A Case Report of Spitzoid Melanoma in a Patient with Breast Cancer.

Dear Editor:

A previous study showed increased risks of cutaneous melanoma in patients with breast cancer in Western populations1. Asians have a lower incidence of melanoma, with the most common type being acral lentiginous melanoma2.

A 42-year-old female presented with a 1-cm sized brown nodule and a separate, small brown macule on her right temple. The lesion had appeared the preceding month (Fig. 1A). A year prior, she had been diagnosed with cancer of the right breast. Punch biopsy of skin lesion revealed epithelioid melanocytes with pleomorphic, hyperchromatic nuclei that formed a tumor mass with coarse melanin granules (Fig. 2A, B). A high mitotic rate (3/mm2) was also observed in the deep dermis (Fig. 2C). The satellite lesion showed an atypical epithelioid melanocytes (Fig. 2D). Immunohistochemical staining of these cells revealed MelanA, Human Melanoma Black-45, and Ki-67 positivity (Fig. 2E~G). Immunohistochemistry for p16 was negative (Fig. 2H). The patient was finally diagnosed with cutaneous melanoma of the spitzoid subtype. After diagnosis, she was transferred to the department of plastic surgery to undergo wide excision (Fig. 1B, C). On preoperative radiological evaluation including 18F-FDG PET/CT, brain magnetic resonance imaging, chest and abdominal CT, any evidence of metastasis was not observed. After lymphatic mapping, a wide local excision with a 1.5-cm margin and sentinel-node biopsy were performed. Breslow depth was 2.77 mm. Tumor-infiltrating lymphocytes were observed. Tumor-positive sentinel lymph nodes (right mastoid process area) were confirmed, and radical neck lymph node excision was performed immediately. On pathological staging, stage IIId was confirmed (pT3aN3cM0).

Fig. 1

(A) A dark brown nodular lesion with a brown macule on the patient’s right temple. (B) Before excision, (C) wide excision specimen. We received the patient’s consent form about publishing all photographic materials.

Fig. 2

(A, B) Histologic examination shows an epithelioid-shaped melanocyte, with pleomorphic, hyperchromatic nuclei, forming a tumor mass with coarse melanin granules. A cleft between the nests of melanocytes and adjacent keratinocytes is observed. The epidermis is thin, and Kamino bodies are absent (H&E A: ×40, B: ×100). (C) The deep dermis also demonstrates a high mitotic rate (arrow). Nested melanocytes within the deep dermis lack maturation (H&E, ×400). (D) A satellite lesion also shows a nested pattern of atypical epithelioid melanocytes (H&E, ×100). (E) The tumor cells are diffusely positive for MelanA (MelanA, ×40) and (F) Human Melanoma Black-45 (HMB-45, ×40). (G) Ki-67 index has been estimated as 50% in the superficial dermis and 20% in the deep dermis (Ki-67, ×40). (H) Negative for p16 (p16, ×40).

We have tested for BRAF V600E and its mutation was detected. Spitzoid melanoma should also be distinguished from nevoid melanoma and epidermotropic metastatic melanoma. Nevoid melanoma usually shows smaller nuclei and less cytoplasm3. Epidermotropic metastatic melanoma is usually characterized by the presence of vascular invasion and shows focal epidermal involvement and a wider dermal component which were not seen in the present case4. Based on the histological findings, spitzoid melanoma was the most appropriate diagnosis.

With improvements in survival rates of patients with breast cancer, the prevalence of second primary malignancies has increased. One potential explanation for this association is that radiotherapy increases the risk of other cancers. Another possible mechanism for this phenomenon is mutation in cyclindependent kinase inhibitor 2A (CDKN2A) or breast cancer 2 (BRCA2). However, our patient tested negative for BRCA2 mutation. CDKN2A is a tumor suppressor gene that encodes two protein products, namely, p16, a cyclin-dependent kinase inhibitor, and p145. Previous studies have suggested a tumor suppressor role for p16/CDKN2A in melanoma5. In our patient, immunohistochemical staining for p16 was negative, and this absence of p16 expression is associated with a loss of a genomic CDKN2A copy5. Unlike B-RAF and N-RAS, loss of the CDKN2A gene has been suggested as a useful tool for the diagnosis of spitzoid melanoma, supporting the hypothesis that this type of cancer is associated with distinct pathways5.

This case suggests that physicians should be aware of the possibility of melanoma as a second primary cancer in patients with breast cancer.