This case was originally published in 2017. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.
A 76-year-old woman was brought to medical attention by her family for confusion, right frontal headaches, generalized weakness, poor appetite, and some left arm/hand clumsiness for one week. Her past medical history was notable for coronary artery disease (status post coronary artery bypass graft placement), congestive heart failure, lung carcinoma (status post right upper lobectomy, chemotherapy, and radiation therapy several years ago), chronic obstructive pulmonary disease, and tobacco smoking (quit 10 years ago). Neurological exam found her to be slightly somnolent with a mild left upper extremity pronator drift. Strength was 5/5 throughout. Brain MRI showed a 5 x 3 x 3 cm, centrally necrotic, heterogeneously enhancing, intra-axial, right frontal brain lesion with surrounding vasogenic edema and right-to-left midline shift (Image A). The patient underwent right frontal craniotomy for gross total resection of lesion.
Whole Slide Image
The whole slide image provided is an H&E stain from a brain craniotomy.
What is the BEST diagnosis?
Primary CNS vasculitis
Which is the MOST EFFECTIVE treatment for this disease?
Corticosteroid and other modalities of immunosuppression
Gamma knife treatment
Prolonged antibiotics based on susceptibility testing
Surgical biopsy followed by irradiation
Total surgical resection
Which of the following statements about this disease is TRUE?
A majority of cases have this condition only in the central nervous system.
It occurs almost exclusively in immunosuppressed patients.
Its overall prognosis is very good with over 90% recovery after treatment.
Selective histochemical stains illustrate its characteristic etiology.
The exact etiology remains unknown.
The pathologic diagnosis is Nocardia abscess of the central nervous system (CNS). The resected brain tissue was gray-tan and soft. Microscopic examination showed suppurative and necrotizing active inflammation (Image B and Image C) walled by gliotic brain parenchyma with fibrosis, microglial activation and perivascular lymphoplasmacytic infiltration (Image D). No discrete microglial nodules, epithelioid granulomas, multinucleated giant cells, protozoan forms, viral inclusions, or sulfur granules were detected. Gram-positive filamentous and branching bacteria were seen in the necrotic areas (Image E). These organisms were argyrophilic and somewhat “beady” on Grocott’s methenamine-silver (GMS) stain (Image F). Rare filamentous organisms were seen on acid-fast stain (Image G). The morphologic and histochemical features of the bacilli identified are those of Nocardia species, later confirmed by microbiologic culture. No radiographic lesions were found in the lungs or elsewhere. Appropriate antibiotic treatment was started after surgery, and the patient recovered fully over the next 12 months.
Nocardiosis is an infectious disease that occurs in three forms: cutaneous (via direct inoculation), pulmonary (inhalation), and disseminated (involving two or more non-contiguous organs via hematogenous spread). The disseminated form most commonly manifests with lesions the lungs and CNS. However, CNS Nocardiosis - whether part of disseminated disease or isolated - is rare, accounting for only 1% to2% of all CNS abscesses. About 40% of patients with CNS Nocardiosis have no evidence of systemic disease (isolated CNS Nocardiosis), presumably from hematogenous spread of healed or occult pulmonary disease. Only an estimated 60% of patients are immunosuppressed, so this diagnosis should be considered even in an immunocompetent individual with a brain abscess. Nocardia species are Gram-positive, weakly acid-fast, filamentous, aerobic and saprophytic bacilli that are ubiquitous in standing water, decaying plants, and soil. A dry, warm, windy climate (eg, southwestern US and Australia) predisposes residents to pulmonary Nocardiosis via inhalation. The genus Nocardia includes more than a dozen pathogenic species (eg, N. asteroids and N. farcinica), many of which seem to be neurotropic. Clinical symptoms of CNS Nocardiosis are determined by the lesion’s location. Histopathologic and radiologic appearance of CNS Nocardiosis depends on the stage of the lesion, varying from cerebritis to encapsulated necrotic abscess. Long-term antibiotic treatment (including trimethoprim-sulfomethoxazole) based on susceptibility testing is necessary for a cure; but drug resistance, disease progression, and relapse are frequent. Therefore, CNS Nocardiosis carries a prognosis worse than that of other brain abscesses, with an overall mortality of 31% to 44%.
A definitive diagnosis of nocardiosis requires demonstration of the organisms by DNA sequencing, microbiologic culture, or microscopic examination of cerebrospinal fluid, aspirated fluid or biopsied tissue. Diagnostic yield of culture is relatively low due to the slow growth rate of Nocardia species. Histochemical recognition of Nocardia species can be missed due to variable staining results and high background staining. All brain abscesses examined histologically should be interrogated by a panel of histochemical stains to see if a specific pathogen can be identified. As usual, a high index of suspicion and familiarity of characteristic findings are essential in this exercise. GMS stain is known to faithfully highlight fungal hyphae and yeasts, as well as many types of bacteria. Specifically, Nocardia organisms appear as aggregates of slender, filamentous, branching and “beady” structures on GMS stain. Nocardia organisms are also Gram-positive (at least focally). When present, the organisms are often found in necrotic debris - as illustrated in this case.
Take Home Points
- CNS nocardiosis is rare and can be diagnosed by DNA sequencing, culture and histochemistry.
- Radiographically and clinically, CNS nocardiosis mimics primary and metastatic malignancies.
- On histochemical stains, Nocardia organisms appear as Gram-positive, GMS-argyrophilic, acid-fast (variable), filamentous and branching bacilli.
- Patients with CNS nocardiosis are not necessarily immunosuppressed.
- Overall prognosis of CNS nocardiosis is worse than that seen in the setting of other brain abscesses due to difficulty in organism identification, inadequate antibiotic treatment, and development of drug resistance.
- Anagnostou T, Arvanitis M, Kourkoumpetis TK, et al. Nocardiosis of the central nervous system. Experience from a general hospital and review of 84 cases from the literature. Medicine. 2014;93:19-32.
- Baldawa S, Nayak N, Kukreja S, et al. Cerebral Nocardiosis. Asian J Neurosurg. 2014;9:245.
- Cooper CJ, Said S, Popp M, et al. A complicated case of an immunocompetent patient with disseminated Nocardiosis. Inf Dis Rep. 2014;6:5327.
- Kennedy KJ, Chung KH, Bowden FJ, et al. A cluster of nocardial brain abscesses. Surg Neurol. 2007;68:43-9.
- Kranick SM and Zerbe CS. Challenges in clinical neuroinfectious disease: CNS Nocardiosis. J Neurovirol. 2013;19:505-7.
- Tatti KM, Shieh WJ, Phillips S, et al. Molecular diagnosis of Nocardia farcinica from a cerebral abscess. Hum Pathol. 2006;37:1117-21.
- What is the BEST diagnosis?
- A. Glioblastoma
- B. Multiple sclerosis
- C. Nocardiosis
- D. Primary CNS vasculitis
- E. Tuberculoma
- Which is the MOST EFFECTIVE treatment for this disease?
- A. Corticosteroid and other modalities of immunosuppression
- B. Gamma knife treatment
- C. Prolonged antibiotics based on susceptibility testing
- D. Surgical biopsy followed by irradiation
- E. Total surgical resection
- Which of the following statements about this disease is TRUE?
- A. A majority of cases have this condition only in the central nervous system.
- B. It occurs almost exclusively in immunosuppressed patients.
- C. Its overall prognosis is very good with over 90% recovery after treatment.
- D. Selective histochemical stains illustrate its characteristic etiology.
- E. The exact etiology remains unknown.