TY - JOUR
T1 - Lacrimal Sac Malignant Melanoma in 15 Japanese Patients
T2 - Case Report and Literature Review
AU - Matsuo, Toshihiko
AU - Tanaka, Takehiro
AU - Yamasaki, Osamu
N1 - Funding Information:
The present patient showed local recurrence of malignant melanoma along the nasolacrimal duct in addition to the subcutaneous infiltration. The recurrent melanoma was unresectable, and thus, a combined therapy with oral dabrafenib and trametinib was applicable since the tumor had the BRAF mutation. 38 , 39 The patient maintained the stable disease with no local recurrence but with small lymphadenopathy later in one and a half year after the initial surgery of dacryocystectomy. He was in good quality of life and had only tolerable adverse event as mild nausea. In the development of distant lymphadenopathy with mild abnormal uptake on PET/CT, we decided to continue dabrafenib and trametinib and not to switch to PD-1 or PD-L1anitbodies because PD-1 or PD-L1 antibodies might cause adverse event, resulting in poor quality of life. It should be noted that foci of infiltration with small lymphocytes were present among the large melanoma cells. This fact suggests that PD-1 or PD-L1 antibodies might work in recovering the immune surveillance to neoplastic cells. In literature review of Japanese patients with lacrimal sac melanoma, only 14 patients were found as case reports. The main features of lacrimal sac melanoma in 15 patients, including the present patient, were no dominance in gender and laterality. One third of patients had neither local recurrence nor distant metastasis after the initial surgery of dacryocystectomy. The patients with lymphadenopathy or distant metastasis or their combination usually underwent systemic chemotherapy based on dacarbazine and nimustine at that time, but died within 2 years after the initial surgery. Therefore, the prognosis was basically poor when metastasis was present. In the emerging trend with new therapeutic drugs, BRAF inhibitor and MEK inhibitor, 38 , 39 the strategy for management of lacrimal sac melanoma would be drastically changing. As complete as possible extirpation of the lacrimal sac remains the basis for local control and pathological diagnosis. In the case of nasolacrimal duct epithelial infiltration noted during the surgery, removal of pigmented lesions as deep in the nasolacrimal duct as possible would be recommended. In case of local recurrence mainly from the nasolacrimal duct lesion, further radical surgery would not be recommended and molecular target drugs would be better tried in the situation of unresectable tumor after the BRAF mutation is confirmed. Lymph node metastasis and distant metastasis are, of course, the indication of chemotherapy with molecular target drugs. Clinical staging by PET/CT is the standard in the assessment of lacrimal sac melanoma as are melanomas which arise in other sites of the body, including conjunctival melanoma 39 and choroidal melanoma 40 in the field of ophthalmology. Authors’ Note Data are available on reasonable request to the corresponding author. Author Contributions TM as an ophthalmologist followed the patient and did the surgery. TT as a pathologist made pathological diagnosis. OY as a dermatologist prescribed molecular target drugs and followed the patient. TM wrote the manuscript; TT and OY did critical review of the manuscript. All authors read and approved the manuscript. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Funding The author(s) received no financial support for the research, authorship, and/or publication of this article: Ethics Approval Not applicable to case reports, based on ethical guidelines for medical and health research involving human subjects issued by the Government of Japan. Informed Consent Oral informed consent was obtained from the patient. ORCID iD Toshihiko Matsuo https://orcid.org/0000-0001-6570-0030
PY - 2019
Y1 - 2019
N2 - 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 (SUVmax = 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.
AB - 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 (SUVmax = 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.
KW - BRAF inhibitor
KW - BRAF mutation
KW - MEK inhibitor
KW - PET/CT
KW - dabrafenib
KW - lacrimal sac
KW - malignant melanoma
KW - trametinib
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U2 - 10.1177/2324709619888052
DO - 10.1177/2324709619888052
M3 - Article
C2 - 31747798
AN - SCOPUS:85075611483
VL - 7
JO - Journal of Investigative Medicine High Impact Case Reports
JF - Journal of Investigative Medicine High Impact Case Reports
SN - 2324-7096
ER -