Endemic mycoses in children in North America: a review of radiologic findings.

Clinically significant endemic mycoses (fungal infections) in the United States (U.S.) include Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides immitis/posadasii. While the majority of infections go clinically unnoticed, symptomatic disease can occur in immunocompromised or hospitalized patients, and occasionally in immune-competent individuals. Clinical manifestations vary widely and their diagnosis may require fungal culture, making the rapid diagnosis a challenge. Imaging can be helpful in making a clinical diagnosis prior to laboratory confirmation, as well as assist in characterizing disease extent and severity. In this review, we discuss the three major endemic fungal infections that occur in the U.S., including mycology, epidemiology, clinical presentations, and typical imaging features with an emphasis on the pediatric population.

Improving lung cancer diagnosis with cancer, fungal, and imaging biomarkers.

OBJECTIVE: Indeterminate pulmonary nodules (IPNs) represent a significant diagnostic burden in health care. We aimed to compare a combination clinical prediction model (Mayo Clinic model), fungal (histoplasmosis serology), imaging (computed tomography [CT] radiomics), and cancer (high-sensitivity cytokeratin fraction 21; hsCYFRA 21-1) biomarker approach to a validated prediction model in diagnosing lung cancer. METHODS: A prospective specimen collection, retrospective blinded evaluation study was performed in 3 independent cohorts with 6- to 30-mm IPNs (n = 281). Serum histoplasmosis immunoglobulin G and immunoglobulin M antibodies and hsCYFRA 21-1 levels were measured and a validated CT radiomic score was calculated. Multivariable logistic regression models were estimated with Mayo Clinic model variables, histoplasmosis antibody levels, CT radiomic score, and hsCYFRA 21-1. Diagnostic performance of the combination model was compared with that of the Mayo Clinic model. Bias-corrected clinical net reclassification index (cNRI) was used to estimate the clinical utility of a combination biomarker approach. RESULTS: A total of 281 patients were included (111 from a histoplasmosis-endemic region). The combination biomarker model including the Mayo Clinic model score, histoplasmosis antibody levels, radiomics, and hsCYFRA 21-1 level showed improved diagnostic accuracy for IPNs compared with the Mayo Clinic model alone with an area under the receiver operating characteristics curve of 0.80 (95% CI, 0.76-0.84) versus 0.72 (95% CI, 0.66-0.78). Use of this combination model correctly reclassified intermediate risk IPNs into low- or high-risk category (cNRI benign = 0.11 and cNRI malignant = 0.16). CONCLUSIONS: The addition of cancer, fungal, and imaging biomarkers improves the diagnostic accuracy for IPNs. Integrating a combination biomarker approach into the diagnostic algorithm of IPNs might decrease unnecessary invasive testing of benign nodules and reduce time to diagnosis for cancer.

North American Endemic Fungal Infections.

Histoplasmosis, blastomycosis, and coccidioidomycosis are endemic fungal infections in North America. Many infections are subclinical, and many symptomatic infections are mild. Pneumonia is the most common clinical manifestation. All can occur in immunocompetent and immunocompromised patients, with the latter at greater risk for disseminated and more severe disease. As with other acute respiratory illness, imaging can play a role in diagnosis. Knowledge of the acute and chronic imaging findings of endemic fungal infections is important for radiologists so that they can assist in establishing these often-elusive diagnoses, recognize normal evolution of imaging findings of infection, and identify complications.

Histoplasmosis pulmonar cavitada en un paciente pediátrico: reporte de caso / Acute cavitated pulmonary histoplasmosis in a pediatric patient: a case report

La histoplasmosis es una micosis producida por el Histoplasma capsulatum. Esta condición es endémica en Estados Unidos, Suramérica, América central y África. Suele presentarse en todas las edades, pero en niños; en especial en aquellos inmunodeprimidos, se han descrito presentaciones graves o atípicas. Se presenta el caso de un paciente de 16 años con antecedentes de trasplante renal, que inicia con síntomas respiratorios inespecíficos, tos y alzas térmicas intermitentes. La radiografía de tórax mostró una imagen de condensación cavitada en el lóbulo superior izquierdo, por lo que se realiza una fibrobroncoscopia, lavado broncoalveolar y cultivos para patógenos habituales, micobacterias y hongos, lográndose aislar al Histoplasma capsulatum. EL objetivo de este trabajo es el de resaltar la consideración de histoplasmosis como diagnóstico diferencial de lesiones cavitadas en parénquima pulmonar en pacientes inmunodeprimidos con la presentación de un caso clínico.

Histoplasmosis is a mycosis caused by Histoplasma capsulatum. This condition is endemic in the United States, South America, Central America, and Africa. It usually occurs in all ages, but in children, especially those immunosuppressed, serious or atypical presentations have been described. We present the case of a 16-year-old patient with a history of kidney transplantation that began with nonspecific respiratory symptoms, cough, and intermittent fever peaks. Imaging findings suggestive of cavitation were found, which by means of a fiberoptic bronchoscopy and bronchoalveolar lavage study isolated Histoplasma capsulatum by means of a deep mycosis culture. The main interest of the case presented is the consideration of histoplasmosis in the presence of cavitated lesions in the lung parenchyma in immunosuppressed patients.

