Nontuberculous Mycobacterial Infection of a Metastatic Brain Neoplasm in an Immunocompromised Patient

OBSERVATION Nontuberculous Mycobacterial Infection of a Metastatic Brain Neoplasm in an Immunocompromised Patient

Ann A. Little, MD; Stephen S. Gebarski, MD; Mila Blaivas, MD, PhD

Background: Nontuberculous mycobacterial infec- cyclosporine was seen in the emergency department af- tions occur in immunocompromised patients but so rarely ter a syncopal episode. Head computed tomography re- involve the central nervous system (CNS) that they may vealed a single focal occipital lesion with vasogenic edema. not be included in a differential diagnosis of CNS Hospital admission and further workup led to diagnosis lesions in such patients. of metastatic carcinoma infected with nontuberculous mycobacteria in the setting of a disseminated nontubercu- Objective: To illustrate a putative mechanism for lous mycobacterial infection. nontuberculous mycobacterial infection of the CNS via breakdown of the blood-brain barrier by metastatic Conclusion: This case illustrates that breakdown of the neoplasm. blood-brain barrier by metastatic neoplasm may pro- vide a route of access for a pathogen that is not normally Results: A 56-year-old man who had undergone renal seen in the CNS. transplantation in February 2003 and was taking an im- munosuppressive regimen of mycophenolate mofetil and Arch Neurol. 2006;63:763-765

ONTUBERCULOUS MYCO- compromised state3,4 mention tubercu- bacterial (NTM) infec- lous but not NTM infections. The litera- tions with or without dis- ture contains only a few case reports of semination are well NTM infections of the CNS. These in- documented in immuno- clude focal lesions5-10 and diffuse involve- compromised patients and patients with ment such as chronic meningitis.11 We re- N 1,2 lung disease, such as cystic fibrosis. Non- port a unique case of metastatic neoplasm tuberculous mycobacteria are ubiquitous infiltrated with NTM in an immunocom- in the environment but rarely are sources promised patient who had undergone a of disease in immunocompetent individu- solid organ transplantation. als because of their low virulence. These infections usually manifest with local- METHODS ized involvement, such as cutaneous disease, pulmonary disease, lymphadenitis, skeletal disease, and foreign body infec- A 56-year-old patient with a 40–pack-year his- tions. Cutaneous and pulmonary disease tory of tobacco use who had undergone renal are most prevalent in patients who have transplantation in February 2003 was seen in undergone solid organ transplantation. the emergency department in January 2005 after a syncopal episode. A head computed to- Foreign body infections, such as venous mographic (CT) scan revealed a single, ap- catheter infections, are often seen in he- proximately 2.5-cm, left occipital lesion with 1 matopoietic stem cell recipients. A small surrounding vasogenic edema, local mass effect, percentage of cases may initially be seen and nearby bone destruction (Figure 1A). with disseminated disease involving a On hospital admission, immunosuppres- number of organ systems. Disseminated sive therapy consisted of mycophenolate disease is most often associated with the mofetil, cyclosporine, and prednisone. human immunodeficiency virus popula- Because of the vasogenic edema and mass tion, which represents a small but signifi- effect, dexamethasone administration was Author Affiliations: cant subset of NTM infections in any im- initiated. Departments of Neurology Initial physical examination revealed a (Dr Little), Radiology munocompromised group examined. cachectic appearance and an enlarged left (Dr Gebarski), and Pathology Involvement of the central nervous sys- supraclavicular lymph node. Neurological (Dr Blaivas), University of tem (CNS) by NTM is exceedingly rare un- examination revealed a right homonymous Michigan Medical Center, der any circumstance. Recent reviews of hemianopsia. Laboratory studies on hospital Ann Arbor. CNS infections related to the immuno- admission were significant for microcytic ane-

