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Hindawi Case Reports in Immunology Volume 2019, Article ID 5476383, 5 pages https://doi.org/10.1155/2019/5476383 Case Report Castleman Disease in a Patient with Common Variable Immunodeficiency 1 1 2 3 Luisa Ricciardi , Fabiana Furci, Antonio Ieni , and Antonio Macrì Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, Medical School Hospital G. Martino, University of Messina, Messina, Italy Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Unit of Pathological Anatomy, University Medical School Hospital G. Martino, University of Messina, Messina, Italy Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, Messina University Medical School Hospital, Messina, Italy Correspondence should be addressed to Luisa Ricciardi; firstname.lastname@example.org Received 3 January 2019; Revised 21 January 2019; Accepted 28 January 2019; Published 14 February 2019 Academic Editor: Necil Kut ¨ uk ¨ c¸¨uler Copyright © 2019 Luisa Ricciardi et al. is Th is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Common variable immunodeficiency (CVID) is a primary immunodeficiency due to a disorder of the adaptive immune system which causes hypogammaglobulinemia and therefore an increased susceptibility to infection; noninfectious, inflammatory conditions including systemic autoimmunity and lymphoproliferative complications are also commonly associated with CVID. Castleman disease (CD) is a systemic disease clinically characterized by diffuse lymphadenopathy, splenomegaly, anemia, and systemic inflammatory symptoms. is Th makes CD a great mimicker of more common benign and malignant masses in the neck, chest, abdomen, and pelvis. A novel case of primary immunodeficiency (CVID) in a middle-aged woman, who developed multicentric CD (MDC) with splenomegaly, is described. The authors suggest that the onset of MCD and of the correlated splenomegaly was due to incorrect management of the hypogammaglobulinemia as immunoglobulin G (IgG) levels were not kept within normal ranges. Correct management of the hypogammaglobulinemia allowed splenectomy to be performed without any infectious surgical complications. MCD is reported for the first time in association with an adult case of CVID. The above reported case highlights the need for a timely correct diagnosis and treatment of CVID to avoid complications, which could cause recourse to splenectomy, such as in our case or development of malignancies. 1. Introduction is cure of the infections and chronic administration of immunoglobulins [1–3]. Common variable immunodeficiency (CVID) is the most Castleman disease (CD), also known as angio-follicular common primary immunodeficiency of young adolescents lymph node hyperplasia, is a rare disorder that can be unicen- and adults, which also aeff cts children. It is characterized tric or multicentric. Unicentric Castleman disease (UCD) is by low antibody levels of immunoglobulins (IgG, IgA, IgM) localized and usually has an excellent prognosis. Multicentric that cause recurrent infections, especially bacterial, which Castleman disease (MCD) is a systemic disease clinically predominantly affect the respiratory and gastrointestinal characterized by diffuse lymphadenopathy, splenomegaly, tract. In the lung, it is common to find granulomatous anemia, and systemic inflammatory symptoms [4, 5]. This lymphocytic interstitial lung disease (GLILD) for which it makes MCD a great mimicker of more common benign and is necessary to make differential diagnosis with lymphoma. malignant masses in the neck, chest, abdomen, and pelvis as These granulomatous lymphoid aggregates may also be found MCD masses commonly raise the suspicion of lymphoma, at other sites. In patients with CVID, there is a greater risk paraganglioma, metastatic adenopathy, solid parenchymal of autoimmune diseases, lymphomas, and other neoplasms or neuroendocrine tumors, and infectious or inflammatory of the gastrointestinal tract. The treatment of this pathology diseases . 2 Case Reports in Immunology MCD is associated with an increased risk of developing spillage in the right and left iliac fossa. A thoracic-abdominal malignancies . CT with contrast medium showed the presence in both lungs of numerous occurrences of parenchymal thickening with It may manifest itself in two forms, and patients may nodular appearance, some confluent, with irregular mor- present with either an indolent disease and very slow phology, and contours. The examination also highlighted the progression, or an acute, fulminant disease; it has been presence of bronchiectasis. Numerous paraaortic and iliac- reported to occur in HIV patients who typically have a obturator lymph nodeswith ashortaxisofabout 12mm were simultaneous infection of human herpes virus 8 (HHV-8) identiefi d. Other lymph nodes were identiefi d in the celiac site . and along the small gastric curvature. The liver, increased in Nevertheless, the term MCD encompasses several dis- volume, did not show focal lesions. Port vein ectasia (24 mm) tinct lymphoproliferative disorders with different underlying and splenic vein ectasia (25 mm) were highlighted (Figure 1). disease pathogenesis; even histopathological features are Surgical counselling recommended splenectomy. As it diverse as they are seen in different clinical variants of was not an emergency surgery, in order to prevent any MCD and in reactive (autoimmune/infectious) and malig- infectious surgical complication, IgG levels were maintained nant (lymphoma) context . over 700 mg/dl for 2 months before splenectomy (Figure 2). A diagnosis of MCD is made by excisional biopsy of Spleen biopsies were performed, which showed a pre- aec ff ted lymph node tissue. Then, a computed tomography dominant lymphocytic infiltration (Figure 3). (CT) of