Abstract
Castleman's disease is a rare clinicopathological entity characterized by non-neoplastic lymph node hypertrophy. Its incidence and etiology is unknown. It has been found in association with Kaposi's sarcoma thus necessitating investigations for HIV. Although its localized variety is benign other types can be multifocal with adverse systemic manifestations. A case report of a 42 yrs old female with a slowly enlarging highly vascular mass in the left iliac fossa is presented which lead to a histological diagnosis of this rare condition (see picture). Furthermore its clinical features, its types, relevant investigations and current treatment modalities are discussed.
Keyword: Castleman's disease, Kaposi's sarcoma, HIV, Lymph nodes
1. Case report
A 42-yr old female presented with a history of a slowly growing mass in her left iliac fossa for 2 yrs. She was largely asymptomatic except for occasional discomfort around the mass. Her past medical and family history was non-specific. On examination a non-tender, firm mass was palpated but there was no generalised lymphadenopathy or organomegaly. All her blood results were normal including those for abnormal hormone production. A MRI scan revealed a highly vascular, 6.6 cm × 4.6 cm mass lying just anterior to the left external iliac artery, possibly lymphoid in nature (Fig. 1).
Fig. 1.
MRI scan revealed a 6.6 cm × 4.6 cm vascular mass, a likely lymphoid lesion, just anterior to the left external iliac artery.
A surgical excision of the mass was carried out under general anaesthetic and histopathology showed hyaline variant of localized Castleman's disease. The patient was referred to a hematologist. Tests for HIV and HHV 8 were done, both of which were negative. The patient remains asymptomatic 8 months post op with no further lymph node enlargement.
2. Discussion
Castleman's disease is an uncommon clinicopathological entity characterized by non-neoplastic lymph node hypertrophy and histologically characterized by angiofollicular lymph node hyperplasia. Castleman et al first described it in 1956 in a group of patients with localized benign lymphadenopathy.1
The incidence is not known and can occur at any age, though it has mostly been reported in adults in the literature.
Etiology of this disease is unknown, though it has been found in association with Kaposi's sarcoma.
Synonyms
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Angiofollicular lymph node hyperplasia
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Angiofollicular lymphoid hyperplasia
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Giant lymph node hyperplasia
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Lymphoid hamartoma
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Benign lymphoma
Types
Clinically the disease has 2 forms:
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Localized as first described by Castleman, which is more common.
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Multicentric disease (MCD) with involvement of several sites, which was first described by Gaba et al. in 1972.2
Histologically the main types are:
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The hyaline vascular type characterized by lymphoid follicular proliferation at different levels of maturity, often forming a layered or ‘onionskin’ pattern surrounding a hyalinised vessel at the center of the follicle. These vessels are often prominent and reactive. This is more commonly seen in the localized form of the disease.
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The plasma cell variant has sheets of mature plasma cells within the interfollicular tissues surrounding larger germinal centers and has significantly less vascularity. The multicentric form of the disease is nearly always associated with this variant.
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A third histological variant showing a mixed picture can also be seen in MCD.
2.1. Clinical features and investigations
The localized form of the disease is mostly asymptomatic with a single site lymph node enlargement. The sites commonly involved are abdomen, peripheral lymph nodes and the mediastinum. It is often discovered incidentally during routine examination, chest X rays or due to discomfort secondary to local compression as is in our case described above. Diagnosis is made by histological analysis of the lymph node biopsy to distinguish it from a thymoma.
MCD, however, presents with systemic symptoms along with multiple lymph node hyperplasia. The systemic symptoms are thought to be primarily a consequence of elevated Interleukin-6 (IL-6) production. They present as asthenia, weight loss, fever, polyadenopathy with a mean of four-site involvement and is often associated with hepatosplenomegaly.
Some forms of MCD have been found in association with Kaposi's sarcoma, which develops in the clinical course of most HIV positive MCD cases3. An association with HIV negative Kaposi's sarcoma has also been seen to a much lesser extent. HIV positive MCD shows an increased prevalence of pulmonary symptoms and can be differentiated from other types of HIV-associated systemic lymphoproliferative disorders. There is also an increased progression of HIV positive MCD to HHV 8 associated malignant non-Hodgkin's lymphoma4.
Routine blood tests usually reveal anaemia, raised ESR, thrombocytopenia and raised polyclonal gamma globulins. Identifying an immunophenotypically varied population of B-lymphocytes with polyclonal surface and cytoplasmic immunoglobulin markers helps to confirm the diagnosis of Castleman's disease and differentiate it from lymphoma5. HIV testing should be undertaken with the patient's permission. Herpes Virus (HHV 8/KSHV) has been isolated in almost all cases of HIV associated Kaposi's sarcoma MCD and some non HIV Kaposi's sarcoma MCD prompting tests for KSHV3. Histological examination of the biopsied lymph node is essential for the diagnosis.
These findings suggest two possibilities concerning the genesis of CD:
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Opportunistic presence of HHV 8, favoured by immune perturbations.
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Direct pathogenic role of HHV 8, in association with dysregulation of cytokines.
2.2. Treatment
Localized CD usually has a good prognosis and requires surgical excision of the enlarged lymph node with no further treatment. The patients generally remain asymptomatic thereafter.
MCD however tends to have a variable prognosis with no documented treatment consensus. A variety of combination treatments have been tried with surgical excision, chemotherapy and steroids. In patients with associated Kaposi's sarcoma monthly polychemotherapy (e.g. cyclophosphamide, vincristine, doxorubicin and prednisone) has been tried with limited success. Anti-IL 6 antibodies have shown success with systemic symptoms, as have steroids. Most treatment modalities involve immunosuppression, increasing the chances of opportunistic infections. Recent suggestions are that treatment with the antiherpesvirus drug gangciclovir or the antiCD20 B cell monoclonal antibody, rituximab, may markedly improve outcome.
3. Conclusion
The aim of this discussion is to revisit this very uncommon condition and emphasis the importance of histology to seal the diagnosis from other lymphoproliferative conditions. Its association with Kaposi's sarcoma and the high prevalence of HIV necessitate investigating this condition.
Conflicts of interest statement
None.
Funding
None.
Patient consent
Obtained.
References
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