Progression of Papillary Thyroid Carcinoma to Anaplastic Carcinoma in Metastatic Lymph Nodes: Solid/Insular Growth and Hobnail Cell Change in Lymph Nodes Are Predictors of Subsequent Anaplastic Transformation

Abstract

Most anaplastic thyroid carcinomas (ATCs) arise from papillary thyroid carcinoma (PTC). This process is also called anaplastic transformation, and the morphological harbingers of this phenomenon in nodal recurrence have not been assessed systematically. For this reason, the current study focused on features of 10 PTCs with regional lymph node recurrence that was accompanied with disease progression due to anaplastic transformation in at least one of the nodal recurrences. The findings of additional 19 PTCs which recurred without anaplastic transformation after ≥ 10 years of follow-up served as the control group. There were no clinicopathological differences between the two groups at initial surgery including age, gender, tumor size, lymph node metastasis, distant metastasis, extrathyroidal extension, histologic subtype, and treatment. The median time from the initial thyroid surgery to anaplastic transformation in the nodal recurrence was 106 months (range 6 to 437 months). Mutational analyses showed recurrent PTCs with anaplastic transformation had a high prevalence of BRAFV600E mutation (8/9) and TERT promoter mutation (9/9), both of which were detected in primary tumors. PIK3CAH1047R mutation was detected in one case. No case had RAS mutation. Nineteen recurrent PTCs without anaplastic transformation harbored BRAFV600E mutation and seventeen of these had TERT promoter mutation. Unlike primary tumors with subsequent nodal anaplastic transformation, TERT promoter mutation was only present in the metastatic nodal recurrence from 4 patients without transformation. No patients had neither high-grade features (necrosis and increased mitotic activity) nor solid/insular growth or hobnail cell features in their primary tumors. In the group of patients with transformation, 3 had solid/insular growth in the lymph node metastasis at the time of primary tumor resection (one displaying nuclear features of PTC and solid growth with increased mitotic activity, one with insular component consistent with poorly differentiated carcinoma component, and one displaying nuclear features of PTC and solid growth), and additional 2 patients had solid/insular growth with no high-grade features or poorly differentiated carcinoma component at the time of subsequent nodal recurrence prior to anaplastic transformation. Hobnail cell features were exclusively seen in subsequent metastatic lymph nodes prior to anaplastic transformation. The control group lacked solid/insular growth and hobnail cell features in the metastatic nodal disease. Aberrant p53 expression and loss of TTF-1 featured tumor components with anaplastic transformation. This series identified a subset of recurrent PTCs with TERT promoter mutation was prone to undergo anaplastic transformation, and that solid/insular growth and hobnail cell features were morphological predictors of anaplastic transformation in the nodal recurrence.

Hobnail variant of papillary thyroid carcinoma with anaplastic dedifferentiation co-existent with tuberculosis lymphadenitis

“…This variant is distinguished histologically and cytologically by three distinct architectural and cytologic features: micro-papillae lacking true fibrovascular cores, cells with eosinophilic cytoplasm and apically placed nuclei with a decreased nucleus/cytoplasm ratio (hobnail appearance), and loss of cellular cohesion that form characteristic hobnail cells in at least 30% of the neoplastic cells [17] , [31] . In recurrent PTCs, an increased mitotic count, the appearance of necrosis, high grade features, might be predictors of a subsequent anaplastic transition [32] . Most typical PTCs do not display solid and insular development, the appearance of these components in recurrent PTCs might indicate an anaplastic transition [32] .…”

“…In recurrent PTCs, an increased mitotic count, the appearance of necrosis, high grade features, might be predictors of a subsequent anaplastic transition [32] . Most typical PTCs do not display solid and insular development, the appearance of these components in recurrent PTCs might indicate an anaplastic transition [32] . Amacher et al reported when hobnail pattern is observed in PTC, it is strongly associated with other histologic variants known to be more clinically aggressive [16] .…”

Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome

“…Among these, four had also focal dedifferentiation characterized by a focal tumor component (less than 30% of the tumor volume) with solid growth, increased mitotic activity and/or necrosis. Focal dedifferentiation has been shown to alter the prognosis of patients with PTCs in former series ( 28 , 29 ). However, the current series also underscored that this finding also correlates with adverse biology.…”

How to identify indolent thyroid tumors unlikely to recur and cause cancer death immediately after surgery—Risk stratification of papillary thyroid carcinoma in young patients—

“…Recently Odate et al published 10 cases of PTC operated on at Ito Hospital and Yamanashi University for 40 years [67]. In these 10 cases, the tumor recurred in the lymph nodes, developed anaplastic transformation, and eight patients died of tumor [67]. The Ki-67 labeling index was low at <5% in 8 cases of primary thyroid PTC, and it was not available in the other 2.…”