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Edema and Castleman's Disease

Related Terms and Synonymns: Angiofollicular hyperplasia, Giant lymph node hyperplasia,  Angiofollicular Lymph Node Hyperplasia, Angiomatous Lymphoid, Giant Benign Lymphoma,  Hamartoma of the Lymphatics, Poems Syndrome

II am including a page on Castleman's disease for two main reasons.  First, it does involve the lymph system and as an information portal, I want to cover as many lymphatic conditions as I can.  Secondly, there are a number of our members who have both lymphedema and Castleman's, so they need information on both conditions.

The condition was first described by Dr. Benjamin Castleman in 1956.


Classification: Also known as giant lymph node hyperplasia and angiofollicular lymph node hyperplasia,  Lymphoproliferative  Disorder, Castleman disease is classified as a lymphoproliferative disorder.

Basic Definition: 

A pathological condition characterized by large, benign, hyperplastic lymph nodes containing concentric perivascular aggregates of lymphocytes. (3)


This condition was first described  by Dr. Benjamin Castleman in 1956.  His study involved 13 patients presenting with localized non-malignant mediastinal lymphadenopathy

The non-cancerous growths involved in Castleman's generally occur in the chest, stomach, and/or neck with the localized form.  Other sites may include the armpit, pelvis and pancreas.

National Organization for Rare Disorders:

Castleman's Disease is a rare disorder characterized by non-cancerous (benign) growths (tumors) that may develop in the lymph node tissue throughout the body (i.e., systemic disease [plasma cell type]). Most often, they occur in the chest, stomach, and/or neck (i.e., localized disease [hyaline-vascular type]). Less common sites include the armpit (axilla), pelvis, and pancreas. Usually the growths represent abnormal enlargement of the lymph nodes normally found in these areas (lymphoid hamartoma).

There are two main types of Castleman's Disease: hyaline-vascular type and plasma cell type.

The hyaline vascular type accounts for approximately 90 percent of the cases. Most individuals exhibit no symptoms of this form of the disorder (asymptomatic) or they may develop non-cancerous growths in the lymph nodes.

About 70% of patients are under 30 years old and  males affected more than females. (3) 

The plasma cell type of Castleman's Disease may be associated with fever, weight loss, skin rash, early destruction of red blood cells, leading to unusually low levels of circulating red blood cells (hemolytic anemia), and/or abnormally increased amounts of certain immune factors in the blood (hypergammaglobulinemia).

 A third type of Castleman's Disease has been reported in the medical literature. This type may affect more than one area of the body (multicentric or generalized Castleman's Disease). Many individuals with Multicentric Castleman's Disease may exhibit an abnormally large liver and spleen (hepatosplenomegaly). Researchers' opinions in the medical literature differ as to whether Multicentric Castleman's Disease is a distinct entity or a multicentric form of the plasma cell type of Castleman's Disease.

A third type of Castleman's disease has been reported in the medical literature. This type may affect more than one area of the body (multicentric or generalized Castleman's disease). Many individuals with Multicentric Castleman's disease may exhibit an abnormally large liver and spleen (multicentric or generalized Castleman's disease).). Researchers' opinions in the medical literature differ as to whether Multicentric Castleman's disease is a distinct entity or a multicentric form of the plasma cell type of Castleman's disease.


Exact cause is unknown, however there is speculation that increased production of interleukin-6 (IL-6) may be involved in the development of Castleman's Disease. IL-6 is a substance produced by structures within the lymph nodes.

Symptoms:  (2)

An enlarged lymph node, usually inside the chest or abdomen, is the only symptom for most people with the localized form of Castleman's disease.

People with multicentric Castleman's disease have more than one enlarged lymph node. The involved nodes may be in the chest or abdomen. More often, lymph nodes near the surface of the body are involved. For example, multicentric Castleman's disease often affects lymph nodes in the groin, the underarm area, and on the sides of the neck. Multicentric Castleman's disease can also affect lymphoid tissue of internal organs, causing the liver, spleen, or other organs to enlarge.

