Leg‐type form of idiopathic multicentric Castleman disease associated with severe lower extremity chronic venous/lymphatic disease

Abstract We report a case of chronic hepatosplenic aspergillosis following immune reconstitution complicating colic aspergillosis in an AIDS patient with multicentric Castleman disease. Symptoms mimicked the clinical presentation of chronic disseminated candidiasis and responded to corticosteroid. This emerging entity enlarges the spectrum of fungal immune reconstitution inflammatory syndrome in the HIV setting.

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Validated International Definition of the TAFRO clinical subtype of idiopathic multicentric Castleman disease

American Journal of Hematology ◽

10.1002/ajh.26292 ◽

2021 ◽

Author(s):

Yoshito Nishimura ◽

David C. Fajgenbaum ◽

Sheila K. Pierson ◽

Noriko Iwaki ◽

Asami Nishikori ◽

...

Keyword(s):

Castleman Disease ◽

Multicentric Castleman Disease ◽

Definition Of ◽

Clinical Subtype

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Coexistence of disseminated Kaposi sarcoma and multicentric Castleman disease in an HIV-infected patient under viral suppression

International Journal of STD & AIDS ◽

10.1177/0956462420968385 ◽

2021 ◽

Vol 32 (3) ◽

pp. 286-289

Author(s):

I-Fan Lin ◽

Jiun-Nong Lin ◽

Tsung-Heng Tsai ◽

Chao-Tien Hsu ◽

Yu-Ying Wu ◽

...

Keyword(s):

Viral Load ◽

Viral Suppression ◽

Liposomal Doxorubicin ◽

Kaposi Sarcoma ◽

Castleman Disease ◽

Severe Thrombocytopenia ◽

Multicentric Castleman Disease ◽

Progressive Pancytopenia ◽

One Year ◽

Cd4 T Cell Count

Coexistence of multicentric Castleman disease and Kaposi sarcoma is rare and might be missed without an experienced pathologists’ interpretation. A 46-year-old man had been diagnosed with HIV infection and treated with combination antiretroviral therapy of dolutegravir/abacavir/lamivudine (Triumeq) for one year. The latest viral load was 49 copies/mL and CD4 T-cell count was 192 cells/uL. He was admitted due to fever off and on, splenomegaly, general lymphadenopathy, and severe thrombocytopenia for two months. Biopsy of a purplish skin lesion and gastric tissue showed Kaposi sarcoma. The pathology of inguinal lymph nodes revealed coexistence of Kaposi sarcoma and multicentric Castleman disease. The plasma Kaposi sarcoma herpesvirus viral load was 365,000 copies/mL. During hospitalization, progressive pancytopenia and spiking fever persisted, and he died of multi-organ failure before completion of chemotherapeutic treatments with rituximab plus liposomal doxorubicin.

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A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease

Biology ◽

10.3390/biology10040251 ◽

2021 ◽

Vol 10 (4) ◽

pp. 251

Author(s):

Alexandra Butzmann ◽

Jyoti Kumar ◽

Kaushik Sridhar ◽

Sumanth Gollapudi ◽

Robert S. Ohgami

Keyword(s):

Plasma Cells ◽

Treatment Options ◽

Disease Process ◽

Castleman Disease ◽

Mitogen Activated Protein Kinase ◽

Human Herpes Virus 8 ◽

Multicentric Castleman Disease ◽

Molecular Abnormalities ◽

Genetic Abnormalities ◽

Mitogen Activated Protein

Castleman disease (CD) is a rare lymphoproliferative disorder known to represent at least four distinct clinicopathologic subtypes. Large advancements in our clinical and histopathologic description of these diverse diseases have been made, resulting in subtyping based on number of enlarged lymph nodes (unicentric versus multicentric), according to viral infection by human herpes virus 8 (HHV-8) and human immunodeficiency virus (HIV), and with relation to clonal plasma cells (POEMS). In recent years, significant molecular and genetic abnormalities associated with CD have been described. However, we continue to lack a foundational understanding of the biological mechanisms driving this disease process. Here, we review all cases of CD with molecular abnormalities described in the literature to date, and correlate cytogenetic, molecular, and genetic abnormalities with disease subtypes and phenotypes. Our review notes complex karyotypes in subsets of cases, specific mutations in PDGFRB N666S in 10% of unicentric CD (UCD) and NCOA4 L261F in 23% of idiopathic multicentric CD (iMCD) cases. Genes affecting chromatin organization and abnormalities in methylation are seen more commonly in iMCD while abnormalities within the mitogen-activated protein kinase (MAPK) and interleukin signaling pathways are more frequent in UCD. Interestingly, there is a paucity of genetic studies evaluating HHV-8 positive multicentric CD (HHV-8+ MCD) and POEMS-associated CD. Our comprehensive review of genetic and molecular abnormalities in CD identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies.

