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1 Squamous entities of the thyroid: Reactive to Neoplastic Michelle D. Williams Associate Professor Dept of Pathology, Head & Neck Section University of Texas MD Anderson Cancer Center Disclosure of Relevant Financial Relationships USCAP requires that all faculty in a position to influence or control the content of CME disclose any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their spouse/partner have, or have had, within the past 12 months, which relates to the content of this educational activity and creates a conflict of interest. Dr. Michelle Williams declares she has no conflict(s) of interest to disclose. FNA evaluation 3months prior FNA =AUS Atypical cells of undetermined significance (Bethesda III) Ultrasound 1.7 cm nodule Now for repeat FNA - Cell block P40 immunohistochemical stain Differential of squamous entities Is this clearly thyroid origin? Does this have to be malignant? TTF1 immunohistochemical stain FNA diagnosis Epithelial neoplasm with squamous features + (descriptive comment) The presence of bland squamous nests raise the differential of squamous metaplasia which may occur in thyroiditis, benign and malignant entities ( PTC, MEC) Differential diagnosis of squamous entities of the thyroid Reactive? Benign? Malignant? Squamous metaplasia in another malignancy vs. Squamous cell carcinoma ^squamous though not metaplastic Post FNA Thyroglossal duct cyst Epidermoid/dermoid cyst^ Follicular or Hurthle Adenoma Papillary thyroid carcinoma -secondary changes or -Diffuse sclerosing variant SCC primary (like-atc) SCC upper aerodigestive 1

2 Squamous in the thyroid Clinical distinctions Squamous metaplasia vs. Reactive 2 nd to background process (i.e. papillary thyroid carcinoma) Which will dictate prognosis Squamous carcinoma High-grade Poor outcome Similar to anaplastic carcinoma Squamous metaplasia thyroid What is it? (follicular cell vs solid cell nests) How frequent is it? 17% (Park et al.) How does it stain? as it looks squamous p63/p40 + TTF1 variable Pax8 variable Is keratinization ok? Yes may be present Park et al. Jpn J Clin Oncol Dec;18(4): p63 Solid cell nests Differentiate from squamous metaplasia/neoplasia embryonic remnants of endodermal origin Ultimobranchial remnant theory 10% of thyroid Positive for p63 cytokeratins CEA Negative for TTF1(few), Thyroglobulin and calcitonin adenomas peripherally thyroid malignancies PAPILLARY THYROID CARCINOMA Diffuse sclerosing variant 2

3 thyroid malignancies papillary thyroid carcinoma post FNA Squamous Cell Carcinoma in the thyroid Morphologically Similar PTC-Diffuse sclerosing variant Young patients (teen s-20 s) Thyroiditis LVI with psammoma bodies tumor percolates through thyroid Fibrosis/sclerosis DIAGNOSTIC PITFALL Post FNA (infarction) with extensive metaplasia Must distinguish from SCC Significant treatment & prognostic significances SCC = XRT SCC = < 6 month survival SCC primary thyroid SCC larynx invading into thyroid Squamous Cell Carcinoma in the thyroid PAX8 is typically retained in SCC thyroid origin 4.5 cm nodule Prominent squamous metaplasia with keratinization Areas of sclerosis Mucicarmine positive extracellular SCC of thyroid Cytokeratins TTF1 Thyroglobulin PAX8 +, may express - ck5/6 Rare up to 100% SCC from adjacent H&N site +, usually CK5/6" Metastatic SCC from another site +, usually CK5/6"

4 Rare mucocytes, inflammatory background Mucicarmine positive mucocytes Inflammation mixed Notable for prominent eosinophils PAX8 (negative) TTF variable p40 positive DX: SCLEROSING MUCOEPIDERMOID CARCINOMA WITH EOSINOPHILIA with prominent squamous metaplasia Mucoepidermoid carcinoma (MEC) vs sclerosing MEC of the thyroid Mucoepidermoid carcinoma (MEC) vs sclerosing MEC of the thyroid Squamous/epidermoid cells and glandular/mucous cell differentiation Plus some sclerotic background with prominent association of eosinophils and lymphocytes Other DDX: Metaplasia in Mucoepidermoid carcinoma 0.5% thyroid cancers F:M (2:1) Lymph nodes metastasis common Immunophenotype Thyroglobulin most focally + p63 (p40) positive TTF1 most focally + Pax8 expressed Sclerosing MEC with eosinophilia ~40 cases literature, F:M (13:1) Generally low grade (1/3 metastasis) Immunophenotype Thyroglobulin negative (91%) p63 (p40) positive (100%) TTF1 Variable (64%) Pax8 Rare/weak (2%) Ref: Shah Modern Pathology (2017) 30, Mucoepidermoid carcinoma May be associated with papillary thyroid carcinoma & anaplastic carcinoma Suggestive of follicle origin Sclerosing MEC with eosinophilia Unclear associations Cell of origin debated Solid cell nest phenotype Farhadt et al. Endocrine Pathology (2013) 24: Shah Modern Pathology (2017) 30,

5 Key points Squamous entities in the thyroid may occur across the spectrum from reactive/benign to malignant. in the background of a primary thyroid diagnosis must be distinguished from true squamous cell carcinoma of the thyroid = ATC and direct extension of a SCC While squamous metaplasia occurs in thyroiditis The mass lesion, sclerosis, mucinous change and background eosinophils combine to aid diagnosis Important Information Regarding CME/SAMs The Online CME/Evaluations/SAMs claim process will only be available on the USCAP website until September 30, No claims can be processed after that date! After September 30, 2017 you will NOT be able to obtain any CME or SAMs credits for attending this meeting. 5