Sayuri Sato

Serum cytokeratin 19 fragment 21‐1 is a useful tumor marker for the assessment of extramammary Paget's disease

Cytokeratin 19 fragment 21‐1 (CYFRA 21‐1) has been used as a tumor marker for several malignancies. However, to date, no studies have assessed whether CYFRA 21‐1 could be a useful marker for extramammary Pagets disease (EMPD). The present study aimed to evaluate the significance of CYFRA 21‐1 as a serum tumor marker for EMPD progression. Concentrations of serum CYFRA 21‐1 and carcinoembryonic antigen (CEA) in 13 cases of EMPD were measured prior to undergoing treatment at Sapporo Medical University Hospital from January 2014 to May 2016. Four of the 13 patients had lymph node metastases at diagnosis, but none had distant metastases. Immunohistochemistry indicated that all 13 primary tumors and four metastatic tumors in lymph nodes were positive for cytokeratin 19. Although none of the 13 patients showed high serum CEA levels, six patients (46.2%) had elevated serum CYFRA 21‐1. Furthermore, CYFRA 21‐1 was reduced in association with post‐treatment tumor reduction in all six patients. Among these six patients, four developed recurrence and metastasis during the follow‐up period. CYFRA 21‐1 was re‐elevated in all four of these patients; however, serum CEA was elevated only in the patient with distant metastasis. These results suggest that CYFRA 21‐1 is more sensitive compared with CEA, and can be useful as a tumor marker for evaluating tumor progression and treatment efficacy in patients with EMPD.

Imiquimod 5% cream as a therapeutic option for extramammary Paget's disease

A wide local excision is the standard treatment for extramammary Pagets disease (EMPD), though this treatment often leads to permanent anogenital mutilation and functional impairment. The purpose of our study is to evaluate the efficacy and safety of the topical application of imiquimod 5% cream for non‐invasive EMPD. We examined nine patients with EMPD. Eight of the nine patients were treated with imiquimod 5% cream three times per week for 16 weeks; one case was treated for 6 weeks. The response rate was 100% including five complete remissions. Local irritation was observed in three patients, which was controlled by a provisional withdrawal of the treatment. These results suggest that imiquimod 5% cream may be considered an alternative therapeutic option for the treatment of non‐invasive EMPD.

Successful TS‐1 monotherapy as the second‐line treatment for advanced extramammary Paget's disease: A report of two cases

There is no standard chemotherapeutic treatment for advanced extramammary Pagets disease, though the effectiveness of some chemotherapy regimens, including docetaxel, has been reported. In this report, we report that TS‐1 monotherapy was effective in two patients with advanced extramammary Pagets disease after docetaxel treatment failure. TS‐1 monotherapy may be useful as the second‐line treatment for patients with advanced extramammary Pagets disease.

Cytokeratin 19 expression is a risk factor for metastasis in cutaneous squamous cell carcinoma

Cytokeratin 19 (CK19) expression has been reported to be a risk factor for metastasis in oral squamous cell carcinoma. However, the significance of CK19 expression in cutaneous squamous cell carcinoma (cSCC) is unclear. Although some studies have reported CK19 expression in cSCC, no study has focused on the relationship between CK19 expression and metastasis in cSCC. Herein, we evaluate whether CK19 expression is related to metastasis in cSCC. This article is protected by copyright. All rights reserved.

Successful rechallenge with nivolumab therapy after radiotherapy in mucosal melanoma

etretinate/yokuinin combination therapy. In our case, the patient’s age limited aggressive treatment options such as surgery and conventional chemotherapy. However, the SCC regressed and still remains in recession after 2 years of etretinate/yokuinin combination therapy with minimal adverse events. Etretinate/yokuinin combination therapy may therefore be an effective therapeutic option in the lip SCC.