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Initial concern was for a metastatic process. Further workup A included plain radiographs of the chest, chest CT, lumbar punc- ture, esophagogastroduodenoscopy, colonoscopy, open biopsy of the left supraclavicular lymph node, and magnetic resonance imaging of the brain. Chest CT revealed a noncalcified left lower lobe lung mass measuring 2.3ϫ1.8 cm with spicu- lated margins and a gas-filled center as well as multiple bilat- eral nodules measuring 2 to 3 mm in diameter scattered dif- fusely through the lungs with enlarged retroperitoneal lymph nodes. Colonoscopy results were grossly normal. Esophago- gastroduodenoscopy revealed abnormal-appearing nodular, edematous mucosa throughout the duodenum. Lumbar punc- ture findings were unrevealing (red blood cells, 0; white blood cells, 4 in tube 4; glucose level, 65 mg/dL [3.61 mmol/L]; protein level, 95 g/dL; cytologic examination results were negative for neoplasm; flow profile results were negative for lym- phoma; acid-fast bacilli, bacterial, and fungal smears and culture results were negative). Sputum tuberculosis–polymerase chain B reaction results were negative. Magnetic resonance imaging of the brain was obtained to further characterize the lesion found on CT and to search for additional lesions. Magnetic resonance imaging showed an approximately 2.5-cm, solitary occipital lesion (Figure 1B and C). This mass lesion had a central fluid-like high–T2 signal com- ponent with restricted diffusion in this fluid, low-peripheral T2 signal showing heterogeneous pathological contrast en- hancement, and local meningeal involvement. As was also shown on CT, the lesion demonstrated vasogenic edema, local mass effect, and erosion of the nearby occipital bone. Tissue specimens from the supraclavicular lymph node, duodenum, and colon were filled with foamy macrophages. Sec- tions of lymph node, duodenal biopsy specimen, and sputum were acid-fast bacilli positive and periodic acid–Schiff negative, consistent with disseminated NTM infection. (Mycobac- terium tuberculosis polymerase chain reaction results were nega- C tive; purified protein derivative findings were nonreactive.) Concern remained high for metastatic vs primary brain tu- mor because NTM so rarely cause focal lesions in the brain. Open brain biopsy was undertaken for definitive diagnosis. The surgi- cal report of the occipital lesion described a focal mass extend- ing to and invading the dura as well as eroding the overlying skull. Pathological examination of the occipital lesion tissue demonstrated both adenocarcinoma and NTM infection (Figure 2A and B). Clusters of foamy macrophages containing colonies of acid-fast bacilli were scattered throughout the neoplasm, associated with small numbers of neutrophils. The neoplasm it- self contained no identifiable brain parenchyma and was consistent with metastatic carcinoma with a focal endocrine pattern. Immunoperoxidase staining for keratin cocktail was positive within the neoplastic cells. Staining for thyroid transcription factor 1 was negative in the neoplastic cell nuclei. The prolif- eration index approached 90% in some areas, as determined Figure 1. Computed tomographic (CT) scan and magnetic resonance images using Ki-67 staining. (MRIs) of the brain of a 56-year-old man with nontuberculous mycobacterial Triple-drug therapy was initiated in treatment of dissemi- infection of an adenocarcinoma metastatic to the left occipital lobe. nated Mycobacterium avium-intracellulare complex infection. A, Intravenous contrast-enhanced axial CT section through the occipital Whole brain radiation was carried out for palliative care of CNS lobes displayed in the brain window shows an approximately 2.5-cm mixed attenuation mass (small arrow) with surrounding vasogenic edema (large metastasis. Given the lung lesion and smoking history, lung arrows). B, T2-weighted axial MRI through the occipital lobes shows the adenocarcinoma was a likely candidate for the primary neo- mass lesion to contain a high-T2 material centrally surrounded with a plasm; however, the patient declined further diagnostic workup. peripheral low-T2 rim (small arrows), as can be seen with densely cellular neoplasm with a liquid necrotic core. Moderate local vasogenic edema is present as well as local bone involvement (large arrow). C, Intravenous COMMENT contrast-enhanced, sagittal, T1-weighted MRI through the lesion also shows the local meningeal involvement (arrows) and bone destruction (arrowhead). Our patient’s state of immunosuppression as a solid or- mia and low sodium (129 mEq/L), low albumin (2.3 g/dL), gan transplant recipient increased his risk for NTM in- and elevated creatinine (1.5 mg/dL [132.6 µmol/L], which was fection. Doucette and Fishman1 searched MEDLINE for the patient’s posttransplantation baseline value) levels. English language articles since 1966 documenting cases

