Successful treatment of occult pancreatic melanoma using BRAF/MEK inhibitors

Abstract

Dear Editor, A 78-year-old female patient with no symptoms had an 11 mm 9 11 mm mass in the pancreatic body determined by ultrasonography. The routine laboratory data were within normal limits, including lactate dehydrogenase levels (165 U/L). Histological examination of a fine-needle aspiration biopsy specimen showed small nests of atypical cells in the pancreatic tissue. Atypical cells with mild nuclear pleomorphism with scant cytoplasm suggested pancreatic neuroendocrine tumor and other pancreatic epithelial tumors, lymphoma and malignant melanoma (MM) (Fig. 1a). The atypical cells were finally diagnosed as MM with positive immunohistochemical staining for Melan-A, HMB-45 and S-100 (Fig. 1b). Lymphoma and primary pancreatic epithelial tumors including ductal carcinoma, acinar cell carcinoma, neuroendocrine tumor and solid pseudopapillary neoplasm were ruled out based on the negative immunohistochemical results for CD3, CD79a, AE1/AE3, CAM5.2, trypsin, insulinoma-associated protein 1 and CD10. Contrastenhanced computed tomography (CT) revealed tumor lesions in the liver (S4, 19.1 mm; S6, 17.2 mm, respectively) in addition to the pancreatic lesion, while positron emission tomography CT, upper/lower gastrointestinal endoscopy, and ophthalmological, gynecological and otolaryngological examinations demonstrated no other tumor lesions. The patient was diagnosed with occult metastatic MM in the pancreas (pT9N9M1c, stage IV, based on the American Joint Committee on Cancer 8th classification). Surgical treatment was considered; however, the option was thought to be challenging due to the presence of several metastatic lesions including the liver (S4 and S6), in addition to the pancreatic lesion. Cytogenetic testing revealed the BRAF V600E mutation and the patient opted to be treated with dabrafenib and trametinib, which are BRAF/MEK inhibitors. In addition, immune checkpoint inhibitors (ICI) were proposed as alternatives and were rejected as the first-line medication owing to the possible side-effects. Therefore, treatment with dabrafenib (300 mg) and trametinib (2 mg) was started. Three weeks later, drug doses were reduced to 200 mg (dabrafenib) and 1.5 mg (trametinib) due to fever as a side-effect. Six weeks after treatment, CT indicated that the pancreatic lesion had almost disappeared (Fig. 1c), and the size of the liver metastatic lesion was also reduced (S4, 8.2 mm; S6, 14.1 mm, respectively). This patient is still under treatment with dabrafenib and trametinib for 3 months. Although surgical treatment for pancreatic metastasis of MM is a potential option, it is controversial owing to empirical observations that metastasis sometimes occurs just after major surgical invasion. The mechanisms underlying this phenomenon may be related to the immunosuppressive changes after surgery. Moreover, while ICI can be used as alternatives, a distinct first-line treatment in patients with BRAF mutation-positive MM has not been established. Additionally, the efficacy of BRAF/MEK inhibitors is shorter compared with ICI, necessitating careful explanations to patients prior to treatment and cautious follow up after treatment. Furthermore, owing to the rarity and lack of reports on occult pancreatic MM with BRAF mutations treated with BRAF/MEK inhibitors, additional evidence is crucial for treatment, including the actual effectiveness of BRAF/MEK inhibitors. This case study Figure 1. (a) Hematoxylin–eosin staining and (b) immunohistochemical staining are shown as indicated (bars, [a, left] 500 μm, [a, right; b] 50 μm). (c) Contrast-enhanced computed tomography before treatment and at 6 weeks after treatment with dabrafenib and trametinib are shown.