ACCME/Disclosures. Everything is spindle - how far can we go with limited FNA material? Everything is spindle how far can we go? Everything is spindle

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1 ACCME/Disclosures The USCAP requires that anyone in a position to influence or control the content of CME disclose any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their spouse/partner have, or have had, within the past 12 months, which relates to the content of this educational activity and creates a conflict of interest. P.E. Wakely, Jr., M.D. declares he/she has no conflict(s) of interest to disclose. Everything is spindle - how far can we go with limited FNA material? USCAP Annual Meeting Seattle, WA March, 2016 P.E. Wakely, Jr., M.D. The Ohio State University Wexner Medical Center Columbus, OH U.S.A. Everything is spindle how far can we go? Not That Far. Everything is spindle how far can we go? Not That Far. All The Way. 1

2 Barriers To FNA Dx ST Lesions absent/difficult to appreciate features procedural performance cytomorphologic overlap sampling error tumor heterogeneity necrosis limited experience/exposure to soft tissue tumors lack of architectural features spatial relationships patterns architecturally defined fascicular storiform lobulated plexiform distinctive vasculature hemangiopericytomatous peritheliomatous hyalinized vessels hobnail endothelial cells tumor border infiltrative pushing capsule mitotic activity subtypes of Spindle Cell Lesions (SCL) Subtypes of Spindle cell lesions (SCL) with nuclear pleomorphism w/o nuclear pleomorphism with nuclear pleomorphism w/o nuclear pleomorphism w/o bkgd. elements w/o bkgd. elements w/o bkgd. elements w/o bkgd. elements with bkgd. elements myxoid/ chondromyxoid stroma fat other cell types inflammatory cells giant cells with bkgd. elements myxoid/ chondromyxoid stroma fat other cell types inflammatory cells giant cells with bkgd. elements myxoid/ chondromyxoid stroma fat other cell types inflammatory cells giant cells with bkgd. elements myxoid/ chondromyxoid stroma fat other cell types inflammatory cells giant cells 2

3 BENIGN Fibromatosis Schwannoma Leiomyoma Misc. Spindle Cell Lesions MALIGNANT GIST Synovial Sarcoma MPNST Misc. Spindle Cell Sarcomas Superficial - Plantar/ Palmar / Penile / Knuckle Pads Deep Abdominal (Desmoid) Extra-Abdominal Intra-Abdominal (Mesenteric/Pelvic Fibromatosis 3

4 fibromatosis normal connective tissue 4

5 Acta Orthopaed * 2006;77:92. Cancer 2007;111: 166. # cases FNA - Fibromatosis FNA = fibromatosis FNA = benign (51%) 26 (38%) FNA = malignant FNA = nondiagnostic 4 (5%) 4 (5%) 17 5 (29%) 7 (40%) 0 5 (29%) Fibromatosis [n=17]* susp. spindle cell lipoma [1] OSU data* (76%) 4 (24%) 0 0 spindle cell neoplasm [2] susp. IM hemangioma [1] *no ancillary testing *no ancillary testing 5

6 Fibromatosis [n=17]* Schwannoma yrs. actual FNA Dx fibromatosis [8] susp. fibromatosis [5] 76% spindle cell neoplasm [2] susp. spindle cell lipoma [1] susp. IM hemangioma [1] *no ancillary testing head & neck / flexor regions of extremities histopathology: Antoni A Antoni B Verocay bodies encapsulated, cystic change vasculature hyalinization S100, SOX10 + syncytial cluster 6

7 fibrillar, monotonous frayed edges schwannoma FNA = 58 v. non-schwannoma FNA = highlighted 5 morphologic features: high number of cell clusters few/no single cells pointed tip nuclei fibrillary stroma anisonucleosis if all 5 present sensitivity: 22% PPV: 81% specificity: 97% NPV: 68% Cancer. 2015; 123: 171. anisonucleosis 7