Dermoscopic features distinctive for extraocular sebaceous carcinoma

We examined dermoscopic features of three cases of extraocular sebaceous carcinoma and reviewed the literatures. The yellowish structures, polymorphous vessels and ulceration were common findings in our cases and all cases of the previous reports. The appearance of whitish‐pink areas has not been described previously. Our results suggested that the combination of four dermoscopic features, whitish‐pink areas, yellowish structures, polymorphous vessels and ulceration might be distinctive in extraocular sebaceous carcinoma.

Prognostic role of neutrophil to lymphocyte ratio in advanced melanoma treated with anti-programmed death-1 therapy

Dear Editor, Recent studies have reported that the neutrophil to lymphocyte ratio (NLR) may be a prognostic factor in solid tumors. However, melanoma has not been included in these studies and it is unknown whether NLR is associated with outcomes in melanoma patients treated with anti-programmed death-1 (PD-1) therapy. The aim of this study is to investigate NLR as a predictive marker of clinical response and overall survival (OS) in advanced melanoma treated with anti-PD-1 therapy. This study was conducted from 2014 to 2016 at Sapporo Medical University Hospital and was approved by the research ethics board of our institution. Laboratory data were examined within 1 week before initiation of anti-PD-1. Statistical analysis was performed using the Brunner–Munzel test, Kaplan–Meier method and log–rank test. The optimal cut-off value for NLR was determined through receiver–operator curve analysis. We considered P < 0.05 statistically significant. Data from a total of 21 patients were collected. The median age was 74 years (range, 34–91) and 11 patients were male. The most frequent primary site was mucosal melanoma (47.6%). With one exception, all patients presented with stage IV disease. Lactate dehydrogenase (LDH) was elevated in 11 (52.4%) patients (upper limit of normal, 229 U/L). One patient had complete response (CR), three had partial response (PR), while the other patients had progressive disease (PD). Among the responders (CR + PR), the mean and median values of NLR were 2.51 and 2.71, respectively. Among the non-responders, the mean and median values of NLR were 4.90 and 2.90, respectively. There were no statistically significant differences in NLR (P = 0.070) (Fig. 1a). Patients were next categorized into two groups: NLR of 3.4 or more and of less than 3.4. Twelve patients were in the NLR of less than 3.4 group, while nine had NLR of 3.4 or more. Patients with NLR of 3.4 or more showed poorer OS than those in the NLR of less than 3.4 group (P = 0.0021) (Fig. 1b). Additionally, all of the responders had NLR of less than 3.4. Previous studies have suggested that higher NLR is associated with shorter OS in melanoma treated with ipilimumab. Recently, Yu et al. has also reported similar results in patients treated with high-dose a-interferon-2b. Therefore, NLR may be a prognostic factor regardless of treatment regimen. However,

Granulocyte colony‐stimulating factor‐producing melanoma treated with the combination of dabrafenib and trametinib

raise the suspicion for DS diagnosis. Purpura and petechiae, which may form thumb-sized lesions known as the “fingerprint signal”, located on the periumbilical region and on the thighs, are described. The periumbilical thumbprint purpuric eruption occurs because of the involvement of the dermis by the Strongyloides stercoralis larva migrating through the vascular wall, into the dermal connective tissue, because of erythrocyte extravasation. In addition to DS, some nonvasculitic vascular disorders may mimic vasculitis as the result of dermal hemorrhage because of blood vessel wall incompetence or infarction secondary to luminal obstruction, including embolization because of cholesterol and oxalate emboli, cutaneous intravascular metastasis from visceral malignancies, intravascular angiosarcoma and lymphomas, intralymphatic histiocytosis, endocarditis, crystal globulin vasculopathy, hypereosinophilic syndrome, and foreign material. Distinct cutaneous infections and infestations are better visualized by dermoscopy. To our knowledge, this is the first report to illustrate the dermatoscopic aspects of periumbilical purpura related to disseminated strongyloidiasis. Although the dermoscopic structures are not pathognomonic of disseminated strongiloidiasis, it might be useful in ruling out other inflammatory conditions that present with necrotic or intense erythematous areas.

