Castleman’s disease is characterized by localized or multicentric hyperplasia of lymph nodes. We present here a case of abdominal mass with eosinophilia and a review of the literature. Castleman’s disease should be suspected in a mediastinal or retroperitoneal mass, particularly in the presence of haematological abnormalities such as eosinophilia and hypergammaglobulinaemia.
Castleman’s disease (CD) is an uncommon
disorder characterized by benign tumours that may develop in the lymph node tissue throughout the body. Most often, they occur as isolated or multiple tumours in the chest, abdomen and neck. Less common sites include the axilla, pelvis, and pancreas. Clinically, solitary and multicentric types are seen, the former usually amenable to partial or complete surgical extirpation with low recurrence rates; while multicentric variant has a stormy clinical course and is less responsive to surgery, and medical management in the form of immunosuppression forms the mainstay of treatment in such cases.
A 28 year old lady presented with an abdominal lump of 2 years duration. She was previously explored for the same lump; however the tumour could not be removed. She presented with abdominal pain. Examination showed a 10 x 9 x 6 cm, non tender, firm, mobile lump in the upper abdomen. Her eosinophil count was extremely raised (35%). All other biochemical investigations were normal. Computed tomography scan showed a large, enhancing, homogenous retroperitoneal mass suggesting a leiomyoma (Fig. 1). At laparotomy, the tumour was found to be well encapsulated and extremely vascular, displacing the kidney and ureter posterolaterally and pushing the descending colon anteriorly. There was no invasion of any of these structures. The tumour was completely removed and the patient had an uneventful recovery.
Pathology - The specimen showed a well encapsulated tumour with an external bossellated surface. Cut surface was fleshy and yellowish brown in colour (Fig. 2). Microscopically it showed a well encapsulated lesion composed of numerous follicles with interfollicular regions. Follicles showed presence of central arteriole with
|Fig. 1 : CT plate showing homogenous non enhancing tumour.
||Fig. 2 : Photograph showing cut surface of specimen.
surrounding small lymphocyte population. Interfollicular regions showed numerous small vascular channels with lymphocytes and plasma cells. Final report mentioned hyaline vascular variant of Castleman’s disease.
CD is an uncommon and poorly understood lymphoproliferative disorder of unknown aetiology, described first by Castleman in 1956. It is known by various names including Angiofollicular Lymph Node Hyperplasia, Angiomatous Lymphoid Castleman tumour, Giant Benign Lymphoma, Hamartoma of the Lymphatics or Giant Lymph Node Hyperplasia.1 It commonly presents as a mediastinal mass. Less frequently involved sites include the neck, retroperitoneum, mesentery and axilla. Two distinct clinical presentations are described. A localized and a multicentric variety. Histologically, three types have been described, hyaline vascular, plasma cell, and mixed type.
The case we have reported classically presented with an abdominal lump and pain. Computed tomography showed a retroperitoneal non enhancing tumour. Such a retroperitoneal pararenal location for CD is uncommon and infrequently reported in the literature.2
Most patients with the hyaline vascular sub-type are generally asymptomatic and detected incidentally as a solitary middle or posterior mediastinal mass on chest radiographs.
In Plasma Cell variety there is usually multicentric lymph node involvement and hepatosplenomegaly (although focal disease can be found in 10% of cases). Patients tend to be older individuals in their 5th or 6th decade presenting with fever, weight loss, moderate anaemia, elevated ESR, polyclonal hypergammaglobulinaemia, and hypoalbuminaemia. Dysregulation of interleukin-6, and recently interleukin-5 has been implicated in the pathogenesis of plasma cell CD.3 The increased IL-6 production is responsible for the marked plasma cell infiltration and elevated gammaglobulin levels. Reported associations include POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes), paraneoplastic pemphigus. Hodgkin’s and non-Hodgkin’s disease, Kaposi’s sarcoma, follicular dendritic cell sarcoma and myasthenia gravis.
Radiological findings in localized CD are generally non specific and accurate preoperative diagnosis can be difficult. Plain film typically reveals a well defined mass with smooth or lobulated borders within the mediastinum or hila. Plain CT shows the masses are usually homogeneous, but they can also appear heterogeneous. Contrast enhancement is less with the plasma cell variant. Calcification is more common in abdominal than in thoracic lesions. Radial or star shaped calcification is said to be characteristic of CD.
MR imaging shows heterogeneous signal intensity higher than skeletal muscle on T1 images and marked hyperintensity on T2 images. Peripheral foci of decreased signal correspond to vascular flow voids. The lesions enhance after the administration of gadolinium.
Mulicentric variant (predominantly plasma cell type) characteristically shows no dominant mass. Multiple enhancing nodes, splenomegaly and ascites may be seen. Thin section CT findings in mediastinal CD include the presence of poorly defined centrilobular nodules, thin-walled cysts, thickening of the bronchovascular bundles and interlobular septal thickening, possibly due to an associated lymphocytic interstitial pneumonitis.4
Surgical removal of a unicentric mass of hyaline-vascular or mixed type is curative. Partial resection, radiotherapy, or observation alone may avoid the need for excessively aggressive therapy. Following excision, chances of recurrence are almost nil.
Patients with multicentric disease, either hyaline-vascular or plasma cell type, do not benefit from surgical management and should be candidates for multimodality therapy.5 Complete remissions in patients with multicentric disease have occasionally been achieved with combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine and prednisone.
Humanized anti-IL-6 receptor antibody has been used to treat patients with multicentric CD. Patients improved symptomatically with decreased lymphadenopathy and hypergammaglobulinaemia, and reduced follicular hyperplasia and vascularity on histopathology. Thalidomide, a powerful cytokine disruptor, has also been reported to have good therapeutic efficacy in treating multicentric CD.
Castleman's disease is a rare benign hyperplasia of the lymph nodes. It should be suspected in patients presenting with mediastinal or abdominal masses with haematological abnormalities like hypergammaglobulinaemia. Unifocal disease is cured by surgery; whereas for multicentric disease treatment remains unsatisfactory.
- Juan Seco, Fermin Velasco, Javier Manuel, et al. Retroperitoneal Castlemans disease. Surgery 1992; 112 (5) : 850-55.
- Marwah N, Sharma R, Marwah S, Singh S, et al. Castleman’s disease of the retroperitoneum - a case report. Indian J Pathol Microbiol 2002; 45 (3) : 335-6.
- Ishii T, Tatekawa T, Koseto M, et al. A case of multicentric Castleman’s disease demonstrating severe eosinophilia and enhanced production of interleukin-5. Eur J Haematol 2003; 70 (2) : 115-8.
- Johkoh T, Muller NL, Ichikado K, et al. Intrathoracic multicentric Castleman disease: CT findings in 12 patients. Radiology 1998; 209 (2) : 477-81.
- Bowne WB, Lewis JJ, Filippa DA, et al. The management of unicentric and multicentric Castleman’s disease: a report of 16 cases and a review of the literature. Caner 1999; 85 (3) : 706-17.