Mimics of Sarcoma. I have no conflict of interest to declare
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1 Maastricht 2018 Mimics of Sarcoma Cyril Fisher MA MD DSc FRCPath Consultant Pathologist, Royal Orthopaedic Hospital, Birmingham, UK Emeritus Professor of Tumour Pathology Institute of Cancer Research, University of London Discrepancies vs Referring diagnoses Cases Dx % Grade % 1978 Baker US Tetu CAN Presant US SECSG Coindre FR panel Alvegaard SSG Shiraki US ECOG Harris UK Prescott UK Meis-K SSG Randall US Van Dalen NE rpl Thway UK Lurkin FR Thway UK Maastricht 2018 Mimics of Sarcoma I have no conflict of interest to declare Reactive/transiently neoplastic Nodular fasciitis Proliferative fasciitis Proliferative myositis Ischaemic fasciitis With heterotopic ossification Ossifying fasciitis Fibro-osseous pseudotumour Myositis ossificans Heterotopic mesenteric ossification Massive localised lymphoedema of morbid obesity Benign tumours with focal atypia Pleomorphic fibroma Leiomyoma with bizarre nuclei Pleomorphic lipoma Atypical cutaneous FH Atypical neurofibroma Cellular schwannoma Pleomorphic lipoma Benign tumours with diffuse atypia Pleomorphic hyalinising angiectatic tumour Atypical fibroxanthoma Non-mesenchymal tumours Sarcomatoid carcinoma Melanoma
2 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 April 5, 2018 SMA SMA Young adults Limbs, HN, trunk Rapidly growing Up to 5 cm Dermal S/c, fascial Intramuscular Does not recur calponin h-caldesmon
3 t(17;22)(p13;q ) 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 t(17;22)(p13;q ) USP6-MYH9 fusion USP6 rearranged in 74% of NF USP6 rearranged in Cellular fibroma tendon sheath Myositis ossificans Aneurysmal bone cyst Giant cell reparative granuloma of hands, feet Fibro-osseous pseudotumour Zonation Myxoid cellular fibrous Loose storiform, fascicular Mitoses, no atypia No necrosis Red blood cells, lymphocytes Small giant cells SMA+, USP6 rearrangement Sukov 2008; Erickson-Johnson 2011; Amary 2013; Oliveira 2014; Guo 2016; Patel 2017; Bekers 2018; Erber 2018; Flucke 2018
4 Differential Diagnosis Fibrous histiocytoma Fibroma of tendon sheath Fibromatosis Inflammatory myofibroblastic tumour Low grade myofibrosarcoma Leiomyosarcoma Myxofibrosarcoma Inflammatory Myofibroblastic Tumour F>M 2 mos -74 yrs (8) Lung, intra-abdominal HN, urinary tract Systemic symptoms Multinodular, infiltrative 29% recur 4% met 12.5% DOD Meis 1991; Coffin 1995 Fibromatosis Inflammatory Myofibroblastic Tumour Beta-catenin SMA ALK
5 ALK Protein Expression in IMT Epithelioid Inflammatory Myofibroblastic Sarcoma 2001 Yousem Lung 33% 2001 Coffin All sites 36% 2002 Cessna All sites 40% 2006 Montgomery GU 57% 2007 Coffin All sites 55% 2015 Antonescu All sites 56% Childhood, abdominal/pulmonary IMT Also some of: MPNST, RMS, leiomyosa. Predominantly males 7 mos to 63 yrs (m 39) Omentum, mesentery, pleural cavity, lung 8-26 cm, some multifocal ALK+, Desmin+, CD30+ 8/8 recurred mets to liver (2), lung & lymph node (1) Response to crizotinib Butrynski 2010; Marino-Enriquez, 2011; Kozu 2014; Fu 2015; Rafee 2015 Fusions & IHC in IMT Epithelioid IM Sarcoma 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 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-PDGFR t(5;12;)(q33;q13.3) ETV6-NTRK3 t(12;15)(p13;q26) ALK Lovly 2014; Hornick 2015; Antonescu 2015; Alassiri 2015
