Castleman’s disease (CD) is a rare lymphoproliferative disorder of unknown aetiology presenting with different clinical manifestations in young adults. There are two main types, unicentric occurring in a younger age group and multicentric occurring in older people. We report the case of 22-year-old man who initially presented with acute appendicitis. During his admission he had a routine chest radiograph which demonstrated a mass lesion, later diagnosed as Castleman’s disease of hyaline vascular type. He underwent a right pneumonectomy for complete excision and made an unremarkable recovery.
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This case report highlights the possibility of Castleman’s disease in an asymptomatic patient and shows that a definitive histological approach is mandatory to diagnose the disease along with other investigations to rule out dissemination.
We report the case of 22-year-old man who was incidentally found to have a mass in his right lung on chest radiograph. He had initially presented with right iliac fossa pain and was diagnosed as having appendicitis. He underwent an appendicectomy. Histology confirmed necrotic, non-malignant appendicitis.
The patient had a past history of childhood asthma with eczema but was otherwise medically fit and healthy with no history of weight loss or fevers. Despite his young age, he had a 9-pack-year smoking history and no significant family history of chest disease. On examination his oxygen saturations were 97% with a clear chest. No other abnormalities were found. After appendicectomy he was investigated further for the lung mass.
During the pre-operative check-up, the mass was detected on routine chest radiograph (figure 1). The patient later had a contrast enhanced computer tomogram (CT) of his chest and upper abdomen which revealed a right sided lung mass measuring 50 mm in transverse diameter with significant mediastinal lymphadenopathy in the subcarinal space (figure 2). There was no evidence of metastases, other lesions or any abnormality below the diaphragm. He had a bronchoscopy which demonstrated normal airways and lavage was taken for microscopy, culture and sensitivity, and cytology, which were all negative. Other investigations including full blood count, vasculitis screen, HIV test, immunoglobulins and liver function tests were unremarkable.
The patient was subsequently referred to the regional cardiothoracic centre where he was reviewed and treated with a right pneumonectomy with removal of involved lymph nodes. The resected specimen of the right lung consisted of a homogeneous tumour, tan to light brown in colour, in the middle lobe measuring 50×42×28 mm, slightly away from the bronchial resection margins. Cut surfaces were homogenous pale brown with patchy white areas. The paraffin sections of the mass and lymph nodes were reported as showing reactive hyperplasia and nodular lymphoid proliferation with the nodules being composed essentially of B cells expressing CD20 and CD79a but no follicle centre subset markers bcl-6 or CD10. There was also strong expression of bcl-2 protein. The nodules contained dense dendritic cells particularly in the hyalinised areas in the centre, with strong expression of CD21 and CD35. There was no expression of viral associated proteins and no evidence of any neoplasia was found. The diagnosis was angiofollicular hyperplasia, Castleman’s disease of hyaline vascular type.
Outcome and follow-up
The patient has made a very good recovery after surgery. He is currently under follow-up with the haematologists.
Castleman’s disease, a very rare lymphoproliferative disorder of unknown cause, was first described over 50 years ago in 1956 by Dr Benjamin Castleman, a pathologist at Massachusetts General Hospital.1,2 It was first reported in a group of patients with benign localised hyperplastic lymph nodes.2 Although the aetiology is not completely understood, the pivotal roles of HHV8 and overproduction of interleukin-6 (IL-6) have been emphasised.1 The causative association with IL-6 is based on several observations. The removal of the lymph node masses causes an abrupt drop in IL-6 levels and resolution of symptoms.3 Also, treatment with IL-6 receptor antibody relieves the symptoms and signs of the disorder.3 In addition to overproduction of IL-6, tumour necrosis factor-β and γ-interferon have been proved to be at high levels in Castleman’s disease.4 The combined effects of these two cytokines explain the clinical findings of fever, cachexia, autoimmune disease and abnormal lymph node architecture in Castleman’s disease.4 Increased vascular endothelial growth factor (VEGF) expression has been observed in the interfollicular area of Castleman’s disease lymph nodes and in the supernatant of cultured plasma cell variant (PCV) lymph nodes.3 In one study, VEGF expression was observed in five out of eight cases of Castleman’s disease in germinal centres containing small vessels by in situ hybridisation.5
Other aetiologies such as chronic inflammation or infection, autoimmune processes or immunocompromised states, have been considered.1,3,6 Depending on the number of areas of origin, the disease is been classified as unicentric or multicentric.1 As regards histology, it is classified into the three main types of hyaline vascular (HV) pattern, PCV and mixed cellularity type.7
Unicentric Castleman’s disease is the localised or solitary form predominantly found in young adults.6 It is equally distributed in either sex. The HV type is the most common, occurring in about 85% of cases, with the PCV type being rare.7
Patients with the HV type are usually asymptomatic.6 They generally present with a mass in the mediastinum, but masses have also been reported in the neck, axilla, mesentery, retroperitoneum and soft tissues of the extremities.6 The PCV type presents with fever, night sweats, malaise, lymphadenopathy, splenomegaly, anaemia and thrombocytopenia.7
Surgical resection is the primary treatment for localised Castleman’s disease and is curative in most cases. Prognosis is usually excellent.2,3,8
Multicentric Castleman’s disease, being the least common, presents at an older age, involves more than one group of lymph nodes and presents with manifestations of multisystem involvement.1 It affects males slightly more than females with ratio of about 2:1. It carries a poor prognosis in comparison with unicentric Castleman’s disease.1 Most multicentric cases are of the PCV type presenting with marked lymphadenopathy, hepatosplenomegaly, cytopaenias, hypergammaglobulinaemia, hypoalbunaemia, etc.1,7
Various treatment modalities including chemotherapy, corticosteroids, anti-IL-6, radiotherapy, α-interferon and rituximab (anti-CD20) have been used but with little benefit.1,2,9,10 Surgery although curative in unicentric Castleman’s disease, is the least feasible option in multicentric disease.2,8
Due to the small number of patients with multicentric Castleman’s disease receiving different types of treatment and also the relapsing and remitting nature of the disease with continuing uncertainty about the pathophysiology, optimal definitive therapy is still uncertain. Further research is warranted to determine the treatment regimens that would be most effective.
The possibility of Castleman’s disease in an asymptomatic individual should be considered.
Detailed investigation along with a histological approach to rule out dissemination is required.
Surgery can be curative in unicentric disease.
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.