A typical presentation of primary pulmonary epithelioid sarcoma misdiagnosed as non‐small cell lung cancer

To the Editor: Epithelioid sarcoma (ES) is rare type of soft tissue sarcoma, accounting for <1% of all soft tissue sarcomas. Two clinicopathological subtypes are recognized: The classic distal type and the more recently described proximal type. The classic subtype mostly occurs in the distal upper extremities, with >60% arising in the fingers and hands. On the other hand, the proximal subtype tends to arise in the deep part of the pelvis, perineum, and proximal extremities. Here, we describe a case of primary pulmonary ES initially misdiagnosed as non-small cell lung carcinoma (NSCLC), and discuss the clinical aspects of primary pulmonary ES. A 58-year-old man, who was a non-smoker, presented with hemoptysis. His past medical history was unremarkable. In the referring hospital, chest computed tomography (CT) revealed a 28 mm-sized ill-shaped nodule in the right upper lobe (S2) (Fig. S1a). The tumor was accompanied by bronchial wall thickening. Carcinomatous lymphangiosis with interlobular septal thickening and ground glass appearance around the tumor was revealed. Moreover, the tumor was found to invade the mediastinum and thoracic vertebrae, with lymph node metastasis (Fig. S1b, c). Transbronchial needle aspiration was performed. Microscopically, the tumor showed a multinodular or sheet-like arrangement of short spindle to epithelioid cells with stromal fibrosis and hyalinosis. The tumor cells had eccentrically placed prominent nuclei and lightly eosinophilic cytoplasm (Fig. 1). Immunohistochemical analyses revealed that the tumor was negative for p63, thyroid transcription factor-1, napsin A, cytokeratin 7, and cytokeratin 20. The most important differential diagnosis was a metastatic lesion; however, the patient had no evidence of another primary cancer or soft tissue tumor. On the basis of the radiological and pathological findings, the tumor was thus initially diagnosed as NSCLC, cT4N1M1a. The tumor did not harbor epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) rearrangement mutations. As there were no surgical indications, four cycles of systemic chemotherapy with the CDDPþPEM regimen (cisplatin 75mg/m, pemetrexed 500mg/m) was administered. Subsequently, two cycles of carboplatin and pemetrexed, and five cycles of carboplatinþ docetaxel were administered, however, the tumor was gradually enlarging. Therefore, intensity-modulated radiation therapy (60 Gy/30 fractions) was performed for the pulmonary and pleural lesions. Three and a half years after the initial treatment, the patient noticed a 20 to 30 mm-sized painless firm nodule with an ulcer on the scalp, and resection biopsy was consequently performed. In a low-power view, multinodular, granuloma-like lesions with central necrosis were seen in the dermis. The spindled to epithelioid tumor cells had oval nuclei with vesicular chromatin and prominent nuclei, and clear to eosinophilic cytoplasm (Fig. S3). This feature differs from that of proximal type ES which comprise pleomorphic epithelioid cells with abundant, deeply eosinophilic cytoplasm and enlarged vesicular nuclei with prominent nucleoli. Immunohistochemical analyses revealed that the tumor cells were positive for AE1/ AE3, EMA, CA125, and CD34 (Fig. S3). Immunohistochemical study of INI1 (BAF47) was negative and FISH analysis using the INI1/CEP22 probe for INI1 gene deletion revealed that the deletion signal rate was 70% (Fig. S3). The diagnosis was ES. Second review of the previous pulmonary neoplasm was consistent with the scalp lesion on immunohistochemical analysis (Fig. S2), and the INI1 deletion signal detection rate was 52% (Fig. 1). Therefore, we concluded that the pulmonary tumor had been a primary ES and the scalp lesion was metastatic tumor. Four years after the initial treatment, PET-CT revealed metastatic involvement in the left lung, right ninth and eleventh ribs, sixth cervical spine and third and fourth thoracic vertebrae, right ilium, and right inguinal lymph node. The patient later died due to left pulmonary metastases and pneumonia. An autopsy was not conducted.

An adult case of cardiofaciocutaneous syndrome with BRAF mutation

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