Case Presentation: A 57 year-old man presented with new-onset shortness of breath and fatigue. He was admitted for symptomatic anemia which improved after receiving a unit of red blood cells. He endorsed mild fatigue and night sweats but no fevers. Further questioning revealed recent unintentional weight loss of 40 pounds and an outpatient anemia workup without clear etiology. Past medical history was significant for hematuria, for which pelvic imaging had revealed bilateral inguinal lymphadenopathy (LAD). A prior fine needle biopsy attempt was nondiagnostic. Physical exam was significant for left cervical LAD and bilateral inguinal LAD. Labs revealed a protein gap of 8.5 (total protein 10.3; albumin 1.8). HIV testing was non-reactive. Inflammatory markers, ESR and CRP, were > 120 and 23, respectively. Hematology/Oncology was consulted due to concern for malignancy and recommended imaging. CT scan showed widespread LAD in the neck, chest, and inguinal region. The largest nodes were 9.5 cm in the right cervical chain and 9.3 cm on the left. An excisional biopsy showed features consistent with Human Herpesvirus 8 (HHV-8) negative multicentric Castleman Disease (plasma cell variant), including numerous germinal centers with onion skinning, “lollipop follicles”, and occasional hyaline deposits but no atypical or tumor cells.
Discussion: Castleman Disease (CD) is a rare condition encompassing a diverse group of benign lymphoproliferative disorders frequently mistaken for lymphoma, particularly in patients presenting with stereotypical “B symptoms”. Two forms of CD are seen: unicentric, presenting with a solitary enlarged lymph node, and multicentric, presenting with symptoms from an IL-6 driven cytokine storm. The multicentric form of Castleman disease can be further subdivided into idiopathic and HHV-8 associated, the latter being more common in patients with HIV. Diagnosis of CD requires lymph node excisional biopsy, as opposed to fine needle biopsy, to distinguish from a malignant lymphoproliferative disorder. The recommended treatment for unicentric Castle man’s disease is lymph node resection. For multicentric CD, treatment is systemic. Options include rituximab, etoposide, steroids and anti-IL-6 therapies, such as siltuximab. Recurrence is not uncommon thus patients require regular surveillance. Our patient was discharged to follow up with Hematology/Oncology for initiation of siltuximab infusion every three weeks.
Conclusions: Castleman Disease is an alternative benign diagnosis that should be included in the differential for patients presenting with lymphadenopathy (diffuse or solitary), B symptoms, and lab abnormalities suggestive of malignancy.