Search

Since bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis, lupus vulgaris (LV) is reported as one of the rare complications after BCG vaccination, correlating with immunosuppression in the lesional skin. In this report, we describe a case of LV arising from the BCG vaccination site 22 years after vaccination. Interestingly, in the present case, granuloma cells were composed of M2-polarized macrophages. Our case might explain the contribution of M2-polarized macrophages to the biology of LV arising from a BCG vaccination site.

Ectopic extramammary Paget’s disease (EMPD) is a rare variant of EMPD that develops in nonapocrine regions. Since reports about ectopic EMPD are limited, little is known about the biological and immunological background of ectopic EMPD. In this report, we present a case of ectopic EMPD on the lower abdomen that expressed RANKL but lacked the expression of MMP7. As we previously reported, Paget’s cells express RANKL and MMP7, release soluble RANKL in the tumor microenvironment, and stimulate tumor-associated macrophages to produce tumor-loading factors in conventional EMPD. In our present case, both CCL5-expressing cells and MMP25-bearing cells were lacking, whereas substantial numbers of CCL5-expressing cells and MMP25-bearing cells were found in conventional EMPD. Our case suggested that the lack of MMP7 on Paget’s cells might be one of the possible explanations for the biology of ectopic EMPD.

Mycosis fungoides palmaris et plantaris (MFPP) is a rare variant of mycosis fungoides limited to the palms and soles. Although little is known about the pathogenesis of MFPP, this variant of mycosis fungoides presents a relatively good prognosis. In this report, we describe an 85-year-old Japanese man with MFPP. Immunohistochemical staining revealed the dense deposition of periostin in the cancer stroma, as well as infiltration of CD163+CD206- tumor-associated macrophages (TAMs), which suggested the phenotypes of TAMs were not polarized to the M2 phenotype in the lesional skin of MFPP. Our present case might suggest one of the possible reasons for the good prognosis of MFPP.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma that only rarely regresses spontaneously. Since little is known about the immunological mechanisms involved in the spontaneous regression of MCC, we describe a case of MCC with spontaneous regression and employed immunohistochemical staining for cytotoxic and immunosuppressive molecules to investigate possible mechanisms involved in the spontaneous regression of MCC. Interestingly, compared to conventional MCC, tumor-infiltrating lymphocytes in MCC with spontaneous regression contained higher numbers of CD8+ cells and granulysin-bearing cells and lower numbers of CD206+ cells. Our present study suggests one of the possible reasons for the spontaneous regression of MCC.

Plexiform fibrohistiocytic tumor (PFT) is a rare mesenchymal neoplasm of intermediate malignant potential with a high local recurrence rate. In this report, we describe a case of PFT on the ear, which showed a dense deposition of periostin (POSTN) in the stromal areas of the tumor. In addition, dense infiltration of CD163+CD206- tumor-associated macrophages (TAMs) was detected in the same areas as POSTN. Since POSTN was previously reported to possess immunomodulatory effects on TAMs, our present report suggested the significance of the POSTN/TAMs axis in the progression of PFT.

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 BRAFV600E-mutated LCH with cutaneous involvement successfully diagnosed by immunohistochemical staining. Our report suggests that immunohistochemical staining for the BRAFV600E gene could be a diagnostic tool to determine the clinical type of LCH.

Abatacept is a biological immune modifier that is used for the treatment of rheumatoid arthritis. Although psoriasiform drug eruption is reported as one of the cutaneous adverse effects of abatacept, the precise mechanisms are not fully understood. In this report, we describe a 65-year-old Japanese man with psoriasiform drug eruption caused by abatacept. Interestingly, immunohistochemical staining revealed that the epidermal keratinocytes in the basal layer and lower layers of the stratum spinosum were positive for pSTAT3, partially positive for pSTAT1 and negative for pSTAT6, which is similar to conventional psoriasis vulgaris. Our present study suggests that psoriasiform drug eruption caused by abatacept might develop by similar immunological mechanisms as those of psoriasis vulgaris.

Lipodystrophy is a group of metabolic disorders, possibly caused by autoimmune disease. In this report, we describe a case of adult-onset acquired partial lipodystrophy accompanied by rheumatoid arthritis without a family history. Interestingly, immunohistochemical staining revealed dense infiltration of IL-27-producing cells as well as MMP-7- and MMP-28-expressing cells, both of which have been reported to facilitate the development of autoimmune disease. Our present case might suggest possible mechanisms for acquired partial lipodystrophy.

Both morphea and lichen sclerosus et atrophicus (LSA) are connective tissue diseases that mainly affect the skin. A recent report suggested that a substantial portion of morphea coexists with LSA. In this report, we describe a case of LSA on the abdomen accompanied by morphea; we employed immunohistochemical staining for periostin as well as MMP-7 and MMP-28, both of which are reported to facilitate fibrosis in the development of various organs, including skin. To our knowledge, this is first English language paper that demonstrates the immunohistochemical staining of periostin, MMP-7 and MMP-28 for morphea and LSA. Our present case might suggest possible mechanisms for the coexistence of two different sclerotic skin disorders.

