A 65-year-old man presented with a red-brown nodule and a brown-black macule at the periphery of a brown plaque measuring 14×3cm on the right side of his back. Although the brown plaque was a congenital lesion, the nodule was recently detected by his primary care physician. Histopathological examination of the lesion revealed a compound nevus and concomitant malignant melanoma showing solitary proliferation and nests of atypical melanocytes in the epidermis and superficial dermis. The tumor thickness was 2.7 mm. Positron emission tomography-computed tomography showed no metastasis. We excised the lesion with a 2-cm margin from the scar at the biopsy site and a 5-mm margin from the nevus. After excision, right axillary and inguinal sentinel lymph node biopsies, followed by right axillary lymphadenectomy, were performed. Based on these results, we diagnosed him with malignant melanoma (pT3aN1aM0, stage IIIA). We administered 3 courses of postoperative interferon beta therapy, and no recurrence or metastasis has occurred during 1-year follow-up. Although malignant melanoma rarely originates in a medium-sized congenital melanocytic nevus, it is important to educate patients regarding the need for prompt dermatological consultation if a lesion changes in color and/or form.[Skin Cancer (Japan) 2018 ; 33 : 173-178]

We report two cases of mycosis fungoides (MFs).

Case 1 : A 66-year-old man was diagnosed with MF 40 years previously. At the age of 65 years, masses and ulcers appeared on his trunk, limbs, and eyelids. He was first treated with etretinate and narrow-band ultraviolet B phototherapy, which did not lead to any improvement.

Case 2 : A 66-year-old man was diagnosed with psoriasis 45 years previously. He was treated with corticosteroids, which maintained the symptoms well under control. However, he developed glaucoma, and the treatment was discontinued. Subsequently, the erythema on his trunk and face gradually spread, and tumors appeared.

We diagnosed both patients with MF (stage IIB) and treated them with low-dose oral etoposide and local electron beam radiation. This combination therapy markedly alleviated both the erythema and tumors within a few months. Although etoposide is a classical therapy, radiation in combination with etoposide is useful for the treatment of MF.[Skin Cancer (Japan) 2018 ; 33 : 179-184]

Case 1 : An 85-year-old woman presented with a tumor on her left knee that had appeared 5 months before, followed by many papules and nodules on her face and limbs. Histopathology and immunohistochemistry of the skin biopsy sample led to the diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN). Case 2 : A 91-year-old man presented with excessive purplish erythema on his trunk that had appeared 7 months before. Case 3 : A 67-year-old man presented with many papules and nodules on his limbs and trunk that had appeared a month before. These cases suggest that there are a variety of clinical features of BPDCN. We reviewed previous reports of BPDCN from the last 10 years. The clinical features of BPDCN can be divided into two types, namely, features associated with nodules and tumors and features associated with erythema and purpura. Cases with multiple nodules and tumors tend to be associated with poor prognosis.[Skin Cancer (Japan) 2018 ; 33 : 185-191]

A 42-year-old Japanese man was referred to our hospital in September 2013 with a growing brown macule on his back. We diagnosed it as malignant melanoma. Histopathological examination of an excisional biopsy specimen showed that it measured 2.0 mm in thickness. Metastatic lesions were not observed on whole-body computed tomography or in sentinel lymph node biopsy specimens. Approximately 2 years postoperatively, computed tomography revealed pulmonary metastatic lesions, and he was administered nivolumab. However, renal hilar lymph node metastasis was observed, which continued to progress. In November 2017, he was referred to our hospital with severe bilateral lower leg edema. Contrast-enhanced computed tomography showed obvious invasion of the inferior vena cava by metastatic renal hilar lymph nodes. Tumor thrombus secondary to direct invasion of metastatic melanoma is rare. We report a rare case of a patient with this condition and additionally present a literature review.[Skin Cancer (Japan) 2018 ; 33 : 192-195]

