Gastric mucormycosis presenting as diffuse thickening of the gastric wall with enhancement.

We report the case of a 63-year-old woman who presented with abdominal distension and pain two months ago, which worsened after eating. An abdominal CT examination revealed uneven thickening of the gastric wall on the greater curvature side of the gastric body, with progressive obviously enhancement. She was then examined by an upper endoscopy, which showed mucosal swelling on the greater curvature side of the lower gastric body with exudation of necrotic materials. Biopsies of the lesion were taken and histological results revealed a large number of broad-based and non-septate hyphae, with positive expression of PAS (Periodic Acid-Schiff) and hexamine silver stains, The patient was treated with amphotericin B liposomal antifungal therapy and remained under surveillance for six months without evidence of disease progression by follow-up upper endoscopy.

Transcutaneous retrobulbar amphotericin B for rhino-orbital-cerebral mucormycosis: a multi-center retrospective comparative study.

PURPOSE: To assess whether transcutaneous retrobulbar amphotericin B injections (TRAMB) reduce exenteration rate without increasing mortality in rhino-orbital-cerebral mucormycosis (ROCM). METHODS: In this retrospective case-control study, 46 patients (51 eyes) with biopsy-proven ROCM were evaluated at 9 tertiary care institutions from 1998 to 2021. Patients were stratified by radiographic evidence of local orbital versus extensive involvement at presentation. Extensive involvement was defined by MRI or CT evidence of abnormal or loss of contrast enhancement of the orbital apex with or without cavernous sinus, bilateral orbital, or intracranial extension. Cases (+TRAMB) received TRAMB as adjunctive therapy while controls (-TRAMB) did not. Patient survival, globe survival, and vision/motility loss were compared between +TRAMB and -TRAMB groups. A generalized linear mixed effects model including demographic and clinical covariates was used to evaluate the impact of TRAMB on orbital exenteration and disease-specific mortality. RESULTS: Among eyes with local orbital involvement, exenteration was significantly lower in the +TRAMB group (1/8) versus -TRAMB (8/14) (p = 0.04). No significant difference in mortality was observed between the ±TRAMB groups. Among eyes with extensive involvement, there was no significant difference in exenteration or mortality rates between the ±TRAMB groups. Across all eyes, the number of TRAMB injections correlated with a statistically significant decreased rate of exenteration (p = 0.048); there was no correlation with mortality. CONCLUSIONS: Patients with ROCM with local orbital involvement treated with adjunctive TRAMB demonstrated a lower exenteration rate and no increased risk of mortality. For extensive involvement, adjunctive TRAMB does not improve or worsen these outcomes.

Rhizopus homothallicus rhino-orbital-cerebral mucormycosis: Six cases from a tertiary care Centre, North India.

OBJECTIVE: To report six cases of Rhizopus homothallicus rhino-orbital-cerebral mucormycosis in North India between April 2021 and July 2021. CASE DETAILS: All six patients had diabetes, concomitant SARS-CoV-2 infection, a history of oxygen requirement and steroid intake. Among these six cases 4 were female. All patients presented with sinus pain and peri-orbital swelling. COVID-19-associated mucormycosis (CAM) was diagnosed based on microbiological examination of the biopsied tissue, and its staging was determined radiologically by CT and MRI. Three patients were in stage III-C, the others were in stage II-C, II-D and IV-A. A multidisciplinary team treated the patients with extensive surgical debridement of the affected tissue, correction of predisposing comorbidities and administration of an antifungal agents. Patients were followed up for 6 months with routine direct nasal endoscopy to check the sinonasal cavity for any recurrence. All the six patients survived at 6 months of follow-up. CONCLUSION: A timely initiated multidisciplinary team-based approach can reduce the mortality in rhino-orbital-cerebral mucormycosis cases caused by R. homothallicus.

Magnetic resonance imaging of rhino-orbito-cerebral mucormycosis: a pictorial review.

