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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 3  |  Issue : 2  |  Page : 72-76

10-Year Radiological Follow-Up of Multifocal Recurrent Eosinophilic Granuloma With Vertebra Plana: A Case Report and Review of Literature


1 Department of Orthopedics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
2 Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
3 Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
4 Department of Pediatrics, All Institute of Medical Sciences, New Delhi, India

Date of Web Publication16-Jul-2018

Correspondence Address:
Amit Kumar
Department of Orthopaedics, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pors.pors_10_16

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  Abstract 

Eosinophilic granuloma (EG) is the benign localized form of histiocytosis. Owing to the relative rarity of the condition, diagnosis is often delayed or missed, and many questions remain unanswered, ranging from cause and pathogenesis to therapy. Observation and immobilization are adequate for improvement of the condition in most patients. However, treatment other than simple observation is recommended in patients with symptomatic EG. This article presents a 10-year follow-up study of a 15-year-old girl with a symptomatic multifocal EG treated effectively by monitored chemotherapy and orthosis.

Keywords: Eosinophilic granuloma, langerhans cell histiocytosis, osteochondritis, osteogenesis imperfecta, tuberculosis, vertebra plana


How to cite this article:
Kumar A, Sinha S, Saraf SK, Gupta V, Rani D, Kumari J. 10-Year Radiological Follow-Up of Multifocal Recurrent Eosinophilic Granuloma With Vertebra Plana: A Case Report and Review of Literature. Paediatr Orthop Relat Sci 2017;3:72-6

How to cite this URL:
Kumar A, Sinha S, Saraf SK, Gupta V, Rani D, Kumari J. 10-Year Radiological Follow-Up of Multifocal Recurrent Eosinophilic Granuloma With Vertebra Plana: A Case Report and Review of Literature. Paediatr Orthop Relat Sci [serial online] 2017 [cited 2018 Dec 11];3:72-6. Available from: http://www.pors.co.in/text.asp?2017/3/2/72/236709


  Introduction Top


Langerhans cell histiocytosis (LCH) of the bone is a clonal proliferation of Langerhans-type histiocytes X.[1] The bones that are most commonly involved are the flat bones of skull, face, pelvis, ribs and the diaphysis of the long bones.[2] The involvement of the spine is not uncommon. Eosinophilic granuloma (EG) is the benign localized form of histiocytosis.[3] It is a relatively uncommon disease, accounting for <1% of all bone tumors, but constituting about 75% of all reported cases of LCH.[4],[5] Approximately 80% of patients present before age 10, making this a childhood disease.[6] Observation and immobilization are adequate for the improvement of the condition in most patients. However, in patients with symptomatic EG, treatment other than simple observation is recommended.[7],[8],[9],[10]

Case Report

A 5 years old girl presented in 2005, with low back pain and limp in department of paediatrics. She was admitted and investigated. On examination, she was noted to have lumbar tenderness with no neurological deficit. No deformity or limb length discrepancy was observed. All systemic findings were within normal limits. Her hemogram [Table 1] and ultrasonography reports were normal. X-ray of the lumbosacral spine [Figure 1] showed a silver dollar appearance of the L2 vertebra with type IIA collapse[11] and type IB wedge collapse of the D11 vertebra.[11] Magnetic resonance imaging of spine (MRI SPINE) [Figure 2] revealed a partial collapse of D11 and a complete collapse of L2 vertebrae without any signal alteration of the adjacent disc with a minimal indentation of the thecal sac. computer tomography (CT)-guided biopsy was advised with differential diagnosis of tuberculosis, EG, osteochondritis (Calve’s disease) and neoplasm. In the absence of facilities for biopsy, there was diagnostic dilemma. She was given antitubercular drugs, as her diagnosis was likely to be tuberculosis. Bed rest was recommended and orthotic support was given. She continued Antitubercular drugs (ATT) for 8 months, with no relief in her symptoms. In June 2006, she sustained a fracture of the proximal ulna of the right side. X-ray [Figure 3] showed a well-defined expansile lytic lesion in the proximal metaphyseal region. All systemic findings were within normal limits. Biopsy confirmed the diagnosis as LCH. Thereafter, chemotherapy was started for multifocal histiocytosis involving the ulna and spine. After 18 months of observed chemotherapy with vinblastin and prednisolone, she was relived of her pain. Radiologically [[Figure 4]a and [Figure 4]b], lesions started showing signs of healing and gain in vertebral height. In January 2009, she developed a scalp swelling. X-ray [Figure 5] showed a similar picture as in the ulna. Biopsy proved the finding as LCH. This was a new lesion, and the emergence of pain in the ulna and spine suggested reactivation. Chemotherapy was again started with the following three drugs: vinblastin, prednisolone, and 6-mercaptopurine. After 7 months of treatment, her condition showed signs of improvement. She was regularly followed-up. In June 2015, X-ray [[Figure 6]a-c] showed near restoration of L2 vertebral height and decrease in size of lesions in ulna and skull.
Table 1: Hemogram profile

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Figure 1: X-ray L-S spine shows silver dollar appearance of L2 vertebra with type II A collapse and type I B wedge collapse of D11 vertebra.

