CLINICAL
AND
LABORATORY OBSERVATIONS
Nocardia farcinica Meningitis Masquerading as Central Nervous System Metastasis in a Child With Cerebellar Pilocytic Astrocytoma Jennifer Davis, DO,* Andrew J. Kreppel, MD,w Rebecca C. Brady, MD,z Blaise Jones, MD,y Charles B. Stevenson, MD,8 Maryam Fouladi, MD,* and Trent R. Hummel, MD*
Summary: Juvenile pilocytic astrocytoma, the most common pediatric central nervous system (CNS) neoplasm, characteristically displays an indolent growth pattern and rarely demonstrates metastatic dissemination. Reports of infections mimicking CNS metastatic disease are also rare and can impact treatment. We report the youngest known case of a child with a CNS Nocardia farcinica infection who had a known cerebellar pilocytic astrocytoma, review other infections that may masquerade as CNS neoplasms, and discuss N. farcinica CNS infections. Key Words: CNS tumors, infectious disease, low-grade gliomas
(J Pediatr Hematol Oncol 2015;37:482–485)
L
ow-grade gliomas (LGG) account for the majority of central nervous system (CNS) tumors in children and comprise a heterogenous set of tumors. Juvenile pilocytic astrocytoma (JPA) is a WHO grade I glioma that typically does not exhibit aggressive clinical behavior nor undergo malignant transformation. Surgical gross total resection (GTR) is the most consistent prognostic factor for prolonged overall survival.1 Five-year overall survival after GTR is 90%,2,3 with dissemination rarely reported.1 Despite LGG being the commonest of childhood CNS tumors, the incidence of postresection CNS infection in astrocytoma is quite rare, with only 1 such pediatric case discussed previously in the literature. Infectious agents may enter the CNS either through hematogenous spread or direct inoculation, following trauma or surgery. Nocardia species live in soil and water and may enter the CNS by either route, leading to meningitis or brain abscesses. Certain species, especially Nocardia farcinica, have a predilection for dissemination to the CNS from extraneural sites. In 2000, Torres et al4 reviewed 118 cases of N. farcinica infection; 30% involved the CNS. Although Nocardia brain abscesses account for only about 2% of all brain abscesses,5
Received for publication September 17, 2014; accepted April 21, 2015. From the Divisions of *Oncology, Cancer and Blood Diseases Institute; 8Pediatric Neurosurgery; Departments of zPediatrics, Division of Infectious Diseases; yRadiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; and wDepartment of Pediatrics, Division of Infectious Diseases, University of Illinois at Chicago, Chicago, IL. The authors declare no conflict of interest. Reprints: Trent R. Hummel, MD, Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, MLC 7015, Cincinnati, OH 45229 (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
their early recognition is important because reported mortality rates range from 30% to 90%.6
CASE REPORT A 4-year-old boy with a subtotally resected cerebellar JPA diagnosed 1 month prior was admitted with a 1-week history of fever and diarrhea to another institution. Evaluations there included a stable computed tomography (CT) scan of the brain and cerebrospinal fluid (CSF) examination with a marked leukocytosis of >3000/mcL. He received 4 days of empiric antibiotics for meningitis. Antibiotics were discontinued when CSF cultures were reported to be negative and he was prescribed steroids for presumed chemical meningitis. Approximately 10 days after discharge, he presented again to the outside institution with fever and diarrhea. He was diagnosed with a rotavirus infection and discharged home. He was subsequently admitted for a third time to the same facility, nearly 2 months after diagnosis, with symptoms of lethargy, nausea, fever, and meningismus and was transferred to our institution. Initial laboratory findings at our institution