Case report. Fatal rhinocerebral zygomycosis due to Rhizopus oryzae

A case of rhinocerebral zygomycosis due to Rhizopus oryzae, arising after trauma in a 53-year-old diabetic man, is reported. Diagnosis was based on histological and mycological examination. Fragments of the colonies were observed by scanning electron microscopy. This is the first case diagnosed in Tuscany.     

Risk factor for invasive zygomycosis in patients with hematologic malignancies

Zygomycosis (mucormycosis) is a relatively uncommon infection in immunocompromised patients most often diagnosed in patients with haematological malignancies and neutropenia. Postmortem series demonstrate a high mortality rate up to 80%. Pulmonary involvement mimicking the more frequently diagnosed invasive aspergillosis is the typical clinical presentation. Other risk factors for the development of zygomycosis that have been described in other patient populations include diabetic ketoacidosis, iron overload, use of deferoxamine and steroids. If these factors are also associated with zygomycosis in patients with haematological malignancies has not been described. In a retrospective case-control study including 13 patients with zygomycosis and 13 control patients with the same underlying diseases, without zygomycosis we determined the frequency of various risk factors. Patients with zygomycosis experienced a longer period of neutropenia (17 vs. 13 days) and lymphopenia (23 vs. 20 days). A relapse of their underlying disease was diagnosed more frequently in patients with zygomycosis (7/13 vs. 3/13) as were a diagnosis of diabetes mellitus (6/13 vs. 3/13) and a cardiovascular disease (6/13 vs. 1/13). The previous use of steroids was more frequent in patients with zygomycosis (8/13 vs. 4/13) as was a systemic antifungal prophylaxis with itraconazole (9/13 vs. 4/13). Knowledge of these risk factors may be of benefit in diagnosing and monitoring zygomycosis in patients with haematological malignancies.     

Pulmonary zygomycosis--a rare angioinvasive fungal infection

Zygomycosis caused by Rhizopus species is an aggressive and rapidly progressive opportunistic fungal infection in immunocompromised patients. It comprises mucocutaneous, rhinocerebral, pulmonary, urological and disseminated infections. Predisposing factors are immunosuppression owing to severe diseases, immunological defects or metabolic disturbances like diabetic ketoacidosis. Rhizopus infections are characterized by angioinvasive growth, necroses of infected tissue and perineural invasion. The histopathologic demonstrable invasion of blood vessels is remarkable for a fungal infection. The mortality of zygomycosis is very high, especially for disseminated disease and when immunosuppression cannot be corrected. We report about two cases of pulmonary zygomycosis, caused by Rhizopus spp.: patient 1, female 73 years old: Delayed clinical course according to hip arthroplasty infection and infection of a femoropopliteal bypass of the right leg, eventually exarticulation of the right hip joint, Pseudomonas pneumonia, severe sepsis caused by staphylococci, acute respiratory distress syndrome (ARDs), acute renal failure and multiple use of antibiotics. Subsequently detection of Rhizopus spp. in the bronchoalveolar lavage and treatment with amphotericin B for this reason. Patient 2, male 68 years old: transplantation of kidney in past medical history, presenting with acute renal failure and with quite a few infections before. In the sequel development of abscessing pneumonia on the right side with a pleural empyema. Rhizopus spp. were detected by microbiological testing in the empyema fluid. These findings required surgical intervention, resection of the lower lobe of the right lung and within the same operation of the renal graft because of rejection. The patient was treated with caspofungin. The further course was delayed by several septic phases. Both patients died later on in spite of all efforts. The very rarely seen pulmonary zygomycosis caused by infection with Rhizopus spp. developed in both patients owing to immunosuppression, in one patient iatrogenically induced by immunosuppressive drugs after organ transplantation, in the other as a result of prolonged severe sepsis. In comparison with other mycoses treatment of Rhizopus infections remains difficult. The affinity to blood vessels, where the fungi multiply, and their feature of vascular invasion with thrombosis and infarction complicate therapeutic efforts.     