Combined frameless stereotactical biopsy and intraoperative cerebral angiography by 3D-rotational fluoroscopy with intravenous contrast administration: a feasibility study.

BACKGROUND: Mobile 3-dimensional fluoroscopes are an integral part of modern neurosurgical operating theatres and can also be used in combination with free available image post processing to depict cerebral vessels. In preparation of stereotactic surgery, preoperative Computed Tomography (CT) may be required for image fusion. Contrast CT may be of further advantage for image fusion as it regards the vessel anatomy in trajectory planning. Time-consuming in-hospital transports are necessary for this purpose. Mobile 3D-fluoroscopes may be used to generate a CT equal preoperative data set without an in-hospital transport. This study was performed to determine the feasibility and image quality of intraoperative 3-dimensional fluoroscopy with intravenous contrast administration in combination with stereotactical procedures. METHODS: 6 patients were included in this feasibility study. After fixation in a radiolucent Mayfield clamp a rotational fluoroscopy scan was performed with 50 mL iodine contrast agent. The image data sets were merged with the existing MRI images at a planning station and visually evaluated by two observer. The operation times were compared between the frame-based and frameless systems ("skin-to-skin" and "OR entry to exit"). RESULTS: The procedure proves to be safe. The entire procedure from fluoroscope positioning to the transfer to the planning station took 5-6 min with an image acquisition time of 24 s. In 5 of 6 cases, the fused imaging was able to reproduce the vascular anatomy accurately and in good quality. Both time end-points were significantly shorter compared to frame-based interventions. CONCLUSION: The images could easily be transferred to the planning and navigation system and were successfully merged with the MRI data set. The procedure can be completely integrated into the surgical workflow. Preoperative CT imaging or transport under anaesthesia may even be replaced by this technique in the future. Furthermore, hemorrhages can be successfully visualized intraoperatively and might prevent time delays in emergencies.

Case Report: Incidental Finding of COVID-19 Infection after Positron Emission Tomography/CT Imaging in a Patient with a Diagnosis of Histoplasmosis and Recurring Fever.

This is a case report of a 37-year-old woman evaluated with 18F-fludeoxyglucose (18F-FDG) positron emission computed tomography/CT with recurrent fever after treatment with itraconazole for 6 weeks for histoplasmosis. The examination demonstrated a decrease in the dimensions of the pulmonary opacities previously identified in the left lower lobe and attributed to histoplasmosis. In addition to these pulmonary opacities, increased FDG uptake was also observed in lymph nodes present in the cervical region, mediastinum, left lung hilum, and hepatic hilum. Notably, other pulmonary opacities with ground-glass pattern that were not present in the previous computed tomography were detected in the right lower lobe, with mild 18F-FDG uptake. Nasal swab performed shortly after the examination was positive for COVID-19. In this case, the 18F-FDG positron emission computed tomography/CT study demonstrated findings consistent with active COVID-19 infection coexisting with inflammatory changes associated with histoplasmosis infection.

Disseminated Histoplasmosis Presenting as Weight Loss and Hypercalcemia in a Renal Transplant Patient With Prior History of Subtotal Parathyroidectomy.

Hypercalcemia and weight loss in a renal transplant patient especially with history of parathyroidectomy raises concern for an underlying malignancy, fungal infections or granulomatous disease. We present a case of 45-year-old male with history of subtotal parathyroidectomy presented with severe persistent hypercalcemia, acute kidney injury (AKI) and significant weight loss. An extensive workup revealed disseminated histoplasmosis. Hypercalcemia (which was refractory to initial medical management) and other symptoms resolved after a few weeks of initiating the antifungal treatment.

Histoplasmosis tenosynovitis of the forearm and wrist: imaging, surgical and pathologic findings.

Histoplasmosis is a disease endemic to several parts of the world, including South America. It progresses in a mostly asymptomatic and self-limiting manner but has the potential to cause disseminated pulmonary infection, especially in immunocompromised patients. Rare reports from the literature describe musculoskeletal manifestations related to the two varieties of the pathogen that cause histoplasmosis, namely, the capsulatum or duboissi variety. In this report, we describe the case of a previously healthy, middle-aged man, with slowly progressing pain in the right forearm, wrist, and fingers, diagnosed with a case of pathologically confirmed histoplasmosis tenosynovitis. We also describe the imaging, surgical, and histological findings and discuss the differential diagnoses for tenosynovitis, in case of atypical infections.

Histoplasmosis in Inflammatory Bowel Disease with Tumor Necrosis Factor-Alpha Inhibitors: Safe to Continue Biologics?

