Therapy-Resistant, Spontaneously Remitting Generalized Neutrophilic Eccrine Hidradenitis in a Healthy Patient Decreases the Expression of Dermcidin in Affected Eccrine Glands

We describe a healthy 69-year-old Japanese man with generalized neutrophilic eccrine hidradenitis (NEH). He visited our outpatient clinic with a 15-year history of disseminated pruritic papules on his trunk and extremities; the eruptions, however, were limited to the summer months. Histological findings reveal a dense accumulation of neutrophils around the sweat glands with degenerated secretary coils. Interestingly, immunohistochemical staining showed that the expression of dermcidin on the secretory portion of eccrine glands was significantly decreased in the affected lesion. To our knowledge, this is the first report in English of generalized NEH in a healthy adult that shows the downregulation of the expression of dermcidin in affected eccrine glands

Basal Cell Carcinoma with Spontaneous Regression: A Case Report and Immunohistochemical Study

Spontaneous regression of basal cell carcinoma (BCC) is rare, and characterized by various tumor-infiltrating lymphocytes (TILs) in the tumor. A previous report suggested that these infiltrated lymphocytes consist of type 1 helper T cells, but no detailed phenotypical analysis of other TILs has been demonstrated yet. In this report, we describe an 84-year-old Japanese patient with spontaneous regression of BCC. In the present case, we investigated the immunohistochemical profiles of TILs, not only focusing on the cytotoxic T cells, but the profiles of immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages. Our present study sheds light on the immunological mechanisms of tumor rejection in human BCC

Tumor-Associated Macrophages: Therapeutic Targets for Skin Cancer

Tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) are significant components of the microenvironment of solid tumors in the majority of cancers. TAMs sequentially develop from monocytes into functional macrophages. In each differentiation stage, TAMs obtain various immunosuppressive functions to maintain the tumor microenvironment (e.g., expression of immune checkpoint molecules, production of Treg-related chemokines and cytokines, production of arginase I). Although the main population of TAMs is immunosuppressive M2 macrophages, TAMs can be modulated into M1-type macrophages in each differential stage, leading to the suppression of tumor growth. Because the administration of certain drugs or stromal factors can stimulate TAMs to produce specific chemokines, leading to the recruitment of various tumor-infiltrating lymphocytes, TAMs can serve as targets for cancer immunotherapy. In this review, we discuss the differentiation, activation, and immunosuppressive function of TAMs, as well as their benefits in cancer immunotherapy

Successful Treatment of MMP-9-Expressing Angiosarcoma with Low-Dose Docetaxel and Bisphosphonate

We describe a 78-year-old Japanese patient with angiosarcoma on the scalp. Interestingly, immunohistochemical staining revealed this tumor as positive for matrix metalloproteinase 9 (MMP-9). After conventional therapy for angiosarcoma with surgical treatment and radiation therapy, we intravenously administered docetaxel at 40 mg/m2 body surface area together with oral administration of 17.5 mg sodium risedronate hydrate. One and a half years after the standard treatment, there was no evidence of local recurrence or metastasis

Recurrent, Tumor Mutation Burden-High, Cutaneous Angiosarcoma of the Scalp Treated with Pembrolizumab

Introduction: Chemoradiotherapy with taxanes is well-recognized as a first-line therapy for cutaneous angiosarcoma (CAS), but second-line therapy for CAS is still controversial. Case Presentation: In this report, we described a 75-year-old Japanese case of recurrent, tumor mutation burden-high CAS on the scalp treated with pembrolizumab. Our present case survived for 1 year despite of taxane refractory CAS with mediastinal lymph node metastasis, though the administration of anti-PD-1 Abs alone could not fully suppress the tumor progression of CAS. Conclusion: Since various factors such as pro-angiogenic molecules are correlated with the tumor progression in CAS, the administration of anti-PD-1 Abs alone could not fully suppress the tumor progression of CAS. Further novel anticancer drugs are needed in the future for the treatment of CAS

Keratoacanthoma Centrifugum Marginatum with Spontaneous Regression and Its Possible Differential Diagnosis

Keratoacanthoma centrifugum marignatum (KCM) is a rare variant of keratoacanthoma, which is characterized by the dense infiltration of inflammatory cells throughout the dermis, especially around the keratinocytic islands. Therefore, it is sometimes difficult to differentiate between KCM and cutaneous T-cell lymphomas. In this report, we describe a case of KCM with spontaneous regression that showed dense infiltration of CD3+CD8+ T cells. Our present case suggested the importance of investigating tumor-infiltrating lymphocytes to avoid the misdiagnosis of KCM as cutaneous T-cell lymphoma

Association of Baseline Serum Levels of CXCL5 With the Efficacy of Nivolumab in Advanced Melanoma

Anti-programmed cell death protein 1 (PD1) antibodies are in wide use for the treatment of various cancers. PD1 antibody-based immunotherapy, co-administration of nivolumab and ipilimumab, is one of the optimal immunotherapies, especially in advanced melanoma with high tumor mutation burden. Since this combined therapy leads to a high frequency of serious immune-related adverse events (irAEs) in patients with advanced melanoma, biomarkers are needed to evaluate nivolumab efficacy to avoid serious irAEs caused by ipilimumab. This study analyzed baseline serum levels of CXCL5, CXCL10, and CCL22 in 46 cases of advanced cutaneous melanoma treated with nivolumab. Baseline serum levels of CXCL5 were significantly higher in responders than in non-responders. In contrast, there were no significant differences in baseline serum levels of CXCL10 and CCL22 between responders and non-responders. These results suggest that baseline serum levels of CXCL5 may be useful as a biomarker for identifying patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy

Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma

Antibodies against programmed cell death protein 1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. Nivolumab significantly prolongs survival in patients with metastatic melanoma, and sequential administration with lipilimumab may improve outcomes when switched at the appropriate time. Biomarkers are therefore needed to evaluate nivolumab efficacy soon after first administration. This study analyzed serum levels of soluble cluster of differentiation 163 (sCD163) in 59 cases of advanced cutaneous melanoma and 16 cases of advanced mucosal melanoma treated using nivolumab. Serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after initial administration of nivolumab for cutaneous melanoma. In contrast, no significant difference between responders and non-responders was seen among patients with non-cutaneous melanoma. These results suggest that sCD163 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy

Profiles of Cytotoxic T Lymphocytes in Cutaneous Lymphoid Hyperplasia of the Face

Cutaneous lymphoid hyperplasia (CLH) is difficult to differentiate from primary malignant cutaneous lymphomas that may present as solitary nodules, and sometimes it requires much time to achieve a final diagnosis. A recent report [Park et al.: Acta Haematol 2011;126:79-86] suggested that the expression of granulysin correlates with the prognosis of cancer patients, even in hematological disorders. In this report, we immunohistochemically examine the expression of cytotoxic molecules (e.g. granulysin, TIA-1 and perforin) in tumor-infiltrating lymphocytes of 10 patients with CLH and 3 patients with cutaneous diffuse large B cell lymphoma, not otherwise specified (CDLBCL-NOS) of the face. In the patients with CLH, the number of granulysin-bearing cells was higher than in the patients with CDLBCL-NOS. In contrast, there was no difference in the number of TIA-1+ or perforin+ cells. The present study attempts to explain the different biological behaviors of these two hematological disorders and suggests granulysin as a possible diagnostic tool for CLH and CDLBCL-NOS of the face