Yukiko Teramoto

Correlation between vitiligo occurrence and clinical benefit in advanced melanoma patients treated with nivolumab: A multi-institutional retrospective study

Vitiligo is occasionally seen in melanoma patients. Although several studies indicate a correlation between vitiligo occurrence and clinical response in melanoma patients receiving immunotherapy, most studies have included heterogeneous patient and treatment settings. The aim of this study is to investigate the correlation between the occurrence of vitiligo and clinical benefit of nivolumab treatment in advanced melanoma patients. We retrospectively reviewed unresectable stage III or IV melanoma patients treated with nivolumab. Of 35 melanoma patients treated with nivolumab, 25.7% (9/35) developed vitiligo during treatment. The time from the start of nivolumab treatment to occurrence of vitiligo ranged 2–9 months (mean, 5.2). Of nine patients who developed vitiligo, two (22.2%) had a complete response to nivolumab and two (22.2%) had a partial response. The objective response rate was significantly higher in patients with vitiligo than in patients without vitiligo (4/9 [44.4%] vs 2/26 [7.7%]; P = 0.027). The mean time to vitiligo occurrence in patients achieving an objective response was significantly less than that in patients who showed no response (3.1 vs 6.8 months, P = 0.004). Vitiligo occurrence was significantly associated with prolonged progression‐free and overall survival (hazard ratio, 0.24 and 0.16; 95% confidence interval, 0.11–0.55 and 0.03–0.79; P = 0.005, and 0.047, respectively). At the 20‐week landmark analysis, however, vitiligo was not associated with a statistically significant overall survival benefit (P = 0.28). The occurrence of vitiligo during nivolumab treatment may be correlated with favorable clinical outcome.

Case of type 1 diabetes associated with less-dose nivolumab therapy in a melanoma patient.

gates of foamy histiocytes in the dermis and verrucous acanthosis. Regarding its pathogenesis, it is thought that the epithelial damage and degeneration cause the release of lipid materials and subsequent phagocytosis by macrophages in the dermis, followed by the accumulation of numerous foamy cells and the proliferation of reactive keratinocytes. In addition to human papillomavirus infection, localized lymphatic stasis caused by congenital or acquired factors (e.g. trauma, skin grafting, radiation or chronic inflammatory dermatosis) has been described as a predisposing factor for the development of VX. The direct pathogenic association of VX with lymphedema remains unclear; however, lymphatic stasis, which is the obstructive stasis of proteinor lipid-rich interstitial fluid, causes susceptibility to various external stimuli, such as bacterial infection and friction as well as a prolonged inflammation, all of which can be predisposing factors for the development of VX. In this case, the patient suffered from a long-standing severe lymphedema resistant to the lymphatic venous anastomosis, accompanied by acquired LC, which is a relatively rare sequela. Additionally, the skin of vulvar region had been repeatedly affected by both infection and friction, which might have facilitated the prolipidogenic degeneration of keratinocytes and resulted in the formation of a VX. CONFLICT OF INTEREST: None declared.

Effects of non‐amputative wide local excision on the local control and prognosis of in situ and invasive subungual melanoma

Subungual melanomas (SUM) are rare, and amputation is often required. Non‐amputative wide local excision (WLE) of the nail unit with the periosteum of the distal phalanx, followed by skin graft, has been accepted for in situ or SUM of 0.5 mm or less thickness. However, previous reports have included a limited number of cases, and not all more than 0.5‐mm thick SUM exhibit invasion or attachment to the distal phalanx. The aim of the present study was to investigate the local recurrence and prognosis for in situ, minimally invasive and invasive SUM that were treated using WLE. We retrospectively reviewed 50 patients with in situ (n = 48) or minimally invasive SUM (n = 2) (in situ or minimally invasive group) and 12 patients with more than 0.5‐mm thick invasive SUM (invasive group) who were treated using WLE. All patients survived the follow‐up period (24–207 months), although four patients with in situ SUM experienced local recurrence at the lateral margin and re‐excision was required. In the invasive group, no patients experienced local recurrence, although one patient (8.3%) developed nodal metastasis at 86 months and regional lymph node dissection was required. WLE may provide acceptable local control for in situ and intermediate thickness SUM, without compromising the vital prognosis. However, a larger randomized prospective study with long‐term follow up is required to evaluate adequately the risks associated with a non‐amputative WLE for in situ and invasive SUM.

Tumor-to-bone distance of invasive subungual melanoma: An analysis of 30 cases

Subungual melanoma (SUM) is rare and represents approximately 2–3% and 20% of all cutaneous melanomas in Caucasians and Asians, respectively. Amputation has usually been performed for invasive SUM; however, not all invasive SUMs invade or attach to the distal phalanx. To investigate the possibility of non‐amputative surgery for patients with invasive SUM, the distances between the deepest base of the melanoma cells and the bony surface in the surgical specimens of invasive SUM were measured. Thirty surgical specimens of invasive SUM were retrospectively reviewed. The contents of the specimens were as follows: 14 first toes, 10 thumbs, three second fingers, two third fingers, and one fifth finger. Four specimens showed bone invasion, and the tumor was attached to the bone in four specimens. The tumor‐to‐bone distance exceeded 0.9 mm in all the specimens with thicknesses <4 mm. In the non‐ulcerated SUMs (nine specimens), only one SUM specimen showed bone attachment. There was a higher likelihood of bone attachment or invasion when tumor thickness (TT) exceeded 4 mm (Pearson chi‐square test, P = 0.009; Fisher exact test, P = 0.004; student t test, 0.033). Univariate and multivariate analysis also revealed that thick TT had a statistically significant affect (odds ratio 1.807 and 1.865, 95% CI 1.11–3.01 and 1.11–3.13, P = 0.023 and 0.018). Non‐amputative surgery may be possible for SUM tumors that are of intermediate‐thickness. However, there has been little evidence demonstrating survival with non‐amputative surgery for invasive SUM. A large, randomized, prospective clinical study is required to address this issue.