Rhino-orbito-cerebral mucormycosis is a potentially fatal disease requiring early magnetic resonance imaging (MRI) for disease evaluation and timely detection of intracranial complications. Angio-invasive nature leading to necrosis and infarction is the hallmark of mucormycosis. The disease follows a fulminant course extending from the paranasal sinuses to involve the orbit, deep neck spaces, skull base, facial bones, and intracranial compartment. Loss of vision either due to direct extension into the orbit or optic nerve infarction adds to disease morbidity. Prompt MRI using dedicated sequences can help in assessing the exact disease extent including early osseous and intracranial changes, which aid in precise disease management.

[Small intestinal mucormycosis associated with acute myeloid leukemia: a case report].

The patient was a man in his 70s. During the treatment for acute myeloid leukemia, abdominal pain and bloody stools appeared. A diagnosis of small intestinal ileus was made by computed tomography scan. Treatment with an ileus tube did not improve his condition, and enteroscopy revealed the presence of ileal ulcers. Based on histological examination, small intestinal mucormycosis was suspected, and thus, antifungal drugs were administered. However, the patient developed perforated peritonitis and underwent small intestine resection. He was finally diagnosed with small intestinal mucormycosis with the help of the resected specimen. The gastrointestinal form of mucormycosis rarely occurs, and small intestinal lesions are very rare. Enteroscopy was helpful in its diagnosis and treatment.

SARS-CoV-19-associated Rhino-orbital and cerebral mucormycosis: clinical and radiological presentations.

We describe presenting clinical and imaging manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated Rhino-oculo-cerebral mucormycosis (ROCM) in a hospital setting during the second wave of SARS-CoV-2 pandemic in India. Data on the presenting manifestations were collected from 1 March to 31 May 2021. Associations between clinical and imaging findings were explored, specifically: (1) the presence or absence of orbital pain and infiltration of a superior orbital fissure on imaging; (2) the presence of unilateral facial nerve palsy and pterygopalatine fossa infiltration and geniculate ganglion signal on contrast magnetic resonance imaging, and (3) vision loss and optic nerve findings on imaging. Orbital pain was reported by 6/36 subjects. A fixed, frozen eye with proptosis and congestion was documented in 26 (72%), complete vision loss in 23 (64%), and a unilateral lower motor neuron facial nerve palsy in 18 (50%). No association was found between the presence of orbital pain and superior orbital fissure infiltration on imaging. The ipsilateral geniculate ganglion was found to enhance more profoundly in 7/11 subjects with facial palsy and available magnetic resonance (MR) imaging, and the ipsilateral pterygopalatine fossa was found infiltrated in 14. Among 23 subjects with complete loss of vision, 9 (39%) demonstrated long-segment bright signal in the posterior optic nerve on diffusion MR images. We conclude that orbital pain might be absent in SARS-CoV-2-associated ROCM. Facial nerve palsy is more common than previously appreciated and ischemic lesions of the posterior portion of the optic nerve underlie complete vision loss.

Unique clinical and radiological manifestations identified in the outbreak of Rhino-oculo-cerebral mucormycosis (ROCM) during the second epidemic wave of coronavirus disease 2019 (COVID-19) infection included the common occurrence of facial paralysis, frequent absence of ocular pain, and long segments of optic nerve damage.

Imaging features of rhinocerebral mucormycosis: from onset to vascular complications.

Rhinocerebral mucormycosis (RCM) may result in severe intracranial ischemic and hemorrhagic lesions. Both computed tomography (CT) and magnetic resonance imaging (MRI) play an essential role in the diagnosis of RCM, but whereas CT is better for assessing bone erosion, MRI is superior in evaluating soft tissue, intraorbital extension, and in assessing intracranial and vascular invasion. Specific CT and MRI techniques, such as CT angiography or enhanced MR angiography, and more advanced MRI sequences such as gadolinium-3D Black Blood imaging, contribute to the assessment of the extension of vascular invasion.In this pictorial review, we describe specific CT and MRI signs of RCM, mainly focusing on its life-threatening complications due to vascular involvement.

Transcutaneous retrobulbar injection of amphotericin B in rhino-orbital-cerebral mucormycosis: a review.

