Cryptococcal Granuloma Research Articles

Mechanism of extracellular space changes in cryptococcal brain granuloma revealed by MRI tracer.

This study aimed to investigate the changes in extracellular space (ECS) in cryptococcal brain granuloma and its pathological mechanism. The animal model of cryptococcal brain granuloma was established by injecting 1 × 106 CFU/ml of Cryptococcus neoformans type A suspension into the caudate nucleus of Sprague-Dawley rats with stereotactic technology. The infection in the brain was observed by conventional MRI scanning on days 14, 21, and 28 of modeling. The tracer-based MRI with a gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) as a magnetic tracer was performed on the rats with cryptococcal granuloma and the rats in the control group. The parameters of ECS in each area of cryptococcal brain granuloma were measured. The parameters of ECS in the two groups were compared by independent sample t-test, and the changes in ECS and its mechanism were analyzed. Up to 28 days of modeling, the success rate of establishing the brain cryptococcal granuloma model with 1 × 106 CFU/ml Cryptococcus neoformans suspension was 60%. In the internal area of cryptococcal granuloma, the effective diffusion coefficient D* was significantly higher than that of the control group (t = 2.76, P < 0.05), and the same trend showed in the volume ratio α (t = 3.71, P < 0.05), the clearance rate constant k (t = 3.137, P < 0.05), and the tracer half-life T1/2 (t = 3.837, P < 0.05). The tortuosity λ decreased compared with the control group (t = -2.70, P < 0.05). At the edge of the cryptococcal granuloma, the D* and α decreased, while the λ increased compared with the control group (D*:t = -6.05, P < 0.05; α: t = -4.988, P < 0.05; λ: t = 6.222, P < 0.05). The internal area of the lesion demonstrated a quicker, broader, and more extended distribution of the tracer, while the edge of the lesion exhibited a slower and narrower distribution. MRI tracer method can monitor morphological and functional changes of ECS in pathological conditions and provide a theoretical basis for the treatment via ECS.

The granuloma in cryptococcal disease.

Although we have recognized cryptococcosis as a disease entity for well over 100 years, there are many details about its pathogenesis which remain unknown. A major barrier to better understanding is the very broad range of clinical and pathological forms cryptococcal infections can take. One such form has been historically called the cryptococcal granuloma, or the cryptococcoma. These words have been used to describe essentially any mass lesion associated with infection, due to their presumed similarity to the quintessential granuloma, the tubercle in tuberculosis. Although clear distinctions between tuberculosis and cryptococcal disease have been discovered, cellular and molecular studies still confirm some important parallels between these 2 diseases and what we now call granulomatous inflammation. In this review, we shall sketch out some of the history behind the term “granuloma” as it pertains to cryptococcal disease, explore our current understanding of the biology of granuloma formation, and try to place that understanding in the context of the myriad pathological presentations of this infection. Finally, we shall summarize the role of the granuloma in cryptococcal latency and present opportunities for future investigations.

Cryptococcal granuloma of the frontal lobe in an immunocompromised HIV-negative patient

BackgroundCryptococcal infection of the brain usually occurs in immunocompromised individuals and manifests with signs and symptoms suggestive of meningoencephalitis. It is rare to come across this infection as a brain granuloma manifesting with focal neurological deficits and without any overt immune deficiency.Case presentationA 55-year-old male presented with dysphasia. His vital signs were normal at presentation and he was afebrile. Computed tomography (CT) and MRI (magnetic resonance imaging) suggested left frontal mass lesion. A possibility of a solitary metastasis from an occult primary was considered and contrast-enhanced computed tomography abdomen and chest were done which revealed no significant abnormality.The patient underwent craniotomy and excision of lesion. The excised tissue was soft, greyish and friable. He started to have fever on post-operative day 5, and CSF study was done to rule out post-operative bacterial meningitis. However, the CSF returned positive for cryptococcus. Subsequently, the histopathology report from the excised tissue showed cryptococcal granuloma. He remained an inpatient for 32 days during which he received intravenous amphotericin B and flucytosine along with oral fluconazole. After discharge, he was continued on oral fluconazole for 47 days.ConclusionCryptococcal granuloma of the brain, especially of the frontal lobe, is rare. Its clinical and radiological features mimic that of a neoplastic process. The diagnosis can be especially difficult if the usual pointer for immunosuppression in the form of HIV-positive status is missing. Such cases need operative intervention. However, once the diagnosis is made histologically, it is important to investigate for other causes of immunosuppression as in our case where the patient turned out to be deficient in natural killer cells.

