Pulmonary mucormycosis diagnosed by fine needle aspiration cytology. A case report

BACKGROUND: The usefulness of fine needle aspiration cytology (FNAC) in the diagnosis of lung lesions is well documented. Fungal lesions are among nonneoplastic lesions of the lung in which FNAC has proven a useful technique in both immunocompromised and immunocompetent patients. These include cryptococcosis, aspergillosis, histoplasmosis and coccidiodomycosis. Pulmonary mucormycosis, an aggressive fungal infection, is rarely diagnosed on FNAC. We report a case of isolated pulmonary mucormycosis diagnosed on FNAC. CASE: A 62-year-old renal transplant recipient with diabetes mellitus and hypertension, asymptomatic for four months, presented with tachypnea, generalized malaise and weakness. Radiologic studies showed an enlarging, cavitating lesion in the right lung. Computed tomography-guided fine needle aspiration performed on the lung lesion showed fungal profiles with broad, ribbonlike, aseptate hyphae with right-angled branching consistent with the Zygomycetes class of fungi, which includes Rhizopus and Mucor species. Fungal cultures confirmed the presence of Rhizopus. The patient underwent right pneumonectomy, was placed on liposomal amphotericin B therapy and discharged with good pulmonary status and stable kidney function. CONCLUSION: FNAC is a useful technique in the diagnosis of pulmonary mucormycosis.     

Chlamydospores of Rhizopus microsporus var. rhizopodiformis in Tissue of Pulmonary Mucormycosis

Hyphae are usually the only fungal elements found in tissue of mucormycosis, and other fungal elements are quite rarely encountered. We found chlamydospores in bronchial lumina in autopsied tissue of pulmonary mucormycosis of a diabetic patient. Chlamydospores are thick-walled, asexually produced spores arising from the modification of a hyphal segment. This is the first histologic demonstration of chlamydospores in mucormycosis in which the causative fungus is culturally identified to species level. Rhizopus microsporus var. rhizopodiformis was isolated from the present autopsied pulmonary tissue. A literature review of human infection by this fungus found 27 cases with histopathologic evidence.     

Pulmonary Mucormycosis due to Lichtheimia ramosa in a Patient with HIV Infection

Mucormycosis is increasingly common in patients with risk factors such as diabetes mellitus, neutropenia, and corticosteroid therapy. However, mucormycosis seems to be less common in patients with human immunodeficiency virus (HIV) infection compared to patients with other risk factors. Despite their lower virulence, Lichtheimia species should be regarded as emerging pathogens among Mucoralean fungi. We report a fatal case of pulmonary mucormycosis due to Lichtheimia ramosa in a 52-year-old man with an end-stage HIV infection. He had a cachectic appearance and his CD4 count was 8 cells/mm³. The fungal infection was diagnosed based on a positive sputum culture with histopathologic confirmation. The fungus was resistant to caspofungin, anidulafungin, and voriconazole [minimum inhibitory concentration (MCI) >32 µg/ml], whereas the E test MIC values of itraconazole, posaconazole, and amphotericin B were 0.38, 0.38, and 0.5 µg/ml, respectively. Although intravenous drug use is the main risk factor for the development of mucormycosis in HIV-infected patients, it may also develop in patients with low CD4 count, opportunistic infections and/or additional diseases, such as Kaposi’s sarcoma or severe immunodeficiency, as in our case.     

Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): Case Report and Systematic Review of Literature

Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients. While COVID-19 associated pulmonary aspergillosis is increasingly recognized, mucormycosis is rare. We describe a case of probable pulmonary mucormycosis in a 55-year-old man with diabetes, end-stage kidney disease, and COVID-19. The index case was diagnosed with pulmonary mucormycosis 21 days following admission for severe COVID-19. He received 5 g of liposomal amphotericin B and was discharged after 54 days from the hospital. We also performed a systematic review of the literature and identified seven additional cases of COVID-19 associated mucormycosis (CAM). Of the eight cases included in our review, diabetes mellitus was the most common risk factor. Three subjects had no risk factor other than glucocorticoids for COVID-19. Mucormycosis usually developed 10–14 days after hospitalization. All except the index case died. In two subjects, CAM was diagnosed postmortem. Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. A high index of suspicion and aggressive management is required to improve outcomes.

     

IFN-γ Mediated Signaling Improves Fungal Clearance in Experimental Pulmonary Mucormycosis

Mycopathologia - We established three immunocompetent murine models of pulmonary mucormycosis to determine the involvement of the adaptive immune response in host resistance in pulmonary...     

