Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Immunohistochemistry & special stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Magliocca K, Martinez A. Langerhans cell histiocytosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/mandiblemaxillaLCH.html. Accessed September 22nd, 2023.
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
- Unique ultrastructural features (see Electron microscopy description below)
- 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
- Jaws are involved in 30% of adults and ~10% of children
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
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"
- Risk organs in LCH include liver, spleen and bone marrow
- Multisystem LCH are subdivided into "low risk" and "risk" groups
- High rate of relapse, approximately 95%
- 75% disease free survival
- ~17% die of disease (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100:S42)
- Single system LCH
Case reports
- 5 year old boy with intermittent pain on the lower right side of the face for one month (J Clin Diagn Res 2016;10:ZD19)
- 9 year old boy with a firm swelling in right lower jaw along with bilateral submandibular lymphadenopathy for 1 month (J Cytol 2014;31:227)
- 29 year old male patient presented with a history of painless swelling in the lower jaw for 2 months (BMJ Case Rep 2015 Jan 14;2015)
- 39 year old man who complained of recurrent pain, swelling of the gingiva and an occasional pus-like discharge in the right mandible for one year (Oncol Lett 2014:8:1075)
- 39 year old man with pain in the anterior region of the mandible for several months (Imaging Sci Dent 2013;43:117)
- Langerhans cell histiocytosis in a periapical cyst (J Tenn Dent Assoc 2008;88:26)
- Multiple cases of inflammatory periapical disease with small aggregates of Langerhans cells as a minor component (Oral Surg Oral Med Oral Pathol 1992;74:186)
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)
- Unifocal bone lesions
- 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)
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
Immunohistochemistry & special stains
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
- Laminated dense bodies with a concentric myelin-like morphology
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 (Wegener's):
- 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:
- Lymphoma
- Odontogenic cysts
- Benign and malignant odontogenic tumors
- Reactive / inflammatory processes related to odontogenic infection or inflammation
- Other metastases
Additional references
Board review style 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:
- LCH with vermiform bodies is resistant to treatment
- Vermiform bodies are only present in CD1a negative LCH
- Vermiform bodies are only seen in congenital self healing LCH
- Vermiform bodies exclude the diagnosis of LCH
Board review style answer #1
C. Vermiform bodies are only seen in congenital self healing LCH
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Reference: Langerhans cell histiocytosis
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Reference: Langerhans cell histiocytosis