Case Description

A 65-year-old woman presented to the hospital with a mass in the right flank area during a routine physical examination. The patient claimed not to have a fever, hypertension, diabetes, or any other hormone disorders. Laboratory investigations showed that noradrenaline and vanillylmandelic acid in the urine were slightly elevated, and the levels of peripheral CD3⁺ T cells and CD4⁺ T cells were reduced while the number of natural killer cells was increased. Abdominal CT was performed, and it revealed a 4.6 × 2.9 cm solid right retroperitoneal mass with a well-defined boundary which moderately and heterogeneously enhanced after contrast-enhanced scanning (Fig. 1). Subsequently, laparoscopic retroperitoneal tumor resection was carried out and the surgical sample was stained with hematoxylin and eosin. Surprisingly, it was a large lymph node with loss of normal structure not a primary tumor of the adrenal gland (Fig. 2). Combined with the expression profiles of CD5-positive, Bcl-2-positive, CD20-negative, CD3-negative, CD21-negative, Bcl-6-negative, CD23-negative, CD38-negative, and Cyclin D1-negative immunohistochemistry methods, it coincided with the clinicopathological features of the Castleman disease. No abnormalities were found during the follow-up.

Discussion

Castleman disease was first reported by Castleman in 1954, who described a mass of the mediastinum whose histopathology showed obvious hyperplasia of lymphatic follicles and capillaries. Virus infection, abnormal immune regulation, and inflammatory factors are thought to be related to its development, although the etiology and pathogenesis are still uncertain.^1,2 Nishimoto et al found that interleukin 6 (IL-6) plays an important role in the occurrence and development of Castleman disease and is often at high levels in the serum of patients.³ In our case, the patient also had abnormal immune function, which was characterized by low cellular immune response and inversion of the CD4⁺/CD8⁺ ratio, but the level of IL-6 was normal. At present, there are no unified criteria for the diagnosis of Castleman disease, which mainly depends on pathological diagnosis. Theoretically, Castleman disease could occur in any lymphatic tissue of the body with the presentation of lymph node enlargement. The localized type and multicentric type are the 2 most common types of Castleman disease despite the high heterogeneity of clinical manifestations. The retroperitoneal Castleman disease we report herein belongs to localized Castleman disease, and usually has the potential for surgical cure. However, multicentric Castleman disease often requires systemic therapy, which implies a search for lymphadenopathy elsewhere in patients having single lymph node enlargement in the chest and abdomen.

In recent years, researchers have been seeking insights on the pathogenesis of Castleman disease. Goodman et al reported 4 novel somatic mutations that may be involved in the neoplastic process of Castleman disease using next-generation sequencing.⁴ Wing et al found that the upregulated expression of IL-6 and VEGF is more likely to occur in patients with multicentric Castleman disease.⁵ GSK3β- and CCR6-positive megakaryocytes of the bone marrow may be potential factors that activate multiple pathological processes of multicentric Castleman disease.⁶ Nevertheless, current studies are only based on a small number of cases, and we still lack a deep understanding of Castleman disease. Only by establishing a worldwide sample bank of Castleman disease as well as integrating traditional methods and modern new technology platforms can we truly explore the essence of Castleman disease.