Castleman’s disease


Rare process associated with lymph node enlargement at a single site or throughout the body.

A non-malignant lymphoproliferative disorder.

It is a  heterogeneous  group of the diseases under one heading.

A polyclonal lymphoproliferative disorder.

Involves the proliferation of B cells that produce cytokines.

Associated with hyper secretion of the cytokine IL-6.

Unicentric disease implies enlargement of lymph nodes at a single site.

In 90% of cases removal of a single node is curative.

Multicentric disease involves enlarged lymph nodes at multiple sites ad 50% of cases are caused by Kaposi[s sarcoma-associated Herpesvirus (KSHV).

Histopathological features are classified as hypervascular or hyaline vascular, plasmacytic, or mixed.

May be associated with POEMS.

Human herpesvirus (HHV)-8 and IL6 are etiologic factors and therapeutic targets.

More than half of patients with HIV associated Castleman disease also have concomitant Kaposi’s sarcoma (HHV-8).

Localized or unicentric disease affects a single lymph node and the chest and abdomen are affected most often.

In unicentric Castleman’s disease 80% of cases have chest lymphadenopathy.

Unicentric Castleman’s disease is almost hyaline vascular subtype and is usually HIV negative and HHV-8  negative and commonly presents in younger adults age 30 to 40 years, with a slight predominance in women.

Unicentric Castleman’s disease presentation includes the chest, neck, and abdomen and less commonly retroperitoneum.

Unicentric Castleman’s disease usually presents is localized, asymptomatic adenppathy and is commonly diagnosed through incidental imaging.

Unicentric Castleman’s disease rarely present with peripheral adenopathy.

Unicentric Castleman’s disease is associated with a greater than  90% relapse free survival after surgical reception.

Unresectable disease can be treated with local Radiation, Rituximab, and/or steroids to reduce the mass to convert it to being socially surgically resectable.

50% of cases of multicentric Castleman’s disease (MCD) of unknown cause.

A nonclonal lymphoproliferative disorder that can affect single lymph node, or generalized involvement.

IL-6 plays role in pathogenesis of the disease.

Human herpesvirus 8, encodes for viral homolog of IL6 and is a driving force in HIV positive patients.

Outcome in HIV negative CD is excellent.

Responds to monoclonal antibody therapy directed at IL-6 receptor or IL-6 itself.

IL6 elaborated by B lymphocytes in germinal centers of CD lymph nodes

Multicentric disease (MCD) associated with Kaposi’s sarcoma Herpesvirus is the plasmacytic form of Castleman’s disease.

Affects roughly 1600 patients annually in the US.

Historical five year overall survival 55 to 77%, as it is a life-threatening disease.

Multicentric Castleman disease is associated with a range of signs and symptoms including multicentric lymphadenopathy, and an inflammatory syndrome with fluid accumulation.

Multi organ system dysfunction may develop as a consequence of a cytokine storm.

It has two pathologic sub types: a highly vascular tumor and the plasmacytic variant.

Approximately half of all cases of MCD are caused by uncontrolled infection with HHV8 or monoclonal plasma cell population associated with POEMS syndrome, and the remaining cases are idiopathic.

Cases can be divided into clinical subtypes involving thrombocytopenia, anasarca, fever, bone marrow fibrosis, renal dysfunction, and organomegaly.

The hyaline vascular form of Castleman’s disease is negative for the KSHV.

Multicentric disease may be associated with fever, anemia, weight loss, anorexia and leukopenia, all of which may be associated with excess interleukin 6.

HHV8 positive MCD is generally associated with an IL-6 mediated inflammatory syndrome, is most commonly seen in the setting of HIV, but may be seen in other immunocompromised hosts.

MCD histology is mostly plasmacytic or mixed histology, with a male predominant.

Because of the nonspecific nature of the presentation diagnosis is difficult.

Prognosis for unicentric disease is excellent.

Treatment of multicentric disease has no standard approach as of this time.

AIDS related multicentric disease treated by management for HIV disease.

Multicentric form acts like lymphoma, and in fact, many patients develop lymphomas.

HHV-8 Associated MCD can be seen in patients with polyneuropathy, organomegaly, and organomegally, M proteins, and skin changes (POEMS).

HHV-8 associated MCD arises from replication of HHV-8 in plasmablasts resulting in constitutional symptoms and diffuse lymphadenopathy and is most commonly associated with chronic immunodeficient states such as HIV.

Idiopathic clinical subtype of multicentric Castleman’s disease called TAFRO is characterized by thrombocytopenia, anasarca, fever, elevated C-reactive proteins, renal insufficiency or reticulum fibrosis for both, and organomegaly.

Diagnostic criteria: enlarged lymph nodes in multiple stations, morphologic changes consistent with Castleman disease in an excised lymph node that is negative for HHV8 by immunochemistry, the presence of at least two minor criteria: which include clinical and laboratory findings consistent with MCD and inflammatory syndrome, and exclusion of infections, autoimmune, and malignant disorders that can mimic MCD.

Histopathologic features in include a constellation of regression of hyperplastic germinal centers, follicular dendritic cell prominence, hyper vascularization, and polytypic plasmacytosis.

Minor criteria include elevated erythrocyte sedimentation rate or C reactive protein, anemia, thrombocytopenia, thrombocytosis, polyclonal hypogammaglobulinemia, hypoalbuminemia, renal dysfunction, constitutional symptoms, effusions or edema, hepatosplenomegaly, eruptive cherry hemangiomatossis or violaceous papules and lymphocytic interstitial pneumonitis.

There is presently no standard treatment for multicentric CD.

The prognosis for HHV positive MCD has improved with  the use of highly active antiretroviral therapy for HIV and biologic therapy for Castleman disease.

Bortezomib therapy may be efficacious.

Rituximab is efficacious in HHV associated MCD.

Siltuximab,  a monoclonal antibody that binds to interleukin-6 is utilized for the treatment of patients with multicentric Cattleman’s disease:it is first line therapy.

Other agents used for this disease include tocilizumab,, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and high-dose steroids.

Lifelong therapy may be necessary to prevent relapse.

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