Two cases of BRAF-mutated, bulbar conjunctival melanoma, and review of the published literature.

We describe two patients with BRAF-mutated melanoma of the epithelioid cell type arising from primary acquired melanosis with severe atypia of the right bulbar conjunctiva. Patient 1 was a 71-year-old Japanese man. After adjuvant cryotherapy and enucleation of the right eyeball, therapy with vemurafenib was administered for a distant metastasis to a lumbar vertebra, accompanied by erythema multiforme and two keratinous tumours. The patient died due to metastases to the liver and multiple vertebrae, despite therapy with nivolumab and combination therapy with dabrafenib plus trametinib. Patient 2 was a 72-year-old Japanese man. After adjuvant cryotherapy, periodic mitomycin C eye drops, and excision of the superficial portion of the right parotid gland and the dissection of cervical lymph nodes, he was treated with adjuvant combination therapy with dabrafenib plus trametinib. Dermatologists should be familiar with BRAF-mutated conjunctival melanoma, which is usually located on the bulbar conjunctiva and associated with more frequent distant metastasis.

[A Case of central venous catheter-related infection with Malassezia sympodialis].

We report a 63-year-old male with central venous catheter-related infection caused by Malassezia sympodialis after total gastrectomy for a gastric cancer. He had fever and his leukocyte counts and C-reactive protein were elevated 14 days after his operation. After his central venous hyperalimentation catheter was removed, the inflammatory signs immediately disappeared, suggesting an intravenous catheter-related infection. A yeast-like fungus was cultured in brain-heart infection semi-solid agar ten days later, and was diagnosed morphologically as Malassezia sp. This strain was identified as M. sympodialis by Tween assimilation test and was confirmed by whole-sequence of internal transcribed spacer 1 regions (ITS1). This is the first report of catheter-related infection caused by M. sympodialis. This strain grew and was subcultured on CHROMagar Candida, potato dextrose agar and Sabouraud agar. There have been no reports of such a lipid-independent Malassezia sp. except for M. pachydermatis. The mechanism of lipid independence of this strain is undetermined and future work is needed. Malassezia sp. is receiving increased attention as an etiologic pathogen of catheter-related fungemia in clinical microbiology laboratories and infectious disease sections.

Immunohistochemical diagnosis of Cryptococcus neoformans var. gattii infection in chronic meningoencephalitis: the first case in Japan.

Cryptococcus neoformans (C. neoformans) var. gattii infection usually occurs in tropical and subtropical areas, and rarely in the northern hemisphere. We report the first Japanese with cryptococcal meningoencephalitis caused by C. neoformans var. gattii infection that occurred during a trip to Australia. This agent was identified in a cerebellar biopsy specimen by immunohistochemical technique with serotype-specific anti-sera. Because the meningitis caused by it did not respond well to conventional therapy, we used an aggressive therapeutic regimen to successfully treat the patient. Even in areas where C. neoformans var. gattii does not exist, this infection should be considered possible as a travel-related infection.

Successful polymerase chain reaction-based diagnosis of fungal meningitis in a patient with chronic granulomatous disease.

Meningitis is not a common complication of chronic granulomatous disease (CGD). Here, we present details of a 3-year-old boy with X-linked CGD, who suffered from fungal meningitis. While 19 samplings using conventional cerebrospinal fluid (CSF) cultures failed to detect any organisms, fungal DNA was identified in the CSF by a new polymerase chain reaction (PCR)-based method. The patient recovered without any sequelae after treatment with a combination of antifungal agents, interferon-gamma and granulocyte infusions. This case report demonstrates that fungal meningitis must be included in the differential diagnosis of infections in CGD patients and that the PCR-based detection of fungal DNA is a powerful tool for diagnosis.

[Hansenula anomala fungemia in a patient undergoing IVH-treatment with ascending colon carcinoma].

A case of catheter-related fungemia due to Hansenula anomala is reported. A 61-year-old male was diagnosed as having stage 3 ascending colon carcinoma stenosing the colon severely and was admitted to our hospital to receive an operation of the carcinoma. Just after admission, an intravenous hyperalimentation (IVH) catheter was inserted and IVH was started to prevent development of ileus and to prepare for laparotomy. Nine days later, he developed a fever. On the next day, the IVH catheter was removed and cultures of blood and the catheter revealed the presence of yeast-like organisms that were identified as H. anomala. Laboratory data showed hypogranulocytemia, slight disturbances of liver and kidney, a prolongation of PT, an increase of FDP and positive reaction of candida antigen by CAND-TEC. He improved after the removal of the catheter, and treatment with intravenous infusion of fluconazole 2 days after the removal was thought to be useful for recovery and to prevent the reappearance of infection though susceptibility to fluconazole was not good. Human infections due to H. anomala are rare and this is the 8th case of H. anomala fungemia in Japan. From this report and a review of the literature, risk factors for developing this fungemia include the use and abuse of central venous catheters such as IVH-catheter. It appears that H. anomala has recently emerged as a potential pathogen in the immunocompromised hosts and patients after insertion of central venous catheters and that these organisms should be added to the growing list of unusual fungal pathogens in these patients.

Catheter-related infections by Hansenula anomala in children.

During August and September, 1992, we experienced 4 cases of Hansenula anomala (H. anomala, synonym Pichia anomala) fungemia in immunocompromised patients. Two patients had been suffering from a malignant disease, 3 of them had received broad-spectrum antibiotics and a central venous catheter (CVC) had been inserted in all of them. H. anomala was isolated as the sole pathogen from all 4 patients. Three of them responded favorably to fluconazole after withdrawal of the catheter, but one failed. H. anomala should be considered as a possible cause of catheter-related infections.