included a hemoglobin of 11.5 g/L, leukocyte count of 12.4k/mcL with 68% polymorphonuclear cells (PMNs), 9% monocytes, and 22% lymphocytes. Lumbar puncture revealed cloudy CSF with 12 RBC/ mcL and 1156 WBC/mcL (74% PMNs, 5% lymphocytes, and 21% monocytes). Glucose was 27 mg/dL and protein was 220 mg/dL. Initial Gram stain was positive for WBC but no organisms were seen. CSF polymerase chain reactions were negative for enterovirus, CMV, EBV, and HSV. Cryptococcal antigen was negative and fungal and AFB cultures showed no growth. Empiric vancomycin and ceftriaxone were initiated. The patient’s tumor pathology was reviewed and exhibited biphasic growth pattern, a clear astrocytic morphology diffusely positive for GFAP and negative for IDH1 with a proliferation index of 6%, consistent with a JPA. Blood and CSF cultures remained negative but the child continued to have fevers (Fig. 1). MRI performed on hospital day 3 showed abnormal signal and enhancement in previous resection bed suspicious for residual tumor. On hospital day 6, the CSF culture at our institution grew a beaded, branching, weakly gram-positive rod that was subsequently determined to be modified acid fast positive, concerning for Nocardia species. The child was not able to tolerate oral or nasogastric administration of trimethoprim/sulfamethoxazole (TMP/SMX) and intravenous TMP/SMX was in short supply. Therefore, intravenous amikacin was added to ceftriaxone to provide combination therapy for presumed Nocardia CNS infection and vancomycin was discontinued. Because of persistent fevers on day 17 of admission, CT scans of the neck, chest, abdomen, and pelvis were obtained. The CT of the neck revealed new nodular areas of enhancement along the surface of the cervical cord centered at the C2 and C4 levels (Fig. 2A). Subsequent MRI of brain and spine revealed enhancing nodules seen along the dorsal aspect of the cord at C2, C3-C4, C6C7, and T4-T5, as well as more mass-like enhancement surrounding the conus (Fig. 2C).
482 | www.jpho-online.com J Pediatr Hematol Oncol Volume 37, Number 6, August 2015 Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
Volume 37, Number 6, August 2015
Nocardia Infection Masquerading as Neoplasm
FIGURE 1. Gray vertical bars demonstrate trend in cerebrospinal fluid WBC: initial WBC/mcL = 1156, day 59 WBC/mcL = 12. Gray line demonstrates fever trend. Day 27 (arrow) is first day without a fever. Bars below x-axis represent antimicrobial courses: Vanc (vancomycin) days 1 to 10, Amikacin days 10 to 56, Linezolid days 56 to 69, Ceftriaxone days 1 to 16, Bactrim (trimethorprim-sulfamethoxazole) day 16 to 24 months. On hospital day 16, the CSF culture isolate was identified as N. farcinica with the following minimal inhibitory concentrations in mcg/mL with S = susceptible and R = resistant: amikacin 1 S, TMP/SMX 0.25 S, linezolid 4 S, and ceftriaxone >64 R. Ceftriaxone was discontinued and intravenous TMP/SMX was started despite the national shortage to provide coverage against the resistance pattern of N. farcinica reported in the literature. Amikacin was discontinued on hospital day 56 when the child developed severe sensorineural hearing loss; linezolid was added and continued until day 69. Repeat MRI of the spine 20 days after starting TMP/SMX demonstrated a marked decrease in the size and extent of the enhancing lesions within the cervical and lumbosacral canal compared with the previous study. MRI of the spine obtained 136 days after initiating TMP/SMX revealed resolution of all nodular enhancement in the spine (Figs. 2B, D). He completed a 24-month course of daily oral TMP/SMX. Twenty-eight months after initial resection, routine surveillance MRI revealed progression of the residual tumor in the surgical bed (Figs. 2E, F). The patient underwent a second resection and surveillance MRIs have been stable for 15 months.
