bs_bs_banner

Neuropathology 2015; 35, 497–501

doi:10.1111/neup.12207

N eur opatho l o g y E d u ca t i o n

A 15-year-old girl with a rapidly progressing tumor-like lesion Benison Keung1 and Anita Huttner2 1

Department of Neurology, Yale-New Haven Hospital, Yale University School of Medicine and 2Yale-New Haven Hospital, Yale Pathology, New Haven, Connecticut, USA

CLINICAL COURSE A 15-year-old girl presented with headache and falls. She has a history of attention deficit hyperactivity disorder and stereotypical migraine headaches that were bifrontal, aching in quality and associated with photophobia. Two months prior to presentation, she developed a different headache that remained constant, poorly responsive to zolmitriptan and tramadol, and was associated with fatigue, blurry vision and falls. These symptoms compelled her to stop participating in track activities at school. A MRI scan of the brain without gadolinium revealed a small focal hyperintense periventricular lesion on fluid-attenuated inversion recovery (FLAIR) sequence, located lateral to the posterior horn of the right lateral ventricle (Fig. 1A). Sixteen days later, a follow-up MRI brain study, now with gadolinium, showed interval enlargement of the lesion to 14 mm, which was well circumscribed, ring enhancing, and demonstrated hypointense T1 and hyperintense FLAIR signal characteristics (Fig. 1B–C). Two days following this scan, her headache became intolerable and so she presented to the emergency department of our institution. Examination revealed left hemianopsia, left arm and leg ataxia, and brisk left patellar reflex. Lumbar puncture opening pressure was 16.5 cm of water. CSF analysis showed protein 15 mg/dL, glucose 52 mg/dL, and three nucleated cells. CSF Gram stain and bacterial cultures were unremarkable. CSF and serum oligoclonal band studies were being processed. However, since neoplasm was highly suspected and the rapid radiographic growth of the lesion paralleled clinical deterioration, a craniotomy

Correspondence: Benison Keung, MD, Department of Neurology, Yale-New Haven Hospital, Yale University School of Medicine, PO Box 208018, New Haven, CT 06520, USA. Email: benison.keung@ yale.edu Received 10 November 2015; revised and accepted 20 February 2015; published online 25 May 2015.

© 2015 Japanese Society of Neuropathology

with biopsy was performed before oligoclonal studies were completed. Intraoperative frozen sections of numerous biopsies that were taken from the lesion revealed reactive astrocytes and areas of necrosis. The lesion was then fully resected.

NEUROPATHOLOGICAL FINDINGS In situ, the lesion was soft, friable and appeared brown. On HE and Luxol fast blue stains, there was a sharp transition between normal and disease-appearing white matter (Fig. 2A,B). CD68 testing for macrophages was positive within areas of demyelination (Fig. 2C). The macrophages contained myelin debris within their cytoplasm with Luxol fast blue staining (Fig. 2D). Silver staining demonstrated relative axon sparring (Fig. 2E). Occasional Creutzfeldt cells were seen (Fig. 2F). Features of CNS tumors, such as nuclear atypical, cellular pleomorphism and mitotic figures, were not seen.

DIAGNOSIS Tumefactive multiple sclerosis.

DISCUSSION Multiple sclerosis (MS) is an inflammatory disease of the CNS characterized by demyelinating plaques that occur over space (throughout the brain and cervical and thoracic spines) and time (chronic course). The incidence of MS is 3.6/100 000 in women and 2.0/100 000 in men.1 About 3–5% of all MS patients will suffer their first attack in childhood.2 The disease course can vary (i.e., relapsingremitting, primary and secondary progressive, clinically isolated syndrome) but for the most part MS is a progressive disorder that results in neurodegeneration. The initial description by Charcot in 1868 of multifocal demyelinating plaques in the brain and spinal cord remains the principal pathological feature. However, different variations on the

498

B Keung and A Huttner

A

B

C

Fig. 1 MRI of the lesion. On fluid-attenuated inversion recovery sequence of the initial study without gadolinium, a small focal hyperintense lesion located lateral to the posterior horn of the right lateral ventricle is seen (A, arrow). On the same sequence from the repeat study with gadolinium performed 16 days later, the lesion appears to have enlarged. It is ring-enhancing on the T1 sequence with gadolinium, suggesting inflammation (C).

