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|Year : 2020 | Volume
| Issue : 6 | Page : 1439-1442
Solitary Intracranial Juvenile Xanthogranuloma Masquerading as Low-Grade Glioma – A Rare Case Report
Salapathi Shanmugam1, Rajeshwari Buttannavar1, Ghosh Mitra1, Siddhartha Ghosh2
1 Department of Histopathology, Apollo Speciality Hospitals, Vanagaram, Chennai, Tamil Nadu, India
2 Department of Neurosciences, Apollo Speciality Hospitals, Vanagaram, Chennai, Tamil Nadu, India
|Date of Web Publication||19-Dec-2020|
Dr. Salapathi Shanmugam
Department of Histopathology, Apollo Speciality Hospitals, Vanagaram, Chennai, Tamil Nadu - 600 095
Source of Support: None, Conflict of Interest: None
Juvenile xanthogranuloma (JXG) is a rare, benign histiocytic disorder of young children. It is most often present with cutaneous involvement of the head, neck and trunk region. Systemic JXG causes cutaneous lesions with extracutaneous involvements frequently seen in the orbit, liver, spleen, lung, kidney and bones. Central nervous system (CNS) involvement is uncommon and is usually seen as a component of systemic disease. Isolated JXG of CNS is very rare and only few cases have been reported till date. Here we report a case of isolated solitary intracranial JXG mimicking clinically and radiologically as a low-grade glioma with no signs of cutaneous or other systemic involvement. Gross total excision of the tumour was done and final diagnosis was made by histopathological and immunohistochemical examination. CNS involvement of JXG can cause significant morbidity and mortality. These cases are usually misdiagnosed on radiology as glioma or meningioma and the diagnosis is usually made by histopathology. Surgery is the mainstay of treatment and these patients should be on long-term follow-up since the natural history of the disease is still unknown. The case is presented here for its rarity and for its clinical significance.
Keywords: Central nervous system, histiocytic disorder, isolated juvenile xanthogranuloma
Key Messages: Systemic involvement of JXG especially CNS involvement can cause significant morbidity and mortality. Primary CNS involvement is rare and can mimic radiologically and clinically as primary intracranial tumours like meningioma and gliomas. For solitary intracranial lesions complete excision is curative. The differential diagnosis includes other histiocytic neoplasms, which can be ruled out by correlating with clinicoradiological, histopathological and immunohistochemical findings.
|How to cite this article:|
Shanmugam S, Buttannavar R, Mitra G, Ghosh S. Solitary Intracranial Juvenile Xanthogranuloma Masquerading as Low-Grade Glioma – A Rare Case Report. Neurol India 2020;68:1439-42
|How to cite this URL:|
Shanmugam S, Buttannavar R, Mitra G, Ghosh S. Solitary Intracranial Juvenile Xanthogranuloma Masquerading as Low-Grade Glioma – A Rare Case Report. Neurol India [serial online] 2020 [cited 2021 Jan 22];68:1439-42. Available from: https://www.neurologyindia.com/text.asp?2020/68/6/1439/304109
Juvenile xanthogranuloma (JXG) is a benign histiocytic lesion of non-Langerhans cell histiocytes. It is commonly seen in young children. Skin is most commonly involved with a predilection for the head and neck region. However, systemic involvement occurs in approximately 4% of patients usually involving the liver, spleen, lungs, kidneys, eye, subcutaneous soft tissue, bones and central nervous system (CNS). CNS involvement is rare and is usually seen as a component of systemic disease.
