Disclosures I have nothing to disclose. Spindle cell sarcomas of soft tissue: Beyond herringbones and fibrosarcoma Andrew Horvai, MD, PhD Clinical Professor, Pathology Introduction Introduction Bick EM. Ann Surg 1935; 101(2):759-65. 1
Introduction Introduction Fibrosarcoma: Malignant tumor, composed of � Fibrosarcoma as % of soft tissue sarcomas fibroblasts with variable collagen and, in classical cases, 70% a herringbone architecture (WHO, 2002) 60% 50% Fibrosarcoma: Malignant tumor, composed of � fibroblasts with variable collagen and, in classical cases, 40% a herringbone architecture. It is a diagnosis of exclusion (WHO, 2013) 30% 20% Problem: What is the definition of a fibroblast? � 10% 0% 1936 1974 1989 2010 Fisher, C., et al. (2002). Adult Fibrosarcoma. WHO Pathology and Genetics Tumours of Soft Tissue and Bone: Meyerding H et al. Surg Gynecol Obstet 1936; 62: 1010-1019. 100-101. Pritchard DJ et al. Cancer 1974; 33(3):888-97. Folpe, A. L. (2013). Adult fibrosarcoma. WHO Classification of Tumours of Soft Tissue and Bone: 91-92. Scott SM et al. Cancer 1989; 65(4):925-31. Bahrami A, Folpe AL. Am J Surg Pathol 2010;34(10):1504-13 Questions Called fibrosarcoma Looks like fibrosarcoma � Monophasic synovial 1. How have tumors formerly known as fibrosarcoma � Infantile fibrosarcoma sarcoma been reclassified? � Myxofibrosarcoma � Malignant peripheral nerve sheath tumor � Sclerosing epithelioid 2. Are there any true fibrosarcomas? fibrosarcoma � Adult fibrosarcoma � Low-grade � Undifferentiated fibromyxoid sarcoma spindle cell sarcoma � Spindle cell rhabdomyosarcoma � Dermatofibrosarcoma Fibrosarcomatous DFSP protuberans (DFSP) 2
Monophasic synovial sarcoma Monophasic synovial sarcoma Clinical � � Young adults � 80% extremity, but can arise anywhere � 5 year survival 36-76%, chemotherapy + surgery Pathology � � Highly uniform spindle cells, short fascicles, occasionally herringbone � Hyperchromatic nuclei � Branching vessels, calcification IHC � � Keratin, EMA – at most focal, patchy � S100 in ~30% � CD34 negative Genetics � � t(X;18), SS18-SSX fusion Monophasic synovial sarcoma Monophasic synovial sarcoma 3
EMA Keratin Monophasic synovial sarcoma SS18 break apart FISH Malignant peripheral nerve sheath Malignant peripheral nerve sheath tumor tumor (MPNST) Clinical � � Middle aged adults, post-radiation � 50% in NF1 patients, 50% sporadic � Prognosis related to grade Pathology � � Tight fascicular pattern is only one of many � Tapering, hyperchromatic nuclei � More mitotic activity (>5/10) and pleomorphism than SS � Herniation into vessels, pre-existing benign NF IHC � � ~50% S100 or SOX10, usually very focally � Keratin, desmin, EMA, CD34 usually negative � H3K27 Me3 loss Genetics � � No reproducible changes Prieto-Granada CN et al. Am J Surg Pathol 2015 (epub). 4
Malignant peripheral nerve sheath tumor Malignant peripheral nerve sheath tumor Malignant peripheral nerve sheath tumor: herniation into vessels Malignant peripheral nerve sheath tumor S100 SOX10 5
DFSP Fibrosarcomatous DFSP Clinical � � Trunk, proximal extremity mid-age, > 5cm � Synchronous or metachronous DFSP � Controversial if prognosis worse than DFSP after complete excision Pathology � � Usually precursor DFSP can be found at periphery � Normal epidermis, uniform storiform, “Swiss cheese” � Transition to fascicular, herringbone, hypercellular area � High mitotic activity (>7 / 10 hpf), necrosis IHC � � CD34 positive but weaker than DFSP Genetics � � t(17;22)(q21;q13) COL1A1 : PDGF β fusion Fibrosarcoma Dermatofibrosarcoma protuberans Fibrosarcomatous DFSP 6
Fibrosarcomatous DFSP Fibrosarcomatous DFSP DFSP + Fibrosarcoma CD34 Adult fibrosarcoma “undifferentiated spindle cell sarcoma” Clinical � � Trunk, proximal extremity mid-age � Deep soft tissue � Poor prognosis (<55% 5 year survival) Pathology � � Monomorphic spindle cells � Fascicles, herringbone and/or storiform � Rarely fibromatosis like areas � Collagen can be wispy or keloidal IHC � � Negative except focal SMA Genetics � � Variable 7
Adult Fibrosarcoma Adult Fibrosarcoma Adult Fibrosarcoma Adult Fibrosarcoma Keratin SMA CD34 Caldesmon S100 CD10 … and more 8
Adult Fibrosarcoma Adult Fibrosarcoma Infantile Fibrosarcoma Infantile fibrosarcoma Clinical � � Very rare, distal extremity but wide distribution � Congenital (1/3 rd ) to 1 year � Relatively good prognosis, does not correlate with grade Pathology � � Highly cellular, monomorphic ovoid to spindled � Herringbone to sheets � HPC-like vessels IHC � � Negative, weak focal SMA Genetics � � t(12;15) ETV6:NTRK3 � Same as congenital pulmonary fibrosarcoma, congenital mesoblastic nephroma � Also in secretory breast cancer and AML 9
Infantile Fibrosarcoma Infantile Fibrosarcoma Infantile Fibrosarcoma Ancillary tests summary Synovial MPNST FS in Infantile Adult FS sarcoma DFSP FS Keratin Rare cells - - - - S100 Weak, Weak, - - - patchy patchy CD34 - Rare cells Weak - - Other SS18 FISH SOX10 PDGF ETV6 FISH - FISH 10
Take-home messages 1. Adult fibrosarcoma is a diagnosis of exclusion 2. Some diagnoses that retain the diagnosis of “fibrosarcoma” are not uniformly herringbone 3. Most herringbone spindle cell neoplasms in adults can be classified as synovial sarcoma, MPNST or fibrosarcomatous DFSP 4. Immunohistochemistry and, in some cases, genetics are needed in most cases to classify these tumors 11
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