The performance of serum cryptococcal capsular polysaccharide antigen test, histopathology and culture of the lung tissue for diagnosis of pulmonary cryptococcosis in patients without HIV infection.

BackgroundClinicians may fail to make an early diagnosis of pulmonary cryptococcosis (PC) without HIV infection. Serum cryptococcal capsular polysaccharide antigen (CrAg) test, histopathology and culture of lung tissue play different roles in diagnosis of PC.ObjectiveTo investigate the performance of serum CrAg test, histopathology and culture of the lung tissue in diagnosis of PC without HIV infection.Patients/methodsFrom January 2011 to September 2017, patients with proven PC were recruited from a teaching hospital in southern China. Those patients with HIV infection, PC confirmed by surgery or PC with probable or possible diagnosis were excluded from the study. Latex agglutination test and CrAg lateral flow assay were used for detection of serum CrAg. Lung biopsy and needle aspiration were performed under computed tomography guidance.ResultsEighty-nine patients with proven PC including 41 male (46.1%) and 48 female (53.9%) were enrolled. Fifty-one (57.3%) patients had underlying disease. Positive CrAg test was found in 83 (93.3%) cases. Among six cases with negative CrAg test, PC was confirmed by histology in two cases and positive culture in four cases. The histopathological results of 77 (86.5%) cases revealed cryptococcal granuloma and 12 cases showed chronic inflammation, which was confirmed by positive culture. Among 65 cases, the diseased tissue of 46 (70.8%) cases presented Cryptococcus neoformans in the culture and one case was diagnosed with lung cancer coexisting with PC.ConclusionOur findings showed that serum CrAg test is rapid and sensitive in diagnosing PC, histology is important for confirming PC and culture plays a complementary role. Biopsied lung tissue should be submitted for cultures whenever feasible.

Magnetic resonance imaging features of Cryptococcus infection in central nervous system in patients with AIDS

To investigate the magnetic resonance imaging (MRI) features of Cryptococcus infection in central nervous system patients with acquired immune deficiency syndrome (AIDS). Methods: The retrospective study on magnetic resonance imaging (MRI) and clinical data of cryptococcal meningitis (CM) was carried out between July 2011 and March 2017. These patients had not received anti-retroviral treatment. Patients with other specific or suspicious diseases in the central nervous system were not included in the analysis. Results: A total of 39 patients were included in the analysis, with CD4 cell counts of 13.0×106/L [(0-205)×106/L], and 94.9% (37/39) of patients with CD4 cell count <100×106/L. Of the 39 patients, 26 patients showed abnormal MRI signals in the brain, which were most frequently involved in the basal ganglia (20/26, 76.9%). The basal ganglia lesions showed dilated Virchow-Robin space (VRS)/gelatinous spseudocysts (18/20, 90%). Postcontrast T1-weighted MRI revealed no significant enhancement (3/5, 60%) and mild enhancement (2/5, 40%). The incidence of cerebral cryptococcal granuloma were 35% (7/20). Nineteen of 26 patients with lesions outside the basal ganglia, of which 13 patients also complicated with basal ganglia lesions. Postcontrast T1-weighted MRI revealed no significant enhancement. The incidence of cryptococcal granuloma and meningeal thickening were 15.7% (3/19) and 26.3% (5/19), respectively. Postcontrast T1-weighted MRI meningeal thickening revealed enhancement (5/5, 100%). Conclusion: The incidence of brain MRI abnormality in AIDS complicated with central nervous system Cryptococcus infection may not be low, and the lesions are mostly located in the basal ganglia. It most frequently displays the dilated VRS/gelatinous spseudocysts. It can also be showed cryptococcal granuloma. Postcontrast T1-weighted MRI often reveals no enhancement or mild enhancement.

