<%server.execute "isdev.asp"%> Isolated langerhans cell histiocytosis masquerading as intradural extramedullary meningioma: Review on histiocytic disorders of spine Singh S, Kumar A, Pandey S, Kumar R, Singh I, Kumari N - J Pediatr Neurosci
home : about us : ahead of print : current issue : archives search instructions : subscriptionLogin 
Users online: 1122      Small font sizeDefault font sizeIncrease font size Print this page Email this page

  Table of Contents    
Year : 2019  |  Volume : 14  |  Issue : 1  |  Page : 46-51

Isolated langerhans cell histiocytosis masquerading as intradural extramedullary meningioma: Review on histiocytic disorders of spine

1 Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India
2 Department of MDM Hospital and Medical College, Jodhpur, Rajasthan, India
3 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India

Date of Web Publication18-Jun-2019

Correspondence Address:
Prof. Raj Kumar
Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014, Uttar Pradesh
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JPN.JPN_72_18

Rights and Permissions



The histiocytic disorders are pathological diagnosis and rarely affects spine. The spinal involvement is characterized by lytic lesions and painful symptoms. Isolated intradural extramedullary involvement is rare presentation. A 15-year-old female patient presented with nontraumatic cervical compressive myelopathy and was operated electively with preoperative diagnosis of meningioma. The histopathology was surprisingly Langerhans cell histiocytosis. In lineage of histiocytic development, the Langerhans cells develop into matured dendritic cells and lose its Birbeck granules and CD1a antigenicity. With the understanding of histiocyte lineage system, the disorders concerned with central nervous system are classified into dendritic cell disorders and macrophages-related disorders. In this article, we have discussed on histiocytic disorders of central nervous system and management guidelines in case one comes across such histopathology.

Keywords: Dendritic cell disorders, Erdheim–Chester disease, hemophagocytic lymphohistiocytosis, juvenile xanthogranuloma, Langerhans cell histiocytosis, Rosai–Dorfman disease

How to cite this article:
Singh S, Kumar A, Pandey S, Kumar R, Singh I, Kumari N. Isolated langerhans cell histiocytosis masquerading as intradural extramedullary meningioma: Review on histiocytic disorders of spine. J Pediatr Neurosci 2019;14:46-51

How to cite this URL:
Singh S, Kumar A, Pandey S, Kumar R, Singh I, Kumari N. Isolated langerhans cell histiocytosis masquerading as intradural extramedullary meningioma: Review on histiocytic disorders of spine. J Pediatr Neurosci [serial online] 2019 [cited 2022 Dec 9];14:46-51. Available from: https://www.pediatricneurosciences.com/text.asp?2019/14/1/46/260620

   Introduction Top

“Histiocytic disorder” is the generalized term used for a group of diseases with a common pathological finding of “abnormal proliferation of macrophages or dendritic cells.” This group includes Langerhans cell histiocytosis (LCH), Erdheim–Chester disease (ECD), Juvenile xanthogranuloma, Rosai–Dorfman disease (RDD) and hemophagocytic lymphohistiocytosis. The rarity of literature on histiocytic disorders at central nervous system (CNS) location leaves a management dilemma when one comes across such pathology. Although an isolated eosinophilic granuloma (EG) involving cervical spine has been reported earlier, it is extremely uncommon for LCH presenting isolated in cervical spine and that too at “intradural” location. Herein, we report a case of isolated cervical intradural extramedullary LCH, masquerading as meningioma, in an elderly female patient presented with a history of progressive spastic quadriparesis. To the best of our knowledge, this is the first such case reported in English literature from India.