Mucormycosis is an aggressive and potentially fatal invasive fungal infection. The most common form of mucormycosis is rhino-orbital-cerebral mucormycosis (ROCM). While it is commonly seen in immunocompromised patients, it is also known to affect healthy individuals. The global disease burden of ROCM has increased significantly following the surge in cases during the COVID-19 pandemic. Endoscopic sinus debridement, systemic antifungal therapy, and control of the underlying immunosuppressive condition are essential for the management of ROCM. Orbital involvement, however, presents a challenge to clinicians. Intervention strategies that have been described to treat orbital disease include orbital exenteration, conservative orbital debridement with or without irrigation with amphotericin B and transcutaneous retrobulbar injection of amphotericin B (TRAMB). Currently, there is a lack of clarity regarding the indications and outcomes of TRAMB as a treatment modality. In this review, the drug formulations used, the complications, and outcomes of previously described cases that have used TRAMB in cases of ROCM are discussed. Favorable outcomes following TRAMB depend on appropriate patient selection and radiological evidence of the orbital burden of the disease. This review aims to familiarize clinicians with objective parameters for patient selection for TRAMB, namely the extent of the disease, the clinical features, and radiological findings; viz. the clinical interpretation of areas of contrast uptake and those of necrosis. TRAMB can be considered as a viable option in select cases of orbital mucormycosis where exenteration or debridement are not indicated, or when there is limited orbital disease.

Guidance on Imaging for Invasive Pulmonary Aspergillosis and Mucormycosis: From the Imaging Working Group for the Revision and Update of the Consensus Definitions of Fungal Disease from the EORTC/MSGERC.

BACKGROUND: Clinical imaging in suspected invasive fungal disease (IFD) has a significant role in early detection of disease and helps direct further testing and treatment. Revised definitions of IFD from the EORTC/MSGERC were recently published and provide clarity on the role of imaging for the definition of IFD. Here, we provide evidence to support these revised diagnostic guidelines. METHODS: We reviewed data on imaging modalities and techniques used to characterize IFDs. RESULTS: Volumetric high-resolution computed tomography (CT) is the method of choice for lung imaging. Although no CT radiologic pattern is pathognomonic of IFD, the halo sign, in the appropriate clinical setting, is highly suggestive of invasive pulmonary aspergillosis (IPA) and associated with specific stages of the disease. The ACS is not specific for IFD and occurs in the later stages of infection. By contrast, the reversed halo sign and the hypodense sign are typical of pulmonary mucormycosis but occur less frequently. In noncancer populations, both invasive pulmonary aspergillosis and mucormycosis are associated with "atypical" nonnodular presentations, including consolidation and ground-glass opacities. CONCLUSIONS: A uniform definition of IFD could improve the quality of clinical studies and aid in differentiating IFD from other pathology in clinical practice. Radiologic assessment of the lung is an important component of the diagnostic work-up and management of IFD. Periodic review of imaging studies that characterize findings in patients with IFD will inform future diagnostic guidelines.

CT and MRI Findings of Invasive Mucormycosis in the Setting of COVID-19: Experience From a Single Center in India.

An increasing incidence of rhinoorbitocerebral mucormycosis (ROCM) among patients with COVID-19 has recently been reported in India. We report the imaging findings for 25 patients with COVID-19 and invasive ROCM at a single hospital in India. Findings included sinus wall erosions (n = 20), air within bony sinus structures (n = 11), and focal mucosal nonenhancement (n = 8). Orbital, vascular, and intracranial complications were also observed. Radiologists should recognize the increasing incidence of ROCM among patients with COVID-19 to facilitate early diagnosis.

Imaging of COVID-19-associated craniofacial mucormycosis: a black and white review of the "black fungus".

