Diagnostic pitfalls in cytological diagnosis of subcutaneous fungal infection in renal transplant recipients

Renal transplant recipients (RTRs) are at increased risk of the development of a variety of skin infections that can result from graft-preserving immuno-suppressive therapy. In this study, we aimed to determine cytomorphological findings of fungal subcutaneous swelling in seven RTRs and to analyze diagnostic pitfalls in fungal cytology. A retrospective review of fine needle aspiration cytology (FNAC) smears of subcutaneous swelling with positive fungal elements in RTRs from 2008 to 2010 was performed. We had seven cases (all males; age range, 34-58 years, mean, 46.3 years). The time interval between the renal transplantation and appearance of swelling ranged from 8 to 19 months (mean, 13.4 months). The swelling was located on lower limb (six cases) and arm (one case). The lesion was solitary (six cases) and multiple (one case). The cytology of aspirated material showed branched septate fungal hyphae in six cases. These were well delineated on Periodic acid schiffs (PAS) and chromic silver methenamine (CSM) stains. One case showed presence of faint, thin walled, broad ribbon like hyphae. Culture of aspirated material was performed in four cases which grew phaeohyphomycosis in all. Histology of excised tissue showed numerous septate, branched, pigmented fungal elements suggestive of pheohyphomycosis in four cases and broad ribbon hyphae suggestive of zygomycosis in one case. All of our cases responded well with anti-fungal treatment. Fungal infection can manifest as subcutaneous swelling in RTRs. It is often severe, rapidly progressive and difficult to diagnose. FNAC is an important diagnostic tool which is simple, cost effective and rapid method.     

Mucormycosis isolated from perilymphatic tissue: an unusual presentation

We present a rare case of a patient who presented with atypical cranial nerve palsies, with subsequent isolation of mucormycosis from an upper neck subcutaneous swelling. This is an unusual initial site of isolation of mucormycosis. We believe that this should be considered among the differentials when a diabetic or immunosupressed patient presents with cervical lymphadenopathy and cranial nerve palsies.     

Fine-needle aspiration cytology of desmoplastic malignant melanoma metastatic to the parotid gland: case report and review of the literature

Rhinocerebral mucormycosis is a rapidly progressing, often fatal fungal infection that occurs commonly in diabetics and immunocompromised individuals. We present 2 cases of rhinocerebral mucormycosis with a paranasal mass. One patient had an intracranial extension. Nasal scrapings and fine-needle aspiration cytology (FNAC) of the paranasal masses showed fungal hyphae morphologically resembling Mucor. Surgical material showed features of mucormycosis. FNAC and scrape smears can give a conclusive diagnosis of mucormycosis, and the patient can be treated with appropriate antifungal therapy and surgical debridement. Preoperative cytology is an effective technique to establish a diagnosis of mucormycosis and obviates the need for a preoperative biopsy.     

Fatal ileal mucormycosis after abdominal aortic aneurysm repair – a case report

Mucormycosis (zygomycosis) is a rare fungal infection seen most commonly in association with immunosuppression. Intestinal mucormycosis is extremely rare and difficult to diagnose. Early medical and surgical treatment is known to improve survival. This report describes a fatal case of ileal mucormycosis following repair of an abdominal aortic aneurysm in an otherwise healthy elderly man.     

COVID-19-associated mixed mold infection: A case report of aspergillosis and mucormycosis and a literature review

COVID-19-associated mold infections have been increasingly reported, and the main entity is COVID-19-associated aspergillosis (CAPA). Similarly, COVID-19-associated mucormycosis has been reported in hematology, and its prevalence is high and has been increasing in the diabetic population in India during the third COVID-19 pandemic wave. Simultaneous infection with Mucorales and Aspergillus is rare and even rarer during COVID-19. Here, we report the case of a previously immunocompetent patient with severe SARS-CoV-2 infection complicated with probable CAPA and mucormycosis co-infection. Specific diagnostic tools for mucormycosis are lacking, and this case highlights the advantages of analyzing blood and respiratory samples using the quantitative polymerase chain reaction to detect these fungi. We further reviewed the literature on mixed Aspergillus/Mucorales invasive fungal diseases to provide an overview of patients presenting with both fungi and to identify characteristics of this rare infection.     

