Imaging diagnosis
Case 243
【Progress】
She underwent tumor resection under endoscopic control. Histologic examination revealed Castleman lymphoma.
【Discussion】
Lymphoma is a kind of cancer, automatically proliferating and spreading, while Castleman disease is lymphoid tissue proliferating disease stimulated by Interleukin 6. Lymph-node composed of cortex, paracortex and medulla. Tubercle exists like septum for passage of lymph flow from several afferent lymphatic vessels to medulla via cortex and paracortex. Follicle and germ center which compose of B cells are present in the cortex. Germ center enlarges from follicle to respond antigen from afferent lymphatic vessels. Mantle zone surrounding germ cells or follicles composes of B cell or plasma cells producing antibody stimulated by antigen. Paracortex composes of T cells and dendritic cells. Medulla composes of macrophages, lymphocytes, plasma cells, mast cells dendritic cells to phagocyte foreign body or antigen to filter the lymph fluid.
Histological examination of Castleman lymph node showed characteristic findings: regressed germinal centers, follicular hyperplasia (handcuff appearance), prominent mantle zone (onion skin appearance), plasmacytosis, hypervascularity of tubercle (hyalinized capillaries, lollipop appearance) (1-4).
Cytokine is peptide, polypeptide or small protein which communicate between cell and cell. Interleukin is termed a communicating substance between leukocytes. Lymphokine is a communicating substance between lymphocytes. Interleukin 6 (IL6) is first found as cytokine and categorized into the substance communicating among leukocytes. IL6 secrete from macrophages and helper T cells causing B cells to produce antibody, and neutrocytes come or support to inflammatory sites. However, subsequently, it became clear that IL6 play roles of not only communicating between leukocytes but various communications between leukocytes and other cells IL6 causes fever to act on hypothalamus, CRP & ferritin elevation to act on hepatocytes, arthritis to act on synovial cells and osteoclasts, platelet production on megakaryocytes (5,6). Further, IL6 is secreted from various cells rather than leukocytes. IL6 is secreted from fibroblasts, endothelial cells and epidermal keratinocytes and induces new vessels and skin eruption (5,6).
As a result, IL6 is secreted to oppose antigen or foreign body and activate immune cells, hepatocytes, endothelial cells and skin keratinocytes.
Castleman disease is histologically characteristic of prominent mantle zone and plasmacytosis which produce antibody, hyalinized capillaries (new vessel formation) (1-4). These histologic findings are not contradictory with effects of IL6 on lymph node.
The similar diseases caused by IL6 are listed : adult Still disease and TAFLO syndrome (5, 6).
Castleman disease is categorized into unicentric, idiopathic multicentric and herpes virus 8 related multicentric. Of these, unicentric Castleman disease are most common. Unicentric Castleman disease arises from only one lymph-node, leading to swollen mass (1-4). If the concentration of IL6 is related to arise the disease, unicentric Castleman disease might be caused by secretion of macrophages or dendric cells habiting in the lymph node.
In our case, CT showed retroperitoneal mass with hypervascularity. An arterial phase on contrast-CT and EOB-MRI showed hyper vascular islands probably corresponded to germ center. These findings meet the outcomes of IL6 activity by macrophages or dendric cells.
【Summary】
We presented a sixty five-year-old female with liver dysfunction due to hepatitis B infection. She took contrast-enhanced CT and EOB-MRI for detection of possible hepatocellular carcinoma. They showed a mass in the retroperitoneal space with hyper vascularity. She underwent surgical resection whose histologic examination revealed unicentric Castleman disease. It is borne in mind that normal lymph-node composes of cortex, paracortex and medulla. Germinal center enlarge when exposed by antigen and mantle zone accumulated B cells surrounding germ center produce antibody. Castleman disease causes prominent mantle zone and new vessel formation in the center of germ center. These findings meet the outcomes of IL6 activity by macrophages or dendric cells in the local lymph-node. IL6 is secreted from macrophages, T cell fibroblasts, endothelial cells and epidermal keratinocytes, leading to antibody production, causes new vessel formation and skin eruption, meeting the findings of Castleman disease.
【References】
1.Dispenzieri A, et al. Overview of Castleman disease. Blood 2020; 135: 1353–1364.
2.Yoshizaki K, et al. The Role of Interleukin-6 in Castleman Disease. Hematology/Oncology Clinics of North America 2018; 32:23-36
3.Leger-Ravet MB, et al. Interleukin-6 gene expression in Castleman's disease. Blood 1991 ;78:2923-2930 Fajgenbaum DC, Uldrick TS, Bagg A, et al: International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood 129: 1646-1657, 2017
4.Liu AY, Nabel CS, Finkelman BS, et al: Idiopathic multicentric Castleman's disease: a systematic literature review. The Lancet Haematology 3: e163-175, 2016
5.Nishimoto N, Terao K, Mima T, et al: Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 112: 3959-3964, 2008
6.Iwaki N, et al. Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease. American Journal of Hematology 2016; 91 (2): 220-226..
2021.9.10