Masatomo Kimura

Disseminated Human Conidiobolomycosis Due to Conidiobolus lamprauges

ABSTRACT We describe a disseminated fungal infection by Conidiobolus lamprauges in a patient with malignant lymphoma. Histopathology and mycological studies were performed, along with molecular analyses. This is the first record of this species causing human disease and the fifth reported disseminated infection by a Conidiobolus sp. in humans.

Involvement of angiotensin II and reactive oxygen species in pancreatic fibrosis.

Background: Pancreatic cancers often develop in the context of pancreatic fibrosis caused by chronic pancreas inflammation, which also results in the accumulation of reactive oxygen species (ROS), pancreatic parenchymal cell death, and stellate cell activation. Angiotensin II, which is converted from angiotensin I by the angiotensin-converting enzyme (ACE), stimulates ROS production via NADPH oxidase. In stellate cells, angiotensin II activates the stress-activated protein kinase p38. However, the molecular mechanism by which angiotensin II regulates pancreatic inflammation and fibrosis remains to be determined. Methods: Wistar Bonn/Kobori (WBN/Kob) rats spontaneously develop chronic pancreatic inflammation. To examine whether blockade of the renin-angiotensin system affects the development of pancreatic fibrosis, WBN/Kob rats were given angiotensin II type 1 receptor (AT1R) blocker or ACE inhibitor (ACEI). Next, we assessed the role of angiotensin II and its possible downstream target p38α in stellate cell activation using primary stellate cells. Results: Treatment with AT1R blocker and ACEI prevented the development of chronic pancreatitis and fibrosis. In stellate cells, angiotensin II upregulated the expression of angiotensin II receptors, α-smooth muscle actin (SMA) and transforming growth factor-β. In addition, p38α was found to be essential to collagen type I production and α-SMA expression. ROS accumulation is enhanced in chronic pancreatic inflammation, which increases the risk of pancreatic cancer. Conclusions: Inhibition of the angiotensin II signaling pathway might be a promising strategy to prevent pancreatic fibrogenesis and subsequent carcinogenesis.

Multifocal Subcutaneous Phaeohyphomycosis Caused by Phialophora verrucosa

An otherwise healthy 85-year-old woman presented with purulent multifocal subcutaneous nodules on the dorsal side of the right forearm and hand. Histopathologic examination of the biopsied specimen showed a subcutaneous granuloma with central abscess and necrosis, consistent with phaeomycotic cyst. Faint brown septate hyphae and moniliform fungal elements were found in the granuloma. Culture of the discharge grew Phialophora verrucosa. This fungus has rarely been reported as a pathogen of subcutaneous phaeohyphomycosis. Subcutaneous phaeohyphomycosis usually presents as a single lesion. In this case of multifocal lesions, initial imperfect excision seems to have caused satellite lesions. To our knowledge, this is the first report of multifocal subcutaneous phaeohyphomycosis caused by P verrucosa. The disease responded to oral itraconazole administration.

Development of Langerhans cell histiocytosis associated with chronic active Epstein–Barr virus infection

Chronic active Epstein–Barr virus (CAEBV) infection is characterized by a status of lymphoproliferative disease of EBV‐infected cells, resulting in chronic or recurrent infectious mononucleosis‐like symptoms. CAEBV is always accompanied by life‐threatening complications. We report the case of a 2‐year‐old female patient with CAEBV who subsequently developed Langerhans cell histiocytosis (LCH) presenting with bilateral exophthalmos, bone, and skin involvement. In situ hybridization for EBER revealed EBV‐infected B‐cells present in lesional tissue implying that interactions between EBV‐infected B‐cells and lesional Langerhans cells may be associated with the development of LCH. Pediatr Blood Cancer 2008;50:924–927.

Unique histological characteristics of Scedosporium that could aid in its identification.

Scedosporium prolificans has been increasingly recognized as an etiological agent of disseminated mycelial infections in profoundly immunocompromised patients. Reported herein is a case of disseminated S. prolificans infection in a patient undergoing anti‐neoplastic chemotherapy for acute myeloid leukemia. Antemortem blood culture yielded S. prolificans, which was confirmed on conventional morphological examination and polymerase chain reaction‐based DNA sequencing targeting internally transcribed spacer regions. Histopathology of autopsy specimens indicated fungal infection in the heart, lungs, liver, kidneys, spleen, pancreas and gastrointestinal tract, with the development of hemorrhagic and ischemic necrosis. The infecting fungus had developing septate hyphae and was identified as belonging to the genus Scedosporium, on in situ hybridization of tissue. The combination of haphazardly branching hyphae and lemon‐shaped conidia appeared to be the most useful distinguishing features to allow differentiation of this fungus from other filamentous fungi in tissue. Three other unique histopathological characteristics of the fungus were noted: (i) parallel hyphae bridged at right angles to produce letter‐H patterns; (ii) intravascular conidiation; and (iii) purple conidia in tissue, though these are usually described as brown in most text books. Precise histopathology, in addition to other techniques such as in situ hybridization, can aid in the identification of etiological fungi.