The immune checkpoint inhibitors anti-PD-1/PD-L1 and anti-CTLA-4 antibodies are often selected to treat unresectable BRAF mutation-negative melanomas. However, the response rates of these frequently used drugs are only 30% and 10%, respectively, and in some cases, treatment cannot be continued owing to adverse effects including overactivation of autoimmune response mechanisms. We used dacarbazine as the third-line treatment in 3 melanoma cases and observed the following clinical effects : partial response in 1, stable disease in 1, and progression of disease in 1 patient. In these 3 cases, the treatment effects of dacarbazine correlated with changes in serum lactate dehydrogenase (LDH) and 5-S-cysteinyldopa (5-SCD) levels. Going forward, accumulating more data on cases, reporting the response rate of dacarbazine, and investigating whether serum LDH and 5-SCD are useful as markers to evaluate the treatment effects will provide useful information for selecting the appropriate melanoma treatment.[Skin Cancer (Japan) 2018 ; 33 : 196-200]

An 83-year-old woman with rheumatoid arthritis noticed black nodules on her left heel. We observed a pedunculated black nodule sized 22×19×7mm on the left heel and left inguinal lymph node swelling. Positron emission tomography computed tomography (CT) showed abnormal uptake in 3 left inguinal lymph nodes. We performed total tumor resection with left inguinal lymph node dissection, and the diagnosis of malignant melanoma was confirmed. The left inguinal lymph node was positive (5/12) and staged as ⅢC, pT4bN3M0. As multiple organ metastases appeared on CT examination 3 months after surgery, we administered pembrolizumab. Three weeks after the initial administration, the patient’s serum creatinine level increased to 5.06 mg/dL. We diagnosed a grade 4 renal immune-related adverse event (irAE). After the administration of prednisolone at 30 mg/day (0.8 mg/kg/day), renal function gradually improved. In the present case, it was noteworthy that renal irAE appeared after a single administration of pembrolizumab.[Skin Cancer (Japan) 2018 ; 33 : 201-205]

A 17-year-old woman was diagnosed as having a pT4aN3M0 stage ⅢC malignant melanoma of the head. She underwent adjuvant chemotherapy and local injection of interferon-beta ; however, metastases appeared in the pituitary gland and breast. Surgery was performed for the metastases, but relapse occurred at an early stage. As the BRAF V600E mutation was positive, administration of dabrafenib and trametinib was initiated, which led to the rapid shrinkage of the metastatic lesion in the brain. Worsening of the lesion was confirmed after 10 months and the treatment was changed to stereotactic radiosurgery and pembrolizumab. However, the tumor expanded, and therefore, a rechallenge with dabrafenib plus trametinib was attempted. The patient did not respond to the treatment and she died 34 months after the initial surgery.

It has been reported that a rechallenge after discontinuation of BRAF inhibitors can yield good results ; however, the expected effect was not obtained in the present case. When performing a rechallenge with BRAF inhibitors, we need to fully consider the adaptation, including factors such as such as LDL level, number of metastases, and the effect of the combination of BRAF inhibitors and MEK inhibitors.[Skin Cancer (Japan) 2018 ; 33 : 206-210]

We report a case of 50-year-old man with a warty plaque along the lateral nail fold of his right fourth finger. A longitudinal pigmented streak of the nail plate was observed just beside the warty plaque. Following confirmation of a diagnosis of Bowen's disease according to nail fold biopsy, en bloc removal of the lateral nail unit was performed. Histopathological examinations of the resected specimen revealed atypical keratinocytes in the epidermis of the lateral nail fold and nail bed epithelium. Polymerase chain reaction (PCR) revealed human papillomavirus (HPV) DNA in the specimen. Analysis of the PCR product using direct DNA sequencing revealed that the sequence corresponded to the L1 gene of HPV type 34. Immunohistochemical staining for HPV showed positive results in the epithelium. Although periungual Bowen's disease is rare, the clinical distinction of this condition from periungual warts is very difficult. Longitudinal melanonychia adjacent to the warty lesion provides a clue to the diagnosis of Bowen's disease of the nail unit.[Skin Cancer (Japan) 2018 ; 33 : 211-214]