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Figure 2: (a and b) Midsagital T1W & T2W images are showing Partial collapse of D11 & complete concentric collapse of L2 vertebrae without any signal alteration of adjacent disc with minimal indentation of thecal sac

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Figure 3: X-ray shows a well-defined expansile lytic lesion in proximal metaphyseal region of ulna

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Figure 4: (a and b) After 18 months of observed chemotherapy with vinblastin and prednisolone, Radiologically lesions started showing sign of healing and gain in vertebral height

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Figure 5: X-ray shows a well-defined expansile lytic lesion in skull bone

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Figure 6: (a, b and c) X-ray shows near restoration of D11 & L2 vertebral height and decreased in lesion size of ulna and skull

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  Discussion Top


LCH, a disorder of antigen-presenting cells, is the most common disorder of the mononuclear phagocytic system. The clinical presentation of Langerhans cell histiocytosis ranges from a potentially lethal leukemia-like disorder to a solitary lytic lesion of the bone. The diagnosis is clinicopathological, based on classical clinical findings and histological/immunohistochemical criteria, to avoid misdiagnosis. An absolute criteria for diagnosis depends on finding CD1a by immunohistochemistry or Birbeck granules by electron microscopy.[12] In LCH, the pathological LCH cells create a “cytokine storm.”[13] The cytokines produced directly contribute to the pathologic sequelae, including fibrosis, bone resorption and necrosis.

Bone involvement in eosinophilic granuloma

EG accounts for <1% of bone tumors and primarily involves skull, mandible, spine, ribs and long bones. In 80% of the cases, it affects children and young adults and is characterized by either single or multiple lytic bone lesions.[14],[15],[16],[17],[18],[19] 81% of all patients with LCH have a solitary EG, and 7% have multifocal EG.[14],[15],[16],[17],[18],[19] The most common presentation of LCH in childhood is a single mass lesion on the skull. All bones may be involved, however, except for hands and feet. Vertebral body involvement is seen in 7–15% of all EG cases.[17] The usual presentation is swelling and/or pain that initially may be present only at night.[20] LCH is the most common cause of vertebra plana in children.[21] This finding can also be seen in those having Ewing’s sarcoma and other tumors, infections such as tuberculosis, osteochondritis (Calve’s disease) and osteogenesis imperfecta.[22] In addition, the cases of spinal EG without vertebra plana are numerous.[9] Cervical spine EG more often manifests with osteolytic lesions rather than vertebra plana.[9]

Grossly, the tumors are reddish brown to yellow granular mass interrupted by bony spicules[12] The tumors are formed by aggregation of histiocytes and multinucleated giant cells [Figure 7]. Electron microscopy may show Birbeck’s granules in the cytoplasm of the histiocytes. Immune histological staining for S-100 protein found on the Langerhans’ histiocytes is the diagnostic tool for the condition.[12]
Figure 7: Histopathology of Eosinophilic Granuloma: Eosinophilic granuloma is composed of a polymorphous infiltrate of characteristic lobulated histiocytes, eosinophils, polymorphonuclear leukocytes, and giant cells

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In most single bone lesions, curettage of the center of the lesion provides tissue for diagnosis and usually starts the healing process. Surgical resection is unnecessary and may lead to long-term deformity. Observation is limited to lesions in “nonrisk” bones in patients with a pathological diagnosis.[23] Most tumors will heal with curettage alone, but those that have a significant soft tissue component extending internally, particularly if it involves the dura, should be considered as risk bones for progression to diabetes insipidus and neurological disease, and, therefore, should be candidates for low-risk chemotherapy.[24] Low-dose radiation therapy remains an effective modality, but it is usually restricted to the involvement of critical organs such as spinal cord or optic nerve.

For single or multiple lesions, indomethacin, a potent prostaglandin E2 inhibitor, and other nonsteroidal anti-inflammatory drugs (NSAIDs), have proven efficacy.[25] The use of bisphosphonates is supported by the report of da Costa et al., who demonstrated that the bony destruction is likely mediated by osteoclast-like giant cells that produce matrix-degrading enzymes, resulting in destructive lesions and bone pain.[26] The role of NSAIDs and bisphosphonates in preventing reactivations and late complications is unclear, as is the long-term effect of bisphosphonates in young children. Intralesional infiltration with corticosteroids, either as an adjunct to treatment or as primary treatment, was recommended by Capanna et al. as effective, convenient, and safe.[10] Egeler et al. found that the results of treatment with intralesional steroids were comparable to those of other forms of treatment reported in the literature.[23] A variety of therapeutic approaches have been used either singly or in combination in the treatment of EG; however, there is a distinct lack of consensus.

