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

Abstract

Thyroid pathology encompasses a heterogenous group of clinicopathological entities including rare and diagnostically challenging neoplasms. The review is focused on morphological, immunohistochemical, and molecular features of rare thyroid neoplasms that can pose diagnostic problems. The tumors are organized based on growth patterns including thyroid neoplasms with predominantly papillary, follicular, solid, and spindle cell growth pattern, as well as neoplasms with distinct cytological characteristics. A special section is also dedicated to rare thyroid tumors with peculiar patterns including thyroid carcinoma with Ewing family tumor elements and intrathyroidal thymic-related neoplasms.

Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

“…Because of the morphological features of C-MV of TC, distinction from other primary or metastatic lesions may be necessary [ 147 ]. C-MV of TC can simulate a colonic or metastatic breast carcinoma, but positivity for TTF1 can help determine the correct diagnosis.…”

“…The lack of morular structures, positivity for thyroglobulin and negativity for nuclear β-catenin distinguish columnar cell variant of PTC from C-MV of TC. Solid areas in the C-MV of TC can simulate a poorly differentiated thyroid carcinoma, but coexistence with a cribriform and/or morular pattern together with a lower mitotic index are typical of the C-MV of TC [ 147 ]. On the other hand, lung metastasis from C-MV of TC should not be misinterpreted as a primary adenocarcinoma of the lung based exclusively on the positivity for CK7 and TTF1 [ 148 ] can be helpful in this situation.…”

“…FNAB samples from C-MV of TC are commonly indicative of thyroid carcinoma, showing hypercellularity, papillary structures, epithelial flat monolayers, and/or morular structures [ 134 , 137 , 146 , 147 ]. Tumor cells are tall and columnar with spindle cytoplasm and obscure nuclei, but typical nuclear features of PTC (grooves, pallor, and cytoplasmic inclusions) are usually seen.…”

“…Tumor cells are tall and columnar with spindle cytoplasm and obscure nuclei, but typical nuclear features of PTC (grooves, pallor, and cytoplasmic inclusions) are usually seen. The presence of cribriform and/or morular areas as well as nuclear staining for β-catenin however, are the keys to the diagnosis of C-MV of TC [ 134 , 147 ].…”

Intratumoral Heterogeneity in Differentiated Thyroid Tumors: An Intriguing Reappraisal in the Era of Personalized Medicine

“…To define morphological ITH in DTTs, we need to introduce the new classification of thyroid tumors, in which some changes were introduced [ 30 , 31 , 32 , 33 , 34 ]. In fact, together with follicular adenoma (FA), some borderline entities were added, such as tumors with uncertain malignant potential (UMP), noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and hyalinizing trabecular tumor (HTT) [ 30 , 32 ] ( Figure 3 ).…”