Magnetic resonance imaging findings in central nervous system cryptococcosis: comparison between immunocompetent and immunocompromised patients.

ObjectiveTo assess the magnetic resonance imaging (MRI) patterns associated with central nervous system infection with Cryptococcus sp. in relation to patient immune status.Materials and MethodsThis was a retrospective study of MRI data for 19 patients with neurocryptococcosis who underwent the examination between January 2000 and March 2014. The MRI characteristics examined included lesion topography, aspects of diffusion, T1-weighted images, T2-weighted images, and contrast enhancement patterns.ResultsIn all cases, cryptococcal infection was confirmed by cerebrospinal fluid analysis. Of the 19 patients, 10 were immunocompromised and 9 were immunocompetent. Abnormal imaging patterns occurred alone or in conjunction with other manifestations. The imaging patterns found in immunocompromised patients included the following: leptomeningeal enhancement, in 6; pachymeningeal enhancement, in 3 (due to intracranial hypotension in 2); perivascular space involvement, in 4; granulomas, in 2; hydrocephalus, in 2; miliary nodules, in 1; and plexitis, in 1. In immunocompetent patients, the following imaging patterns were observed: leptomeningeal enhancement, in 5; perivascular space involvement, in 3; granulomas, in 3; cryptococcoma, in 1; ventriculitis, in 1; and hydrocephalus, in 1. In 2 immunocompetent patients, diffusion-weighted imaging showed diffusion restriction in cerebral cryptococcal granuloma.ConclusionIn both groups, the most common imaging finding was leptomeningeal enhancement, followed by dilatation of perivascular spaces with the presence of mucoid material. Rare presentations, such as miliary nodules, plexitis, ventriculitis, and pachymeningeal enhancement, were also observed. None of the imaging patterns common to immunocompetent and immunocompromised patients differed significantly in frequency between them.

Surgical algorithm for heterogeneous bilateral quadruple pulmonary nodules

A 65-year old female with no history of smoking reported experiencing 6 months of tightness in the chest. Chest computed tomography showed two pulmonary nodules in the left upper lobe (one in S3 segment, the other in S4 segment), one nodule in the left lower lobe and a ground-glass opacity (GGO) in the right upper lobe. Synchronous bilateral thoracoscopic wedge resections of the lung were performed to investigate the nodules. Intraoperative frozen section pathology revealed that the two nodules in the left upper lobe were malignant, the nodule in the left lower lobe was a benign lesion and the GGO in the right upper lobe was an atypical adenomatous hyperplasia. As a result, a left upper lobectomy with lymph node dissection was performed. The final pathological diagnosis of the nodule in the left S3 segment was well differentiated adenocarcinoma (pT1bN0M0, IA), the nodule in the left S4 segment was moderately to poorly differentiated adenocarcinoma (pT1aN0M0, IA), the nodule in the left lower lobe was cryptococcal granuloma and the GGO in the right upper lobe was adenocarcinoma in situ. The patient is currently following a favourable course in her recovery. Here, we would like to share the surgical algorithm used for the treatment of heterogeneous bilateral quadruple pulmonary nodules.

