We report a case of clear cell sarcoma on the heel. The patient was a 31-year-old woman who noticed a subcutaneous nodule on the heel 1 year ago, and visited our department. We followed up the lesion without administering treatment because the nodule, which was 15×10 mm in size, was suspected to be a benign tumor, such as an epidermal cyst at that time. Since the nodule size increased, an excisional biopsy was performed after 2 years. Histological examination of the nodule revealed an asymmetric multi-nodular tumor with clear cytoplasm separated by fibrous septa. Immunohistochemically, tumor cells were positive for vimentin, S-100 protein, human melanoma black-45, and Melan-A. We diagnosed her with clear cell sarcoma based on fluorescence in situ hybridization of EWSR1 rearrangement. Therefore, we performed a wide local excision for the tumor, and neither metastasis nor recurrence have been observed for 1 year and 2 months after the surgery.[Skin Cancer (Japan) 2018 ; 33 : 1-6]

A 76-year-old man had complained of dacryorrhea and visited a hospital, where he was diagnosed with primary ductal adenocarcinoma of the right orbital region based on an excisional biopsy. Radiotherapy was administered. After one year, dark reddish macular lesions appeared on the right side of his neck and gradually increased in size. At the first consultation in our hospital, angiosarcoma was suspected from the clinical findings. Histopathological analysis revealed skin metastasis of the primary ductal adenocarcinoma. Taken together, the extensive erythema of the neck was diagnosed as carcinoma erysipelatodes. An imaging examination demonstrated right cervical lymph node metastasis, multiple bone metastases, and lung metastasis. Radiotherapy and chemotherapy were administered. The skin symptoms remarkably improved and the dysphagia was also relieved with these therapies. Only a few reports have been published describing primary ductal adenocarcinoma of the right orbital region ; cases of skin metastasis, such as ours, have rarely been reported.[Skin Cancer (Japan) 2018 ; 33 : 7-12]

A 55-year-old man was referred to our hospital with a right axillary subcutaneous mass, which gradually increased in size and had appeared approximately 6 months prior to initial examination. Histopathological examination revealed a solid tumor comprised of CD30-positive large heteromorphic cells, which was first presumed to be primary cutaneous anaplastic large cell lymphoma (PCALCL). However, since the patient revealed anti-human T-lymphotropic virus (HTLV)-1 antibodies, an alternative diagnosis of adult T-cell leukemia/lymphoma was considered. As only a single tumor was observed, we performed total excision of the tumor. The diagnosis of adult T-cell leukemia/lymphoma was established following confirmation of clonal uptake of HTLV-1 proviral DNA by the tumor tissue. As the prognoses of PCALCL and adult T-cell leukemia/lymphoma are different, it is important to differentiate between these diseases.[Skin Cancer (Japan) 2018 ; 33 : 13-16]

A 53-year-old woman underwent surgical treatment for left femoral malignant melanoma, pT4aN2aM0 stage IIIA, with a tumor thickness of 12 mm, and postoperative follow-up observation was performed. Since pulmonary metastasis appeared 5 months after surgery, 3 courses of treatment with dacarbazine (DTIC) were administered, but no effect was observed, and the treatment was changed to nivolumub. After initiation of administration, shrinkage of the temporary lung metastatic lesion was observed ; however, this was followed by exacerbation and multiple subcutaneous metastases were confirmed. Therefore, the treatment was changed to ipilimumab. She developed a severe eating disorder after four administrations of ipilimumub, and upper gastrointestinal endoscopy was performed. As a result, the condition of acute gastritis was confirmed ; a steroid internal dose of 20 mg/day was initiated and the symptoms improved promptly. Through this case, it was elucidated that when administering an immune checkpoint inhibitor treatment, it is necessary to consider the possibility of mucosal damage, not only in the colon, but also in the upper gastrointestinal tract.[Skin Cancer (Japan) 2018 ; 33 : 17-21]

Case 1 : A 64-year-old woman underwent surgical excision of a primary vaginal malignant melanoma, which later metastasized to her lungs and brain. She developed fulminant type 1 diabetes mellitus following the administration of the 7^th course of nivolumab. She developed hypothyroidism preceded by reduction in her thyroid stimulating hormone levels following the administration of the 2^nd course of ipilimumab and developed severe diarrhea after the administration of the 3^rd course of ipilimumab. Although she demonstrated severe adverse effects, brain metastases were observed to have disappeared after the administration of combined radiation therapy.

