Among diseases associated with plasma cell dyscrasia, both Castleman’s disease and POEMS syndrome (syn. Crow－Fukase syndrome, PEP syndrome) are well known. Other diseases related to plasma cell dyscrasia include TAFRO syndrome/Castleman－Kojima syndrome, TEMPI syndrome, AESOP syndrome, and immunoglobulin G4 (IgG4)－related disease. Diseases associated with the overproduction of interleukin－6 (IL－6), including Castleman’s disease, are grouped under the hyper－IL－6 syndrome. Since these diseases often share clinical symptoms, differential diagnosis of each disease is sometimes difficult. Plasmacytosis preferentially occurs in Asian inhabitants, and similar cases have been reported under different diagnoses including cutaneous Castleman’s disease, skin involvement of multicentric Castleman’s disease (MCD), and a possible cutaneous involvement of IgG4－related disease. Among the above－mentioned diseases, idiopathic MCD, POEMS syndrome, and IgG4－related disease are officially listed as Japan Intractable Diseases, and a research team has been organized for TAFRO syndrome. TEMPI syndrome has formally been listed in the World Health Organization classification 2017. This article reviews current knowledge on plasma cell dyscrasia－related syndromes and refers to the comprehensive pathogenic link of the diseases.[Skin Cancer (Japan) 2019 ; 34 : 1－9]

Serum 5－S－cysteinyldopa (5－S－CD) has been reported as a diagnostic marker of malignant melanoma, but its utility as a biomarker for targeted therapy remains unknown. We assessed serum 5－S－CD in 8 patients with metastatic melanoma (median age : 64.5 years) who were treated with targeted agents at Shinshu University Hospital between 2014 and 2016. 5－S－CD concentrations before and at 3－6 weeks after the treatment were measured, and their changes were compared with clinical responses as defined by the response evaluation criteria in solid tumors (version 1.1). A decrease of ≥10 nmol/L in 5－S－CD was observed only in patients who achieved partial response (n=3), whereas the change was within ±10 nmol/L in patients with stable disease (n=3) and progressive disease (n=2). In 2 patients who acquired resistance to the targeted therapy, 5－S－CD concentration continuously increased before imaging examination. These results suggest that 5－S－CD is a useful predictive biomarker in targeted therapy for metastatic melanoma.[Skin Cancer (Japan) 2019 ; 34 : 10－16]

A 44－year－old man with a 3－year history of erythema on the chest was diagnosed with mycosis fungoides (MF). His disease was stable for three years owing to treatments with topical steroids, narrow－band UVB irradiation, and oral etretinate. However, 4 years later, tumors developed in his scalp and perianal region. He was treated with oral prednisolone, bexarotene, intravenous administration of mogamulizumab, and radiation therapy, all of which showed limited effects. One year later, as 30% of his tumor cells expressed CD30, he was started on brentuximab vedotin, which was beneficial in reducing the size of the tumors. However, new lesions developed in the pharynx and larynx a few months later. Administration of gemcitabine was not effective, and the airway of the patient narrowed owing to enlarged tumors in the pharyngolarynx. He died three months later. Pathological dissection revealed multiple MF lesions in the internal organs, along with pneumonia and sepsis.[Skin Cancer (Japan) 2019 ; 34 : 17－23]

A 77－year－old man had a tylosis－like lesion on his left sole, which was first noticed six months before his visit. Ulceration occurred on the lesions, and the ulcer enlarged ; therefore, he was referred to our hospital. On examination, hard and coalescent subcutaneous nodules with ulcers were present on his left foot, from the sole to dorsal side. A skin biopsy revealed that tumor cells with atypical nuclei were distributed from the reticular dermis to the hypodermis. The tumor cells were positive for CD30 and negative for CD3, CD4, CD8, CD56, ALK, and EBER. No extracutaneous lesion was found by PET/ CT. Thus, the patient was diagnosed with primary cutaneous anaplastic large cell lymphoma. The tumor was treated with radiation therapy, but recurred on his left lower leg. Therefore, multi－drug combination chemotherapy with radiation (36 Gy) was performed. [Skin Cancer (Japan) 2019 ; 34 : 24－27]

Subcutaneous panniculitis－like T－cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma of mature cytotoxic T－cells, in which lymphoma cells infiltrate preferentially into subcutaneous adipose tissue. We retrospectively reviewed five cases of patients with SPTCL who were treated at the University of Miyazaki Hospital, between 2004 and 2017. The median age of the patients at diagnosis was 27 years (range, 22 to 79 years), with a female predominance (male to female ratio, 1 : 4). Almost all patients presented with painful erythema, predominantly on the thigh (n=1), lower leg (n=2), upper arm (n=2), and abdomen (n=1). Four patients also had high fever and fatigue. When the patients were classified using the TNM classification system, we found one patient with T2cN0M0, one patient with T3aN0M0, and three patients with T3bN0M0 disease. Of the five patients, one (T2cN0M0) was treated with local radiation therapy, and a complete response was achieved. Of the two patients (T3bN0M0) who were treated with combination chemotherapy, one had a complete response. Two patients (T2cN0M0 and T3aN0M0) were treated with oral steroids ; of them, one showed a complete response, and one experienced recurrence. Among the two patients with local recurrence, one was treated with oral bexarotene, and the other was treated with local steroid injections and local radiation therapy.[Skin Cancer (Japan) 2019 ; 34 : 28－34]

We report two cases of malignant melanoma of the esophagus treated with nivolumab.