   Case Example Top

A 15-year-old girl was referred to our side with a history of progressive spastic quadriparesis for 2 months. On examination, tone was increased in all four limbs with upper limb MAS grade II and grade III in lower limb. Power was 0–1/5 in all four limbs. Deep tendon reflexes were exaggerated at all joints. Superficial abdominal reflexes were absent in all quadrants and plantars were bilateral extensor. There was graded sensory loss below C4 spinous process from 20% to 80% with both joint position and vibration sense. On magnetic resonance imaging (MRI), there was a 3×3.5cm ventrally placed intradural extramedullary dural-based mass lesion with loss of cerebrospinal fluid (CSF) column [Figure 1]A. The lesion was more toward left and pushing spinal cord toward right side. The lesion showed homogenous contrast enhancement with dural tail [Figure 1]B; no diffusion restriction was demonstrated. There was no evidence of bony involvement or paraspinal muscle intensity changes. Considering a clinicoradiological diagnosis of intradural meningioma, patient was planned for elective surgery following routine investigation. C4-5 laminectomy and C3 partial laminectomy were performed. Dura was tense; hence, denticulate ligament was divided following dural incision. After opening the dura linearly, lateral cuts were made. To our surprise, the lesion was soft, friable, and mildly vascular with no dural attachment contrary to what we expect in meningioma. The tumor was highly suckable. Total excision was performed. The squash was benign mesenchymal pathology. Patient had improvement in spasticity in postoperative period but power remained unchanged. The histopathological section showed histiocytes and multinucleated giant cells mixed with dense inflammatory infiltrates composed of lymphocytes, neutrophils, eosinophils, and plasma cells [Figure 2]A–C. The immunohistochemistry (IHC) showed positivity for S100 and focal positivity for CD1a [[Figure 2]D–E. The diagnosis was made LCH and we did a Tc 99 MDP bone scan in follow-up. The scan showed no evidence of any abnormal osteoblastic activity with just physiological increased tracer uptake in end growth plates. At the time of submission of report, patient is under follow-up of 2 months and is doing well, power is improved to 1–2/5, and no further treatment is needed for LCH.
Figure 1: (A) MRI of cervical spine showing a 3×3.5cm ventrally placed intradural extramedullary dural-based mass lesion with loss of CSF column. (B) Contrast-enhanced magnetic resonance imaging of cervical spine showing homogenous enhancement of dural-based lesion

Click here to view
Figure 2: (A–C) Low power view histopathology section showing histiocytes and multinucleated giant cells mixed with dense inflammatory infiltrates. (D and E) IHC showing positivity for S100 and focal positivity for CD1a

Click here to view

   Discussion Top

Histiocytes are the differentiated “end cell” of monocyte/macrophage and dendritic cell/Langerhans cell lineage. It includes sinusoidal macrophages in the spleen; alveolar macrophages in the lung; Kupffer cells in the liver; Langerhans cells of the skin; interdigitating dendritic cells of the lymph nodes, thymus, and spleen; and dendritic reticulum cells found principally in the germinal centers of lymph nodes [Figure 3]. The Langerhans cells develop from a population of CD4 and CD5 blood cells. In the lineage of histiocytic development, Langerhans cells develop into matured dendritic cells and lose its Birbeck granules and CD1a antigenicity. With understanding the pathogenesis of histiocyte lineage system, the disorders concerned with CNS are classified into two subgroups [Figure 4]. The dendritic cell disorders include LCH, ECD, and juvenile xanthogranuloma whereas macrophages-related disorders include RDD and hemophagocytic lymphohistiocytosis.
Figure 3: Schematic diagram showing origin of tissue macrophages and dendritic cells. From hematopoietic stem cells in bone marrow, the myeloid system differentiates into mast cells, megakaryocytes, neutrophils, monocytes, etc. The monocyte further differentiates into macrophages and dendritic cells. These cells cross circulatory barrier and enter various tissues for local phagocytic activity

Click here to view
Figure 4: Schematic diagram showing various histiocytic disorders with its origin and radiological characteristics

Click here to view

These histiocytic disorders are usually lower down in the list of differentials for an intradural extramedullary contrast-enhancing cervical lesions whereas meningioma being most common. It is not unusual when patients with LCH are misdiagnosed as meningioma. The meningioma usually manifest after fourth decade with prediction for females and thoracic and cervical regions being more common location. Microscopically, meningioma characteristically show typical meningothelial cells arranged in whorls and fascicles. The calcified psammomatous variant is more frequent in spinal region.[1]

A similar case reported at intradural location, but at lumbar level, was similarly misdiagnosed as meningioma before a surprising histopathology diagnosis was made.[2] In that case, Birbeck granules was also demonstrated in electron microscopy. We did not used electron microscopy because IHC is equally sensitive and specific.[3] Similarly Ming Zhu et al.[4] had also reported a case of right dural-based lesion in frontoparietal region that mimics meningioma and histopathology was LCH.[5]

