Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is an uncommon, benign proliferative histiocytic disease (1). Emperipolesis, the process by which histiocytes phagocytize intact lymphocytes or plasma cells, is characteristic of RDD (1). Typical forms of this disease present in young adults with lymphadenopathy in the neck. Extranodal RDD may involve various anatomic sites and is observed in up to 43% of RDD cases, showing various imaging features (2). Extranodal RDD has a higher tendency toward chronic relapsing processes and affects older adults. Cardiac involvement in RDD was previously documented as occurring in <0.1% of cases (3) and only a few cases of pericardial RDD with prognosis and imaging findings have been reported (4, 5). Notably, extranodal RDD arising in unusual sites may cause diagnostic pitfalls.

Herein, we describe a unique case of pericardial involvement of RDD which was initially mistaken for amyloidosis due to the coexistence of monoclonal gammopathy. In addition, the radiological characteristics observed on chest CT and PET scans are discussed to help prevent delays in diagnosis by raising suspicion of RDD as a differential diagnosis and for timely administration of proper treatment.

A 79-year-old man with a history of hypertension and idiopathic pulmonary fibrosis visited our institution due to dyspnea and chest discomfort for a week. On physical examination, no lymphadenopathy was identified. His chest anteroposterior radiograph revealed a globular enlargement of the cardiac shadow indicating pericardial effusion (Fig. 1A). The Electrocardiogram demonstrated normal sinus rhythm except for the right bundle branch block. Abundant pericardial effusion and mild left ventricular diastolic dysfunction were observed on echocardiography. Laboratory findings, including peripheral blood and urine analyses, showed anemia, elevated erythrocyte sedimentation rate and C-reactive protein (29 mm/h and 62.6 mg/L, respectively), serum immunoglobulin G (IgG) of 2787 mg/dL, a monoclonal spike on gamma globulin in serum and urine protein electrophoresis, and reversed albumin-to-globulin ratios. Serum IgG4 was in the normal range. Further assessment included serum-free light chain assay using fixed-time nephelometry and bone marrow biopsy. Serum-free kappa was 47.38 mg/L, serum-free lambda 3371.78 mg/L and the kappa-to-lambda ratio was 0.01, indicating excessive light chain secretion. On bone marrow biopsy, 9.1% plasma cells were observed, indicative of monoclonal gammopathy of undetermined significance. Enhanced chest CT scan showed a moderate amount of pericardial effusion, diffuse enhancing pericardial thickening, and a mild degree of bilateral pleural effusions (Fig. 1B). LN enlargement was not seen in the thoracic inlet and mediastinum (Fig. 1C). Subsequent ¹⁸F-fluorodeoxyglucose PET scan showed irregular thickening of the pericardium with a marked increase of metabolic activity (Fig. 1D). However, PET further showed moderate to a marked increase of metabolic activity not only in the pericardium but also in the bilateral adrenal glands, left epididymis, testis, and a slight increase of metabolic activity in the periportal area of the liver. This led to a retrospective CT review that showed bilateral adrenal gland enlargements, infiltrative soft tissue lesions, and enhancement in the left epididymis and testis, with no obvious CT abnormalities in the periportal area. Based on laboratory findings, bone marrow biopsy results, and imaging findings, this pericardial disease was indicative of amyloidosis.

Fig. 1
A 79-year-old man with Rosai-Dorfman disease of the pericardium.
A. The anteroposterior chest radiograph shows a globular enlargement of the cardiac shadow indicating pericardial effusion.

B. A mediastinal window image of chest CT shows a moderate volume of pericardial effusion, diffuse enhancing pericardial thickening, and a mild degree of bilateral pleural effusion.

C. LN enlargement is not seen in the thoracic inlet and mediastinum.

D. ¹⁸F-fluorodeoxyglucose PET scan reveals irregular thickening of the pericardium with a significant increase in metabolic activity.

E. Chest CT scan obtained after 2 months shows no obvious remission of the pericardial thickening and aggravated bilateral pleural effusions with subtle pleural thickening despite intravenous injection of dexamethasone.

F. Under the light microscope, low power view (left upper) shows histiocytic aggregation (arrow) in the thickened pericardium with fibrosis and hemorrhage. The high-power view (right upper) shows a large histiocyte (arrow) with engulfed lymphocyte and plasma cell, known as emperipolesis. On immunohistochemistry, the histiocytes are positive for S100 protein (left lower) and CD68 (right lower), as evidenced by their brown staining.

H&E = hematoxylin and eosin

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The patient underwent pericardial window surgery for pathological evaluation. The histologic examination of the tissues showed histiocytic aggregation with emperipolesis, which engulfed intact inflammatory cells in the cytoplasm, a characteristic finding of RDD (Fig. 1F). On the immunohistochemical study, the histiocytes were positive for S100 protein and CD68 (Fig. 1F). However, they were negative for CD1a immunohistochemical stain, excluding Langerhans cell histiocytosis. There was no histopathological evidence for amyloidosis.