Pulmonary mycotic infections; allergic and immunologic factors

The mechanisms of immunity and allergy, at play in every infectious disease, must be comprehended before the pathogenesis of an infection can be appreciated.Immunity, allergy and serology are concerned with specific antigen-antibody reactions. In immunity the principal concern is with the final disposition of antigen (agglutination, lysis, and phagocytosis). In allergy attention is focused upon tissue damage resulting from antigen-antibody union. In serology interest is devoted to the presence of antibody as evaluated by certain visible in vitro reactions-precipitin, agglutination, opsonization and complement fixation tests. There are two types of allergic reaction-the immediate or anaphylactic type and the delayed type or the allergic disease of infection. Neither kind takes part in the mechanism of immunity. At this time the allergic antibody and the immune antibody must be considered as two different and distinct antibodies. Skin and serologic tests are important diagnostic aids in certain pulmonary mycotic infections-for example, coccidioidomycosis, blastomycosis, histoplasmosis and moniliasis. Clinical expressions of allergy may appear in coccidioidomycosis, histoplasmosis and moniliasis. Pulmonary mycoses are divided into three groups, that is, the endogenous mycoses (actinomycosis, moniliasis, geotrichosis), the endogenous-exogenous mycoses (cryptococcosis, aspergillosis, mucormycosis) and the exogenous mycoses (nocardiosis, coccidioidomycosis, histoplasmosis, North American blastomycosis). The diagnosis and treatment of the important mycotic infections that invade lung tissue are discussed.     

Novel dual-function CellDetect® staining technology: wedding morphology and tinctorial discrimination to detect cervical neoplasia

Immunocompromised patients who develop invasive filamentous mycotic infections can be efficiently treated if rapid identification of the causative fungus is obtained. We report a case of fatal necrotic pneumonia caused by combined pulmonary invasive mucormycosis and aspergillosis in a 66 year-old renal transplant recipient. Aspergillus was first identified during the course of the disease by cytological examination and culture (A. fumigatus) of bronchoalveolar fluid. Hyphae of Mucorales (Rhizopus microsporus) were subsequently identified by culture of a tissue specimen taken from the left inferior pulmonary lobe, which was surgically resected two days before the patient died. Histological analysis of the lung parenchyma showed the association of two different filamentous mycoses for which the morphological features were evocative of aspergillosis and mucormycosis. However, the definitive identification of the associative infection was made by polymerase chain reaction (PCR) performed on deparaffinized tissue sections using specific primers for aspergillosis and mucormycosis. This case demonstrates that discrepancies between histological, cytological and mycological analyses can occur in cases of combined mycotic infection. In this regard, it shows that PCR on selected paraffin blocks is a very powerful method for making or confirming the association of different filamentous mycoses and that this method should be made available to pathology laboratories.     

<Emphasis Type="Italic">Rhizopus homothallicus</Emphasis> Causing Invasive Infections: Series of Three Cases from a Single Centre in North India

Mucormycoses are opportunistic fungal infections with a high mortality rate. Rhizopus oryzae is the most common agent implicated in human infections. Although R. homothallicus has been previously reported to be a cause of pulmonary mucormycosis, it is the first time that we are reporting as a causative agent of rhino-orbital and cutaneous mucormycosis.     

Successful Treatment of Pulmonary Mucormycosis Caused by <Emphasis Type="Italic">Cunninghamella bertholletiae</Emphasis> with High-Dose Liposomal Amphotericin B (10 mg/kg/day) Followed by a Lobectomy in Cord Blood Transplant Recipients

Infection caused by Cunninghamella bertholletiae carries one of the highest mortality rates among mucormycosis, and there are no reported cases that survived from the infection in allogeneic hematopoietic stem cell transplantation recipients occurring before neutrophil engraftment. Here, we present two cases of pulmonary mucormycosis caused by C. bertholletiae occurring before neutrophil engraftment after cord blood transplantation. Both were successfully treated with high-dose liposomal amphotericin B (10 mg/kg/day) combined with micafungin, which was then followed by neutrophil recovery, reduction in immunosuppressive agents, and a subsequent lobectomy. The intensive antifungal therapy immediately administered upon suspicion of mucormycosis greatly suppressed the infection in its early stage and was well tolerated despite its prolonged administration and simultaneous use of nephrotoxic agents after transplantation. Although the synergic effect of micafungin remains unclear, these cases highlight the importance of prompt administration of high-dose lipid polyene when suspecting mucormycosis in highly immunocompromised patients, which enables subsequent diagnostic and therapeutic interventions, resulting in a favorable outcome.     