Axillary giant lipoma: a report of two cases and published work review.

Lipomas are common, benign, small‐sized, soft‐tissue tumors. However, giant lipomas are uncommon and the tumor size can cause pain and nerve compression syndrome. The axilla is an extremely rare location for development of giant lipomas. We report two cases of axillary giant lipoma. A 47‐year‐old man (case 1) and a 42‐year‐old woman (case 2) presented with a large mass in the axillary region. Case 2 had tenderness in the shoulder and numbness in the upper arm. Magnetic resonance imaging of each tumor showed a homogenous soft‐tissue mass in the axillary region, suggestive of lipoma. In case 2, the tumor extended from the axilla to the supraclavicular region and split and compressed the neurovascular bundle. Each lesion was successfully excised surgically without serious complications and recurrence. In case 2, the tenderness and numbness disappeared. Histologically, each lesion was composed of multilobulated, mature adipose cells, which led to a diagnosis of benign lipoma. Axillary giant lipoma is preferably excised surgically to avoid damage caused by tumor compression to the major vessels or nerves, to offer better local control and to establish a correct final diagnosis.

Oral S-1 in advanced cutaneous squamous cell carcinoma

Squamous cell carcinoma (SCC) is the second most common type of skin cancer in Japan, and its incidence has been increasing in recent years. Early diagnosis and complete excision can provide a high cure rate. However, advanced cases of SCC showing local invasion, regional lymph node metastasis or distant metastasis are not curative and are difficult to treat with surgery alone. Some chemotherapy regimens have been used for treating advanced cutaneous SCC. However, almost all these regimens require intravenous administration and result in serious toxicities in elderly people. We gave S‐1, a novel oral chemotherapeutic agent, for six patients with advanced cutaneous SCC. Three patients achieved complete response and one achieved partial response. Two patients showed stable disease. The overall response rate was 66.7% (four of six patients), and the disease control rate was 100%. Two of six patients developed grade 3 anaemia. Oral S‐1 treatment is safe and effective for treating advanced cutaneous SCC. However, a prospective trial is necessary to confirm the effectiveness of oral S‐1 for advanced cutaneous SCC.

Induction of Immune Reaction in Benign Melanocytic Nevi Without Halo During Nivolumab Therapy in a Patient With Melanoma

Induction of Immune Reaction in Benign Melanocytic Nevi Without Halo During Nivolumab Therapy in a Patient With Melanoma Immune reactions in benign melanocytic nevi (BMN) without halo phenomenon are extremely rare, although humoral and cellular immune responses are involved in their development. Herein, we report a rare case of a patient with metastatic melanomas who showed a remarkable clinical response to nivolumab with a simultaneous prominent immune reaction in multiple BMN without halo phenomenon.

Nivolumab Therapy for Treatment-Related Vitiligo in a Patient With Relapsed Metastatic Melanoma

Nivolumab Therapy for Treatment-Related Vitiligo in a Patient With Relapsed Metastatic Melanoma Treatment-related vitiligo is sometimes observed in patients with melanoma1 and is associated with a good clinical response to anti–PD-1 (programmed cell death 1 protein) antibodies.2-4 Although cellular and humoral immune responses may be key factors for vitiligo occurrence, data on reduced immune responses in association with vitiligo repigmentation are lacking in patients with melanoma. We report a rare case of metastatic melanoma with a complete response and simultaneous vitiligo during nivolumab therapy. To our knowledge, vitiligo repigmentation developing in association with tumor relapse has not been reported previously.

Case of giant basal cell carcinoma around the base of the penis in an elderly patient

We report a case of an 85‐year‐old man with a doughnut‐shaped basal cell carcinoma around the base of the penis invading the cavernosum urethra. In cases in which curative resection is planned, the penis is resected, cystostomy is performed, and postoperative self‐management is required. In line with the patients wishes and the fact that he was an elderly person living alone without family support, we decided to perform penis‐conserving surgery. Relapse occurred once, for which additional resection was conducted. Two years after the resection, there was no evidence of tumor recurrence. The therapeutic plan for elderly patients should be modified after considering the patients social background, wishes, activity and life expectancy.

Surgical management of umbilical basal cell carcinoma: Published work review and the optimal depth of surgical excision

Basal cell carcinoma (BCC) is a common malignant skin tumor. However, BCC that arise at the umbilicus is rare. We present three cases of umbilical BCC. Each BCC was excised at a different depth level, and all deep surgical margins were negative. All patients had no evidence of local recurrence or metastasis during the follow‐up periods (12, 24, and 52 months). Reviewing the reported cases of umbilical BCC, the BCC cells did not seem to invade into the umbilical scar in most cases, and the deepest invasion levels of tumor cells were up to the middle layer of the subcutaneous tissue. However, the dermatological surgeons have to consider the possibility of surgical excision down to and including the umbilical attachment to the peritoneum, and intraoperative margin assessment should be necessary to avoid the risk of excessive or incomplete excision.