DISCUSSION This child presented 2 months after a subtotal resection of a cerebellar JPA with meningismus, CSF leukocytosis, and new CNS lesions identified on MRI, which raised concerns of progression with possible metastatic dissemination. There was also concern for CNS infection. This case illustrates that the differential diagnosis for progressive CNS malignancy should include opportunistic infections when patients present atypically. The reported frequency of dissemination in pediatric LGG varies. Pollack et al7 reviewed 72 cases over a 10-year period and reported 3 cases (4%) with CNS metastasis. The multicenter study HIT-LGG 1996 accrued 1181 children and adolescents with LGG. Sixty-one patients (5.2%) were found to have tumor dissemination, with 2.8% being present at diagnosis.8 Other reviews have found similar frequencies of dissemination ranging from 4% to 10%.9,10 Various infectious and inflammatory lesions, immunemediated demyelinating or vascular disorders, and therapyinduced complications can produce lesions that mimic CNS neoplasms.11 Common examples include bacterial infections and fungal infections, which masquerade as malignancy. Fouladi and colleagues described a 16-year-old male with a history of successfully treated medulloblastoma, who Copyright
r
demonstrated asymptomatic nodular leptomeningeal enhancement of the brain and spinal cord. CSF examination disclosed Staphylococcus epidermidis meningitis. Two weeks after completion of vancomycin therapy, the original MRI imaging findings resolved.12 Menku and colleagues reported 2 cases of Nocardia asteroides brain abscess simulating brain tumor in immunocompetent patients. Both patients underwent GTR followed by antibiotic therapy.13 In addition, Damek et al14 described a case of Aspergillus mimicking tumor progression in a patient with a high-grade glioma. In our case, widespread Nocardia in the spine mimicked tumor dissemination, but the abnormal enhancement in the surgical bed reflected a true-positive site of residual neoplasm. Distinction of inflammatory disease from spread of CNS neoplasm by imaging can be difficult. Both categories of disease can present with enhancing lesions that may be cystic or solid, as well as nodular foci of enhancement, as in this example. Diffusion-weighted imaging is nearly always positive in brain abscess, but is also frequently positive in neoplasms. Because it is prone to susceptibility artifacts and has limited spatial resolution, diffusion-weighted imaging has not been commonly used for spinal imaging in children. Newer techniques have mitigated some of these problems and improved results,15,16 but both intraspinal metastatic disease and infection can be positive on diffusion-weighted imaging.16,17 No diffusion-weighted imaging was performed on the spinal lesions in this case, but the intracranial tumor was not positive. Nocardia species, a rare cause of CNS infection, present as persistent neutrophilic meningitis18 or more often, brain abscesses.6,18,19 Microbiological diagnosis of Nocardia infection is hampered by its slow growth rate (days to weeks) and similar Gram-stain appearance to other gram-positive branching rods such as Actinomyces, Streptomyces, and Mycobacterium species.20 Certain species of Nocardia, especially N. farcinica, are often resistant to third-generation cephalosporins, first-line agents for empiric treatment of CNS infections. Once appropriate antibiotics are chosen based on susceptibility data, therapy should be continued for at least 12 months because relapse rates are high.6 In conclusion, we recommend a high index of suspicion for non-neoplastic lesions, particularly infectious organisms, which may masquerade as progressive
2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jpho-online.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
483
Davis et al
J Pediatr Hematol Oncol
Volume 37, Number 6, August 2015
FIGURE 2. Sagittal CT with contrast (A) shows an enhancing nodule dorsal to the cervical cord at C4. Sagittal MR with contrast after treatment (B) shows complete resolution. Sagittal MR of the lumbar spine at presentation (C) shows multiple enhancing nodules (arrows), all of which resolve after appropriate antibiotic treatment (D). Sagittal MR of the brain with contrast before (E) and after (F) antibiotic treatment shows growth of residual tumor in the fourth ventricle operative bed. Arrows reference the enhancing portion on the corresponding MRI.
neoplasms when the clinical presentation veers from the expected clinical course. The microbiology laboratory should be alerted to incubate CSF cultures longer to allow
fastidious organisms to grow. Isolates should be sent to reference laboratories for species identification and susceptibility testing to facilitate antimicrobial selection.
