Background: Simple pulmonary aspergilloma (SPA) in chronic pulmonary aspergillosis (CPA) is characterized by a ball-like lesion within a pre-existing lung cavity. The detection rate of Aspergillus in cultures is low. There are no established clinical diagnostic methods specifically focused on SPA indicated for surgery. This study aimed to develop a simple and reliable diagnostic approach by integrating imaging and serological findings.
Methods: A retrospective study was conducted on 15 patients with ball-like lesions in lung cavities who underwent lung resection. Four imaging characteristics of CPA (cavity wall thickening, infiltrative shadow around the cavity, air crescent sign, and Monod sign) and three serological markers (elevated β-D-glucan, positive Aspergillus antibody, and positive Aspergillus antigens) were evaluated for their sensitivity and specificity. Positive likelihood ratio (PLR) was calculated. Two high-PLR factors—one from imaging and one from serology—were combined to construct a simplified diagnostic approach.
Results: Of the 15 patients, 7 were diagnosed with aspergilloma, 3 with lung cancer and 5 with other diseases. The two factors with the highest PLR were Aspergillus IgG antibody and cavity wall thickening. The combination was analyzed with Fisher's exact test with a sensitivity of 71.4%, specificity of 87.5% and a p-value of 0.041.
Conclusion: This study demonstrated that combining Aspergillus IgG antibody and cavity wall thickening provides a simple and reliable approach to distinguish aspergilloma from other cavitary lung lesions.

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This study aimed to investigate the species distribution and antifungal susceptibility of fungal blood isolates collected at a university hospital between 2008 and 2023. A total of 395 fungal isolates were identified, with Candida albicans being the most prevalent species (46.1%), followed by Candida parapsilosis (23.5%), Candida glabrata (13.7%), and Candida tropicalis (6.3%). Antifungal susceptibility to three azoles and micafungin was assessed using the Clinical and Laboratory Standards Institute guidelines, M27-A3 (2008) and M27M44S ED3 (2022). Susceptibility categorization was defined as susceptible (S) or susceptible-dose-dependent (SDD). The findings revealed high susceptibility rates for C. albicans, C. glabrata, and C. parapsilosis to fluconazole, itraconazole, and voriconazole under the 2008 criteria (S + SDD = 89.5%–100%). In contrast, according to the 2022 criteria, C. albicans and C. parapsilosis exhibited 100% susceptibilities to fluconazole and voriconazole, whereas C. glabrata was only susceptible to fluconazole at the SDD (97.4%). Susceptibility of C. tropicalis to the tested azoles was notably lower, with rates of S + SDD = 52.4% under the 2008 criteria and S + SDD = 47.3% and 52.4% for fluconazole and voriconazole, respectively, under the 2022 criteria. Susceptibility to micafungin was high in all four common Candida species, with rates of S ≥ 97.4% under the 2008 criteria and S ≥ 94.7% under the 2022 criteria. These results indicate that antifungal susceptibility among fungal blood isolates has remained stable, except decreasing susceptibility of C. tropicalis to azoles. Continuous surveillance is essential to inform the optimization of treatment strategies for invasive fungal infections.

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A Japanese man in his 70s presented with multiple blackish-brown papules on the nasal wing region, which had appeared 3 months prior to his initial visit. He was initially treated at a local clinic with clindamycin phosphate gel, but showed poor improvement. Subsequently, he visited our hospital for further evaluation. A skin biopsy was performed, granulomas consisting of histiocytes were observed in the tissue, and spore-like brown cells were observed sporadically within the granulomas. Fungal culture of biopsy tissue showed the development of black villiform colonies. Molecular biological identification confirmed the pathogen as Knufia epidermidis. Based on these findings, we thought it the patient with chromoblastomycosis due to K. epidermidis.
He received 200 mg/day itraconazole (ITCZ) orally for 6 months, the multiple papules on the nasal region resolved, and the condition was considered cured. However, the papules recurred 2 months after discontinuation of ITCZ. ITCZ was restarted, and within 1 month, the recurrent papules had flattened. The patient remains on continuous ITCZ therapy at present.
Recent years have seen a rise in reports of chromomycosis caused by rare and unrecognized pathogens. When diagnosing chromomycosis, it is necessary to identify of the species by molecular biological methods actively to avoid overlooking the diversity of causative pathogens.

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Dysbiosis of the lung microbiome may be associated with the development and progression of respiratory diseases. As fungal spores invade the lungs more easily than bacteria, it seems likely that fungi colonizing the lungs are also involved in respiratory diseases. In this study, we investigated the relationship between fungal flora (mycobiome) and diffuse lung disease. Of the 185 patients who underwent bronchoalveolar lavage (BAL) during the diagnostic process, 42 with diffuse lung disease were selected for a mycobacterial analysis of BAL fluid. Twenty patients with idiopathic interstitial pneumonia (IIP), 8 with collagen tissue disease-related interstitial lung disease (CTD-ILD), 8 with sarcoidosis, and 6 with other diseases were included. Fungal DNA was extracted, and internal transcribed spacer 2 (ITS2) regions were sequenced. Of the 42 patients, 29 had polymerase chain reaction amplification products in the ITS2 region. Significant differences in alpha diversity (observed species, Shannon, and Simpson indices) were found between the CTD-ILD and sarcoidosis groups, and between the IIP and sarcoidosis groups. A comparison of the mycobiomes of individual patients (beta diversity) showed that the clustering patterns differed among the groups. In particular, BAL fluid samples from patients with sarcoidosis showed a clear clustering pattern of mycobacterial composition. Our results may lead to significant advances in our understanding of the etiology of these diseases.

