Persistent congenital milia involving the skin of the whole body in an infant with trisomy 13 syndrome.

Milia are tiny pearly-white cysts on the surface of the skin. In newborns, milia are usually located around the nose and eyes and generally disappear after the first several weeks of life. Trisomy 13 is a severe chromosomal disorder, with various complications. Here, we report a case of a 9-month-old female infant with trisomy 13 who had persistent congenital milia covering her entire body surface.

Immunohistological analysis of peptide-induced delayed-type hypersensitivity in advanced melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination.

BACKGROUND: In melanoma patients vaccinated with monocyte-derived melanoma peptide-pulsed dendritic cells (DC), the delayed-type hypersensitivity (DTH) reactions have been examined as a surrogate marker to determine if acquired immunity is induced by DC vaccination. To date, however, only limited information has been reported as for histopathological analyses of DTH. OBJECTIVE: To evaluate tumor-specific immunomonitoring histopathologically after DC vaccination in melanoma patients. METHODS: Seven patients previously vaccinated with monocyte-derived melanoma peptide-pulsed DCs were challenged with recall antigenic peptide injection in the skin of the forearm. Using immunohistochemical techniques, the presence of immune cells and the expression of CD4, CD8, interleukin (IL)-2, IL-4, IL-10, Foxp3, CD1a, CD1d, and interferon (IFN)-gamma was investigated at the site of injection where a DTH reaction developed. RESULTS: Strong DTH reactions from infiltrated erythema to bullae formation were detected in all 7 cases. Biopsies taken from the DTH site revealed heavy infiltration of mononuclear cells and eosinophils in the dermis and subcutaneous tissue. Cells staining positively for CD4, CD8, IL-2, IL-4, Foxp3, CD1d, and IFN-gamma were increased at the site 48h after antigen injection in all cases. Cells positive for IL-10 were never found in any patient. Regulatory T cells appeared 6h after injection and reached their maximum at day 7. CONCLUSIONS: The significant induction of CD8(+)T cells as well as both Th1 and Th2-type cells at the site of DTH suggests that effective antigen presentation leading to anti-tumor immune responses has taken place. Inhibitory mechanisms may also develop as the disappearance of the DTH response could be related to an increase in Foxp3+ cells.

Ecthyma gangrenosum without pseudomonas septicemia in a kidney transplant recipient.

We report a case of ecthyma gangrenosum (EG) without septicemia in a renal transplant recipient who presented with a 1-month history of painful ulcers, vesicles and bullae on the face and extremities. Histopathological findings revealed subepidermal bullae covered by a necrotic epidermis containing an infiltrate of a moderate number of lymphocytes, neutrophils and necrotic collagen. Many dilated and congested capillaries were also present due to thrombi beneath the bullae, with alteration of collagen fibers through the superficial to middle dermis with some infiltrate. A culture from the ulcers revealed the presence of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus, whereas the results of repeated blood cultures were negative. The ulcers were completely cured by early appropriate i.v. antibiotic therapy with granulocyte colony-stimulating factor, without progression to EG with septicemia. An immunocompromised state due to immunosuppressive drugs, in addition to diabetes mellitus, hypogammaglobulinemia and hypoproteinemia, may have caused the EG and herpes zoster may have exacerbated the condition.

Vaccination of Japanese patients with advanced melanoma with peptide, tumor lysate or both peptide and tumor lysate-pulsed mature, monocyte-derived dendritic cells.

We performed a clinical trial to assess the feasibility and efficacy of immunotherapy with peptides, tumor lysate or both peptides and tumor lysate-pulsed mature, monocyte-derived dendritic cells (DC) for advanced malignant melanoma patients that are resistant to conventional therapies. Sixteen patients were enrolled in this trial. All patients received DC vaccines i.d. in the proximal thigh, close to the inguinal lymph nodes, one treatment per week or 2 weeks. Several factors such as clinical findings, computed tomography (CT) images, delayed type hypersensitivity (DTH) response, enzyme-linked immunosorbent spot (ELISPOT) assay, and immunohistochemistry in primary, metastatic lesions and the DTH site were evaluated. Clinical results through DC vaccination were as follows: in 11 evaluable cases, three stable disease, six progression of disease and two disease-free from the time of study entry to the completion of one vaccination course. One patient showed reduction of the tumors in the metastases on chest CT during the first and second course of DC vaccination. Ten out of 14 evaluable cases showed positive DTH responses to more than one treatment with melanoma peptides or tumor lysate. Eight out of 13 evaluable cases showed positive immunological responses to more than one treatment with melanoma peptides or tumor lysate in an ELISPOT assay. As for the experiences with toxicity and adverse reactions, autosensitization dermatitis-like eruptions appeared in five cases during DC vaccination. No severe adverse effects were seen in any of the patients. In our study, the clinical efficacy in prolongation of the patients' survival was confirmed. At the same time, cancer immunoediting of the tumor was also found. It will be necessary to improve the tumor-specificity of this therapeutic approach and to analyze the mechanism(s) of tumor escape from immunosurveillance in melanoma.

Mouth and Genital Ulcers with Inflamed Cartilage Syndrome: Case Report and Review of the Published Work.

Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome are disease that fulfilled criteria for diagnosis of Behcet's disease (BD) and relapsing polychondritis (RP). We report a 22-year-old Japanese woman presented with MAGIC syndrome and we described the clinicopathological characteristics of MAGIC syndrome based on a review of published cases from July 1985 to December 2015. In our case, the patient with oral aphthae, erythema nodosum, acne-like eruptions, uveitis, and polyarthritis fulfilled criteria for diagnosis of incomplete form of BD. The patient with uveitis, polyarthritis, and histological confirmation of chondritis also fulfilled criteria for diagnosis of RP. The patient was successfully treated with oral colchicine followed by prednisolone. The symptoms of MAGIC syndrome gradually disappeared, and the prednisolone dosage was gradually decreased and stopped. She has been in remission without active medication for a further 8 months. In the previous reports, some authors suggested that MAGIC syndrome was not a disease entity and might be RP occurring secondary to BD, another association of an autoimmune disease, or vasculitis with RP. However, the pathogenic association between MAGIC syndrome, BD, and RP is still unclear, and the number of reported cases of MAGIC syndrome is insufficient to establish a clear explanation. Therefore, further accumulation of data and careful observation of the clinical course are required to improve the understanding of MAGIC syndrome.

Atypical fibroxanthoma on a bald scalp.

We present the clinical, histopathological and immunohistochemical findings of an atypical fibroxanthoma (AFX) on the bald scalp of an 81-year-old French man who had worked at a private high school in Japan as a janitor for over 40 years. The patient had a history of basal cell carcinoma on the nape, and chronic solar radiation seemed to be a predisposing factor in the pathogenesis of this association. This case showed the typical clinical and histopathological characteristics of AFX, and the immunohistochemical results suggested differentiation of histiocytes and myofibroblasts. The AFX was completely resected, and the patient has not had tumor recurrence or metastasis for over four postoperative years. This case therefore provides further support to the theory that AFX displays a clinically benign course, even though it is essentially a malignant tumor histologically located in the dermis. Therefore, we must excise AFX completely with great care and perform regular physical examinations for several years after operation.

Clinical usefulness of Mohs' chemosurgery for palliative purposes in patients with cutaneous squamous cell carcinoma with risk factors or without indication for surgery: three case reports.

Mohs' chemosurgery is a technique of chemical fixation of a cutaneous tumor using 20% zinc chloride, and the surgeon performs a sequential series of excisions until no residual tumor can be found in the bottom layer of the specimen by microscopic examination. This technique has also been gradually accepted as one of the palliative treatment options in patients with cutaneous tumors with risk factors for surgery. We report three cases of cutaneous squamous cell carcinoma that were treated with Mohs' chemosurgery for palliative purposes. In case 1, Mohs' chemosurgery could prevent rapid tumor growth and control the bleeding, exudation and offensive odor from ulcerated tumors. The patient was able to live enjoyably at home with her family before she was transferred to a palliative care hospital. In case 2, Mohs' chemosurgery followed by debridement of residual tumor and a full-thickness skin graft contributed to an early hospital discharge, which prevented the progression of cognitive decline. In case 3, remission of the tumor was achieved by concurrent treatment with local radiotherapy and Mohs' chemosurgery. Mohs' chemosurgery for palliative purposes is not a radical treatment, but contributes to the patient's quality of life. It has the possibility of becoming a radical treatment if eligible patients and concurrent treatment are carefully selected. An increase in the number of skin cancer patients with risk factors for surgery has been predicted because of the progression of the aging society. Mohs' chemosurgery may become one of the treatment options for such patients.

Acute generalized exanthematous pustulosis caused by dihydrocodeine phosphate in a patient with psoriasis vulgaris and a heterozygous IL36RN mutation.

IMPORTANCE: Acute generalized exanthematous pustulosis (AGEP) is a rare and severe type of drug eruption. Dihydrocodeine phosphate is a semisynthetic opioid analgesic. Recently, recessive mutations in IL36RN have been identified in generalized pustular psoriasis (GPP). To date, 4 cases of AGEP and IL36RN mutation without previous history of psoriasis vulgaris (PV) have been reported. OBSERVATIONS: A woman in her 60s with PV presented with diffuse erythema, nonfollicular pustules, and fever. She had been treated with dextromethorphan hydrobromide hydrate, amoxicillin hydrate, clarithromycin, dihydrocodeine phosphate, tipepidine hibenzate, and tulobuterol tape for a cough and common cold. Based on histopathologic results and a positive result in a drug provocation test with dihydrocodeine phosphate, she was diagnosed with AGEP. A heterozygous IL36RN mutation c.28C>T (p.Arg10X) was also confirmed by mutation analysis. CONCLUSIONS AND RELEVANCE: This is the first report of dihydrocodeine phosphate-induced AGEP. In this case, helper T cells, type 17, might have been activated because of morphine and underlying PV, followed by increased production of interleukin (IL) 36. However, because of the IL36RN mutation, IL-36 signaling was uncontrolled, which might have resulted in the occurrence of AGEP. An IL36RN mutation might underlie several different pustular skin eruptions, including AGEP and GPP, and further accumulation of patient data is required.