484 | www.jpho-online.com Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
Volume 37, Number 6, August 2015
REFERENCES 1. Pollack IF, Claassen D, al-Shboul Q, et al. Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases. J Neurosurg. 1995;82:536–547. 2. Fisher PG, Tihan T, Goldthwaite PT, et al. Outcome analysis of childhood low-grade astrocytomas. Pediatr Blood Cancer. 2008;51:245–250. 3. Desai KI, Nadkarni TD, Muzumdar DP, et al. Prognostic factors for cerebellar astrocytomas in children: a study of 102 cases. Pediatr Neurosurg. 2001;35:311–317. 4. Torres OH, Domingo P, Pericas R, et al. Infection caused by Nocardia farcinica: case report and review. Eur J Clin Microbiol Infect Dis. 2000;19:205–212. 5. Yamada SM, Nakai E, Toyonaga S, et al. A rapidly enlarging nocardial brain abscess mimicking malignant glioma. J Nippon Med Sch. 2005;72:308–311. 6. Mamelak AN, Obana WG, Flaherty JF, et al. Nocardial brain abscess: treatment strategies and factors influencing outcome. Neurosurgery. 1994;35:622–631. 7. Pollack IF, Hurtt M, Pang D, et al. Dissemination of low grade intracranial astrocytomas in children. Cancer. 1994;73:2869–2878. 8. von Hornstein S, Kortmann RD, Pietsch T, et al. Impact of chemotherapy on disseminated low-grade glioma in children and adolescents: report from the hit-lgg 1996 trial. Pediatr Blood Cancer. 2011;56:1046–1054. 9. Hukin J, Siffert J, Velasquez L, et al. Leptomeningeal dissemination in children with progressive low-grade neuroepithelial tumors. Neurooncology. 2002;4:253–260. 10. Perilongo G, Garre MLGiangaspero F. Low-grade gliomas and leptomeningeal dissemination: A poorly understood phenomenon. Childs Nerv Syst. 2003;19:197–203.
Copyright
r
Nocardia Infection Masquerading as Neoplasm
11. Santosh V, Mahadevan A, Chickabasaviah YT, et al. Infectious lesions mimicking central nervous system neoplasms. Semin Diagn Pathol. 2010;27:122–135. 12. Fouladi M, Heideman R, Langston JW, et al. Infectious meningitis mimicking recurrent medulloblastoma on magnetic resonance imaging. Case report. J Neurosurg. 1999;91:499–502. 13. Menku A, Kurtsoy A, Tucer B, et al. Nocardia brain abscess mimicking brain tumour in immunocompetent patients: report of two cases and review of the literature. Acta Neurochir. 2004;146:411–414; discussion 414. 14. Damek DM, Lillehei KO, Kleinschmidt-DeMasters BK. Aspergillus terreus brain abscess mimicking tumor progression in a patient with treated glioblastoma multiforme. Clin Neuropathol. 2008;27:400–407. 15. Andre JB, Zaharchuk G, Saritas E, et al. Clinical evaluation of reduced field-of-view diffusion-weighted imaging of the cervical and thoracic spine and spinal cord. Am J Neuroradiol. 2012;33:1860–1866. 16. Hayes LL, Jones RA, Palasis S, et al. Drop metastases to the pediatric spine revealed with diffusion-weighted MR imaging. Pediatr Radiol. 2012;42:1009–1013. 17. Moritani T, Kim J, Capizzano AA, et al. Pyogenic and nonpyogenic spinal infections: emphasis on diffusion-weighted imaging for the detection of abscesses and pus collections. Br J Radiol. 2014;87:1041. 18. Al-Tawfiq JA, Al-Khatti AA. Disseminated systemic Nocardia farcinica infection complicating alefacept and infliximab therapy in a patient with severe psoriasis. Int J Infect Dis. 2010;14:e153–e157. 19. Bross JE, Gordon G. Nocardial meningitis: case reports and review. Rev Infect Dis. 1991;13:160–165. 20. Beaman BL, Beaman L. Nocardia species: host-parasite relationships. Clin Microbiol Rev. 1994;7:213–264.
