Prognostic impact of fibrosclerotic changes in non-papillary, non-anaplastic, follicular cell-derived thyroid carcinomas.

In non-papillary follicular cell-derived thyroid carcinomas, prognostic factors are scarce. Intratumoral fibrosis was identified as an adverse factor in papillary and medullary carcinomas, but it has not been investigated in other subtypes. We aimed at exploring the presence of intratumoral fibrosclerosis in a cohort of 132 non-papillary follicular cell-derived thyroid carcinomas (53 follicular and 31 oncocytic carcinomas, including 10 high grade differentiated thyroid carcinomas and 48 poorly differentiated carcinomas) and correlating its presence and extent with clinical and pathological features and survival. For each case, all available hematoxylin and eosin slides were reviewed, and the presence of fibrosclerosis was assessed as the percentage of tumor area and semi-quantitatively scored as absent, mild (≤ 10%) or extensive (> 10%). In addition, digital image analysis was applied in 65 cases. Scoring of intratumoral fibrosis showed a strong agreement between two observers and between observers and digital image quantification. The presence and extent of intratumoral fibrosis were significantly associated with poorly differentiated carcinoma histology, large tumor size, extent of vascular invasion, presence of necrosis, high mitotic index, positive nodal status, and aggressive clinical outcome, and with a shorter disease-free and disease-specific survival, the former also in follicular and oncocytic carcinomas analyzed separately. These data support the potential use of fibrosis in the clinical practice since it is both easily assessable and significantly associated with the presence of parameters of aggressiveness. In addition, fibrosis is correlated with decreased survival rate independently from the tumor histotypes, suggesting its potential role as novel prognostic factor in non-papillary follicular cell-derived thyroid carcinomas.