Case presentations 04/10/ th Annual Seminar in Pathology Pittsburgh, PA, April 26-29, 2018
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1 25th Annual Seminar in Pathology Pittsburgh, PA, April 26-29, 2018 Case presentations Kiril Trpkov, MD FRCPC Department of Pathology and Laboratory Medicine 45 y/o male, pink tumor, looks funny! 1
2 2
3 Differential diagnosis A.Oncocytoma (weird) B. Chromophobe RCC, eosinophilic C. Maybe not a renal tumor?! D. Unclassified renal tumor (really have no clue!) PAX-8 SDHB 3
4 SDH deficient RCC vs. Oncocytoma ISUP Vancouver Classification of Renal Neoplasia Emerging/provisional entities Succinate dehydrogenase B (SDHB) mutation/deficient RCC Thyroid-like follicular RCC ALK translocation RCC Malaysia
5 Am J Surg Pathol 2014 (July) Mod Pathol 2014 (July a week after!) SDH deficient neoplasia PHEO/PGL syndrome type 4 SDH mutated PGL SDH deficient GIST SDH deficient pituitary adenoma All are SDHB negative by IHC = mutated mitochondrial complex 2 SDH deficient GIST Gill AJ. Histopathology 2018; 72, SD HC Electron t ransport chain Inner mitochondr ial membrane Co Q.. I l l.. Cyt C t IV S uccinate e- + KREBS cycle Fumarate ADP t v.. ATP 5
6 SDH deficient RCC 36 tumors from 27 patiens Younger adults Age 37y (range 14-76y) Oncocytoma-like Solid or nested growth Flocculent cytoplasm, Often low grade nuclei, Intracytoplasmic vacuoles, Focal cysts C-kit, panck, CK7 = typically negative! Vimentin mostly neg. (some pos.) SDHB negative on IHC Dysfunction of the mitochondrial complex 2 SDH germline mutation SDH deficient RCC Whole slide digital microscopy available at: ISUP Consensus Meeting on Adult Renal Tumors Vancouver 2012 / WHO 2016 Clear cell renal cell carcinoma Multilocular clear cell renal cell neoplasm of low malignant potential Papillary renal cell carcinoma Type 1 Type 2 Chromophobe renal cell carcinoma Collecting duct carcinoma Renal medullary carcinoma MiT family translocation renal cell carcinoma Mucinous tubular and spindle cell carcinoma Tubulocystic renal cell carcinoma Acquired cystic disease associated renal cell carcinoma Clear cell papillary/tubulopapillary renal cell carcinoma Hereditary leiomyomatosis and renal cell carcinomaassociated renal cell carcinoma Succinate dehydrogenase (SDH) deficient renal carcinoma Renal cell carcinoma, unclassified Papillary adenoma Renal oncocytoma 6
7 Grossly solid or cystic 7
8 High grade transformation in SDH deficient RCC!!! 8
9 High grade transformation in SDH deficient RCC Variant morphology in SDH deficient RCC SDHA deficient RCC Am J Surg Pathol
10 SDH deficient RCC summary Rare and unique type of RCC ( %) Loss of IHC for SDHB Dysfunction of the mitochondrial complex 2 SDH germline mutation Stereotypical morphology (great majority) May de-differentiate and metastasize 53 y/o female, solid and cystic renal mass Pink, solid and cystic (macro- and micro- ) 10
11 Hobnail cell lining, variable thickness of septae Diffuse eosinophilic growth Tight acinar growth Aggregates of histiocytes and lymphocytes, calcifications 11
12 Scattered aggregates of histiocytes and lymphocytes! Cytoplasmic 'stippling' (coarse granularity)!!! Cytoplasmic 'stippling' (coarse granularity)!!! 12
13 Cytoplasmic 'stippling' (coarse granularity)!!! Cytoplasmic globules with rim ('Leishmaniasis-like') Immunohistochemistry Pax8 AMACR CK20 CK20 CK7 CD117 13
14 Diagnosis Pink (eosinophilic) renal tumor (solid and cystic?) Differential Diagnosis: Oncocytoma Chromophobe RCC (eosinophilic) Epithelioid AML Papillary RCC (oncocytic) Clear cell RCC ( pink ) MiT RCC SDH deficient RCC 6 RCC: eosinophilic macrocystic morphology All in females, indolent clinical course! Am J Surg Pathol 2014;38: Tuberous Sclerosis-associated Renal Cell Carcinoma A Clinicopathologic Study of 57 Separate Carcinomas in 18 Patients Am 1Surg Patho/ 2014;38:
