The anti-PD-1 antibody nivolumab has been used to treat malignant melanoma, although its response rate is low and it shows high individual variation. The effect of combination therapy with the anti-CTLA-4 antibody ipilimumab is not very beneficial given the increased side effects associated with it. Although anti-PD-1 therapy after stereotactic radiosurgery has been attempted, there is not enough evidence to support its efficacy. We report the case of a 67-year-old man with postoperative recurrent head melanoma that was treated using anti-PD-1 antibody administration after PEG IFN-α adjuvant therapy. Rapid reduction in tumor size was observed after this sequential administration, and no immune-related adverse events were observed after treatment with both the drugs. Our observations suggest that pegylated interferon-alpha adjuvant therapy followed by anti-PD-1 antibody treatment is clinically efficacious and well tolerated by patients with metastatic melanoma.[Skin Cancer (Japan) 2016 ; 31 : 216-221]

A 46-year-old man noticed a swelling on his right axilla. Although it was suspected to be related to a malignant lymphoma at first, histological examination revealed that it was an axillary lymph node metastasis of an amelanotic melanoma of unknown primary origin. The patient also developed multiple lung metastases and was treated with DAV-Feron and DAC-Tam chemotherapy. Subsequently, V600E BRAF mutations were identified and the patient was referred to our clinic for vemurafenib treatment. Although this treatment led to a significant and rapid reduction in the sizes of all the metastatic lesions, the lesions recurred 4 months after the vemurafenib treatment. We changed the treatment to nivolumab followed by ipilimumab. However, the tumors continued to progress, and the patient died a year after the initiation of the treatment. It was difficult for us to decide on an ideal course of treatment as it was difficult to make a quick and accurate diagnosis while the tumor continued to expand rapidly. Herein, we describe our patient, who was treated with every possible therapy that could be used for such tumors, including molecular target therapy and immune checkpoint inhibitors.[Skin Cancer (Japan) 2016 ; 31 : 222-226]

Dermatofibrosarcoma protuberans (DFSP) is known as an infiltrative skin tumor of intermediate malignancy, characterized by high rates of local recurrence and a low risk of metastasis. Microscopic findings show the tumor diffusely infiltrates the dermis and subcutis. The main portion of the tumor is composed of fibroblasts arranged in a storiform pattern, with little nuclear pleomorphism. In deep regions, the tumor intricately indigitates with subcutaneous fat, creating a honeycomb-like appearance. Immunohistochemically, DFSP is characterized by the presence of CD34 in a significant proportion of its cells. There are some histological variants in DFSP, and it is difficult to diagnose subtypes of DFSP, except for typical DFSP. In this report, we describe a case of pedunculated and massive DFSP on the right thigh region of a 68-year-old Japanese man, which showed the histological features of a myxoid type. A definite diagnosis of the case was established using detection of the COL1A1-PDGFB fusion gene. Therefore, detection of the COL1A1-PDGFB fusion gene is useful for the diagnosis of a rare subtype of DFSP.[Skin Cancer (Japan) 2016 ; 31 : 227-232]

The present case was of a 67-year-old male patient, who detected a black spot under his left hallux nail plate approximately one year prior to his initial medical examination. Subsequently, the lesion expanded, causing destruction of the nail ; this led the patient to undergo an examination at the department of dermatology at our hospital. Clinical analysis revealed primary malignant melanoma in the left hallux. Based on positron emission tomography-computed tomography results, the patient was suspected to have popliteal and inguinal lymph node metastasis ; he was therefore referred to our department. We performed a primary tumor resection, a sentinel lymph node biopsy, and a popliteal lymph node dissection. The primary tumor had a thickness of 11 mm and had infiltrated the periosteum. The inguinal lymph node biopsy was 1/3 positive (denoting metastasis to superficial inguinal lymph node) and the popliteal lymph node dissection was 1/2 positive (denoting metastasis to deep popliteal lymph node). At a later date, we performed an inguinal lymph node dissection and lymph node metastasis was no longer observed. Invasion of the primary tumor up to the hallux periosteum suggested that the tumor may have metastasized to the deep popliteal lymph node from the periosteum via deep lymphatic vessels. In conclusion, in cases where a primary tumor extends to deep tissues, it is important to consider the possibility of flow to deep lymphatic vessels.[Skin Cancer (Japan) 2016 ; 31 : 233-237]