In addition, people with either type of Castleman's disease may have other symptoms. The most common include:

These symptoms occur about twice as often in multicentric than in localized Castleman disease.(1)


Nodal biopsies are one method of diagnosis.  The biopsies may be either small needle or excisional. In addition to the nodal biopsies  radiology tests which can include CT scans, MRI, Chest x-ray and/or gallium scan may be indicated.

The condition is often difficult to diagnose because most patients present asymptomatic (58%-97%).  Generally follow up testing is done when a large mass is noted in a x-ray.. 


Pericardial and pleural effusions, axillary, inguinal and abdominal lymphadenopathy, and splenomegaly.  Patient may experience infections as well.

Unicentric Castleman disease

People with unicentric Castleman disease usually do well once the affected lymph node is removed, although having Castleman disease may increase your risk of lymphoma.

Mulricentric Castleman disease

On the other hand, multicentric Castleman disease is much more sserious and often life-threatening. Death from multicentric disease usually occurs due to a serious infection, failure of multiple organs, cancer, such as lymphoma or Kaposi's sarcoma.  The presence of HIV/AIDS tends to worsen the outcome. (CNN International Sept. 3, 2011)


Treatment programs will ne based on whether the patient has unicentric Castlemans or multicentric Castlemans.

For the hyaline vascular sub-type, surgical excision is the usual treatment with a low recurrence rate. Treatment for the plasma cell variant  may include radiation therapy and chemotherapy.

Drugs used in the chemotherapy treatment involve doxorubicin, vincristine, cyclophosphamide, melphalan and chlorambucil. They may be used invidiually or in combination (CHOP).

Other treatments may include corticosteroids, antiviral drugs and immune modulators.  


For localized Castleman's, the prognosis is actually quite good.  However, there may be a recurrence of the condition.

For multicentric Castleman's, the prognosis is not so good.  The morbidity rate for multicentric Castleman's was 50% in two and a half years.  Other factors that dim the prognosis is if the condition accompanies AIDS.  Also, approximately 20% of people with Castleman's will develop lymphoma.


Abstracts and Studies:


Surgical treatment of unicentric plasma cell histological type Castleman's disease].

Sept 2011

[Article in Serbian]
Marić N, Stanić V, Cvijanović V, Ristanović A, Kovacević S, Krivokapić Z, Radić OT.


Vojnomedicinska akademija, Klinika za grudnu hirurgiju, Beograd, Srbija.



Castleman's disease or angiofollicular lymph hyperplasia is a rare disease with two identified clinical forms. Unicentric or localized form is characterized by isolated growth of lymph nodes, most often in mediastinum, and multicentric form is expressed as systemic disease with spread lymphadenopathy, organomegaly and presence of general symptoms of the disease. Histological types are hyalovascular, plasma-cell and transitive (mixed) cell.


This case report shows a woman, 59 years old, with unicentric form of plasma-cell type of Castleman'sdisease. Unicentric form is usually shown as hyalovascular histological type, extremely rare as plasma-cell type, and transitive (mixed) cell type was never described in literature as localized clinical form. The disease was manifested with chest pain, loss of body weight, exhaustion and weakness of legs. Further diagnostic procedures found the presence of enlarged lymph nodes paratracheally right, in a close contact with vena cava superior. The disease was confirmed by histopathological analysis of bioptated mediastinal lymph node after mediastinoscopy. Surgical treatment included extirpation of enlarged lymph nodes. After the regular postoperative condition, a full therapy effect was confirmed.


Unicentric form of Castleman's disease is expressed with enlarged lymph nodes on predilected places, usually in mediastinum. Surgical treatment is best method for the management of the disease and brings a full recovery of patient.


Multicentric plasma cell variant Castleman's disease presenting with cutaneous vasculitis and pulmonary parenchymal involvement in a patient with ankylosing spondylitis: case report and review of the literature. 

Jul-Aug 2011

Wolf M, Van Offel JF, Van de Velde A, Stevens WJ, De Clerck LS.