15 Eosinophilic macrocystic renal tumors sporadic (non TSC)? Several identical index cases identified in files from: University of Calgary (CLS) Cleveland Clinic Multiinstitutional search in large GU practices 16 cases Not included or recognized as provisional entity in ISUP Vancouver Classification! Am J Surg Pathol 2016;60: RCC sporadic (in non-tsc): Eosinophilic Solid and Cystic (ESC) All in females, indolent clinical course! Gross features Solid-cystic or solid All in females, majority no TSC! All single tumors 15
16 Clinical features Age: 57y (31-75y) Size: 5cm (median, 3.8) range cm Stage: 13 pt1 (pt1a - 9, pt1b - 4) 2 pt2 (1 pt2a; 1pT2b) 1 pt3a Left 7; right 9 Multinucleation and vacuolated cytoplasm Multinucleation and vacuolated cytoplasm 16
17 Basophilic, nested, insular growth pattern (focal) Other growth patterns (at least focal) Immunohistochemistry Pax8 AMACR CK 11/ , CK7 - immunoprofile 3/16 CK20 CK20 CK7 CD117 17
18 Abundant rough endoplasmic reticulum, accompanied by granular material Follow-up Available 14/16 patients 13/14 ANED One patient DOC (after 14 mo) Follow-up: Mean: 53 mo; median: 37.5 mo Range: 2 to 138 mo Am J Surg Pathol 2017;41: Frequent repetitive molecular features, different from other RCC 18
19 CN gains and losses CN gains and losses CN gains and losses 19
20 If you hope to find something truly novel you may as well find it! Eosinophilic Solid and Cystic (ESC) RCC Summary Novel tumor with generally indolent behaviour Two recent reports on metastatic tumors (2/60) Characteristic morphology, IHC (CK20+/CK7-) Frequent molecular karyotype changes stay tuned! Large predominance of females with sporadic ESC tumors Two patients described post-neuroblastoma ESC RCC - all you need to know! Females TSC and non-tsc CK20 J McKenney TM Good prognosis 20
21 U SCAP FOUNDATION \'41 I f/ U F O U N WHY SHOULD I BECOME A USCAP MEMBER? Discounted registration for the USCAP Annual Meeting (the world s largest gathering of pathologists at 5,000+) and other educational meetings. Eligible to receive travel grants to the USCAP Annual Meeting. A M B A S S A D O R S C o n n e c t i n g to Y O U R A c a d e m y 21
22 75 year-old male, bladder mass (BIOPSY) a. Urothelial neoplasm low malignant potential b. Low grade inverted urothelial Ca c. High grade inverted urothelial Ca (non-invasive) Patterns of growth of urothelial neoplasms Papillary (exophytic) growth, with or without invasion) Flat growth, with or without invasion Inverted (endophytic) growth, with or without invasion 22
23 Flat lesion ain t gonna be always like a pancake (early papillary lesions)! Patterns of growth of urothelial neoplasms Inverted (endophytic) urothelial growth Non-invasive Invasive Urothelial neoplasms with inverted (endophytic) growth Inverted urothelial papilloma Inverted UNLMP Inverted low grade UC Inverted high grade UC (+/- invasion) Papillary and inverted growth can coexist! 23
24 Inverted papilloma Inverted papilloma Inverted UNLMP Inverted UNLMP (IUNLMP) (focal confluent growth, minimal atypia) Inverted UNLMP 24
25 Maxwell eta/. Diagnostic Pathology (2015) 10:3 DOI / s13000-<l z A DIAGNOSTIC PATHOLOGY RESEARCH Open Access Long-term outcome of primary Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP) including PUNLMP with inverted growth Jay P Maxwellt, Cheng Wangt, Nicholas Wiebe, Asli Yilmaz and Kiril Trpkov Inverted UNLMP Inverted low grade UC Inverted high grade UC (non-invasive) 25
26 Inverted high grade UC (invasive) Criteria for diagnosis of invasion into lamina propria Invading epithelium Single cell infiltration Stromal response Retraction artefact Finger-like projections Irregular nests Absent basement membrane Invasive component morphologically different Inflammation Desmoplasia or sclerosis Myxoid stroma Absent stromal response 26
27 Cancer with atrophic features (atrophic cancer pattern) 27
28 Cancer with atrophic features (atrophic cancer pattern) Cancer with atrophic features (atrophic cancer pattern) Cancer mimicks benign Deceptive patterns Atrophic 28
29 CK 5/6-AMACR 29
30 ' f ' 04/10/2018 Pseudohyperplastic cancer pattern I Ị..,'. ';....,.,, 30
31 Foamy (xanthomatous) cancer (AMACR negative in ~30%) CK 5/6 AMACR 31