2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jpho-online.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
485
AND
LABORATORY OBSERVATIONS
Nocardia farcinica Meningitis Masquerading as Central Nervous System Metastasis in a Child With Cerebellar Pilocytic Astrocytoma Jennifer Davis, DO,* Andrew J. Kreppel, MD,w Rebecca C. Brady, MD,z Blaise Jones, MD,y Charles B. Stevenson, MD,8 Maryam Fouladi, MD,* and Trent R. Hummel, MD*
Summary: Juvenile pilocytic astrocytoma, the most common pediatric central nervous system (CNS) neoplasm, characteristically displays an indolent growth pattern and rarely demonstrates metastatic dissemination. Reports of infections mimicking CNS metastatic disease are also rare and can impact treatment. We report the youngest known case of a child with a CNS Nocardia farcinica infection who had a known cerebellar pilocytic astrocytoma, review other infections that may masquerade as CNS neoplasms, and discuss N. farcinica CNS infections. Key Words: CNS tumors, infectious disease, low-grade gliomas
(J Pediatr Hematol Oncol 2015;37:482–485)
L
ow-grade gliomas (LGG) account for the majority of central nervous system (CNS) tumors in children and comprise a heterogenous set of tumors. Juvenile pilocytic astrocytoma (JPA) is a WHO grade I glioma that typically does not exhibit aggressive clinical behavior nor undergo malignant transformation. Surgical gross total resection (GTR) is the most consistent prognostic factor for prolonged overall survival.1 Five-year overall survival after GTR is 90%,2,3 with dissemination rarely reported.1 Despite LGG being the commonest of childhood CNS tumors, the incidence of postresection CNS infection in astrocytoma is quite rare, with only 1 such pediatric case discussed previously in the literature. Infectious agents may enter the CNS either through hematogenous spread or direct inoculation, following trauma or surgery. Nocardia species live in soil and water and may enter the CNS by either route, leading to meningitis or brain abscesses. Certain species, especially Nocardia farcinica, have a predilection for dissemination to the CNS from extraneural sites. In 2000, Torres et al4 reviewed 118 cases of N. farcinica infection; 30% involved the CNS. Although Nocardia brain abscesses account for only about 2% of all brain abscesses,5
Received for publication September 17, 2014; accepted April 21, 2015. From the Divisions of *Oncology, Cancer and Blood Diseases Institute; 8Pediatric Neurosurgery; Departments of zPediatrics, Division of Infectious Diseases; yRadiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; and wDepartment of Pediatrics, Division of Infectious Diseases, University of Illinois at Chicago, Chicago, IL. The authors declare no conflict of interest. Reprints: Trent R. Hummel, MD, Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, MLC 7015, Cincinnati, OH 45229 (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
their early recognition is important because reported mortality rates range from 30% to 90%.6
CASE REPORT A 4-year-old boy with a subtotally resected cerebellar JPA diagnosed 1 month prior was admitted with a 1-week history of fever and diarrhea to another institution. Evaluations there included a stable computed tomography (CT) scan of the brain and cerebrospinal fluid (CSF) examination with a marked leukocytosis of >3000/mcL. He received 4 days of empiric antibiotics for meningitis. Antibiotics were discontinued when CSF cultures were reported to be negative and he was prescribed steroids for presumed chemical meningitis. Approximately 10 days after discharge, he presented again to the outside institution with fever and diarrhea. He was diagnosed with a rotavirus infection and discharged home. He was subsequently admitted for a third time to the same facility, nearly 2 months after diagnosis, with symptoms of lethargy, nausea, fever, and meningismus and was transferred to