Anaplastic or undifferentiated carcinoma is a malignant neoplasm behaving in a very aggressive fashion, and is constituted by undifferentiated cells. It has an epithelial origin but, in the most cases, it lacks immunoreactivity for follicular markers such as thyroglobulin or TTF- 1. It typically presents itself as a large mass (medium 6 cm) with a rapid growth (it may duplicate its volume in less than one week) and with a fatal outcome of a few months.
Anaplastic carcinoma is a rare neoplasm, representing about 5% of all malignant thyroid tumours, and it is a typical neoplasm of adult patients, the majority of whom are older than 60 years, whereas patients younger than 40 years are very rarely affected by the tumour. It is a little more common in females than in men (ratio F/ M:1.5:1). The etiological factors of anaplastic cancer include the pre- existence of a malignant or of a benign thyroid neoplasia. The aetiology is described by the clinical histories of patients followed- up for goitre or for differentiated thyroid cancer and who have developed anaplastic carcinoma. Another proof of the possibility of transformation from differentiated to undifferentiated or anaplastic carcinoma is sometimes the presence of residual areas of differentiated carcinoma (i.e. papillary carcinoma areas) in the context of anaplastic cancer. Another certain etiological factor is the lack of iodine. The introduction of iodine in a diet (in areas with chronic deficiency) has demonstrated a high decrease of anaplastic cancer. The genetic alterations include somatic point mutations. As already explained for poorly differentiated carcinoma, they include very early event, important for tumorigenesis and predisposition for further mutations (such as Ras mutations or BRAF mutations), and also gene alterations that drive the de- differentiation (like TP- 53 and β- catenin mutations).
On gross examination, anaplastic carcinoma appears as a large mass infiltrating all the thyroid gland and often the adjacent structures. Size varies from 1 cm to 20 cm (medium about 6 cm). The lesions are friable with multiple necrotic or haemorrhagic foci. In the paucicellular variant of anaplastic carcinoma the lesions may be hard to cut and present a whitish aspect. On light microscopy, anaplastic carcinoma may show heterogeneous aspects, which can coexist in the same tumour. The cells display marked anaplasia and can show spindle, epithelial, giant, rhabdoid features. The nuclei are extremely pleomorphic with irregular edge and granular chromatin. The mitoses, especially atypical mitoses, are very frequent and coagulative necrosis is a recurring feature. Regardless of its morphology, anaplastic carcinoma infiltrates the thyroid gland and its nearby structures as well as the veins and arteries.
The cells of anaplastic carcinoma may show immunohistochemical positivity for epithelial markers (i.e. cytokeratin), but usually lack expression for follicular markers such as thyroglobulin or TTF- 1.
Anaplastic cancer is rare but, if present, it rapidly leads to fatal neoplasia. It presents itself as a large infiltrating mass that extends to the neck structures such as the oesophagus, trachea, or big vessels. Distant metastases are present in more than 45% of patients, at diagnosis time, and they are localized in the bone, lung, or brain. Anaplastic carcinoma does not respond to radiometabolic therapy.
