An 89－year－old female had been treated with hydroxycarbamide (HC) for polycythemia vera since 2008. She had noticed a rice－sized red nodule on her back in 2006, which began to grow around 2010. At the first visit in 2016, a 30 mm－sized red nodule with erosion was noted on her middle back. Although squamous cell carcinoma (SCC) was suspected, she refused further examination. In 2020, she returned to us due to bleeding from the tumor, which was irregularly shaped, pale red, and elevated and had enlarged to 60×35 mm. In addition, she had a 30－mm keratotic tumor on the dorsum of her left hand and soybean－sized black scabs on the dorsum of her right hand. Biopsy from the tumor on her back confirmed the diagnosis of SCC and tumor resection was performed. Subsequently, the tumors on the left and right hands were resected and diagnosed as Bowen’s disease and SCC, respectively. HC is an anti－metabolic agent used for treating myeloproliferative disease. Recently, there have been increasing number of reports regarding non－melanoma skin cancer associated with long－term HC treatment. Multiple skin cancers could arise, as in our case, following the long－term use of HC. Careful monitoring is essential for the early detection of skin malignancy, particularly in patients treated with HC for long periods.[Skin Cancer (Japan) 2021 ; 36 : 190－196]

We report the case of a 33－year－old Japanese male who had previously been diagnosed with malignant melanoma on his back and left big toe, with new pigmented macules on his back and left lower leg being excised. Histopathological examination had revealed malignant melanoma（superficial spreading, in situ). His family history was significant for malignant melanoma in his mother and in two of his great－aunt’s children ; therefore, we diagnosed familial malignant melanoma.

In Europe and the United States, various genetic mutations, including CDKN2A, CDK4, BAP1, POT1, and TERT, have been reported as causes of familial malignant melanoma. In Japan, seven families have reported familial malignant melanoma, two of which underwent a genetic analysis with no reports of pathogenetic mutations. Although we performed genetic analysis by whole－exome sequencing, no pathogenic mutation was found here either. Future analyses are needed to clarify possible genetic mutations and their trends in familial malignant melanoma in Japan. [Skin Cancer (Japan) 2021 ; 36 :197－202]

A 41－year－old Japanese woman was referred to the Department of Otorhinolaryngology at our hospital with a diagnosis of right parotid tumor and cervical lymph node metastasis. The patient underwent right parotidectomy and right cervical lymph node dissection, and was referred to our department because of a histopathological diagnosis of malignant melanoma. A black nodule observed on the right preauricular area was excised as the primary melanoma. Two months after surgery, metastases were observed by computed tomography, which revealed the presence of an enlarged right axillary lymph node, a right breast subcutaneous nodule, and a right lower abdominal subcutaneous nodule. The right lower abdominal subcutaneous nodule was excised, and histopathological examination revealed metastatic melanoma. Although we planned to perform a right axillary dissection and partial right mastectomy, the operation was postponed due to the outbreak of Coronavirus Disease 2019 . Therefore, the patient was treated with dabrafenib/trametinib as for unresectable melanoma. Two months after the initiation of dabrafenib/trametinib, the right enlarged axillary lymph node and breast subcutaneous nodule disappeared. Four months after the initiation of dabrafenib/trametinib, the patient finally underwent a right axillary dissection and right partial mastectomy ; histopathological findings showed no residual melanoma. To summarize, the patient was successfully treated with dabrafenib/trametinib as neoadjuvant therapy. The neoadjuvant regimen of dabrafenib/trametinib, although uncovered by insurance in Japan, may be a useful therapeutic option for resectable advanced melanoma. [Skin Cancer (Japan) 2021 ; 36 : 203－211]

Adjuvant therapy for the postoperative prevention of advanced malignant melanoma recurrence is covered by medical insurance. The detailed analysis of the postoperative adjuvant treatment at a single institution can be useful to obtain important information about treatment preferences.