Invasive extramammary Paget's disease (EMPD) is highly metastatic to lymph nodes and other organs, including bone, and when metastatic lesions have expanded beyond the inguinal lymph node, it is difficult to cure. In this report, we present a case of multiple metastasized, receptor activator of nuclear factor kappa-B ligand-expressing EMPD in the pelvic lymph nodes successfully cured with continuous administration of bisphosphonate risedronate sodium after intensive CyberKnife radiotherapy and docetaxel monochemotherapy. Our present case suggested the usefulness of bisphosphonates as a maintenance therapy for metastatic invasive EMPD after the intensive chemoradiotherapy.

Hypopigmented mycosis fungoides (HMF) is a clinical variant of MF presenting a good prognosis. In this report, we describe a case of HMF with dense infiltration of tumor-infiltrating leukocytes that bear several cytotoxic molecules, such as granulysin and T-cell intracellular antigen-1. In addition, our immunohistochemical study revealed that the ratio of Foxp3+ regulatory T cells to the total CD4+ cells is decreased in the lesional skin of HMF, compared with that of conventional MF. Our case suggested possible mechanisms for the hypopigmentation and good prognosis of this type of MF.

Keratoacanthoma (KA) is a benign keratinocytic neoplasm that spontaneously regresses after 3-6 months and shares features with well-differentiated squamous cell carcinoma (SCC). An increased incidence of both KA and non-melanoma skin tumor, including SCC, is seen among immunosuppressed, organ-transplant recipients. In this report we describe a case of KA accompanied by multiple lung SCCs developing in a renal transplant recipient.

Adult-onset erythromelalgia (EM) is a rare disease characterized by episodic bouts of burning pain and erythema for which the optimal therapy is unclear. In this report, we describe a 68-year-old Japanese woman with adult-onset EM. Intravenous administration of methylprednisolone sodium succinate 1,000 mg/day dramatically improved her pain as evaluated by the visual analog scale. Although the patient’s pain gradually developed again, it could be controlled with pregabalin. Our present case might suggest a possible, optimal therapy for adult-onset EM.

Th17 cells, characterized by IL-17 production, play a critical role in the pathogenesis of autoimmune diseases, including autoimmune bullous disorders and aplastic anemia (AA). In this report, we describe a 58-year-old Japanese man with bullous pemphigoid (BP) accompanied by AA. Interestingly, immunohistochemical staining revealed the existence of IL-17-producing cells in the skin biopsy specimens from BP. Our findings might suggest relationships between IL-17 and the pathogenesis of these autoimmune diseases, and, to our knowledge, this is the first English report of BP accompanied by AA.

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.

Pseudolymphomatous folliculitis (PLF), which sometimes mimicks cutaneous lymphoma, is a rare manifestation of cutaneous pseudolymphoma and cutaneous lymphoid hyperplasia. We describe a 57-year-old Japanese woman with PLF on the nose that resembled cutaneous lymphoma clinically. The biopsy specimen revealed dense lymphocytes, especially CD1a+ cells, infiltrated around the hair follicles. Without any additional treatment, her nodule rapidly decreased before we performed a second biopsy for analysis of the clonal gene rearrangement. Though PLF typically behaves as benign lymphohyperplasia, differentiation from cutaneous lymphoma is necessary.

An imbalance of immunosuppressive cells and cytotoxic cells plays an important role in the tumor-bearing host. Together with regulatory T cells (Tregs), tumor-associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Since interferon beta (IFN-β) has been clinically used for the treatment of malignant melanoma, we investigated the immunomodulatory effect of IFN-β during melanoma growth to elucidate the effects of IFN-β on the tumor microenvironment by using the B16F10 melanoma model. Peritumorally administered IFN-β significantly decreased the mRNA expression and production of Th2-related chemokines, which suppressed the recruitment of Tregs in B16F10 melanoma. Since the administration of IFN-β augments the expression of PD-1 on TILs, the co-administration of anti-PD-1 Ab augmented the therapeutic effect of IFN-β for the treatment of B16F10 melanoma. Moreover, in parallel with the mouse model, in the human system, IFN-β decreased the production of Th2-related chemokines and augmented the production of Th1-related chemokines from monocyte-derived M2 macrophages. Since these immunomodulatory effects of IFN-β on macrophages were also observed in the lesional skin of human in-transit melanoma, our present data suggest one of the possible immunomodulatory effects of IFN-β and support the possibility of IFN-β in combination with anti-PD-1 Ab for the treatment of melanoma.

An imbalance of immunosuppressive cells and cytotoxic cells plays an important role in inhibiting the antitumor immune response of the tumor-bearing host. We previously reported the profiles of tumor infiltrating leukocytes in cutaneous angiosarcoma (AS) and suggested that a combination of docetaxel (DTX) with bisphosphonate risedronate sodium (RS) might be effective for MMP9-expressing AS by targeting immunosuppressive cells such as M2 macrophages. To further confirm the effect of this combination therapy, in this report we investigated the immunomodulatory effect of DTX and RS on CD163+ arginase 1 (Arg1)+ M2 macrophages in vitro. Interestingly, our present study demonstrated that DTX in combination with RS significantly upregulated the mRNA expression of CXCL10 on M2 macrophages and significantly decreased the mRNA expression of CCL17 and Arg1. Moreover, the production of CXCL10 and CXCL11 from M2 macrophages was significantly increased by DTX with RS though there was no effect of DTX with RS on the production of CCL5 and CCL17. Furthermore, DTX with RS significantly decreased the production of CCL18, which was previously reported to correlate with the severity and prognosis in cancer patients. Our present report suggests one of the possible mechanisms of DTX with RS in the supportive therapy for angiosarcoma.