Erdheim Chester’s disease with mesenteric involvement

A 54-year-old man reporting no medical history was admitted to our hospital for altered general condition with loss of 10kg in a few weeks, night sweats, abdominal pain and lower limbs oedema. Blood test revealed a 10.8g/dL anaemia, a 0.79G/L lymphopenia, and an elevated C-reactive protein (74mg/L).

A thoraco-abdomino-pelvic angioscan (CTA), performed to rule out inferior vena cava thrombosis or neoplasia showed pulmonary interlobular septal thickening and small centrilobular nodules (Figure 1) without ground glass opacities nor cardiac cavities or pulmonary veins dilation. Abdomino-pelvic examination revealed an homogeneous tissular mesenteric mass, sheathing the vessels (Figure 2a and Figure 2b). Small bowel and colon were normally enhanced.  A perivascular infiltration, away from the mesenteric mass, predominantly around the celiac trunk was found, associated with splenic artery thrombosis and splenic infarction (Figure 3). Both peri-renal spaces were infiltrated, with a mild dilation of the left pyelon, but no peri-aortic nor ureteral extension (Figure 2a and Figure 3). Sacral, iliac and femoral patchy osteocondensing lesions were found (Figure 4). Lymphoma and Erdheim-Chester disease (ECD) were initially suspected. Peri-renal, mesenteric, and bone biopsies were performed to diagnose ECD.

ECD is a rare non-Langerhans cell histiocytosis, usually occurring in middle-aged patients, with a slight male predominance [1]. The cause is not known. Histologically, ECD is characterized by variable amounts of foamy histiocytes [positive for CD68KP1 and negative for CD1a] in dense collagenous tissue [2]. As ECD is diffuse and infiltrative, it can affect many organs and shows a tropism for connective, adipose, and perivascular tissue. Its clinical manifestations are nonspecific and depend on the affected organs, varying from asymptomatic to life-threatening presentations [3]. General signs [fever, weight loss, asthenia] are often found [4]. Bone anomalies are the most frequent radiologic finding, consisting in symmetric osteosclerosis of the long tubular bones, predominating in the metaphysis and diaphysis of the lower limbs, but remains asymptomatic in most of the cases [5]. ECD without any bone lesions is rare [<10%]. Pulmonary involvement is frequently asymptomatic. Chest CT features are non-specific, consisting in smooth thickening of the pleura, fissures, and septas, usually bilateral and relatively symmetric. Small centrilobular nodules, parenchymal consolidation, cystic lesions and ground-glass opacities can be found [6]. Circumferential peri-aortic infiltration is the most common vascular finding. This infiltration may extend to the aortic branches, such as supra-aortic and coronary arteries, celiac trunk, renal and mesenteric arteries. It may cause severe arterial stenosis or occlusion, leading to ischemic complications, as in our patient [7]. Retroperitoneal anomalies with perirenal infiltration, resulting in a "hairy kidney" appearance is highly suggestive of Erdheim Chester's disease [3][5]. Retroperitoneal fibrosis is one of the main differential diagnoses, but the periaortic infiltration usually extends from the level of the renal arteries to the iliac vessels. Perirenal and mesenteric lesions can rarely be found in retroperitoneal fibrosis associated with Ig-G4 antibodies [8]. Similar retroperitoneal and peri-renal involvement can also be found in lymphoma. Mesenteric involvement is extremely rare in ECD [9]. Desmoid tumour, sclerosing mesenteritis or solitary fibrous tumour are the main differential diagnosis regarding the mesenteric involvement, but they are usually isolated, without extra-abdominal lesions [10].

To sum up, bilateral symmetric osteosclerosis of metadiaphysis of femur, tibia, and fibula is pathognomonic for ECD. Infiltrative perirenal soft tissue is seen in approximately 50% of patients, is highly suggestive of the diagnosis but retroperitoneal fibrosis and lymphoma should be ruled out. Pulmonary, cardiac, orbital or central nervous system lesions are found in a variable proportion of patients. Mesenteric involvement is extremely rare.

A biopsy is strongly recommended even in circumstances of highly suggestive clinical and imaging features to confirm ECD diagnosis but also to allow identification of associated mutations for therapeutic purposes [BRAF and MAPK-ERK] [1]. Baseline full-body FDG-PET-CT is recommended in all cases to aid in diagnosis and define the extent of disease [1].