Solitary pulmonary mass in a patient with a history of lymphoma: a case report

IntroductionWith the progress made in treatments, the survival rate for patients with malignant lymphoma in the last 30 years has significantly improved. However, the risk of experiencing a second primary malignancy or other disease has increased significantly.Case presentationA 44-year-old Mongolian man with a large mass in his right lower abdomen was admitted to our hospital 15 years previously. The mass was removed, and confirmed via pathological examination to be a malignant B-cell lymphoma in the appendix and distal small bowel. Post-operative chemotherapy with standard cyclophosphamide, hydroxydaunomycin, vincristine (Oncovin®) and prednisolone regimen was given for six cycles. No obvious recurrence was detected over the following 12 years. Subsequently, a mass in the right lung was found on a regular X-ray follow-up; our patient did not report chills, fever or cough. Chest computed tomography and positron emission tomography scans confirmed the mass. A primary lung carcinoma was considered to be the most likely diagnosis. However, after an exploratory thoracotomy and right upper lobectomy was performed a pathological examination of tissue samples demonstrated a lung cryptococcal granuloma, with positive staining for periodic acid Schiff and periodic acid-silver metheramine.ConclusionsCompared to the normal population, second primary malignancy (in particular leukaemia and lung cancer) in patients with malignant lymphoma during their long-term survival has been seen occasionally. However, other diagnoses should also be considered such as pulmonary cryptococcosis. Other than computed-tomography-guided needle biopsy, surgery for some patients is a much more appropriate choice, which could also help attain correct diagnosis and treatment.

Calcified Cerebral Cryptococcal Granuloma

The authors report a 12-mo-old girl with calcified cerebral cryptococcal granuloma. She was admitted with a 6-mo history of seizures. Laboratory examinations showed no abnormal findings. Electroencephalography revealed bilateral slow wave activity, greater in the right occipital region. CT showed an irregular calcified focus with small surrounding low density in the right parieto-occipital region. MRI demonstrated mixed signals without edema and visible flow-voids. The clinical symptoms mimicked intracranial vascular malformations. The diagnosis of cerebral cryptococcal granuloma was made by histopathology. Partial resection of the lesion with post-operatively antifungal and anticonvulsant therapy offered the satisfactory result. Cerebral cryptococcal granuloma is extremely rare, especially in infants. Calcification is indeed unusual. Cerebral cryptococcal granuloma should be included in the differential diagnosis of intracranial mass with calcification in infants.

Ectopic ACTH syndrome caused by bronchial carcinoid tumor indistinguishable from Cushing's disease

A 75-year-old woman was admitted to our hospital because of a poor glycemic control. She was found to have Cushingoid feature and dynamic endocrine tests showed elevated plasma ACTH and cortisol levels, lack of their circadian rhythm, non-suppressibility to high-dose dexamethasone, responsiveness to CRH, but not to DDAVP, and suppression to octreotide. Pituitary MRI showed an equivocal small lesion. CT scan of the chest showed two nodular lesions in the right lung (S5, S7), while a mild uptake was noted only in S5 lesion by FDG-PET, but positive uptake was only in S7 lesion by somatostatin receptor scintigraphy (SRS). Inferior petrosal sinus sampling revealed a gradient of plasma ACTH after CRH stimulation, consistent with the diagnosis of Cushing' s disease. She underwent middle and inferior lobectomy of the right lung. The resected tumor in S7 was consistent with the diagnosis of a bronchial carcinoid tumor with positive ACTH immunoreactivity, while that of S5 was cryptococcal granuloma. RT-PCR revealed abundant expressions of POMC and SSTR (-1, -2, -5), but not of CRHR and V1bR. Postoperatively, abnormal endocrine data were normalized along with improvement of hypertension and diabetes. This was a diagnostic challenging case with ectopic ACTH syndrome indistinguishable from Cushing' s disease by various endocrine and imaging tests, among which SRS successfully localized the tumor responsible for ectopic ACTH secretion.

Central nervous system cryptococcoma in immunocompetent patients: a short review illustrated by a new case

Cryptococcal infection in CNS is frequently seen in HIV patients and those with other immunosuppressed conditions. However, cryptococcal granuloma in CNS in immunocompetent patient is rare. We present one new case of cryptococcoma and review literature to illustrate diagnosis and treatment of these lesions. We conducted literature search in Pubmed search engine of the National Center for Biotechnology Information. Seventeen cases of CNS cryptoccoma in immunocompetent patients, including ours, have been reported to date. Of them, two patients had lesions inside spinal cord, and C. neoformans var. gattii was identified in three cases. All patients were symptomatic with normal immunocompetency although two patients had type 2 diabetes mellitus and one had torsades de pointes. Eight patients received surgical treatment and all were given antifungal agents except one suspected of teniasis. With literature reports and our experiences, we suggest that ring shaped enhancement of mass lesion with or without cystic changes in MR scan may indicate cryptococcoma, but definitive diagnosis relies on pathology study of lesion specimen. Open surgery and anti-fungal therapy should be scheduled, and outcome of cryptococcoma is largely determined by its locations.