A 56-year-old woman noticed erosion of her oral mucosa and tongue 8 years prior to presentation. The mucosal lesions were initially diagnosed as oral lichen planus and were resistant to various treatments, including prednisolone, etretinate, and mizoribine, among others. She reported a 1-year history of a rapidly growing verrucous lesion on her upper lip, which was histopathologically diagnosed as squamous cell carcinoma (SCC). Although we administered intralesional radiotherapy, the tumor recurred 9 months after treatment. Additionally, she developed whitish protuberant lesions on the buccal mucosa and the hard palate. Subsequently, she received intra-arterial pepleomycin infusion using retrograde catheters via the bilateral superficial temporal arteries for a final diagnosis of oral florid papillomatosis (OFP). The tumors showed remarkable shrinkage without any recurrence 7 months after treatment. Patients with OFP clinically present with multiple whitish and verrucous lesions in the oral cavity and on the lips. OFP is a well-differentiated subtype (variant) of SCC. In our view, intra-arterial pepleomycin infusion should be considered curative treatment for OFP affecting the lips and the oral cavity.[Skin Cancer (Japan) 2018 ; 33 : 215-220]

A 76-year-old man noticed a keratotic nodule in the right preauricular region in 2016. Physical examination in April 2017 revealed a red keratotic nodule measuring 25×20 mm in size. An incisional biopsy confirmed the diagnosis of a well-differentiated squamous cell carcinoma (SCC). Invasion of the superficial parotid gland by the SCC was suspected on neck computed tomography (CT). Magnetic resonance imaging and positron emission tomography-CT revealed nodules in and around the superficial aspect of the parotid gland. Wide local excision of the cutaneous SCC, superficial parotidectomy, and a biopsy of lymph nodes around the parotid gland were performed using the Nerve Integrity Monitor system to avoid facial nerve injury. Histopathologically, atypical squamous cells with formation of horn pearls were identified proliferating into the dermis and the deep subcutis, without invading or metastasizing to the parotid gland and the lymph nodes. Dense peri-tumoral lymphocytic infiltrate and fibrosis of the adipose tissue were also observed. No apparent recurrence, metastasis, or facial nerve palsy has been observed over 15 months postoperatively.[Skin Cancer (Japan) 2018 ; 33 : 221-225]

The combined technique of using a radioactive tracer and fluorescent dye with indocyanine green (ICG) has been approved by the health insurance system to detect sentinel lymph nodes (SLN) in patients with malignant melanomas. In this study, the ICG fluorescence system (LIGHTVISION ; Shimadzu Corporation, Japan) was used in 2 cases of malignant melanoma to detect SLNs and lymphatic flows during operation. This unique system can simultaneously display 3 images of an optical image, a near-infrared fluorescence image, and a combined visible plus near-infrared fluorescence image and capture. Furthermore, to improve the visualization of the lymphatic basin, the color for the near-infrared fluorescence image can be manually changed to white, green, or blue. On the basis of our experience, we propose that LIGHTVISION can identify SLNs with higher sensitivity and contrast than other detection systems. Further prospective study to compare its usefulness with that of other on-label fluorescent detection devices is warranted in patients with malignant melanoma. The fluorescent detection system is expected to be widely utilized in dynamic examinations other than those for lymph vessel detection and remaining liver or cardiovascular function.[Skin Cancer (Japan) 2018 ; 33 : 226-230]

A 75-year-old woman had received hemodialysis for 24 years. She underwent total mastectomy, bilateral axillary lymph node dissection, and radiotherapy for bilateral breast cancer 13 years ago. Purpuric macules appeared on her left upper arm 2 years ago and gradually developed. On the first visit to our hospital, multiple hemorrhagic nodules were observed on the whole left upper arm with lymphedema. As histological findings of the nodule revealed angiosarcoma, we diagnosed her with Stewart Treves syndrome with lymphedema that appeared on the upper arm after surgery for breast cancer. Left axillary lymph node metastasis, but no distant metastasis was observed at that time. Although radiation therapy diminished tumor sizes, local recurrence occurred, and lung metastasis was also observed 2 and a half months after the treatment. Therefore, the administration of pazopanib was initiated. Recurrent skin lesions and lung metastasis disappeared after oral administration of pazopanib (400 mg/day for 3 months), but local recurrence appeared again 11 months after the pazopanib treatment. Pazopanib has been administered continuously because of the recurrent skin lesions that have developed slowly. Based on these findings, we consider that pazopanib may be one of the effective therapies for angiosarcoma in patients receiving hemodialysis.[Skin Cancer (Japan) 2018 ; 33 : 231-237]