A total of 12 patients exhibiting negative BRAF mutation received adjuvant therapy with anti－PD－1 antibody ; three cases presented favorable outcomes, but one case showed recurrence within 1 year of successful execution. Moreover, a recurrence was noted in nine of the 12 cases during administration, with the average recurrence period being 5 months. Three of the seven patients exhibiting positive BRAF mutation received adjuvant therapy with anti－PD－1 antibody. All cases presented successful results with no recurrence. The remaining four patients received adjuvant therapy with BRAF/MEK inhibitor, and three cases showed positive results with no recurrence. The therapy was discontinued in a case with rhabdomyolysis, and recurrence was noted after 5 months. Nine of the ten patients, showing recurrence after receiving adjuvant therapy with anti－PD－1 antibody, were cured after nivolumab and ipilimumab administration, and one patient was cured using dacarbazine. The response rate of the therapy with nivolumab and ipilimumab was 33%. [Skin Cancer (Japan) 2021 ; 36 : 212－217]

Seventeen patients with basal cell carcinoma of the face were included in the study. FDG－PET/CT was used for imaging before surgery. PET images showed marked hot uptake in three patients and mild hot uptake in three. Histologically, three cases of nodular type, one case of glandular type, one case of infiltrative type plus patchy scleroderma type, and one case of superficial type plus infiltrative type were observed. The remaining 11 patients failed to demonstrate identifiable tumor activity on PET. In particular, a nodular case with a major axis of 15 mm did not show accumulation. In contrast, one patient exhibited asymptomatic malignant lymphoma before surgery, and another presented squamous cell cancer. In addition, in one case presenting a mild hot spot before surgery, small cell lung cancer, which was not observed before surgery, was detected using FDG－PET/CT 1 year post－surgery. [Skin Cancer (Japan) 2021 ; 36 : 218－223]

Immune－related adverse events (irAEs) in 38 patients ( 36 patients with melanoma and 2 patients with Merkel cell carcinoma) treated with immune checkpoint inhibitors in our department between December 2014 and February 2021 were retrospectively reviewed. Among them, 16 patients were treated with nivolumab, 20 patients with pembrolizumab, 6 patients with ipilimumab, 10 patients with a combination of nivolumab and ipilimumab, and 2 patients with avelumab. irAEs were observed in 72.7% of patients who received monotherapy and in 90 . 0 % of those who received combination therapy. Grade 3 and 4 irAEs occurred in 22 . 7 % and 40 . 0 % of all patients, respectively. In some patients, multiple severe irAEs occurred at the same time and rapidly exacerbated. In this article, we will summarize our experience with irAEs caused by immune checkpoint inhibitors and discuss the appropriate management for such cases. [Skin Cancer (Japan) 2021 ; 36 : 224－229]

A 60－year－old man presented with a 7－year history of red patches that spread on his abdomen. Physical examination revealed multiple red patches and plaques on his trunk, arms, and legs. A biopsy specimen from a plaque on his back revealed atypical lymphoid cells that infiltrated the basal and suprabasal layers of the epidermis and Pautrier’s microabscesses. Immunohistochemistry showed that the tumor cells were positive for CD 2 , CD 3 , and CD 5 , but negative for CD 4 , CD 8 , CD 45 RO, CD 56 , CCR4, and TIA－1. CD7 was not expressed in 40% of the tumor cells. Ki－67－positive cells were less than 10 %. His white blood cell count was 3 , 840 /μL without abnormal lymphocytes. Computed tomography images revealed no evidence of the involvement of lymph nodes and other organs. Thus, the diagnosis was CD 4 /CD8 double－negative mycosis fungoides. The patient was treated with topical corticosteroids and narrow－band ultraviolet B irradiation. CD 4 /CD 8 double－negative T cells are an extremely rare immunophenotype of mycosis fungoides. [Skin Cancer (Japan) 2021 ; 36 : 230－234]