Department of Immunology, Allergology and Rheumatology, Antwerp University Hospital, Faculty of Medicine, University of Antwerp, Edegem, Belgium.


We present a case of the multicentric plasma cell variant of Castleman's disease (CD) with two rare manifestations. The patient consulted us because of cutaneous vasculitis of the lower limbs, while constitutional symptoms were nearly absent. Imaging studies also revealed pulmonary parenchymal involvement. Furthermore, our patient is the first case in whom association of ankylosing spondylitis with CD is reported. In addition, we present a review of the literature with emphasis on the clinical presentation of CD and its difficult discrimination from autoimmune and infectious disorders. An overview of the therapeutic options is also provided.


PUBMED List of Castleman Abstracts and Studies


Successful treatment with bortezomib and thalidomide for POEMS syndrome associated with multicentric mixed-type Castleman's disease

Oct. 2011


Castleman's disease of the pleura. 

Aug 2011


A case of Castleman disease with status epileptics originating from focal cortical dysplasia]. 

Jul 2011


An unusual case of cutaneous hyaline-vascular Castleman's disease with multicentric involvement and systemic symptoms. 

Aug 2011


Comparison of plasma cell type of Castleman's disease and IgG4-related sclerosing disease: a histopathological and immunohistochemical study. 


Key Words: Castleman’s disease; IgG4-related sclerosing disease; Plasma cell; Immunohistochemistry


Improved outcome with rituximab in patients with HIV-associated multicentric Castleman disease

Sept. 2011


Meningeal Castleman's disease with 
multifocal involvement: a case report and review of literature.

J Neurooncol. 2008 May



Fluorodeoxyglucose-positron emission tomography/computed tomography in the staging and evaluation of treatment response in a patient with Castleman's disease: a case report

J Med Case Reports. 2008 Apr

PubMed Central


Multicentric Castleman's Disease in HIV Infection: a Systematic Review of the Literature.

AIDS Rev. 2008 Jan-Mar

Permanyer Publication


Local Castlemanos Disease: A Report of 17 Cases witn Literature Review

Ai Zheng. 2008 Mar

Chinese Journal of Cancer


Acute renal failure due to thrombotic microangiopathy associated with Castleman's disease

An Med Interna. 2007 Dec



Castleman's disease and related disorders.

Frizzera G.

Department of Laboratory Medicine and Pathology, University of MinnesotaMedical School, Minneapolis 55455.

Three disorders that bear the eponym of Castleman's disease (CD) are discussed. The localized CD of hyaline-vascular (HV) type features an architecturally abnormal, hypervascular lymphoid tissue with burned-out germinal centers, and presents as an asymptomatic, slowly growing mass. It may represent a lymphoid hyperplasia associated with excessive angiogenesis. The localized CD of plasma cell (PC) type, instead, features an architecturally recognizable lymph node with solid sheets of PCs and presents with systemic manifestations of inflammation and B cell hyperreactivity. It appears as a localized chronic reaction to unknown antigens. "Multicentric" CD indicates a clinicopathologic entity characterized by the histology of CD of "mixed" type, a predominantly lymphadenopathic presentation consistently involving peripheral nodes, manifestations of multisystem involvement, and an idiopathic nature. It is best considered as a systemic B cell lymphoproliferation, which probably arises in a setting of immunoregulatory deficit, and may result in the outgrowth of clonal B cell populations. An attempt is presented to place the latter two forms of CD in the larger perspective of idiopathic PC disorders, by taking into account both the nature of the diseases (hyperplastic, dysplastic, neoplastic) and the lymphocyte traffic system that is involved (bone marrow-bound, mucosa-associated or peripheral-node-bound). In such a scheme, localized CD, PC type, and multicentric CD appear as a hyperplastic and a dysplastic disorder, respectively, of peripheral-node-bound B cells, related to, and often associated with, primary nodal plasmacytoma and osteosclerotic myeloma (so-called POEMS, Takatsuki's or Crow-Fukase's syndrome).


Angiofollicular lymph node hyperplasia (Castleman's disease).

