Mandible - Maxilla
Benign tumors / tumorlike conditions
Langerhans cell histiocytosis

Author: Anthony Martinez, M.D. (see Authors page)
Editor: Kelly Magliocca D.D.S., M.P.H.

Revised: 10 May 2017, last major update May 2017

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Langerhans cell histiocytosis [title] mandible

Cite this page: Langerhans cell histiocytosis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/mandiblemaxillaLCH.html. Accessed August 17th, 2017.
Definition / general
  • Clonal proliferation of Langerhans cells (immature dendritic cells)
  • The World Health Organization classification of hematopoietic and lymphoid tumors classifies Langerhan cell histiocytosis (LCH) as a dendritic cells disorder
    • This grouping includes Langerhans cell histiocytosis, secondary dendritic cell processes, juvenile xanthogranuloma, solitary histiocytomas with a dendritic phenotype and Erdheim-Chester disease
Essential features
  • Clonal proliferation of reniform or cleaved histiocytes with eosinophils
  • Langerhans histiocytes are positive for CD1a and show Birbeck granules by EM
    • Vermiform bodies are characteristic of congenital self healing LCH
  • Treatment and prognosis based on single or multisystem involvement
Terminology
  • Langerhans cell histiocytosis (LCH)
  • Eosinophilic granuloma (EG)
  • Histiocytosis X
    • Encompasses all terminology including Letter-Siwe syndrome and Hand-Schuller-Christian disease
  • Congential self healing LCH
    • Important special subtype of LCH to recognize because of spontaneously resolution
Epidemiology
  • The incidence appears to be 3 - 5 cases per million children and 1 - 2 cases per million adults
  • Primarily affects individuals in the first three decades
    • 80% are diagnosed in patients younger than 30 years
    • 50% are diagnosed in patents younger than 10 years
  • Peak incidence is 1 - 4 year of age
Sites
  • Bone is the most common site of involvement (77%)
  • Craniofacial bones are most frequently affected
    • Jaws are involved in 30% of adults and ~10% of children
      • Skull lesions are more common in children
    • Jaws involvement is 2× more common than the oral soft tissues
      • Mandible 3× more common than maxilla
Etiology
  • Clonal population of immature dendritic cells
    • This is in contrast to normal, mature Langerhans cells
    • LCH cells tend to lose ability to present antigen but still secrete cytokines that function in lesion establishment and persistence
Clinical features
  • Most common intraoral signs and symptoms at presentation include an intraoral mass, pain, gingivitis and loose teeth
  • Diabetes insipidus, exophthalmos and hepatosplenomegaly are less common
    • Triad of osteolytic lesion with exophthalmos and diabetes insipidus was used traditionally to described Hand-Schuller-Christian disease
Diagnosis
  • Diagnosis dependent on clinical, radiologic and pathologic correlation
Radiology description
  • Osteolytic jaw lesions tend to have a well defined radiolucent appearance
  • Erosion of the bone around the teeth often gives the appearance that the teeth are floating on the radiolucent lesion
  • Root resorption of the involved teeth may occur but is not common
Radiology images

Images hosted on other servers:

Lesion on the right side mandible

Multiple ill defined radiolucencies

Lytic lesion

Radiolucent lesion

Root canal treatment

Prognostic factors
  • LCH is clinically stratified as:
    • Single system LCH
      • Patients with single system LCH such as bone LCH generally have a favorable outcome and higher change of spontaneous remission
      • Unifocal bone disease has a good prognosis with relapse rate of ~10% and a disease free survival of 95%
      • Multifocal bone disease has a high relapse rate, ~75%
    • Multisystem LCH with two or more organs / systems involved, with or without involvement of "risk organs"
Case reports
Treatment
  • Surgical management is used alone in ~50% of cases
    • Additionally, therapy is often dictated by type of involvement (single vs. multisystem LCH)
  • For single system LCH
    • Unifocal bone lesions
      • In most cases, simple curettage or biopsy is diagnostic and will result in healing
      • Indications for treatment include severe pain, restriction of mobility, risk of imminent bone fracture and spinal cord or optic nerve compression (Cancer Treat Rev 2010;36:354)
        • Local therapies include steroid and low dose radiation for optic nerve or spinal cord compression
        • Systemic therapies include indomethacin, bisphosphonates and chemotherapy
          • Important to remember that bisphosphonate use has been associated with osteonecrosis
        • The Histiocyte Society recommends chemotherapy in craniofacial bone lesions with a soft tissue mass extending into the dura (Cancer Treat Rev 2010;36:354)
  • For Multisystem LCH
    • Initial induction or "intensive" chemotherapy is given to all patients with the goal of achieving complete resolution of signs and symptoms
    • The combination of vinblastine plus prednisolone is most common induction regimen
  • Clinical trials for BRAF inhibitors are currently ongoing (ClinicalTrials.gov)
Clinical images

