eMedicine Specialties > Pediatrics: General Medicine > Hematology

Histiocytosis: Differential Diagnoses & Workup

Author: Cameron K Tebbi, MD, Medical Director, Department of Pediatric Hematology-Oncology, Tampa Children's Hospital
Coauthor(s): Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine; Thomas W Loew, MD, Clinical Professor of Pediatrics, Director of Pediatric Hematology/Oncology Subspecialty Training Program, University of Iowa Hospitals and Clinics
Contributor Information and Disclosures

Updated: Jul 30, 2009

Differential Diagnoses

Acute Lymphoblastic Leukemia
Lymphoproliferative Disorders
Acute Myelocytic Leukemia
Mastoiditis
Anemia, Chronic
Non-Hodgkin Lymphoma
Atopic Dermatitis
Osteomyelitis
Craniopharyngioma
Otitis Media
Diabetes Insipidus
Splenomegaly
Diaper Dermatitis
Lymphadenopathy
Lymphohistiocytosis

Other Problems to Be Considered

Establishing a diagnosis of Langerhans cell histiocytosis (LCH) largely depends on a high degree of suspicion. With the widely varied presentations of histiocytosis disorders, the differential diagnosis can be broad. Clinical differential diagnoses range from seborrheic dermatitis and chronic otitis media to acute leukemias, lymphomas, myeloproliferative disorders, storage diseases, Rosai-Dorfman syndrome, and solid tumors.

Bone involvement

The differential diagnoses of bone lesions include malignant disorders (eg, metastatic neoplasms), neuroblastomas, primary sarcomas of the bone, and even leukemias. The lesions of Langerhans cell histiocytosis can involve any bone and may be singular or multicentric.132,133,21

Other lesions that radiologically produce bone defects must be considered. These include congenital disorders, such as meningioma, hemangioma, neurofibromatosis, congenital or developmental defect (eg, lacunar skull), parietal foramina, parietal thinning, pacchionian depressions, primary cholesteatoma, arachnoid cyst, dermoid cyst, meningocele or encephalocele, arteriovenous malformation, fibrous dysplasia, cysts, sarcoidosis, hyperthyroidism, and radiation necrosis.

Because the initial signs and symptoms of patients with bone disease often include local pain and swelling,134,132,133 infections such as osteomyelitis and tuberculosis (TB) should be considered. Paget disease and calvarial doughnut, although rare, must also be included in the differential diagnosis of bone lesions.

Skin disorders

Skin lesions of Langerhans cell histiocytosis must be differentiated from other dermatologic disorders, such as diaper rash, seborrheic dermatitis, juvenile xanthogranulomas, xanthoma disseminatum, and various other skin eruptions.

Lymphatic disorders

In patients with localized disease (especially those in whom solitary nodes are present), malignant lymphoma, malignant histiocytosis, metastatic disorders, and leukemic infiltrates, and (uncommonly) Spitz nevus and mastocytosis must be considered. The differential diagnosis of enlarged lymph nodes also includes infectious disorders, granulomatous diseases, and lymphomas.

Otorrhea must be distinguished from infectious otitis media. Oral lesions should be differentiated from relatively common maxillofacial bone and soft tissue lesions.135

With multisystemic disease, Langerhans cell histiocytosis must be distinguished from familial hemophagocytic lymphohistiocytosis (FHLH) and viral-associated hemophagocytic syndrome.

Lung, liver, and GI involvement are often, but not always, associated with systemic disease and must be differentiated from immune deficiency, leukemia, and metastatic solid tumors. Single-system disease has been reported in the eyes136 and lungs13,137 in patients, including a newborn.138 Serum KL-6 levels have been used as a marker and appeared to be correlated with pulmonary involvement in an infant with Langerhans cell histiocytosis.139

In patients with pituitary and hypothalamic lesions, other causes of diabetes insipidus, such as adenomas, craniopharyngioma, sellar chondromas, meningiomas, gangliocytomas, hypothalamic and optic gliomas, and germ-cell tumors, should be considered.

Involvement of hypothalamic-pituitary region and neurodegenerative changes in the cerebellum, basal ganglia, and pons are seen in Langerhans cell histiocytosis.140 Intracerebral Langerhans cell histiocytosis is rare, but a case report describes involvement of temporal lobe.141

Genetic syndromes with chromosomal disorders, such as multiple endocrine neoplasia type 1 (MEN-1), familial acromegaly, McCune-Albright syndrome, and Carney syndrome, can also be associated with pituitary tumors.