McCarty MJ, Vukelja SJ, Banks PM, Weiss RB.

Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, TX 78234, USA.

This review provides a comprehensive assessment of angiofollicular lymph node hyperplasia (ALNH) or Castleman's disease including pathogenesis, clinical presentation, histomorphologic and immunophenotypic findings, laboratory results, treatment, and prognosis. A division of ALNH into clinically relevant subtypes provides a framework for the consideration of the disorder. A comprehensive search of the medical literature involving ALNH using Medline was performed. Reports judged to be significant for the understanding of the disorder were analyzed and their findings incorporated into this review. ALNH is divided into localized/unicentric ALNH and generalized/multicentric ALNH due to the profound clinical differences seen between these variants. Localized/unicentric ALNH is separated by clinical and histomorphologic criteria into hyaline-vascular (HV) and plasma-cell (PC) subtypes. Generalized/multicentric ALNH may be divided by clinical criteria into generalized/multicentric ALNH without neuropathy (non-neuropathic) and generalized/multicentric ALNH with neuropathy (POEMS-associated or neuropathic). The dichotomy between these two subtypes is not absolute, with considerable clinical overlap occurring among patients presenting with generalized disease. Immunophenotypic and molecular probe studies demonstrate clonal B-cell lymphocyte populations in some cases, particularly those with generalized/multicentric ALNH. However, the finding of clonal populations is of no value in predicting malignant clinical progression. We conclude that using this division of ALNH, patients presenting with symptoms and histomorphology consistent with ALNH can be subdivided into the appropriate category of ALNH. Localized or unicentric disease, either HV or PC subtype, has an excellent prognosis with surgery being curative in the majority of cases. Generalized or multicentric disease indicates a poor prognosis with short survival, with the neuropathic variant possessing resistance to steroids and chemotherapy and a corresponding worse prognosis.

Pub Med

National Library of Medicine


Castleman's disease

Larroche C, Cacoub P, Godeau P.

Service de medecine interne, hopital de la Pitie-Salpetriere, Paris, France.

Castleman's disease, also called angiofollicular lymph node hyperplasia was first described as a distinct entity by Castleman et al in 1956. Two forms are now described a localized and a multicentric. The clinical and biological signs are varied and heterogeneous, and the diagnostic is made on the histologic examination. This atypical lymphoproliferative disorder is of unknown origin, but interleukin 6 play a central part in this disease. Despite the benignity of this "prelymphoma state", an aggressive course with poor prognosis occur usually in the multicentric form. Malignant lymphomas and Kaposi's sarcoma have been associated with Castleman's disease.


Poems Syndrome - Related medical Condtions

Synonyms of POEMS Syndrome

Disorder Subdivisions

General Discussion
POEMS syndrome is an extremely rare multisystem disorder. POEMS is an acronym that stands for (P)olyneuropathy, disease affecting many nerves; (O)rganomegaly, abnormal enlargement of an organ; (E)ndocrinoapthy, disease affecting certain hormone-producing glands that help to regulate the rate of growth, sexual development, and certain metabolic functions (endocrine system); (M)onoclonal gammopathy or M proteins; and (S)kin defects. Common symptoms include progressive weakness of the nerves in the arms and legs, an abnormally enlarged liver and/or spleen (hepatosplenomegaly), abnormally darkening of the skin (hyperpigmentation) and excessive hair growth (hypertrichosis). Endocrine abnormalities such as failure of the ovaries and testes (gonads) to function properly (primary gonadal failure) and diabetes mellitus type I may be present. Specific endocrine abnormalities associated with POEMS syndrome vary from case to case.

POEMS syndrome is associated with a group of disorders known as monoclonal gammopathies or plasma cell dyscrasias. These disorders are characterized the uncontrolled growth of a single clone (monoclonal) of plasma cells, which results in the abnormal accumulation of M-proteins (also known as immunoglobulin M or IgM) in the blood. M-proteins are supposed to fight foreign substances in the body such as viruses and bacteria, but researchers suspect that they play a role in the development of POEMS syndrome. However, the specific role M-proteins play and the exact cause of POEMS syndrome is unknown.