the chest, abdomen, and pelvis should be performed A further thoracic-abdominal CT scan was performed to investigate the presence, or not, of adenopathy and three months after surgery, which showed a reduced size of splenomegaly. Nodal lesions in MCD more closely resemble the numerous paraaortic and iliac-obturator lymph nodes reactive or neoplastic nodal disease and calcifications are with a short axis of about 8 mm. uncommon; intralesional necrosis or b fi rosis may cause a heterogenous appearance [5, 10]. We present the first clinical case of a patient with CVID 3. Discussion who also developed MCD. CVID is a pathology which includes different phenotype presentations. Among the various phenotypes, the clinical 2. Case Report case presented represents one of considerable importance. This phenotype of CVID and Castleman’s disease is charac- A 51-year-old woman was diagnosed with CVID since terized by recurrent or chronic infections, lymphoid nodular 2000. Diagnosis was reached after her having contracted hyperplasia, hepatosplenomegaly, progressive chronic lung two episodes of pneumonia and developing chronic diar- disease with bronchiectasis, and increased risk of lymphoma rhea. IVIG treatment was delivered every 45 days (4 gr/kg). [2, 11]. Furthermore, the case we describe is the rs fi t case Patient’s IgG levels reached normal blood levels (> 700 mg/dl) of adult CVID associated with Castleman’s disease as in with good clinical conditions. Since 2012, due to patient’s literature only a pediatric case was previously reported . personal reasons, IgG levels were not correctly kept within The case evolution is suggestive for a role of hypogam- normal ranges; in 2017, the patient developed bilateral lat- maglobulinemia in the development of MCD as a CT erocervical lymph nodes (1 subtributary lymph node of scan after six months of correct IVIG treatment showed a 6.5 mm), lymph nodes in the mediastinal space (3.5 mm), and decrease in size of lymph nodes. Therefore, we hypothesize splenomegaly. Histological examination on supraclavicular that the multicentric adenopathy with splenomegaly was and abdominal lymph node biopsies was negative for neo- a consequence of inappropriate treatment of CVID. The plasm. Clinical signs of fatigue, fevers, and night sweats as constant low levels of blood immunoglobulins most likely, well as anemia elevated CRP levels, and hepatosplenomegaly as already reported, hyperstimulated the immune system was present. The patient was diagnosed with MCD and causing a lymphoproliferative disorder with adenopathy and referred to our clinical immunology unit due to severe splenomegaly . hypogammaglobulinemia and splenomegaly. Idiopathic MCD, usually diagnosed aer ft excision biopsy Blood count detected hypochromic microcytic anemia, and comprehensive work-up of symptomatic lymph node mild neutropenia, and thrombocytopenia. The study of lym- masses, has been reported to be characterized by an exagger- phocyte subpopulations showed an inverted CD4/CD8 T- ated systemic inflammatory response secondary to a cytokine cell ratio due to the numerically expansion of CD8 T-cells. storm involving Interleukin-6 (IL-6). Immunoglobulin levels were low: IgG 345, IgA 2, and IgM 4 mg/dl. Wright agglutination test, markers of hepatitis B, A therapeutic approach for MCD is, in fact, anti-IL-6 hepatitis C, HIV, HHV8, tumor markers, serum and urine therapy siltuximab . immunofixation, and fecal antigen H. Pylori were normal. Surgeons may also have an important role in the diagnos- IVIG treatment was started at 5 g/Kg maintaining IgG ticwork-up of MCD ; in thecasewedescribe, MCDwith severe splenomegaly secondary to CVID was the reason why levels > 700 mg/dl as well as i.v. iron therapy. A complete abdomen ultrasound detected hepatomegaly the patient was referred to the surgeon for splenectomy. Cor- (large wing 22 cm), splenomegaly (greater than 30 cm), with rect management of the hypogammaglobulinemia allowed a lesion at the splenic pole of 26 mm, increased portal vein splenectomy to be performed without any infectious surgical (20 mm), thick gastric and mesenteric walls, and modest free complications. Case Reports in Immunology 3 Figure 1: Thoracic -abdominal CT with contrast medium which confirmed the presence of adenopathy in the mediastinal space. Figure 2: Patient’s spleen aer ft splenectomy. In the light of the different phenotype presentations of Consent CVID, further research on this pathology is increasingly Written informed consent was given by the patient. necessary . In the case we reported, we hypothesize that MCD associated with CVID was secondary to an incorrect maintenance of IgG circulating blood levels. CVID treatment, Conflicts of Interest focused on maintaining IgG levels within normal ranges, is essential to avoid consequences due to infections and The authors declare that there are no conflicts of interest lymphoproliferative disorders. regarding the publication of this article. 4 Case Reports in Immunology (b) (a) (a) (b) (c) (d) (c) (d) Figure 3: Histopathological analysis showed a diffuse plurifocal nodular white pulp hyperplasia characterized by an admixture of lymphocytes and aggregates of macrophages (H&E, 100x), follicular lymphoid hyperplasia (H&E, 100x) and pseudonodular necrotic area surrounded by prominent haemorrhagic parenchyma (H&E, 100x). References  J. Soulier, L. Grollet, E. Oksenhendler et al., “Molecular analysis of clonality in Castleman’s disease,” Blood,vol.86,no.3,pp.1131–  A. Cant and A. Battersby, “When to think of immunodefi- 1138, 1995. ciency?” Advances in Experimental Medicine and Biology,vol.  D. Wu, M. S. Lim, and E. S. 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Published: Feb 14, 2019
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