BACKGROUND: The advent of tumor necrosis factor-α (TNF-α) inhibitor therapy has transformed inflammatory bowel disease management; however, these medications carry a boxed warning for risk of serious infections, including invasive fungal infections. AIMS: We aimed to study the clinical features, severity, and outcomes of histoplasmosis in patients on TNF-α inhibitors for IBD. METHODS: We performed a retrospective review of IBD patients receiving TNF-α inhibitors who developed histoplasmosis from January 1, 2001, to May 31, 2018. Patients with drug indications other than ulcerative colitis or Crohn's disease were excluded. IBD was diagnosed histologically, radiographically, or endoscopically. RESULTS: We identified 49 patients (median age 44 years; range 19-76) with histoplasmosis on TNF-α inhibitors. Patients with disseminated disease had a median urine antigen of 10.76 ng/mL compared with pulmonary disease alone 0.375 ng/mL (p < 0.001). Charlson Comorbidity Index and urine antigen levels showed a trend toward predicting disease severity (p > 0.05). Median length of stay was 9.5 days. Itraconazole was used for maintenance in all patients. Median follow-up was 4.7 years. Total treatment duration ranged from 3 to 15 months. TNF-α inhibitor therapy was continued in nine and resumed in ten patients after completing antifungals. Three deaths occurred (6%). CONCLUSIONS: Histoplasmosis outcomes were mostly favorable. Many patients were young with few comorbidities; however, those with more comorbidities experienced more severe histoplasmosis. Compared to prior studies, many of these patients resumed or continued biologic therapy. There were no histoplasmosis recurrences after resuming TNF-α inhibitor therapy. Vigilance for disseminated fungal infections in this patient population is essential.

Ultrasonographic findings of gastrointestinal histoplasmosis in dogs.

Histoplasmosis, a mycotic infection caused by Histoplasma spp, can infect the gastrointestinal tract of dogs. Clinical signs of gastrointestinal histoplasmosis can include diarrhea, profound weight loss, anorexia, and vomiting. Rectal scrape for cytology can provide a quick diagnosis, but if negative abdominal ultrasound is often pursued. Ultrasonographic abnormalities in dogs with gastrointestinal histoplasmosis have rarely been reported. This retrospective, single-center case series aimed to describe the ultrasonographic features of gastrointestinal histoplasmosis in dogs. Nineteen cases with a diagnosis of gastrointestinal histoplasmosis confirmed with gastrointestinal cytology or histopathology (N = 15) or gastrointestinal lymph node cytology (N = 4) that had undergone an abdominal ultrasound examination from 2005 to 2020 were included. Ultrasound images were reviewed by an American College of Veterinary Radiology (ACVR)-certified veterinary radiologist and diagnostic imaging resident. Eighteen cases had sonographic abnormalities within the gastrointestinal tract. The colon was the most affected organ. Colonic thickening and abnormal wall layering were the most frequent findings (N = 16 dogs); thickening ranged from 0.36 to 1.2 cm. Diffuse, multifocal, and focal thickening patterns were seen. Sixteen patients had abnormal wall layering of the colon (complete loss of layering or altered with partial loss of layering). Other frequent findings included lymphadenopathy, small intestinal thickening with abnormal wall layering and peritoneal effusion. Based on the authors' review of the literature, this is the first description of ultrasonographic findings of gastrointestinal histoplasmosis in a group of dogs. Although abnormal gastrointestinal wall layering seen sonographically is most frequently associated with neoplasia, this is not pathognomonic. Gastrointestinal histoplasmosis should be considered as a differential diagnosis due to the similarities and overlap of ultrasonographic features.

Flip flop fungus sign: an FDG PET sign of benign pulmonary nodules.

A 71-year-old man was referred to pulmonary clinic for incidental findings of hypermetabolic lung nodule and mediastinal adenopathy on CT FDG PET performed for evaluation of cough. The patient underwent bronchoscopy with endobronchial ultrasound that was non-diagnostic. The patient was subsequently sent for video-assisted thoracoscopic lymph node biopsy notable for confluent caseating granulomas due to chronic infection by Histoplasma capsulatum Review of previous PDG PET was notable for the flip flop fungus sign-a PDG PET finding that could have altered the patients' clinical course by potentially avoiding the need for invasive surgical tissue diagnosis.

Bilateral adrenal histoplasmosis presenting as adrenal insufficiency in an immunocompetent host in the Philippines.

Disseminated histoplasmosis, with the adrenal glands as being the only site of demonstrable disease in an immunocompetent adult, is a rare infection leading to adrenal insufficiency. This disease carries high mortality when unrecognised. We describe the first reported case of adrenal histoplasmosis in the Philippines in a 72-year-old immunocompetent, Filipino man who presented with a 3-month history of intermittent flank pain, weight loss and generalised weakness. His imaging demonstrated bilateral adrenal masses on ultrasonography and contrast-enhanced CT scan. The initial impression was adrenal cancer, however, fine-needle aspiration cytology revealed the presence of yeast cells and blood culture grew Histoplasma capsulatum The diagnosis of the case represents a diagnostic challenge in immunocompetent individuals because they manifest with non-specific symptoms. A heightened suspicion is therefore needed to prevent significant morbidity and mortality.