our institution. Initial laboratory findings at our institution included a hemoglobin of 11.5 g/L, leukocyte count of 12.4k/mcL with 68% polymorphonuclear cells (PMNs), 9% monocytes, and 22% lymphocytes. Lumbar puncture revealed cloudy CSF with 12 RBC/ mcL and 1156 WBC/mcL (74% PMNs, 5% lymphocytes, and 21% monocytes). Glucose was 27 mg/dL and protein was 220 mg/dL. Initial Gram stain was positive for WBC but no organisms were seen. CSF polymerase chain reactions were negative for enterovirus, CMV, EBV, and HSV. Cryptococcal antigen was negative and fungal and AFB cultures showed no growth. Empiric vancomycin and ceftriaxone were initiated. The patient’s tumor pathology was reviewed and exhibited biphasic growth pattern, a clear astrocytic morphology diffusely positive for GFAP and negative for IDH1 with a proliferation index of 6%, consistent with a JPA. Blood and CSF cultures remained negative but the child continued to have fevers (Fig. 1). MRI performed on hospital day 3 showed abnormal signal and enhancement in previous resection bed suspicious for residual tumor. On hospital day 6, the CSF culture at our institution grew a beaded, branching, weakly gram-positive rod that was subsequently determined to be modified acid fast positive, concerning for Nocardia species. The child was not able to tolerate oral or nasogastric administration of trimethoprim/sulfamethoxazole (TMP/SMX) and intravenous TMP/SMX was in short supply. Therefore, intravenous amikacin was added to ceftriaxone to provide combination therapy for presumed Nocardia CNS infection and vancomycin was discontinued. Because of persistent fevers on day 17 of admission, CT scans of the neck, chest, abdomen, and pelvis were obtained. The CT of the neck revealed new nodular areas of enhancement along the surface of the cervical cord centered at the C2 and C4 levels (Fig. 2A). Subsequent MRI of brain and spine revealed enhancing nodules seen along the dorsal aspect of the cord at C2, C3-C4, C6C7, and T4-T5, as well as more mass-like enhancement surrounding the conus (Fig. 2C).
482 | www.jpho-online.com J Pediatr Hematol Oncol Volume 37, Number 6, August 2015 Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
Volume 37, Number 6, August 2015
Nocardia Infection Masquerading as Neoplasm
FIGURE 1. Gray vertical bars demonstrate trend in cerebrospinal fluid WBC: initial WBC/mcL = 1156, day 59 WBC/mcL = 12. Gray line demonstrates fever trend. Day 27 (arrow) is first day without a fever. Bars below x-axis represent antimicrobial courses: Vanc (vancomycin) days 1 to 10, Amikacin days 10 to 56, Linezolid days 56 to 69, Ceftriaxone days 1 to 16, Bactrim (trimethorprim-sulfamethoxazole) day 16 to 24 months. On hospital day 16, the CSF culture isolate was identified as N. farcinica with the following minimal inhibitory concentrations in mcg/mL with S = susceptible and R = resistant: amikacin 1 S, TMP/SMX 0.25 S, linezolid 4 S, and ceftriaxone >64 R. Ceftriaxone was discontinued and intravenous TMP/SMX was started despite the national shortage to provide coverage against the resistance pattern of N. farcinica reported in the literature. Amikacin was discontinued on hospital day 56 when the child developed severe sensorineural hearing loss; linezolid was added and continued until day 69. Repeat MRI of the spine 20 days after starting TMP/SMX demonstrated a marked decrease in the size and extent of the enhancing lesions within the cervical and lumbosacral canal compared with the previous study. MRI of the spine obtained 136 days after initiating TMP/SMX revealed resolution of all nodular enhancement in the spine (Figs. 2B, D). He completed a 24-month course of daily oral TMP/SMX. Twenty-eight months after initial resection, routine surveillance MRI revealed progression of the residual tumor in the surgical bed (Figs. 2E, F). The patient underwent a second resection and surveillance MRIs have been stable for 15 months.
