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Cutaneous Myxoid Tumors Myxoid Tumors 43-Year-Old Man Presents

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Cutaneous Myxoid Tumors Myxoid Tumors 43-Year-Old Man Presents 21/07/2017 Myxoid tumors • Dermatopathologists rely on pattern recognition • Myxoid tumors: Cutaneous Myxoid Tumors – Accumulation of myxoid stroma – Diagnosis defining pattern subtle Steven D. Billings, MD – Careful attention to detail allows diagnosis Cleveland Clinic [email protected] 43-year-old man presents with a nodule on the chest Superficial angiomyxoma/ cutaneous myxoma • Clinical features – More common in males – Trunk, lower extremities and head/neck – Multiple lesions associated with Carney’s complex: • Lentigines, blue nevi, cutaneous and cardiac myxoma, endocrine overactivity, mutation in PRKAR1A • Benign with some local recurrences 1 21/07/2017 Superficial angiomyxoma/ cutaneous myxoma • Microscopic features – Multinodular, lobular – Prominent arborizing, thin-walled vessels – Bland spindled cells – Neutrophils commonly present – Entrapped epithelial structures Differential diagnosis Focal dermal mucinosis • Focal collection of dermal mucin in upper dermis Case • Vasculature less prominent • Stromal neutrophils absent • Intercalates between collagen 41-year-old man presented with a firm subcutaneous bundles mass on the posterior • Difficult neck 2 21/07/2017 Spindle Cell Lipoma Spindle Cell Lipoma • Clinical • Classic Microscopic Features – Middle aged and older men – Short fascicles in ‘school of fish’ pattern – Head and neck, shoulders, upper back – Bland spindled cells – – Painless mass Ropey collagen – Myxoid stroma (common) and in some cases prominent – Rarely multiple – Admixed mature fat cells – CD34+ – Loss of 13q (Loss of RB1 expression) • Some cases have no or only a small amount of fat 3 21/07/2017 Spindle cell lipoma • Always consider this diagnosis in lesions from the upper back, posterior head and neck of middle aged and older men • Caveat: spindle cell lipomas in women have broader range of clinical locations • Cutaneous solitary fibrous tumor very rare • 10/33 based in the dermis • Dermal spindle cell lipomas less circumscribed • Little to no mature adipose tissue • 34/34 SFT STAT6 + • 0/10 Spindle cell lipomas STAT6 4 21/07/2017 A 56-year-old man presented with a recurrent spindle cell lipoma of the scalp Diagnosis? 5 21/07/2017 Myxoid Dermatofibrosarcoma Protuberans Myxoid DFSP • First described Frierson and Cooper in 1983 (Am J Surg Pathol • Clinical Features • Microscopic features 7:445-50, 1983) – Middle aged patients (9 mo – 74 – Bland spindled to stellate cells yrs) – • Rare case reports Random pattern – Extremities, head and neck, groin, – Uniform cellularity • Two larger series trunk – No ropy collagen – – Reimann and Fletcher (Am J Surg Pathol 31:1371-77, 2007) Clinical diagnosis: – Vasculature, variable thin-walled • Benign cyst vessels – Mentzel, et al (Am J Dermatopathol 29:443-448, 2007) • Lipoma – CD34+ • Pyogenic granuloma • Enlarged lymph node Myxoid DFSP Giant cell fibroblastoma • Present in ~10% of cases • Pseudovascular spaces lined by tumor cells • Multinucleated tumor cells Myxoid DFSP Differential Diagnosis • Conventional DFSP • Myxoid DFSP • Myxoid Spindle cell lipoma – Present in >60% of cases – Clinical overlap – Clinical overlap – May be focal – Spindled to stellate cells – Spindled cells – Adequate sampling – Random pattern – Often fascicles – No ropy collagen – Ropy collagen – CD34+ – CD34+ – t(17;22) rearrangement of PDGFRB – Loss of 13q 6 21/07/2017 DDx: Myxoid Liposarcoma • Clinical features – Middle aged adults – Deep soft tissue mass (almost never occurs above the fascia as a primary tumor) • Microscopic features – Uniform round to spindled cells – Lipoblasts – Myxoid pools – Delicate branching vasculature Myxoid Liposarcoma Vs. Myxoid DFSP Myxoid Liposarcoma Myxoid DFSP • Deep • Superficial 67-year-old man with a calf mass. A punch • Plexiform vasculature • Variable vasculature • Round to spindled cells • Spindled to stellate cells biopsy was performed • Lipoblasts • No lipoblasts • t(12;16) • t(17;22) 7 21/07/2017 Myxofibrosarcoma • Clinical • Microscopic features – Superficial sarcoma – Infiltrative: often extend along – Usually in older patients subcutaneous septae Diagnosis? – Thigh most common location – Myxoid tumors – Rare in head and neck area – Relatively hypocellular – Hyperchromatic spindled cells with mild to moderate atypia – Curvilinear vasculature – Tumor cells often aggregate around vessels – Pseudolipoblasts – Mitotic rate often low 8 21/07/2017 Myxofibrosarcoma • Some cases are intermediate or • Myxofibrosarcoma grade 2,3 high grade sarcomas – More cellular • Recurrent cases often undergo – More atypia histologic progression – Fibrous areas • Higher grade tumors show – More solid areas of tumor different histologic features from proliferation