Hobnail Variant of Papillary Thyroid Carcinoma

Abstract

The hobnail variant (HV) of papillary thyroid carcinoma (PTC) is an unusual entity recently proposed as an aggressive variant of PTC. We describe the pathologic and molecular features of 2 cases of HV of PTC. Both tumors presented in stage III (pT3 pN1a M0). The first case was diagnosed in a 62-year-old man, whereas the second was in a 53-year-old woman. Both patients were treated with total thyroidectomy and radioactive iodine. The primary tumors showed a hobnail/micropapillary pattern in ≥50% of the neoplasm, and positivity for TTF-1, TTF-2, thyroglobulin (TG), cyclin D1, and p53. The Ki-67 index was 4.6% and 5%, respectively. In case 1, the tumor disclosed BRAFV600E and TERT C228T (124:G>A) promoter gene mutation, negativity for NRAS, HRAS, and KRAS mutations, and negativity for RET/PTC1, RET/PTC3, and PAX8/PPARγ rearrangements. After 11 years the patient died with cervical lymph node, bone, and liver metastases. In the liver metastasis, the tumor displayed columnar cell PTC areas (positive for TTF-1, TG, and BRAFV600E) merging with undifferentiated carcinoma (UC) areas (positive for TTF-1 and BRAFV600E; negative for TG). In case 2, the patient died 6 years after treatment with local recurrence and disseminated metastases to the lung, pleura, bone, and liver. The tumor recurrence showed a UC component (positive for cyclin D1 and p53; negative for TTF-1 and TG) with a residual HV of PTC (positive for cyclin D1, p53, TTF-1, and TG). No BRAF, TERT, NRAS, HRAS, nor KRAS mutations were detected in the primary tumor or recurrence in case 2. Our findings suggest that p53-positive HV is a very aggressive form of PTC prone to progression to UC.

Genomic profile of columnar cell variant of papillary thyroid carcinoma

“…Both tall cell and hobnail variants are primarily BRAF-driven neoplasms; more than 90% of tall cell variant harbour the BRAF V600E mutation, 21,22 while this mutation is identified in 60-90% of hobnail variant. [23][24][25][26][27][28] We found that 44% of CCV possess the BRAF V600E driver mutation, which is somewhat higher than the previous single study, 8 but lower than the frequency seen in tall cell and hobnail variants. However, we found alternative mechanisms of BRAF activation in 33% of Recurrent broad copy number alterations.…”

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

“…They are, to some extent, genetically similar to PDTC in that p53 and TERT promoter mutations are more frequent in this variant than in classical PTCs [32]. Cameselle-Teijeiro et al reported that two PTCs with the hobnail cell features transformed into ATC in lymph nodes [33]. In that study, hobnail cell components were positive for p53.…”

Pitfalls in Challenging Thyroid Tumors: Emphasis on Differential Diagnosis and Ancillary Biomarkers

“…Concomitant tall cell areas were seen in around 40% of cases [ 16 ]. Hobnail cell variants with columnar cell change were also reported [ 18 , 19 ]. Synchronous or metachronous association of this variant with poorly differentiated thyroid carcinoma [ 19 , 20 ] or with anaplastic thyroid carcinoma [ 18 , 19 ] has also been described.…”

“…The overall immunohistochemical profile of this cytological variant of PTC is not much different than that of the classic PTC [ 18 ]. However, these tumors show strong nuclear staining for p53 in most cases [ 13 , 16 , 18 , 19 , 21 , 22 ].…”

“…BRAF V600E and TP53 mutations are the most common molecular alterations in this variant of PTC [ 18 , 19 , 21 , 23 , 24 ]. TERT promoter mutations [ 18 , 23 , 24 ], PIK3CA , CTNNB1 , EGFR , AKT1 and NOTCH1 mutations [ 24 ], and RET/PTC1 rearrangements [ 19 ] have also been reported.…”