Other histiocytosis disorders, such as sinus hyperplasia and sinus histiocytosis with sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease, must be differentiated from viral, bacterial, acid-fast bacterial, and parasitic infections. These infections may produce signs, symptoms, and hematologic findings similar to those of SHML. When tests for rheumatoid factor and lupus erythematosus yield positive results, these disorders may need to be considered.

Workup

Laboratory Studies

  • Laboratory investigations and diagnostic tests should partly be tailored to the extent of disease suspected on the basis of the patient's history and physical findings. 
    • Table 3 shows minimal frequencies of follow-up. Testing more frequent than that shown might be necessary.Table 3. Laboratory and Imaging Studies in Patients With Langerhans Cell Histiocytosis (LCH)*

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      Table
      Type of StudyStudyInvolvementWith Monostotic Lesion
      LaboratoryHemoglobin and/or hematocritMonthlyEvery 6 moNone
      Leukocyte count and differential cell countMonthlyEvery 6 moNone
      Liver function tests* MonthlyEvery 6 moNone
      Coagulation studiesMonthlyEvery 6 moNone
      Urine osmolality test after overnight water fastEvery 6 moEvery 6 moNone
      RadiographyChest, posteroanterior and lateralMonthlyEvery 6 moNone
      Skeletal surveyEvery 6 moNoneOnce at 6 mo
      Type of StudyStudyInvolvementWith Monostotic Lesion
      LaboratoryHemoglobin and/or hematocritMonthlyEvery 6 moNone
      Leukocyte count and differential cell countMonthlyEvery 6 moNone
      Liver function tests* MonthlyEvery 6 moNone
      Coagulation studiesMonthlyEvery 6 moNone
      Urine osmolality test after overnight water fastEvery 6 moEvery 6 moNone
      RadiographyChest, posteroanterior and lateralMonthlyEvery 6 moNone
      Skeletal surveyEvery 6 moNoneOnce at 6 mo
      * Measurements of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase.
    • Table 4 lists the indications for various laboratory evaluations, with the minimal frequencies of follow-up. Testing more frequent than that shown might be necessary. Table 4. Indication for Laboratory Evaluations Based on Findings in Langerhans cell histiocytosis

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      Table
      EvaluationIndicationFollow-Up Interval
      Bone-marrow aspiration biopsyAnemia, leukopenia, or thrombocytopenia6 mo
      Pulmonary function testsAbnormal chest radiographic findings, tachypnea, intercostal retractions6 mo
      Lung biopsy after bronchoalveolar lavage, if available* Abnormal findings on pretreatment chest radiography to rule out infectionNone
      Small-bowel series and biopsyUnexplained chronic diarrhea, failure to thrive, malabsorptionNone
      Hepatic ERCP, angiography, or biopsyHigh liver enzyme levels and hypoproteinemia not caused by protein-losing enteropathy to rule out active LCH vs liver cirrhosisWhen all evidence of disease resolves but hepatic dysfunction persists
      IV gadolinium-enhanced MRI of brain and hypothalamic-pituitaryVisual, neurologic, hormonal abnormalities6 mo
      Panoramic radiography of the teeth, mandible, and maxilla; consultation with an oral surgeonOral involvement6 mo
      Endocrine investigationGrowth failure, diabetes insipidus, hypothalamic syndromes, galactorrhea, precocious or delayed puberty; hypothalamic and/or pituitary abnormality on CT or MRINone
      Consultation with an audiologist and an otolaryngologistAural discharge, impaired hearing6 mo
      EvaluationIndicationFollow-Up Interval
      Bone-marrow aspiration biopsyAnemia, leukopenia, or thrombocytopenia6 mo
      Pulmonary function testsAbnormal chest radiographic findings, tachypnea, intercostal retractions6 mo
      Lung biopsy after bronchoalveolar lavage, if available* Abnormal findings on pretreatment chest radiography to rule out infectionNone
      Small-bowel series and biopsyUnexplained chronic diarrhea, failure to thrive, malabsorptionNone
      Hepatic ERCP, angiography, or biopsyHigh liver enzyme levels and hypoproteinemia not caused by protein-losing enteropathy to rule out active LCH vs liver cirrhosisWhen all evidence of disease resolves but hepatic dysfunction persists
      IV gadolinium-enhanced MRI of brain and hypothalamic-pituitaryVisual, neurologic, hormonal abnormalities6 mo
      Panoramic radiography of the teeth, mandible, and maxilla; consultation with an oral surgeonOral involvement6 mo
      Endocrine investigationGrowth failure, diabetes insipidus, hypothalamic syndromes, galactorrhea, precocious or delayed puberty; hypothalamic and/or pituitary abnormality on CT or MRINone
      Consultation with an audiologist and an otolaryngologistAural discharge, impaired hearing6 mo
      Note.—ERCP = endoscopic retrograde cholangiopancreatography; IV = intravenous.* Diagnostic findings on bronchoalveolar lavage obviate lung biopsy.

