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An official publication of the Middle-Eastern Association for Cancer Research
Clinical Cancer Investigation Journal
ISSN Print: 2278-1668, Online: 2278-0513
ARTICLE
Year: 2022   |   Volume: 11   |   Issue: 4   |   Page: 15-18     View issue

Erdheim-Chester Disease: Histopathological Perspective of a Rare Condition  

Banyameen Iqbal1*, Indranil Dey1, Iqra Mushtaq2

1Department of Pathology, Dr. D.Y Patil Medical College, Hospital and Research center, Pimpri, Pune – 411018, India. 2Department of Ophthalmology, Dr. D.Y Patil Medical College, Hospital and Research center, Pimpri, Pune – 411018, India.


Abstract

Erdheim-Chester disease (ECD) is a rare, multisystem non-Langerhans cell histiocytosis of unknown etiology with characteristic radiological and histopathological features. It usually affects middle-aged individuals with slight male predominance. Radiologically symmetrical sclerotic lesions are seen mainly in the long bones. The histopathological hallmark is infiltration by foamy histiocytes at multiple sites of involvement. Immunohistochemistry (IHC) with CD68 confirms the diagnosis. This case report describes the case of a 60year old Indian male who presented with complaints of cerebellar ataxia with chorea and autonomic involvement. Radiological and histopathological investigations confirmed ECD with multisystem involvement, involving- CNS, skeletal, pulmonary, cardiovascular, adrenal gland, lymph nodes, retroperitoneal, and perinephric soft tissue. The variable presentations require consideration and ruling out of numerous differential diagnoses such as histiocytosis X (LCH), multiple sclerosis, neuro-sarcoidosis, amyloidosis, metabolic disorders, Rosai–Dorfman disease, malignancies, and mycobacterial infections. No definitive therapy exists for ECD presently, with the prognosis being dependent on the extent and distribution of the extra-skeletal manifestations.

Keywords: CD68, Erdheim-Chester, Histiocytosis, Non-Langerhans cell


Introduction

Erdheim-Chester disease (ECD) is a rare, multisystem non-Langerhans cell histiocytosis of unknown etiology. It is characterized pathologically by xanthogranulomatous infiltrates which are found mainly in the central nervous system, the long bones of the lower extremities, retroperitoneum, heart, lung, kidneys, skin, spleen, liver, and orbit. Clinically and radiologically, it is characterized by symmetric sclerosis of long bones along with increased uptake on bone scans. The ECD diagnosis is dependent upon the combination of imaging features and clinical presentations which are confirmed by histopathologic findings.[1]

This disorder was first described in 1930 by American pathologist William Chester as a lipogranulomatous disorder and it was later designated as Erdheim-Chester disease after the Austrian pathologist Jakob Erdheim, with whom he worked.[2] It usually affects middle-aged individuals, and it is more common in males as compared to females. ECD may be asymptomatic, or it might exist as an aggressive multi-systemic disease affecting the skeletal, central nervous system, cardiovascular, respiratory, and renal systems and it is also known to involve the retroperitoneum and skin. The most common complaint among symptomatic patients is bone pain. Extra-skeletal manifestations are seen in up to 50% of cases,[3] and it includes clinical features such as - xanthelasmas, papilledema, exophthalmos, severe lung disease, diabetes insipidus, papulonodular skin lesions, cardiomyopathy, retroperitoneal fibrosis, and renal failure. Neurological manifestations include ataxia, paresis, seizures, sensory disturbances, and diabetes insipidus.[1]

According to the World Health Organization (WHO) proposed classification system for histiocytic disorders; Class I is Langerhans' cell histiocytosis (LCH) and Class II is the non-Langerhans histiocytosis, which includes juvenile xanthogranuloma (JXG), ECD, and Rosai-Dorfman disease. The Class III category includes malignant histiocytic disorders.[4]