A 77-year-old man presented to our hospital complaining of perianal erosive erythema. Based on findings from computed tomography scans, colonoscopy, and immunohistochemistry (IHC) for CK20 and GCDFP15, he was diagnosed with advanced extramammary Paget's disease (EMPD) with multiple metastases. IHC also revealed that the Paget's cells strongly expressed the human epidermal growth factor receptor 2 (HER2) protein. Therefore, he was treated using trastuzumab and paclitaxel according to the protocol for HER2-positive metastatic breast cancers. After 2 courses of this regimen, the primary skin lesion showed near-complete disappearance and the metastatic lesions dramatically regressed (partial response). The patient continues to show a response during the 16-month follow-up.[Skin Cancer (Japan) 2018 ; 33 : 238-243]

A 60-year-old woman was first reported to have a lesion on her head around 2008 ; several years later, she was referred to our department because of a suspected malignant tumor ; however, she did not visit us. In 2015, she visited our department for the first time with a chief complaint of bleeding from the lesion. An irregular lesion accompanied by easy bruising and an odor were observed, extending from the patient's parietal region to the forehead. The lesion showed a self-destructive tendency ; a part of the crown was recessed, the dura mater was exposed, and an arterial pulse was palpable. The pathological findings indicated squamous cell carcinoma. Lymph node and distant metastases were not observed on imaging examinations. Magnetic resonance imaging revealed parietal bone destruction and cranial infiltration. The patient was diagnosed with a stage IV (T4N0M0) lesion. She was treated with radiotherapy and docetaxel/cisplatin/5-fluorouracil (TPF) chemotherapy after resecting maximum tumor possible. After 5 courses of TPF therapy were administered, brain invasion was observed, and the patient was judged to have a progressive disease. Disease progression was subsequently halted when the chemotherapy was changed to gemcitabine/paclitaxel. A random biopsy of the ulcer remaining in the parietal region was performed after 5 courses of gemcitabine/paclitaxel therapy was administered, and the absence of tumor cells was confirmed. Thereafter, debridement and divisional grafting surgery was performed. We compared the present case with other cases of squamous cell carcinoma with intracranial invasion in Japan.[Skin Cancer (Japan) 2018 ; 33 : 244-249]

Lipofibromatosis is a rare, benign, but infiltrative soft tissue tumor seen in children. It is histologically distinct from other fibromatoses such as juvenile fibromatosis, fibrous hamartoma of infancy, calcifying aponeurotic fibroma, and lipoblastoma. Distinguishing histopathologic features of lipofibromatosis include abundant and disorganized adipose lobules traversed by bundles of spindled fibroblast-like cells. It most commonly presents in the extremities. We present a case of lipofibromatosis occurring on the back of a young girl and briefly review the related literature.[Skin Cancer (Japan) 2018 ; 33 : 250-254]

We report a case of locally advanced cutaneous squamous cell carcinoma of the left groin. A 63-year-old man presented with a painful tumor on the left groin, which he noticed 2 years ago without seeking medical attention. When he visited our hospital, he had a foul-smelling ulcerated tumor measuring 10×5×1cm. A biopsied specimen revealed squamous cell carcinoma. Computed tomography (CT) showed lymphadenopathy, which appeared to be adhering to the left femoral artery and vein. No distant metastases were detected using positron emission tomography-CT. We diagnosed him with stage IVA (T3N2M0) squamous cell carcinoma of the skin, and he was treated with chemoradiation therapy containing cisplatin and 5-fluorouracil together with electron beam irradiation without any serious adverse effects. After this series of therapy, the primary tumor and metastatic node showed partial regression and could be resected completely with sufficient margins.[Skin Cancer (Japan) 2018 ; 33 : 255-259]

Merkel cell carcinoma (MCC) is a highly malignant tumor that frequently occurs on the face of elderly patients. Many cases have been reported to be associated with other skin tumors. We experienced a case of MCC with Bowen's disease on a burn scar in which the neoplastic cells were negative for both CK20 and CK7. Summarizing the cases of MCC with Bowen's disease, the rate of CK20 positivity tends to be low. When diagnosing MCC, immunostaining for chromogranin A, synaptophysin, and CD56, is necessary. In addition, some reports indicate that cases of MCC associated with other epithelial tumors or those without expression of CK20 in neoplastic cells tend to be negative for Merkel cell polyomavirus. In these cases, sun exposure, immunosuppression, irradiation, and burns such as in this case may be involved as factors triggering onset.[Skin Cancer (Japan) 2018 ; 33 : 260-264]