Multicentric Angiofollicular Lymph Node Hyperplasia Research Articles

IL-1RA Agonist (Anakinra) in the Treatment of Multifocal Castleman Disease

Multicentric Castleman disease (MCD), or multicentric angiofollicular lymph node hyperplasia, is an idiopathic lymphoproliferative disorder that is only seldom reported in children. The clinical and laboratory findings that characterize this peculiar disorder are thought to result from increased interleukin (IL)-6 production. We report herein the case of a 13-year-old boy with a long history of hectic fevers and abdominal pain, accompanied by stunted growth and elevated biologic markers of inflammation. Surgical biopsies of a pancreatico-splenic mass and of mesenteric lymph nodes revealed mixed-type MCD, which was diagnosed 6 years after the first clinical symptoms appeared. He received combination chemotherapy (cyclophosphamide, vinblastine) associated with a monoclonal B-cell antibody (Rituximab). This treatment was well tolerated but ineffective. Given the reported success of IL-1 blocking agents for treating Still disease, another IL-6 linked disorder, we attempted to treat him with anakinra, an IL-1RA agonist. His overall state normalized and both his clinical and biologic signs dramatically improved. This is the first report of anakinra treatment for MCD. We conclude that anti-IL-1 blocking agents could be an interesting treatment alternative for MCD, a chronic debilitating disease, which still carries a poor prognosis.

Renal Involvement in Multicentric Castleman Disease With Glomeruloid Hemangioma of Skin and Plasmacytoma

A 47-year-old man presented with fever of unknown origin, generalized weakness, edema, and renal failure. He had left-sided pleural effusion, generalized lymphadenopathy, multiple nontender cutaneous nodules, hepatomegaly, renal failure, and hypergammaglobulinemia. Axillary lymph node biopsy showed findings consistent with Castleman disease of the hyaline vascular type associated with interfollicular plasmacytosis. A renal biopsy performed in view of proteinuria and acute renal failure showed hypercellular glomeruli with capillary loop thickening and double contours consistent with membranoproliferative glomerulonephritis. Skin nodule biopsy showed a glomeruloid hemangioma characterized by dermal proliferation of capillary loops in a nodular manner resembling a glomerulus. He experienced clinical and biochemical remission with steroids. Discontinuation of steroid therapy was associated with recurrence of renal failure, reappearance of nodules, lymphadenopathy, and appearance of bony lytic lesions. Biopsy of bony lytic lesions showed plasmacytoma. The patient achieved complete remission on treatment with steroids and cyclophosphamide and is free of symptoms at the end of 40 months of follow-up. To our knowledge, this is the first case report of the occurrence of membranoproliferative glomerulonephritis, glomeruloid hemangioma of the skin, and plasmacytoma in a patient with multicentric Castleman disease without human immunodeficiency virus infection.

Severe polyneuropathy: Initial manifestation of Castleman's disease associated with POEMS syndrome

Castleman's disease is a rare clinicopathological entity characterized by multicentric angiofollicular lymph node hyperplasia. Peripheral neuropathy has infrequently been described in patients with Castleman's disease. A patient is described who presented initially with severe painful sensorimotor polyneuropathy of his lower limbs diagnosed as a plasma cell variant of Castleman's disease associated with features of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin change). The patient was treated with plasmapheresis, immunosuppressive agents, and intensive rehabilitation. His functional status improved from being wheelchair bound to ambulating independently with crutches. Clinicians should be alert to the relationship of Castleman's disease and mixed polyneuropathy because physical improvement is possible with treatment. Also, the evaluation of patients presenting with peripheral neuropathy of unknown etiology and lymphadenopathy should include lymph node biopsy to rule out Castleman's disease.

Chronic Relapsing Neuropathy Associated with Castleman’s Disease (Angiofollicular Lymph Node Hyperplasia)

We report a 17-year-old patient who presented a chronic relapsing sensorimotor demyelinating neuropathy with 6 relapses over a 7-year period, preceding by 4 years the diagnosis of a multicentric angiofollicular lymph node hyperplasia. A role for Epstein-Barr virus (EBV) as a trigger of the neuropathy may be suggested by the presence of EBV DNA in the biopsied abdominal abdominal adenopathies. This unusual reported association seems to have a better prognosis than the known chronic progressive form of neuropathy associated with Castleman's disease and the Crow-Fukase syndrome.

Renal lymphoma in castleman's disease

An unusual case of renal lymphoma occurring in a patient with Castleman's disease is presented. The radiographic features and the relationship to the lymphoproliferative disorders, Castleman's disease, and multicentric angiofollicular lymph node hyperplasia are described.

