H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma.

Melanoma represents a public health issue. One of the biggest goals of current research is to develop new therapeutic options for patients affected by this aggressive tumor. We conducted a retrospective study including 105 patients diagnosed with cutaneous and ocular melanoma, with stages varying from pT1a to pT4b and pT4e, respectively, and we performed immunohistochemistry reactions with the new potential prognostic marker, VISTA (V-domain Ig suppressor of T cell activation). We quantified the expression by applying the H-score adapted for VISTA and divided the patients, based on the median value, into groups that presented high, low, and negative expression. Therefore, we obtained 65 cases with positive expression for cutaneous melanoma and 8 cases with positive expression for ocular melanoma. Forty-one cases presented high expression in cutaneous melanoma and three cases presented high expression in ocular melanoma. In cutaneous melanoma, analytic statistics showed that VISTA expression was associated with a high Breslow index, high mitotic count, high Ki67 expression, and advanced clinicopathological stage. The majority of ocular melanoma cases demonstrating a positive reaction were classified as stage pT3, whereas earlier stages showed a negative reaction. Our findings underscore a significant correlation between VISTA expression and key prognostic factors in melanoma. Looking ahead, the prospect of future randomized studies holds promise in corroborating the clinical relevance of our findings. By further elucidating the intricate relationship between VISTA expression and melanoma progression, new treatment strategies could be found, improving patient outcomes in this challenging neoplasm.

Risk stratification of papillary thyroid microcarcinomas via an easy-to-use system based on tumor size and location: clinical and pathological correlations.

INTRODUCTION: We aimed to determine whether two clinically accessible parameters, tumor size and location within the thyroid, correlate with clinicopathological features that are predictors of high risk in papillary thyroid microcarcinomas (PTMCs). MATERIALS AND METHODS: PTMC cases were obtained from the database of the Department of Pathology, Emergency County Hospital, Târgu Mures, Romania. Four tumor groups were created based on tumor size and location: Group I (≥5 mm, subcapsular), Group II (≥5 mm, nonsubcapsular), Group III (<5 mm, subcapsular), and Group IV (<5 mm, nonsubcapsular) PTMCs. Clinicopathological features and follow-up data were compared by univariate and multivariate analysis. RESULTS: Our study included 164 PTMCs (n=70/20/19/55 in Groups I∕II∕III∕IV, respectively). High-grade morphological features, such as plump pink cells (p=0.010), tumor desmoplasia (p=0.022) and sclerosis (p=0.001), infiltrative tumor borders (p=0.005), positive resection margins (p=0.005), invasion into the perithyroid adipose tissue (p=0.001), irregular nuclear membranes (p=0.004), and pseudoinclusions (p=0.001) were significantly more prevalent among Group I PTMCs. Group IV PTMCs were characterized by a paucity of the above-mentioned morphological features, while Group II and III PTMCs displayed intermediate morphological profiles. CONCLUSIONS: Group I PTMCs proved to be associated with more aggressive morphological features and might need a more careful clinical approach.

Morphological features predictive for BRAF(V600E) mutation in papillary thyroid microcarcinomas.

BACKGROUND: The B-Raf proto-oncogene serine∕threonine kinase (BRAF) V600E (BRAF(V600E)) mutation represents a very specific marker for papillary thyroid carcinoma (PTC), including microcarcinomas (PTMCs). However, assessment of the BRAF(V600E) mutational status is expensive and not available in all pathology laboratories. AIM: We aimed to evaluate if we can identify those morphological features that could predict the presence of the BRAF(V600E) mutation in a series of PTMCs. MATERIALS AND METHODS: Nineteen PTMCs with analysis of 25 tumor foci were included. The following histological features were evaluated: size of the tumor, multifocality, extrathyroidal extension, tumor's border, characteristic PTC nuclear features, tumor-associated stromal reaction and histological variant. All PTMCs foci were subject to real-time polymerase chain reaction (RT-PCR) amplification targeting the BRAF gene. BRAF(V600E) mutation was assessed by high resolution melting (HRM) analysis and confirmed by Sanger sequencing. Morphological features associated with BRAF(V600E) positive and BRAF(V600E) negative PTMCs were compared using the two-tailed Fisher's exact test, with α set at ≤0.05. RESULTS: Out of the 25 PTMC foci, 16 (64%) were BRAF(V600E) negative, whereas nine (36%) were BRAF(V600E) positive. Our data showed that subcapsular localization (p=0.013), conventional histological type (p=0.05) and tumor-associated stromal reaction (moderate∕extensive fibrosis) (p=0.032) were significantly associated with the mutation. CONCLUSIONS: We have demonstrated the value of several morphological features in predicting a BRAF(V600E) mutation profile in PTMCs. All these parameters should be documented in the histopathological report, as they seem to be associated with this mutation and could serve as a risk stratification tool in the selection of patients in need for adjuvant post-surgery therapy.