Blastic plasmacytoid dendritic cell neoplasm: a comprehensive review in pediatrics, adolescents, and young adults (AYA) and an update of novel therapies

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that can involve the bone marrow, peripheral blood, skin, lymph nodes, and the central nervous system. Though more common in older adults, BPDCN has been reported across all age groups, including infants and children. The incidence of pediatric BPDCN is extremely low and little is known about the disease. Pediatric BPDCN is believed to be clinically less aggressive but often with more dissemination at presentation than adult cases. Unlike adults who almost always proceed to a hematopoietic stem cell transplantation in first complete remission if transplant-eligible, the majority of children can be cured with a high-risk acute lymphoblastic leukemia-like regimen. Hematopoietic stem cell transplantation is recommended for children with high-risk disease, the definition of which continues to evolve, or those in relapse and refractory settings where outcomes continue to be dismal. Novel agents used in other hematologic malignancies and CD123 targeted agents, including chimeric antigen receptor T-cells and monoclonal/bispecific antibodies, are being brought into research and practice. Our goal is to provide a comprehensive review of presentation, diagnosis, and treatment by review of pediatric cases reported for the last 20 years, and a review of novel targeted therapies and therapies under investigation for adult and pediatric patients.

Fig. 1. Pediatric BPDCN cases—age and sex distribution at diagnosis.

The histogram depicts the distribution of age and sex at the diagnosis of pediatric cases of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN).

Fig. 2. Histological Presentation Patterns of BPDCN.

BPDCN involving the skin of a 14-year-old female. Staining with hematoxylin and eosin reveals a diffuse monotonous dermal-based infiltrate of medium-sized blastoid cells that spares the Grenz zone and epidermis and focally extends into the subcutaneous tissue (A, ×2; B, ×200). Occasional mitotic figures are present (C, ×500). Tumor cells are positive for CD4, CD56, and CD123 but negative for CD3, CD19, and myeloperoxidase (not shown). BPDCN involving the BM of a 16-year-old male. Staining with hematoxylin and eosin reveals an interstitial and diffuse infiltrate displacing hematopoietic elements (D, ×200;). A Wright-Giemsa–stained BM smear shows numerous blastic cells with irregular nuclear contours, immature chromatin, occasional small nucleoli, and variable light basophilic cytoplasm with occasional tail-like protrusions (E, ×1000). By immunohistochemistry, tumor cells are positive for TCF4/CD123 (F, ×500) and CD56 (G, ×500) but negative for CD3, CD19, and myeloperoxidase (not shown).

Fig. 3

Typical cell surface markers of BPDCN and their overlap with those of other hematologic malignancies.

Fig. 4

Locations of BPDCN involvement at diagnosis in a review of 69 pediatric cases.

Fig. 5. Radiologic Manifestations of BPDCN.

Axial CT and fused PET/CT of a teenage female with BPDCN show nodular skin and subcutaneous soft tissue thickening in the left breast that is fluorodeoxyglucose-avid (arrows in A and B) and associated with fluorodeoxyglucose-avid left axillary lymphadenopathy (arrows in C and D) as well as a fluorodeoxyglucose-avid bone lesion in the left distal humerus (arrow in E). MRI of the spine shows enhancing nerve roots in the lumbar spinal canal, consistent with leptomeningeal disease (arrows in F and G).

Fig. 6. Imaging Findings in CNS BPDCN.

Axial MRI of the face of a teenage male with BPDCN shows diffusely enlarged lacrimal glands (arrows in A), diffusely enlarged parotid glands (arrows in B), and a diffusely enlarged adenoid (arrowhead in B). CT of the neck, chest, abdomen, and pelvis reveals multicompartmental lymphadenopathy (involving the cervical, axillary, hilar, mediastinal, periportal, retroperitoneal, and iliac chain and inguinal lymph nodes) and hepatosplenomegaly (not shown). Brain and spine MRI reveal no leptomeningeal disease. Periorbital ecchymosis (“raccoon eyes”) at presentation in a patient later diagnosed with BPDCN (C).

Fig. 7

Outcomes from initial type of therapy regimen utilized.