微小根毛霉感染机理研究

本文在首次报告二例肺结核、糖尿病患者合并感染肺微小根毛霉的基础上,进一步探讨免疫功能受损与微小根毛霉感染关系。本文采用不同剂量~(60)Co-γ全身辐照小鼠,然后以不同途径注射同剂量的微小根毛霉的孢囊孢子,观察动物的感染情况和感染后的真菌检出率,结果发现各种辐射剂量均在辐射后7-14日感染菌的检出率最高;各种脏器感染菌的检出率以脾脏最高(66.7—81.8％);淋巴结最低(0.0—25.0％);其他脏器的感染菌检出率也有不同程度的差异。     

Pulmonary Embolectomy

Embolectomy was carried out in eight patients with pulmonary emboli. Angiographic diagnosis was obtained in six, and in two cases pulmonary angiography could not be done because of the very critical condition of the patients. In the latter two, diagnosis was made based only on clinical findings. Two patients died in the operating room (25 percent). Six patients were discharged in good condition.It is emphasized that pulmonary embolectomy should be done in cases of pulmonary emboli when a clinical status of shock is present (systolic blood pressure less than 80 mm of mercury and the patient in low cardiac output syndrome) and when there is no response to medical treatment regardless of the degree of obstruction in the pulmonary arterial tree.     

Systemic and Pulmonary Vascular Remodelling in Chronic Obstructive Pulmonary Disease

BackgroundChronic Obstructive Pulmonary Disease (COPD) is associated with subclinical systemic atherosclerosis and pulmonary vascular remodelling characterized by intimal hyperplasia and luminal narrowing. We aimed to determine differences in the intimal thickening of systemic and pulmonary arteries in COPD subjects and smokers. Secondary aims include comparisons with a non-smokers group; determining the clinical variables associated with systemic and pulmonary intimal thickening, and the correlations between systemic and pulmonary remodelling changes.MethodsAll consecutive subjects undergoing lung resection were included and divided into 3 groups: 1) COPD, 2) smokers, and 3) non-smokers. Sections of the 5th intercostal artery and muscular pulmonary arteries were measured by histo-morphometry. Four parameters of intimal thickening were evaluated: 1) percentage of intimal area (%IA), 2) percentage of luminal narrowing, 3) intimal thickness index, and 4) intima-to-media ratio.ResultsIn the adjusted analysis, the systemic arteries of COPD subjects showed greater intimal thickening (%IA) than those of smokers (15.6±1.5% vs. 14.2±1.6%, p = 0.038). In the pulmonary arteries, significant differences were observed for %IA between the 2 groups (37.3±2.2% vs. 29.3±2.3%, p = 0.016). Among clinical factors, metabolic syndrome, gender and COPD status were associated with the systemic intimal thickening, while only COPD status was associated with pulmonary intimal thickening. A correlation between the %IA of the systemic and pulmonary arteries was observed (Spearman’s rho = 0.46, p = 0.008).ConclusionsGreater intimal thickening in systemic and pulmonary arteries is observed in COPD patients than in smokers. There is a correlation between systemic and pulmonary vascular remodelling in the overall population.     

Passive immunization in murine mucormycosis

Antibody raised in mice against mycelial homogenates of Rhizomucor pusillus was effective in passive immunization against pulmonary and disseminated mucormycosis (phycomycosis) in immunocompromised mice. Mice intranasally inoculated and infected with Rh. pusillus and treated with antisera had a statistically significant increased resistance to infection and a diminished secondary dissemination of viable fungal fragments. Histological examination of infected lung tissues showed that antibody treated animals were apparently able to degrade hyphal fragments.     

Isavuconazole in a Successful Combination Treatment of Disseminated Mucormycosis in a Child with Acute Lymphoblastic Leukaemia and Generalized Haemochromatosis: A Case Report and Review of the Literature

Invasive mucormycosis in immunocompromised children is a life-threatening fungal infection. We report a case of a 7-year-old girl treated for acute lymphoblastic leukaemia complicated by disseminated mucormycosis during induction therapy. Microscopic examination of surgically removed lung tissue revealed wide, pauci-septate hyphae suggesting a Mucorales infection. This diagnosis was confirmed immunohistochemically and by PCR analysis followed by a final identification of Cunninghamella sp. The patient was treated successfully with surgical debridement and antifungal combination therapy with amphotericin B, caspofungin and isavuconazole. The use of isavuconazole in a child was not previously reported. Additionally, case reports concerning pulmonary mucormycoses in paediatric population published after 2010 were reviewed. Nineteen out of 26 identified patients suffered from haematological diseases. Reported mortality reached 38.5%. By the fact of rising morbidity, unsatisfactory results of treatment and remaining high mortality of mucormycoses in immunocompromised patients, new therapeutic options are warrant. Isavuconazole, with its broad-spectrum activity, good safety profile and favourable pharmacokinetics, is a promising drug. However, further studies are necessary to confirm positive impact of isavuconazole on mucormycosis treatment in children.