Case 1 involves a 60－year－old man diagnosed in 2015. The cancer cell lines showed a wild－type BRAF mutation. Nivolumab was started because of multiple metastasis to the retroperitoneum and mesentery. Although the peritoneal lesions disappeared, the primary tumor and regional lymph node metastases persisted. Subsequently, subtotal esophagectomy with lymph node dissection was performed. Nivolumab was restarted after surgery ; however, brain metastasis was observed. Despite replacing nivolumab with ipilimumab and performing whole brain irradiation, the patient died.

Case 2 involves a 72－year－old woman who was diagnosed in 2015. Cancer cells obtained from the patient also showed a wild－type BRAF mutation. Combined positron－emission tomography and computed tomography revealed L2 vertebral body metastasis. Although the metastatic lesion disappeared after treatment with nivolumab, among the primary lesions, only pigmented lesions were affected. Despite continuation of nivolumab, the esophageal primary lesion recurred. Subsequently, subtotal esophagectomy with lymph node dissection was performed. Thus far, no evidence of cancer recurrence without treatment has been reported in this case.[Skin Cancer (Japan) 2019 ; 34 : 35－40]

Angiosarcoma is known as a malignant soft tissue tumor that originates from the endothelial cells of blood vessels or lymphatic vessels. Cutaneous angiosarcoma usually arises on the scalp of elderly individuals, and is characterized by rapid metastasis. A novel fusion gene NUP160－SLC43A3 was identified in 2015, and rapid tumor progression is reported in patients with tumors expressing the fusion gene.

We report a case of angiosarcoma on the right cheek of a 69－year－old Japanese man ; the tumor was positive for the NUP160－SLC43A3 fusion gene, but it showed slow progression. Although chemotherapy was highly effective for this patient, the tumor recurred on the right lower jaw eight years after his first hospital visit. The clinical significance of this fusion gene in tumor progression is still unclear, and future studies to elucidate this are warranted.[Skin Cancer (Japan) 2019 ; 34 : 41－45]

A 66－year－old man presented with a mass on the right side of the chest, which he had noticed 2 years before the first visit. Although he underwent resection, relapse was confirmed at the same site approximately after 1 year. Subsequently, a marginal excision of the tumor was performed ; however, cancer cells remained after the surgery. Histopathology of the excised tumor specimen indicated cutaneous leiomyosarcoma. A positron emission tomography－computed tomography scan revealed an accumulation of fluorine－18 deoxyglucose in the lymph node of the right axilla. We performed an enlarged resection, and a right axillary lymph node biopsy specimen was obtained. Histopathology revealed that the tumor cells infiltrated into the deep dermis of the primary tumor but were not present in the lymph node. This patient with cutaneous leiomyosarcoma can be considered as having a good prognosis ; however, because of the infiltration of tumor cells into dermal layers, a careful follow－up is necessary.[Skin Cancer (Japan) 2019 ; 34 : 46－49]

A 63－year－old woman presented with a red nodule measuring 11 mm on her left lower leg. The nodule had gradually enlarged over the course of 1 year. A skin biopsy revealed Merkel cell carcinoma ; subsequently, the tumor was resected. During tumor resection, another red nodule measuring 5 mm appeared on the right cheek of the patient. This new lesion was also diagnosed as Merkel cell carcinoma on biopsy. This tumor was also resected and postoperative radiotherapy was performed. In this case, lesions appeared at anatomically distant sites on contralateral sides of the body in a short period of time. At a follow－up conducted 4 years later, there was no sign of distant metastasis to other organs. The prognosis of cancer depends on the tumor stage, which differs according to the relationship between the lesions. In this case, we evaluated the two lesions histopathologically and immunohistochemically, and found no difference between them. There was no difference in the expression of Merkel cell polyomavirus between the lesions, making it difficult to classify them as double primary or skin metastasis. [Skin Cancer (Japan) 2019 ; 34 : 50－56]

A 74－year－old man presented with a left cheek nodule. He had a surgical history of excision of the cheek lesion nine years previously, which was diagnosed as a benign neoplasm with sweat gland differentiation. Histopathologically, the nodule consisted of nests embedded in mucin pools, while immunohistochemically, the tumor cells were positive for cytokeratin 7 (CK7) and gross cystic disease fluid protein 15 (GCDFP－15) and negative for CK20. No lesions were observed in the other visceral organs. Based on a diagnosis of primary cutaneous mucinous carcinoma (PMC) with left parotid lymph node metastasis, he underwent a wide local excision and radical neck dissection. He received additional excision and radiation therapy for local recurrence 20 months later. We retrospectively reviewed specimens from past excisions. The tumor consisted of sweat gland－like epithelium and was positive for CK7 and GCDFP－15. The pre－existing lesion was diagnosed as endocrine mucin－producing sweat gland carcinoma, which most likely progressed to PMC. [Skin Cancer (Japan) 2019 ; 34 : 57－62]

A 59－year－old man presented with pruritic erythema on his head, which had not responded to oral corticosteroids, cyclosporine, or diaminodiphenyl sulfone. Erythematous cerebriform plaques were found on his whole face with leonine facies, which were accompanied by depilation of his head. Additionally, some papules were found on his neck. A biopsy specimen from his forehead lesion showed perifollicular and intrafollicular infiltrates of medium－to－large atypical lymphocytes and follicular mucinosis. Immunohistochemical stains of the atypical lymphocytes were positive for CD3 and CD4 and negative for CD8 and CD20. Southern blotting did not identify a clonal rearrangement of the T－cell receptor. Computed tomography showed multiple lymphadenopathy in his head and neck ; and therefore, we diagnosed the patient with stage IIB of folliculotropic mycosis fungoides. We started combination therapy with vorinostat and electron beam irradiation by tomotherapy. Ten months later, we stopped vorinostat because he developed cerebral infarction. Subsequently, bexarotene was administered, and he showed a partial response.[Skin Cancer (Japan) 2019 ; 34 : 63－68]