Follicular Dendritic Cell Sarcoma: Cytogenetics and pathological findings

Udayakumar, Achandira M.; Al-Bahri, Maiya; Burney, Ikram A.; Al-Haddabi, Ibrahim

doi:10.18295/squmj.2015.15.03.017

Cited by 6 publications

(4 citation statements)

References 6 publications

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“…It is known that HRD in cancer promotes genomic instability leading to chromosomal alterations. 42 In FDCS chromosomal alterations are often reported by classical karyotyping [21][22][23][24][25][26] and were found also by WGS in this study. This suggests that chromosomal "scarring" in FDCS may be a secondary pathogenic event, a consequence of HRD and further studies are warranted to specifically evaluate the correlation between HRD and chromosomal alterations in this setting.…”

Section: Discussionsupporting

confidence: 73%

“…The karyotype of case #13 was complex, however, by comparison with previously publishes studies we could not identify analogy with previously reported SV. [21][22][23][24][25][26] In order to evaluate the impact of NGS findings in identifying recurrent translocations of diagnostic significance, variations occurring in regions of interest in cancer biology were explored by FISH probes on tissues slides of case #13. FISH probe for the 18q11.2 locus did not identify rearrangements reported on the same locus by WGS, t(16;18) (p11.2;q11.2) and t(18;22)(q11.2;q11.23), additionally, the CIC and 19q co-deletion probes confirmed the CNV gain detected by WGS but did not identify rearrangements (data not shown).…”

Section: Structural Variants and Copy Number Variations Detection In ...mentioning

confidence: 99%

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Massive parallel sequencing unveils homologous recombination deficiency in follicular dendritic cell sarcoma

Lorenzi,

Haferlach,

Mori

et al. 2023

haematol

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Standardized treatment options are lacking for patients with unresectable or multifocal follicular dendritic cell sarcoma (FDCS) and disease-related mortality is as high as 20%. Applying whole genome sequencing (WGS) in one case and whole exome sequencing (WES) in additional twelve, this study adds information on the molecular landscape of FDCS, expanding knowledge on pathobiological mechanisms and identifying novel markers of potential theragnostic significance. Massive parallel sequencing showed high frequency of mutations on oncosuppressor genes, particularly in RB1, CARS and BRCA2 and unveiled alterations on homologous recombination DNA damage repair related genes in 70% (9/13) of cases. This indicates that patients with high stage FDCS may be eligible for poly ADP ribose polymerase inhibition protocols. Low tumor mutational burden was confirmed in this study despite common PDL1 expression in FDCS arguing on the efficacy of immune checkpoint inhibitors. CDKN2A deletion, detected by WGS and confirmed by FISH in 41% of cases (9/22) indicates that impairment of cell cycle regulation may sustain oncogenesis in FDCS. Absence of mutations in the RAS/RAF/MAPK pathway and lack of clonal hematopoiesis related mutations in FDCS sanction its differences from dendritic cell-derived neoplasms of haematopoietic derivation. WGS and WES in FDCS provides additional information on the molecular landscape of this rare tumor, proposing novel candidate genes for innovative therapeutical approaches to improve survival of patients with multifocal disease.

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Section: Discussionsupporting

confidence: 73%

Section: Structural Variants and Copy Number Variations Detection In ...mentioning

confidence: 99%

Massive parallel sequencing unveils homologous recombination deficiency in follicular dendritic cell sarcoma

Lorenzi,

Haferlach,

Mori

et al. 2023

haematol

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“…The neoplastic nature of FDCS was originally supported by identification of aberrant clonal karyotype and EBV clonality in the IPT-like variant 73 , 74 , and subsequently proven by the demonstration of chromosomal structural alterations, by classical karyotyping 75-78 , inversion probe array 79 and RNA, massive or targeted, parallel sequencing 80-82 . Notably, loss-type structural alterations were recorded as the most common event in FDCS (including loss of arms or of entire chromosomes) 75 , 77 , 78 , and often occur in regions encoding for important oncosuppressor genes 79 .…”

Section: Genetics and Molecular Findingsmentioning

confidence: 99%

Follicular dendritic cell sarcoma

2021

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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.

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“…The genetics underlying follicular dendritic cell sarcoma are poorly understood. Cytogenetic findings across 7 abnormal cases recently reviewed by Udayakumar et al 9 included variable ploidy states (from hypodiploid to near-tetraploid) and mostly non-recurrent alterations, which may in part be due to technical challenges in obtaining sufficient, representative metaphase spreads from these tumor samples. On the molecular level, Go et al 10 identified the BRAF V600E mutation, a potentially drugtargetable gain-of-function mutation that is variably present in other histiocytic and dendritic cell tumors, in a subset of follicular dendritic cell sarcoma tumors (18.5%, n = 27).…”

mentioning

confidence: 99%

Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology

et al. 2017

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Follicular dendritic cell sarcoma is a rare malignant neoplasm of dendritic cell origin that is currently poorly characterized by genetic studies. To investigate whether recurrent genomic alterations may underlie the biology of follicular dendritic cell sarcoma and to identify potential contributory regions and genes, molecular inversion probe array analysis was performed on 14 independent formalin-fixed, paraffin-embedded samples. Abnormal genomic profiles were observed in 11 out of 14 (79%) cases. The majority showed extensive genomic complexity that was predominantly represented by hemizygous losses affecting multiple chromosomes. Alterations of chromosomal regions 1p (55%), 2p (55%), 3p (82%), 3q (45%), 6q (55%), 7q (73%), 8p (45%), 9p (64%), 11q (64%), 13q (91%), 14q (82%), 15q (64%), 17p (55%), 18q (64%), and 22q (55%) were recurrent across the 11 samples showing abnormal genomic profiles. Many recurrent genomic alterations in follicular dendritic cell sarcoma overlap deletions that are frequently observed across human cancers, suggesting selection, or an active role for these alterations in follicular dendritic cell sarcoma pathogenesis. In support of a tumor suppressor-driven biology, homozygous deletions involving tumor suppressor genes CDKN2A, RB1, BIRC3, and CYLD were also observed. Neither recurrent gains nor amplifications were observed. This genomic characterization provides new information regarding follicular dendritic cell sarcoma biology that may improve understanding about the underlying pathophysiology, provide better prognostication, and identify potential therapeutic markers for this rare disease.

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Follicular Dendritic Cell Sarcoma: Cytogenetics and pathological findings

Cited by 6 publications

References 6 publications

Massive parallel sequencing unveils homologous recombination deficiency in follicular dendritic cell sarcoma

Massive parallel sequencing unveils homologous recombination deficiency in follicular dendritic cell sarcoma

Follicular dendritic cell sarcoma

Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology

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