Organizations related to POEMS Syndrome


Poems syndrome

A combination of plasma cell dyscrasia, chronic progressive polyneuropathy, and endocrine abnormalities such as diabetes mellitus. This syndrome is of unknown cause and takes its name from the typical features: polyneuropathy, organomegaly, endocrinopathy, M proteins and skin changes. Numerous other characteristics can be noted. However, patients do not have an increased prevalence of amyloidosis and rarely reveal Bence Jones proteinuria. Bone proliferation occurs at entheses (sites of tendon and ligament attachment to bone). Particularly characteristic are irregular bony excrescences on the posterior elements of the spine and about the sacroiliac and costovertebral joints (Fig.1).


POEMS syndrome: definitions and long-term outcome.

Dispenzieri A, Kyle RA, Lacy MQ, Rajkumar SV, Therneau TM, Larson DR, Greipp PR, Witzig TE, Basu R, Suarez GA, Fonseca R, Lust JA, Gertz MA.

Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.

The POEMS syndrome (coined to refer to polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) remains poorly understood. Ambiguity exists over the features necessary to establish the diagnosis, treatment efficacy, and prognosis. We identified 99 patients with POEMS syndrome. Minimal criteria were a sensorimotor peripheral neuropathy and evidence of a monoclonal plasmaproliferative disorder. To distinguish POEMS from neuropathy associated with monoclonal gammopathy of undetermined significance, additional criteria were included: a bone lesion, Castleman disease, organomegaly (or lymphadenopathy), endocrinopathy, edema (peripheral edema, ascites, or effusions), and skin changes. The median age at presentation was 51 years; 63% were men. Median survival was 165 months. With the exception of fingernail clubbing (P =.03) and extravascular volume overload (P =.04), no presenting feature, including the number of presenting features, was predictive of survival. Response to therapy (P <.001) was predictive of survival. Pulmonary hypertension, renal failure, thrombotic events, and congestive heart failure were observed and appear to be part of the syndrome. In 18 patients (18%), new disease manifestations developed over time. More than 50% of patients had a response to radiation, and 22% to 50% had responses to prednisone and a combination of melphalan and prednisone, respectively. We conclude that the median survival of patients with POEMS syndrome is 165 months, independent of the number of syndrome features, bone lesions, or plasma cells at diagnosis. Additional features of the syndrome often develop, but the complications of classic multiple myeloma rarely develop.

PMID: 12456500 [PubMed - indexed for MEDLINE]


Treatment of POEMS syndrome.

Dispenzieri A, Gertz MA.

Division of Hematology and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome is a rare multisystemic paraneoplastic syndrome driven by an underlying plasma cell dyscrasia. More than 95% of patients will have monoclonal lambda sclerotic plasmacytoma(s) or bone marrow infiltration. Recognition of the complex of a combination of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, skin changes, sclerotic bone lesions, Castleman disease, thrombocytosis, papilledema, peripheral edema, pleural effusions, ascites, fingernail clubbing, and white nails is the first step in effectively managing the disease. Once a patient has been completely evaluated, each component of the disease should be addressed, while finalizing a treatment plan for the underlying plasma cell proliferative disorder. In patients with a dominant sclerotic plasmacytoma, first-line therapy should include radiation to the lesion. Retrospective analysis and personal experience would dictate that systemic therapy be considered for patients with diffuse sclerotic lesions or absence of any bone lesion and for patients who have not demonstrated stabilization of their disease 3 to 6 months after completing radiation therapy. Treatments with demonstrated benefit include corticosteroids, low-dose alkylator therapy, and high-dose chemotherapy with peripheral blood stem cell transplant. Until the pathogenesis is fully understood, these are the mainstays of treatment for patients with POEMS syndrome.


Treatment of POEMS Syndrome

POEMS syndrome is a very rare type of bone marrow disorder whose cause is unknown. It involves an overgrowth of bone marrow cells called plasma cells, which produce chemicals that damage other parts of the body. It is not inherited, nor is it contagious.