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HHV8-Positive Castleman Disease and In Situ Mantle Cell Neoplasia within Dermatopathic Lymphadenitis, in Longstanding Psoriasis

Diagnostics ◽

10.3390/diagnostics11071150 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1150

Author(s):

Magda Zanelli ◽

Luca Stingeni ◽

Maurizio Zizzo ◽

Giovanni Martino ◽

Francesca Sanguedolce ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Rare Event ◽

Castleman Disease ◽

Axillary Lymph ◽

Tnf Inhibitor ◽

Dermatopathic Lymphadenitis ◽

Multicentric Castleman Disease ◽

Mantle Cell

A 73-year-old man presented with multiple lymphadenopathy. He had a 20-year history of palmoplantar psoriasis evolved to a diffuse erythrodermic picture in the last two years. Topic and systemic medications including prednisolone, acitretin, anti-IL17 (ixekizumab), TNF inhibitor (adalimumab), anti-IL23 (guselkumab), methotrexate, cyclosporine, and phosphodiesterase 4 inhibitor (apremilast) were ineffective. Repeated skin biopsies excluded mycosis fungoides, confirming psoriasis; molecular analysis of T-cell receptor genes ruled out clonality. The axillary lymph node histology documented a dermatopathic lymphadenitis, often associated with chronic cutaneous inflammatory diseases. At an accurate morphological evaluation, features of HHV8-positive multicentric Castleman disease were observed. Moreover, in a few follicles, in situ mantle cell neoplasia was identified. The translocation t(11;14)(q13;q32), characteristic of mantle cell lymphoma, and the monoclonal IGH gene rearrangement were present. HHV8 DNA was identified on plasma sample. Multicentric Castleman disease in psoriatic patients is a rare event and it might be favored by the immunomodulatory treatment in longstanding psoriasis. Multicentric Castleman disease patients are predisposed to developing simultaneous or subsequent lymphoma. In situ mantle cell neoplasia often behaves indolently, although it may progress to overt mantle cell lymphoma. Rituximab achieved a good control of psoriasis. Unfortunately, the patient developed Staphylococcus aureus sepsis for which he is currently on antibiotic therapy.

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Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease

American Journal of Hematology ◽

10.1002/ajh.24242 ◽

2016 ◽

Vol 91 (2) ◽

pp. 220-226 ◽

Cited By ~ 111

Author(s):

Noriko Iwaki ◽

David C. Fajgenbaum ◽

Christopher S. Nabel ◽

Yuka Gion ◽

Eisei Kondo ◽

...

Keyword(s):

Castleman Disease ◽

Tafro Syndrome ◽

Multicentric Castleman Disease ◽

Distinct Subtype

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KSHV- and EBV-associated germinotropic lymphoproliferative disorder

Blood ◽

10.1182/blood-2002-02-0487 ◽

2002 ◽

Vol 100 (9) ◽

pp. 3415-3418 ◽

Cited By ~ 141

Author(s):

Ming-Qing Du ◽

Tim C. Diss ◽

Hongxiang Liu ◽

Hongtao Ye ◽

Rifat A. Hamoudi ◽

...

Keyword(s):

Lymphoproliferative Disorder ◽

Gene Rearrangement ◽

Primary Effusion Lymphoma ◽

Kaposi Sarcoma ◽

Castleman Disease ◽

Lymphoproliferative Disorders ◽

Multicentric Castleman Disease ◽

Tissue Sections ◽

Response To Chemotherapy ◽

Ig Heavy Chain

Abstract Kaposi sarcoma–associated herpesvirus (KSHV) is known to be associated with 3 distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma. We report 3 cases of a previously undescribed KSHV-associated lymphoproliferative disorder. The disease presented as localized lymphadenopathy and showed a favorable response to chemotherapy or radiotherapy. Histologically, the lymphoproliferation is characterized by plasmablasts that preferentially involved germinal centers of the lymphoid follicles, forming confluent aggregates. They were negative for CD20, CD27, CD79a, CD138, BCL6, and CD10 but showed monotypic κ or λ light chain. Clusters of CD10+CD20+ residual follicle center cells were identified in some of the follicles. The plasmablasts were positive for both KSHV and EBV, and most of them also expressed viral interleukin-6 (vIL-6). Unexpectedly, molecular analysis of whole tissue sections or microdissected KSHV-positive aggregates demonstrated a polyclonal or oligoclonal pattern of immunoglobulin (Ig) gene rearrangement. The plasmablasts showed somatic mutation and intraclonal variation in the rearranged Ig genes, and one case expressed switched Ig heavy chain (IgA), suggesting that they originated from germinal center B cells. We propose calling this distinctive entity “KSHV-associated germinotropic lymphoproliferative disorder.”

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