Rocha-Maguey et al.[6] reported a case of intradural mass lesion at cervical level with histopathology of RDD. Their patient presented at 27 years of age contrary to the younger age of our patient. In RDD, the histiocytes consistently show S100 positivity but are CD1a negative and lack Birbeck granules. The finding of emperipolesis (lymphophagocytosis) is characteristic.[7]

The histiocytic group of disorders have wide spectrum of clinical presentation from total regression to fatal condition. They involve almost all organ including skin and eyes, usually classified as nodal and extra nodal spread. The prognosis depends on the number of nodal and extranodal involvement, age of presentation, and general condition of patient.

LCH can present as unifocal (EG), multifocal (Hand–Schuller–Christian disease) and systemic (Abt – Letterer Siwe disease). Out of these three, unifocal presentation is the most common and bone is the most common site for the same.[8] Although, the intradural extramedullary is a rare site for LCH, the disease is believed to occur in all the places where mesenchymal tissue (such as dura mater layer) is present. That is why the LCH is dural based and in our case looked like meningioma.[9]

LCH is typically diagnosed between 1 and 5 years of age, but our case unusually presented in second decade. The clinical manifestations of LCH depend on severity and the number of organs involved. It has predilection for flat bones, most commonly skull, followed by mandible and rib. The vertebral body is the most common affected part of spine in LCH. Then bony lytic lesions lead to severe pain. Apart from skull bone, CNS manifestation is found in approximately 16% of cases.[10] Diabetes insipidus is most frequent manifestation with infiltration of posterior pituitary. Neurocognitive disorders and ataxia are other manifestations.[11]

The diagnosis of LCH is mainly histopathological. Under light microscopy, the presence of large histiocytes with grooved nuclei under background of mononuclear histiocytes and multinucleated giant cells, lymphocytes, plasma cells, and neutrophils is suggestive of LCH. Immunohistochemistry shows S-100 protein and CD1a expression. The confirmatory test is electron microscopy, which reveals “tennis racket” shaped cytoplasmic inclusions within histiocytes (Birbeck granules). The latest guidelines do not include electron microscopy in diagnostic panel because they consider diagnostic value of S100 and CD1a is same as finding Birbeck granules. Radiologically, MRI shows thickened pituitary stalk or white matter changes.

The treatment options available are curettage, intralesional steroids, chemotherapy, and radiotherapy depending on size or number of lesions [Table 1]. The involvement of liver, spleen, and lymph nodes is considered as poor prognosis. Isolated disease involving functionally critical anatomical sites may justify systemic therapy.[12]
Table 1: Management of histiocytic disorders

Click here to view

The systemic therapy includes cladribine, etoposide, or radiation [Figure 5]. In addition to pituitary stalk lesions, any brain or meningeal lesion (except local reaction to a skull vault lesion) is considered as an indication for systemic therapy. The standard therapy with vinblastine and steroid or cladribine monotherapy can be effective in this situation.
Figure 5: Postoperative chemoradiotherapy plan of action in patients diagnosed with Langerhans cells histiocytosis

Click here to view

It is difficult to differentiate LCH from ECD, which is characteristically negative for CD1a and S 100 and positive for CD 68. The absence of Birbeck granules differentiates the disease from more common LCH. In ECD, diabetes insipidus is a common manifestation of CNS involvement and occurs in the form of orbital and neuroendocrine manifestations.[13],[14] In hemophagocytic lymphohistiocytosis, CD1a is negative with hyperferritinemia.[15] In RDD, head and neck involvement is seen in 22% of extranodal disease including involvement of the nasal cavity, the paranasal sinuses, the nasopharynx, submandibular glands, the parotid, the larynx, the temporal bone, the infratemporal fossa, the pterygoid fossa, the meninges, and the orbit.[16],[17]