     

A Case of Rhinoorbital Mucormycosis in a Leukemic Patient with a Literature Review from Turkey

Mucormycosis (Zygomycosis) is a rare, invasive, opportunistic fungal infection of the paranasal sinuses, caused by a fungus of the order Mucorales. We report a case of rhinoorbital mucormycosis caused by Rhizopus oryzae in an acute lymphoblastic leukemia patient and review the 79 Mucormycosis cases reported in the last decade from Turkey. In our case, the diagnosis was made with endoscopic appearance, computerized tomography of the paranasal sinuses, and culture of the surgical materials. Following aggressive surgical debridement and parenteral amphotericin B therapy, the patient recovered completely. In Turkish literature, rhinocerebral manifestations were the most common form of the mucormycosis (64 cases), followed by pulmonary form (6 cases). The most common risk factor was hematologic malignancies (32 cases) and diabetes mellitus (32 cases), similar to those reported from the rest of the world. The etiologic agents responsible for the review cases were Rhizopus sp., Mucor spp., Rhizomucor spp., Rhizopus oryzae, Mucor circinelloides, and Lichtheimia corymbifera. Although various treatment modalities were used, amphotericin B was the mainstay of therapy. Mortality rate was found to be 49.4% in review cases. It seems that strong clinical suspicion and early diagnosis, along with aggressive antifungal therapy and endoscopic sinus surgery, have great importance for better prognosis in mucormycosis.     

Características clínicas y evolución de los pacientes diagnosticados de mucormicosis en un hospital de tercer nivel (2012-2016)

Background

The most common presentation of mucormycosis in the past was the nasosinusal involvement in patients with diabetic ketoacidosis. However, in the last few years, new groups of patients with risk of mucormycosis have emerged.

肺动脉栓塞的64层螺旋CT血管成像技术分析

目的从技术上探讨64层螺旋CT肺动脉造影对肺栓塞的诊断的价值。方法对62例临床疑诊肺栓塞的患者行64排螺旋CT肺动脉造影检查,采用最大密度投影(MIP)、多平面重建(MPR)、曲面重建(CPR)、容积漫游(VR)及仿真内窥镜等后处理技术,分析所获得的相关CT资料。结果64排多层螺旋CT肺动脉造影可较准确、清晰、全面地显示24例累及肺动脉及其分支共152处栓子的位置、形态、范围和程度。结论64排多层螺旋CT肺动脉造影是肺栓塞及时准确无创的诊断方法,是临床诊断肺栓塞的首选筛查办法,对肺动脉栓塞的诊断具有明显的技术优势。     

Cytology of Bronchoalveolar Lavage In Some Rare Pulmonary Disorders: Pulmonary Alveolar Proteinosis and Amiodarone Pulmonary Toxicity

Cytological patterns of bronchoalveolar lavage (BAL) in pulmonary alveolar proteinosis (PAP) and amiodarone pulmonary toxicity (APT) are presented together with light and electron microscopy (EM). the differential cell count of BAL in both diseases is similar in that alveolar macrophages predominate. However, the cytology of PAP is characterized by scanty macrophages and alveolar epithelial cells in abundant periodic acid-Schiff (PAS)-positive extracellular material. the gross appearance of the BAL fluid is therefore opaque. In contrast, the cytology of APT is characterized by foamy alveolar macrophages with numerous lamellar bodies in their cytoplasm, and the BAL fluid is clear.     

Pulmonary arterial transit times

To begin to characterize the pulmonary arterial transport function we rapidly injected a bolus containing a radiopaque dye and a fluorescence dye into the right atrium of anesthetized dogs. The concentrations of the dye indicators were measured in the main pulmonary artery (fluoroscopically) and in a subpleural pulmonary arteriole (by fluorescence microscopy). The resulting concentration vs. time curves were subjected to numerical deconvolution and moment analysis to determine how the bolus was dispersed as it traveled through the arteriole stream tube from the main pulmonary artery to the arteriole. The mean transit time and standard deviation of the transport function from the main pulmonary artery to the arterioles studied averaged 1.94 and 1.23 s, respectively, and the relative dispersion (ratio of standard deviation to mean transit time) was approximately 64%. This relative dispersion is at least as large as those reported for the whole dog lung, indicating that relative to their respective mean transit times the dispersion upstream from the arterioles is comparable to that taking place in capillaries and/or veins. The standard deviations of the transport functions were proportional to their mean transit times. Thus the relative dispersion from the main pulmonary artery to the various arterioles studied was fairly consistent. However, there were variations in mean transit time even between closely adjacent arterioles, suggesting that variations in mean transit times between arteriole stream tubes also contribute to the dispersion in the pulmonary arterial tree.