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Mimics of Sarcoma I Have No Conflict of Interest to Declare Maastricht 2018 Discrepancies vs Referring diagnoses Cases Dx % Grade % 1978 Baker US 130 32 - 1984 Tetu CAN 260 35 - 1986 Presant US SECSG 216 28 24 Mimics of 1986 Coindre FR panel 25 39 25 1989 Alvegaard SSG 240 25 40 Sarcoma 1989 Shiraki US ECOG 488 26 - 1991 Harris UK 376 24 - 1995 Prescott UK 17 29 - 1999 Meis-K SSG 1000 20 25 Cyril Fisher MA MD DSc FRCPath 2004 Randall US 104 37 25 2004 Van Dalen NE rpl 143 24 36 Consultant Pathologist, Royal Orthopaedic Hospital, Birmingham, UK 2009 Thway UK 349 22 23 Emeritus Professor of Tumour Pathology 2009 Lurkin FR 366 25 19 Institute of Cancer Research, University of London 2014 Thway UK 250 16 Maastricht 2018 Mimics of Sarcoma Reactive/‘transiently neoplastic’ Benign tumours with focal atypia • Nodular fasciitis • Pleomorphic fibroma • Proliferative fasciitis • Leiomyoma with bizarre nuclei • Proliferative myositis • Pleomorphic lipoma • Ischaemic fasciitis • Atypical cutaneous FH I have no conflict of interest • With heterotopic ossification • Atypical neurofibroma • Ossifying fasciitis • Cellular schwannoma to declare • Fibro-osseous pseudotumour • Pleomorphic lipoma • Myositis ossificans Benign tumours with diffuse atypia • Heterotopic mesenteric • Pleomorphic hyalinising angiectatic ossification tumour • Massive localised lymphoedema of • Atypical fibroxanthoma morbid obesity Non-mesenchymal tumours • Sarcomatoid carcinoma • Melanoma Nodular Fasciitis Benign/Malignant Discordance • 2,425 patients • 341(14%) had received discordant diagnoses. • 124 benign tumours diagnosed as sarcomas • 14 (11%) fasciitis • 38 (31%) lipomas • 77 non-sarcoma malignancies diagnosed as sarcomas • 49 (64%) carcinoma • 12 (16%) melanoma Perrier at al PLOS ONE | https://doi.org/10.1371/journal.pone.0193330 April 5, 2018 SMA Nodular Fasciitis SMA Nodular Fasciitis • Young adults • Limbs, HN, trunk • Rapidly growing • Up to 5 cm • Dermal calponin h-caldesmon • S/c, fascial • Intramuscular • Does not recur Nodular Fasciitis Nodular Fasciitis • t(17;22)(p13;q12.3-13.1) • USP6-MYH9 fusion • USP6 rearranged in 74% of NF • Other partners identified • RRBP1 • CALU • CTNNB1 • MIR22HG • SPARC • TSBH2 • COL6A2 • CDH11 Erickson-Johnson 2011; Amary 2013; Oliveira 2014; Guo 2016; Patel 2017; Bekers 2018; Erber 2018 Nodular Fasciitis Nodular Fasciitis • t(17;22)(p13;q12.3-13.1) • Zonation • USP6-MYH9 fusion • Myxoid ® cellular ® fibrous • USP6 rearranged in 74% of NF • Loose storiform, fascicular • USP6 rearranged in • Mitoses, no atypia • Cellular fibroma tendon sheath • No necrosis • Myositis ossificans • Aneurysmal bone cyst • Red blood cells, lymphocytes • Giant cell reparative • Small giant cells granuloma of hands, feet • SMA+, USP6 rearrangement • Fibro-osseous pseudotumour Sukov 2008; Erickson-Johnson 2011; Amary 2013; Oliveira 2014; Guo 2016; Patel 2017; Bekers 2018; Erber 2018; Flucke 2018 Nodular Fasciitis Inflammatory Myofibroblastic Tumour Differential Diagnosis • Fibrous histiocytoma • F>M 2 mos -74 yrs (8) • Fibroma of tendon sheath • Lung, intra-abdominal • Fibromatosis • HN, urinary tract • Inflammatory myofibroblastic tumour • Systemic symptoms • Low grade myofibrosarcoma • Multinodular, infiltrative • Leiomyosarcoma • 29% recur 4% met • 12.5% DOD • Myxofibrosarcoma Meis 1991; Coffin 1995 Inflammatory Myofibroblastic Tumour Fibromatosis Beta-catenin SMA ALK ALK Protein Expression in IMT Epithelioid Inflammatory Myofibroblastic Sarcoma 2001 Yousem Lung 33% • Predominantly males 2001 Coffin All sites 36% • 7 mos to 63 yrs (m 39) 2002 Cessna All sites 40% • Omentum, mesentery, pleural cavity, lung 2006 Montgomery GU 57% • 8-26 cm, some multifocal 2007 Coffin All sites 55% • ALK+, Desmin+, CD30+ 2015 Antonescu All sites 56% • 8/8 recurred • mets to liver (2), lung & lymph node (1) • Childhood, abdominal/pulmonary IMT • Response to crizotinib • Also some of: MPNST, RMS, leiomyosa. Butrynski 2010; Marino-Enriquez, 2011; Kozu 2014; Fu 2015; Rafee 2015 Epithelioid IM Sarcoma Fusions & IHC in IMT • TPM3-ALK t(1;2)(q22;p23) cytoplasmic • TPM4-ALK t(2;19)(p23;p13) cytoplasmic • ATIC-ALK t(2;2)(p23;q35) cytoplasmic inv(2)(p23q35) • SEC31A-ALK t(2;4)(p23;q21) cytoplasmic • CARS-ALK t(2;11)(p23;p15) cytoplasmic • CLTC-ALK t(2;17)(p23;q23) granular ALK • RANBP2-ALK t(2;2)(p23;q13) nuclear membrane • ELM4-ALK t(2;2)(p23;p21) • TFG-ROS1 t(3;6)(q22;q12.2) cytoplasmic dot • YWHAE-ROS1 t(6;17)(q22;p13.3) nuclear, cytoplasmic • NAB2-PDGFRβ t(5;12;)(q33;q13.3) • ETV6-NTRK3 t(12;15)(p13;q26) Lovly 2014; Hornick 2015; Antonescu 2015; Alassiri 2015 Low-grade Myofibrosarcoma Nodular Fasciitis Myxofibrosarcoma Various copy number changes No specific rearrangement Fasciitis: Subtypes Nodular Fasciitis Leiomyosarcoma h-CAL • Usual • nodular • cranial • intravascular • Proliferative • Ischaemic Proliferative Fasciitis Proliferative Fasciitis/Myositis Differential Diagnosis • Adults 40-70, M = F • Forearm, thigh • Carcinoma CK, EMA • Rapid growth • Rhabdomyosarcoma desmin, myogenin • < 5cm • Melanoma S100 protein, SOX10, mel-A • Trauma in 30% • Epithelioid sarcoma CK, EMA, CD34, INI1- • Self-limiting • ES-like (pseudomyogenic) ERG, CD31, AE1/AE3 haemangioendothelioma Proliferative Myositis Ischaemic Fasciitis • F =M, 15-95 years • Immobilization, trauma • Shoulder, back, buttock • Desmin negative • Sacrum, greater trochanter • CK negative • S100pr negative • No ulcer – deep subcutis • CD34 negative • Painless mass 1 – 8 cm • CD31 negative • Rarely recurs Montgomery 1992; Perosio 1993; Liegl 2008 Ischaemic Fasciitis Massive Localised Lymphoedema of Morbidly Obese • Adults, mean 47 years, 186 kg • Thigh, leg, genitalia, abdominal wall • Some had lymphadenectomy • Ill-defined mass, mean 33cm, 7.4 kg • Can persist or recur • Rarely è angiosarcoma Farshid 1998; Manduch 2009; Shon 2011 Massive Localised Lymphoedema of Morbidly Obese Ischaemic Fasciitis • Lobular, zonal Atypical Lipomatous Tumour/WDL • Fibrinoid necrosis • Myxoid stroma • Ectatic thin vessels • Atypical fibroblasts • SMA, desmin, CD34 Massive Localised Lymphoedema of Atypical Schwannoma Leiomyoma with Bizarre Nuclei Morbidly Obese • Lobules of mature fat • Expanded connective tissue septa • fine, fibrillary collagen • oedema fluid • uniformly distributed fibroblasts Atypical Cutaneous FH Atypical Cutaneous FH • Capillaries at interface • No atypia Mimics of Sarcoma Pleomorphic Lipoma Reactive/‘transiently neoplastic’ Benign tumours with focal atypia • Clinically like SCL but rarer • Nodular fasciitis • Pleomorphic fibroma • S/C, encapsulated • Proliferative fasciitis • Leiomyoma with bizarre nuclei • Proliferative myositis • Atypical cutaneous FH • Lipomatous areas • Ischemic fasciitis • Atypical neurofibroma • Spindle cells in collagen • With heterotopic ossification • Cellular schwannoma • Ossifying fasciitis • Pleomorphic lipoma • Multinucleated/floret cells • Fibro-osseous pseudotumour Benign tumours with diffuse atypia • Lipoblasts • Myositis ossificans • Pleomorphic hyalinising angiectatic tumour • ‘Atypical’ variant • Heterotopic mesenteric ossification • Atypical fibroxanthoma • 13q14 del, Rb loss • Massive localised lymphoedema of Non-mesenchymal tumours morbid obesity • Sarcomatoid carcinoma • Melanoma Creytens 2017; Michal 2018; Creytens 2018 WD Liposarcoma/ALT Pleomorphic Liposarcoma MDM2 Myxoid SCL vs Myxoid Liposarcoma Fat Necrosis Lochkerne • Rb loss • DDIT3 rearrangement Sarcomatoid Carcinoma Spindle Cell Melanoma vs MPNST • Organ-based – not sarcoma? • Junctional component • In situ component • S100pr, SOX10 • Epithelial component • H3K27me3 • Heterologous elements • Both lack melanoma Ags • CK positive • BRAF, NRAS mutation CK CKSOX10 • No heterologous elements Synovial Sarcoma vs Sarcomatoid Ca Conclusion • No in situ component • Be aware of the clinical history • location • Not pleomorphic • duration • CK more focal • rate of growth • Bcl-2, CD56 positive • antecedent event • Mast cells CK • Be familiar with the diagnostic possibilities • No heterologous elements • Seek a further opinion • SS18 rearrangement The End .
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