Acta Dermato-Venereologica 99-6CompleteContent | Page 21

612
SHORT COMMUNICATION
Therapeutic Effectiveness of Immunoradiotherapy on Brain-metastatic BRAF/MEK Inhibitor-resistant
Melanoma with Balloon Cell Change
Haruka GOTO 1 , Takatoshi SHIMAUCHI 1 *, Kensuke FUKUCHI 1 , Naoki YOKOTA 2 , Shinichiro KOIZUMI 3 , Masahiro AOSHIMA 1 ,
Yuno ENDO 1 , Yurika MASUDA 1 , Hidehiko MIYAZAWA 1 , Akira KASUYA 1 , Katsumasa NAKAMURA 4 , Taisuke ITO 1 and Yoshiki
TOKURA 1
Departments of 1 Dermatology, 3 Neurosurgery and 4 Radiation Oncology, Hamamatsu University School of Medicine, 1-20-1 Handayama,
Higashi-ku, Hamamatsu 431-3192, and 2 Radiation Oncology Center, Suzukake Central Hospital, Hamamatsu, Japan. *E-mail: t-shima@
hama-med.ac.jp
Accepted Jan 23, 2019; E-published Jan 23, 2019
Balloon cell malignant melanoma (BCMM) is a rare vari-
ant of melanoma, first reported by Gardner & Vasquez in
1970 (1). BCMM is histologically characterized by large
and polyhedral foamy cells with abundant cytoplasmic
vacuoles (2). In general, brain metastasis is common and
is a poor prognostic factor in patients with melanoma,
even in the era when immune checkpoints and BRAF/
MEK inhibitors are used as therapeutic modalities (3).
Recent studies have shown that combined stereotactic
irradiation (STI) with immune checkpoints or with
BRAF/MEK inhibitors can significantly improve overall
survival for patients with melanoma brain metastases (4,
5). We report here a rare case of BCMM in which BRAF/
MEK inhibitors and subsequent anti-PD-1 antibody
(nivolumab) were ineffective, but the brain metastatic
lesions were completely resolved by STI in combination
with nivolumab.
CASE REPORT
A 71-year-old Japanese woman had a primary nodular melanoma
in the right posterior cervix and underwent a wide local excision
and sentinel lymph node (SLN) biopsy in the posterior cervix 4
years before she was referred to us. Histopathologically, both the
primary lesion (Fig. 1a, b) and SLN showed dense proliferation
of large atypical spindle or epithelioid melanocytes. She was diag-
nosed as having melanoma, stage IIIA (pT4a, N1a, M0; Breslow
tumour thickness, 5 mm; Clark’s level IV, without ulceration).
She received 3 courses of dacarbazine post-operative adjuvant
therapy, followed by monthly interferon-β intralesional injection
as maintenance therapy. Two years after the operation, however,
she developed multiple metastatic lesions in the lung, abdominal
subcutis, and brain without neurological abnormalities. Brain
magnetic resonance imaging (MRI) showed an isolated tumour
in the right frontal cortex (Fig. S1a 1 ). Biopsy specimens obtained
from the abdominal subcutaneous nodule confirmed the diagnosis
of metastatic melanoma (Fig. 1c), which had the same Melan
A + (Fig. 1d) HMB-45 + (Fig. 1e) cytological phenotype as the
primary melanoma, with a BRAF V600E mutation. She was treated
with a combination of BRAF (dabrafenib; 300 mg/day) and MEK
inhibitors (trametinib; 2 mg/day) with a therapeutic effect on the
metastases in the lung and abdominal subcutis, while the size of
brain lesion had been unchanged. At 13 months after initiation of
BRAF/MEK inhibitors, the metastatic brain lesion expanded from
25 to 41 mm in diameter (Fig. S1b 1 ). She underwent a tumour
resection, while BRAF/MEK inhibitors continued. Histologi-
https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3134
1
Fig. 1. Histopathology of primary lesion, metastases of abdominal and brain lesions. (a and b) Primary melanoma, excisional biopsy. A low-power
view of the lesion shows a hemisphere and pedunculated tumour. A high-power view demonstrates large atypical spindle or epithelioid melanocytes. (c)
Subcutaneous metastatic melanoma in the abdominal lesion, incisional biopsy. Solid proliferation of polygonal melanocytes with abundant cytoplasm,
irregular nuclei, and melanin. (d and e) Immunohistochemical staining of the subcutaneous metastatic tumour, positive for (d) Melan A and (e) HMB-45. (f)
Brain metastatic melanoma, excisional biopsy. A high-power view shows histiocytoid, foamy cells with abundant cytoplasm. (g and h) Immunohistochemical
staining of the brain metastatic melanoma, positive for (g) Melan A, but negative for (h) HMB-45. Scale bars: (a) 3 mm, (b–h) 100 μm.
doi: 10.2340/00015555-3134
Acta Derm Venereol 2019; 99: 612–613
This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta
Journal Compilation © 2019 Acta Dermato-Venereologica.