pattern of demyelination have been observed, for example Balo’s concentric MS, Marburg MS and tumefactive MS.3 The plaques of tumefactive MS are large, >2 cm areas of demyelination surrounded by edema and can mimic space-occupying lesions, such as tumors and abscesses. Initially, they were thought to be unifocal and have a monophasic course.4 However, recent studies have shown

that they can be accompanied by smaller multifocal lesions and are a manifestation of or can progress to relapsing-remitting MS.5,6 They can affect any part of the brain but the vast majority of them are supratentorial with frontal and parietal white matter being the most commonly affected sites.6 The area affected and the size of the plaque determines the clinical presentation. Motor, © 2015 Japanese Society of Neuropathology

Pediatric tumefactive MS

A

C

E

499

B

D

F

Fig. 2 Histological sections of the tumefactive demyelinating lesion. The top panels show a low-power view of the lesion in the sections stained with HE (A) and Luxol fast blue (LFB) in (B); scale bar = 1 mm. It demonstrates the typical sharp demarcation between the area of demyelination and uninvolved brain. (C) A high-power view of CD68-stained macrophages within demyelination; scale bar = 50 μm. (D) Demonstrates macrophages containing small LFB-stained myelin fragments within their cytoplasm; scale bar = 50 μm. (E) The silver impregnation of the area of demyelination shows partial preservation of axons; scale bar = 100 μm. (F) HE section is highlighting a Creutzfeldt cell (arrow head); scale bar = 20 μm.

sensory, and cognitive impairments are frequent.6 Additionally, symptoms mimicking mass lesions, such as headaches, nausea, and seizures, can occur. Tumefactive plaques commonly exhibit ring enhancement, either closed or open, on MRI gadolinium-enhanced T1-weighted sequences. They appear iso- or hypointense on non-contrast studies. MRI T2-weighted sequences will commonly show surrounding vasogenic edema. Although most tumefactive lesions are ring enhancing, not all demyelinating plaques are ring enhancing, The most common enhancing pattern of MS is nodular.7 Additionally, a case series of 221 patients with ring-enhancing lesions on MRI © 2015 Japanese Society of Neuropathology

showed that only 6% were diagnosed with MS and 40% and 30% were with gliomas and metastases, respectively.8 Because of the clinical and radiographic resemblance of tumefactive lesions to life-threatening diseases, diagnosing tumefactive MS can be challenging. The overall diagnosis of MS requires the dissemination of demyelinating lesions in space and time.The most recent revision of the McDonald criteria from 2010 provides the framework to establish a diagnosis based on the number of attacks or relapses, MRI findings and other clinical information.9 The diagnosis of tumefactive MS may be readily achieved if a diagnosis of MS is already present. In cases

500 where the tumefactive lesion presents itself as the first neurologic event, tumefactive MS is the likely diagnosis if there are smaller demyelinating plaques associated with the larger lesion. The diagnostic challenge arises if there is only one solitary tumefactive lesion present without any associated smaller plaques, or if a history of MS is not already established. Biopsies are frequently necessary. The decision to biopsy is always difficult but should be guided by the goal to confidently determine the exact diagnosis in order to provide the appropriate and correct treatment, especially if the history and imaging findings do not help distinguish among different possible diseases. The pathological findings of tumefactive plaques resemble those of typical MS plaques. These features include confluent demyelination on Luxol fast blue stains, foamy macrophages with myelin debris, axonal sparring, lymphocytic infiltrates, reactive astrocytes and gliosis.3 Crueztfeldt cells, which are large astrocytes with fragmented nuclear inclusions, may be seen.10 They are relatively nonspecific but are typically observed in MS or in reactive conditions. The presence of hypercellularity, occasional necrosis, and the misinterpretation of Crueztfeldt cells to be mitotic figures can mislead the assessment to neoplasm. The distinct pathogenesis of tumefactive MS is unknown. However, the largest case series on tumefactive MS suggests that it is part of the spectrum of MS, rather than a clinical variant or an intermediate state between MS and acute disseminated encephalomyelitis, a postinfectious form of demyelination.6 Regardless of the cause, acute tumefactive MS is treated like any other acute MS attack, with corticosteroids. In the setting of treatment failure, intravenous immunoglobulin and plasma exchange can be tried. Our case represents the pitfalls in diagnosing tumefactive MS. Among all of our patient’s neurologic issues, the most significant chief complaint was headache. The size of the lesion on two MRIs was not large enough nor had any mass effect to produce the degree of severe pain that she experienced. It is likely that her stereotypical migraines evolved into a different pattern with the presence of the lesion.Additionally, non-specific white matter lesions on FLAIR-weighted images, such as the one on her initial MRI, can be seen in chronic migraine patients. Nevertheless, the rate of growth of the lesion between the two MRI scans 16 days apart and the appearance of ring enhancement surrounding the lesion were alarming signs and suggested a fast-growing neoplasm, such as glioblastoma multiforme. However, her age and the relative lack of vasogenic edema on MRI would be atypical for this. CSF analysis was unremarkable and oligoclonal band study results were not available at the time of surgery. The decision for biopsy was based on the patient’s clinical deterio-