Imaging Studies

  • See Table 3-4 for appropriate imaging studies when Langerhans cell histiocytosis is suspected.
  • Radiographic imaging of lytic lesions of the skull reveals a punched-out pattern without evidence of periosteal reaction or marginal sclerosis (see Media file 9).

    Radiograph of lytic lesions of the skull reveals ...

    Radiograph of lytic lesions of the skull reveals a punched-out pattern without evidence of periosteal reaction or marginal sclerosis.

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    Radiograph of lytic lesions of the skull reveals ...

    Radiograph of lytic lesions of the skull reveals a punched-out pattern without evidence of periosteal reaction or marginal sclerosis.

  • Radionuclide bone scanning with technetium-99m polyphosphate may reveal a localized increased uptake. This study is complementary to plain radiography.
  • MRI sometimes helps in identifying lesions that cannot be detected with other modalities. For example, in one study, 28% of children with Langerhans cell histiocytosis had MRI findings suggestive of neurodegenerative disease.69
  • Neurologic findings may not always be correlated with the MRI results and may lag behind findings on MRI.142
  • CT and MRI can show the detailed anatomic pattern of involvement and can help in staging the disease.143
  • Positron emission tomography (PET) with 18F-fluoro-deoxyglucose (FDG) may be an effective tool for evaluating LCH and may provide additional information regarding the activity of the lesions.144 However, this ability has not been definitively studied.
  • With pulmonary involvement, CT scanning is the best modality to reveal cysts and micronodular infiltrates.

Other Tests

  • When pulmonary involvement occurs, pulmonary function may be abnormal.97,31
    • Diffuse cystic changes, nodular infiltrate, pleural effusion, and pneumothorax are known to occur.
    • Pulmonary function tests may reveal restrictive lung disease with decreased pulmonary volume.97,31
  • Pulmonary function tests are critical components of follow-up in patients with pulmonary involvement.

Procedures

  • Biopsy is needed to establish the diagnosis of Langerhans cell histiocytosis.

Histologic Findings

  • Regardless of the clinical severity, the histopathology of Langerhans cell histiocytosis is generally uniform. To some extent, the location and age of the lesion may influence the histopathology of the disease.145 Early in the course of the disease, lesions tend to be cellular and contain aggregates of pathologic Langerhans cells (PLCs), intermediate cells, interdigitating cells, macrophages, T cells, and giant histiocytes. Mitotic figures number 0-23 per 10 high-power fields.15
  • Multinucleated giant cells are common, and some may exhibit phagocytosis. Lesions may also include eosinophils, necrotic cells, and Langerhans cell histiocytosis cells. With time, the cellularity and number of Langerhans cell histiocytosis cells are reduced, and macrophages and fibrosis become eminent. The infiltrates tend to destroy epithelial cells. Table 5 shows the phenotypes and cell-marker characteristics of Langerhans cell histiocytosis.
  • Table 5. Cell Markers and Phenotypes of Histiocytic and Related Disorders

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    Table
    Cell MarkerLCHSHMLFollicular Dendritic TumorHistiocytic SarcomaAcute Monocytic LeukemiaAnaplastic Large-Cell Lymphoma
    CD1a+-----
    CD4++-+++
    CD21-+/-+---
    CD25-+-++++
    CD30-----++
    CD35-++---
    CD45-+-+/-++/-
    CD68-+-+++/-
    ALK-1-----+
    S-100++-+/1--
    Lysozyme-+-++-
    Cell MarkerLCHSHMLFollicular Dendritic TumorHistiocytic SarcomaAcute Monocytic LeukemiaAnaplastic Large-Cell Lymphoma
    CD1a+-----
    CD4++-+++
    CD21-+/-+---
    CD25-+-++++
    CD30-----++
    CD35-++---
    CD45-+-+/-++/-
    CD68-+-+++/-
    ALK-1-----+
    S-100++-+/1--
    Lysozyme-+-++-
  • Table 6 shows specialized stains for diagnosing these disorders, and Table 7 shows labeling pattern of histiocytes and dendritic cells.