Case 2 : A 38-year-old man underwent surgical excision of a primary malignant melanoma of his right sole, which was followed by the development of multiple metastases to the skin. Administration of nivolumab suppressed the progression of the skin metastases. However, after the administration of the 8^th course of nivolumab, he developed sustained fever and nausea in addition to hyperthyroidism and liver dysfunction. In both afore-mentioned cases, although immune checkpoint inhibitors showed a good therapeutic effect in managing malignant melanoma, their use was associated with the development of severe immune-related adverse events. We temporarily discontinued the administration of immune checkpoint inhibitors. Close follow-up and monitoring of patients is required to detect immune-related adverse events. A prompt response/treatment is important to prevent worsening of the patient's condition.[Skin Cancer (Japan) 2018 ; 33 : 22-29]

A 39-year-old man presented with a fist-sized tumor on his right waist that had arisen 15 years previously. Histopathologically, the tumor comprised of spindle cells that showed a herringbone proliferation pattern with cluster of differentiation (CD) 34 negativity and storiform proliferation pattern with CD34 positivity, resulting in a diagnosis of fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP). Within 2 years, he developed multiple bilateral lung metastases and iliac bone metastases. After receiving treatment of imatinib and pazopanib, trabectedin was initiated as a third-line therapy. However, the tumor showed rapid growth, resulting in a fatal outcome. In the present case, trabectedin did not show efficacy.[Skin Cancer (Japan) 2018 ; 33 : 30-34]

A 50-year-old woman developed myoepithelioma in the pubic region. A nodular tumor approximately 7 cm in size along the longest dimension was located on the subcutaneous tissue with no adhesion to the surrounding structures. On microscopic examination, sections showed proliferation of epithelioid- to spindled-shaped cells arranged in a cord-like and small nested pattern, on a background of myxoid and fibrous stroma. Immunohistochemically, the tumor cells were positive for epithelial membrane antigen, α-smooth muscle actin, and negative for S-100, desmin, and pan-cytokeratin. The tumor was excised with negative margins and there was no recurrence or metastasis after the 2-year follow-up. [Skin Cancer (Japan) 2018 ; 33 : 35-39]

A 66-year-old man was referred to our hospital with a pale reddish and tender nodule on his temporal scalp, which was first identified 2 months prior to his presentation. The nodule measured approximately 5 mm in diameter, was slightly elevated, flat-shaped, elastic, and hard without perinodular erythema or purpura.

Histopathological examination revealed spindle cell proliferation, several mitotic figures, a few irregular vascular channels with swollen endothelial cells, and hemorrhage. Immunostaining showed that the tumor cells were positive for CD31, Factor VIII-related antigen, and D2-40 stains. Based on these findings, the patient was diagnosed with angiosarcoma.

The nodule was removed with a 4-cm periosteal margin, and there has been no recurrence or metastasis following the surgery. Solitary nodular angiosarcoma without erythema and purpura is rare.[Skin Cancer (Japan) 2018 ; 33 : 40-44]

