Histiocytosis Differential Diagnoses

Updated: Jan 11, 2023
  • Author: Cameron K Tebbi, MD; Chief Editor: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK)  more...
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Diagnostic Considerations

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. [218, 219]

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, [218, 220] 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. [221]

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

Lung, liver, [82] 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 eyes [222] and lungs [24, 223] in patients, including a newborn. [224] 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. [225]

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. [226] Intracerebral Langerhans cell histiocytosis is rare, but a case report describes involvement of temporal lobe. [227]

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.

Differential Diagnoses