Successful treatment of pulmonary zygomycosis in two transplant recipients with liposomal amphotericin B and partial surgical resection followed by posaconazole

Pulmonary zygomycosis is a relatively uncommon complication of solid organ or peripheral blood stem cell transplantation and has a high associated mortality. Optimal therapy consists of complete resection of infected tissue and treatment with amphotericin B (AmB). We describe two patients, one of whom underwent orthotopic heart transplantation and the other who received a peripheral blood stem cell transplant, who were diagnosed with invasive pulmonary zygomycosis. Both patients were treated with a liposomal preparation of AmB and early partial resection of the infected structures followed by prolonged posaconazole maintenance therapy. Despite incomplete resection, this treatment regimen resulted in a favourable outcome in both patients, including survival of more than 17 months in one patient at last follow up. For patients in whom complete resection of pulmonary zygomycosis is not possible, subtotal resection and treatment with liposomal AmB followed by therapy with posaconazole may be an effective treatment option.     

Rhinocerebral zygomycosis caused by Saksenae vasiformis in a diabetic patient

We report a rare case of invasive rhinocerebral Saksenae vasiformis infection in a 71-year-old man with type 2 diabetes mellitus ketoacidosis. Combined histological and microbiological examination of two biopsy specimens taken at four days' intervals showed broad non-septate hyphae on direct smears of biopsies and necrosis and angioinvasion by hyphae were seen in the tissue. S. vasiformis was cultured from both biopsies. The patient had a fatal outcome even though partial debridement, liposomal amphotericin B treatment and control of diabetes were instituted. Permission for necropsy was denied. Clinical, epidemiological and pathological features of the case and manifestations of S. vasiformis infections are discussed. Most cases involve cutaneous sites and only two cases of rhinocerebral infections (both with fatal outcome) have been described. The present case is the third documented case of involvement of the sinuses and the second case of S. vasiformis infection documented in Europe.     

Secondary central nervous system involvement by non-Hodgkin's lymphoma: the risk factors

The risk of secondary central nervous system (CNS) was estimated in 833 cases of non-Hodgkin's lymphoma diagnosed between January 1975 and December 1988. Fifty-one of them had CNS disease (51/833, 6.1 per cent). No case of low grade lymphoma developed CNS disease. However, 6.5 per cent and 16.7 per cent of patients with intermediate and high grade lymphomas, respectively, had secondary CNS involvement. Stage IV disease and the presence of B symptoms were also associated with an increased risk of CNS disease. Significantly higher incidence of CNS disease was seen in patients with lymphoma involving orbit (43 per cent), testis (40 per cent), peripheral blood (33 per cent), bone (29 per cent), nasal/paranasal sinuses region (23 per cent) and bone marrow (20 per cent). CNS prophylaxis is recommended to patients with an increased risk of CNS disease.     

Autopsy findings in AIDS-related lymphoma

Autopsies in 20 patients with the acquired immune deficiency syndrome (AIDS)-related lymphoma were studied retrospectively to ascertain the precise cause of death and the extent of lymphomatous disease. Eight patients had primary central nervous system (CNS) lymphoma: two of them were diagnosed antemortem; CNS lymphoma was suspected in three others by computerized tomographic (CT) scan and was confirmed at autopsy. The remaining three were diagnosed incidentally at autopsy. All had concurrent infections at autopsy, including opportunistic infection in six and pyogenic infections in two. Opportunistic infections at autopsy in these patients outnumbered those diagnosed clinically. Twelve patients had systemic lymphoma. Three were diagnosed only at autopsy, two of whom had extensive Kaposi's sarcoma (KS) as well. Eight patients were treated with chemotherapy, but died with disseminated disease. Opportunistic infections were found at autopsy in five patients. Secondary involvement of the CNS by lymphoma was frequent (66%) and was not related to previous bone marrow involvement. The authors conclude that the incidence of lymphoma occurring in AIDS may be more frequent than diagnosed clinically. Similarly, multiple opportunistic infections occur in these patients which are not diagnosed premortem and may contribute to early death.     

