis: Plasmacytoid Neoplasm • Very poorly defined (or so I’m told) • Gross description describes tiny bits • I worked in one of the largest myeloma centers in the world • CD138 +++++++++++++++++++++ • Kappa and Lambda have high background staining, not useful 14

5/26/2017 Two months later…….. Mistakes Made • Attend CME conference where John Goldblum • Should have known the literature better speaks about new GIST variants • Did not know all the vagaries of immunostains employed • Describes a strikingly plasmacytoid variant of GIST • Allowed context of where I worked to influence • Uh-oh. !@#$%!! differential Plasmacytoid (pleomorphic) GIST •Majority of GISTs are monomorphic •Small subset are pleomorphic •Myxoid/hyalinized stroma •Variant of epithelioid GIST •Some have very distinctive plasmacytoid features 15

5/26/2017 Immunostains will get you into trouble Immunostains will get you into trouble • DOG-1 positivity • CD117 • Non-mesenchymal • Plasma cells • Gastric adenocarcinoma • GIST • Acinic cell carcinoma of • Melanoma salivary gland • Neuroendocrine • Melanoma tumors • Rare mesenchymal • Thymic and other carcinomas • Synovial sarcoma • Kaposi’s sarcoma • MPNST • PEComa DOG-1 Molecular studies Hemminger and Iwenofu. Histopathology 2012;61;170-77. Immunostains will get you into trouble Lessons Learned • CD138 • Remove oneself from context before making final • Plasma cells • Plasmacytoid urothelial diagnosis carcinoma • Papillary thyroid carcinoma • Keep up with literature • Other plasmacytoid carcinomas and mesenchymal tumors • Understand your immunostains • Endometrium 16

5/26/2017 Case #4 Forced Error Solitary liver mass in young woman with “renal cell carcinoma” Zoe and Alys contemplate the pitfalls of immunohistochemistry. 17

5/26/2017 Frozen Section Conversation • LWL: What kind of renal cell carcinoma did she have? • Surgeon: The regular kind. • LWL: Clear cell? • Surgeon: Yeah. 18

5/26/2017 In my defense…….. Mistakes Made • LWL (looking at frozens of multiple spindled nodules on serosa of • Should have worked harder to find out history on bowel and stomach): This looks like a neurofibroma. our own • Surgeon: No way!! options in the differential diagnosis of “ renal cell carcinoma ” • Should have more strongly considered all the SILENCE………… • Surgeon: Huh. Maybe that explains the bumps all over him and his family. • Noncirrhotic liver…… Nodules in Cirrhotic vs. Noncirrhotic Livers • KC (looking at frozen of weird metastatic liver • NONCIRRHOTIC LIVER lesion): It says here that the patient had cancer in • Focal nodular the tail of the pancreas. Do you know what kind of • CIRRHOTIC LIVER hyperplasia cancer it was? • Regenerative nodule • Adenoma • HGDN • Nodular regenerative • Hepatocellular hyperplasia • Surgeon: The kind that is in the tail of the pancreas. carcinoma • Hepatocellular carcinoma • Mets 19

5/26/2017 HCC, well differentiated Normal HCC 20

5/26/2017 Quiz: RCC vs. HCC Quiz: RCC vs. HCC Quiz: RCC vs. HCC 21

5/26/2017 Helpful hint: put in more sections Quiz: RCC vs. HCC Differentiation Between HCC and Other Trabecular Neoplasms Feature HCC RCC ACC Clear Cells Yes Yes Yes Prominent vessels Common Common +/- - EMA + - Hepatocyte Antigen, + - - Arginase-1, etc. Inhibin, SF1 Negative Negative Positive PAX2 and PAX8 - + - Helpful hint: HCC, clear cell variant, Hepatocyte Antigen 22

5/26/2017 A few last minute IHC warnings • CD10 can stain HCC • PEComa can lose reticulin (but will be HMB45 positive) • Hepatocyte antigen can stain carcinoids, and neuroendocrine markers can stain HCC • Some adenocarcinomas can stain with HSA, but it ’ s still better than • HCC can stain with CK7 and CK20 and CK19 AFP Pulmonary adenocarcinoma: HSA+ What do you mean Lessons Learned that’s a watering can? It’s not a renal cell carcinoma? I • Always leave yourself a little wiggle room on difficult am shocked! cases • Most people have metastases rather than a new weird primary • Always treat unproven verbal information relayed by surgeon with healthy degree of skepticism • Morphologic pitfalls are even harder to deal with on frozen section 23

5/26/2017 Duodenal biopsy Case #5 Errors from the Stands 60 year old man with “refractory sprue” 24