What is New in Cutaneous Soft Tissue Pathology? By Konstantinos Linos MD, FCAP, FASDP Bone, Soft Tissue and Dermatopathology Assistant Professor of Pathology Dartmouth-Hitchcock Medical Center Geisel School of Medicine at Dartmouth Hanover, NH, USA Financial disclosures • Book Royalties Benign/Low Grade Fibroblastic Tumors • Calcifying aponeurotic fibroma • Recurrent FN1-EGF fusion • Fibrous hamartoma of infancy • EGFR internal tandem duplications • Myofibroma/myopericytoma • PDGFR mutations • Lipofibromatosis-like neural tumors • Recurrent NTRK1-related gene fusions Angiofibroma of Soft Tissue • Slow growing tumor of subcutis and deep soft tissue • Commonly in the extremities of adults • Benign neoplasm • May occasionally recur (~15%) • Does not metastasize IHC • EMA in approximately half of the cases • Focal staining for desmin, CD34, SMA EMA • Negative S100- protein Differential Diagnosis • Myxoid Liposarcoma • Low-Grade Fibromyxoid Sarcoma • Solitary Fibrous Tumor • Low-Grade Myxofibrosarcoma • Cellular Angiofibroma EWSR1-SMAD3 Fibroblastic Neoplasm ERG ERG Calcifying Aponeurotic Fibroma • Predilection for hands and feet of pediatric patients • Subcutaneous tissue or attached aponeurosis/fascia • Biphasic morphology • Bland fibroblasts merging with fibrocartilginous nodules and osteoclasts • Recurrences ~40-50% Diagnostic Pathology: Soft Tissue Tumors Elsevier 2016 Diagnostic Pathology: Soft Tissue Tumors Elsevier 2016 Superficial CD34-positive Fibroblastic Tumor Ki-67 CD 34 AE1/AE3 INI1 p53 FISH for MGEA5 and TGFBR3 negative Differential Diagnosis Undifferentiated pleomorphic sarcoma Myxofibrosarcoma Atypical fibroxanthoma Pleomorphic hyalinizing angiectatic tumor (PHAT) Myxoinflammatory fibroblastic sarcoma Epithelioid sarcoma Lipofibromatosis • Rare soft tissue tumor that occurs mainly in children • Preferentially involves hands and feet • Distinctive admixture of mature adipose tissue and fascicle of bland cuboidal to spindle cells • Recurrences in 1/3 of cases • No metastatic potential NTRK1 NTRK1 Epithelioid Fibrous Histiocytoma Epithelioid Fibrous histiocytoma (EFH) • By current definition, a variant of FH with at least 50% of lesional cells having an epithelioid morphology • Recent data showing a distinct immunohistochemical and genetic profile support that EFH is likely a distinct neoplasm Microscopic findings ALK ALK ALK FISH ALK ALK and Epithelioid Fibrous Histiocytoma • Nosologically, a distinct tumor type, biologically unrelated to other variants of cutaneous fibrous histiocytoma • Diagnostically a useful marker to distinguish epithelioid fibrous histiocytoma from histologic mimics • Biologically, further illustrating the remarkable plasticity of ALK as an oncogenic driver, and highlighting the diverse role of similar genetic changes in different histologic entities Inflammatory Myofibroblastic Tumor (IMT) • Spindle cell tumor of intermediate malignancy • Local recurrence and rarely metastasis • Mainly in the lung and abdomen of children and young adults • Approximately 50% ALK rearrangements • ALK is receptor tyrosine kinase (RTK) • ALK IHC useful surrogate • 5A4 antibody more sensitive than ALK1 IMT and kinase fusions • ALK ~ 50% • ETV6 ~5-10% • ROS ~ 10% • RET • PDGFRB • NTRK ALK SMA DDx • Nodular fasciitis • Solitary fibrous tumor • DFSP • Myofibroma/myofibromatosis • Follicular dendritic cell tumor (inflammatory pseudotumor variant) • Epithelioid fibrous histiocytoma Perivascular Myoid Tumors • Glomus tumor • Myopericytoma • Myofibroma • Angioleiomyoma Myofibroma • Benign myofibroblastic tumors classically occurring in male infants and children • Adults less frequently affected • Solitary and multicentric with excellent prognosis • May spontaneously regress • Generalized myofibromatosis may result in death SMA SM-MHC • Email: [email protected] • @ @ KonstantinosLin.