Images hosted on other servers:

Histiocytosis X

Swelling in the right vestibule

Microscopic (histologic) description
  • Cellular proliferation of sheets of oval mononuclear cells characterized by unique reniform or cleaved nuclei with pale cytoplasm
    • Mitotic figures may be abundant
  • Interspersed inflammation, characteristically eosinophils but plasma cells and lymphocytes can be present
  • Giant cells are nearly always present and foci of necrosis is common
Microscopic (histologic) images

Images hosted on other servers:

Proliferation of neoplastic Langerhans cells

Various Images

CD1a

Immunohistochemistry
Electron microscopy description
  • Birbeck granules (electron dense cross striations)
  • For Congenital LCH
    • Laminated dense bodies with a concentric myelin-like morphology
      • Also known as vermiform bodies
    • Any child less than 2 years with evidence of LCH should have transmission electron microscopy
Electron microscopy images

Images hosted on PathOut server:

Birbeck granules - contributed by Dr. Mark R. Wick

Electron micrograph
contributed by
Dr. Mark R. Wick

Molecular / cytogenetics description
  • BRAF V600E mutation identified
    • Identified in 57% of LCH
  • Often loss of DNA sequences involving several chromosomes and 1p (Hum Pathol 2002;33:555)
  • P53 is overexpressed in LCH but the mechanism is mostly not understood and is not the result of a mutation in TP53
Differential diagnosis
  • Granulomatosis with polyangiitis (GPA):
    • Formerly Wegener granulomatosis
    • Granulomatous and often necrotizing process can target oral tissues (clinically: "strawberry gingivitis")
    • Presence of classic triad: vasculitis, tissue necrosis and granulomatous (necrotizing or nonnecrotizing) inflammation is uncommon
      • Other accompanying features may include: fat necrosis, mixed acute and chronic inflammation, geographic fibrinoid degeneration and microabscess formation
    • Unusual findings that may lead to consideration of GPA: collagen alterations (mummification of collagen, granular degeneration or frank necrosis) with a rich inflammatory infiltrate that may include many plasma cells, lymphocytes, neutrophils, eosinophils and epithelioid histiocytes
  • Rosai Dorfman (RD)
    • Characterized by enlarged, round histiocytes in contrast to the cleaved, reniform nuclei of LCH
    • RD typically has plasma cells instead of eosinophils
    • Emperilpoeisis can be highlighted by S100 protein
    • RD negative for CD1a
  • Central xanthoma of the jaw:
    • Sheets of of foamy cells with abundant cytoplasm and small hyperchromatic nuclei
    • Foreign body type giant cells occasionally present when associated with cholesterol clefts
    • Hemorrhage and hemosiderin and chronic inflammatory cells, such as lymphocytes and plasma cells
  • Radiographically, the differential is broad and includes:
Board review question #1
A 2 year old child is diagnosed with LCH and transmission electron microscopy shows laminated dense bodies with a concentric myelin-like morphology also known as vermiform bodies. This finding is important because:

  1. LCH with vermiform bodies is resistant to treatment
  2. Vermiform bodies are only present in CD1a negative LCH
  3. Vermiform bodies are only seen in congenital self healing LCH
  4. Vermiform bodies exclude the diagnosis of LCH
Board review answer #1
C. Vermiform bodies are only seen in congenital self healing LCH