What Is New in Cutaneous Soft Tissue Pathology?

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

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