Unique Composite Hematolymphoid Tumor Consisting of a Pro-T Lymphoblastic Lymphoma and an Indeterminate Dendritic Cell Tumor: Evidence for Divergent Common Progenitor Cell Differentiation

Buser, Lorenz; Bihl, Michel; Rufle, Alex; Mickys, Ugnius; Tavoriene, Ilma; Griškevičius, Laimonas; Tzankov, Alexandar

doi:10.1159/000365396

Cited by 20 publications

(21 citation statements)

References 27 publications

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“…Buser et al . reported about trans -differentiation of a T lymphoblastic lymphoma into an indeterminate dendritic cell tumour carrying a G13D mutation of the NRAS gene 29 . Interestingly, our patient had both BRAF and NRAS mutations that may be involved in the trans -differentiation process.…”

Section: Discussionmentioning

confidence: 99%

Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition

et al. 2016

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Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole-exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma. Using droplet-microfluidic technology and growth kinetic analyses, we demonstrate the presence of ibrutinib-resistant subclones and estimate subclone size before treatment initiation. Haploinsufficiency of TRAIL-R, a consequence of del(8p), results in TRAIL insensitivity, which may contribute to ibrutinib resistance. These findings demonstrate that the ibrutinib therapy favours selection and expansion of rare subclones already present before ibrutinib treatment, and provide insight into the heterogeneity of genetic changes associated with ibrutinib resistance.

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Section: Discussionmentioning

confidence: 99%

Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition

et al. 2016

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“…Together with 14 analogous cases submitted to the EAHP workshop on histiocytic neoplasms involving the lymph nodes [ 35 ], the above cases add further strong evidence in support of the frequent clonal relationship between mature B cell lymphomas and T-ALL/lymphoblastic lymphomas on the one hand and histiocytic neoplasms on the other [ 33 , 34 , 53 – 60 ]. While transdifferentiation of a neoplastic lymphoid cell after loss of the lineage transcription program has initially been proposed as an explanation [ 33 , 45 , 54 ], evidence now points towards divergent differentiation of a common progenitor cell into multiple lineages as an alternative pathogenic mechanism [ 34 , 58 , 60 ].…”

Section: Cases and Discussionmentioning

confidence: 99%

Histiocytic cell neoplasms involving the bone marrow: summary of the workshop cases submitted to the 18th Meeting of the European Association for Haematopathology (EAHP) organized by the European Bone Marrow Working Group, Basel 2016

et al. 2018

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The bone marrow is a preferential site for both reactive and neoplastic histiocytic proliferations. The differential diagnosis ranges from reactive histiocyte hyperplasia in systemic infections, vaccinations, storage diseases, post myeloablative therapy, due to increased cell turnover, and in hemophagocytic lymphohistiocytosis, through extranodal Rosai-Dorfman disease to neoplasms derived from histiocytes, including histiocytic sarcomas (HS), Langerhans cell histiocytoses (LCH), Erdheim-Chester disease (ECD), and disseminated juvenile xanthogranuloma (JXG). One of the most important recent developments in understanding the biology of histiocytic neoplasms and in contributing to diagnosis was the detection of recurrent mutations of genes of the Ras/Raf/MEK/ERK signaling pathway, in particular the BRAFV600E mutation, in LCH and ECD. Here, we summarize clinical and pathological findings of 17 histiocytic neoplasms that were presented during the bone marrow symposium and workshop of the 18th European Association for Haematopathology (EAHP) meeting held in Basel, Switzerland, in 2016. A substantial proportion of these histiocytic neoplasms was combined with clonally related lymphoid (n = 2) or myeloid diseases (n = 5, all ECD). Based on the latter observation, we suggest excluding co-existent myeloid neoplasms at initial staging of elderly ECD patients. The recurrent nature of Ras/Raf/MEK/ERK signaling pathway mutations in histiocytic neoplasms was confirmed in 6 of the 17 workshop cases, illustrating their diagnostic significance and suggesting apotential target for tailored treatments.

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“…hematopoietic malignancy has been demonstrated in only 3 reported cases, using fluorescence in-situ hybridization for trisomy 8, trisomy 21 and IgH-BCL2 translocation in the setting CMML, T lymphoblastic lymphoma and follicular lymphoma, respectively. 11,14,23 In the setting of CMML, a clonal relationship between the myeloid neoplasm and cutaneous IDCN is favored and supported by the ability of malignant monocytes to differentiate into dendritic cells in vitro. 34 IDCN can occasionally precede a diagnosis of a myeloid neoplasm for months or even years.…”

Section: So Far a Clonal Relationship Between The Idcn And An Associmentioning

confidence: 99%

Indeterminate dendritic cell neoplasm of the skin: A 2‐case report and review of the literature

et al. 2017

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Indeterminate dendritic cell neoplasm (IDCN) is an exceedingly rare and mostly cutaneous histiocytosis, frequently associated with other hematopoietic malignancies. We report 2 cases of multilesional cutaneous IDCN. A 55-year-old male with no associated malignancy and complete response to ultraviolet phototherapy; and a 72-year-old male with chronic myelomonocytic leukemia (CMML). Both cases showed histiocytoid cytology, positivity for CD1a and no expression of langerin or BRAF . With our patients, the literature describes 79 cases of IDCNs, including 65 (82%) with only skin involvement, 7 cases (9%) with involvement of skin and a second site, 5 cases (6%) involving lymph nodes only, 1 splenic lesion and 1 systemic disease. Seventeen cases (22%) were associated with other hematopoietic malignancies, most commonly CMML (6 cases), follicular lymphoma (4 cases) and acute myeloid leukemia (3 cases). All IDCNs associated with myeloid malignancies were limited to the skin, while most cases associated with lymphoma were limited to lymph nodes. Reported responses of cutaneous lesions to ultraviolet phototherapy are encouraging, while systemic chemotherapy is appropriate for clinically aggressive cases and treatment of associated malignancies. Recognition of the clinico-morphologic spectrum of IDCNs should prevent misdiagnoses and prompt investigation of possible associated neoplasms.

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Unique Composite Hematolymphoid Tumor Consisting of a Pro-T Lymphoblastic Lymphoma and an Indeterminate Dendritic Cell Tumor: Evidence for Divergent Common Progenitor Cell Differentiation

Cited by 20 publications

References 27 publications

Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition

Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition

Histiocytic cell neoplasms involving the bone marrow: summary of the workshop cases submitted to the 18th Meeting of the European Association for Haematopathology (EAHP) organized by the European Bone Marrow Working Group, Basel 2016

Indeterminate dendritic cell neoplasm of the skin: A 2‐case report and review of the literature

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