B Keung and A Huttner ration and the need to firmly establish a diagnosis to institute prompt therapy. Frozen sections of the biopsy did reveal hypercellularity, reactive astrocytes and necrosis, which are seen in both tumefactive MS and malignant neoplasm. These findings prompted resection of the entire lesion. Eventually, Luxol fast blue staining showed significant axonal sparing, demyelination, myelin-laden macrophages, and Creutzfeldt cells, consistent with a demyelinating plaque and not neoplasm. Oligoclonal band study results returned positive in the CSF a week after resection. The diagnosis may have been achieved earlier if this result was more readily available. The patient did not undergo steroid therapy as the tumefactive lesion was removed. She did not suffer any new neurologic issues from the resection. To date, she has not had a relapse of her inflammatory demyelinating disease and her exam is normal. This case is similar to many other cases reported in the literature wherein a diagnosis of tumefactive MS was achieved following a challenging diagnostic course. Increased awareness of this unique inflammatory demyelinating disease could help limit the need for complicated and invasive evaluations.

DISCLOSURES The authors have no disclosures to report.

REFERENCES 1. Alonso A, Hernán M. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology 2008; 71: 129–135. 2. Renoux C, Vukusic S, Confavreux C. The natural history of multiple sclerosis with childhood onset. Clin Neurol Neurosurg 2008; 110: 897–904. 3. Hu W, Lucchinetti CF. The pathological spectrum of CNS inflammatory demyelinating diseases. Semin Immunopathol 2009; 31: 439–453. 4. Kepes J. Large focal tumor-like demyelinating lesions of the brain: intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients. Ann Neurol 1993; 33: 18–27. 5. Dastgir J, DiMario F. Acute tumefactive demyelinating lesions in a pediatric patient with known diagnosis of multiple sclerosis: review of the literature and treatment proposal. J Child Neurol 2009; 24: 431–437. 6. Lucchinetti CF, Gavrilova RH, Metz I et al. Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis. Brain 2008; 131: 1759– 1775. 7. He J, Grossman RI, Mannon LJ. Enhancing patterns in multiple sclerosis: evolution and persistence. AJNR Am J Neuroradiol 2001; 22: 664–669. © 2015 Japanese Society of Neuropathology

Pediatric tumefactive MS 8. Schwartz KM, Erickson BJ, Lucchinetti C. Pattern of T2 hypointensity associated with ring-enhancing brain lesions can help to differentiate pathology. Neuroradiology 2006; 48: 143–149. 9. Polman CH, Reingold SC, Banwell B et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292–302.

© 2015 Japanese Society of Neuropathology

501 10. Creutzfeldt HG. Zur Frage der sogenannten akuten multiplen Sklerose (Encephalomyelitis disseminate non purulenta scleroticans subacuta). Arch Psychiatr Nervenkr 1923; 68: 485–517.

A 15-year-old girl with a rapidly progressing tumor-like lesion.

A 15-year-old girl with a rapidly progressing tumor-like lesion. - PDF Download Free
702KB Sizes 2 Downloads 9 Views