The full spectrum of Castleman disease: 273 patients studied over 20 years

Abstract

The spectrum of Castleman disease (CD) has considerably extended since its first description in 1956. Recently, an international collaborative working group has reached consensus on the diagnostic criteria and classification of CD. We herein report 273 patients with lymph node histopathology consistent with CD and investigate the newly established diagnostic criteria. Twenty of these patients with Castleman-like histopathology were removed from analyses, because they were diagnosed with an exclusionary disorder (18 with haematological malignancy). Among the 253 remaining patients, 57 were considered unicentric CD (UCD), 169 were multicentric CD associated with Human Herpesvirus 8 (HHV-8+MCD), including 140 patients with human immunodeficiency virus (HIV) infection and 29 patients without HIV infection, and 27 were HHV-8 negative/idiopathic multicentric CD (iMCD). 2-( F)fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography was useful in 62 patients for staging/classification of the disease and for excluding associated lymphoma. UCD was mainly associated with hyaline-vascular histopathological features, and most patients were asymptomatic. Of the 27 patients that we had originally diagnosed with iMCD, 26 met the newly established diagnostic criteria. Patients with iMCD and HHV-8+ MCD demonstrated similar characteristics, including fever, splenomegaly, cytopenia and inflammatory symptoms. However, the disease was more aggressive in HHV-8+ MCD, particularly in HIV-infected patients.

Castleman disease in pediatrics: Insights on presentation, treatment, and outcomes from a two‐site retrospective cohort study

“…Although laboratory inflammation is expected among MCD patients, our UCD population appeared to have increased inflammation compared with adult cohorts. For example, whereas in our cohort, 45% of UCD patients had an elevated ESR, in an adult UCD cohort this rate was 19%, and 50% had an elevated CRP …”

“…Similarly, in our pediatric/AYA cohort, systemic symptoms were more common among MCD patients than UCD patients, although this difference in presentations by centricity is less striking than in adults. For example, 44% presented with systemic symptoms, which is above the upper range of the reported 10–40% rate of systemic symptoms reported in adult UCD reports . Among HHV8‐negative MCD patients in this cohort, four and six (67%) had systemic symptoms, which is at the lower end of the 60–80% range reported in adult cohorts …”

“…One patient met criteria for thrombocytopenia, anasarca, myelofibrosis, renal failure, and organomegaly (TAFRO) syndrome by modified consensus criteria . No patients had polyneuropathy, which is described in adult populations . Four had HV disease and two had PCV disease (Table ).…”

“…In adults, histopathologic variant is associated with variation in presentation. Adults with the HV variant are likely to have UCD and often lack systemic or constitutional symptoms; when adults with HV variant present with MCD, it is often associated TAFRO and inflammatory milieu . In contrast, patients with the PCV, regardless of centricity, often have fevers, diaphoresis, arthralgia, neuropathies, and laboratory derangements such as elevated IL‐6, hypoalbuminemia, microcytic anemia, elevated ESR, amyloidosis, and association with HHV8 .…”

“…Although complete surgical resection is typically curative for patients with UCD, patients with MCD or unresectable UCD disease have significantly worse prognosis due to lack of consistently effective therapies, with no consensus regarding first‐line treatment until recently . New consensus guidelines recommend use of anti‐interleukin‐6 (IL‐6) monoclonal antibody (siltuximab or tocilizumab) with or without corticosteroids as first‐line therapy for idiopathic MCD .…”