Update on anaplastic thyroid carcinoma: morphological, molecular, and genetic features of the most aggressive thyroid cancer

Abstract

Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features.

Figure 1

Grossly, ATC shows a diffusely infiltrative pattern of growth. The cut surface can be brownish (a) or whitish (b); in both specimens discrete yellowish areas of necrosis are evident.

Figure 2

FNAB smears are usually made up of polymorphic neoplastic cells in a dirty necrotic background ((a) Papanicolaou stain, (b) May-Grunwald Giemsa stain).

Figure 3

(a) In sarcomatoid ATCs, neoplastic cells are morphologically indistinguishable from a primary sarcoma. At higher power view (b), spindle cells are pleomorphic and show a storiform pattern of growth. (c) Anastomosing cords of neoplastic cells resembling neoplastic vessels are the dominant features in this case.

Figure 4

Neoplastic giant cells are characterized by deep pleomorphism, with bizarre multiple hyperchromatic nuclei (a). They differ from reactive osteoclast-like giant cells (b) that show bland cytological features and are typically immunoreactive for CD68-KP1 (inset).

Figure 5

In the epithelioid-squamoid category, neoplastic cells show a solid (a) or nested (b) architecture. They are plump and have abundant cytoplasm with a variable degree of squamous differentiation (c).

Figure 6

A significant rate of ATC is associated with WDTC. In this case, residual foci of papillary carcinoma are seen in the lower right corner but the main bulk of the tumor is composed of strands of squamoid atypical cells and spindle neoplastic elements.

Figure 7

An ATC made up of pleomorphic epithelioid cells arranged in loosely cohesive nests; focally, intracytoplasmic vacuoles are present ((a), (b)). Immunohistochemical stains with keratin 7 (c) and TTF1 (d) highlight entrapped thyroid follicles.

Figure 8

Schematic representation of molecular pathways altered in ATCs.

Figure 9

Lymph node metastasis of WDTC with anaplastic areas. Residual foci of papillary carcinoma are present in the right upper corner but the metastatic deposits are constituted mainly by spindle cells with wide necrotic areas (a). While both WDTC and ATC are immunoreactive with pankeratin (b), TTF1 is positive only in the WDTC (c).