Consequently, an intravenous injection of dexamethasone at 40 mg/day was administered, however, obvious remission of the pericardial thickening was not observed, and aggravated bilateral pleural effusions with subtle pleural thickening occurred, which required drainage (Fig. 1E). The pleural fluid analysis demonstrated nonspecific findings (segmented neutrophil, 9%; lymphocyte, 42%; histiocyte 49%), but clinically determined a possible RDD involvement. Finally, the patient died due to multiple organ dysfunction syndrome.

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of VHS Medical Center, Seoul, Republic of Korea (IRB No. 2024-01-015). Written informed consent was waived for the single case report.

RDD is a rare, benign histiocytic proliferative disorder accompanied by massive cervical lymphadenopathy as the most common clinical symptom (1). The etiology of RDD is not yet well defined; however, a viral cause has been postulated, such as human herpes virus 6 and Epstein-Barr virus (1). It mainly manifests in the 2nd to 3rd decades of life. Extranodal RDD with the head and neck manifestation is also frequent, but other sites such as the skin, bone, and central nervous system have been reported in the literature (1). Patients with extranodal sites tend to have a fulminant course. The current diagnosis of RDD is based on identifying invasive pale eosinophilic histiocytes that show emperipolesis and are S100-positive, CD68-positive, and CD1a-negative on immunohistochemistry (1).

Cardiac manifestation of RDD is a rare occurrence and was previously documented as occurring in <0.1% of cases (1, 3). Furthermore, only a few cases of pericardial RDD with prognosis and imaging findings have been reported (4, 5). Our case shows diffuse infiltrative pericardial thickening with effusion on the chest CT scan and markedly increased metabolic activity on PET. The CT was useful for understanding the anatomical extent and the PET scan analysed the lesion's metabolic features. Imaging contributes to better characterizing the pericardial abnormality and plays a pivotal role in evaluating its complications by revealing the involvement of adjacent structures. Many relevant clinical questions that determine further management can be determined based on appropriate imaging. Thus, the CT and PET scans in the present case showed RDD presenting as a diffuse pericardial thickening with effusion.

In this case report, PET confirmed possible organ involvement other than the pericardium (bilateral adrenal glands, left epididymis, testis, and the periportal area of the liver), and CT showed abnormalities in the above areas, which led us to differentiate the possibility of systemic infiltrative disease. Considering the patient's monoclonal gammopathy, we considered AL amyloidosis to be the most likely diagnosis. Myocardial involvement (i.e., left ventricular hypertrophy) as the most common form of cardiac involvement in patients with amyloidosis was not evident in this case. However, there is a case report of amyloidosis showing isolated pericardial infiltration without myocardial involvement in the literature (6). Thus, the authors could not exclude the possibility of amyloidosis in this patient presenting with monoclonal gammopathy.

However, in the literature, monoclonal gammopathy has been observed in several RDD cases (7, 8, 9) similar to our case. Three cases of RDD with monoclonal gammopathy showing IgA paraproteinemia (7, 8) and one case of RDD with IgG paraproteinemia (9) (as in our case) were reported. The sites involved in these cases included lymph nodes, skin, head and neck, abdomen, and testis. Notably, polyclonal hypergammaglobulinemia was reported in approximately 90% of RDD patients (10). In addition, RDD has been associated with various types of neoplasms or immune diseases (1, 10).

Unfortunately, an effective treatment for RDD does not currently exist. Various immunosuppressant and chemotherapeutic drugs have been attempted unsuccessfully (1). Surgical removal or radiotherapy is often required for complete resection or local control of the lesion (1). As in the present case, corticosteroids have been used in RDD because steroids were shown to decrease the nodal size and symptoms. Steroids alone do not elicit a stable response among patients with extranodal RDD according to the consensus recommendations published in 2018 (1, 10)

The diagnosis of RDD is rarely considered, mainly because of the rarity of the disease and low probability index. In the present case, several difficulties in diagnosing were encountered. There was no superficial lymphadenopathy or involvement of the skin, bone, or other superficial organs that could perform biopsy promptly. In addition, the patient had underlying monoclonal gammopathy and possible involvement of other organs which confused a differential diagnosis of pericardial involvement such as amyloidosis. Eventually, we made a pathologic diagnosis in this patient, but unfortunately, the patient showed little response to corticosteroid treatment, leading to continuous progression with a poor prognosis. We presumed that the patient's death probably followed a worsening of the multiorgan involvement of the RDD. However, this case report is valuable because it can increase the suspicion index for RDD so that similar cases can be considered as a differential diagnosis and increase the importance of imaging in the management and follow-up of such cases, and it provides a basis for future imaging studies of similar or different forms of RDD with cardiac or pericardial involvement and accumulate relevant data by sharing an example of a very rare form of pericardial involvement although the CT and PET findings in this case are nonspecific.