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Figure 2. Histopathologic features of the lesion. A, Metastatic adenocarcinoma with a large amount of connective tissue stroma and scattered foamy macrophages (hematoxylin-eosin, original magnification ϫ200). B, Acid-fast bacilli–positive microorganisms within the macrophages and stroma of the neoplasm (Fite, original magnification ϫ200).

of NTM infection in patients who had undergone trans- REFERENCES plantation and identified reports of 183 solid organ transplantation cases complicated by NTM infection. Ninety- 1. Doucette K, Fishman JA. Nontuberculous mycobacterial infection in hematopoi- four of 183 solid organ transplantation cases were renal etic stem cell and solid organ transplant recipients. Clin Infect Dis. 2004;38: transplantations. In patients who had undergone renal 1428-1439. transplantation, cutaneous NTM was most common, fol- 2. Wagner D, Young LS. Nontuberculous mycobacterial infections: a clinical review lowed by disseminated disease (approximately one third Infection. 2004;32:257-270. of cases identified). Our patient had a disseminated NTM 3. Zunt JR. Central nervous system infection during immunosuppression. Neurol Clin. 2002;20:1-22. infection that appeared to be highly active based on dense 4. Singh N, Husain S. Infections of the central nervous system in transplant recipients. infiltration of macrophages and profusely positive acid- Transpl Infect Dis. 2000;2:101-111. fast bacilli staining throughout all tissues in which a bi- 5. Murray R, Mallal S, Heath C, French M. Cerebral Mycobacterium avium infec- opsy was performed. tion in an HIV-infected patient following immune reconstitution and cessation of We postulate that the breakdown of the blood-brain bar- therapy for disseminated mycobacterium avium complex infection. Eur J Clin rier caused by metastatic neoplasm allowed an entry point Microbiol Infect Dis. 2001;20:199-201. for NTM infection to the CNS. The edema seen on imag- 6. Berger P, Lepidi H, Drogoul-Vey MP, Poizot-Martin I, Drancourt M. Mycobacte- rium avium brain abscess at the initiation of highly active antiretroviral therapy. ing corresponds to abnormal capillary permeability con- Eur J Clin Microbiol Infect Dis. 2004;23:142-144. 12 sistent with disruption of the blood-brain barrier. 7. Dickerman RD, Stevens QE, Rak R, Dorman SE, Holland SM, Nguyen T. Isolated intracranial infection with Mycobacterium avium complex. J Neurosurg Sci. 2003; Accepted for Publication: December 15, 2005. 47:101-105. Correspondence: Ann A. Little, MD, Department of 8. Morrison A, Gyure KA, Stone J, et al. Mycobacterial spindle cell pseudotumor of Neurology, University of Michigan Medical Center, 1924 the brain: a case report and review of the literature. Am J Surg Pathol. 1999; 23:1294-1299. Taubman Center, 1500 E Medical Center Dr, Ann 9. Uldry PA, Bogousslavsky J, Regli F, Chave JP, Beer V. Chronic Mycobacterium Arbor, MI 48109 ([email protected]). avium complex infection of the central nervous system in a nonimmunosup- Author Contributions: Study concept and design: Little pressed woman. Eur Neurol. 1992;32:285-288. and Gebarski. Acquisition of data: Little, Gebarski, and 10. Gyure KA, Prayson RA, Estes ML, Hall GS. Symptomatic Mycobacterium avium Blaivas. Analysis and interpretation of data: Little, Gebarski, complex infection of the central nervous system: a case report and review of the and Blaivas. Drafting of the manuscript: Little and Gebarski. literature. Arch Pathol Lab Med. 1995;119:836-839. 11. Lascaux AS, Lesprit P, Deforges L, Gutierrez C, Levy Y. Late cerebral relapse of Critical revision of the manuscript for important intellec- a Mycobacterium avium complex disseminated infection in an HIV-infected pa- tual content: Little, Gebarski, and Blaivas. Administra- tient after cessation of antiretroviral therapy. AIDS. 2003;17:1410-1411. tive, technical, and material support: Gebarski. Study su- 12. Davies DC. Blood-brain barrier breakdown in septic encephalopathy and brain pervision: Gebarski. tumours. J Anat. 2002;200:639-646.

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