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Histopathological examination is a key method for confirming fungal infections, which are often challenging to diagnose using culture and serological tests alone. Additionally, identifying the causative fungal species through histopathology provides guidance for selecting antifungal agents and treatment strategies. However, as histopathological diagnosis relies primarily on fungal morphology, distinguishing species can be difficult when rare fungi share similar features. Molecular techniques, such as polymerase chain reaction and sequencing, increasingly applied to formalin-fixed paraffin-embedded tissue, have become valuable tools for diagnosing rare fungal infections. The most effective approach combines detailed fungal morphological assessment with molecular testing. However, molecular test results must be interpreted in the context of the histopathological findings from the examined material. Notably, enhanced diagnostic accuracy through histopathology and molecular techniques enables more precise antifungal treatment, improving patient outcomes. This review highlights the importance of histopathological examination in diagnosing rare invasive fungal infections and underscores the pathologist’s essential role in identifying them.

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Various mycological tests, including culture and biomarker assays, are used for diagnosing invasive fungal diseases (IFDs) or deep-seated mycosis. However, these conventional diagnostics often have limitations in sensitivity and specificity. Accurate identification of the causative fungus is essential for appropriate treatment, yet this often requires invasive sampling procedures. Recently, molecular diagnostics with greater accuracy than conventional methods have been increasingly used for diagnosis of IFDs. Multiplex polymerase chain reaction (PCR) assays covered by health insurance, such as the FilmArray Blood Culture Panel and Meningitis/Encephalitis Panel, include select fungal pathogens and are used in specific diagnostic contexts. Additionally, several fungal PCR tests are available in Japan but not yet covered by health insurance system. Species-specific PCR assays, such as real-time PCR for Pneumocystis jirovecii and Aspergillus spp., have been incorporated into the revised consensus definition for IFDs published by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium in 2020, although standardization across laboratories remains a challenge. Panfungal PCR assays, which detect and identify fungi from clinical specimens (e.g., blood, body fluids, biopsy samples, formalin-fixed paraffin-embedded tissues), are also in use. Furthermore, next-generation sequencing-based fungal diagnostics targeting microbial cell-free DNA in blood, also referred to as liquid biopsy, are already commercially available in the United States. This review provides an overview of the clinical utility of molecular diagnostics for IFDs.

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Gastrointestinal mucormycosis is a rare form of mucormycosis that can potentially result in fatal outcomes. We encountered a case of gastric mucormycosis, first identified at postmortem following the death of a patient with malignant lymphoma. This paper highlights the unique pathological features of this rare gastric mucormycosis, which were suspected to be the primary source of the infection. Additionally, we made a little thought to the potential possibility that unheated vegetables that might be contaminated with the causative fungus could have played as a vector for carrying the fungus into the gastric mucosa.

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This report presents the case of a Thai male in his twenties presenting prolonged fever, generalized lymphadenopathy and hepatosplenomegaly. Blood cultures isolated Campylobacter jejuni, while lymph node cultures isolated Histoplasma capsulatum. A gene panel for immunodeficiency revealed nuclear factor kappa B subunit 1 (NFKB1) deficiency, leading to a final diagnosis of common variable immunodeficiency (CVID) due to autosomal dominant NFKB1 deficiency. The patient was initially treated with amphotericin B (0.7 mg/kg/day) for 3 weeks, followed by itraconazole 200 mg orally twice daily, and received intravenous azithromycin 500 mg once daily for C. jejuni bacteremia for 14 days. After three months of treatment, the patient demonstrated partial clinical and radiologic improvement. Additionally, intravenous immunoglobulin was administered to treat CVID. After 12 months of itraconazole, the follow-up computed tomography showed reduced lymphadenopathy to subcentimetric nodes and resolved hepatomegaly. Patients with disseminated atypical infections should be evaluated for primary immunodeficiency disorders, even when considered healthy.

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We report the case of chromoblastomycosis caused by Phialophora europaea in Japan. A woman in her 60s presented with an erythematous plaque with pustules on her right buttock. Skin biopsy was performed, and the specimen showed hyperkeratosis, acanthosis with parakeratosis, and dermal granulomatous infiltrate with multinucleated histiocytic giant cells. Muriform cells were found in the inflammatory tissue. The patient was diagnosed as having chromoblastomycosis and was referred to our department. A direct examination of the crust using potassium hydroxide solution revealed the presence of fungal elements as muriform cells. The culture of the crust revealed felty, grayish-to-black colonies. The isolate was identified as P. europaea by molecular identification of the internal transcribed spacer sequences on the rRNA gene. The patient's condition improved after surgical excision, and oral itraconazole was administered postoperatively. To our knowledge, this is the first reported case of a skin infection caused by P. europaea outside of Europe.

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