PMC4322808_01
Histopathological findings. (A) The bone marrow appeared hypercellular with a marked expansion of granulopoiesis and a moderate increase of megakaryocytes (Periodic acid-Schiff (PAS), 20X). (B) On sections stained with the Gomori's silver impregnation technique, a diffuse and dense increase in reticulin with extensive intersections, occasionally with only focal bundles of collagen was evident. Fiber density was considered as grade 2 according to the European Consensus Criteria for grading myelofibrosis by Thiele et al. (20X). (C,D) Multiple fragments of lymph node tissue were excised from the mediastinum of this patient. The architecture was preserved, showing CD20+ B-follicles and germinal centers with onion-skin appearance around prominent arterioles. The interfollicular areas showed abundant plasma cells with normal kappa:lambda ratio. Immunohistochemistry did not reveal aberrant B- or T-cell phenotype. Molecular testing was negative for B-cell or T-cell monoclonality. The search for HHV8 and EBV was also negative. The histology pattern was considered not diagnostic for malignant lymphoma and related to a lymphadenopathy with features resembling multicentric Castleman's disease. The diagnosis was reviewed at the referral center of Bologna (Prof. Pileri) and confirmed.
40164_2014_99_Fig1_HTML.jpg
PMC4322808_01_40164_2014_99_Fig1_HTML.jpg
Fig1
A bone marrow biopsy revealed a diffuse and dense increase in reticulin with reactive hyperplastic pattern (Figure 1A,B), and a mononuclear cells immunophenotyping was substantially normal. A surgical mediastinal lymph node biopsy finally showed an histological picture suggestive for mixed-type (hyaline-vascular and plasma cell type) Castleman's disease (Figure 1C,D).
CT images. (A, B) Contrast enhanced thoracic computed tomography (CT) before (A) and after (B) six months of chemotherapy, showing resolution of pleural effusion and the shrinking of axillar and mediastinal lymphnodes. (C, D) Contrast enhanced abdominal CT before (C) and after (D) six months of chemotherapy, showing the reduction of hepato-splenomegaly and celiac and perisplenic lymphadenopathy.
40164_2014_99_Fig2_HTML.jpg
PMC4322808_01_40164_2014_99_Fig2_HTML.jpg
Fig2
A whole body computed tomography (CT) showed bilateral axillar, mediastinal and abdominal para-aortic, celiac and perisplenic lymph nodes, hepatosplenomegaly, pleural and peritoneal effusion (Figure 2A,C). Seven months after disease onset, a CT scan revealed no ascites or pleural effusion and reduction of lymphadenopathy (Figure 2B,D).
Patient's disease course (12 months-follow-up). CT: computed tomography; MRI: magnetic resonance imaging; PET: positron emission tomography; TCZ: tocilizumab 8 mg/kg; R-CVP: rituximab 375 mg/m3, cyclophosphamide 750 mg/m3, vincristine 1.4 mg/m3 and prednisone 40 mg/m3; RTX: rituximab 375 mg/m3; Hb: hemoglobin; PLT: platelet counts; CRP: C reactive protein; IL6: interleukin 6.
40164_2014_99_Fig3_HTML.jpg
PMC4322808_01_40164_2014_99_Fig3_HTML.jpg
Fig3
Clinical course and main diagnostic and therapeutic procedures are summarized in Figure 3.