PAX5 P80R-mutated B-cell acute lymphoblastic leukemia with transformation to histiocytic sarcoma: clonal evolution assessment using NGS-based immunoglobulin clonality and mutation analysis

Kroeze, Leonie I.; Scheijen, Blanca; Hebeda, Konnie M.; Rijntjes, Jos; Luijks, Jeroen A.C.W.; Evers, Dorothea; Hobo, Willemijn; Groenen, Patricia J.T.A.; Brand, Michiel van den

doi:10.1007/s00428-022-03428-y

Cited by 6 publications

(7 citation statements)

References 15 publications

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“…Six of these 11 patients have been reported previously. 7,[13][14][15] The remaining five cases comprised one patient with KRAS p.G12A mutated ECD and chronic myelomonocytic leukaemia and four patients with MH and B-lineage lymphoid cancers harbouring identical immunoglobulin gene rearrangements (Figures S3-S6). In one case (Case #7) of a 19-year-old male with B-cell acute lymphoblastic leukaemia (B-ALL) and secondary HS (Figure 2E), identical NRAS p.G12V and PAX5 p.P80R mutations were also detected in the B-ALL and HS.…”

Section: Resultsmentioning

confidence: 99%

“…In 11 patients, identical genetic alterations were identified in both haematologic neoplasms (Table 1). Six of these 11 patients have been reported previously 7,13–15 . The remaining five cases comprised one patient with KRAS p.G12A mutated ECD and chronic myelomonocytic leukaemia and four patients with MH and B‐lineage lymphoid cancers harbouring identical immunoglobulin gene rearrangements (Figures S3–S6).…”

Section: Resultsmentioning

confidence: 99%

“…21 Interestingly, we report the second case of PAX5 p.P80R mutated B-ALL and secondary histiocytic sarcoma, further supporting that PAX5 alterations may predispose (precursor) B cells to differentiate into the myeloid lineage. 14,22 Furthermore, the frequent observation of shared N/KRAS mutations is remarkable (Table 1), suggesting that patients with activating mutations in these oncogenes may be particularly at risk of developing clonally related second cancers. 7 In addition to shared genetic alterations, several mutations unique to either the histiocytic/dendritic cell neoplasm or associated haematologic malignancy were detected-which might have contributed to the transformation to the secondary neoplasm (Table 1).…”

Section: Discussionmentioning

confidence: 99%

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Demographics and additional haematologic cancers of patients with histiocytic/dendritic cell neoplasms

Kemps,

Kester,

Scheijde‐Vermeulen

et al. 2024

Histopathology

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AimsThe discovery of somatic genetic alterations established many histiocytic disorders as haematologic neoplasms. We aimed to investigate the demographic characteristics and additional haematologic cancers of patients diagnosed with histiocytic disorders in The Netherlands.Methods and resultsWe retrieved data on histiocytosis patients from the Dutch Nationwide Pathology Databank (Palga). During 1993 to 2022, more than 4000 patients with a pathologist‐assigned diagnosis of a histiocytic disorder were registered in Palga. Xanthogranulomas were the most common subtype, challenging the prevailing assumption that Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. LCH and juvenile xanthogranuloma (JXG) had a peak incidence in the first years of life; males were overrepresented among all histiocytosis subgroups. 118 patients had a histiocytic disorder and an additional haematologic malignancy, including 107 (91%) adults at the time of histiocytosis diagnosis. In 16/118 patients, both entities had been analysed for the same genetic alteration(s). In 11 of these 16 patients, identical genetic alterations had been detected in both haematologic neoplasms. This included two patients with PAX5 p.P80R mutated B cell acute lymphoblastic leukaemia and secondary histiocytic sarcoma, further supporting that PAX5 alterations may predispose (precursor) B cells to differentiate into the myeloid lineage. All 4/11 patients with myeloid neoplasms as their additional haematologic malignancy had shared N/KRAS mutations.ConclusionsThis population‐based study highlights the frequency of xanthogranulomas. Furthermore, our data add to the growing evidence supporting clonal relationships between histiocytic/dendritic cell neoplasms and additional myeloid or lymphoid malignancies. Particularly adult histiocytosis patients should be carefully evaluated for the development of these associated haematologic cancers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Demographics and additional haematologic cancers of patients with histiocytic/dendritic cell neoplasms