| » Case Report|| |
A 8-year old boy presented with the complaint of intermittent and episodic headache since two years. Initially one episode in 3-4 months. There was no history of diurnal variation and no aggravating or relieving factors. Episodes of headache increased since last two months to about 5-6 episodes per month. It was followed by abnormal movements of right hand and lip smacking. He had absent stare during these episodes lasting for about 2-3 minutes, resolving spontaneously. He had no memory of such event postictally. The seizure episodes were preceded with sudden severe abdominal pain sometimes. On general examination the boy was conscious, oriented and afebrile. There was no pallor or icterus or lymphadenopathy. Ear, nose and throat examination was normal. CNS examination revealed normal higher mental functions with grossly intact cranial nerves. Power in all four limbs, deep tendon reflexes and gait were within normal limits with flexor bilateral plantar reflex. There were no skin lesions. The detailed clinical examination of respiratory, cardiovascular system and abdomen was within normal limits. Magnetic resonance imaging (MRI) of brain with contrast showed a mildly hyperintense space, occupying lesion in the left temporal lobe. The lesion has caused effacement of the left temporal sulci and thickening of the gyri. Peri focal oedema was seen. The lesion measured 3.6 Õ 3.2 Õ 1.8 cm and was faintly hyperintense on T2-weighted images and hypointense on T1-weighted images. On contrast administration, the lesion showed intense heterogeneous enhancement and well-defined smooth margins. Relatively non-enhancing areas were seen in the centre of the tumour. No significant calcified or haemorrhagic areas were seen within the lesion. The tumour was abutting the surface of the temporal lobe [Figure 1]. Radiological findings were suggestive of low-grade glioma with possibilities of pleomorphic xanthoastrocytoma and ganglioglioma. There was no abnormality detected on chest X-ray, echocardiogram and abdominal ultrasound. The patient underwent left temporal craniotomy. Intraoperatively the tumour was seen to be cortical based occupying anterior middle and inferior temporal gyri extending on basi-temporal surface. Tumour was soft, greyish, suckable with moderate vascularity. There was no attachment of dura noted. Gross total resection of the lesion done and tissue was sent for histopathology examination. Histopathological findings revealed brain parenchyma with dense areas of reactive gliosis surrounding a fairly circumscribed lesion showing sheets of cells having oval, pale nuclei with focal spindling [Figure 2]. Foamy histiocyte collections with abundant lipidised cytoplasm and scattered touton type giant cells with interspersed small lymphocytes were seen. There was no significant emperipolesis or plasma cell infiltrate. There was no evidence of significant nuclear atypia or mitosis or necrosis. Perivascular lymphocytic infiltrates are also noted. There were no granulomas seen. Acid fast stain and fungal stains were negative. Luxol fast blue stain for myelin showed presence of myelin in the adjacent brain parenchyma and in gliotic areas, but absent in the lymphohistiocytic area. On immunohistochemistry (IHC), majority of the tumour cells showed strong CD68 positivity confirming the cells as histiocytes with vague S100 positivity and negativity for CD1a [Figure 3]. The lymphocytes were predominantly CD3 positive with equal population of CD4 & CD8 positive cells. GFAP was positive in the gliotic areas and negative in the circumscribed histiocytic lesional areas. Ki-67 proliferation index was low (<2%). IHC for IDH-1, p53, EMA & CD34 was negative. Based on the histopathology and IHC findings, the case was reported as juvenile xanthogranuloma. Post-operative period was uneventful. The patient is being followed up and MRI scan done after 6 months of surgery showed no evidence of any residual or recurrent tumour.
|Figure 1: MRI with contrast, sagittal & coronal sections showing a fairly circumscribed lesion in the left temporal lobe (arrows) with smooth margin, perilesional edema and heterogeneous contrast enhancement|
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|Figure 2: (a) Showing a fairly circumscribed lesion, H&E stain, 40X (b) Focal spindling of tumour cells, 100x (c) Sheets of oval shaped cells with pale nuclei, & Touton type giant cells (arrows), 400x (d) Foamy histiocyte aggregates with small lymphocytes, 400x|
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|Figure 3: IHC showing (a&b) diffuse & strong CD68 positivity, 100X & 400X (c) GFAP showing entrapped glial tissue, 100X (d) CD1a negativity, 100X|
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| » Discussion|| |
JXG was first described in 1905 by Adamson as a “congenital xanthoma multiplex”. It is clinically classified into the cutaneous form and the systemic form. Cutaneous JXG is clinically characterized by single or multiple yellow–red nodular skin lesions, commonly in the head and neck region. It is usually benign and self-limiting. Systemic JXG causes cutaneous lesions with extracutaneous involvements frequently seen in the central nervous system, liver, spleen, lung, kidneys and bones. It is rare to see a isolated solitary CNS JXG with no cutaneous lesion. Patients presenting with isolated solitary CNS JXG lesions range in age from 5 months to 15 years (median 7 years), in contrast to cutaneous JXG, which is often diagnosed in patients less than one year of age and is frequently congenital., Although the exact histogenesis of primary intracranial JXG is yet to be known, the probable sites of origin are macrophages/histiocytes in the choroid plexus