MLANA (Melan-A)

Clinically, the case was challenging because it mimicked a non-neoplastic proliferative process and, microscopically, presented as an amelanotic variant. An immunohistochemical panel is recommended to avoid diagnostic pitfalls; this is the first report of TRP-2 immunoexpression in oral amelanotic melanoma.

Pembrolizumab was initiated, but disease progression ultimately occurred after several months, accompanied by functional decline...Endobronchial metastasis should be considered in patients with a remote history of melanoma presenting with new respiratory symptoms. Prompt diagnosis through bronchoscopy and immunohistochemistry enables timely implementation of palliative and supportive management.

This case highlights the role of TPR::NTRK1 fusion in driving abnormal melanocyte proliferation and the potential contribution of MCL1 amplification to tumor progression. These findings provide insights into the genetic underpinnings of APN in CMN and suggest potential therapeutic targets for high-risk lesions.

Compound heterozygosity for MC1R high-risk alleles may explain the extensive nevus burden and support intensified surveillance. Personalized follow-up strategies guided by advanced imaging and genomics can improve early detection and prevention of melanoma.

The diagnosis of this rare manifestation of melanoma is technically challenging and rectal melanomas are often clinically misinterpreted as conditions such as hemorrhoidal disease. To date, there is no standardized therapy, but surgical intervention should be considered for local control. The role of adjuvant radiotherapy, chemotherapy, or immunotherapy in this disease has not yet been determined. Coil embolization can be a viable palliative treatment alternative for recurrent bleeding in patients unfit for surgery, which, has not been reported specifically for rectal melanoma.

Adjuvant intensity-modulated radiotherapy was subsequently delivered. This case highlights the pivotal role of multimodality imaging in characterizing sinonasal tumors, guiding staging and therapeutic decision-making, and emphasizes the importance of maintaining a high index of suspicion when encountering atypical or persistent maxillary sinus lesions.

Definitive diagnosis relies on pathology and immunohistochemistry. Surgical resection remains the primary treatment, and the prognosis is generally favorable.

Our report highlights that fibroma-like PEComa can serve as an early indicator of occult TSC and underscores the diagnostic utility of GPNMB immunohistochemistry as a surrogate marker of TSC1/2/MTOR pathway activation. Comprehensive clinical and genetic evaluation for TSC is recommended upon diagnosis of this rare tumor.

As a result, the use of synaptophysin alone should be discouraged, and more specific markers such as chromogranin and INSM1 should be used in conjunction. A broad immunohistochemical panel and a high index of suspicion are essential to avoid misclassification of head and neck mucosal melanomas.

CP-GEP demonstrated good prognostic performance, particularly for patients with pT1b-pT2a melanoma and thus could be considered a noninvasive alternative for a SLNB.

CDKN2A and PCTH1 mutations, frequently detected in melanoma and basal cell carcinoma, respectively, were detected in the second case. The presence of 2 components with distinct immunoprofile yet with some common genetic aberration suggests that basomelanocytic tumors may arise from a common progenitor.

NGS identified an AKAP9 (exon 32)::BRAF (exon 9) fusion, without TERT promoter mutations or other high-risk alterations. This case highlights a rare molecular subset of Spitz melanocytoma and underscores the importance of integrated molecular and histopathological assessment for accurate diagnosis, prognostic evaluation, and potential targeted therapy.