Fulminant mucormycosis of maxillary sinuses after dental extraction inpatients with uncontrolled diabetic: Two case reports

Mucormycosis is a rare but fulminant opportunistic fungal infection, which occurs most often in diabetic and immunocompromised patients. Dental extractions may create a portal of entry for the fungal infection. The mucormycosis may be the original cause of the pain and can be misdiagnosed as dental pain. In this paper, two cases of mucormycosis are reported after dental extractions and successfully treated with amphotericin B (case #1) and combined with posaconazole (case #2). The two cases we describe exemplify the fulminant mucormycosis of maxillary sinuses after dental extraction inpatients with uncontrolled diabetic support the findings that this predisposing condition created a suitable environment for the Mucorales growth. These case reports emphasize early recognition and urgent treatment of mucormycosis is necessary to prevent the spread of infection Therefore, dental surgeons and healthcare practitioners should become familiar with mucormycosis.     

Mucormycosis after Coronavirus disease 2019 infection in a heart transplant recipient – Case report and review of literature

Mucormycosis is an invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities (including organ transplantation). During the ongoing Coronavirus disease 2019 (COVID-19) pandemic, there have been increasing reports of bacterial and fungal co-infections occurring in COVID-19 patients, including COVID-19 associated pulmonary aspergillosis (CAPA). We describe a case of mucormycosis occurring after COVID-19, in an individual who received a recent heart transplant for severe heart failure. Two months after heart transplant, our patient developed upper respiratory and systemic symptoms and was diagnosed with COVID-19. He was managed with convalescent plasma therapy and supportive care. Approximately three months after COVID-19 diagnosis, he developed cutaneous mucormycosis at an old intravascular device site. He underwent extensive surgical interventions, combined with broad-spectrum antifungal therapy. Despite the aggressive therapeutic measures, he died after a prolonged hospital stay. In this case report, we also review the prior well-reported cases of mucormycosis occurring in COVID-19 patients and discuss potential mechanisms by which COVID-19 may predispose to IFIs. Similar to CAPA, mucormycosis with COVID-19 may need to be evaluated as an emerging disease association. Clinicians should be vigilant to evaluate for invasive fungal infections such as mucormycosis in patients with COVID-19 infection.     

Coincidence or reality behind Mucormycosis,diabetes mellitus and Covid-19 association: A systematic review

Mucormycosis is a rare but life-threatening disease with high morbidity and mortality and is difficult to diagnose. Mucormycosis, is a severe but rare fungal infection caused by a group of molds called mucormycetes. Diabetes, use of corticosteroids, metabolic/diabetic acidosis and Covid-19 mediated immunosuppression are reported in more than 70% of cases in mucormycosis patients. Coexisting mucormycosis, Covid-19 along with diabetes mellitus increase the likelihood of mortality. Despite its occurrence since the beginning of the pandemic, there are still unanswered concerns regarding the origin of this fungal infection and mortality rate and/or relation with diabetic patients. In this review, we describe the detailed view of causative pathogens responsible for mucormycosis, diabetes mellitus and Covid-19 association along with the morbidity cases during the latest Covid-19 crisis. In the case of mucormycosis diagnosis, imaging, histopathological confirmation, fungal culture and molecular identification methods should be considered. Once mucormycosis is diagnosed, a combined treating method consisting of antifungals administration like amphotericin B, surgical intervention is needed for the reversal of the underlying condition. Early detection of this potentially life-threatening infection and timely care is needed in lowering mortality rates.     

Primary breast mucormycosis, a case report

Mucormycosis is a rare fungal infection caused by organisms of the order Mucorales often occurring in diabetics or immunologically compromised patients. To date, only one case of primary mucormycosis of breast has been reported in the English literature. We describe a further case of mucormycosis that was localized to the breast in a patient with no underlying disease and was successfully treated with a simple mastectomy and intravenous antifungal therapy.     

Fulminant myocarditis and pulmonary cavity lesion induced by disseminated mucormycosis in a chronic hemodialysis patient: Report of an autopsied case