Successful treatment of a sinonasal cryptococcal granuloma in a horse

A 12-year-old 500-kg (1,100-lb) American Quarter Horse mare was evaluated because of chronic mucopurulent, bloody discharge from the left nostril, inspiratory dyspnea, and respiratory noise. The horse had severe inspiratory dyspnea and stertorous respiration with no airflow from the left nostril. A temporary tracheostomy was performed. Endoscopy revealed a tan mass protruding from the left middle nasal meatus into the left common nasal meatus; it extended caudally into the nasopharynx and around the caudal edge of the nasal septum into the right nasal cavity. Radiographically, a soft tissue opacity was evident in most of the left nasal cavity and left paranasal sinuses. Cytologic examination of mass tissue revealed evidence of pyogranulomatous rhinitis; thickly encapsulated, budding yeast typical of Cryptococcus neoformans were detected. While the horse was sedated and in a standing position, the fungal granuloma was removed from the paranasal sinuses. Treatment with fluconazole (5 mg/kg [2.27 mg/lb], PO, q 24 h for 4 weeks) was initiated; enilconazole (50 mL of a 10% solution) was instilled into the paranasal sinuses every other day (7 lavages). Six weeks after surgery, infection had not recurred and epithelialization appeared normal in the left paranasal sinuses. In horses with cryptococcosis of the paranasal sinuses, surgical removal of granulomatous lesions and systemic and topical administrations of antifungal drugs may be curative. Successful surgery may be performed in standing horses. Concommitant removal of a large portion of the conchae allows follow-up rhinoscopic evaluation of the paranasal sinuses.

Isolated intramedullary cryptococcal granuloma of the conus medullaris: Case report and review of the literature

Infection of the nervous system by Cryptococcus neoformans most often causes meningitis and meningoencephalitis. While there have been several cases of cerebral cryptoccal granuloma published in the literature, the isolated occurrence of intramedullary cryptococcal granuloma is very rare. We present an immunocompetent patient with such a lesion of the conus medullaris. The patient's clinical symptoms mimicked an intramedullary spinal cord tumor. The diagnosis was made by histopathology, rather than by image or laboratory examinations. The case was successfully managed with surgical removal of the lesion and postoperative anti-fungal treatment.

A solitary cryptococcal granuloma in an immunocompetent host

A solitary cryptococcal granuloma in an immunocompetent host

Cerebral cryptococcal granuloma in a cat

A 7-year-old cat was presented for seizures. Cerebrospinal fluid cytology and serology were consistent with a diagnosis of toxoplasmosis. The cat was treated with clindamycin but seizures continued and additional neurological signs developed over 6 months. A mass lesion was identified in the left cerebral hemisphere using magnetic resonance imaging (MRI). The lesion enhanced after gadolidium and a tumour was considered likely. Histologically, the lesion proved to be a cryptococcal granuloma and retrospective serology confirmed that the cat had cryptococcosis at its initial presentation. This report provides the first description in the veterinary literature of the MRI appearance of a cerebral cryptococcoma and emphasises the importance of performing cryptococcal antigen determination in cats with signs of intracranial disease.