Currently, an evaluation of imiquimod therapy (IT) response against actinic keratosis (AK) includes only ocular inspection. The therapy is deemed effective when the skin manifestations disappear. Following IT, the lesions usually leave behind some amount of erythema. Observational data were compared with histopathology findings of biopsies taken before and after IT from 15 patients with AK. Since all of 9 lesions clinically judged as marked relief and one out of four lesions judged as slight relief had histologically no tumor cells, they should be included in disappearance group. The ineffective 3 patients showed reduced skin findings with absence of tumor cells in the follow-up period, which was regarded as the late effect of IT. Finally 93.3% of the cases were judged effective. Though the time of evaluation should be 8 weeks after final imiquimod application routinely, some cases should be judged at later time point with histological confirmation. [Skin Cancer (Japan) 2016 ; 31 : 238-243]

A 52-year-old woman had a tumor in her right lower leg that gradually increased in size over several years. At presentation, it was an oozing, erosive 50-×80-mm tumor. Metastatic lesions in the liver, lungs, multiple lymph nodes, and calf muscle were apparent on fluorodeoxyglucose (FDG)-positron emission tomography. We diagnosed a stage Ⅳ malignant melanoma and initiated chemotherapy with nivolumab in May. Mohs paste was topically applied on the tumor, which resulted in partial regression. Because the tumor had a BRAF mutation, nivolumab was changed to vemurafenib. FDG enhancement vanished or decreased 3 months later. Her serum 5-S-CD reduced to 16.8 nmol/L, but magnetic resonance imaging revealed an enlarged lymph node in the right cervix. In November, she received treatment with ipilimumab. However, neck pain developed owing to metastases in the mouth and right cervix. Therefore, vemurafenib was administrated again. After the retreatment with vemurafenib, the mouth tumor promptly decreased in size. We will discuss the mechanism of tumor regression after retreatment with vemurafenib.[Skin Cancer (Japan) 2016 ; 31 : 244-248]

A 25-year-old woman noticed a black-colored line on her right ring fingernail that had been present since she was 16 years old. The 5 mm-wide brownish streak was observed on the nail when she visited our hospital for the first time at the age of 19 years. The micro-Hutchinson sign was positive. The pigmented band became broader, while its color became darker and then lighter during the follow-up observations. After a 3.5-year absence, she visited the hospital again at the age of 25 years as the nail pigmentation became darker with a crack at the tip of the nail. We diagnosed the patient with malignant melanoma in situ, and excised the lesion. Histological findings of the lesion were compatible with those of nail apparatus melanoma in situ. We report this case of nail apparatus melanoma in situ, followed-up for a long time, with clinical observation of its dermoscopic features, along with a literature review.[Skin Cancer (Japan) 2016 ; 31 : 249-254]

A 63-year-old man was diagnosed with malignant melanoma on the right side of his back. Recurrence was detected in the form of right axillary lymph node metastasis in the same year, and axillary dissection was immediately performed. The patient received postoperative chemotherapy and interferon therapy for 9 years and was recurrence-free during this period. Following this, he developed dyspnea and a right atrium tumor was detected. The tumor was resected and he was diagnosed with metastatic melanoma. The cardiac metastasis of a malignant melanoma is often seen as a part of systemic metastasis. However, many of these metastases are asymptomatic and remain undiagnosed until their progression. We also summarize data from 9 autopsies of patients with malignant melanoma who visited our hospital between 2000 and 2015.[Skin Cancer (Japan) 2016 ; 31 : 255-260]

A small, red nodule developed on the metatarsophalangeal joint of the left index finger in 2007 and was surgically resected in November 2013. It was histopathologically diagnosed as Bowen's disease. The patient was admitted to a regional hospital in May 2015 due to tumor recurrence at the operated site. Because the tumor rapidly expanded despite liquid nitrogen therapy, the patient consulted our hospital in August 2015. The tumor was surgically resected with a 2 cm surgical margin. Histopathological study revealed that the erythematous part showed findings of Bowen's disease and squamous cell carcinoma with differentiation into the skin appendages (sweat apparatus and hair follicle). In contrast, the mass part showed sarcoma-like findings with osteoblastic differentiation. We diagnosed the tumor as metaplastic carcinoma (carcinosarcoma) (CS) because the tumor consisted of 2 different parts : epithelial and sarcomatous. Cases of CS occurring originally in the skin have been rarely reported. Thus, we report herein a case of CS and a literature review.[Skin Cancer (Japan) 2016 ; 31 : 261-267]

