NTRK Gene Fusion Detection in Atypical Spitz Tumors

Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical features and are now regarded as an intermediate category of melanocytic tumors with uncertain malignant potential. Activating NTRK1/NTRK3 fusions elicit oncogenic events in Spitz lesions and are targetable with kinase inhibitors. However, their prevalence among ASTs and the optimal approach for their detection is yet to be determined. A series of 180 ASTs were screened with pan-TRK immunohistochemistry and the presence of NTRK fusions was confirmed using FISH, two different RNA-based NGS panels for solid tumors, and a specific real time RT-PCR panel. Overall, 26 ASTs showed pan-TRK immunostaining. NTRK1 fusions were detected in 15 of these cases showing cytoplasmic immunoreaction, whereas NTRK3 was detected in one case showing nuclear immunoreaction. Molecular tests resulted all positive in only two ASTs (included the NTRK3 translocated), RNA-based NGS and real time RT-PCR were both positive in three cases, and FISH and real time RT-PCR in another two cases. In seven ASTs NTRK1 fusions were detected only by FISH and in two cases only by real time RT-PCR. The frequency of NTRK fusions in ASTs is 9%, with a clear prevalence of NTRK1 compared to NTRK3 alterations. Pan-TRK immunohistochemistry is an excellent screening test. Confirmation of NTRK fusions may require the use of different molecular techniques.

Role of CALLA/CD10 Expression in Progression of Melanocytic Tumors: A Study in Egypt

BACKGROUND: Although most of melanocytic lesions can be diagnosed using morphology, there is a significant subset of lesions that are difficult to diagnose. These are a source of anxiety for patients, clinicians, and pathologists. This arouses the possible benefits of using ancillary techniques to solve this problem. CD10 is a zinc-dependent metalloproteinase, its expression is known to be associated with biological aggressiveness in various malignancies. AIM: This research observes the efficacy of CD10 in the progression of melanocytic tumors as well as the differential diagnosis between nevus and melanoma. METHODS: The material of this study included 49 paraffin blocks of Egyptian melanocytic tumors. CD10 expression either membranous and/or cytoplasmic in tumor cells was considered positive and scored, based on the percentage of cells stained and compared to Ki67 expression as a prognostic marker. RESULTS: In benign melanocytic nevi, only 16.7% of cases showed positive expression, all were + 1 score, compared to 82.6% of melanoma cases, mostly +1 score followed by +3 score and finally +2 score. The difference in CD10 expression among melanocytic tumors showed a highly statistically significant correlation between nevus and melanoma cases as well as in Spitz nevi versus other nevi. Another highly statistically significant correlation was observed between CD10 expression and both Ki67 expression and ulceration. CONCLUSION: CD10 expression was significantly higher expressed in melanomas rather than nevi with highly statistically significant positive relation with Ki67 and ulcer formation which supports its role as a potential biomarker in the development of malignant melanoma and marker of aggression.

Expression of SEC62 Oncogene in Benign, Malignant and Borderline Melanocytic Tumors—Unmasking the Wolf in Sheep’s Clothing?

SEC62 oncogene located at chromosomal region 3q26 encodes for a transmembrane protein of the endoplasmic reticulum (ER) and is expressed at high levels in numerous human malignancies. SEC62 overexpression has been associated with worse prognosis and high risk for lymphatic and distant metastases in head and neck cancer, cervical cancer, hepatocellular cancer, and lung cancer. However, its role in the development and tumor biology of melanocytic lesions has not been investigated so far. An immunohistochemical study including 209 patients with melanocytic lesions (malignant melanoma (MM), n = 93; melanoma metastases (MET), n = 28; Spitz nevi (SN), n = 29; blue nevi (BN), n = 21; congenital nevi (CN), n = 38) was conducted and SEC62 expression was correlated with clinical data including patient survival and histopathological characteristics. SN showed the highest SEC62 expression levels followed by MET, MM, CN, and BN. High SEC62 expression correlated with a shorter overall and progression-free survival in MM patients. Additionally, high Sec62 levels correlated significantly with higher tumor size (T stage), the presence of tumor ulceration, and the presence of lymph node as well as distant metastases. Strikingly, SEC62 expression showed a strong correlation with Clark level. Taken together, these data demonstrate that SEC62 is a promising prognostic marker in MM and has the potential to predict biological behavior and clinical aggressiveness of melanocytic lesions.

SPITZ NEVUS (JUVENILE MELANOMA) IN THE PEDIATRICIANS PRACTICE: CLINICAL PICTURE, DIAGNOSIS, PROGNOSIS AND TREATMENT

Spitz nevi (epithelioid and spindle-cell nevi) are a special group of melanocytic neoplasms with a specific clinical, dermatoscopic and histological picture. There are typical and atypical Spitz nevus. The typical Spitz nevus is more common in pediatric practice and has a benign course. Of particular interest are atypical forms that combine the characteristics of a typical Spitz nevus and melanoma. The article presents an analysis of the clinical picture, dermatoscopic, immunohistochemical, histological and genetic characteristics in various forms of Spitz nevus. The existing classification according to the metastasis risk degree is presented. The last recommendations on the tactics of managing patients with this nosology are discussed with examples of original observations.