Angiofollicular Lymph Node Hyperplasia and Peripheral Neuropathy

A man with multicentric angiofollicular lymph node hyperplasia and a polyclonal gammopathy developed a debilitating sensory-motor peripheral neuropathy that resolved with plasma-pheresis and immunosuppressive therapy. Fourteen similar cases have been reported in the literature; however, to our knowledge, this is the first report of successful treatment with plasma-pheresis. Severe peripheral neuropathy usually occurs in the setting of multicentric, plasma cell-type disease with hypergammaglobulinemia and is often responsive to immunosuppressive therapy.

Castleman Disease-POEMS Syndrome Overlap

To the Editors: Feigert and colleagues (1) have described an unusual association between multicentric angiofollicular lymph node hyperplasia (AFLNH) (multicentric Castleman disease) and a unique cl...

Multicentric Angiofollicular Lymph Node Hyperplasia with Peripheral Neuropathy, Pseudotumor Cerebri, IgA Dysproteinemia, and Thrombocytosis in Women

Four women with multicentric angiofollicular lymph node hyperplasia had a distinct clinical syndrome characterized by peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis. The nodes displayed typical morphologic changes of the plasma cell variant of multicentric angiofollicular lymph node hyperplasia. The pathologic changes are morphologically distinct from angioimmunoblastic lymphadenopathy with dysproteinemia although clinical similarities do exist. In these four cases, the lymphadenopathy was usually bulky and multicentric. There was frequent splenic involvement. The neuropathies were severe and disabling. Clinical courses have been variable with some responses to therapy with steroids and alkylating agents. No neoplastic transformations have occurred. Multicentric angiofollicular lymph node hyperplasia may represent a reactive lesion in which the antigenic stimulus is unknown but results in follicular hyperplasia, angiogenesis, and the systemic manifestations of hyperimmune stimulation. We believe this clinical syndrome may represent a distinct variant of multicentric angiofollicular lymph node hyperplasia, and it requires close observation for neoplastic transformation and other complications of its multisystem nature.

Multicentric Angiofollicular Lymph Node Hyperplasia Associated with a Solitary Osteolytic Costal IgG Lambda Myeloma: POEMS Syndrome in a South American (Paraguayan) Patient

We report the case of a 46-year-old woman presenting with a disorder characterized by the association of multicentric Castleman's disease, organomegaly, a solitary IgA lambda myeloma with lytic bone lesions but no serum monoclonal peak, peripheral neuropathy and skin changes. This unusual association resulted in an incomplete form of that peculiar multisystem syndrome described under a variety of names: Crow-Fukase syndrome, Shimpo's syndrome, Takatsuki's syndrome, PEP syndrome or POEMS syndrome. The possible relationship between localized and multicentric Castleman's disease with myeloma or extramedullary plasmacytoma on one hand and on the other hand with polyneuropathy and the other symptoms of the POEMS syndrome is discussed.

Multicentric angiofollicular lymph node hyperplasia. Pathology of the spleen.

Splenomegaly is a frequent clinical finding in multicentric angiofollicular lymph node hyperplasia (MAFH). However, pathologic descriptions of the spleen in MAFH have been reported in only a few cases. The author studied the spleens of seven patients with MAFH (two hyaline-vascular type and five plasma cell type) and reviewed the literature on the pathology of the spleen in this disorder. The histologic features of the seven spleens paralleled those of the lymph nodes. The two hyaline-vascular cases were characterized by white pulp hyperplasia with numerous atrophic and hyaline-vascular germinal centers, and rare plasma cells. In contrast, four plasma cell cases exhibited white pulp hyperplasia with a spectrum of germinal centers ranging from large, hyperplastic centers to typical hyaline-vascular centers, and prominent plasmacytosis. Marked white pulp fibrosis with severe lymphocyte depletion was seen in the fifth plasma cell case, and marginal zone fibrosis with prominent plasmacytosis was seen in one of the other plasma cell cases. The author concludes that the presence of altered germinal centers, white pulp or marginal zone fibrosis, and prominent plasmacytosis should suggest a diagnosis of MAFH in the spleen.