Patients sometimes confuse POEMS syndrome with multiple myeloma. The symptoms and potential complications of these diseases are very different. The average expected life span is better in patients with POEMS (who may have osteosclerotic myeloma) than it is in patients with multiple myeloma.

The diagnosis of POEMS syndrome is made by combining the information from a thorough history, physical examination, and blood, urine, X-ray and bone marrow tests. The overgrowth of plasma cells can often be detected by finding an abnormal protein in the blood or urine (a monoclonal protein), by an abnormality on a bone X-ray and/or a bone marrow biopsy. POEMS is a syndrome, which means that several features must be present to make the diagnosis. Because it is so rare, the diagnosis is often missed. Initially, people may have been told that they have a nerve problem without any known cause. Or they may have been told that they have multiple myeloma, a type of bone marrow cancer.

Mayo Clinic approach

Mayo Clinic uses an integrated approach involving a multispecialty team of physicians in caring for patients with POEMS syndrome. Working together, Mayo clinicians develop a treatment plan based on the patient's individual needs and health issues.

Treatment Options

People with POEMS suffer many symptoms; most commonly, the worst is caused by nerve damage. Patients can develop extreme, progressive weakness (neuropathy) of their extremities (feet, legs, hands and arms). The most effective method of stopping the progression or advancement of this weakness is to kill the plasma cell clone (the osteosclerotic myeloma). The doctor may recommend radiation therapy, corticosteroids, chemotherapy or even a bone marrow transplant. If there are only one or two spots of osteosclerotic myeloma, the doctor may recommend radiation therapy alone. The choice of treatment must be made with care, balancing the risks and benefits of treatment.

If there are hormonal abnormalities, hormone replacement may be needed. Physical therapy is highly recommended if there has been significant disability caused by the neuropathy. As the osteosclerotic myeloma is treated, many of the other symptoms will improve, including the skin changes, the swelling of the extremities and the enlarged organs. The hormonal abnormalities may or may not improve. The nerve problem may or may not improve, depending on how advanced the disease is by the time treatment begins.

All patients need lifelong follow-up for this condition because relapses are possible


External Links:


National Organizations and Web Sites

National Organization for Rare Disorders (NORD)
55 Kenosia Avenue
PO Box 1968
Danbury, CT 06813

Toll-free: (800) 999-6673 (voicemail only)
Telephone: (203) 744-0100

Internet address:


Castleman's Disease Homepage - International Castleman's Disease Organizatino (3)

Patient Resources:


Castleman's Disease (2)

American Cancer Society


Castleman's disease Information


Castleman's Disease - Signs and Symptoms (1)


Alleviation of Systemic Manifestations of Castleman's Disease by Monoclonal Anti-Interleukin-6 Antibody

New England Journal of Medicine


Castleman's Disease



Castleman's Disease

The Doctors Doctor


An unusual presentation of Castleman's Disease:a case report


Who Named It (3)


NIH/National Heart, Lung and Blood Institute Information Center
P.O. Box 30105
Bethesda, MD 20824-0105
Tel: (301)592-8573
Fax: (301)251-1223


UCSF Hemophilia Treatment Center
400 Parnassus Ave.
First Floor
San Francisco, CA 94143
Tel: (415)353-2986
Fax: (415)353-2600


International Castleman's Disease Organization
4 Brazos Court
Santa Fe, NM 87508
Tel: (505)424-7947
Fax: (505)424-7948


ICD-10 and ICD-9


Poems Syndrome - 

Orpha number: Poems Syndrome ORPHA2905


Castleman's Disease

Hyaline vascular types D21.9; Connective and other soft tissue unspecified M8000/0; Plams cell type where the histology is difficult to prefidct D47.9; Neoplasm of uncertain or unknown behaviour of lymphoid haematoporietic and related tissue, unspecified M8000/1


Castleman's (mediastinal lymph node hyperplasia) 785.6


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