32 Microcystic cancer (variant of pseudohyperplastic and atrophic) Yaskiv et al. Am J Surg Pathol 2010; 34: Microcystic cancer (variant of pseudohyperplastic and atrophic) CK 5/6-AMACR 32
33 Cancer or PIN? Cancer or PIN? 33
34 PIN-like cancer Cancer mimicking benign Deceptive patterns (false negative): Atrophic Pseudohyperplastic Foamy (xantomatous) Microcystic PIN-like Benign mimicking cancer (false positive) 34
35 Cancer? ATYPICAL (ATYP), suspicious? Not sure? How many glands for cancer diagnosis? Only one? If around a nerve (PNI) Appropriate morphology Confirmatory immunos! Depends on the features Location, immunos Three reasonable minimum! Algaba et al. Cancer 1996; 78:
36 HMWK-AMACR 1. Cancer? 2. PIN? 3. ATYP? PIN-ATYP PIN with adjacent atypical glands (outpouching/tangential PIN sections vs. microfocus of cancer) - Repeat biopsy as in ATYP (cancer rates 40-50% ) CK 5/6-AMACR 36
37 Atypical Glands, Suspicious (ATYP) ATYP glands can be: Small Large Cribriform ATYP, suspicious general term for all! Atypical small acinar proliferation (ASAP) ATYP Glands, Suspicious Not an entity, but diagnostic uncertainty not enough glands or diagnostic features glands disappear on deeper levels immunos did not work (as expected) pathologist not brave (or experienced) enough Work-up with immunos and deeper levels Consultation - intra or extra-departmental If found in up to 5% of all biopsies OK! Immunos and deeper levels if uncertain about the Dx 3 Initial levels Immuno 3 Deeper levels 37
38 Use immunos to support H&E diagnosis not to make it! HMWK AMACR ATYP Glands, Suspicious (ASAP) Sign out with comment/note suspicious Insufficient findings for definite diagnosis Recommend repeat biopsy (3 months) If repeat negative close follow-up Additional biopsies as necessary Cancer usually detected on 1 st or 2 nd biopsy Increased sampling from atypical sites Improves diagnostic yield on repeat biopsy If you want absolute certainty If you want a profession where everything is certain - better give up medicine! Sir William Osler ( ) 38
39 A. pt2 B. pt3 C. I don t know D. Not in the TNM Seminoma in the hilar paratesticular tissue; Stage? TNM classification of testicular GCT 7 th edition ptnm pathological classification pt Primary tumour ptx pt0 ptis pt1 pt2 pt3 pt4 Primary tumour cannot be assessed (See T primary tumour, above) No evidence of primary tumour (e.g. histologic scar in testis) Intratubular germ cell neoplasia (carcinoma in situ) Tumour limited to testis and epididymis without vascular/lymphatic invasion; tumour may invade tunica albuginea but not tunica vaginalis Tumour limited to testis and epididymis with vascular/lymphatic invasion, or tumour extending through tunica albuginea with involvement of tunica vaginalis Tumour invades spermatic cord with or without vascular/lymphatic invasion Tumour invades scrotum with or without vascular/lymphatic invasion Several changes in AJCC/TNM 8 th edition Tunica albuginea (TA) and tunica vaginalis (TV) TV TA 39
40 "...through tunica albuginea with involvement of tunica vaginal is"? Tumor perforates through TV TV invasion is rare! Testicular Hilum?? Extratesticular extension of GCT preferentially occurs in the hilum 40
41 Testicular hilum Hilar soft tissue Rete testis Rete testis involvement: pagetoid pattern Always report pattern of spread! Rete testis invasion: direct/ stromal pattern AJCC 8 th edition pt1 and pt2 pt1 TU limited to testis (including rete testis invasion) without LV invasion pt1a <3cm; pt1b >3cm ONLY for seminoma! pt2 TU limited to testis (including rete testis invasion) with LV invasion - OR - Tumor invading hilar soft tissue or epididymis or penetrating visceral mesotelium +/- LV invasion 41
42 Rete testis Vascular invasion If you don t sample the hilum, you will not see the hilar invasion! Hilar soft tissue is now pt2 (AJCC 8 th edition) Invasion into hilar soft tissue Invasion into epididymis (now pt2) Direct invasion into spermatic cord (pt3) 42
43 Spermatic cord with lymphovascular invasion only pt3 Thank you! 43
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