A subset of diabetic COVID-19 patients treated with steroids, oxygen, and/or prolonged intensive care admission develop rhino-orbito-cerebral mucormycosis. Radiologists must have a high index of suspicion for early diagnosis, which prompts immediate institution of antifungal therapy that limits morbidity and mortality. Assessment of disease extent by imaging is crucial for planning surgical debridement. Complete debridement of necrotic tissue improves survival. Imaging features reflect the angioinvasive behaviour of fungal hyphae from the Mucoraceae family, which cause necrotising vasculitis and thrombosis resulting in extensive tissue infarction. Contrast-enhanced magnetic resonance imaging (MRI) is the imaging technique of choice. The classic "black turbinate" on contrast-enhanced imaging represents localised invasive fungal rhinosinusitis (IFRS). A striking radiological feature of disseminated craniofacial disease is non-enhancing devitalised and necrotic soft tissue at the orbits and central skull base. Sinonasal and extrasinonasal non-enhancing lesions in IFRS are secondary to coagulative necrosis induced by fungal elements. Multicompartmental and extrasinonasal tissue infarction is possible without overt bone involvement and caused by the propensity of fungal elements to disseminate from the nasal cavity via perineural and perivascular routes. Fungal vasculitis can result in internal carotid artery occlusion and cerebral infarction. Remnant non-enhancing lesions after surgical debridement portend a poor prognosis. Assessment for the non-enhancing MRI lesion is crucial, as it is a sole independent prognostic factor for IFRS-specific mortality. In this review, we describe common and uncommon imaging presentations of biopsy-proven rhino-orbito-cerebral mucormycosis in a cohort of nearly 40 COVID-19 patients.

Imaging findings using a combined MRI/CT protocol to identify the "entire iceberg" in post-COVID-19 mucormycosis presenting clinically as only "the tip".

AIM: To analyse combined computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of invasive rhino-orbital mucormycosis (IROM) in post-COVID-19 infection patients for accurate diagnosis and delineation of the extent of involvement. MATERIALS AND METHODS: A retrospective analysis was undertaken of 50 patients who developed IROM post-COVID-19 infection who underwent combined CT/MRI evaluation. RESULTS: The age range of the 50 affected patients was 23-73 years. Out of these, 41 were diabetic. CT/MRI showed predominant involvement of the maxillary (n=26) and ethmoid (n=19) sinuses. Extension of disease to the orbit (n=35), cavernous sinus (n=18), hard palate (n=15), skull base (n=8), and intracranial involvement (n=3) was seen. Perineural spread of the disease was analysed along all divisions of the trigeminal nerve and its branches. MRI showed T2-hypointense soft-tissue thickening with heterogeneous contrast enhancement with corresponding hyperdensities on CT diagnosing the presence of fungal elements. CONCLUSION: Clinicians should be aware of the possibility of IROM post-COVID-19 infection. Conjunctive use of CT, which depicts bone destruction and other reactive bony changes along with MRI, which reveals characteristic findings of soft-tissue thickening of the involved sinuses with extension of disease to the orbits, cavernous sinus, dura, hard palate, skull base, and intracranial structures. Accurate diagnosis and early recognition of the disease and its extension with appropriate use of these techniques helps to initiate appropriate and timely treatment, which is vital to prevent a fatal outcome.

Increased incidence of rhino-orbital mucormycosis in an educational therapeutic hospital during the COVID-19 pandemic in western Iran: An observational study.

BACKGROUND: COVID-19 patients, especially the patients requiring hospitalisation, have a high risk of several complications such as opportunistic bacterial and fungal infections. Mucormycosis is a rare and opportunistic fungal infection that mainly affects diabetic and immunocompromised patients. An increase has been observed in the number of rhino-orbital mucormycosis in patients with COVID-19 admitted to Imam Khomeini Hospital, Kermanshah, Iran, since October 2020. This is a report of the frequency, risk factors, clinical manifestations, treatment and prognosis of COVID-19 associated with mucormycosis infection. METHODS: The medical records of COVID-19 patients with rhino-orbital mucormycosis who were diagnosed in an educational therapeutic hospital in Kermanshah, west of Iran were surveyed. Several parameters were analysed including demographic, clinical, therapeutic and laboratory characteristics. RESULTS: Twelve patients with COVID-19-associated rhino-orbital mucormycosis were identified from 12 October to 18 November 2020. All cases reported as proven mucormycosis had a history of hospitalisation due to COVID-19. Comorbidities mainly included diabetes mellitus (83.33%) and hypertension (58.33%). Seventy-five per cent of patients received corticosteroids for COVID- 19 treatment. The sites of involvement were rhino-sino-orbital (83%) and rhino-sino (17%). Amphotericin B/liposomal amphotericin B alone or in combination with surgical debridement or orbital exenteration was used as the first-line therapy. The overall mortality rate was 66.7% (8/12). CONCLUSIONS: We found a high incidence of mucormycosis among COVID-19 patients. Diabetes mellitus and corticosteroid use were the dominant predisposing factor of mucormycosis. Mucormycosis is a life-threatening and opportunistic infection; therefore, physicians should know the signs and symptoms of the disease so that a timely diagnosis and therapy can be performed.