A 76-year-old female presented with a 2-year history of a solitary tumor extending from the right vulva to the buttock, which grew slowly initially, and then rapidly during the last two months. It was a well-circumscribed, elastic, hard, and pedunculated tumor, 19×12.5×6cm in size, showing deep adhesion with a lower bed, with papillomatosis, erosion, and maceration. Right inguinal lymph nodes were enlarged and palpable. Laboratory tests revealed increases in white blood cell count (19500/μL) with neutrophilia, serum squamous cell carcinoma antigen levels of 30 ng/mL, circulating granulocyte-colony stimulating factor (G-CSF) levels of 96.2 pg/mL, and serum C-reactive protein levels of 1.34 mg/dL. Biopsy was performed, and histopathology revealed squamoid cells with nuclear atypia and mitosis ; these cells were contiguous to the epidermis, and proliferated downward into the deep dermis irregularly, accompanying scattered acantholysis and cancer pearls. The patient was diagnosed with a well-differentiated squamous cell carcinoma. The rectum, uterus, and bladder were resected, and pelvic and right inguinal lymphadenectomies were performed together with gracilis muscle flap reconstruction. Immunohistochemistry tests showed that tumor cells were focally stained with anti-G-CSF antibody. Although the circulating G-CSF levels decreased after the surgery, they increased again 50 days later. She died of metastasis 63 days after the surgery.[Skin Cancer (Japan) 2018 ; 33 : 45-49]

A 79-year-old Japanese woman, who was diagnosed with squamous cell carcinoma (SCC) of the right upper eyelid invading the bulbar conjunctiva, refused surgical therapy and initiated chemotherapy. In the present case, weekly intramuscular injection of peplomycin was not useful ; however, the combination of oral titanium silicate (TS)-1 plus topical fluorouracil (5FU) was effective for the tumor lesion. One year and 10 months after her first visit, the tumor was almost undetectable with only slight erythematous change without local enlargement, eye problems, and the development of distant metastasis and adverse events due to chemotherapy remaining. Non-surgical treatment using TS-1 and topical 5FU may be an option to maintain quality of life, especially in elderly patients with eyelid SCC infiltrating the surface of the eyeball.[Skin Cancer (Japan) 2018 ; 33 : 50-54]

We report a case of primary cutaneous anaplastic large cell lymphoma (C-ALCL) in a 77-year-old woman that recurred 20 years after the initial diagnosis. She presented with erythema and erosion on her right hallux, which developed into a gangrenous ulcer. A sixth skin biopsy performed showed perivascular infiltration of atypical lymphocytes in the mid dermis, which were positive for the CD30 stain. A right inguinal node was observed to be involved (T2cN1M0). She received treatment with oral prednisolone (PSL) and methotrexate (MTX) and local radiation therapy, which were very effective. We reduced the dose of MTX owing to the development of MTX-induced pancytopenia. She showed recurrence of C-ALCL, and her treatment was changed to oral PSL and low-dose etoposide. She has shown no recurrence over 3 years using the current therapy. [Skin Cancer (Japan) 2018 ; 33 : 55-60]

A 40-year-old man presented with a 20×13 mm brown macule on the right index finger pad, which had been noted and had gradually enlarged and darkened over a year. The macule was ill-defined and indistinct. Dermoscopy revealed a parallel ridge pattern with globules of various sizes and densities. The lesion was entirely excised and full-thickness skin grafting was performed. Histopathological examination showed proliferation of melanocytes with minimally atypical nuclei at the basal layer, mainly at the crista profunda intermedia. A new, similar macule appeared on the right middle finger pad 1 month later. As another melanoma seemed to be unlikely considering the short period, the new lesion was monitored without administering treatment. The new lesion spontaneously disappeared after 8 months and reappeared after 10 months. Although the parallel ridge pattern on dermoscopy strongly suggested the possibility of melanoma, benign lesions could also be included in the differential diagnoses. The lesion in the present case was thought to be a reactive lesion, but did not fit the characteristics of any known entity, and remained undiagnosed.[Skin Cancer (Japan) 2018 ; 33 : 61-65]

Burn scar carcinoma is known as Marjolin's disease in Western countries. However, the etiology of burn scar carcinoma remains unclear. Skin biopsies are often useful to diagnose squamous cell carcinoma (SCC), but in some cases, it may be difficult to determine if the individual scar includes a malignant tumor based on only histological examination of small pieces of the scar tissue. Here, we report two cases of SCC that developed in burn scars of the lower extremities.[Skin Cancer (Japan) 2018 ; 33 : 66-70]