DISCUSSION This child presented 2 months after a subtotal resection of a cerebellar JPA with meningismus, CSF leukocytosis, and new CNS lesions identified on MRI, which raised concerns of progression with possible metastatic dissemination. There was also concern for CNS infection. This case illustrates that the differential diagnosis for progressive CNS malignancy should include opportunistic infections when patients present atypically. The reported frequency of dissemination in pediatric LGG varies. Pollack et al7 reviewed 72 cases over a 10-year period and reported 3 cases (4%) with CNS metastasis. The multicenter study HIT-LGG 1996 accrued 1181 children and adolescents with LGG. Sixty-one patients (5.2%) were found to have tumor dissemination, with 2.8% being present at diagnosis.8 Other reviews have found similar frequencies of dissemination ranging from 4% to 10%.9,10 Various infectious and inflammatory lesions, immunemediated demyelinating or vascular disorders, and therapyinduced complications can produce lesions that mimic CNS neoplasms.11 Common examples include bacterial infections and fungal infections, which masquerade as malignancy. Fouladi and colleagues described a 16-year-old male with a history of successfully treated medulloblastoma, who Copyright
r
demonstrated asymptomatic nodular leptomeningeal enhancement of the brain and spinal cord. CSF examination disclosed Staphylococcus epidermidis meningitis. Two weeks after completion of vancomycin therapy, the original MRI imaging findings resolved.12 Menku and colleagues reported 2 cases of Nocardia asteroides brain abscess simulating brain tumor in immunocompetent patients. Both patients underwent GTR followed by antibiotic therapy.13 In addition, Damek et al14 described a case of Aspergillus mimicking tumor progression in a patient with a high-grade glioma. In our case, widespread Nocardia in the spine mimicked tumor dissemination, but the abnormal enhancement in the surgical bed reflected a true-positive site of residual neoplasm. Distinction of inflammatory disease from spread of CNS neoplasm by imaging can be difficult. Both categories of disease can present with enhancing lesions that may be cystic or solid, as well as nodular foci of enhancement, as in this example. Diffusion-weighted imaging is nearly always positive in brain abscess, but is also frequently positive in neoplasms. Because it is prone to susceptibility artifacts and has limited spatial resolution, diffusion-weighted imaging has not been commonly used for spinal imaging in children. Newer techniques have mitigated some of these problems and improved results,15,16 but both intraspinal metastatic disease and infection can be positive on diffusion-weighted imaging.16,17 No diffusion-weighted imaging was performed on the spinal lesions in this case, but the intracranial tumor was not positive. Nocardia species, a rare cause of CNS infection, present as persistent neutrophilic meningitis18 or more often, brain abscesses.6,18,19 Microbiological diagnosis of Nocardia infection is hampered by its slow growth rate (days to weeks) and similar Gram-stain appearance to other gram-positive branching rods such as Actinomyces, Streptomyces, and Mycobacterium species.20 Certain species of Nocardia, especially N. farcinica, are often resistant to third-generation cephalosporins, first-line agents for empiric treatment of CNS infections. Once appropriate antibiotics are chosen based on susceptibility data, therapy should be continued for at least 12 months because relapse rates are high.6 In conclusion, we recommend a high index of suspicion for non-neoplastic lesions, particularly infectious organisms, which may masquerade as progressive
2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jpho-online.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
483
Davis et al
J Pediatr Hematol Oncol
Volume 37, Number 6, August 2015
FIGURE 2. Sagittal CT with contrast (A) shows an enhancing nodule dorsal to the cervical cord at C4. Sagittal MR with contrast after treatment (B) shows complete resolution. Sagittal MR of the lumbar spine at presentation (C) shows multiple enhancing nodules (arrows), all of which resolve after appropriate antibiotic treatment (D). Sagittal MR of the brain with contrast before (E) and after (F) antibiotic treatment shows growth of residual tumor in the fourth ventricle operative bed. Arrows reference the enhancing portion on the corresponding MRI.
neoplasms when the clinical presentation veers from the expected clinical course. The microbiology laboratory should be alerted to incubate CSF cultures longer to allow
fastidious organisms to grow. Isolates should be sent to reference laboratories for species identification and susceptibility testing to facilitate antimicrobial selection.
