29 Year‐Old Male with Seizure and Syncope

Clinical History

A 29 year‐old male with limited health care interactions, previously diagnosed hypertension, and history of tobacco use presented following rapid onset nausea, dizziness, blurry vision, and tremors, resulting in a syncopal episode. At the initial formal assessment, physical examination revealed no specific abnormalities. Specifically, the neurologic examination demonstrated no focal deficits. Laboratory values were within normal limits, and toxicology studies were all negative. A CT scan of the brain revealed a 1.3 cm solitary, ring‐enhancing lesion in the right temporal‐parietal region, with associated vasogenic edema.

The patient subsequently underwent a craniotomy with attempt at gross total resection, yielding a discrete, 1.4 cm intact nodular tissue fragment. Concurrent infectious disease evaluations later reported negative results.

Microscopic Pathology

Histologic examination shows a nodular tissue fragment composed of an eosinophil‐rich infiltrate admixed with histiocytes (Figure 1a). The histiocytes are characterized by grooved, reniform nuclei (Figure 1b). Histiocytic elements show diffuse, intense nuclear and cytoplasmic reactivity for S‐100 protein (Figure 1c) and for CD1a (Figure 1d).

Figure 1.

 

Diagnosis

Intracerebral Langerhans cell histiocytosis.

Discussion

Langerhans cell histiocytosis (LCH) is a dendritic cell‐related disorder that is characterized by tumor and tumor‐like masses composed of histiocytes. Cranial lesions are typically accompanied by identical extracranial foci as well 8. Previously, LCH was referred to as histiocytosis X, a group of histiocytic disorder which occurred as a clinical spectrum, ranging from solitary eosinophilic granuloma of the skull, to skull base and hypothalamic involvement with resultant diabetes insipidus (Hand‐Schüller‐Christian disease), to disseminated disease involving skin, lymph nodes, visceral organs, and rarely, the central nervous system (Abt‐Lettterer‐Siwe disease) 8. Cranial tumors typically are typically extra‐axial lytic lesions; from an osseous center, such lesions may extend to involve the axial cerebral parenchyma. Discrete CNS intra‐axial lesions are rare 2, 3, 4, 7. A case of intracerebral LCH and concurrent Erdheim‐Chester disease, a non‐Langerhans cell histiocytosis, has also been described 5.

LCH can be readily recognized on, or suggested by H&E examination, where a mixture of inflammatory cells is present; these include macrophages, lymphocytes, plasma cells, and Langerhans cells, characterized by slightly eccentric, ovoid, reniform or convoluted nuclei. Eosinophils may also be evident. The Langerhans cells should demonstrate reactivity for S‐100 protein. In order for a definitive diagnosis of LCH to be rendered, there must be either expression of CD1a, or demonstration of Birbeck granules by electron microscopy 8. Although the significance of atypica and mitotic activity is undetermined, a distinct clinical entity of malignant LCH, with cytologically malignant Langerhans cells, atypical organ involvement, and a male predominance, has been characterized 1.

The behavior of LCH is variable. Unifocal cases may spontaneously regress or require minimal intervention, such as surgery 6, 8. Multisystem disease may follow a more aggressive course, and be refractory to chemotherapy 8.

In this patient, following the diagnosis of LCH, additional body imaging revealed multiple pulmonary nodules, all measuring less than 5 mm in greatest dimension. No other sizable mass lesion, lymphadenopathy, or effusions were observed. These pulmonary findings, in consideration the intracerebral pathology, are clinically interpreted as also consistent with involvement by LCH, indicating multifocal disease.

Abstract

Langerhans cell histiocytosis (LCH), previously referred to as histiocytosis X, is a dendritic cell histiocytic tumor that demonstrates a variable spectrum of organ involvement. Clinical syndromes within this entity include eosinophilic granuloma, Hand‐Schuller‐Christian disease, Abt‐Letterer‐Siwe Disease, and Hashimoto‐Pritzker disease. Currently, it is classified on the basis of extent, such as unifocal, multifocal, or disseminated disease. LCH typically occurs in childhood and adolescence as solitary osteolytic lesions. When involving the central nervous system, it is usually either a result of extra‐axial extension from skull vault epicenters, or is restricted to the hypothalamic‐pituitary axis. Discrete intraparenchymal, intra‐axial CNS lesions are rare. This report presents a case of an intra‐axial LCH in a 29 year‐old male who, following this diagnosis, was found to have multiple pulmonary lesions on imaging, attributed to the same disease process.