Trends in zygomycosis in children

Zygomycosis, or mucormycosis, is associated with significant morbidity and mortality in both children and adults. Studies in adults have shown an increase in the incidence of zygomycosis, particularly among haemtopoietic stem cell transplant (HSCT) recipients and patients with haematologic malignancies. There is a paucity of data on the epidemiology of zygomycosis in children. We performed a retrospective analysis to describe trends in zygomycosis between 1 January 2003 and 31 December 2010. We used the Pediatric Health Information System (PHIS) database to identify paediatric patients who were diagnosed with zygomycosis during the study period. Administrative data on diagnoses, demographics, underlying conditions and clinical experiences were collected. Summary statistics were calculated and tests for trend were conducted. We identified 156 unique patients with zygomycosis. The prevalence of zygomycosis did not significantly increase over time (P=0.284). The most common underlying condition was malignancy (58%) and over half received intensive care. Voriconazole utilisation among all hospitalised children significantly increased during the period (P=0.010). Our study demonstrates that the incidence of zygomycosis is not significantly increasing. During the time period there was a significant increase in the use of voriconazole among children.     

Rhinocerebral zygomycosis in a patient with acute lymphoblastic leukemia

We report a case of a 28-year-old man with acute lymphoblastic leukemia whodeveloped rhinocerebral zygomycosis during induction chemotherapy. Thislife-threatening fungal infection is an infrequent cause of neutropenic fever,and is occasionally found in patients with leukemia and lymphoma, or patientswith severely compromised defence mechanisms due to other diseases. Itis caused by moulds belonging to theMucoraceaefamily, and ischaracterized by local destruction of the affected organ. In our patient, theinfection spread from the paranasal sinuses to the right orbit, destroyedintraorbital structures and resulted in blindness within days. Biopsy from theright maxillary sinus was performed and mucormycosis was suspected throughmicroscopic examination. Culture of the resected specimen identifiedRhizopus arrhizusas the causing agent.Treatment of zygomycosis should consist of radical surgical debridement ofthe infected tissue, together with intensive broad-spectrum antimycotictherapy with amphotericin B. What could be learned from this case is, thataggressive approaches to identify the cause of infection is necessary, andthat aggressive treatment strategies are inevitable to overcome the infection.Furthermore, treatment of the underlying disease should be continued as soonas possible.     

Zygomycosis--a case report and overview of the disease in India

A case of zygomycosis caused by Rhizopus oryzae in a diabetic patient previously misdiagnosed as invasive pulmonary aspergillosis and an overview of the disease in India are presented. The case was diagnosed by direct microscopy, histopathologic examination and culture. Following surgical resection of pulmonary cavity under cover of amphotericin B administration, the patient recovered completely. Of 461 cases reported to-date, approximately 70% had been diagnosed at the Postgraduate Institute of Medical Education and Research, Chandigarh, in north India. This may be attributed to better awareness, expertise and infrastructural facilities for mycological diagnosis than to any particular regional preponderance of the disease. Rhino-orbito-cerebral manifestations were the most common feature of zygomycosis (269 cases), followed by cutaneous disease (66 cases), which is in conformity with the pattern prevalent worldwide. The etiologic agents encountered were Rhizopus oryzae, Apophysomyces elegans, Saksenaea vasiformis, Cunninghamella bertholletiae, Absidia corymbifera, Basidiobolus ranarum and Conidiobolus coronatus. In contrast to cases from the developed world where transplant recipients and patients with haematological malignancies seem to be most vulnerable to zygomycosis, the most common risk factor in India was uncontrolled diabetes mellitus. Amphotericin B was the mainstay of various treatment modalities employed. The relevance of a strong clinical suspicion and early diagnosis of zygomycosis for favourable prognosis can hardly be over-emphasised.     

Rhinocerebral mucormycosis,risk factors and the type of oral manifestations in patients referred to a University Hospital in Tabriz,Iran 2007‐2017

Inadequate data are available on the global epidemiology of mucormycosis, mainly derived from the evaluation of specific population groups. Rhinocerebral mucormycosis is an invading and fatal mycosis, particularly among diabetic patients. In the present study, patients hospitalised in Imam Reza Hospital in Tabriz, from 2007 to 2017, were evaluated. The hospital information system (HIS) was used to collect the records of the patients. A total of 42 patients with a diagnosis of mucormycosis were included in the study, 40 cases (95%) of which had a diagnosis of the rhinocerebral form. Of these 40 patients, 21 (52.5%) and 19 (47.5%) were male and female, respectively. Seven cases (17.5%) of rhinocerebral mucormycosis were due to dental procedures. The most predisposing factor in the patients was diabetes with 36 (90%) cases. In our study, the role of tooth extraction in patients with uncontrolled diabetes was identified as an important factor. It may show the important role of dentists in preventing of the disease in diabetic patients.     

