Eosinophilic Granuloma

Author: Anay Patel

Topic updated on 05/17/13 7:28pm


Introduction
Histiocytosis X or Langerhans cell histiocytosis is a spectrum of diseases of the reticuloendothelial system with one of three general presentations Eosinophilic granuloma (EG) usually a single self-limited lesion found in younger patients Hand-Schuller-Christian disease (HSC) chronic, disseminated form with bone and visceral lesions also known as Langerhans cell histiocytosis with visceral involvement Letterer-Siwe disease (LSD) fatal form that occurs in young children Epidemiology demographics most commonly occurs in children (80% of afflicted < 20 years of age) HSC disease presents in children > 3 years of age LSD occurs in children < 3 years of age Male to female ratio of 2:1 location eosinophilic granuloma commonly presents in the skull, ribs, clavicle, scapula, mandible isolated lesions of the spine (thoracic most common) can also occur in diaphyseal regions of long bones and the pelvis HSC multiple boney site involvement multiple lytic skull lesions visceral involvement of the lungs, spleen, liver, skin, lymph nodes Genetics no clear genetic pattern of inheritance or locus has been determined Associated conditions HSC classic tried of multiple lytic skull lesions diabetes insipidus exopthalmos Prognosis EG isolated involvement generally treatable with local management spine lesions can spontaneously resolve HSC prognosis depends on response to chemotherapy worsening prognosis with increasing extraskeletal involvement LSD generally fatal in children < 3 years of age

Presentation

Symptoms
- skeletal involvement
  - pain and swelling at the region of involvement
  - limping can be seen with pelvic or lower extremity involvement
- vertebral involvement
  - localized or diffuse back pain
  - increasingly kyphotic posture
  - radiculopathy can occur with more aggressive lesions
- HSC
  - diabetes insipidus
    - increased thirst and water intake
  - visceral involvement
    - diffuse or nonspecific abdominal or chest pain

Imaging

Radiographs
- general
  - known as "the great mimicker" as it appears similar to many lesions
  - radiographic differential includes osteomyelitis, leukemia, lymphoma, fibrous dysplasia, or Ewing's sarcoma
- diaphyseal lesions
  - well defined intramedullary lytic or "punched-out" lesion
  - cortex may be thinned, expanded, or destroyed
  - may have periosteal reaction
- metaphyseal lesions
  - extend up to but not through the physis
  - less central location than diaphyseal lesions
- spinal lesions
  - vertebra plana (flattened vertebrae) in spine
  - increased kyphosis
- cranial involvement
  - multiple "punched-out" lytic lesions
MRI
- may show a soft tissue mass adjacent to boney lesions
Bone scan
- generally shows increased uptake in the region of boney lesion

Studies

Histology
- Langerhan's cells
  - mononuclear histiocyte-like cells with oval nuclei with well-defined round or oval cytoplasm.
  - a prominent nuclear groove (coffee bean nuclei) can be seen in most of the nuclei
  - eosinophilic cytoplasm (pink generally)
  - stain with CD1A
  - electronmicroscopy
    - birbeck granules seen inside Langerhan's cells
- mixture of inflammatory cells also present
- giant cells are present
- lack of nuclear atypia and atypical mitoses
  - differentiates this condition from malignant conditions such as Ewings sarcoma, lymphoma of bone, and metastatic neuroblastoma, which may look similar based on the round cells alone

Treatment

Nonoperative
- observation alone
  - indications
    - a self-limited process and it is reasonable to treat with observation alone
- bracing
  - indications
    - to prevent progressive kyphosis of the spine
  - outcomes
    - will correct deformity in 90% of patients
    - vertebral lesions generally regain 50% of their height
- low dose irradiation (600-800 cGy)
  - indications
    - indicated for lesions in the spine that compromise stability, neurologic status
    - lesions not amenable to injection or open treatment
  - outcomes
    - effective for most lesions
- chemotherapy
  - indications
    - diffuse HSC
  - outcomes
- corticosteroid injection
  - indications
    - isolated lesions
    - can be performed after curettage as well
Operative
- curettage and bone grafting
  - indications
    - for lesions that endanger the articular surface or are a risk for impending fractures
- spinal deformity correction
  - indications
    - progressive spine deformity refractory to bracing
      - approximately 10% of patients with spine lesion will need operative intervention for deformity correction

Differentials & Groups

	Destructive lesion in young patients	Multiple lesions in young patients (1)	Treatment is Observation alone (2)
Eosinophilic granuloma	•	•	•
Osteomyelitis	•
Osteosarcoma	•
Ewing's sarcoma	•
Desmoplastic fibroma	•
Lymphoma	•	•
Leukemia	•	•
Fibrous dysplasia		•	•
Enchondroma / Olliers / Marfucci's		•	•
Osteochondroma / MHE		•	•
Hemangioendothelioma		•
NOF / Jaffe-Campanacci syndrome		•	•
Paget's			•
ASSUMPTIONS: (1) Younger patient is < 40 yrs; (2) assuming asymptomatic and no impending fracture

Ibank

	Location	Xray	Xray	CT	B. Scan	MRI	MRI	Histo(1)
Case A	spine
Case B	radius
Case C	humerus
Case D	femur, 13 yo female
Case E	skull

(1) - histology does not always correspond to clinical case

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Qbank (2 Questions)

TAG

(OBQ11.32) A 5-year-old child presents with skin lesions and a limp. He has met all developmental milestones accordingly but his parents have noticed he has recently stopped gaining weight. Clinical photograph of his skin lesion, radiograph of his left hip, and histology slide representative of his hip lesion are shown in Figures A, B, and C. What is the most likely diagnosis? Topic