Kemps,

Kester,

Scheijde‐Vermeulen

et al. 2024

Histopathology

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“…Because of the sequence information and the high sensitivity, the NGS-based clonality assays are very valuable to solve complex rearrangement patterns ( 17 ). They allow detailed comparison of sequential lesions or multiple lymphomas at different locations within a patient ( 18 ). The technical improvements due to the advent of NGS will allow higher sensitivity, more detailed analysis and broader applications, as will be discussed below.…”

Section: Ngs-amplicon Based Clonality Assessmentmentioning

confidence: 99%

Read the clonotype: Next-generation sequencing-based lymphocyte clonality analysis and perspectives for application in pathology

Groenen

Brand²,

Kroeze³

et al. 2023

Front. Oncol.

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Clonality assessment using the unique rearrangements of immunoglobulin (IG) and T-cell receptor (TR) genes in lymphocytes is a widely applied supplementary test for the diagnosis of B-cell and T-cell lymphoma. To enable a more sensitive detection and a more precise comparison of clones compared with conventional clonality analysis based on fragment analysis, the EuroClonality NGS Working Group developed and validated a next-generation sequencing (NGS)-based clonality assay for detection of the IG heavy and kappa light chain and TR gene rearrangements for formalin-fixed and paraffin-embedded tissues. We outline the features and advantages of NGS-based clonality detection and discuss potential applications for NGS-based clonality testing in pathology, including site specific lymphoproliferations, immunodeficiency and autoimmune disease and primary and relapsed lymphomas. Also, we briefly discuss the role of T-cell repertoire of reactive lymphocytic infiltrations in solid tumors and B-lymphoma.

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“…14 The history of B-ALL further confounded the diagnosis in our case, since B-ALL may transform into histiocytic sarcoma. [15][16][17][18] The infiltrate in such cases shows histiocytic morphology and immunohistochemical expression similar to mature tissue histiocytes (expressing CD68, CD163) along with B-cell lineage markers (e.g., CD20, PAX5) and a rapidly deteriorating clinical course. 19 However, the expression of B-cell markers was not seen in large cells in our case.…”

Section: Case Reportmentioning

confidence: 99%

Neoplastic or inflammatory? A case report of Sweet syndrome with CD30+ cells in a patient with B‐lymphoblastic leukemia

Ehyaee,

Reddy,

Ahmed

2023

J Cutan Pathol

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CD30+ cells are typically part of lymphoproliferative disorders but can also be seen in inflammatory dermatoses. We present a case of 47‐year‐old man with a history of B‐lymphoblastic leukemia (B‐ALL) who presented with fever, leukocytosis, and papulonodular skin lesions, involving the extremities and trunk. A punch biopsy specimen demonstrated papillary dermal edema with a neutrophilic and histiocytic infiltrate extending into the subcutis. The infiltrate also harbored scattered large cells that were positive for CD30 and demonstrated the immunohistochemical profile of monocytes. A diagnosis of histiocytoid Sweet syndrome with CD30+ cells was made. The case is unique, demonstrating a combination of Sweet syndrome variants with subcutis involvement, histiocytoid morphology, and large CD30+ cells. A prior history of B‐ALL and immunohistochemical profile of monocytes with immature morphology broadened the differential diagnosis and added to the diagnostic challenge.

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PAX5 P80R-mutated B-cell acute lymphoblastic leukemia with transformation to histiocytic sarcoma: clonal evolution assessment using NGS-based immunoglobulin clonality and mutation analysis

Cited by 6 publications

References 15 publications

Demographics and additional haematologic cancers of patients with histiocytic/dendritic cell neoplasms

Demographics and additional haematologic cancers of patients with histiocytic/dendritic cell neoplasms

Read the clonotype: Next-generation sequencing-based lymphocyte clonality analysis and perspectives for application in pathology

Neoplastic or inflammatory? A case report of Sweet syndrome with CD30+ cells in a patient with B‐lymphoblastic leukemia

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