6 Low-grade Myofibrosarcoma Myxofibrosarcoma Various copy number changes No specific rearrangement Leiomyosarcoma h-cal Fasciitis: Subtypes Usual nodular cranial intravascular Proliferative Ischaemic
7 Adults 40-70, M = F Forearm, thigh Rapid growth < 5cm Trauma in 30% Self-limiting Proliferative Fasciitis Proliferative Fasciitis/Myositis Differential Diagnosis Carcinoma CK, EMA Rhabdomyosarcoma desmin, myogenin Melanoma S100 protein, SOX10, mel-a Epithelioid sarcoma CK, EMA, CD34, INI1- ES-like (pseudomyogenic) ERG, CD31, AE1/AE3 haemangioendothelioma Proliferative Myositis Ischaemic Fasciitis F =M, years Immobilization, trauma Desmin negative CK negative S100pr negative CD34 negative CD31 negative Shoulder, back, buttock Sacrum, greater trochanter No ulcer deep subcutis Painless mass 1 8 cm Rarely recurs Montgomery 1992; Perosio 1993; Liegl 2008
8 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 angiosarcoma Farshid 1998; Manduch 2009; Shon 2011 Ischaemic Fasciitis Lobular, zonal Fibrinoid necrosis Myxoid stroma Ectatic thin vessels Atypical fibroblasts SMA, desmin, CD34 Massive Localised Lymphoedema of Morbidly Obese Atypical Lipomatous Tumour/WDL
9 Massive Localised Lymphoedema of Morbidly Obese Atypical Schwannoma Leiomyoma with Bizarre Nuclei Lobules of mature fat Expanded connective tissue septa fine, fibrillary collagen oedema fluid uniformly distributed fibroblasts Capillaries at interface Atypical Cutaneous FH Atypical Cutaneous FH No atypia Mimics of Sarcoma Pleomorphic Lipoma Reactive/transiently neoplastic Nodular fasciitis Proliferative fasciitis Proliferative myositis Ischemic fasciitis With heterotopic ossification Ossifying fasciitis Fibro-osseous pseudotumour Myositis ossificans Heterotopic mesenteric ossification Massive localised lymphoedema of morbid obesity Benign tumours with focal atypia Pleomorphic fibroma Leiomyoma with bizarre nuclei Atypical cutaneous FH Atypical neurofibroma Cellular schwannoma Pleomorphic lipoma Benign tumours with diffuse atypia Pleomorphic hyalinising angiectatic tumour Atypical fibroxanthoma Non-mesenchymal tumours Sarcomatoid carcinoma Clinically like SCL but rarer S/C, encapsulated Lipomatous areas Spindle cells in collagen Multinucleated/floret cells Lipoblasts Atypical variant 13q14 del, Rb loss Melanoma Creytens 2017; Michal 2018; Creytens 2018
10 WD Liposarcoma/ALT Pleomorphic Liposarcoma MDM2 Fat Necrosis Lochkerne Myxoid SCL vs Myxoid Liposarcoma Rb loss DDIT3 rearrangement
11 Sarcomatoid Carcinoma Spindle Cell Melanoma vs MPNST Organ-based not sarcoma? In situ component Epithelial component Heterologous elements CK positive CK Junctional component S100pr, SOX10 H3K27me3 Both lack melanoma Ags BRAF, NRAS mutation No heterologous elements CK SOX10 Synovial Sarcoma vs Sarcomatoid Ca Conclusion No in situ component Not pleomorphic CK more focal Bcl-2, CD56 positive Mast cells No heterologous elements SS18 rearrangement CK Be aware of the clinical history location duration rate of growth antecedent event Be familiar with the diagnostic possibilities Seek a further opinion
12 The End
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