Review Topic

FIGURES: A

1. Neuroblastoma
2. Ewing's sarcoma
3. Eosinophilic granuloma
4. Acute lymphoblastic leukemia
5. Fifth's disease

PREFERRED RESPONSE ▶

DISCUSSION: The clinical presentation, radiograph, and histology slide are diagnostic of eosinophilic granuloma. Eosinophillic granuloma is a tumor like condition secondary to proliferation of histiocytes and most commonly occurs in the skull, skin, or skeleton. It can occur in just about any bone but is common in the spine or the flat bones of the pelvis or shoulder girdle, long bones, and skull. Radiographically, eosinophilic granuloma occurs as lytic lesions without significant surrounding sclerosis as seen in Figure A. Histology shows the characteristic multiple eosinophils with their characteristic oval "coffee bean" nuclei and staining pattern of purple/red/pink cytoplasm (depending on the stain). Importantly, the histology slide lacks a malignant appearance (no cellular atypia or mytotic complexes and low nuclear:cytoplasmic ratio). Skin lesions like those shown in Figure A are common.

Neuroblastoma, Ewing's sarcoma, and acute lymphoblastic leukemia are all common pediatric neoplasms which have classic presentations such as the young age and abdominal mass common for neuroblastoma, the characteristic translocation in Ewing's sarcoma, and the diagnostic histology and toxic clinical presentation in acute lymphoblastic leukemia. Fifth's disease is an infectious disease caused by the parvovirus B19.

REFERENCES:

1. Simon MA, Springfield D, eds. Surgery for Bone and Soft-Tissue Tumors. Philadelphia, PA: Lippincott-Raven; 1998:198-200.

2. Springfield DS, Bolander ME, Friedlaender GE, Lane N. Molecular and cellular biology of inflammation and neoplasia. In: Simon SR, ed. Orthopaedic Basic Science. Rosemont, IL: American Academy of Orthopaedic Surgeons; 1994:219-276.

Question Authors:

Patrick O'Donnell MD/PhD, John Badylak MD,

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(OBQ10.275) A 7-year-old boy complains of pain in the right thigh for 1 month with no history of traumatic injury. A radiograph is provided in Figure A. A histology specimen from incisional biopsy is provided in Figures B and C. Which of the following is the most appropriate management? Topic

Review Topic

FIGURES: A

1. Conservative treatment with crutches and repeat radiographs in 6 weeks
2. Wide excision
3. Wide excision and chemotherapy
4. Radiation therapy alone
5. Curettage and bone grafting

PREFERRED RESPONSE ▶

DISCUSSION: The clinical presentation, imaging, and histology is consistent with eosinophilic granuloma, a benign neoplasm of histiocytes. The radiograph shows a poorly defined lesion that has invaded the cortex of the femoral diaphysis. The diagnosis is confirmed by histology with the proliferation of Langerhans cells and the presence of eosinophils (red with bilobed nuclei). This form of histiocytosis is self-limiting and may be managed conservatively. Worsening pain and further destruction of the cortical bone would be indications for radiation therapy or curettage and grafting/cementation to prevent pathologic fracture. Pathognomonic findings for eosinophilic granuloma include coffee bean indented nuclei in Langerhans cells (blue arrow in Illustration A) and tennis-racket shaped Bierbeck granules within the Langerhans cell (shown on electron microscopy in Illustration B). Other commonly tested features of eosinophilic granuloma include spinal involvement resulting in vertebra plana, and the two histiocytosis syndromes (Hans Schuller Christian and Letterer-Siwe). The unrelated publication by Elliot et al demonstrates patient safety with use of monoclonal antibody to TNF-alpha.

Illustrations: A

REFERENCES:

1. Vaccaro AR (ed): Orthopaedic Knowledge Update 8. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2005, pp 229-244.

2. Elliot MJ, Maini RN, Feldmann M: Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum 2008;58:S92-S101. PMID:18240199 (Link to Abstract)

Question Authors:

John Badylak MD,

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Videos

Langerhans Cell Histiocytosis - Dr. Ken McClain

Pathology - Educational Presentation - Eosinophilic Granuloma

In this 7-part series, Dr. McClain presents a thorough description of the clinic...

3/10/2013

68 views

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Groups

ABOS II: Eosinophilic Granuloma (Langerhan's cell histocytosis, Histiocytosis X)

General - Oral Boards Review

7/29/2011

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Evidence & References Show References

Textbooks

Review of Orthopaedics, 6th Edition, Mark D. Miller MD, Stephen R. Thompson MBBS MEd FRCSC, Jennifer Hart MPAS PA-C ATC, an imprint of Elsevier, Philadelphia, Copyright 2012
AAOS Comprehensive Orthopaedic Review, Jay R. Leiberman. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2009
Orthopaedic Knowledge Update 10, John M Flyn. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2011
Hoppenfeld SP. Surgical Exposures in Orthopaedics: The Anatomic Approach. Lipponcott, Williams, and Wilkins, Philadelphia, PA, Copyright 2009
Orthopaedic In-training Examination (OITE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Self-Assessment Examination (SAE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Simon MA, Springfield D, eds. Surgery for Bone and Soft-Tissue Tumors. Philadelphia, PA: Lippincott-Raven; 1998:198-200.
Springfield DS, Bolander ME, Friedlaender GE, Lane N. Molecular and cellular biology of inflammation and neoplasia. In: Simon SR, ed. Orthopaedic Basic Science. Rosemont, IL: American Academy of Orthopaedic Surgeons; 1994:219-276.
Vaccaro AR (ed): Orthopaedic Knowledge Update 8. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2005, pp 229-244.

Undefined

Elliot MJ, Maini RN, Feldmann M: Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum 2008;58:S92-S101. PMID:18240199 (Link to Abstract)

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Eosinophilic Granuloma

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