Radiological evaluation of vertebra plana

Vertebral body collapse is classified [Figure 8] as grade I (0–50% collapse) or grade II (51–100% collapse) and is subclassified as either A (symmetric collapse) or B (asymmetric collapse, such as lateral, anterior, or posterior wedging). The lesions of the posterior elements of the spine (transverse process, spinous process, facet joints, pedicle, and/or lamina) are classified as grade III. The classical finding of vertebra plana would be assigned as grade IIA with this system. The extent of maximum collapse is assessed by measuring the vertebral height and comparing it with the mean of the heights of the vertebrae immediately cephalad and caudad to the affected vertebra. Garg et al. reported no relationship between the grade of the initial collapse and the subsequent development of spinal deformity.[11] Progressive spontaneous recovery of vertebral height, which is known to occasionally occur in patients with this condition, is documented in serial radiographic follow-up by Raab et al.[27]
Figure 8: Radiological classification of vertebra plana [source : J Bone Joint Surg Am, 2004 Aug; 86-A (8)1740-50]

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The evaluation of response in bone is difficult. Fluorodeoxyglucose (FDG)-PET, a sensitive technique for identifying metabolically active LCH, has been shown to detect more lesions than conventional methods at diagnosis and reactivation, and FDG avidity correlates with response. Availability, expense, irradiation dose, and need for sedation in young children may limit its utility.[28]

For patients who respond to initial therapy, survival is very good. Reactivation, if it occurs, usually occurs in nonrisk organs such as skin or bone and is rarely fatal. One of the major challenges facing investigators is to design therapy that prevents reactivations and, hopefully, the significant permanent consequences. A review of 391 multisystem patients registered on LCH-II showed that for multifocal bone patients local therapy resulted in 52% reactivation rate, compared with 45% with single drug and 20% with two-drug therapy.[29]

Reactivations occur at a rate of 3–12% for unifocal bone, 11–25% for multifocal bone, and 50–70% for bone which is a part of multisystem LCH.[29] The greater the reactivation rate, the higher the incidence of diabetes insipidus and other late complications.


  Conclusion Top


EG is a benign form of LCH. The tumor has predilection for children, in whom it commonly presents as lesions in scalp and spine. Treatment modalities include observation, injections of steroid, local excision and curettage with or without bone grafting, chemotherapy, and irradiation. Surgical resection is rarely indicated. The reactivation of tumor is common in multifocal and multisystem LCH.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Willman CL, Busque L, Griffith BB, Favara BE, McClain KL, Duncan MH et al. Langerhans histiocytosis (histiocytosis X): A clonal proliferative disease. New Engl J Med 1994;331:154-60.  Back to cited text no. 1
    
2.
Lichtenstein L. Histiocytosis X (eosinophilic granuloma of bone ‘Letterer-Siwe disease and Schuller-Christian disease’): Further observations of pathological and clinical importance. J Bone Joint Surg Am 1964;46:76-90.  Back to cited text no. 2
    
3.
Ladish S, Jaffe ES. The histiocytocis. In: Pizzo PA, Poplack DG, editors. Principles and Practices of Pediatric Oncology. Philadelphia: J. B. Lippincott Company; 1989. p. 491-504.  Back to cited text no. 3
    
4.
Huvos AG. Bone tumors. Diagnosis, Treatment and Prognosis. 2nd ed. Philadelphia: WB Saunders; 1990.  Back to cited text no. 4
    
5.
Sweasey TA, Dauser RC. Eosinophilic granuloma of the cervicothoracic junction. J Neurosurg 1989;71:942-4.  Back to cited text no. 5
    
6.
Nesbit ME Jr. Bone tumours in infants and children. Paediatrician 1972 /73;1:273-87.  Back to cited text no. 6
    
7.
Tanaka N, Fujimoto Y, Okuda T, Nakanishi K, Sumida T, Manabe H et al. Langerhans cell histiocytosis of the atlas. A report of three cases. J Bone Joint Surg Am 2005;87:2313-7.  Back to cited text no. 7
    
8.
Dickinson LD, Farhat SM. Eosinophilic granuloma of the cervical spine. A case report and review of the literature. Surg Neurol 1991;35:57-63.  Back to cited text no. 8
    
9.
Bertram C, Madert J, Eggers C. Eosinophilic granuloma of the cervical spine. Spine (Phila Pa 1976) 2002;27:1408-13.  Back to cited text no. 9
    
10.
Capanna R, Springfield DS, Ruggieri P, Biagini R, Picci P, Bacci G et al. Direct cortisone injection in eosinophilic granuloma of bone: A preliminary report on 11 patients. J Pediatr Orthop 1985;5:339-42.  Back to cited text no. 10
    