and in the meninges. Other possible sites of origin have been suggested, which includes mesenchymal stem cells, dura, blood vessel walls, or from the perivascular soft tissues. The radiological characteristics of this tumour are variable and can mimic other primary intracranial tumours, such as meningioma, schwannoma, nerve sheath tumour, ependymoma, glioma, and Rosai–Dorfman disease, as well as granulomatous lesions such as neurosarcoidosis and tuberculosis., The presence of high-signal intensity on T1-weighted images and relatively low-signal intensity on T2-weighted MR images relative to the cerebral cortex, homogeneous enhancement and decreased diffusivity may suggest the possibility of JXG, and it should be included in the radiological differential diagnosis. However MRI alone is not sufficient to distinguish JXG from other intracranial tumours. Hence, most patients with isolated CNS disease undergo surgery for biopsy or tumour removal, and the diagnosis is made post-operatively by histopathological examination. The main differential diagnosis is other histiocytic neoplasms. Langerhans cell histiocytosis (LCH) is a clonal proliferation of Langerhans-type cells that express CD1a, langerin (CD207) and S100 protein. Most cases of LCH occur in individuals aged <15 years. Erdheim–Chester disease is primarily a tumour of adults (mean patient age is 53 years) may involve brain (preferentially cerebellum & brainstem) and meninges. The histiocytes will be CD68 positive and negative for CD1a & S100. Erdheim–Chester disease is typically progressive with systemic involvement, and the prognosis is poor. Rosai–Dorfman disease (RDD) commonly presents as dural mass, but can have parenchymal lesions. It may affect either paediatric or adult populations with mean patient age of 21 years. Emperipolesis with histiocytic engulfment of intact lymphocytes, plasma cells, and neutrophils is typical with plasma cell–rich inflammatory infiltrate. The neoplastic histiocytes are positive for CD68 & S100, negative for CD1a. Most cases of RDD are self-limited, and the prognosis is excellent. JXG is a histiocytic neoplastic process, whereas xanthogranulomatous reactions are secondary to chronic inflammation, haemorrhage or degeneration. These lesions are characterized by inflammatory granulation tissue with cholesterol clefts, foreign body giant cells, hemosiderin deposits and foamy macrophage (xanthoma cells) accumulation.
Sun et al. reported a case of isolated solitary intracranial JXG in an infant who presented with elevated anterior fontanel with no evidence of cutaneous or systemic disease. The tumour was excised and there was no recurrence of tumour over 6 months of follow up. Tamir et al. reported two cases of JXG in two toddlers. One of whom presented with a parietal-occipital lesion, underwent total resection with no surgical morbidity and no recurrence at 16-months follow-up. The other patient who underwent subtotal resection of a tumour extending from the left Meckel's cave and invading the cavernous sinus and left orbit with extensive cranial nerve involvement, showed tumour regrowth with leptomeningeal spread at 9-month and 12-month follow-up was managed with steroids and chemotherapy. Shenoy et al. reported a case of solitary JXG in an infant presenting as an intraspinal mass. Rare cases of malignant transformation have been reported. Orsey et al. reported a case of CNS JXG with malignant transformation who presented with JXG diffusely involving CNS. Although patient responded to initial treatment but subsequently had disseminated disease involving bone marrow and peritoneum.
The prognosis of cutaneous JXG is good as the lesions are self-resolving. Extracutaneous manifestations are rare, and the systemic form of JXG may contribute significantly to morbidity and mortality especially in CNS involvement., Currently, there is no standard treatment for solitary JXG involving the CNS because of extremely low incidence. Unlike the more commonly seen cutaneous lesions, intracranial JXG is not sensitive to medical management. If a solitary intracranial lesion without systemic involvement in symptomatic patients is confirmed, surgery seems to be the first line of treatment, which is often curative.,, Recurrence has not been reported after complete surgical removal. However, the tumours involving the spine may grow slowly without regression and gradually worsen. If intracranial lesions cannot be fully excised and are multifocal, adjuvant chemotherapy or combined chemoradiotherapy are recommended.,,, The patients should be followed up for long-term after total resection because the natural course of solitary CNS Juvenile xanthogranuloma is unknown.
In conclusion, primary intracranial JXG is a rare lesion, which is usually misdiagnosed on radiology because of its variability in radiological characteristics. Hence the diagnosis is usually made by histopathology. The lesion has a benign course and there is no standard treatment recommended. Surgery is mostly curative except in those cases which are not amenable to complete excision and require adjuvant chemotherapy or chemoradiotherapy. The patient should be followed up for long-term after complete resection because the natural course of solitary CNS xanthogranuloma is not fully known. Systemic involvement of JXG especially CNS involvement can cause significant morbidity and mortality. The case is presented here for its rarity and for its clinical significance.
We sincerely acknowledge our technical staffs, Mrs P Shivashankari, Mr R Bhuvaneshwaran, Mrs Lavanya Latha, Mrs J Rukmani, for their technical help.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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