A 58-year-old Japanese woman presented with a one-year history of onychomadesis and a mass over her whole left ring finger. She had worked as a filling station attendant for 30 years and had not worn rubber gloves at work. She had repeatedly developed erythema and blisters around the digit. Physical examination revealed erythema with desquamation on her thumb, erythematous plaques on her middle finger, and onychomadesis and edematous erythema with nodules on her ring finger. Examination of specimen biopsy of the left ring finger indicated squamous cell carcinoma, which had dysplastic keratinocytes with abundant amounts of eosinophilic cytoplasm and pleomorphic hyperchromatic nuclei. Given there was no evidence of actinic keratosis or history of burn injury or chemical exposure, we estimated that the SCC was caused by chronic inflammation due to contact with petrol. Our case is important to note as it describes atypical onset of SCC due to exposure to chemicals such as petrol.[Skin Cancer (Japan) 2016 ; 31 : 268-271]

A 92-year-old woman had a blackish-brown plaque on her left lower back, which was diagnosed as seborrheic keratosis by incisional biopsy 5 years ago. She presented to our hospital because the tumor had become larger and hemorrhagic. There was a reddish tumor at the center of the blackish-brown plaque, which was surrounded by a brown macule. Histopathology, the reddish tumor was diagnosed as squamous cell carcinoma. The blackish-brown plaque and brown macule exhibited the findings of clonal seborrheic keratosis and solar lentigo, respectively. Seborrheic keratosis and solar lentigo are diseases on the same spectrum. We considered this case as squamous cell carcinoma arising from seborrheic keratosis.[Skin Cancer (Japan) 2016 ; 31 : 272-275]

A 46-year-old man presented with a rapidly growing mass overlying a discoid lupus erythematosus scar on the lower lip. Biopsy revealed squamous cell carcinoma. The patient was successfully treated with selective intra-arterial chemotherapy using cisplatin combined with radiation therapy. Five months after the treatment, lymph node metastasis in the right neck was detected, and he underwent cervical lymph node dissection. Furthermore, multiple lymph node metastases had developed in the neck, medial mandibular, and axillary areas and rapidly progressed, even after the patient received radiation therapy and chemotherapy with cisplatin and S-1. Due to the EGFR mutation positivity of the tumor cells, the patient was treated with chemotherapy with cetuximab and paclitaxel, which was very effective in shrinking the metastatic tumor.[Skin Cancer (Japan) 2016 ; 31 : 276-279]

A woman in her twenties visited our hospital presenting with a subcutaneous tumor on the back, which gradually enlarged to 5 cm in diameter over a year. A biopsy was performed with the provisional diagnosis of an epidermoid cyst. The tumor contained prominent mucinous fluid. A histological examination revealed the proliferation of small round tumor cells in an alveolar configuration. Immunohistochemistry studies found that the tumor cells were positive for vimentin and CD99, while cytogenetic studies revealed the reciprocal translocation t (22 ; 11) (q24 ; q12) and the fusion gene EWS/FLI-1. A systemic examination revealed no other lesions suggesting malignancy ; thus, we diagnosed the tumor as a primary cutaneous extraskeletal Ewing's sarcoma. We excised the tumor with a margin of 4 cm, and administered adjuvant chemotherapy to the patient. We found no recurrence or distant metastasis over a 3-year follow-up period. According to previous literature and as seen in the present case, primary cutaneous extraskeletal Ewing's sarcoma is very rare, although its prognosis is better than that of Ewing's sarcoma of the bone.[Skin Cancer (Japan) 2016 ; 31 : 280-284]

A 69-year-old male was referred for the evaluation and excision of histologically diagnosed squamous cell carcinoma of his lower back. The tumor was dome-shaped, eroded, hemorrhagic, and 50×50×7 mm in size. Notably, numerous black to dark bluish punctate spots surrounded the tumor base. The pigmented spots indicated numerous acupuncture sites from treatments that the patient had undergone over a period of 20 years. Histopathology of the spots showed lichenification, suggesting a connection with the genesis of squamous cell carcinoma, as well as with the local trauma caused by excessive acupuncture treatments.[Skin Cancer (Japan) 2016 ; 31 : 285-289]

The shape and position of the eyebrows play an important role in the overall appearance of the face. To perform a cosmetically satisfactory repair in two cases of partial eyebrow defect due to surgical removal of squamous cell carcinoma, successful reconstruction of the eyebrows has been performed using free grafts harvested from the postauricular temporoparietal region. The reconstructed eyebrows had an almost natural appearance in terms of the flow and thickness of the hair, which resulted in great satisfaction for the patients.[Skin Cancer (Japan) 2016 ; 31 : 290-293]