11.
Garg S, Mehta S, Dormans JP. Langerhans cell histiocytosis of the spine in children long-term follow-up. J Bone Joint Surg Am 2004;86:1740-50.  Back to cited text no. 11
    
12.
Bechan GI, Egeler RM, Arceci RJ. Biology of Langerhans cells and Langerhans cell histiocytosis. Int Rev Cytol 2006;254:1-43.  Back to cited text no. 12
    
13.
Egeler RM, Favara BE, van Meurs M, Laman JD, Claassen E. Differential in situ cytokine profiles of Langerhans-like cells and T cells in Langerhans cell histiocytosis: Abundant expression of cytokines relevant to disease and treatment. Blood 1999;94:4195-201.  Back to cited text no. 13
    
14.
Seimon LP. Eosinophil granuloma of the spine. J Pediatr Orthop 1981;1:371-6.  Back to cited text no. 14
    
15.
Brown CW, Jarvis JG, Letts M, Carpenter B. Treatment and outcome of vertebral Langerhans cell histiocytosis at the Children’s Hospital of Eastern Ontario. Can J Surg 2005;48:230-6.  Back to cited text no. 15
    
16.
Greenlee JD, Fenoy AJ, Donovan KA, Menezes AH. Eosinophilic granuloma in the pediatric spine. Pediatr Neurosurg 2007;43:285-92.  Back to cited text no. 16
    
17.
Yeom JS, Lee CK, Shin HY, Lee CS, Han CS, Chang H. Langerhans’ cell histiocytosis of the spine. Analysis of twenty-three cases. Spine 1999;24:1740-9.  Back to cited text no. 17
    
18.
Plasschaert F, Craig C, Bell R, Cole WG, Wunder JS, Alman BA. Eosinophilic granuloma. A different behaviour in children than in adults. J Bone Joint Surg Br 2002;84:870-2.  Back to cited text no. 18
    
19.
Levy EI, Scarrow A, Hamilton RC, Wollman MR, Fitz C, Pollack IF. Medical management of eosinophilic granuloma of the cervical spine. Pediatr Neurosurg 1999;31:159-62.  Back to cited text no. 19
    
20.
Fernández-Latorre F, Menor-Serrano F, Alonso-Charterina S, Arenas-Jiménez J. Langerhans’ cell histiocytosis of the temporal bone in pediatric patients. AJR Am J Roentgenol 2000;174:217-21.  Back to cited text no. 20
    
21.
Kamimura M, Kinoshita T, Itoh H, Yuzawa Y, Takahashi J, Ohtsuka K. Eosinophilic granuloma of the spine: Early spontaneous disappearance of tumor detected on magnetic resonance imaging. J Neurosurg 2000;93(2 Suppl):312-6.  Back to cited text no. 21
    
22.
O’Donnell J, Brown L, Herkowitz H. Vertebra plana-like lesions in children: Case report with special emphasis on the differential diagnosis and indications for biopsy. J Spinal Disord 1991;4:480-5.  Back to cited text no. 22
    
23.
Egeler RM, Thompson RC Jr, Voûte PA, Nesbit ME Jr. Intralesional infiltration of corticosteroids in localized Langerhans cell histiocytosis. J Pediatr Orthop 1992;12:811-4.  Back to cited text no. 23
    
24.
Grois N, Pötschger U, Prosch H, Minkov M, Arico M, Braier J et al. Risk factors for diabetes insipidus in Langerhans cell histiocytosis. Pediatr Blood Cancer 2006;46:228-33.  Back to cited text no. 24
    
25.
Munn SE, Olliver L, Broadbent V, Pritchard J. Use of indomethacin in Langerhans cell histiocytosis. Med Pediatr Oncol 1999;32:247-9.  Back to cited text no. 25
    
26.
da Costa CE, Annels NE, Faaij CM, Forsyth RG, Hogendoorn PC, Egeler RM. Presence of osteoclast-like multinucleated giant cells in the bone and nonostotic lesions of Langerhans cell histiocytosis. J Exp Med 2005;201:687-93.  Back to cited text no. 26
    
27.
Raab P, Hohmann F, Kuhl J, Krauspe R. Vertebral remodelling in eosinophilic granuloma of the spine: A long-term follow-up. Spine 1998;23:1351-4.  Back to cited text no. 27
    
28.
Kaste SC, Rodriguez-Galindo C, McCarville ME, Shulkin BL. PET-CT in pediatric Langerhans cell histiocytosis. Pediatr Radiol 2007;37:615-22.  Back to cited text no. 28
    
29.
Lau LM, Stuurman K, Weitzman S. Skeletal Langerhans cell histiocytosis in children: Permanent consequences and health-related quality of life in long term survivors. Pediatr Blood Cancer 2008;50:607-12.  Back to cited text no. 29
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1]



 

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