484 | www.jpho-online.com Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
Volume 37, Number 6, August 2015
REFERENCES 1. Pollack IF, Claassen D, al-Shboul Q, et al. Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases. J Neurosurg. 1995;82:536–547. 2. Fisher PG, Tihan T, Goldthwaite PT, et al. Outcome analysis of childhood low-grade astrocytomas. Pediatr Blood Cancer. 2008;51:245–250. 3. Desai KI, Nadkarni TD, Muzumdar DP, et al. Prognostic factors for cerebellar astrocytomas in children: a study of 102 cases. Pediatr Neurosurg. 2001;35:311–317. 4. Torres OH, Domingo P, Pericas R, et al. Infection caused by Nocardia farcinica: case report and review. Eur J Clin Microbiol Infect Dis. 2000;19:205–212. 5. Yamada SM, Nakai E, Toyonaga S, et al. A rapidly enlarging nocardial brain abscess mimicking malignant glioma. J Nippon Med Sch. 2005;72:308–311. 6. Mamelak AN, Obana WG, Flaherty JF, et al. Nocardial brain abscess: treatment strategies and factors influencing outcome. Neurosurgery. 1994;35:622–631. 7. Pollack IF, Hurtt M, Pang D, et al. Dissemination of low grade intracranial astrocytomas in children. Cancer. 1994;73:2869–2878. 8. von Hornstein S, Kortmann RD, Pietsch T, et al. Impact of chemotherapy on disseminated low-grade glioma in children and adolescents: report from the hit-lgg 1996 trial. Pediatr Blood Cancer. 2011;56:1046–1054. 9. Hukin J, Siffert J, Velasquez L, et al. Leptomeningeal dissemination in children with progressive low-grade neuroepithelial tumors. Neurooncology. 2002;4:253–260. 10. Perilongo G, Garre MLGiangaspero F. Low-grade gliomas and leptomeningeal dissemination: A poorly understood phenomenon. Childs Nerv Syst. 2003;19:197–203.
Copyright
r
Nocardia Infection Masquerading as Neoplasm
11. Santosh V, Mahadevan A, Chickabasaviah YT, et al. Infectious lesions mimicking central nervous system neoplasms. Semin Diagn Pathol. 2010;27:122–135. 12. Fouladi M, Heideman R, Langston JW, et al. Infectious meningitis mimicking recurrent medulloblastoma on magnetic resonance imaging. Case report. J Neurosurg. 1999;91:499–502. 13. Menku A, Kurtsoy A, Tucer B, et al. Nocardia brain abscess mimicking brain tumour in immunocompetent patients: report of two cases and review of the literature. Acta Neurochir. 2004;146:411–414; discussion 414. 14. Damek DM, Lillehei KO, Kleinschmidt-DeMasters BK. Aspergillus terreus brain abscess mimicking tumor progression in a patient with treated glioblastoma multiforme. Clin Neuropathol. 2008;27:400–407. 15. Andre JB, Zaharchuk G, Saritas E, et al. Clinical evaluation of reduced field-of-view diffusion-weighted imaging of the cervical and thoracic spine and spinal cord. Am J Neuroradiol. 2012;33:1860–1866. 16. Hayes LL, Jones RA, Palasis S, et al. Drop metastases to the pediatric spine revealed with diffusion-weighted MR imaging. Pediatr Radiol. 2012;42:1009–1013. 17. Moritani T, Kim J, Capizzano AA, et al. Pyogenic and nonpyogenic spinal infections: emphasis on diffusion-weighted imaging for the detection of abscesses and pus collections. Br J Radiol. 2014;87:1041. 18. Al-Tawfiq JA, Al-Khatti AA. Disseminated systemic Nocardia farcinica infection complicating alefacept and infliximab therapy in a patient with severe psoriasis. Int J Infect Dis. 2010;14:e153–e157. 19. Bross JE, Gordon G. Nocardial meningitis: case reports and review. Rev Infect Dis. 1991;13:160–165. 20. Beaman BL, Beaman L. Nocardia species: host-parasite relationships. Clin Microbiol Rev. 1994;7:213–264.
2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jpho-online.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
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