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Systemic non-Langerhans cell histiocytic disorder
characterized by development of lipoid granulomas in many organs and tissues
of the body. Clinical manifestations range from asymptomatic to fatal
multisystem involvement.
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Lipid Granulomatosis; Polyostotic Sclerosing
Histiocytosis.
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First described by the American pathologist William
Chester in 1930. Credit was later also given to Chester's mentor during his
time in Vienna, the Austrian pathologist Jakob Erdheim, although he was not
an author on the paper.
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Fewer than 100 cases have been described in the medical
literature. Erdheim-Chester disease (ECD) has a male predilection and most
often affects adults older than 40 years, although the reported age range is
wide.
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Etiology is unknown. No genetic basis has been
described.
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ECD results from infiltration of the bones and
other tissues by foamy histiocytes. These histiocytes are derived from
monocytes/macrophages, lack intracytoplasmic granules (Birbeck granules),
and do not stain positive for S-100 protein, which makes them histologically
distinguishable from histiocytes derived from Langerhans cells. (However,
researchers now have found extensive S-100-positive staining in some ECD
histiocytes, so further evaluation seems necessary.) ECD characteristically
affects the long bones symmetrically.
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Based on clinical and histopathologic findings.
Symmetrical long bone osteosclerosis is the characteristic radiologic
finding. However, histologic confirmation is required for the final
diagnosis, preferentially from specimens from bone or retrobulbar tissue.
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ECD is a systemic, xanthogranulomatous,
proliferative, infiltrative disease with foamy (lipid-laden)
macrophages/histiocytes of unknown etiology. The signs and symptoms are
unspecific and mainly result from the histiocytic infiltration of different
tissues. The bones most often affected are the femora, tibiae, and fibulae;
humeri, ulnae, and radius are less often involved. The axial skeleton is
usually spared. The diaphyses and metaphyses of the long bones are
characterized by a diffuse or patchy increase in density, coarsening of the
trabecular pattern, medullary sclerosis, and cortical thickening. The
epiphyses usually are not affected. The most common presenting features
include lower limb pain (knees, ankles), exophthalmos, diabetes insipidus,
and general symptoms such as fever and weight loss. Retroperitoneal
involvement with paraaortic and perirenal infiltration may cause postrenal
obstructive uropathy. Pulmonary interstitial involvement is seen in
approximately 35% of cases, with the upper parts of the lungs usually
being more severely affected. Pulmonary lesions are characterized by
interstitial accumulations of histiocytes and fibrosis in a mainly
perilymphangitic and subpleural pattern. Computed tomographic scanning may
demonstrate centrilobular nodularity and thickening of the interlobular
septa and the visceral pleura. Other nonbony sites affected may include skin
(pruritic rash, xanthelasma, periorbital xanthomata), retroorbital tissue
(resulting in exophthalmos and rarely blindness), and central nervous system
(dural and falcine masses possibly compressing the brain, seizures,
dysarthria, cerebellar symptoms such as nystagmus, hypermetric saccades,
negative suppression of the vestibuloocular reflex, dysmetria and ataxia,
and diabetes insipidus with polyuria and polydipsia from infiltration of the
pituitary gland). Pericardial effusion and hepatosplenomegaly have been
described. Jaw infiltration (mandibula and maxilla) resulting in
periodontitis and loss of teeth ...