Noninvasive follicular thyroid neoplasm with papillary-like nuclear features and the risk of malignancy in thyroid cytology: Data from Singapore

Introduction: The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on the risk of malignancy (ROM) in fine-needle aspiration cytology (FNAC) per The Bethesda System for Reporting Thyroid Cytopathology has not been well reported in Singapore. Methods: We retrospectively identified 821 thyroid nodules with preoperative FNAC from 788 patients out of 1,279 consecutive thyroidectomies performed between January 2010 and August 2016 in a tertiary general hospital in Singapore. Possible cases of NIFTP were reviewed for reclassification and the impact of NIFTP on ROM was analysed. Results: The incidence of NIFTP was 1.2% (10 out of 821). If NIFTP is considered benign, ROM in Bethesda I through VI were 8.6%, 3.5%, 26.3%, 20.0%, 87.7%, 97.0% versus 8.6%, 4.2%, 28.1%, 26.7%, 89.2% and 100% if NIFTP is considered malignant. Eight patients with NIFTP had follow-up of 15 to 110 months. One had possible rib metastasis as evidenced by I131 uptake but remained free of structural or biochemical disease during a follow-up period of 110 months. None had lymph node metastasis at presentation, nor locoregional or distant recurrence. Conclusion: Classifying NIFTP as benign decreased ROM in Bethesda II through VI, but the benignity of NIFTP requires more prospective studies to ascertain. The impact of NIFTP on ROM in our institution also appears to be lower than that reported in the Western studies Keywords: Bethesda, cytology, NIFTP, risk of malignancy, TBSRTC, thyroid nodule

Signet Ring Cell Adenoma Thyroid – A Case Report

Signet ring cell adenoma is a rare thyroid neoplasm which usually present as a solitary nodule. Histopathologically it can very well be mistaken for a metastatic signet ring cell lesion, as both of them shows cells with intracytoplasmic vacuole and eccentrically pushed nucleus. The intracytoplasmic vacuole in signet ring cell adenoma stain positive for thyroglobulin which help in confirming the diagnosis. Here we describe a case of signet ring cell adenoma of thyroid in a 46-year-old female with its cytological, histological and immunohistochemical features.

Cytomorphologic findings of thyroid carcinoma showing thymus-like (CASTLE) differentiation: A case report

Introduction/Objective Thyroid carcinoma showing thymus-like differentiation also known as intrathyroidal thymic carcinoma is a rare thyroid neoplasm arising from either an ectopic intrathyroidal thymic tissue or from remnants of thymobranchial pouches. On fine needle aspiration (FNA) its diagnosis can be challenging due to overlapping morphologic features with other aggressive thyroid carcinomas. Methods/Case Report A 31-year-old female consulted for 6-month history of neck swelling and tenderness. Thyroid ultrasound demonstrated a 2.6 x 2.5 x 2.1 cm nodule in the right lobe with punctate calcifications. FNA showed cellular smears composed of loosely cohesive and single basaloid neoplastic cells exhibiting significant cellular and nuclear pleomorphism. Focal squamous differentiation with keratinization was noted on the cell block sections. Immunocytochemical stains showed that the tumor was positive for cytokeratin AE1/AE3, p40, p63, CD117 and CD5 consistent with intrathyroidal thymic carcinoma. The Ki67 proliferative index was approximately 40%. A right thyroidectomy with central neck dissection confirmed the diagnosis and showed a 3.0 cm tumor with invasion into skeletal muscle, lymphovascular invasion and positive lymph nodes. The patient completed adjuvant radiotherapy and remain in remission at 3-months follow-up. Results (if a Case Study enter NA) NA Conclusion Intrathyroidal thymic carcinoma is a rare thyroid neoplasm that frequently shows squamous differentiation and therefore overlaps with papillary thyroid carcinoma with squamous morulae, squamous cell carcinoma and anaplastic carcinoma. The coexpression of squamous markers together with CD5 and CD117 allows the recognition of CASTLE on FNA samples.

NTRK3-rearranged thyroid carcinoma, clinical and pathologic features

Introduction/Objective NTRK3 gene encodes a transmembrane protein receptor of the tropomyosin receptor kinase (Trk) family. Gene fusions involving NTRK3 result in a constitutive activation or overexpression of Trk receptor, potentially leading to oncogenesis. NTRK targeted therapies show a promising activity in varied cancer types with NTRK fusions. The aim of this case review is to describe the clinical and pathologic findings of thyroid neoplasm with NTRK3 gene fusions. Methods/Case Report The cytology fine needle aspiration (FNA), molecular testing results and pathology of surgical resections are reviewed in 220 cases of total and hemithyroidectomy from January 2018 to May 2021. Results (if a Case Study enter NA) Three cases with NTRK3 gene fusions are identified by Thyroseq or Afirma GSC from FNA of thyroid nodules with later surgical intervention. No other mutations or gene fusions were identified. Each case had total thyroidectomy. Case 1 is a 41-year-old female with FNA diagnosis of suspicious for papillary thyroid carcinoma (PTC) and ETV6/NTRK3 fusion found by Afirma GSC. Pathology diagnosis is PTC classic type, two tumor nodules 1.1cm and 1.0cm, lymphovascular invasion not identified, three lymph nodes not involved by tumor and pathologic stage pT1b(m) pN0. Case 2 is a 49-year-old female with FNA diagnosis of atypia of undetermined significance and ETV6/NTRK3 fusion detected by Thyroseq. Pathology diagnosis is infiltrative PTC follicular variant, 2.0cm, angioinvasion present, no lymph nodes submitted and pathologic stage pT1b(m) pNX. Case 3 is a 28-year-old female with FNA diagnosis of suspicious for follicular derived neoplasm and NTRK3/RBPMS fusion is detected by Afirma GSC. Pathology diagnosis is infiltrative PTC follicular variant, 1.5cm, 9 of 11 lymph nodes positive for metastatic carcinoma and pathologic stage pT1b pN1b. Conclusion Thyroid neoplasm with NTRK3-rearrangement is rare. Cases 1 and 2 with common ETV6-NTRK3 fusion show PTC classic type and infiltrative PTC follicular variant with angioinvasion. Case 3 with less common NTRK3/RBPMS fusion shows infiltrative PTC follicular variant and significant lymph node involvement. Our limited cases of NTRK3-rearranged thyroid carcinoma demonstrate infiltrative growth, diverse phenotypes, one case with angioinvasion and no lymph nodes submitted and one case with multiple lymph node metastasis. This suggests aggressive behavior of thyroid cancer with NTRK3 gene fusion and patients may benefit from targeted NTRK therapy.