classic (grade 1) – More mitotic activity myxofibrosarcoma – Necrosis Myxofibrosarcoma • Immunophenotype: no consistent pattern • Cytogenetics: no consistent abnormality • Behavior: – Frequent recurrence (20-70%) – Recurrences frequently undergo histologic progression – Metastatic risk low for grade 1 tumors (<10%) – Metastatic risk increases in higher grade tumors (20-40%) Epithelioid Myxofibrosarcoma • Clinical presentation similar to conventional myxofibrosarcoma • Histologic features – Multinodular tumor – Myxoid stroma – Curvilinear blood vessels – Epithelioid cells with eosinophilic cytoplasm 9 21/07/2017 Epithelioid myxofibrosarcoma • More aggressive than conventional myxofibrosarcoma • Recurrence rate >70% • Metastatic rate 50% – Visceral and lymph nodes Myxofibrosarcoma vs. Myxoid DFSP DDx: Myxoinflammatory fibroblastic sarcoma Myxofibrosarcoma Myxoid DFSP • Clinical features • Microscopic features • Curvilinear vessels • Delicate vessels – Middle-aged adults – Multinodular, poorly-circumscribed – Most common on distal extremities mass • More nuclear atypia • Bland nuclei (GCF multinucleated (arms>legs) – Myxoid and hyalinized lobules admixed • Less uniform cellularity cells) – Fingers and hands most common with dense inflammatory aggregates • Pseudolipoblasts • Uniform cellularity location – Amount of components varies from – Clinically can mimic ganglion cyst or case to case • No characteristic cytogenetics • t(17;22) other benign acral tumors – Scattered giant bizarre pleomorphic cells with prominent nucleoli that resemble Reed-Sternberg cells or virally infected cells – Low mitotic rate (<2/50 HPFs) 10 21/07/2017 Differential diagnosis MIFS Myxofibrosarcoma • Acral • Non-acral • Inflammation prominent • No significant inflammation Case • Reed-Sternberg like cells • Reed-Sternberg like cells absent A 4-year-old girl presented with a flank mass 11 21/07/2017 Immunostains • S100 protein negative • CD34 negative • EMA negative • Cytokeratin negative FSH for FUS Hyalinizing Spindle Cell Tumor Low Grade Fibromyxoid Sarcoma with Giant Collagen Rosettes • 1986: First described by Evans • Described in 1997 (Lane et al, AJSP 1997) – 2 cases of deceptively bland sarcomas with paradoxically aggressive • behavior Clinical and histologic similarities to LGFMS • 1993: 12 additional cases • A variant of LGFMS – Similarly bland features • Relationship with LGFMS – Aggressive behavior: supported by presence of focal • Metastasis in 7/12 rosettes and small collagen rosettes in cases of LGFMS (Folpe • 4 DOD et al, AJSP 2000) • 3 AWD 12 21/07/2017 Cytogenetics Clinical Features • Both HSTGR and LGFMS share common cytogenetic • Primarily affects young to abnormality middle-aged adults – 10-20% of cases present in children – t(7;16)(q34;p11) • Predominantly present as deep – Fusion of FUS/CREB3L2 soft tissue mass – FUS: RNA-binding protein – 20% present as superficial tumors of subcutis or dermis (Billings, et al – CREB3L2: member of OASIS B-ZIP family of transcription factors AJSP 2005) – Superficial tumors relatively common in children (~40% of superficial tumors) Histologic features Immunohistochemistry/FISH More a tool of exclusion • FISH: FUS rearranged 70-90% – Vimentin + – Actins +/- – EMA -/+ (30%) – S100 -/+ – CD34 – (rare focal positivity) – Desmin – • Exception: MUC-4 positive >90% LGFMS vs. Perineurioma • 21 patients recurrences after intervals up to 15 years (median • LGFMS • Perineurioma 3.5 yrs) – Swirling growth pattern – Swirling growth pattern – Fibrous and myxoid (often abrupt) – Fibrous and myxoid (not usually • 15 with metastasis after periods up to 45 years (median 5 yrs) – Slight atypia abrupt) • Still aggressive – EMA+ ~30% – No atypia • Patients need lifelong follow-up – MUC4+ (>95%) – EMA+ 100% – t(7;16)(FUS-CREB3) – MUC4+ (0%) – t(7;16) absent 13 21/07/2017 Perineurioma LGFMS vs. Myxofibrosarcoma LGFMS Myxofibrosarcoma • Whorled to fascicular • Random to fascicular • Pushing border • Infiltrative • Myxoid/collagenous • Purely myxoid (grade1) • Less atypia • More atypia • Rosettes sometimes • Rosettes absent • MUC4+ • MUC4- • t(7;16) • No consistent cytogenetics Ossifying fibromyxoid tumor (OFMT) OFMT • Clinical features • Microscopic features – Adult patients, M>F – Vasculature often prominent – Extremities – My have hyalinized blood vessels – Arises in subcutis or deep soft tissue • Immunophenotype • Microscopic features – S100 protein positive in 70-80% of cases – Circumscribed – Focal desmin positivity in ~20% – Peripheral shell of bone in up to 80% of cases – Usually negative for cytokeratins – Uniform round to spindled cells – Sometimes focal MUC4+ – Arranged in cords, nests or sheets • Cytogenetics – Fibrous to myxoid stroma – Rearrangements of PHF1 on chromosome 6 in ~60-80% • May have dense collagen that transitions to osteoid 14 21/07/2017 15 21/07/2017 16 21/07/2017 17 21/07/2017
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