Plasma Cell Castleman Disease:a Clinicopathologic Study

PurposeTo study the clinicopathologic characteristics, immunophenotype and molecular genetics of Plasma cell Castleman disease (PC-CD) with a purpose of exploring the criterion in order to differentiate from Plasma cell tumor and other diseases.Methods1.31cases of PC-CD were retrieved from the files of the Department of Pathology, Cancer Hospital, Fudan University between March2006and March2012and all the histological slides were reviewed for confirmation of pathologic diagnosis by a professional pathologist. The features of clinicopathologic and immunophenotype were analyzed.10cases of Plasma cell tumor,2cases of Marginal zone lymphoma and7cases of reactive lymph node lesions were collected as a control group.2. LNA-1、CD20、CD3、CD38、CD138、IgM、IgG, IgG4、IgD、Ki67、κ、λ proteins were immunohistochemically detected in cases using formalin-fixed, paraffin-embedded tissues by EnVision+two steps.3. Polymerase Chain Reaction (PCR) was performed to detect the immunoglobulin gene rearrangements in20cases.Results1. Clinical characters:(1) Gender:There were19male patients and12female patients (male to female,1.6:1) in31patients.(2) Age:The age of the patients ranged from20to75years with the median age of47.0years (average46.9years).(3) Position:Most cases of PC-CD occurred in lymph nodes. UCD cases were involved with abdominopelvic cavity and deep lymph nodes, but MCD most diagnosed in superficial lymph nodes.(4) Clinical manifestations:There are19cases with clinical data,5cases were diagnosed with unicentric Castleman disease(UCD),14cases were diagnosed with Multicentric Castleman disase (MCD). The clinical manifestations of PC-CD are heterogeneous, ranging from asymptomatic discrete lymphadenopathy to recurrent episodes of diffuse lymphadenopathy with severe systemic symptoms, particularly in MCD. Sever prominent clinical complications were noted in this cohort of patients with MCD. Two cases of MCD presented with POEMS syndrome,1MCD with membranous nephropathy,1UCD with gastrointestinal stromal tumors.(5) Treatment:Five UCD patients were treated with surgery. Five of nine MCD patients accepted chemo-therapy, one MCD accepted traditional Chinese medicine, one MCD accepted prednisone, one MCD accepted anti-IL-6antibody and the last one MCD was not treated at all.2. Prognosis:The course of the patients ranged from40days to30months in14cases with follow-up data. The prognosis of patients with PC-CD was favorable. All of the14patients in follow-up are alive.3. Pathologic findings:(1) Histological findings:PC-CD is characterized by observing lymph node structure(31/31,100%), hyperplasia follicle (19/31,61.2%) with part of follicles coalescing. There are varying degrees of thickening mantle zones (30/31,96.8%) which don’t perform onion skin-like structure. The lymph sinus open in most of cases (18/31,58.1%). The accumulation of copious plasma cells in interfollicular areas (29/31,93.5%) could be mature(23/31,74.2%)or inmature(8/31,25.8%), the immature plasma cells can be atypical hyperplasia (6/8,75.0%) which always presented with enlarge nucleus, deeply stained nucleus, irregular nuclear shape and multinucleated cells. The vascular proliferation almost exist in all cases (29/31,93.5%), partly with perivascular hyalinization (13/31,41.9%), hardly with high endothelial venules (4/31,12.9%). There are varying degrees of stroma collagenzation (19/31,61.3%) Most cases have Russel body (25/31,80.6%) while Dutcher body are not common (2/31,6.5%). It’s difficult to identified UCD from MCD on histopathology.(2) Immunohistochemical findings:Light chian restriction of the28PC-CD cases were tested. There were8cases showed λ. light chain restricted expression.The expression rate is25.8%. The positive expression rate of the UCD and MCD is0and28.6%(4/14) respectively. All cases of PC-CD don’t express LNA-1. The expression of Ki-67proliferation index of25cases is very low, rang from3to25%. Four of16cases have more than50per high power field in IgG4detection, all of them are UCD cases. 4. Molecular genetics:Immunoglobulin gene rearrangement was analysed in20cases, accounting for64.5%of all cases, nine cases showed positive results(9/20,45%).Conclusions1. PC-CD mainly occurs in middle-aged adults with a male predilection.2. The most common sites of PC-CD were lymph nodes. UCD cases were involved with abdominopelvic cavity and deep lymph nodes, but MCD were most diagnosed in superficial lymph nodes.3. Histologically, the PC-CD was characterized by observing lymph node structure and the accumulation of copious plasma cells in interfollicular areas. Plasma cells could be mature or inmature, the immature plasma cells can be atypical hyperplasia.4. The PC-CD light chain restriction expression was28.6%(8/28) which all are λ light chain. There is no statistical significance between the UCD and MCD. All cases of PC-CD don’t express LNA-1.5. The biological essence of the PC-CD are reactive lesions and tumor precursor lesions or potential malignant lesions.6. The PC-CD is divided into two groups:λ light chain restricted expression subtype and non-λ light chain restricted expression subtype. The eight cases with immunoglobulin light chain restricted expression has its unique characteristics:atrophy germinal center, immature plasma cells and most of plasma cells atypical hyperplasia, and it performs a group of tumor precursor lesions or potentially malligant lesions in clinical practice. Non-λ light chain restricted expression subtype represents a group of reactive lesions.7. The immunoglobulin gene rearrangement analysis in UCD is negative while parts of MCD cases are positive.