Yuri Asami

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.

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.

Long-distance alteration of lymphatic drainage in a melanoma patient after axillary lymph node dissection

Since lymphatic mapping and sentinel lymph node biopsy (SLNB) were introduced in the 1990s [1], SLNB has been commonly used for tumor staging and detection of SLN metastases in cutaneous melanoma [2, 3]. Preoperative lymphoscintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) enable accurate detection of the location of SLNs; in 93 % of patients with melanoma on the back, SLNs are located in the ipsilateral axilla [4]. However, lymphatic drainage patterns following axillary LN dissection (ALND) are unpredictable [5]. We report a rare case of melanoma of the upper back with atypical lymphatic drainage and SLN locations in a patient who had previously undergone ipsilateral ALND for breast cancer. A 63-year-old female presented with a one-year history of a pigmented lesion on her left upper back. Her past medical history included left-sided breast cancer, which had been treated with mastectomy and left ALND four years earlier. Physical examination revealed an asymmetric, irregularly pigmented lesion, measuring 1 cm in diameter. Histopathology of the excisional biopsy revealed a proliferation of large, round, atypical, melanin-containing epithelioid cells that infiltrated the dermis. Immunohistochemically, the neoplastic cells were positive for HMB-45, S-100, and Melan-A. Based on the clinical, histopathological, and immunohistochemical findings, melanoma was diagnosed (Breslow’s thickness 0.76 mm, without ulceration). Wide local excision and SLNB were performed. Preoperative lymphoscintigraphy using technetium-99m tin colloid and SPECT/CT revealed two hot spots near the primary site, and two in the left lateroabdominal and inguinal region (Figure 1a–d). There was no lymphatic drainage towards the ipsilateral axilla. On SPECT/CT, the spots near the primary site only involved the skin (Figure 1b). Intraoperatively, the SLNs were identified by blue dye, hand-held gamma counter, and near-infrared camera using real-time fluorescence navigation with indocyanine green (ICG). The hot spots near the primary site showed high radioactivity; however, there was a marked accumulation of blue dye in the skin, indicating the obstruction of lymphatics towards the ipsilateral axilla (Figure 1e). While we did excise this “blue” area along with the underlying subcutaneous fat, histopathology showed no LNs in the specimen. On the other hand, highly radioactive, ICG-fluorescent LNs were identified both in the ipsilateral lateroabdominal and inguinal region (Figure 1f, g), which were excised as SLNs. Histopathology and immunohistochemistry revealed no tumor cells in these SLNs.

Image Gallery: Bowen's disease of a nail unit presenting with ‘woodgrain appearance’ – a new dermoscopic finding

(a) A 52-year-old woman presented with an 8-month history of a widening 2 5 mm pigmented streak on her left fifth fingernail. (b) Dermoscopy showed an inhomogeneous wavy streak with multiple depressed areas in the nail surface. The entire nail apparatus was excised. (c, d) Histopathological examination revealed acanthosis with a proliferation of atypical keratinocytes showing loss of polarity in the nail matrix with a moderate number of Ki67-positive nuclei throughout the keratinocytes. (e) Transepidermal elimination of tumour cell nests was seen in the nail plate. The diagnosis of Bowen’s disease (BD) was confirmed. This is the first report of nail BD with transepidermal elimination of tumour nests, which leads to a ‘woodgrain appearance’ on dermoscopy.

Cutaneous surgery under local anesthesia in very elderly patients 90 years of age and older is as safe as in elderly patients ranging in age from 75 to 80 years old

The number of very elderly patients who require surgery for cutaneous tumors is increasing. However, there is limited information on the safety of cutaneous surgery in such patients.

A Rare Case of a Primary Cutaneous Desmoplastic Atypical Granular Cell Tumor.

Granular cell tumors are uncommon neoplasms and a small number of these neoplasms have been reported as showing malignant behavior. Here, we report a rare case of a solitary granular cell tumor that exhibited atypical histology, including an extensive desmoplastic stroma, in a 69-year-old woman. The surgical specimen revealed localized areas of spindling cells, areas of cellular pleomorphism, and p53 overexpression. Based on previously published criteria, we classified this lesion as an atypical granular cell tumor. To date, only very few case reports have documented this desmoplastic variant of granular cell tumor. However, the classifications of benign, atypical, and malignant granular cell tumors are still controversial, owing to an overlap of morphological and immunohistochemical profiles and lack of consistent histological criteria. Additionally, it is unknown whether the histology of the desmoplastic variant in the present case is significant for the classification of granular cell tumors and prediction of patient prognosis. Regardless of these issues, awareness, and close follow-up are required because of potential recurrences of this rare variant of granular cell tumor.