Erdheim‐Chester Disease and Langerhans Cell Histiocytosis: A Case of Overlap Syndrome

Short abstract

Only 500 cases of Erdheim‐Chester disease have been reported in the literature to date. To increase awareness of this rare disease, this letter to the editor describes the unusual case of a woman who was diagnosed with mixed histiocytosis: Erdheim‐Chester disease and Langerhans cell histiocytosis.

We are reporting the case of a 78‐year‐old woman with a history of myelofibrosis and Langerhans cell histiocytosis (LCH) admitted to the emergency department with fever, polydipsia, asthenia, hypotension, nausea, and weight loss. An increment of the gamma‐glutamyl transferase, alkaline phosphatase, and C‐reactive protein, a mild increment of bilirubin and transaminase, a neutrophil leukocytosis, and low urine specific gravity were found.

Computed tomography scan showed the presence of inhomogeneous tissue surrounding the thoracic and abdominal aorta, extending to the pericardium, around the kidneys' capsule, adrenal glands, ureters, pancreas, in the periportal space, and around intra‐ and extrahepatic biliary ducts. A splenomegaly of 19 cm was observed. Lungs were affected bilaterally with interlobular septal thickening in both upper lobes.

Magnetic resonance imaging showed the so‐called “empty sella” along with a hypointensity of the posterior pituitary, confirming that polydipsia was secondary to diabetes insipidus.

The technetium‐99m (⁹⁹Tc) bones scan scintigraphy demonstrated the presence of symmetric labeling of the distal epiphysis of the femur and proximal and distal epiphysis of the tibias and peroneus.

Erdheim‐Chester disease (ECD) diagnosis was achieved by histopathology showing foam CD68+ CD1a−histiocytes (Fig. 1).

Figure 1.

(A): Axial computed tomography (CT) image in the portal‐venous phase of the thorax set for the evaluation of mediastinum. The image shows fibrous tissue surrounding aorta (“coated aorta”), pulmonary vessels, and pericardium. The chronic inflammatory response of foamy cells causing thickening of pleura lead to pleural reaction and effusion. (B): Axial CT image in the portal‐venous phase of the thorax set for the evaluation of mediastinum obtained 4 years before. (C): The image shows foam cells organized in pathological tissue around the kidneys with “hairy aspect” and along the ureters, causing hydronephrosis. (D): In the near section, it is also appreciable the enlargement and infiltration of the pancreas associated with reactive nodes, simulating pancreatitis. Another alteration is the presence of splenomegaly, as a consequence of bone marrow infiltration and insufficiency. Retroperitoneal thickening involves also the gallbladder, the aorta wall, and the perisplenic peritoneum. (E): Magnetic resonance imaging of the turcic sella. Spin echo T1‐weighted images in the sagittal plane showing the “empty sella,” in particular, it did not recognize the spontaneous hyperintensity of the posterior pituitary gland. (F): technetium‐99m bone scintigraphy confirms the accumulation of foam cells in the epiphysis and the articular region of both femurs and Tibia.

As we reported, the spectrum of ECD manifestations is wide, and only two diagnostic criteria have been identified: (a) the infiltration of tissue by foam CD68+ CD1a−histiocytes associated with gain of function mutation of BRAF V600 (80%), and (b) the symmetrical involvement of the dia‐metaphyseal region of long bones, usually in the periarticular region, seen as high uptake of ⁹⁹Tc in bone scintigraphy [1].

One of the most common imaging features within visceral involvement is the so‐called "hairy kidney," the typical appearance of perirenal fat, and the "coated aorta," the presence of fibrotic tissue that surrounds the vessel, considered radiological hallmarks of ECD, associated with nephrogenic hypertension and obstructive hydronephrosis [2, 3].

A typical manifestation is painful bone involvement (96%), with osteosclerosis in the metaphyseal regions of the long bones. The other extraosseous manifestations include diabetes insipidus, exophthalmos, cerebellar ataxia, panhypopituitarism, and papilledema. Lung parenchyma and pleura can be involved (35%–42%), in particular with inter‐ and intralobular septal thickening. Cardiovascular manifestations (75%) include pericardium thickening and pseudotumor of the right atrium. Pathologic infiltration tissue can be found in the whole body [4, 5, 6, 7]. To finalize a diagnosis of ECD, a histopathological evaluation is necessary [8].

However, it is important to remember that 20% of patients with ECD can develop an overlap syndrome, the so‐called mixed histiocytosis, in particular; it is known to coexist with LCH, and both lesions may contain BRAF V600E mutation [9]. Moreover, because of disrupt proliferation of macrophages, an underlying myeloid neoplasm or myelofibrosis can be common features of the above‐mentioned overlap syndrome [10].

Our case report underlines that mixed histiocytosis, even if rare, is a potentially lethal condition, and reporting every diagnosed case is fundamental to increase the awareness and to instill the suspect of this rare disease in clinical and radiological practice.

Disclosures

The authors indicated no financial relationships.