Isolated pulmonary mucormycosis in an immunocompetent patient: a case report and systematic review of the literature.

BACKGROUND: Pulmonary mucormycosis caused by Mucorales is a highly lethal invasive fungal infection usually found in immunocompromised patients. Isolated pulmonary mucormycosis in immunocompetent patients is very rare. Here, we present a case of a 32-year-old male who developed pulmonary mucormycosis without any known immunodeficiency. CASE PRESENTATION: The patient presented to our hospital because of cough and chest pain along with blood in the sputum. He was first treated for community-acquired pneumonia until bronchoalveolar lavage fluid culture confirmed the growth of Absidia. His symptoms were relieved with the use of amphotericin B, and he eventually recovered. We also provide a systematic review of relevant literature to summarize the characteristics of pulmonary mucormycosis in immunocompetent patients. CONCLUSIONS: Pulmonary mucormycosis has variable clinical presentations and is difficult to identify. Due to its high fatality rate, clinicians should make judgements regarding suspected cases correctly and in a timely manner to avoid misdiagnosis and delayed treatment.

Spectrum of intracranial complications of rhino-orbito-cerebral mucormycosis - resurgence in the era of COVID-19 pandemic: a pictorial essay.

Rhino-orbito-cerebral mucormycosis (ROCM) has regained significance following its resurgence in the second wave of the COVID-19 pandemic in India. Rapid and progressive intracranial spread occurs either by direct extension across the neural foraminae, cribriform plate/ethmoid, walls of sinuses, or angioinvasion. Having known to have a high mortality rate, especially with intracranial extension of disease, it becomes imperative to familiarise oneself with its imaging features. MRI is the imaging modality of choice. This pictorial essay aims to depict and detail the various intracranial complications of mucormycosis and to serve as a broad checklist of structures and pathologies that must be looked for in a known or suspected case of ROCM.

Chronic invasive fungal rhinosinusitis vs sinonasal squamous cell carcinoma: the differentiating value of MRI.

OBJECTIVES: To investigate MRI features in discriminating chronic invasive fungal rhinosinusitis (CIFRS) from sinonasal squamous cell carcinomas (SNSCC). METHODS: MRI findings of 33 patients with CIFRS and 47 patients with SNSCC were retrospectively reviewed and compared. Multivariate logistic regression analysis was performed to identify significant imaging features in distinguishing between CIFRS and SNSCC. The ROC curves and the AUC were used to evaluate diagnostic performance. RESULTS: There were significant differences in cavernous sinus involvement (p < 0.001), sphenoid sinus involvement (p < 0.001), meningeal involvement (p = 0.024), T2 signal intensity (p = 0.006), and enhancement pattern (p < 0.001) between CIFRS and SNSCC. Multivariate logistic regression analysis identified cavernous sinus involvement (odds ratio [OR] = 0.06, 95% confidence interval [95% CI] = 0.02-0.20) and sphenoid sinus involvement (OR = 0.14, 95% CI = 0.05-0.45) as significant indicators for CIFRS and T2 isointensity to gray matter (OR = 4.44, 95% CI = 1.22-16.22) was a significant indicator for SNSCC. ROC curve analysis showed the AUC from a combination of three imaging features was 0.95 in differentiating CIFRS and SNSCC. CONCLUSIONS: MRI showed significant differences between CIFRS and SNSCC features. In immunocompromised patients, a sinonasal hypointense mass on T2WI with septal enhancement or loss of contrast enhancement, and involvement of cavernous sinus, sphenoid sinus, and meninges strongly suggest CIFRS. KEY POINTS: • Chronic invasive fungal rhinosinusitis (CIFRS) is often difficult to distinguish from sinonasal squamous cell carcinomas (SNSCC) in clinical practice. • Cavernous sinus and sphenoid sinus involvement appear to be significant indicators for CIFRS. T2 isointensity to gray matter appears to be a significant indicator for SNSCC. • Loss of contrast enhancement and septal enhancement can be used to distinguish CIFRS from SNSCC with a high degree of specificity.

