Summary: A 21-year-old Caucasian woman presented with new-onset seizures
developing over a 2-week period. The patient was started on phenytoin,
but she experienced recurrent seizure episodes despite reporting
compliance with her medication regimen. A physical examination
demonstrated normal neurologic findings, while laboratory data revealed
a therapeutic phenytoin level. The patient also had a normal cardiac
echo, and an electroencephalogram found no epileptiform activity. A
lumbar puncture was unremarkable.
Primary Langerhans cell histiocytosis of the temporal lobe
A non-contrast computed tomography (CT) scan demonstrated an ill-defined
area of decreased attenuation within the left temporal lobe (Figure 1).
Post-contrast images revealed this to be a 1 × 1.1 cm rim-enhancing
lesion (Figure 1). Subsequent magnetic resonance (MR) imaging showed a
13-mm left temporal lesion that was hypointense and ring-enhancing on
T1-weighted imaging (Figures 2). The mass was hyperintense on T2 FLAIR
with extensive vasogenic edema and local mass-effect (Figure 2). CT
scans of the chest, abdomen, and pelvis were negative, and a whole-body
bone scan showed no osseus lesions. Microscopic examination of the
resected specimen demonstrated sheets of large cells with lobulated
nuclei and an immunohistochemistry profile reactive for CD1a and S100.
Electron microscopy was significant for the presence of numerous Birbeck
granules (Figure 3). These combined features were diagnostic of
Langerhans cell histiocytosis.
Langerhans cell histiocytosis (LCH) is a group of rare and diverse
disorders defined by the pathologic infiltration and proliferation of
Langerhans cells. Previously known as histiocytosis X, the disorder’s
name was changed to LCH as the primary cell involved was elucidated.
encompasses a spectrum of clinical manifestations ranging from a
solitary chronic lesion, known as an eosinophilic granuloma, to a
fulminant multisystem process called Letterer-Siwe disease. An
intermediate form, Hand-Shüller-Christian disease, is composed of the
triad of calvarial lesions, diabetes insipidus, and exophthalmos.
pathophysiology of LCH is incompletely understood, with disagreement
over whether the mechanism is a reactive or neoplastic one.1
The occurrence of spontaneous remissions and the absence of karyotypic
abnormalities support a reactive progression. On the other hand, studies
demonstrating monoclonality and response to chemotherapeutic agents
lend support to a neoplastic process.
Although the brain is often
secondarily involved in systemic disease, solitary lesions of the brain
parenchyma, outside the hypothalamic–pituitary axis, are exceedingly
rare. Only 14 cases have been reported in the literature. Including the
current patient, the median age of affected individuals is 23.2 ± 11.2
years. Males predominate, with the current case being only the fourth
female patient. Most lesions involve the temporal lobe, although some
also involve the parietal and frontal lobes. The most common presenting
complaint is seizure, with every patient reporting at least one episode.
Other common symptoms include headache and hemiparesis.
CT findings generally reveal a low-density mass, although 2 cases reported isodense2 and hyperdense3 lesions. The lesions are contrast-enhancing with either a ring or a homogenous pattern.
6 papers have described MR findings. T1-weighted images typically
demonstrate low-intensity or isointense lesions while T2-weighted images
show high-intensity lesions. In all cases except one, lesions enhanced
Definitive diagnosis always requires
histological evaluation. The diagnostic Langerhans cell (LC) is a large
mononuclear cell with a folded nucleus resembling a coffee bean. The
Birbeck granule, a trilaminar rod-like organelle with a terminal
expansion resembling a tennis racquet, is distinctive.
Immunohistochemical staining can help confirm the diagnosis with
reactivity toward the S100 and CD1a antigens.
of central nervous system (CNS) LCH has not been well studied. Although
clinical manifestations can be partially attributed to mass effect,
neurodegeneration characterized by neuronal and axonal destruction with
secondary demyelination4 has also been described.
While multisystem LCH responds to various chemotherapeutic regimens,5
the treatment of intracranial LCH is not yet well established. A
retrospective study looking at histologically documented CNS LCH
reported that localized lesions could be treated successfully with
either surgery or radiation, while multiple lesions could be controlled
with chemotherapy.6 Notably, gamma knife radiosurgery has been successful in excising a pontine lesion.7 Long-term prognosis following resection has been good, with lesions recurring in only 2 patients.7,8 No cases progressed to systemic disease.
Solitary LCH involving the cerebral hemispheres is a rare entity with
only 14 cases reported in the literature. CT findings are generally of a
contrast-enhancing, low-density mass. On MR, T1-weighted images
typically demonstrate a low-intensity or isointense lesion while
T2-weighted images show a high intensity lesion that enhances with
gadolinium. The authors recommend that LCH be considered in the
differential diagnosis when a patient presents with new-onset recurrent
seizures and suggestive radiographic findings.
- Gonzalez CL, Jaffe ES. The histiocytoses: Clinical presentation and differential diagnosis. Oncology (Williston Park). 1990;4:47-60; discussion 60, 62.
- Penar PL, Kim JH, Chyatte D. Solitary eosinophilic granuloma of the frontal lobe. Neurosurgery. 1987;21: 566-568.
- Itoh H, Waga S, Kojima T, et al. Solitary eosinophilic granuloma in the frontal lobe: Case report. Neurosurgery. 1992;30:295-298.
- Grois N, Prayer D, Prosch H, et al. Neuropathology of CNS disease in Langerhans cell histiocytosis. Brain. 2005;128(Pt 4):829-838.
- Egeler RM, de Kraker J, Voute PA. Cytosine-arabinoside, vincristine,
and prednisolone in the treatment of children with disseminated
Langerhans cell histiocytosis with organ dysfunction: Experience at a
single institution. Med Pediatr Oncol. 1993;21:265-270.
- Hund E, Steiner H, Jansen O, et al. Treatment of cerebral Langerhans cell histiocytosis. J Neurol Sci. 1999;171:145-152.
- Cagli S, Oktar N, Demirtas E. Langerhans’ cell histiocytosis of the temporal lobe and pons. Br J Neurosurg. 2004;18:174-180.
- Sivalingam S, Corkill G, Ellis WG. Focal eosinophilic granuloma of the temporal lobe. Case report. J Neurosurg. 1977;47:941-945.