Multicentric Angiofollicular Lymph Node Hyperplasia (Castleman’s Disease) Followed by Kaposi’s Sarcoma in Two Homosexual Males With the Acquired Immunodefieieney Syndrome (AIDS)

Two homosexual men with the acquired immunodeficiency syndrome (AIDS) who developed a multicentric variant of angiofollicular lymph node hyperplasia (AFLNH) (Castleman's disease) and Kaposi's sarcoma are reported. Both had diffuse adenopathy, splenomegaly, and a systemic inflammatory state. Both had an absolute increase in Leu 1 lymphocytes, which was associated with markedly decreased Leu 3 + lymphocytes, markedly increased Leu-2 lymphocytes, and a very low Leu 3/2 ratio. The lymphocytes of both patients had a normal blastogenic response to PHA. The lymphocytes of patient 1 had a poor response to autologous or allogenic cells in the mixed lymphocyte culture reaction. AFLNH represents another lymphoreticular complication of AIDS. Given the interrelationships between AFLNH, the development of Kaposi's sarcoma, and the aggressive clinical course seen in our two patients and those in the literature, the aggressive use of lymph node biopsy may be an important prognostic tool for the patient with the acquired immunodeficiency syndrome. (

Registry of Angiofollicular Lymph Node Hyperplasia

To the Editor.— A registry of cases of localized and multicentric angiofollicular lymph node hyperplasia (AFH) has been established at the University of Nebraska Medical Center, Omaha. Localized AFH (Castleman's disease) is thought to be a benign process that occurs as solitary lymphoid mass in young patients (median age, 23.5 years). These patients are usually cured of the disorder by local excision of the mass. Recently, a multicentric form of AFH with significant patient morbidity and mortality has been reported. 1,2 Patients with multicentric AFH are generally older (median age, 56 years), and they frequently have constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, anemia, polyclonal hypergammaglobulinemia, and bone marrow plasmacytosis. Patients with multicentric AFH can be placed into three different clinical groups based on their presentation and course: stable disease, chronic relapsing disease, and aggressive disease. 2 Patients with multicentric AFH appear to be predisposed to the development of opportunistic infections, malignant lymphoma,

Multicentric angiofollicular lymph node hyperplasia: A clinicopathologic study of 16 cases

A clinicopathologic analysis of 16 cases of multicentric angiofollicular lymph node hyperplasia (MAFH) was performed. Histologically, the disease was characterized by recognizable lymph node architecture that was at least partially intact, by paracortical hyperplasia with prominent vascular proliferation, and by numerous evenly distributed, apparently benign germinal centers of various types, usually including some typical hyaline-vascular centers. At the onset of the disease, 12 patients had the plasma cell (PC) type of MAFH, three patients had the hyaline-vascular (HV) type, and one patient presented with PC and HV types at separate sites. Transitions between the PC and HV types were observed in two cases. Immunologic studies demonstrated polyclonal populations of plasma cells in the lymph nodes of all patients and the absence of suppressor T lymphocytes in the one patient tested. Clinically, the patients had constitutional symptoms, multicentric lymphadenopathy, hepatosplenomegaly in many cases, and abnormal laboratory findings, including anemia, polyclonal hypergammaglobulinemia, and bone marrow plasmacytosis. The 16 patients were placed in four different clinical groups based on presentation and course: stable disease, chronic relapsing disease, aggressive disease, and development of malignant lymphoma. Ten of the 16 patients died (median survival, 26 months; range, eight to 170 months). Multicentric angiofollicular lymph node hyperplasia appears to be a variant of classic angiofollicular lymph node hyperplasia (Castleman's disease) and is associated with significant morbidity and mortality.

Multicentric angiofollicular lymph node hyperplasia (Castleman's disease) followed by Kaposi's sarcoma in two homosexual males with the acquired immunodeficiency syndrome (AIDS).

Two homosexual men with the acquired immunodeficiency syndrome (AIDS) who developed a multicentric variant of angiofollicular lymph node hyperplasia (AFLNH) (Castleman's disease) and Kaposi's sarcoma are reported. Both had diffuse adenopathy, splenomegaly, and a systemic inflammatory state. Both had an absolute increase in Leu 1+ lymphocytes, which was associated with markedly decreased Leu 3+ lymphocytes, markedly increased Leu-2+ lymphocytes, and a very low Leu 3/2 ratio. The lymphocytes of both patients had a normal blastogenic response to PHA. The lymphocytes of patient 1 had a poor response to autologous or allogenic cells in the mixed lymphocyte culture reaction. AFLNH represents another lymphoreticular complication of AIDS. Given the interrelationships between AFLNH, the development of Kaposi's sarcoma, and the aggressive clinical course seen in our two patients and those in the literature, the aggressive use of lymph node biopsy may be an important prognostic tool for the patient with the acquired immunodeficiency syndrome.