Successful treatment of unresectable recurrent cutaneous squamous cell carcinoma of the scalp with meningeal invasion with nivolumab monotherapy.

Although the number of cutaneous squamous cell carcinoma (cSCC) cases is increasing, the effectiveness of systemic therapy for the treatment of advanced cSCC is limited. Since cSCC possesses a high tumor mutation burden (TMB) compared to other cancer species, and since high TMB correlated with increased neoantigens and the efficacy of anti-PD1 antibodies (Abs) in various cancers, cSCC could be a target for anti-PD1 Abs monotherapy. In this report, we describe a case of unresectable recurrent cSCC of the scalp with meningeal invasion, but highly expressed programmed death-ligand 1 (PD-L1), treated with nivolumab monotherapy.

Case series of modified dermis graft for skin defects of the nasal region.

Local skin flap from the surrounding area is often chosen for reconstruction of skin defects in the nasal region, but it is problematic because it creates new facial scar and requires skill of design. On the other hand, full-thickness skin graft is associated with problems such as color mismatch and scar contracture at the recipient site. We reconstructed nasal defects of seven patients using modified dermis graft technique. In this method, de-epithelialized full-thickness skin graft is transplanted and then epithelialized from the surrounding area. This is a simple and easy procedure without causing a new scar on the face and is aesthetically and functionally superior to a standard full-thickness skin graft; therefore, it is a useful method of reconstruction of the nasal area.

IL-23 Expression in Stewart-Treves Syndrome: Two Case Reports and Immunohistochemical Investigation.

Stewart-Treves syndrome (STS) is a rare cutaneous lymphangiosarcoma developing from chronic lymph edema as a consequence of radical mastectomy or surgical invasion of the groin for the treatment of cervical or penile cancer. Previous reports suggested possible mechanisms in the development of lymphangiosarcoma that correlate with the immunological background of STS patients. In this report, we described two cases of STS developing in patients who underwent radical dissection for cervical cancer, we employed immunohistochemical staining of IL-23 and IL-17.

Reconstruction of the cervical trachea using a prefabricated corticoperiosteal flap from the femur.

We treated a severe cervical fistula with a defect of tracheal cartilage using prefabrication of a corticoperiosteal flap combined with a cutaneous flap.The patient was a 16-year-old male with a cervical tracheal fistula that developed after a tracheostomy. Almost all the circumference of the trachea just below the cricoid cartilage up to the 4th tracheal cartilage had been lost.The reconstruction was performed in 2 series of operations as follows; repair of tracheal framework using a prefabricated corticoperiosteal flap, which was harvested from the femur and composed of a saphenous flap, and then complete closure using a local hinge flap and a free auricular cartilage graft. A free corticoperiosteal flap composed of a saphenous flap was transferred to the site just lateral to the defect. The corticoperiosteal flap, which has a flat shape, was bent in a reverse U-shaped semitubular fashion and the mucosal grafts were used to cover its inner surface. Two months later, the prefabricated corticoperiosteal flap and the saphenous flap were transposed leaving a part of the fistula as a tracheostoma. The remaining tracheostoma was closed secondarily. A satisfactory and stable result was obtained over an 8-year follow-up period.We believe that the procedure demonstrated here should be considered as a choice for the stable reconstruction of a cervical trachea.

Advanced Invasive Extramammary Paget's Disease Concomitant with Cecal Cancer Possessing Rare Variant of TP53 Single Nucleotide Polymorphism.

Patients with invasive extramammary Paget's disease have an increased risk of secondary malignancy, mostly occurring colorectal carcinoma. TP53 is a regulator of apoptosis, cell cycle arrest, and DNA damage response pathways, and has been reported as one of the genetic biomarkers for colorectal carcinoma. In this report, we describe a case of advanced invasive EMPD concomitant with cecal cancer with a rare variant of TP53 single nucleotide polymorphism (rs121912665). To our knowledge, there is no English report that presents EMPD concomitant with cecal carcinoma.

Successful Treatment of Nivolumab-Resistant Multiple In-Transit Melanomas with Ipilimumab and Topical Imiquimod.

Simultaneous or sequential, planned administration of ipilimumab could significantly enhance the antitumor effects of nivolumab in advanced melanoma patients. On the other hand, the efficacy of ipilimumab for nivolumab-resistant advanced melanoma is extremely poor. Therefore, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma has been widely investigated. In this report, we describe a case of multiple in-transit melanomas developing in a nivolumab-resistant patient successfully treated with ipilimumab in combination with imiquimod. Our present case suggested a possible therapy for nivolumab-resistant multiple in-transit melanomas using ipilimumab in combination with topical imiquimod.

Pigmented Epithelioid Melanocytoma (Animal Types of Melanoma) on the Nose.

Pigmented epithelioid melanocytoma (PEM), also known as an animal-type melanoma, is a distinctive group of melanocytic tumors with a more favorable prognosis than conventional melanoma. Since tumor-associated macrophages (TAMs) extend in the premetastatic lymph nodes in several cancers, we hypothesized that the lower rate of lymph node metastasis in PEM might be correlated with the phenotypes of TAMs. Therefore, in this report, we further investigate the subpopulation of TAMs in PEM, revealing that the main population of TAMs in histiocytic lesion is CD163+CD206+PD-L1+ M2-polarized macrophages. In addition, since the PD-L1-expressing CD205+ dendritic cells are also detected in histiocytic lesions, the PD-L1-expressing TAMs and dendritic cells might suggest favorable prognostic factors in patients with PEM.