    Table 6. Stains for Diagnosing Histiocytosis

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    Table
    Type of TestStainMononuclear Phagocytic SystemLangerhans CellsInterdigitating Dendritic CellsDendritic Reticulum Cells
    Frozen-section enzyme histochemistryNonspecific esterase----
    Acid phosphatase+---
    ATPase-++-
    Lambda-mannosidase-+--
    5' nucleotidase---+
    ImmunohistochemistryCD14 (Leu M3/MY4)++++
    CD11 C (Leu M5)++++
    CD68 (EBM 11)+---
    CD1a-++-
    Paraffin-section immunohistochemistryHLA-DR++++
    CD68+---
    Mac 387+---
    Lysozyme+---
    Alpha-antitrypsin+---
    S-100-++-
    Peanut agglutininDiffuseHalo and dotHalo and dot-
    Type of TestStainMononuclear Phagocytic SystemLangerhans CellsInterdigitating Dendritic CellsDendritic Reticulum Cells
    Frozen-section enzyme histochemistryNonspecific esterase----
    Acid phosphatase+---
    ATPase-++-
    Lambda-mannosidase-+--
    5' nucleotidase---+
    ImmunohistochemistryCD14 (Leu M3/MY4)++++
    CD11 C (Leu M5)++++
    CD68 (EBM 11)+---
    CD1a-++-
    Paraffin-section immunohistochemistryHLA-DR++++
    CD68+---
    Mac 387+---
    Lysozyme+---
    Alpha-antitrypsin+---
    S-100-++-
    Peanut agglutininDiffuseHalo and dotHalo and dot-
    Note.—ATPase = adenosine triphosphatase; HLA = human leukocyte antigen.

    Table 7. Labeling Pattern of Histiocytes and Dendritic Cells

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    Table
    MarkerHistiocytesLangerhans CellsInterdigitating CellsFollicular Dendritic Cells
    CD1a0S00
    S-100 protein0SSW
    HLA-DRSSSW
    CD45SWW0
    Alpha-naphthyl acetate esteraseSWWW
    ATPaseWSSS
    Fascin00SS
    R4/23000S
    MarkerHistiocytesLangerhans CellsInterdigitating CellsFollicular Dendritic Cells
    CD1a0S00
    S-100 protein0SSW
    HLA-DRSSSW
    CD45SWW0
    Alpha-naphthyl acetate esteraseSWWW
    ATPaseWSSS
    Fascin00SS
    R4/23000S
  • Note.—0 = no staining; S = strong and constant; W = weak or inconstant.
  • Langerhans cells express CD1a antigen, HLA-DR, and a subunit S-100 protein (see Media file 5).

    Photomicrograph shows sample of Langerhans cell h...

    Photomicrograph shows sample of Langerhans cell histiocytosis (LCH) that immunocytochemically stains positive for S-100 protein.

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    Photomicrograph shows sample of Langerhans cell h...

    Photomicrograph shows sample of Langerhans cell histiocytosis (LCH) that immunocytochemically stains positive for S-100 protein.

  • Upon morphologic evaluation, cells are 12 µm in diameter with moderately abundant cytoplasm and a medium-sized folded, indented, or lobulated nucleus that has vesicular chromatin with 1-3 nucleoli and an elongated central groove producing a coffee-bean appearance (see Media file 6 and Media file 8).146,147,148
  • The histopathology of the Langerhans cell histiocytosis does not appear to be prognostic of the outcome of the disease.15 The aggregation of Langerhans cells is observed in various disorders, such as lymphomas (eg, Hodgkin disease), lung cancer, and thyroid cancer. However, these disorders are secondary and resolve with control of the primary disorder.4,149
  • In Langerhans cell histiocytosis, the cytoplasm and, rarely, the nucleus contain the characteristic structures termed Birbeck granules (see Media file 7).

