A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease

Butzmann, Alexandra; Kumar, Jyoti; Sridhar, Kaushik; Gollapudi, Sumanth; Ohgami, Robert S.

doi:10.3390/biology10040251

Cited by 18 publications

(21 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, the PDGFRB N666S mutation often occurring in HV-CD 92 , 93 , was detected in a case of FDCS with history of Castleman disease 82 , further strengthening the biological relationship between these two diseases.…”

Section: Genetics and Molecular Findingsmentioning

confidence: 75%

Follicular dendritic cell sarcoma

2021

View full text Add to dashboard Cite

Summary Follicular dendritic cells (FDC) are mesenchymal-derived dendritic cells located in B-follicles where they play a pivotal role in triggering and maintaining B-cell adaptive immune response. In 1986 Dr. Juan Rosai first reported a series of neoplasms showing features of FDC and defined it as Follicular Dendritic Cell Tumor, subsequently renamed as “sarcoma” (FDCS). In its seminal and subsequent articles Rosai and colleagues highlighted the heterogeneous microscopic appearance of FDCS and its immunohistochemical and ultrastructural features. FDCS mostly occurs in extranodal sites (79.4% of cases) and lymph nodes (15.1%); in about 7%-10% of cases it is associated with hyaline-vascular Castleman disease. Given its significant growth pattern and cytological variability, FDCS can be confused with various neoplasms and even inflammatory processes. The diagnosis requires the use of a broad spectrum of FDC markers (e.g. CD21, CD23, CD35, clusterin, CXCL13, podoplanin), particularly considering that tumor antigen-loss is frequent. The inflammatory-pseudotumor-like (IPT-like) variant of FDCS, in addition to its peculiar histopathological and clinical features, is characterized by positivity of tumor cells for Epstein-Barr virus, representing a diagnostic requisite. No distinctive genetic and molecular anomalies have been identified in FDCS. It often carries an aberrant clonal karyotype and chromosomal structural alterations, frequently involving onco-suppressor genes. Direct or next generation sequencing showed alterations on genes belonging to the NF-κB regulatory pathway and cell-cycle regulators. In contrast to hematopoietic-derived histiocytic and dendritic cells tumors, FDCS typically lacks mutations in genes related to the MAPK pathway. FDCS recurs locally in 28% and metastasizes in 27% of cases. Extent of the disease, surgical resectability and histopathological features are significantly associated with the outcome. IPT-like FDCS behaves as an indolent tumor, even if it often recurs locally over years. Complete surgical excision is the gold standard of treatment. Data on targeted therapies (e.g.: tyrosine kinase inhibitors) or immune checkpoint inhibitors are very limited and responses are variable. A better understanding of the molecular drivers of this tumor may lead to potential new therapeutic strategies.

show abstract

Section: Genetics and Molecular Findingsmentioning

confidence: 75%

Follicular dendritic cell sarcoma

2021

View full text Add to dashboard Cite

show abstract

“…However, further studies are needed to confirm the roles of NCOA4 in iMCD. Additionally, alterations in genes involved in chromatin organization, including SETD1A , ASH1L , KMT2E and DNMT3A , have also been found in a subset of iMCD patients 88 . Another unanswered question is the cell types that are responsible for driving the iMCD pathogenesis and producing the cytokines.…”

Section: Imcd-nosmentioning

confidence: 99%

Multicentric Castleman disease and the evolution of the concept

et al. 2021

View full text Add to dashboard Cite

Summary The term multicentric Castleman disease (MCD) encompasses a spectrum of conditions that share some overlapping clinicopathological manifestations. The fundamental pathogenetic mechanism involves dysregulated cytokine activity, causing systemic inflammatory symptoms as well as lymphadenopathy. Some of the histological changes in lymph nodes resemble the histology of unicentric Castleman disease (UCD). However, based on current knowledge, the use of this shared nomenclature is unfortunate, since these disorders differ in pathogenesis and prognosis. In Kaposi sarcoma-associated herpesvirus (KSHV)-associated MCD, cytokine overactivity is caused by viral products, which can also lead to atypical lymphoproliferations and potential progression to lymphoma. In idiopathic MCD, the hypercytokinemia can result from various mechanisms, which ultimately lead to different constellations of clinical presentations and varied pathology in lymphoid tissues. The authors review the evolving concepts and definitions of the various conditions under the eponym of multicentric Castleman disease.

show abstract

“…Advanced biological techniques, such as genomics analysis, need to be further incorporated in iMCD-TAFRO research, as previously applied to iMCD in general. 57 - 59 …”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

International definition of iMCD-TAFRO: future perspectives

Nishimura

Sato

2022

JCEH

View full text Add to dashboard Cite

Since thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome was first proposed in 2010, there has been considerable progress in this area, particularly regarding its association with idiopathic multicentric Castleman disease (iMCD). TAFRO syndrome is a heterogeneous category with a constellation of symptoms that can develop in the setting of infection, rheumatologic disorder, malignancy, and iMCD. Now, iMCD with TAFRO symptoms is subtyped as iMCD-TAFRO. However, confusion between TAFRO syndrome and iMCD-TAFRO remains. In this article, we discuss the current understanding and future research agenda of TAFRO syndrome and iMCD-TAFRO from the perspective of its new validated international definition.

show abstract

A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease

Cited by 18 publications

References 48 publications

Follicular dendritic cell sarcoma

Follicular dendritic cell sarcoma

Multicentric Castleman disease and the evolution of the concept

International definition of iMCD-TAFRO: future perspectives

Contact Info

Product

Resources

About