Poorly differentiated thyroid carcinoma

Poorly differentiated thyroid carcinomas of the insular type are usually TGB positive, although the extent of cellular staining is generally weak and focal.Undifferentiated (anaplastic) thyroid carcinomas are most commonly negative for TGB. In the series reported by... 

Thyroid transcription factor-2 (TTF-2) and PAX-8, which are essential for thyroid organogenesis and differentiation, have also been studied in thyroid tumors. TTF-1, TTF-2, and PAX-8 were expressed in differentiated and poorly differentiated thyroid carcinomas, whereas TTF-1 and TTF-2 were expressed in 18% and 7% of anaplastic carcinomas, respectively. PAX-8, on the other hand, was present in 79% of anaplastic carcinomas. TTF-2 was negative in all other neoplastic and non-neoplastic tissues including those of pulmonary origin. Although PAX-8 was present in a variety... 

Approximately 15% of poorly differentiated thyroid carcinomas and a significantly higher proportion of undifferentiated/anaplastic carcinomas are positive for BRAE mutations.Moreover, the mutations occur more commonly in those poorly differentiated and undifferentiated carcinomas with a papillary component. These findings suggest that the high-grade tumors progress from BRAF-positive papillary carcinomas. 

Nikiforova MN, Kimura ET, Gandhi M, et al. BRAE mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003 88 5399-5404. 

Poorly differentiated endocrine neoplasms, depending on the site of origin, may produce characteristic peptide hormones. The group of poorly differentiated neuroendocrine tumors and their hormone production include islet cell tumors (insulin, glucagon, somatostatin, gastrin), pulmonary small cell carcinoma (bombesin in 45% of cases), and medullary thyroid carcinoma (calcitonin). 

Positive in almost all thyroid carcinomas, with reduced immunostaining of poorly differentiated carcinoma to complete absence in anaplastic types... 

The frequency of TGB positivity in thyroid carcinomas is dependent on the degree of differentiation and the histologic subtype. Generally, poorly differentiated carcinomas contain less TGB than do better-differentiated tumors. The levels of TGB mRNA are also correspondingly lower in poorly differentiated than in well-differentiated thyroid carcinomas. TGB immunoreactivity is present in more than 95% of papillary carcinomas (Figs. 10.7 and 10.8) and follicular tumors. Because TGB is also expressed in metastatic lesions, stains for this marker are particularly valuable in... 

The distribution of p53 has been examined in cases of thyroid carcinoma. In the series reported by Soares and coworkers, p53 was absent from 14 cases of goiter and adenoma and from 12 cases of papillary carcinoma. p53 was present in 20% of follicular carcinomas (predominantly of the widely invasive type), 16% of poorly differentiated carcinomas, and 67% of undifferentiated carcinomas. In the series reported by Holm and Nesland, 6 of 32 (19%) papillary carcinomas, 5 of 29 (17%) follicular carcinomas, and 18 of 24 (75%) undifferentiated carcinomas were p53-F. In contrast, the RB gene product was present in all thyroid carcinomas, suggesting that it does not play a major role in thyroid carcinogenesis. "... 

RET/PTCl is responsible for approximately 10%. RET rearrangements are common in pediatric patients and in individuals exposed to accidental or therapeutic irradiation. RET/PTCl is more common in classic PTCs, micro PTCs, and the diffuse sclerosing variant than in other types, whereas RET/PTC3 has been associated with the solid variant. RET rearrangements are less common in the follicular variant than in PTCs of conventional type. Interestingly, RET rearrangements are associated with PTCs that lack evidence of progression to poorly differentiated or undifferentiated thyroid carcinomas. 

Point mutations of RAS genes occur in approximately 20% of poorly differentiated and 50% of undifferentiated thyroid carcinomas, and BRAF mutations occur in 15% to 20% of these tumors (Table 10A)P The PTEN and P1K3CA genes are mutated in 15% to 20% of the cases, respectively. 

The CTNNBl gene encodes 3-catenin, which is an important intermediary in the Wnt signaling pathway.1 0441 Point mutations of CTNNBl occur in 25% and 66% of poorly differentiated and undifferentiated thyroid carcinomas, respectively. As discussed in a previous section, most tumors with mutations have a nuclear pattern of localization, in contrast to the usual plasma membrane staining pattern of differentiated tumors. 

Common sites of mutation in poorly differentiated and undifferentiated thyroid carcinomas include RAS, PTEN, PIK3CA, p53, and CTNNB1 genes. 

Carcangiu ML, Zampi G, Rosai J. Poorly differentiated ( insular ) thyroid carcinoma A reinterpretation of Langhans wuchernde Struma. Am J Surg Pathol. 1984 8 655-668. Ordonez NG, El-Naggar AK, Hickey RC, Samaan NA. Anaplastic thyroid carcinoma Immunocytochemical study of 32 cases. Am J Clin Pathol. 1991 96 15-24. 

Soares P, Cameselle-Teijeiro J, Sobrinho-Simoes M. Immunohistochemical detection of p53 in differentiated, poorly differentiated and undifferentiated carcinomas of the thyroid. Histopathology. 1994 24 205-210. 

Tallin G, Santoro M, Helie M, et al. RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin Cancer Res. 1998 4 287-294. 

Thyroid oaroinoma Papillary oaroinoma Follioular oaroinoma Poorly differentiated carcinoma Undifferentiated (anaplastic) carcinoma Squamous cell carcinoma Mucoepidermoid carcinoma... 

---