| disease | Histiocytosis |
| alias | Reticuloendotheliosis, Reticulocytosis |
Histiocytosis (reticulosis or reticuloendotheliosis) refers to a group of diseases characterized by neoplastic or pseudoneoplastic hyperplasia of tissue cells, which cannot be classified under cervical malignancy with cachexia. This generally includes eosinophilic granuloma of bone, xanthoma, and malignant reticulosis in infants. These three conditions should be considered as chronic and acute processes of the same disease, with transitional and intermediate forms possible. Depending on the stage of development, the lesions can be solitary or multiple, and can occur within or outside the bones. Histiocytosis, including all its variants, is a systemic disorder. These manifestations are more of a syndrome than a disease, and although they differ from each other, the boundaries are not very clear. Many authors have reported cases of eosinophilic granuloma transforming into xanthoma. Histiocytosis can be divided into solitary and multiple types. The former is eosinophilic granuloma of bone, while the latter is further divided into chronic type (with or without sebaceous cyst disease), acute type (malignant reticulosis in children), and intermediate type (transitional type). Some authors classify histiocytosis into localized and diffuse types, with the former more common in older children and adults, and the latter more common in infants. Eosinophilic granuloma is more common in males, with the typical age of onset being 1-15 years, especially between 5-10 years. However, it can also occur in adults. In individuals over 20 years old, eosinophilic granuloma typically occurs in the ribs and mandible, while in those under 20, it is more common in the skull. It is rare in the vertebrae.
bubble_chart Pathological ChangesThe main lesion of vertebral eosinophilic granuloma is the extensive proliferation of reticular histiocytes, accompanied by varying amounts of eosinophils, as well as various inflammatory cells and multinucleated giant cells. Some histiocytes may transform into foam cells and phagocytes containing hemosiderin or cellular debris. Small blood vessels may exhibit fibrinoid necrosis, and in advanced stages, fibrosis may occur. The nuclei of histiocytes are large, oval, gear-shaped, or kidney-shaped, often clustered in groups or arranged in strips.
The main lesion of yellow tumor diseases is histiocyte proliferation, with visible reticular cells, foam cells, and Touton-type giant cells. Foam cells, also known as xanthoma cells, contain needle-shaped cholesterol crystals. Eosinophils are not prominent. In some areas, there is granulation tissue with poor differentiation and a few mitotic figures. Histiocytes are later replaced by fibroblasts, forming connective tissue, sometimes interspersed between foam cells, replacing granulation tissue.
In the same patient, the pathology of the same lesion can vary at different stages. For example, it may start as a histiocytic granuloma dominated by eosinophils, but years later, it may transform into a lipid-rich granuloma dominated by foam cells. Therefore, the presence or absence of foam cells alone cannot be used to definitively diagnose yellow tumor diseases. Even in infantile reticulocytosis, foam cells may occasionally be seen, but they appear scarce due to the rapid progression of the disease, which prevents their full formation.
Histiocytosis may be associated with pulmonary lesions, which can also occur independently. Initially, interstitial granulomas form in the lungs, followed by histiocytes invading small stirred pulse and distal bronchioles, leading to obstructive lung qi swelling, forming cysts and bullae that may rupture. Interstitial granulomas in the lungs are infiltrated with many eosinophils, neutrophils, and lymphocytes.