Two cases of dabrafenib and trametinib therapy-failed advanced melanoma successfully controlled by nivolumab monotherapy.

Although therapies for advanced melanoma have been greatly improved by the development of immune checkpoint inhibitors and BRAF/mitogen-activated protein kinase kinase inhibitors, there are still many concerns about the administration of these novel drugs. Therefore, to combine these therapies sequentially at appropriate time points of the disease is important. In this report, we report two cases in which dabrafenib and trametinib therapy for advanced melanoma failed but were successfully controlled by nivolumab monotherapy, and investigated the sera sCD163, CCL22 and CXCL10 as biomarkers for tumor progression. Interestingly, the sera levels of sCD163, CXCL10 and CCL22, both of which are produced by activated tumor-associated macrophages, were increased in parallel with the tumor progression in each case. Because this report presents only two cases, further data will need to be accumulated to provide more fundamental insights into the usefulness of these biomarkers for predicting disease progression in melanoma.

Phase I study of nivolumab combined with IFN-ß for patients with advanced melanoma.

The efficacy of nivolumab is greater than that of other anti-melanoma drugs, so nivolumab-based combined therapies that enhance anti-tumor immune responses in patients with metastatic melanoma are of great interest to dermato-oncologists. As we have previously reported, IFN-ß enhances the anti-tumor immune response of anti-PD-1 antibodies against B16F10 melanoma in vivo. To explore the potential of this property of IFN-ß as part of a combination therapy for the treatment of metastatic melanoma patients, we performed a phase 1 trial, using a traditional rule-based 3 + 3 design, on patients with advanced melanoma. The nivolumab dose was fixed at 2 mg/kg, every 3 weeks. IFN-ß was administered to three groups at doses of 1 million, 2 million, and 3 million units, respectively. Dose-limiting toxicities were defined as any grade 3-5 adverse events occurring between day 0 and day 42 that might possibly be related to nivolumab and IFN-ß. Of the nine patients who received this combined therapy, none experienced dose-limiting toxicities, and all completed the treatment phase of the study. Patient follow-up continued for 6 months following the final treatment. There were two complete responses (22%) and one partial response (11%), all of which occurred in patients who had received monthly IFN-ß immediately prior to the study. In this study, we determined the safe dose of IFN-ß, when combined with nivolumab, to be 3 million units. To determine the efficacy of this combination therapy, further phase II trials are required.

Successful treatment of multiple in-transit melanomas on the leg with intensity-modulated radiotherapy and immune checkpoint inhibitors: Report of two cases.

Because the efficacy rates of monotherapy with immune checkpoint inhibitors such as nivolumab or ipilimumab are not sufficient, to enhance the antitumor effects of these reagents is of great interest among dermato-oncologists. In this report, we describe two cases of multiple in-transit metastatic melanomas on the leg successfully treated with intensity-modulated radiotherapy (IMRT) using a CyberKnife in combination with ipilimumab or nivolumab. Our cases suggested that IMRT could enhance the antitumor effects of immune checkpoint inhibitors in patients with multiple in-transit melanomas.

Adult Onset of BRAF(V600E)-Mutated Langerhans Cell Histiocytosis with Cutaneous Involvement Successfully Diagnosed by Immunohistochemical Staining.

Langerhans cell histiocytosis (LCH) is characterized by the clonal proliferation of Langerhans cells; it is categorized as a single-system disease with single or multifocal lesions, and as a multi-system disease with or without the risk of organ involvement. Although the skin is not categorized as a risk organ, the precise diagnosis of skin lesions is necessary to determine the protocol for the treatment of LCH. In this report, we describe a 28-year-old Japanese man with adult onset of BRAF(V600E)-mutated LCH with cutaneous involvement successfully diagnosed by immunohistochemical staining. Our report suggests that immunohistochemical staining for the BRAF(V600E) gene could be a diagnostic tool to determine the clinical type of LCH.

Merkel Cell Carcinoma Concomitant with Invasive Bowen's Disease: Immunohistochemical Investigation of Tumor-Infiltrating Leukocytes.

Merkel cell carcinoma (MCC) is an aggressive, cutaneous, neuroendocrine carcinoma and, in rare cases, occurs with Bowen's disease (BD). In this report, we describe a case of MCC concurrent with invasive BD and compare the profiles of tumor-infiltrating leukocytes in the lesional skin of MCC and invasive BD. Interestingly, immunohistochemical study revealed significant numbers of CD8+ cells and caspase 3-expressing cells in the same areas of invasive BD and MCC. Our present case suggests that MCC concurrent with invasive BD might have a good prognosis because of the substantial number of CD8+ cells in the tumor.

Operative technique to harvest an arterial flap from the posterolateral calf region: how can we elevate a lateral gastrocnemius perforating artery flap safely?

The posterior calf region is a useful donor site for skin or composite flaps including muscle and/or nerves. We reported the first clinical use of the lateral gastrocnemius perforating artery flap including a vascularized sural nerve in 2003. This flap was elevated based on a perforator arising from the lateral head of the gastrocnemius muscle. However, we have since encountered vascular variations in these perforators. We subsequently developed a reliable technique for harvesting this flap in the course of treating 10 patients. Safe flap elevation from the lateral aspect of the posterior calf requires preservation of one of the superficial sural arteries until reliable perforators arising from gastrocnemius muscle lateral head are encountered during dissection. When such perforators are not observed, nutrient vessels such as superficial sural arteries or muscle perforators originating from vessels other than the lateral sural artery must be selected as a flap pedicle.