Mucormycosis is a rare fungal infection occurring in the immunocompromised host. It is difficult to diagnose, and its cardiac involvement is extremely rare. Here, we report a 64‐year‐old Japanese man with a 5‐year history of hemodialysis with disseminated mucormycosis causing fulminant myocarditis and pulmonary necrosis under glucocorticoid use. Two months before, he had received an implantable cardioverter defibrillator and started to take amiodarone for recurrent ventricular arrhythmias due to hypertensive cardiomyopathy. He developed amiodarone‐induced interstitial pneumonia and then received glucocorticoid therapy. Although the interstitial pneumonia partially improved, a lung cavitary lesion developed in the upper right lobe. Antibiotics had no effect, and serologic tests, blood and sputum cultures and bronchoalveolar lavage fluid were all negative for infectious pathogens. Eventually, he died of fulminant myocarditis. Autopsy revealed disseminated mucormycosis with vascular invasion and fungal thrombi, hemorrhage and infarction in lung (cavity lesion), heart (severe myocarditis), brain, thyroid and subcutaneous tissue around the implantable cardioverter defibrillator. The lung cavitary lesion was the only clinical finding suggestive of mucormycosis before autopsy. When an immunocompromised patient shows a progressive lung cavity lesion, the possibility of mucormycosis should be considered so that a broad‐spectrum antifungal agent can be empirically administered in a timely fashion.     

Identification of the asexual state of Rhizopus species on histologic tissue sections in a patient with rhinocerebral mucormycosis

Mucormycosis is an infection caused by a group of fungi in the order Mucorales in the phylum Zygomycota. The most well-known form of this disease is rhinocerebral mucormycosis, which usually develops in diabetic or immunocompromised patients. The fungal hyphal elements are easily detected in biopsy specimens by direct or histologic examination. However, the confirmatory identification of the genus or species requires culture of the specimen. This article presents a case of rhinocerebral mucormycosis in which presumptive identification of the genus was made without microbiologic cultures and was based on the extraordinarily rare appearance of fungal sporangia and sporangiospores in histologic tissue sections. Identification of these structures allowed an early and accurate diagnosis of rhinocerebral invasive mucormycosis.     

Orbital aspergillus infection diagnosed by FNAC

Fungal infections of the orbit represent a small minority of orbital infections. However, due to the virulent nature of some of the fungal species, they can have a devastating effect on ocular functions. Most of these fungi are saprophytes, which cause opportunistic infections. Aspergillus is one such fungus that can cause infection at various sites in an immunosuppressed individual. Sinonasal aspergillus infection with orbital extension and orbital aspergillus infection progress relentlessly. They can have a precipitous clinical course resulting in total loss of vision. Fine needle aspiration cytology (FNAC) is rarely used as a preoperative diagnostic tool in the investigation of orbital mass lesions. Further, fungal infections of orbit are seldom diagnosed on FNAC. Two cases of fungal infection of the orbital and periorbital tissue diagnosed on FNAC are presented. A 50-year-old diabetic male presented with diminishing vision, pain, and forward protrusion of the left eye. On examination, he had upper eye lid fullness. A 55-year-old diabetic male presented with a swelling on the right upper eye lid. The patients were evaluated radiologically and then subjected to FNAC. The smears showed giant cells, histiocytes, epithelioid granulomas, and fungal hyphae. A diagnosis of fungal infection was arrived at which was subsequently confirmed by culture and biopsy. Orbital aspergillus infection can have a precipitous course. Computerized tomography and magnetic resonance imaging of the orbit provide crucial information. However, FNAC can help in making an early definitive diagnosis of fungal infection and thus obviate the need for a biopsy.     

Coinfections in Intensive Care Unit with pulmonary tuberculosis and mucormycosis: A clinical dilemma

Herein, we present the case report of an adult male diabetic patient who had coinfection with Mycobacterium tuberculosis and mucormycosis, which otherwise is a rare clinical entity. Diabetes mellitus may predispose a patient to tuberculosis (TB) infection which further weakens immune system thus making him susceptible to other fungal or bacterial infections which may pose various treatment difficulties. Therefore, there is a need for mycological and bacteriological investigations in patients with pulmonary TB to rule out secondary coinfections thus contributing to better management.     

Pneumonia caused by Cunninghamella bertholletiae in a patient with acute lymphoblastic leukemia

Pulmonary mucormycosis occur in immunosuppressed patients with a neutropenic treatment or a malignant neoplasia. Although the histological study alone cannot enable species identification, the pathologist usually makes the diagnosis of mucormycosis and can eliminate other filamentous mycoses such as aspergillosis or scedosporiosis. Pulmonary infection caused by Cunninghamella bertholletiae is a very rare lung mucormycosis, particularly in young patients. The histological features of this filamentous mycosis are unusual making the diagnosis of mucormycosis difficult. Mycological study is then crucial for the diagnosis. We report a case of a pulmonary infection caused by Cunninghamella bertholletiae occurring in a young girl with acute lymphoblastic leukemia.     

