Blastic plasmacytoid dendritic cell neoplasm: challenges and future prospects

Trottier, Amy M.; Cerquozzi, Sonia

doi:10.2147/blctt.s132060

Cited by 13 publications

(10 citation statements)

References 56 publications

(89 reference statements)

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“…We also find a positive association between T-cell exhaustion and T-cell clonal expansion, consistent with other cancers (21,51). A lack of TCR expression by malignant cells is one feature that distinguishes BPDCN from mature T-cell malignancies, such as cutaneous T-cell lymphoma (52,53). However, little research has been done on T-cell biology in BPDCN, and none at the single-cell level.…”

Section: Discussionsupporting

confidence: 84%

Single-cell Multiomics Reveals Clonal T-cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm

DePasquale

Ssozi

Ainciburu

et al. 2021

Preprint

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The immune system represents a major barrier to cancer progression, driving the evolution of immunoregulatory interactions between malignant cells and T-cells in the tumor environment. Blastic plasmacytoid dendritic cell neoplasms (BPDCN), a rare acute leukemia with plasmacytoid dendritic cell (pDC) differentiation, provides a unique opportunity to study these interactions. pDCs are key producers of interferon alpha (IFNA) that play an important role in T-cell activation at the interface between the innate and adaptive immune system. To assess how uncontrolled proliferation of malignant BPDCN cells affects the tumor environment, we catalog immune cell heterogeneity in the bone marrow (BM) of five healthy controls and five BPDCN patients by analyzing 52,803 single-cell transcriptomes, including 18,779 T-cells. We test computational techniques for robust cell type classification and find that T-cells in BPDCN patients consistently upregulate interferon alpha (IFNA) response and downregulate tumor necrosis factor alpha (TNFA) pathways. Integrating transcriptional data with T-cell receptor sequencing via shared barcodes reveals significant T-cell exhaustion in BPDCN that is positively correlated with T-cell clonotype expansion. By highlighting new mechanisms of T-cell exhaustion and immune evasion in BPDCN, our results demonstrate the value of single-cell multiomics to understand immune cell interactions in the tumor environment.

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Section: Discussionsupporting

confidence: 84%

Single-cell Multiomics Reveals Clonal T-cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm

DePasquale

Ssozi

Ainciburu

et al. 2021

Preprint

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“…Interestingly, toxoplasma gondii infects and uses dendritic cells to spread the infection throughout the human body, and toxoplasmosis is furthermore considered a differential diagnosis to BPDCN [15,16]. Whether this connection is of any significance to this case report remains unclear due to the limited literature within the field, but a possible association between toxoplasmosis and hematological malignancies has earlier been suspected [17].…”

Section: Discussionmentioning

confidence: 91%

Blastic plasmacytoid dendritic cell neoplasm and cerebral toxoplasmosis: a case report

Florescu

Sørensen

Nielsen³

et al. 2022

BMC Neurol

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Background The present case contributes to the limited literature on central nervous system involvement of blastic plasmacytoid dendritic cell neoplasm (BPDCN). Case presentation A 63-year-old male presented to the department of neurology with a three-day history of rapidly progressing headache, fatigue, and confusion. Physical examination revealed multiple bruise-like skin lesions. Initial laboratory workup raised suspicion of acute leukemia, and a brain computer tomography identified several hyperdense processes. A bone marrow biopsy gave the diagnosis BPDCN, a rare and aggressive hematologic malignancy derived from plasmacytoid dendritic cells with a poor prognosis. Lumbar puncture showed not only signs of BPDCN, but also cerebral toxoplasmosis, thus providing a differential diagnosis. Despite intensive systemic and intrathecal chemotherapy, the patient died 25 days later due to multi-organ failure. Discussion The exact incidence of BPDCN is unknown and perhaps underestimated but may account for 0.5 – 1% of all hematological malignancies. The median age at onset is 60 to 70 years, and most patients are men. Cutaneous lesions are the most frequent clinical manifestation at diagnosis. Other symptoms present at time of diagnosis or during disease progression include lymphadenopathy, splenomegaly and cytopenia caused by bone marrow involvement. Although the majority of BPDCN patients have no symptoms or signs of central nervous system involvement, plasmacytoid dendritic cells have been detected in the cerebrospinal fluid in more than 50%. Conclusions This case highlights the importance of considering hematological malignancies as a differential diagnosis in patients developing acute neurological symptoms and raises suspicion of a possible association between toxoplasmosis and hematological malignancies.

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“…Nevertheless, instead of skin involvement, T-cell lymphoblastic lymphoma often presents with a mediastinal mass. As an extramedullary myeloid tumor, myeloid sarcoma consists of myeloblasts or premature myeloid cells [ 20 ]. Monoblastic lineage of both BPDCN and myeloid sarcoma express CD56, CD123, and CD4 markers; nevertheless, TdT is exclusively detected in 33% of the BPDCN patients.…”

Section: Discussionmentioning

confidence: 99%

A misdiagnosed case of blastic plasmacytoid dendritic cell neoplasm experiencing multiple recurrences who underwent allogeneic stem cell transplantation: a case report

et al. 2021

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Background Blastic plasmacytoid dendritic cell neoplasm represents a rare type of hematologic malignancy that often manifests itself through various skin lesions. It commonly affects the elderly male population. Lymph nodes, peripheral blood, and bone marrow involvement are the typical findings that justify its aggressive nature and dismal prognosis. On histopathological assessment, malignant cells share some similarities with blastic cells from the myeloid lineage that make immunohistochemistry staining mandatory for blastic plasmacytoid dendritic cell neoplasm diagnosis. Case presentation A 35-year-old Asian man presented with cervical lymphadenopathy followed by an erythematous lesion on his left upper back. At first, the lesion was misdiagnosed as an infectious disease and made the patient receive two ineffective courses of azithromycin and clarithromycin. Six months later, besides persistent skin manifestations, he felt a cervical mass, which was misdiagnosed as follicular center cell lymphoma. Tumor recurrence following the chemoradiation questioned the diagnosis, and further pathologic assessments confirmed blastic plasmacytoid dendritic cell neoplasm. The second recurrence occurred 3 months after chemotherapy. Eventually, he received a bone marrow transplant after complete remission. However, the patient expired 3 months after transplant owing to the third recurrence and gastrointestinal graft versus host disease complications. Conclusions Early clinical suspicion and true pathologic diagnosis play a crucial role in patients’ prognosis. Moreover, allogenic bone marrow transplant should be performed with more caution in aggressive forms of blastic plasmacytoid dendritic cell neoplasm because of transplant side effects and high risk of cancer recurrence.

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Blastic plasmacytoid dendritic cell neoplasm: challenges and future prospects

Cited by 13 publications

References 56 publications

Single-cell Multiomics Reveals Clonal T-cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm

Single-cell Multiomics Reveals Clonal T-cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic plasmacytoid dendritic cell neoplasm and cerebral toxoplasmosis: a case report

A misdiagnosed case of blastic plasmacytoid dendritic cell neoplasm experiencing multiple recurrences who underwent allogeneic stem cell transplantation: a case report

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