Penetration of VP 16-213 into cerebrospinal fluid after high-dose intravenous administration

VP 16-213 in standard doses is active against a number of solid tumors. Its penetration into the cerebrospinal fluid (CSF) is very limited at these dose levels. In 10 patients treated with high-dose VP 16-213 (0.9-2.5 g/m2), CSF levels of up to 0.54 microgram/mL were detected. In two patients with central nervous system (CNS) metastases of small cell lung cancer (SCLC) a response was seen after 1.0 and 1.5 g/m2 intravenously. High-dose VP 16-213 can possibly play a role in the treatment of CNS metastases of SCLC. Its application in late intensification regimens as a form of prophylaxis of CNS metastases should be investigated.     

Clinical analysis of patients with primary and secondary extranodal natural killer/T-cell lymphoma of central nervous system

Extranodal natural killer (NK)/T-cell lymphoma (NKTL) is a rare non-Hodgkin lymphoma that rarely arise exclusively in or metastasizes to the central nervous system (CNS). Globally, CNS involvement of NKTL heralds a serious prognosis and there is no standard treatment. 19 of 414 patients (4.59%) with ENKL followed were diagnosed with CNS involvement between 2006 and 2020. Two patients had primary CNS (PCNS) NKTL, and 17 patients had secondary CNS (SCNS) invasion. A total of 9 patients survived and 10 patients died. The median overall survival time was 55 months, and the median survival time after CNS invasion was 17 months. The 5-year cumulative survival probability was 45.7%. In conclusion, CNS risk evaluation and prophylaxis treatment can be carried out for patients with NK/T-cell lymphoma prognostic index risk group III/IV. In terms of treatment, systemic therapy based on methotrexate combined with radiotherapy and intrathecal chemotherapy can be selected.     

Incidence of endomycoses in autopsy material

From 1970 to 1993, 93 endomycoses confirmed by postmortem examination were diagnosed in the autopsy material of the Berlin Charité, a large hospital with an average of 1,500 Hospital beds and maximum medical care. These comprised 51 candidoses (54.8%), 24 aspergilloses (36.5%), five cryptococcoses (5.4%), one zygomycosis, one trichosporosis and one coccidioidomycosis. This corresponded to 0.7% of the 13,275 deceased persons autopsied during this period. The frequency of autopsy was 85.3%. In 3,770 cases (2,418 adults and 1,352 children), brain dissection was performed. An adequate clinical putative diagnosis was made in only six out of 28 patients (18 adults, 10 children) with histologically confirmed cerebral mycosis: 11 candidoses (39.3%), 10 aspergilloses (35.7%) five cryptococcosis (17.8%), one trichosporosis and one coccidioidomycosis. About 80% of the mycoses of the CNS thus remained undetected while the patients were alive. The observations made in the present paper underscore the importance of clinical autopsy in endomycoses.     

Primary breast lymphoma

Primary breast lymphoma (PBL) is a rare form of localized extranodal lymphoma. Few reports are available in the literature concerning its treatment and outcome. Of the 34 cases of PBL seen at our institution over a 25-year period, 20 consecutive cases were treated with CHOP or CHOP-like chemotherapy regimen and had adequate biopsy specimens for histological review. All these 20 PBL were of B-cell origin including one case of Burkitt lymphoma, and 2 cases of low-grade histologic type. Sixteen of the 20 patients achieved a complete remission (CR) and 2 achieved a partial remission (PR) (>75% tumor regression). Two patients had progressive disease while on therapy. With a median follow-up period of 80 months, 6 patients relapsed. Median time to relapse from diagnosis was 23 months (range, 3-41 months). Two of the relapses involved the central nervous system (CNS): isolated CNS relapse in one case and associated with other relapse sites in 1 case. The two patients who achieved a PR after chemotherapy also had disease progression to the CNS, 4 and 8 months after the end of CHOP chemotherapy. All 4 patients died of their disease 3, 6, 10 and 13 months after CNS involvement. Of the 16 centroblastic diffuse large B-cell lymphoma (DLCL), 3 had CNS disease at relapse. Three (15%) of our study patients developed a controlateral breast relapse. Twelve of the initial 20 patients were alive, including 11 with a persistent CR, 6 patients died of their lymphoma and 2 of unrelated diseases. In conclusion, we observed a high incidence of CNS relapse in this group of localized extranodal lymphoma, strongly suggesting that CNS prophylaxis should be associated with systemic chemotherapy in localized PLB.     

