Contributed by Shaymaa Hegazy, MD and Arivarasan Karunamurthy, MD
A male patient in the sixties, presented with an itchy 1.0 x 1.0 cm blue-black dome-shaped nodule over the left preauricular cheek with superficial erosion for 3 years (Figure 1). No family history of dysplastic nevi or melanoma was noted. The specimen was an excisional biopsy, measuring 1.8 x 1.3 x 1.1 cm that was serially sectioned.
Microscopic examination demonstrated a dermal multinodular melanocytic neoplasm composed of sheets and short fascicles of atypical enlarged pleomorphic epithelioid and spindled cells (Figure 2) with prominent nucleoli and increased cytoplasm with coarse to dusty melanin pigmentation (Figure 3). The neoplasm extended through the dermis into the subcutis, displaying increased mitotic activity and foci of necrosis with clusters of interstitial melanophages (Figure 4).
Tumor cells were positive for HMB45, SOX10 and showed preserved BAP1 expression (Figure 5). Also, the tumor cells displayed nuclear beta-catenin expression (Figure 6).
Our case showed overlapping histological features of deep penetrating nevus like melanoma, pigmented epithelioid melanocytoma, and melanoma ex blue nevi which encouraged molecular studies in this case. Subsequently, targeted DNA/RNA sequencing by Next Generation Sequencing (NGS) revealed BRAF V600K, TERT promoter region C250T, and CTNNB1 S45F mutations and CDKN2A/CDKN2B region loss.
A PET/CT scan revealed extensive bilateral pulmonary nodules with the largest in the left upper lobe measuring 1.1 cm. A subsequent left lower lobe wedge resection of the lung was performed and showed metastatic melanoma. The patient declined targeted therapy and then started on immunotherapy with dual checkpoint blockade (ipilimumab and nivolumab) with an excellent response to treatment.