Pulcrano, Melania (2008) POORLY DIFFERENTIATED FOLLICULAR THYROID CARCINOMA: PROGNOSTIC FACTORS AND RELEVANCE OF HISTOLOGICAL CLASSIFICATION. [Tesi di dottorato] (Unpublished)

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Background. Poorly differentiated follicular carcinomas (PDFC) of the thyroid represent an heterogeneous but distinct group of tumors, clinically and histopathogenetically intermediate between follicular-derived well-differentiated and anaplastic carcinomas. The existence of this group of tumors was first proposed independently by Sakamoto et al. in 1983 and Carcangiu et al. in 1984 according to substantially different diagnostic criteria. Indeed, although the number of articles written on the subject of PD carcinoma has grown exponentially during the last decade, at the present the diagnostic criteria differ between various authors. Moreover, there is no clear definition of the histological, immunohistochemical and genetic characteristics of PDFC. Furthermore, although the majority of studies show the aggressiveness of PDFC with a high propensity for local recurrence and distant metastasis, there is no consensus regarding the prognostic indicators for these tumors. Objective: The work performed during my Doctorate thesis in France contributes to clarify the histological definition and to identify clinical, histological, immunohistochemical characteristics of PDFC. For this purpose, parallel clinical, histological and immunohistochemical investigations have been performed. Methods: Forty patients affected by PDFC were identified on the basis of a trabecular, insular, or solid (TIS) growth pattern, and their clinical outcome was correlated with histological architecture, cytological characteristics and expression of various markers of cell proliferation and differentiation such as cyclin A, B1, D1 and E, Ki67, TPO, galectin 3, Duox, VEGF, EGFR, P53. Results: The mean survival was 5.2  5 years. At 5 years,the survival rate was 63% and the metastasis-free survival rate was 57%. An older age at the time of diagnosis and a larger tumor size were associated with an increased risk of distant metastases and of cancer related death whereas a high expression of Duox was associated with a reduced risk of death. In these patients with PDFC, no histological features or marker expression was prognostic. Conclusion: this study confirmed that PDFC has a more aggressive behavior than well differentiated carcinoma (WDC); prognosis is related to indicators that are relevant in patients with WDC, advanced age and larger tumor size.

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