    Transmission electron micrograph shows a diagnos...

    Transmission electron micrograph shows a diagnostic rod-shaped Langerhans Birbeck granule.

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    Transmission electron micrograph shows a diagnos...

    Transmission electron micrograph shows a diagnostic rod-shaped Langerhans Birbeck granule.

  • These trilaminar organelles are 190-360 nm long and approximately 33 nm wide, with a central striated line. These are derived from cytoplasmic membrane and are involved in receptor (T6)-mediated and non–receptor-mediated endocytosis. An electron microscopic finding of racquet-shaped granules in the cells can be helpful in confirming the pathologic diagnosis.
  • Relatively nonspecific findings include cytoplasmic, trilaminar, membranous loops and laminated substructures of lysosomes.150 Langerin is a type II transmembrane C-type lectin associated with formation of Birbeck granules. This can be used as a selective marker for Langerhans cells and cells involved in Langerhans cell histiocytosis. Langerin expression is present in most cases of Langerhans cell histiocytosis.151  Immunohistochemical determination of Langerin and CD1a may be used to separate Langerhans cell histiocytosis from other histiocyte proliferations.
  • Birbeck granules are the products of internalization of complexes originating from cell-membrane antigens and corresponding antibodies. CD1a antigen can be detected in paraffin-embedded tissues to provide for reliable diagnostic testing.152,153 ATPase peanut lectin and alpha-D-mannoside can be positive in the dendritic reticulum. An electron microscopic finding of racquet-shaped granules in the cells can be helpful to confirm the pathologic diagnosis.154 Enzyme histochemistry and immunocytochemistry can also aid in the diagnosis of histiocytosis.41
  • The organs and tissues most commonly involved are the bones, skin, lymph nodes, bone marrow, lungs, hypothalamic-pituitary axis, spleen, liver, GI tract, and orbits. Multisystemic involvement is common.20 Bones can be involved in isolation or as a part of multisystemic disease. The skull or large bones are often involved. Bone lesions may contain an accumulation of eosinophils, multinucleated giant histiocytes, necrosis, and hemorrhage. The term eosinophilic granuloma was previously used to describe single bone lesions of Langerhans cell histiocytosis.
  • Cutaneous involvement can also be singular or can be a part of generalized involvement.90,91,92,93 A spontaneously regressing nodular form of cutaneous Langerhans cell histiocytosis is reported in infants; it involves deep dermis with a nodular aggregate of histiocyte and is called congenital self-healing reticulohistiocytosis.94,95,96 In general, skin lesions have a pattern of diffuse or multifocal nodular aggregation of PLCs deep in the papillary dermis; destruction of epidermal-dermal interface; and infiltration of histiocytes, T-cell lymphocytes, and eosinophils. The lymph nodes and thymus can be involved as a primary site or as a part of multiorgan and systemic involvement. The most common sites are the cervical, inguinal, axillary mediastinal, and retroperitoneal areas.99,155
  • Five histologic motifs have been recognized. These include sinusoidal, limited sinusoidal, epithelioid granulomatous, partial effacement, and total effacement. However, the prognostic significance of these appearances is not proven. The cellular composition includes Langerhans cells, macrophages, multinucleated giant histiocytes, T lymphocytes, and eosinophils.146,147 Histologic involvement may have different appearances in lesions from separate sites. In some instances, lymph nodes are massive and cause airway obstructions.
  • Suppuration resembling infection has been reported.100 The bone marrow may be normal or heavily involved. Bone marrow lesions may be focal with pathologic infiltration of Langerhans cells or may contain neutrophils, eosinophils, lymphocytes, multinucleated cells, fibrosis, and (in rare cases) eosinophilic accumulation. Pulmonary involvement is more common in adults than in children (especially adults with a history of smoking), but it occurs in 20-40% of all patients.97,31 Small cysts can coalesce and rupture into the pleural cavity, leading to pneumothorax.98
  • CNS involvement, including pituitary involvement, is often part of systemic disease.156,157,158 The CNS is rarely a primary site of Langerhans cell histiocytosis involvement.159,160,161,162,163,164,165,166 The most common site of CNS involvement in persons with Langerhans cell histiocytosis is the hypothalamic-pituitary axis, which results in diabetes insipidus in 10-50% of patients.167 Histiocytosis can be associated with cerebellar white matter abnormalities.164 Pathologic changes in the cerebellum, basal ganglia, and pons have been reported.140
  • Local involvement of the temporal lobe has also been observed and represents a neurodegenerative disorder that is thought to be similar to a paraneoplastic syndrome.164 The neurodegenerative changes may occur well before, during, or long after diagnosis of histiocytosis. Manifestation may include cerebellar and pyramidal dysfunction, hormonal abnormalities, ataxia, spasticity, and cognitive problems.141,164 MRI abnormalities in cerebellar white matter, brain stem, basal ganglia and cerebral white matter are found.164
  • Involvement of the anterior pituitary is relatively uncommon. However, it can result in growth-hormone deficiency or, in rare cases, panhypopituitarism.87 Cerebellar dysfunction with incoordination and white matter changes has been reported.101 Langerhans cell histiocytosis may affect the spleen and liver. Primary involvement of the liver is uncommon.168,7 Involvement of the liver is often part of multiorgan disease. Even when PLCs are not present, sclerosing cholangitis can be observed.168 Liver infiltration may result in tissue damage and increased enzyme levels, jaundice, coagulation disorders, and hypoalbuminemia.
  • Involvement of the GI tract is probably more common than is clinically recognized.169 Lesions in the stomach, small bowel, colon, and rectum have been reported.170,17,169,107,108 The usual pathology of GI involvement with Langerhans cell histiocytosis includes infiltration of lamina propria and submucosa with glandular, mucosal, and, possibly, villus atrophy. Diarrhea and GI bleeding can be the presenting features of the disease. Involvement of the pancreas is rare.171,172
  • Langerhans cell histiocytosis rarely involves the intraocular structures. Isolated eye disease has been reported.136 Lytic lesions of the orbit and resulting soft-tissue extension may cause proptosis. Ptosis and optic atrophy rarely occur. Patients with ear involvement often present with chronic otorrhea, lesions of the external auditory meatus, middle-ear involvement, and mastoid involvement. Although rare, involvement of the genital tract has been reported.173,174,175
  • In patients with Langerhans cell histiocytosis and hematopoietic involvement, Langerhans cell infiltration is often not evident; however, other abnormalities are common. These include abnormal M:E ratio; hyperplasia and dysplasia of megakaryocytes, including mononucleated and bilobed micromegakaryocytes and paratrabecular and grouped megakaryocytes; existence of neutrophil remnants in megakaryocytes (emperipolesis); increased numbers of macrophages; hemophagocytosis; and myelofibrosis.176