Gastrointestinal involvement of unusual Mucormycete Syncephalastrum racemosum in a diabetic patient with adenocarcinoma: rare case presentation with review of literature.

BACKGROUND: Mucormycosis is a serious and often fatal mycotic infection caused by members of class Mucormycetes in populations with immunologic or metabolic disorders. Though several clinical manifestations are associated with mucormycetes, gastrointestinal involvement is quite rare. CASE DESCRIPTION: We described a rare case of invasive fungal infection due to Syncephalastrum racemosum associated with gastric adenocarcinoma in a 48-year-old male patient with type II Diabetes mellitus. He presented with complaints of abdominal pain, nausea, vomiting, dyspepsia, dysphagia, loss of appetite, and weight. Histopathological examination showed broad and aseptate hyphae and culture of endoscopic biopsy tissue from pylorus and antrum yielded the fungal pathogen S. racemosum. The species was confirmed by molecular sequencing of D1/D2 region of the ribosomal DNA. The in vitro susceptibility of S. racemosum was tested by broth microdilution assay as per CLSI guidelines. The MICs suggest that the isolate was susceptible to Amphotericin B (0.25 µg/ml), Itraconazole (0.25 µg/ml) and Posaconazole (0.06 µg/ml) and showed resistance to Micafungin (>16 µg/ml). The patient was successfully treated with radical subtotal gastrectomy with lymphadenectomy and Amphotericin B antifungal therapy. There was a dilemma in concluding the pathogenicity of the isolate since; the symptoms noted were common for both gastric adenocarcinoma and mucormycosis. A review of previously reported cases on Syncephalastrum was presented in the paper with their clinical manifestations, treatment, and outcome. CONCLUSION: To the best of our knowledge, this is the first report from India on the gastrointestinal involvement of S. racemosum. Patients with immunocompromised status are more prone to mucormycotic infections, and any typical presentations should be carefully examined for their etiological agent, and appropriate species directed therapy would help in a better outcome.

Pulmonary Mucormycosis: Risk Factors, Radiologic Findings, and Pathologic Correlation.

Pulmonary mucormycosis (PM) is an uncommon fungal infection most often seen in immunocompromised patients. The fungus grows on decaying food, soil, and animal excrement. Patients usually become infected by inhalation of spores. The most common risk factors include diabetes mellitus, hematologic malignancy, and solid organ or stem cell transplant. PM can have a nonspecific appearance at imaging. For example, early imaging may show peribronchial ground-glass opacity. Later, the disease progresses to consolidation, nodules, or masses. Because patients are usually immunocompromised, the differential diagnosis often includes invasive pulmonary aspergillosis (IPA). Various radiologic findings suggestive of PM have been identified to help differentiate it from IPA. For example, the reverse halo sign is more closely associated with PM than with IPA. The reverse halo sign is an area of ground-glass opacity surrounded by a rim of consolidation. In addition, the presence of pleural effusions and more than 10 nodules is more suggestive of PM than it is of IPA. PM can progress rapidly in neutropenic patients. Identification of the hyphae in tissue by using endobronchial or percutaneous sampling can allow differentiation from IPA and help confirm the diagnosis of mucormycosis. Because of the high mortality rate associated with PM, early identification of the disease is critical for an improved likelihood of survival. A multimodality treatment approach with antifungal agents and surgical débridement has been shown to improve outcomes. The authors review the risk factors for PM, describe its imaging appearance and disease process, and describe the treatment of the disease. ©RSNA, 2020.