Solitary or multiple eosinophilic granulomas have few systemic symptoms. The initial symptom is pain, accompanied by local masses and tenderness in cases of cranial or rib lesions, and pathological fractures and deformities may also occur; in cases with femoral lesions, limping is common. Multiple sexually transmitted disease lesions are generally discovered successively. Patients may have systemic symptoms such as fever, loss of appetite, and weight loss, and may also be accompanied by hilar lesions. Primary eosinophilic granulomas of the spine may occasionally compress the spinal cord, causing paralysis. Yellow tumor diseases generally have three typical signs: cranial defects, exophthalmos, and diabetes insipidus, mainly involving multiple cranial lesions, with the frontal and parietal bones being the most common, followed by the temporal and occipital bones. Usually, only one of these signs is present, and it is rare for all three typical signs to appear simultaneously. In addition to the aforementioned clinical changes, there may also be developmental disorders, hepatosplenomegaly, rashes, pigmentation, and gingival ulcers. The gums are gradually surrounded by granulation tissue, with single or multiple cystic destruction around the tooth sockets, eventually leading to loose and falling teeth. Clinically, chronic gingival ulcers that do not heal for a long time may be one of the early signs of inflammation.
Malignant reticulosis in infants occurs in children under 3 years of age, with clinical manifestations including fever, otitis media, recurrent bacterial infections, anemia, and bleeding. Additionally, there may be hepatosplenomegaly, widespread painless peripheral lymphadenopathy, osteolytic changes, and seborrheic eczema.
Eosinophilic granuloma located in the skull generally manifests as osteolytic destruction of both the inner and outer tables, with the bone appearing as if it has been excavated, without surrounding sclerosis or bone membrane reaction. Its appearance resembles a map, hence it is referred to as "map skull."
In the spine, due to pathological fracture, the vertebral body becomes partially compressed into a wedge shape, and eventually completely compressed, leaving only the cortical margins at the top and bottom, with reduced vertebral height but no horizontal spread. The intervertebral spaces above and below remain unchanged, and spontaneous fusion between vertebral bodies does not occur. Occasionally, a spindle-shaped soft tissue mass may appear beside the vertebra, with increased density of the affected vertebra, presenting as a disc shape. Therefore, the typical X-ray appearance of eosinophilic granuloma in the spine is often described as a flat vertebra, resembling vertebral chondropathy.
When diagnosing eosinophilic granuloma of the bone based on X-ray findings of a flat vertebra, caution should be exercised. The diagnosis should meet the following criteria: (1) only one vertebra is involved; (2) the intervertebral spaces above and below the affected vertebra are normal; (3) the density of the compressed vertebra is uniform. The pulmonary X-ray findings resemble bronchitis or bronchiectasis, with diffuse reticulonodular infiltrates in the lungs, radiating densely from the hilum in fine streaks, and diffuse claw-like shadows, with severe cases presenting a honeycomb pattern, and enlarged and densely textured hila.
bubble_chart Treatment Measures
For single lesions, curettage alone can achieve the goal of treatment. If the lesion is large, bone grafting can be performed after thorough curettage, or low-dose radiation therapy (3-6 Gy) can be administered. In children with vertebral lesions, the height of the flattened vertebra can be restored to varying degrees after radiation therapy. Radiation therapy may injure the bone marrow, so its use should be carefully considered.
For yellow tumor diseases and infantile malignant reticulosis, radiation therapy can be used to repair and harden the areas of cranial destruction. Irradiating the orbital area can cause the protruding eyeball to recede, and irradiating the sella turcica area can repair the destruction and improve symptoms.
For patients with diabetes insipidus, the administration of pituitary hormones can reduce urine volume and improve urine specific gravity.
For diffuse eosinophilic granuloma, vincristine can be administered intravenously at 10 mg every 3 weeks for a total of 8.5 months.
Some authors suggest that if corticosteroids are ineffective for yellow tumor diseases and infantile malignant reticulosis, nitrogen mustard or methotrexate can be administered to temporarily improve symptoms. Multiple small transfusions of fresh whole blood can correct anemia.
Children under 5 years old with a single lesion, if the lesion does not continue to expand within the first 6 to 12 months and no new lesions are found in other areas, generally have a better prognosis. If anemia or hepatosplenomegaly occurs during the course of the disease, it often indicates a worsening condition. The prognosis for infantile malignant reticulosis is poor; long-term survivors are rare, and if there are concurrent lung lesions, the mortality rate is high.