Central nervous system relapse in adults with acute lymphoblastic leukemia

BACKGROUND: Recurrence of acute lymphoblastic leukemia (ALL) in the central nervous system (CNS) in adults is considered a poor prognostic feature. Few reports have analyzed this issue. The objective of this study was to analyze the experience with CNS recurrence in adult patients with ALL. METHODS: Between December 1982 and April 2000, the records of 527 consecutive, newly diagnosed patients with ALL who were treated at the M. D. Anderson Cancer Center were reviewed. Patients were treated with one of two published regimens: vincristine, doxorubicin, and dexamethasone (VAD; n = 237 patients) or hyperfractionated cyclophosphamide plus VAD (hyper-CVAD) (n = 290 patients). Among 439 patients (83%) who achieved complete remission (CR), 32 patients (7%) had a CNS recurrence. All patients had received CNS prophylaxis tailored to the risk of CNS recurrence with systemic chemotherapy with or without intrathecal (IT) chemotherapy; none received cranial radiotherapy for prophylaxis. The records of these patients were reviewed. RESULTS: The median age at the time of diagnosis was 33 years. The median CR duration prior to CNS recurrence was 36 weeks (range, 2-185 weeks). Three groups were identified: 1) patients with an isolated CNS recurrence (n = 17 patients), 2) patients with CNS recurrences after bone marrow (BM) recurrence (n = 8 patients), and 3) patients with simultaneous CNS and BM recurrences (n = 7 patients). IT chemotherapy was effective in achieving a CNS CR in 30 patients (94%), but 10 patients (31%) had a second CNS recurrence. The median survival from CNS recurrence was 6 months; 28% of patients were alive at 1 year, and 6% of patients were alive at 4 years. CONCLUSIONS: Adults with ALL and CNS recurrences have a poor prognosis despite effective IT chemotherapy. Future studies should investigate better approaches in the treatment of these patients to improve their long-term survival. Effective CNS prophylaxis remains the single best approach for treating patients with CNS leukemia.     

Central nervous system imaging in childhood leukaemia

The aim of this study was to document the imaging abnormalities seen in the central nervous system (CNS) in cases of childhood leukaemia or as complications of its treatment. Magnetic Resonance (MR) images and Computed Tomographic (CT) scans were reviewed retrospectively in 22 children and adolescents with neurological manifestations/complications of leukaemia or its treatment. Among the 22 patients, nine had two or more different CNS abnormalities. The imaging abnormalities seen in 15 patients before or during treatment included sinus thrombosis, cortical vein thrombosis, cerebral haemorrhage, meningeal leukaemia, infections, skull leukaemic infiltration and treatment-related neurotoxicity. After therapy, seven patients had CNS abnormalities, including secondary brain tumours, skull tumour, mineralising microangiopathy, leucoencephalopathy, transient white matter abnormalities, spinal intradural haematoma, chronic subdural haematoma, radiation necrosis, meningeal leukaemia and leukaemic infiltration at the vertebral body. CNS complications are related to the inherent risk of leukaemia itself, to the treatment method and to the duration of survival.     

Intracranial malignant lymphomas: clinicopathological study of 26 autopsy cases

We examined 26 autopsy-proven cases of intracranial malignant lymphoma (IML) in immunocompetent patients to determine the extent of neoplastic involvement of the central nervous system (CNS) and to evaluate the effects of radiation on the tumor and brain tissue. All tumors were identified as diffuse non-Hodgkin's lymphomas of B-cell origin. In six patients who had not received radiotherapy, the clinical course of the disease was short and extensive infiltration of the tumor was seen. The remaining 20 patients were treated with radiotherapy and had a longer survival time. Leptomeningeal involvement was common, but extensive subarachnoid proliferation of the tumor was seen in only two cases. The posterior, but not anterior, lobe of the pituitary was involved in 5 of 22 cases, and choroid plexus involvement was seen in 4 of 21. Direct invasion of the tumor into the spinal cord, which tended to occur in patients with posterior fossa masses, was observed in 5 of 21 cases. Following irradiation, coagulation necrosis was frequently found in the invading zone as well as in the tumor mass, and degeneration of the white matter was also seen. We suggest that IML can extensively infiltrate into the CNS, including the posterior lobe of the pituitary and spinal cord, and that radiation injury to the brain appears to occur relatively easily in this disease. This study was presented at the 11th International Congress of Neurological Surgery, Amsterdam, July 6–11, 1997     

