Castleman disease (CD) is a rare lymphoproliferative disorder that presents with various symptoms. CD accompanied with jaundice is uncommon since there are only 11 cases reported in the literature.

Here we report a 62-year-old woman who was admitted to the hospital with signs and symptoms of intermittent jaundice. Biochemical tests showed higher serum levels of total and direct bilirubin, and normal serum levels of tumor markers and interleukin-6. Contrast-enhanced computed tomography detected a 6 cm × 4 cm × 2.5 cm mass between the hepatoduodenal ligament and the inferior vena cava. The mass was successfully excised and the patient had a complete resolution of symptoms. A diagnosis of idiopathic unicentric CD was made based upon histological examination, which demonstrated the pathological features of CD of mixed type, including hyperplasia of follicular lymphoids with abundant plasma cells, degenerative germinal centers, interfollicular vascularity and hyaline degeneration. The diagnosis was corroborated by immunohistochemical analysis which detected multiple biomarkers.

This is the first study that describes the clinicopathological features of CD presenting with jaundice, which may deepen and extend our understanding of this disease.

Castleman disease (CD) is a rare lymphoproliferative disorder that was first described by Benjamin Castleman in 1956[1,2]. Its worldwide annual incidence is only around 15.9 to 19.1 cases per million subjects[3-5], but more cases have been reported recently[3]. This disease can be clinically delineated as unicentric CD (UCD) and multicentric CD (MCD) subtypes with different outcomes[6,7]. MCD occurs systemically, involves multiple groups of lymph nodes and is associated with systemic inflammatory symptoms, and the differential diagnosis is ascertained from lymphoma[8]. By contrast, UCD affects a single lymph node or a group of adjacent lymph nodes in a specific anatomical site, commonly involving the mediastinum and thoracic lymph nodes; and the mass is usually observed incidentally upon physical or medical imaging examination. In some cases, UCD is found symptomatically because of the compression of local structures by the enlarged mass. In most patients, UCD can be curatively treated by surgical excision, while systemic therapy is required for the effective management of MCD[7]. Three pathological types, namely, hyaline vascular, plasmacytic and mixed, have been reported in both UCD and MCD[7]. Here we report a rare case of UCD presenting with intermittent jaundice caused by extrinsic compression of the mass located between the hepatoduodenal ligament and the inferior vena cava. In order to extend our understanding of this disease, we review the relevant literature and summarize a total of 11 cases involving CD accompanied by jaundice.

Based on the above clinicopathological feature and immunohistochemical analyses, a diagnosis of UCD of mixed type was made.

As described above, the mass was surgically removed. No non-surgical treatment was given to the patient.

After surgical treatment, the clinical manifestations disappeared and serum levels of bilirubin returned to normal. The patient remained well without jaundice after a 12-mo follow-up.

Until now, 12 cases of CD presenting with jaundice including the present case have been described in 10 reports in the literature (Table 1)[18-27]. Of the 12 cases, MCD and UCD were equally divided; 7 (58.3%) were of hyaline vascular type, 3 (25%) of plasma cell type, and 2 (16.7%) of mixed type. All the cases of UCD were successfully excised and had a complete symptom resolution within the term of follow-up, while the cases of MCD were either partially controlled or relapsed.

CD comprises a heterogeneous group of disorders and presents with diverse symptoms and signs due to the location, size, extent and diffusion[4]. This leads to difficulties in arriving at a differential diagnosis, and surgical excision is usually not only a diagnostic but also a curative method for the management of the disease, particularly for UCD. Therefore, in addition to clinical manifestations, evaluation of CD should also include pathological analysis with immunohistochemistry, laboratory investigation and systemic imaging.

MCD is classically distinguished from UCD by the presence of systemic symptoms, such as fever, asthenia, pleural effusion, ascites, the presence of lymph nodes in more than one region, hepatosplenomegaly, signs of inflammation and a poorer prognosis[7]. However, in approximately 60% of cases of UCD, the presentation is asymptomatic with accidental detection of a mass[28]. Some patients are diagnosed with UCD because enlarged lymph nodes impede nearby organs. The main manifestation of UCD is related to local complications of a mass with extrinsic compressions, such as renal obstruction, dyspnea, cough, abdominal pain and other signs[6]. The plasma cell variants are the most common type of MCD (75%) but represent only 10%-20% of UCD[6,28,29]. MCD may affect other organs containing lymphoid tissues and often occurs in people infected with the human immunodeficiency virus. Interleukin-6 has been shown to play a major role in the pathogenesis of both UCD and MCD since it stimulates B-cell proliferation and survival through multiple signaling pathways[9].

The majority of UCD cases are the hyaline-vascular variants, characterized by hyalinized blood vessels between follicles with few plasma cells, whereas a small number of cases are plasma cell variants, which show characteristic sheets of mature-appearing plasma cells in the interfollicular region[8]. CD mimics a number of neoplastic entities and therefore immunohistochemistry can help for differential diagnosis[29]. UCD involving the pancreas and bile duct is rare, with only 11 cases reported (Table 1)[18-27]. In this case, UCD should also be differentiated from lymph node metastases of malignancies by using positron emission tomography/CT (PET-CT), magnetic resonance imaging (MRI) and/or endoscopic retrograde cholangiopancreatography (ERCP), which would guide the therapeutic management. An endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNA) would also help to make a pathological diagnosis preoperatively. Unfortunately, none of the above examinations apart from dynamic CT were employed in this case due to the inaccessibility of facilities and high cost. Radiation therapy may be an option for the disease with incomplete excision, or if the patient is in poor health and unable to undergo surgery.

In summary, here we report a case of CD presenting with intermittent jaundice with slight abdominal tenderness. Contrast-enhanced CT scanning detected a mass between the hepatoduodenal ligament and the inferior vena cava, which was successfully excised, and the patient had a complete symptom resolution. Histological examination demonstrated the pathological features of idiopathic UCD of mixed type, supported by immunohistochemical detection of multiple markers. Excluding the current case, there have been only 11 reported cases of CD presenting with jaundice. To our knowledge, this is the first study that combines clinicopathology and immunohistochemistry in diagnosing CD accompanied with jaundice, which may deepen and extend our understanding of this orphan disease.

The case of CD with jaundice presented herein, together with literature review, indicates that CD may present with diverse clinical symptoms and signs because of the location, size, extent and diffusion of the mass. The information from clinical symptoms and signs, laboratory tests, imaging examinations, pathological and immunohistochemical analyses should be comprehensively considered. Other examinations not used in the present case, such as PET-CT, MRI, ERCP and EUS-FNA, may be helpful for an accurate preoperative diagnosis and therapeutic management.