   Conclusion Top

The histiocytic disorder should be kept as a rare differential diagnosis among dural-based lesion of spine even in females. The clues in diagnosis empower the surgeon in prognosticating and follow-up investigations. The LCH may present as isolated mass lesion without bony lytic lesions. The management is surgical excision and regular follow-up. The probability of other histiocytic disorders should be always excluded with IHC.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Pant I, Chaturvedi S. Spectrum of histopathology in spinal lesions. Astrocyte 2016;2:187-99.  Back to cited text no. 1
  [Full text]  
Tortori-Donati P, Danieli D, Meli S, Fondelli MP, Rossi A, Curri D, et al. Langerhans cell histiocytosis presenting as a lumbosacral intradural-extramedullary mass. Pediatr Radiol 1996;26:731-3.  Back to cited text no. 2
Kumar N, Sayed S, Vinayak S. Diagnosis of Langerhans cell histiocytosis on fine needle aspiration cytology: A case report and review of the cytology literature. Patholog Res Int 2011;2011:439518.  Back to cited text no. 3
Zhu M, Yu BB, Zhai JL, Sun G. Case of Langerhans cell histiocytosis that mimics meningioma in CT and MRI. J Korean Neurosurg Soc 2016;59:165-7.  Back to cited text no. 4
Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): Review of the entity. Semin Diagn Pathol 1990;7:19-73.  Back to cited text no. 5
Rocha-Maguey J, Felix-Torrontegui JA, Cabrera-López M, Gutiérrez-Castro M, Montante-Montes de Oca D. A new case of cervical intramedullary sinus histiocytosis causing paraplegia and review of the literature. Surg Neurol Int 2016;7:9.  Back to cited text no. 6
[PUBMED]  [Full text]  
Hayden A, Park S, Giustini D, Lee AY, Chen LY. Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: A systematic scoping review. Blood Rev 2016;30:411-20.  Back to cited text no. 7
Khung S, Budzik JF, Amzallag-Bellenger E, Lambilliote A, Soto Ares G, Cotten A, et al. Skeletal involvement in Langerhans cell histiocytosis. Insights Imaging 2013;4:569-79.  Back to cited text no. 8
Martin JC. Histiocytes and histiocytosis. Blood 1996;84:2840-53.  Back to cited text no. 9
Kumar YP, Agrawal J, Mohanlakshmi J, Kumar PS. Langerhans cell histiocytosis revisited: Case report with review. Contemp Clin Dent 2015;6:432-6.  Back to cited text no. 10
[PUBMED]  [Full text]  
Redhu R, Nadkarni T, Mahesh R. Diabetes insipidus associated with a thickened pituitary stalk in a case of Langerhans cell histiocytosis. J Pediatr Neurosci 2011;6:62-4.  Back to cited text no. 11
  [Full text]  
Haupt R, Minkov M, Astigarraga I, Schäfer E, Nanduri V, Jubran R, et al.; Euro Histio Network. Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years. Pediatr Blood Cancer 2013;60:175-84.  Back to cited text no. 12
Zaveri J, La Q, Yarmish G, Neuman J. More than just Langerhans cell histiocytosis: A radiologic review of histiocytic disorders. Radiographics 2014;34:2008-24.  Back to cited text no. 13
Diamond EL, Dagna L, Hyman DM, Cavalli G, Janku F, Estrada-Veras J, et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood 2014;124:483-92.  Back to cited text no. 14
Maiti TK, Gangadharan J, Mahadevan A, Arivazhagan A, Chandramouli BA, Shankar SK. Rosai-Dorfman disease presenting as cervical extradural lesion: A case report with review of literature. Neurol India 2011;59:438-42.  Back to cited text no. 15
[PUBMED]  [Full text]  
Sandoval-Sus JD, Sandoval-Leon AC, Chapman JR, Velazquez-Vega J, Borja MJ, Rosenberg S, et al. Rosai-Dorfman disease of the central nervous system: Report of 6 cases and review of the literature. Medicine (Baltimore) 2014;93:165-75.  Back to cited text no. 16
Dran G, Rasendrarijao D, Vandenbos F, Paquis P. Rosai-Dorfman disease causing spinal cord compression: Case report. Neurosurgery 2008;62:E977-8; discussion E978.  Back to cited text no. 17


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1]


Print this article  Email this article
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (2,545 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Example
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded49    
    Comments [Add]    

Recommend this journal