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

Abstract

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.

Keywords: Fibrosis; Follicular; Poorly differentiated; Prognosis; Thyroid carcinoma.

Fig. 1

Representative images of intra-tumoral fibrosclerotic changes, occurring as inter-follicular fibrosis (a follicular carcinoma), inter-nodular stemming from the tumor capsule (b follicular carcinoma, d, poorly differentiated carcinoma), and intratumoral fibrosis (c oncocytic carcinoma). Digital imaging evaluation of fibrosclerotic changes areas, manually selected (red areas) and quantified using Aperio Scanner ScanScope XT tools (e, f)

Fig. 2

Spearman’s correlation between observers and digital imaging quantification

Fig. 3

Kaplan–Meier estimates of disease-free and disease-specific survivals according to tumor histotype (p < 0.0001 and p = 0.0001, respectively) (a, b). Kaplan–Meier estimates of disease-free and disease-specific survivals according to the presence and extent of fibrosclerotic changes, in the whole series and in histological type-based subgroup analyses. Fibrosclerotic changes scores are: 0, absent; 1, present mild; 2, present extensive (c–f) (FC: follicular carcinoma; OC: oncocytic carcinoma; PDC: poorly differentiated carcinoma)