Unusual Tumors of the Thyroid: Case 4 Theresa Scognamiglio, M.D. - PowerPoint PPT Presentation

Unusual Tumors of the Thyroid: Case 4 Theresa Scognamiglio, M.D. Assistant Professor of Pathology Weill Cornell Medicine

Case History • 44 year old woman who noticed a lump in neck 6 weeks prior to presentation • No hoarseness, dysphagia • Normal thyroid function tests • Ultrasound was performed o 3.3 x 2.8 x 2.1 cm hypoechoic complex nodule in the left thyroid lobe • Fine needle aspiration was performed o Paucicellular with scant spindle cells

Total Thyroidectomy Well Circumscribed Solid 1 cm Firm White Cut Surface

Prominent Stromal Proliferation

Two Distinct Components Stromal Epithelial

Spindle Cells in Fascicles

Hypercellular Thick Collagen Fibers Myxoid Extravasated RBCs

Bland Spindle Cells

Papillary Thyroid Carcinoma

Epithelial Component: Papillary Thyroid Carcinoma TTF-1 Pax-8

Stromal Component SMA Pan-Keratin

Summary of IHC Immunostains Epithelium Stroma TTF-1 + - PAX-8 + - CKAE1/AE3 + - CK7 + - Cam5.2 + - EMA + - Beta catenin + membranous + nuclear/cytoplasmic SMA - + Desmin - Focal +

Summary of Findings • Spindle cell proliferation with associated conventional PTC • Bland spindle cells o Negative for epithelial markers o Negative for thyroid specific markers o Positive for SMA

β-Catenin Immunostain Papillary Thyroid Carcinoma Stroma Nuclear/Cytoplasmic Membranous

FINAL HISTOLOGIC DIAGNOSIS Papillary Thyroid Carcinoma (PTC) with Nodular Fasciitis-Like Stroma (NF)/Fibromatosis-Like Stroma (FM)

PTC with NF/FM-Like Stroma is a Rare Variant of PTC • Chan et al. 1991 DUAL COMPONENTS • <1% of PTC variants o <50 cases • F>M, 20-82 years • Palpable neck mass • Dual components o Conventional PTC ─BRAF o Stroma resembling nodular fasciitis/fibromatosis • Prognosis similar to conventional PTC STROMAL COMPONENT USUALLY PREDOMINATES

FNA Can Be Diagnostically Challenging • Epithelium is often minor component o Increases the risk of false negative • Stromal component may be misinterpreted o Benign, reactive, malignant spindle cell lesions Yang et al. Arch Pathol Lab Med. 1999; 123: 838‐41 Us‐Krasovec et al. Acta Cytologica . 1999; 43: 1101‐4

Exact Pathogenesis of the Stromal Component Unknown: Reactive vs Neoplastic MOLECULAR IMMUNOHISTOCHEMISTRY ULTRASTRUCTURE • Smooth muscle markers • Activating • Collagen fibers mutation in • TGF beta • Abundant RER CTNNB1 Mediates activation o of fibroblasts • Aberrant nuclear expression of β-catenin PROFILE SIMILAR TO FIBROMATOSIS

Differential Diagnosis of Spindle Cell Lesions in Thyroid BENIGN MALIGNANT • PTC with metaplastic spindle cells • Reidel thyroiditis • Diffuse sclerosing variant of PTC • Hashimoto thyroiditis, (DSCPTC) fibrous variant • Medullary thyroid carcinoma • Post FNA spindle cell nodules • Spindle cell tumor with thymus-like differentiation (SETTLE) • Spindle cell follicular adenoma • Carcinoma showing thymus-like differentiation (CASTLE) • Anaplastic carcinoma • Fibromatosis • Solitary fibrous tumor • Nodular fasciitis • Smooth muscle tumors • Schwannoma • Peripheral nerve sheath tumors • Melanoma Identification of the PTC Component Will Help Narrow the Differential

Differential Diagnosis of Spindle Cell Lesions Arising in Association with PTC • PTC with metaplastic spindle cells, spindle cell variant • Diffuse sclerosing variant of papillary thyroid carcinoma (DSCPTC) • Anaplastic carcinoma, spindle cell and paucicellular variant • PTC with NF/SM-like stroma

Differential Diagnosis PTC NF/FM Reidel Thyroiditis β‐ catenin positive Sclerotic fibrosis Lacks significant inflammation Inflammatory infiltrate Phlebitis Lacks neoplasm

Differential Diagnosis Hashimoto Thyroiditis, PTC NF/FM Fibrous Variant β‐ catenin positive Less cellular Lacks significant inflammation More prominent inflammation Follicular atrophy Lacks neoplasm

Differential Diagnosis PTC with Metaplastic PTC NF/FM Spindle Cells Corrado et al. Endocr Path. 2014; 25:307‐314 β‐ catenin positive β‐ catenin negative TTF-1/Thyroglobulin negative TTF-1/Thyroglobulin positive CK negative CK positive

Differential Diagnosis PTC NF/FM DSCPTV β -catenin positive Stroma is sclerotic TTF-1/Thyroglobulin negative Lymphocytic infiltrate CK negative Psammoma bodies

Differential Diagnosis PTC NF/FM Anaplastic Wenig. Atlas of Head and Neck Pathology. 2008 Lacks significant atypia Significant atypia and mitotic β -catenin positive figures TTF-1/Thyroglobulin negative TTF-1/Thyroglobulin negative Epithelial markers negative Epithelial markers positive

Summary • PTC with NF/FM-like stroma is a rare and unusual variant o Challenging in FNA and histologic specimens • Recognition is important to avoid diagnostic misinterpretation o Benign reactive process o Aggressive histologic variants • Presence of fibroproliferative lesion should prompt adequate sampling of specimen o Stromal proliferation can obscure the epithelial component • IHC in combination with morphology can be helpful in making the correct diagnosis