Pyothorax-associated angiosarcoma of the pleura with metastasis to the brain

Pleural angiosarcoma is an extremely rare, highly malignant neoplasm. Chronic tuberculous pyothorax is one of the etiological factors associated with the development of pleural angiosarcoma. This report details a case of pleural angiosarcoma in a 70‐year‐old woman with a history of tubercul‐ous pyothorax. Coagulated blood surrounded by thickened pleura in the right thorax and hematoma‐like multiple metastases in the brain were noted on autopsy. The pleural lesion was presumed to be the primary site. Microscopic examination revealed rudimentary channels lined by plump neoplastic cells in the coagulated blood of the pleura and the brain. These neoplastic cells stained positive for endothelial markers. A literature review of English language journals revealed this to be the first patient described in detail who developed cerebral metastasis secondary to pleural angiosarcoma.

Pulmonary aspergillosis due to Aspergillus terreus combined with staphylococcal pneumonia and hepatic candidiasis.

A female patient with systemic lupus erythematosus (SLE) developed pulmonary aspergillosis with staphylococcal pneumonia and hepatic candidiasis.Aspergillus terreus, which is a rare causative organism of pulmonary aspergilosis, was identified from a pulmonary lesion by culture. The aleurioconidium production, a characeristic of the genusAspergillus sect.terrei, was demonstrated on short and irregular hyphal features in tissue sections. This report is the first of a combined case of pulmonary aspergillosis due toA. terreus with infections caused by other microorganisms.

Isolation and identification of Rhizomucor pusillus from pleural zygomycosis in an immunocompetent patient

Zygomycosis is usually an invasive mycotic disease caused by fungi in the class Zygomycetes. It often occurs in immunocompromised patients, but sporadic cases without apparent immune impairment have been described. This report presents the first case of pleural zygomycosis caused by Rhizomucor pusillus, an uncommon pathogen of human infection. A 19-year-old man was found to have pleuritis several days after a drainage catheter was implanted to cure a pneumothorax caused by a ruptured bulla. Local pneumonectomy to resect the ruptured bulla and vacuuming of the pleural fluid was performed. Rhizomucor pusillus was cultured from the pleural fluid and irregular broad sparsely septate hyphae, consistent with zygomycetes, were histologically detected in the thickened pleura of the resected bulla. The catheter was suspected of having been contaminated with the fungus, but no evidence could be obtained. His fungal pleuritis subsided without any antifungal medical therapy and his immunocompetence seemed to contribute to limiting the infection.

Report of two cases of pseudoprogression in patients with non–small cell lung cancer treated with nivolumab—including histological analysis of one case after tumor regression

The recent approval of nivolumab and other immune-checkpoint inhibitors for the treatment of certain solid tumors including non-small cell lung cancer (NSCLC) has transformed cancer therapy. However, it will be important to characterize effects of such agents not seen with classical cytotoxic drugs or other targeted therapeutics. We here report two cases of NSCLC showing so-called pseudoprogression during nivolumab treatment. In both cases, imaging assessment revealed that liver metastatic lesions initially progressed but subsequently shrank during continuous nivolumab administration, with treatment also resulting in a decline in serum levels of carcinoembryonic antigen. Histological evaluation of the liver metastatic lesion of one case after regression revealed fibrotic tissue containing infiltrated lymphocytes positive for CD3, CD4, or CD8 but no viable tumor cells, suggestive of a durable immune reaction even after a pathological complete response. Given the increasing use of immune-checkpoint inhibitors in patients with NSCLC or other solid tumors, further clinical evaluation and pathological assessment are warranted to provide a better understanding of such pseudoprogression.

Oncocytic carcinoma of the parotid gland. A case report.

BACKGROUND Oncocytic carcinoma is a rare malignant tumor of the salivary gland. Abundant, granular, eosinophilic cytoplasm is recognized as an oncocytic feature that reflects an accumulation of mitochondria. Ultrastructural study or immunohistochemical staining using antimitochondrial antibody can confirm the oncocytic nature of the tumor. However, there have been no data on whether immunocytochemical staining for human mitochondria aids in the confirmation of the oncocytic nature of oncocytic carcinoma. CASE A 61-year-old man presented with a swelling in the left lower cheek. Computed tomography demonstrated a solid, isodense tumor in the parotid gland. An excisional biopsy of the tumor was performed, and an enlarged regional lymph node was removed. Imprint cytology of the lymph node showed cohesive cell clusters with lymphocytes. The clusters were composed of tumor cells that had characteristic abundant, granular cytoplasm and round to oval, centrally or eccentrically located nuclei with increased, fine chromatin and distinct nucleoli. Immunocytochemical staining revealed granular immunoreactivity of the cytoplasm for human mitochondria. Histology demonstrated tumor invasion in the normal gland and adjacent skeletal muscles. All tumor cells showed positive cytoplasm with antimitochondrial antibody by immunohistochemistry. Ultrastructural studies demonstrated packed mitochondria in the cytoplasm of the tumor. CONCLUSION Immunocytochemical staining for human mitochondria help confirm the oncocytic nature of oncocytic carcinoma in cytologic specimens.