INTRODUCTION: Castleman’s disease, also known as angiofollicular lymphoid hyperplasia, is a rare lymphoproliferative disorder. Multicentric Castleman’s disease (MCD) is a less common variant with combined lympho-plasmacellular predominance. MCD is strongly associated with HIV and HHV-8 infection; here we present the diagnostic challenge of a rare HIV-negative and HHV-8-negative case of MCD.
CASE PRESENTATION: A 64 year-old female with a history of Coombs positive hemolytic anemia, type II diabetes, hypertension, right breast DCIS treated with lumpectomy and tamoxifen, presented with recurrent fevers, cough, poor appetite, and a greater than 40 pound weight loss over the previous six months. Physical examination revealed a cachectic, febrile female with pale conjunctiva, bilateral axillary lymphadenopathy, and bibasilar crackles. On further review of her records, she was noted to have fluctuating bilateral subpleural nodules, infiltrates, bulky mediastinal, paratracheal, and hilar adenopathy dating back to 2004. VATS biopsy of the lung nodules was consistent with a hyalinizing granuloma in 2005. She was a never smoker and emigrated from Haiti approximately 10 years prior to her current presentation. She was intermittently treated with steroids and transfusions for her hemolytic anemia.Chest radiograph showed patchy bilateral infiltrates involving both upper and lower lobes. CT of the abdomen revealed retroperitoneal and pelvic adenopathy. Laboratory data was significant for a hemoglobin 5.9, albumin 1.5, total protein 9.9, ESR >140, and elevated haptoglobulin and reticulocyte counts. Immunofixation revealed a biclonal picture. Sputum culture for TB and fungi were negative. HIV, ANA, ANCA, anti-CCP antibody, histoplasma and cryptococcal antigen, hepatitis B and C panel were all negative. The patient was started on moxifloxacin and underwent a left axillary lymph node biopsy which revealed atypical lymphoid hyperplasia with marked polyclonal plasmacytosis, vascular proliferation, and dilated sinusoids containing eosinophilic fluid with absence of hyaline vascular follicles consistent with the diagnosis of MCD. HHV-8 was negative. The lymphoid cells were CD20 positive and plasma cells were CD 138 positive.
DISCUSSIONS: MCD is characterized by generalized lymphadenopathy with infrequent pleuropulmonary involvement. Patients experience frequent fevers, night sweats, anorexia, and weight loss. Due to its rarity, there are no good estimates of the incidence of MCD in the population (1). Fluctuating subpleural nodules, as were found in our patient, have been very rarely reported. Based on existing literature, less than a dozen cases similar to our patient have been published. Recent studies have shown that HHV-8 is found in 100% of HIV-positive MCD patients but only in 40-50% of HIV-negative MCD patients(2). Nested FISH of peripheral mononuclear cells are occasionally positive for HHV-8 in otherwise HHV-8-negative patients. An interleukin-6 (IL-6) mediated immune response against HHV-8 has been thought to play an important role in the pathogenesis of this disease. HHV-8 infected B cells secrete a virally encoded form of IL-6, which activates the human IL-6 receptor, leading to lymphoproliferation. Additionally, inhibition of human IL-6 has been shown to induce resolution of systemic symptoms in some cases. A recent literature review has identified six patients with HIV-negative, HHV-8-negative disease, four of which are still alive.
CONCLUSION: MCD should be considered in the differential diagnosis of patients with intermittent fevers, generalized lymphadenopathy and pleuropulmonary infiltrates and nodules even in HIV-negative patients. MCD has been treated with antiviral agents, interferon-alpha, steroids, rituximab, chemotherapy, or radiation depending on systemic involvement, cell markers, and the HIV or HHV-8 status. For CD20-positive patients, as is our patient, the treatment of choice is rituximab. Prognosis and response to treatment is variable, but generally poor.
DISCLOSURE: Seema Hameed, No Financial Disclosure Information; No Product/Research Disclosure Information