Macrofollicular Variant of Papillary Thyroid Carcinoma with Extensive Lymph Node Metastases

Abstract

The macrofollicular variant of papillary thyroid carcinoma is a rare subtype of the follicular variant of papillary thyroid carcinoma and is usually characterized by an indolent clinical course. The tumors are prone to be misdiagnosed as benign due to their macrofollicular architecture and bland cytologic features. We report a rare case of the macrofollicular variant of papillary thyroid carcinoma with extensive lymph node metastases. The patient was a 48-year-old female with a right thyroid nodule and multiple enlarged lymph nodes in the right neck. It was not possible to make a definitive diagnosis of malignancy on fine-needle aspiration cytology and intraoperative frozen section. She underwent total thyroidectomy with right modified radical neck dissection. The surgical specimen showed a 2.5 × 1.5 × 10 cm, well-circumscribed macrofollicular variant of papillary thyroid carcinoma in the right lobe and multiple central and right lateral neck lymph node metastases. Molecular testing for BRAF, NRAS, HRAS, and KRAS was all negative. We then reviewed the demographic and clinicopathologic characteristics of 71 patients with the macrofollicular variant of papillary thyroid carcinoma. The cytologic or histopathologic diagnosis of macrofollicular variant of papillary thyroid carcinoma can be difficult. Extensive lymph node metastases caused by the macrofollicular variant of papillary thyroid carcinoma may occur even in the absence of capsular or lymphovascular invasion. This review will help to better understand the nature of the macrofollicular variant of papillary thyroid carcinoma.

Molecular pathology and thyroid FNA

“…Macrofollicular variant of PTC is extremely rare with fewer than 80 cases reported. The very few cases studied have shown no evidence of BRAF or RAS mutations . Cribriform‐morular variant of PTC is an interesting variant, occurring predominantly in young females, either sporadically in patients with germline APC mutations or, in ~40% of cases, it is associated with familial adenomatous polyposis .…”

“…The very few cases studied have shown no evidence of BRAF or RAS mutations. 20 Cribriform-morular variant of PTC is an interesting variant, occurring predominantly in young females, either sporadically in patients with germline APC mutations or, in~40% of cases, it is associated with familial adenomatous polyposis. 21 While the results reported in the literature vary, mutations of CTNNB1, the gene encoding b catenin or APC mutations are most commonly found, or PIK3CA mutations.…”

Update on the cytologic features of papillary thyroid carcinoma variants

“…The macrofollicular variant (MFV) of PTC is an extremely rare morphological variant of PTC/FVPTC with <80 cases reported in the literature. [98][99][100][101][102][103] MFV is arbitrarily defined by the predominance of macrofollicules (>200 mm). [98][99][100][101][102][103] Most cases (85%) are encapsulated and the prognosis appears to be similar to FVPTC, although there are a few case reports with systemic metastases and death.…”

“…[98][99][100][101][102][103] MFV is arbitrarily defined by the predominance of macrofollicules (>200 mm). [98][99][100][101][102][103] Most cases (85%) are encapsulated and the prognosis appears to be similar to FVPTC, although there are a few case reports with systemic metastases and death. 98,99 In addition, although their incidence is usually low (26%), 99 cervical lymph node metastases in MFV may be extensive and/or bulky, and may occur even in non invasive encapsulated cases.…”

“…[98][99][100][101][102][103] Most cases (85%) are encapsulated and the prognosis appears to be similar to FVPTC, although there are a few case reports with systemic metastases and death. 98,99 In addition, although their incidence is usually low (26%), 99 cervical lymph node metastases in MFV may be extensive and/or bulky, and may occur even in non invasive encapsulated cases. 99,100 They also typically retain the macrofollicular architecture of the primary tumor.…”