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Follow-up: Histiocytosis
Multimedia: Histiocytosis
References
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Further Reading

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Keywords

histiocytosis, LCH, Langerhans cell histiocytosis, eosinophilic granuloma, Hand-Schüller-Christian disease, Letterer-Siwe disease, histiocytosis X, familial hemophagocytic lymphohistiocytosis, HLH, FHLH, sinus histiocytosis, SHML, juvenile xanthogranuloma, JXG, reticulohistiocytoma, acute monocyte leukemia, malignant histiocytosis, sinus hyperplasia, hepatosplenic T-cell lymphoma, histiocytic necrotizing lymphadenitis, dendritic lymphadenitis, follicular lymphadenitis, cutaneous LCH, treatment, diagnosis

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Contributor Information and Disclosures

Author

Cameron K Tebbi, MD, Medical Director, Department of Pediatric Hematology-Oncology, Tampa Children's Hospital
Cameron K Tebbi, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, Histiocyte Society, and International Society of Paediatric Oncology
Disclosure: Nothing to disclose.

Coauthor(s)

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Thomas W Loew, MD, Clinical Professor of Pediatrics, Director of Pediatric Hematology/Oncology Subspecialty Training Program, University of Iowa Hospitals and Clinics
Thomas W Loew, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Genzyme Grant/research funds Independent contractor; Genzyme Honoraria Speaking and teaching; Amicus Grant/research funds Independent contractor; Purdue Pharmaceuticals Grant/research funds Independent contractor; Grifols Pharmaceuticals Grant/research funds Independent contractor

Medical Editor

Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories
Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Gary D Crouch, MD, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Associate Professor, Uniformed Services University of the Health Sciences
Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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