A Large Frontonasal Bone Flap for Sinus Surgery in the Horse

A large frontonasal bone flap was created to treat diseases of the paranasal sinuses in 14 horses. The bone flap was made as wide as possible within the confines of the nasolacrimal duct so the floor of the frontal sinus and the dorsal and ventral conchae could be opened. These openings exposed the nasal passages, maxillary sinuses, and ventral conchal sinus thereby facilitating removal of diffuse and localized lesions from these sites. Diseases treated were ethmoid hematomas (4 horses), sinus cysts (5 horses), cryptococcal granuloma, osteoma, hemangiosarcoma, pus in the ventral conchal sinus, and periapical infection of a second molar. Four horses were euthanatized during or after surgery, one because of postsurgical pleuritis and pneumonia (horse with osteoma) and three because of their primary problems (cryptococcal granuloma, hemangiosarcoma, pus in the ventral conchal sinus). Skin suture abscesses that responded to treatment developed in four horses. Ten horses returned to their intended uses, the sinus flaps healed without blemish, and the original problems did not recur. The frontonasal flap technique provided greater access to all paranasal sinuses than methods described previously.

A CASE OF RENAL TRANSPLANT RECIPIENT COMPLICATED WITH CRYPTOCOCCOSIS AND AMPHOTERICIN B INDUCED ACUTE TUBULAR NECROSIS

An adult renal transplant recipient was complicated with cryptococcal lung granuloma and meningitis. Treatment with the antifungal agents, 5-fluorocytocin and clotrimazole had to be discontinued due to side effects. Whereas, the intrathecal administration of amphotericin B proved effective for meningitis but intravenously it induced acute tubular necrosis to the transplanted kidney. In order to cure the persistant fungal lung granulomas in renal transplant patients early surgical excision seems to be essential.

Cryptococcal granuloma (toruloma) of the central nervous system in a patient with schistosomiasis.

A case of cryptococcal granuloma of the brain and lung is described in a Nigerian woman who also had Schistosoma haematobium infection.

Intraventricular cryptococcal granuloma.

A case is reported of a cryptococcal granuloma occurring within the lateral ventricle. The findings on angiography and brain-scanning led to a preoperative diagnosis of intraventricular meningioma. There are no previous reports of an isotope brain-scan in this condition and angiography usually shows an avascular swelling.

Cryptococcosis in a cat.

Abstract Extract Cryptococcosis is a systemic fungal infection caused by the non-mycelial budding yeast Cryptococcus neoformans. The disease is well known in man and has been reported in a variety of animals (Barron, 1955 Barron, C. N. 1955. Cryptococcus in animais. J. Am. vet. med. Ass., 127: 125–132. [PubMed] , [Google Scholar]). In Australia it has been described in cats (Johnston and Lavers, 1963 Johnston, L. A. Y. and Lavers, D. W. 1963. Cryptococcal meningitis in a cat in north Queensland. Aust. vet. J., 39: 306–307. [Google Scholar]; Clark and Roubin, 1970 Clark, L. and Roubin, G. S. 1970. Cryptococcosis in a cat. Aust. vet. J., 46: 544–548. [Google Scholar]), horses (Watt, 1970 Watt, D. A. 1970. A case of cryptococcal granuloma in the nasal cavity of a horse. Aust. vet. J., 46: 493–495. [Google Scholar]; Barton and Knight, 1972 Barton, M. D. and Knight, I. 1972. Cryptococcal meningitis of a horse. Aust. vet. J., 48: 534–534. [Google Scholar]), sheep (Laws and Simmons, 1966 Clark, L. and Roubin, G. S. 1970. Cryptococcosis in a cat. Aust. vet. J., 46: 544–548. [Google Scholar]), cattle (Connole and Johnston, 1967 Connole, M. D. and Johnston, L. A. Y. 1967. A review of animal mycoses in Australia. Vet. Bull., 37: 145–153. [Google Scholar]) and koalas (Bolliger and Finckh, 1962 Bolliger, A. and Finckh, E. S. 1962. The prevalence of Cryptococcus in the koala (Phascolarctos cinereus). Med. J. Aust., I: 545–547. [Google Scholar]). The organism has a marked predilection for the central nervous system and meningitis generally follows haematogenous spread from a primary focus in the lungs (Lewis and Rabinovich, Lewis and Rabinovich, 1972 Lewis, J. L. and Rabinovich, S. 1972. The wide spectrum of cryptococcal infections. Am. J. Med., 53: 315–322. [Google Scholar]).