Erdheim-Chester disease is a rare, non-Langerhans’ cell histiocytosis of unknown aetiology. There are typical radiographical and pathological features, which can lead to the diagnosis, but the clinical spectrum shows a broad variation, ranging from asymptomatic tissue infiltration to fulminant multisystem organ failure. The patient we report was admitted with polydipsia and hypogonadism. Cerebral magnetic resonance imaging showed a 0.5 cm thickened pituitary stalk. Microscopally, the tumour mass consisted of non-specific inflammatory cells and a diagnosis of “pseudoinflammatory” tumour was made. Although our patient lacked the most frequently occurring symptom of bone pain of the lower extremities, diabetes insipidus, dysfunction of the hypothalamic–pituitary axis in combination with an infiltration of mononuclear cells with foamy cytoplasm in almost every examined organ at necropsy is compatible with Erdheim-Chester disease. However, involvement of the testes, thyroid, and lymph nodes is uncommon. A review of the literature revealed three cases of testes involvement (table 1),2–4
one case of thyroid involvement,5
and (to our knowledge) no case with lymph node infiltration.
Table 1 Erdheim-Chester disease and testes involvement
The only involvement of the thyroid was documented by Schmidt et al
. They reported a 21 year old man with Erdheim-Chester disease and simultaneously decreased concentrations of low density lipoprotein cholesterol.5
We assume that immunohistochemistry was not performed. In addition, to our knowledge, this is the first time that involvement of the lymph nodes has been described. Two cases formerly reported and cited by Bancroft and Berquist3
showed lymph node infiltration. The first one described a patient with hypothyroidism but no recognisable pathological evidence.6
The second case report dealt with Erdheim-Chester disease and congenital megacalices but there was no mention of lymph node involvement.7
The involvement of many organs including the testes, thyroid, and lymph nodes emphasises the multisystemic character of Erdheim-Chester disease.
Our patient was initially admitted with hypogonadism and diabetes insipidus. A biopsy taken from the pituitary gland revealed an inflammatory tumour. Inflammatory processes affecting the pituitary gland include infectious diseases, in addition to those with no known infectious agent, such as lymphocytic hypophysitis, sarcoidosis, and Langerhans’ cell histiocytosis.8
Worldwide, only 12 cases with similar clinical features, but excluding a hypothalamic aetiology, Sheehan syndrome, or head injury, have been described so far. Five cases included neurosarcoidosis,9
four patients revealed hypophysitis,10–13
one patient had Langerhans’ cell histiocytosis,14
and one presented with a suprasellar arachnoid cyst.15
In only one case was the diagnosis of Erdheim-Chester disease made.16
Based on the symptoms mentioned, the differential diagnosis of Erdheim-Chester disease includes all forms of hypophysitis, neurosarcoidosis, and Langerhans’ cell histiocytosis involving the central nervous system (table 2). According to a clinicopathological study of 31 cases, hypophysitis can be histologically divided into five different types: lymphocytic, granulomatous, xanthogranulomatous, xanthomatous, and necrotising hypophysitis.13
The characteristic feature of xanthomatous hypophysitis, first described by Folkerth et al
is the presence of foamy to finely granular histiocytes that stain positively for CD68 and negatively for CD1a and S-100. The hypophysitis of three patients reported by Folkerth et al
and two cases by Tashiro and colleagues13
may be attributed to Erdheim-Chester disease because one of the patients presented with amenorrhoea, galactorrhoea, and diabetes insipidus. Neurosarcoidosis and Langerhans’ cell histiocytosis must also be taken into consideration in the differential diagnosis and can be ruled out by histology and immunochemistry in combination with the clinical characteristics.
Table 2 Differential diagnosis of Erdheim-Chester disease
“The involvement of many organs including the testes, thyroid, and lymph nodes emphasises the multisystemic character of Erdheim-Chester disease”
Bone lesions are thought to be specific enough to suggest the diagnosis because they occur in all patients suffering from Erdheim-Chester disease. However, when skeletal complaints are missing, as was the case in our patient, the diagnosis can be missed and not made until necropsy. Although there have been less than 100 published cases to date, the incidence of this disease is much higher, but the lack of diagnostic guidelines makes the diagnosis difficult. The combination of multisystemic symptoms, such as endocrinological abnormalities, respiratory and/or cardiac insufficiency, with typical radiological findings can direct the diagnosis. However, a histological and immunohistochemical examination is crucial for the diagnosis of Erdheim-Chester disease.
Take home messages
- We report a case of Erdheim-Chester disease, a rare non-Langerhans’ cell histiocytosis with characteristic radiological and histological features (mononuclear infiltrate consisting of lipid laden, foamy histiocytes that stain positive for CD68)
- Our patient had extensive organ involvement at necropsy but the diagnosis of Erdheim-Chester disease was missed during his lifetime because the typical skeletal complaints were lacking
- To our knowledge, this is the first report of thyroid and lymph node infiltration in this disease
- Because of the endocrinological symptoms, neurosarcoidosis and hypophysitis are important diseases in the differential diagnosis