Up to 12% of ECD cases show some overlapping with LCH, however, a distinction can be made among them through histopathological and immunohistochemical features. ECD is characterized by xanthogranulomatous infiltration of foamy histiocytes often
 

 

 

 

 

surrounded by fibrosis.[5] They do not have Birbeck granules (a characteristic intracellular organelle found in Langerhans’ cells) and immunohistochemical staining is positive for CD68 and negative for CD1a.[6]

A mutation in the BRAF proto-oncogene (BRAF V600E) has been identified in a majority of ECD patients (40–80%) leading to an oncogenic alteration in this already calamitous disease.[7]

The differential diagnosis for ECD includes Histiocytosis X (LCH), metabolic disorders, neuro-sarcoidosis, amyloidosis, multiple sclerosis, Rosai–Dorfman disease, malignancies, and mycobacterial infections.[8]

The prognosis in ECD is dependent on the extent and distribution of the extra-skeletal manifestations and is especially poor in patients with CNS involvement. Severe pulmonary fibrosis, respiratory distress, and cardiac failure are the most common causes of death. Interferon-A, radiotherapy, chemotherapy, corticosteroids, and surgical resection have been used to combat Erdheim-Chester disease. However, no consensus regarding the best treatment has been established.[9]

Case report

A 60-year-old gentleman presented with complaints of loss of balance for 4 years, involuntary jerky movements for 2 years, and emotional lability and scanning of speech for 1 year which was clinically diagnosed as cerebellar ataxia with chorea with autonomic involvement with pituitary macroadenoma. His only history was alcohol consumption for the past 30 years, which he stopped 4 years back. On admission, his CT scan of the neck, chest, and abdomen revealed a soft tissue-enhancing mass lesion in the mediastinum which was seen encasing the arch of the aorta and the origin of the left subclavian artery, along with an ill-defined enhancing soft tissue mass in the retroperitoneum involving bilateral perinephric fat, intrarenal sinus extension and encasing the renal pelvis and renal vessels. The soft tissue lesion was also seen along para-aortic, and pre-aortic regions along with focal encasement of the aorta. Additional findings on the CT scan were linear fibrotic bands in the medial segment of the right middle lobe, left inferior lingual segment and medial basal segment of the lung, calcified sub-centimetric right hilar lymph nodes, a tiny nodule in the right lower lobe lateral basal segment of the lung, borderline hepatomegaly, occlusion of the coeliac axis, short segment moderate/severe stenosis of the superior mesenteric artery at origin, dilatation of inferior mesenteric artery with the formation of collaterals, diffuse atherosclerotic changes, plaques and moderate stenosis of aorta, renal artery and left common iliac artery. Based on these findings a suspicion of lymphoma was considered. His CT Brain showed a fairly well-defined lesion in the pituitary fossa causing cortical erosions, suggestive of a pituitary macroadenoma measuring 1.4x1x1cm along with chronic ischemic changes and diffuse cerebral cortical atrophy with caudate atrophy. Similar findings were reported on the MRI brain along with atrophy of basal ganglia and dentate nuclei. Following these investigations, a whole-body PET -CT scan was done. PET-CT scan revealed mild diffuse increased FDG activity in midbrain and pons, focally increased FDG activity in an enhancing nodular lesion in the pituitary fossa -? Macroadenoma, mildly FDG avid soft tissue density lesion in the superior mediastinum, bilateral mild perinephric and renal sinus soft tissue thickening with minimal FDG activity, bilateral bulky adrenal glands with mild diffuse FDG activity, mildly enlarged left paraaortic nodes with minimal FDG activity, mildly FDG avid wall thickening was also detected along the abdominal aorta, aortic bifurcation, renal arteries and left common iliac artery with luminal thickening and mild FDG activity was seen in fracture sites in the right 8,9,10th ribs along with intramedullary sclerotic changes in bilateral femoral shafts. Based on the PET-CT scan findings a possibility of Erdheim-Chester disease was favored over neoplastic etiologies/ lymphoma (Figure 1).

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