Cutaneous and subcutaneous metastases from internal malignancies: an analysis of cases diagnosed by fine needle aspiration

Cutaneous and subcutaneous metastases from internal malignancies are rare and indicate a dismal outcome for the patient. This study is designed to analyze cases of cutaneous and subcutaneous metastases from a known or unknown primary and evaluate usefulness of fine needle aspiration cytology as a diagnostic modality. The present study is a retrospective analysis of 83 patients who were diagnosed with metastatic skin deposits on fine needle aspiration cytology. Seventy-four patients were previously diagnosed cases of malignancy and nine patients had metastatic deposits simultaneously with the primary tumor. The commonest malignancies showing cutaneous metastases were from breast, colon and rectum, lung, ovary, and thyroid. The differential diagnoses are from primary cutaneous tumors. FNAC provides a rapid diagnosis and should be used as a preferred first line diagnostic modality in such patients. In our study, FNAC yielded a sensitivity and specificity of 100% as a microscopic method for confirmation.     

Actinomucor elegans as an emerging cause of Mucormycosis

We report an invasive mucormycosis caused by Actinomucor elegans in a patient with refractory aplastic anemia. The organism was isolated from a necrotic skin lesion on the patient's left arm and demonstrated angioinvasive features on histopathology examination. In contrast to three cases described previously, we describe the first case of A. elegans invasive fungal infection in an immunocompromised patient. This report, along with the three previously reported cases, is convincing evidence that A. elegans is an emerging fungal pathogen capable of causing invasive mucormycosis in humans.     

Hematogenously disseminated skin disease caused by Mucor velutinosus in a patient with acute myeloid leukemia

We report here a case of disseminated skin infection caused by Mucor velutinosus, a recently described new species. We believe this to be the first published report of a clinical case of mucormycosis due to M. velutinosus, as well as a rare case of dissemination from a deep site to skin.     

A case of pulmonary mucormycosis presented as Pancoast syndrome and bone destruction in an immunocompetent adult mimicking lung carcinoma

Pulmonary mucormycosis is a rare opportunistic infection caused by Mucormycosis. This fungal infection is uncommon in immunocompetent individuals. Because of its various clinical and imaging manifestations, it is a diagnostic challenge to distinguish pulmonary mucormycosis from other pulmonary diseases, such as carcinoma. Herein, we report a case of pulmonary mucormycosis presenting as Pancoast syndrome and bone destruction of ribs. A 46-year-old Chinese woman was admitted due to pain in chest, right neck and arm for four months and hoarseness for one week. The pre-admission diagnosis via chest CT was pulmonary carcinoma. The subsequent bronchoalveolar lavage fluid analysis and bronchoscopic biopsy were negative for malignant cells, except chronic inflammation. Imaging-guided percutaneous biopsies were carried out after admission and the final pathological diagnosis was pulmonary mucormycosis. Although the patient was started on oral posaconazole of 400 mg bid, the disease condition continued to deteriorate. She finally died of respiratory failure.     

Primary gastrointestinal mucormycosis in an immunocompetent person

In the past decade, mucormycosis has emerged as an important lethal infection in diabetics and other immunocompromised hosts. Rhinosinusitis, pansinusitis, rhino-orbital and rhinocerebral are the common classical manifestations of mucormycosis. However, primary gastrointestinal (GI) mucormycosis is an uncommon disease associated with a high mortality rate. Stomach is the most common site involved in GI mucormycosis. Reported cases of GI mucormycosis in an immunocompetent host are very few in the literature. Here we present a case of a young male with fungal sepsis secondary to GI mucormycosis in an immunocompetent person.     

Gastric mucormycosis: Diagnosis by imprint cytology

The fungi in the order of Mucorales commonly target diabetics and other immunocompromised hosts, producing fatal respiratory and or CNS infections. Gastrointestinal mucormycosis is uncommon and seldom diagnosed in living patients due to nonspecific clinical manifestations. We report a case of gastric mucormycosis in an immmunocompetent male patient, diagnosed by imprint cytology—a rare site and a rare setting. To the best of our knowledge, this is only the second report of gastric mucormycosis being diagnosed on cytology. As the disease is rapidly progressive and often fatal, early diagnosis is critical to the patient survival. Imprint cytology or brush cytology is extremely useful for the rapid diagnosis of gastric mucormycosis as these organisms are morphologically distinct. Familiarity with the cytomorphology of these organisms assists in the correct diagnosis of this disease. Diagn. Cytopathol. 2016;44:820–822. © 2016 Wiley Periodicals, Inc.