8 anisonucleosis schwannoma schwannoma fibromatosis Verocay bodies 8

9 Verocay body 9

10 Schwannoma[n=36]* *all primary Schwannoma[n=36]* *all primary actual FNA Dx schwannoma [30] 83%* # # 63% IHC susp. schwannoma [1] no IHC benign fibrous/ Sp C lesion [3] salivary gland neoplasm [1] benign fibrous/ Sp C lesion [3] salivary gland neoplasm [1] susp. spindle cell sarcoma [1] 0% IHC susp. spindle cell sarcoma [1] Neurofibroma [n=5]* misc. benign/l-g SC lesion/neoplasm (25) FNA diagnosis * benign (21/84%) atypical spindle cell lesion [n=1] NF/BNST [n= 3] susp. MPNST [n=1] malignant (4) DFSP (1) sarcoma, NOS (1) myxofibrosarcoma (1) susp. melanoma (1) *all primary; 4/5 no confirmatory IHC *all primary; no confirmatory IHC 10

11 benign/l-g spindle cell lesion/neoplasm (25) FNA diagnosis * benign (21/84%) malignant (4) DFSP (1) sarcoma (1) myxofibrosarcoma (1) susp. melanoma (1) SFT (10) fibroma (3) elastofibroma (2) hemangioma (2) perineurioma (2) spindle cell lipoma (1) myoepithelioma (1) tissue diagnosis palisading granuloma (1) fibrous histiocytoma (1) nodular fasciitis (1) spindle cell lesion (1) 45 y/o with 4.5 cm. L scapula mass *all primary; no confirmatory IHC 45 y/o with 4.5 cm. L scapula mass 45 y/o with 4.5 cm. L scapula mass elastin stain, smear elastin stain, smear elastofibroma, tissue 11

12 adults, yrs. GIST GIST most common gut mesenchymal tumor ~ 25% malignant spindle, epithelioid, pleomorphic (rare) immunoprofile: - CD34, CD117, DOG-1 Cytomorphology GIST GIST primarily spindle cell clusters & single cells bland stripped nuclei nuclear palisading (some cases) wispy cytoplasmic processes 12

13 GIST, parallel GIST DOG 1, CB 13

14 EUS-Guided FNA of GIST # cases DY (%) sens (%) location GIST [n=61] Sepe PS et al. Gastrointest Endosc. 2009;70: % stomach Hoda KM et al. Gastrointest Endosc. 2009;69:1218. Akahoshi K et al. World J Gastroenterol. 2007;13: NR 62.5% stomach % 81% stomach DY = diagnostic yield favor GIST [n=2] - primary, no CB non-diagnostic [n=1] spindle cell neoplasm [n=1] GIST [n=61] GIST [n=61] actual FNA Dx GIST [n=57] (93%) favor GIST [n=2] primary, no CB non-diagnostic [n=1] spindle cell neoplasm [n=1] actual FNA Dx GIST [n=57]* (93%) favor GIST [n=2] primary, no CB non-diagnostic [n=1] spindle cell neoplasm [n=1] 55 primary; 2 mets *56 confirmatory IHC 1 no IHC (met) 14

15 Leiomyoma [n=14] Leiomyoma [n=14] * esophageal/gej/ stomach * esophageal/gej/ stomach LM[n=8] (57%) susp. LM # [n=1] spindle cell neoplasm # [n=3] LM[n=8] (57%) susp. LM # [n=1] spindle cell neoplasm # [n=3] confirmatory IHC non-diagnostic # [n=2] confirmatory IHC non-diagnostic # [n=2] # equivocal/no IHC # equivocal/no IHC leiomyoma 15

16 Spindle Cell Sarcomas MPNST SS LGFMS de diff LPS 16

17 SC sarcomas that MAY be diagnosed reliably using smears, clinical info and ancillary methods AngioS melanoma Synovial sarcoma MPNST AngioS LGFMS L-G LMS DFSP DFSP MPNST Synovial Sarcoma - 4 th most common ST sarcoma adolescent young adults t(x;18)(p11;q11) fusion of 2 genes 18q11; Xp11 biphasic, monophasic, p-d cytomorphology high cellularity clusters + single cells extreme uniformity oval, rounded, spindle nuclei scant, wispy cytoplasm 13 y/o, 17

