Lacrimal Sac Malignant Melanoma in 15 Japanese Patients: Case Report and Literature Review

Abstract

Background. Primary malignant melanoma of the lacrimal sac is rare. A patient with lacrimal sac melanoma was presented, and 14 Japanese patients with lacrimal sac melanoma in the literature were reviewed. Case Presentation. A 78-year-old Japanese man was presented with painless swelling of the lacrimal sac on the left side. Dacryocystectomy revealed diffuse infiltration with large epithelioid cells, sometimes with pigments, which were positive for cocktail mix of antibodies to tyrosinase, melan A (MART-1), and HMB45, leading to pathological diagnosis of melanoma. One month later, positron emission tomography (PET) revealed 2 high-uptake sites (SUV_max = 10.29 and 15.38) at the levels of medial canthus and nasolacrimal duct, but no abnormal uptake in the other site of the body. The lesion had the BRAF V600E mutation. He began to take daily oral dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor), leading to no abnormal uptake on PET in half a year. He had stable disease in good physical status with small and weak uptake sites of lymph nodes on PET 1 year later. Results. In the review of 15 Japanese patients, including this patient, local recurrence was noted in 4 patients, regional lymph node metastasis only in 3, distant metastasis in 6, and no metastasis in 6. Five patients died within 2 years and the others were alive in short follow-up periods. Conclusions. Chemotherapy was the standard for local recurrence or metastasis. Emerging molecular target drugs, as shown in the present patient, would change the strategy for management of lacrimal sac melanoma.

Keywords: BRAF inhibitor; BRAF mutation; MEK inhibitor; PET/CT; dabrafenib; lacrimal sac; malignant melanoma; trametinib.

Figure 1.

Lacrimal sac mass (E) on the left side on computed tomographic scan (A) at the initial presentation in a 78-year-old man. About 1 month after dacryocystectomy, subcutaneous pigmented lesions (F) were noted and whole-body 2-[¹⁸F]fluoro-2-deoxy-D-glucose positron emission tomography fused with computed tomography (PET/CT) showed 2 high-uptake sites at the levels of medial canthus (SUV_max = 10.29, B) and nasolacrimal duct (SUV_max = 15.38, C). About half a year after oral dabrafenib (Tafinlar) 300 mg daily plus trametinib (Mekinist) 2 mg daily, the subcutaneous lesions subsided (G) with unchanged conjunctival pigmentation on the lacrimal caruncle (H) and no abnormal uptake on PET/CT (D).

Figure 2.

Pathology of lacrimal sac melanoma. (A) Large epithelioid cells with abnormal nuclei arranged in irregular strands and foci. (B) Small lymphocytes infiltrated as a focus among large neoplastic cells. The neoplastic cells are negative for keratin AE1/AE3 (C), and positive for cocktail-mix antibodies against tyrosinase, melan A (MART-1, melanoma antigen recognized by T cells-1), and HMB45 (D). Scale bar = 200 µm in A, C, and D. Scale bar = 50 µm in B.