The Outcomes of Diffuse Large B-cell Lymphoma Patients with Synchronous and Early Central Nervous System Involvement: A Single-Center Experience

Background: Diffuse large B cell lymphoma (DLBCL) is the most commonly diagnosed subtype of non-Hodgkin’s lymphoma (NHL). R-CHOP has significantly improved clinical outcomes in patients with DLBCL, however, its indication in the prevention of CNS relapse and recurrence is still inconsistent. Moreover, prophylactic methotrexate and/or cytarabine have been used prophylactically for DLBCL patients is at high risk of CNS relapse and to treat CNS DLBCL, however, their efficacy remains unclear. Methods: The aim of our retrospective study was to determine the incidence of CNS in-volvement in patients with DLBCL and to describe its risk factors and survival outcomes. Results: A total of 406 patients with DLBCL were identified, and 17 (4.2%) of DLBCL patients had CNS involvement i.e. 9 (2.2 %) at diagnosis and 8 (~2%) at relapse. The patients were younger, had advanced stage, high CNS-IPI, and had extra nodal involvement. Seven out of the 17 patients who survived received chemotherapy and a prophylactic methotrexate. Considering the CNS-IPI, of the 146 patients with high CNS-IPI at presentation, 18 received the prophylactic HDMTX and 3 (16.7%) of them had CNS relapse. Two (1.6%) out of 128 who did not receive the prophylactic HDMTX had CNS relapse. On the other hand, of the 223 patients with intermediate CNS-IPI, 25 received the prophylactic HDMTX and 2 (8%) of them had CNS relapse and in 198 patients who did not receive the prophylactic HDMTX, 2 (1.01%) had CNS relapse. The 5-year progression-free survival and overall survival rates for the entire cohort were 73% and 84%, respectively. The median OS for those who had CNS involvement was 17 months and the 2-year OS was 40%. Conclusion: CNS involvement in DLBCL has a poor prognosis, thus, aggressive CNS-directed therapy should be considered, especially in young patients.     

Do children with optic pathway tumors have an increased frequency of other central nervous system tumors?

We questioned whether children with optic pathway tumors (OPTs) have an increased frequency of other CNS tumors on the basis of experience with a number of such children treated at our institution. The medical records of all patients with OPTs treated at Golisano Children's Hospital at Strong at the University of Rochester from 1957 to 2000 were reviewed to determine the incidence of additional CNS tumors in these children and whether the occurrence of these other CNS tumors is associated with any risk factors. Twenty-six children had OPTs. Twelve of the 26 children had biopsy-proved tumors; the remaining 14 were diagnosed on the basis of CT or MRI scans. Eight of the 26 patients (31%) had a total of 11 additional CNS tumors. (One child had 2 additional CNS neoplasms, and a second child had 3.) Nine were biopsy proved (3 glioblastoma, 3 anaplastic astrocytoma, 3 low-grade astrocytoma), and 2 were diagnosed by imaging studies alone (acoustic neuromas). Eight of the 11 tumors occurred at a median of 5 years (0.8-25 years) subsequent to the diagnosis of the OPTs; 3 were diagnosed simultaneously with the OPT. Of the 17 children with neurofibromatosis (NF) and OPTs, 8 (47%) had additional CNS tumors, while none of the 9 children (0%) without NF had other CNS tumors (P = 0.023). There was no association between radiation treatment of the primary OPT and subsequent development of other CNS tumors in the group as a whole, or when the analysis was confined to children with NF. Despite this lack of statistical association, all 7 CNS tumors that occurred following radiation arose in irradiated areas. The risk of simultaneous or subsequent CNS tumors in children with NF and OPTs is high. These children should be closely monitored for the simultaneous or subsequent occurrence of other CNS tumors.