A 58－year－old woman developed multiple pulmonary metastases 18 months after surgery for malignant melanoma of the left upper arm. She was administered nivolumab/ipilimumab combination therapy. Liver dysfunction, fever, and malaise that occurred after two combination therapies were treated using prednisolone (PSL, 20 mg/day), and the remaining two combination therapies were administered after recovery. The patient showed severe liver dysfunction, and administration of water－soluble PSL ( 1 mg/kg/day) was ineffective. Eventually, the patient responded to mycophenolate mofetil treatment ; however, normalization of liver function occurred after 3 months. Treatment with immune checkpoint inhibitors occasionally results in severe liver dysfunction. Although steroids are considered first－choice treatment, we conclude that prompt administration of mycophenolate mofetil is important in steroid－refractory liver disease. We investigated eight patients who received nivolumab/ipilimumab combination therapy at our hospital and observed various immune－related adverse events associated with immune checkpoint inhibitor administration. These effects showed a tendency to occur at different times depending on the type of inhibitor used. [Skin Cancer (Japan) 2021 ; 36 : 235－240]

A 37－year－old woman underwent tumor resection and sentinel node biopsy for vulvar malignant melanoma at another hospital. She was diagnosed with stage ⅢB (pT3aN1aM0) cancer and was referred to our hospital for additional treatment. The patient was administered adjuvant therapy using nivolumab and did not undergo lymph node dissection. We observed in－transit metastasis to the lower abdomen, following 18 cycles of chemotherapy ; surgical resection was performed, and nivolumab treatment was continued. She showed multiple metastases after 32 chemotherapy cycles, and her regimen was switched to nivolumab－ipilimumab combination therapy. She developed liver dysfunction (Grade 3 ) 7 weeks later, for which prednisolone (PSL) therapy ( 40 mg/day) was initiated. Although liver function improved, she showed neutropenia (Grade 4 ). The PSL dose was increased to 60 mg/day, and she was administered granulocyte colony－stimulating factor, which led to improvement in neutropenia, 9 days later. Although rare, immune checkpoint inhibitors may cause severe neutropenia, and early intervention is necessary for the management of this adverse effect. [Skin Cancer (Japan) 2021 ; 36 : 241－244]

A 59－year－old male patient presented with a mass on his right shoulder 6 months ago. The mass previously disappeared a month after its appearance. Thereafter, however, it exhibited rapid growth within a few weeks. During the initial examination, a solid 60－mm tumor growing outwards was observed. At the time of surgery, there was no invasion of the deep fascia, and the tumor was resected to the subcutaneous tissue layer. A postoperative histopathological examination revealed that the tumor was malignant. However, a more detailed diagnosis required an external consultation, which took time. Meanwhile, on postoperative day 13 , redness of the wound appeared, which suggested that the tumor had recurred. Since the tumor was growing rapidly, we decided to perform an extended resection as soon as possible. A repeat surgery was performed on day 21 following the initial resection. The inferior bed was resected in a single mass, including the trapezius muscle. It was then reconstructed using a parascapular skin valve with a 2－cm margin removed from the redness that appeared around the previous surgical scar. A histopathological examination revealed that the patient had pleomorphic dermal sarcoma (PDS). There was no local recurrence or metastasis at 13 months post－surgery. [Skin Cancer (Japan) 2021 ; 36 : 245－253]

Thyroglossal duct cyst is a benign cystic lesion in the anterior neck but rarely presents an internal malignant tumor. The ectopic thyroid tissue in the cyst is considered to be the origin of the disease, and histopathologi-cally, papillary thyroid cancer is the most common manifestation. It may be overlooked by fine needle aspiration cytology, and histopathological examination often reveals a malignant tumor after surgery. Herein, we report a case of papillary carcinoma occurring in the thyroglossal duct cyst of a young woman, along with a brief review of the literature. [Skin Cancer (Japan) 2021 ; 36 : 254－258]