18 SS, fascicular SS SS, fascicular SS, curvilinear 18

19 SS, rounded SS, molding SS, glandular -19 y/o man. - 8 cm. L shoulder mass - MRI: polylobulated multiloculated cystic mass with fluid-fluid levels - smears: hypocellular - unstained slide sent for SS18 analysis CB, pan keratin SS18 (18q11.2) breakapart probe 19

20 41% correctly diagnosed as SS 21/36 (58%) primary 53.7 % misdiagnosed as another sarcoma 5.1 % non-diagnostic 2 cases (4%) cytogenetic analysis 16 cases: 9 biphasic / 7 monophasic RT-PCR on 6 prospective cases all 6 proven SYT-SSX fusion transcript Syn S [n=16] Syn S [n=16] CCS (1) EWSR1+ actual FNA Dx SS [13, 81%] susp. myxoid LPS (1) * malignant (1)* CCS EWSR1+ actual FNA Dx SS [13, 81%] susp. myxoid LPS * malignant* primary (10) (all SS18+) metastatic (3) SS18+, smear + CB (1) * no ancillary test * no ancillary test 20

21 CCS EWSR1+ Syn S [n=16] actual FNA Dx SS [13, 81%] primary (10) (all SS18+) susp. myxoid LPS * metastatic (3) smear only (2) smear + CB (5) CB only (3) MPNST malignant* SS18+, smear + CB (1) * no ancillary test 4-5% of sarcomas 50-70% assoc. with NF-1 3 rd -6 th decade trunk, extremities pathognomonic histologic features: none most helpful documented nerve origin documented origin from nerve sheath tumor history of NF-1 cytomorphology high cellularity clusters + single cells extreme uniformity nuclei spindle oval rounded ± serpiginous nuclei scant cytoplasm MPNST 21

22 MPNST SS 24 own cases 17% = correct dx 33% = sarcoma, NOS 17% = fibrosarcoma 12.5% = syn sarcoma 12.5% = LMS 4% = MFH 4% = RMS 79 cases (literature) 41% = correct dx 52% = other sarcoma 4% = susp. for sarcoma 4% = FN Diagn Cytopath 2012; 27: 103. why is it so difficult to recognize MPNST even with CB or CNB? no pathognomonic morphologic criteria > 90% exhibit a fascicular spindled morphology FNA dx of either MPNST, c/w MPNST primary cases = 30% locally recurrent cases = 93% metastatic cases = 70% absence of a unique karyotypic/molecular abnormality absence of a consistent, unique IHC signature Cancer 2012; 120:

23 Misc. specific spindle cell sarcomas (17) tissue diagnosis LMS (9) AngioS (2) DFSP (2) RMS, spindle (2) LGFMS (2) FNA diagnosis LMS (5)*, SC neoplasm (3), SC sarcoma (1) AngioS (2)* DFSP (1)*, spindle cell neoplasm(1) RMS (2)* LGFMS (1)*, spindle cell sarcoma (1) Everything is spindle how far can we go? Not That Far. All The Way. * confirmatory IHC or FISH Merely ascertaining the presence of cancer is much simpler than determining its particular variety. The latter is oftentime impossible from smears. Not That Far. Everything is spindle how far can we go? It All Depends. Stewart FW. The Diagnosis of Tumors By Aspiration. Am J Pathol 1933; 9: All The Way. 23

24 Not That Far. Everything is spindle how far can we go? procedural performance/experience Not That Far. Everything is spindle how far can we go? procedural performance/experience nature of the lesion P/Re/M? nature of the lesion P/Re/M It All Depends. clinical/imaging data It All Depends. clinical/imaging data material for ancillary tests genetic anomaly specific IHC phenotype All The Way. All The Way. We must not expect more precision than the subject matter admits. Aristotle 24

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