Diagnosis, management challenging for pediatric BPDCN

December 8, 2020
Morgan Petronelli, Associate Editor

A 13-year-old boy presenting an asymptotic dark violaceous infiltrated nodular lesion located on the left cheek was diagnosed with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare and aggressive hematologic malignancy that often presents with skin manifestations.

A 13-year-old boy with a 10-month history of an asymptotic dark violaceous infiltrated nodular lesion located on the left cheek was referred for further analysis and later diagnosed with blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to a recently published case study in Pediatric Dermatology.1

BPDCN is a rare and aggressive hematologic malignancy that often presents with skin manifestations. Currently, there is only one U.S. Food and Drug Administration (FDA) approved treatment for the disease, tagraxofusp (ELZONRIS, Stemline). Tagraxofusp is a CD123-directed cytotoxin approved for BPDCN treatment in patients 2 years and older. CD123 is one of the major therapeutic targets of new therapies to treat myeloid cancers.2

The boy had previously been treated with systemic and topical steroids which saw partial improvements. The researchers preformed a skin biopsy which revealed a dense dermal infiltrate of monomorphous, poorly differentiated medium-sized cells with blastic morphology.

Immunohistochemical staining was conducted and showed positive CD4, CD56 and CD123 cells that were also negative for CD3, CD8, CD10, CD20, PAX5, TdT, LMP1 and MPO. Also, PET and CT scans displayed hypermetabolic activity localized to the skin.

The researchers diagnosed the child with BPDCN and following a discussion on the risks and benefits, a systemic treatment with high-risk acute lymphoblastic leukemia (ALL) chemotherapy protocol (vincristine, dexamethasone, asparaginase, daunomycin, cytarabine, cyclophosphamide, and methotrexate) was started.

“Age is an independent prognosis factor, BPDCNs in children have more favorable outcomes with better response to chemotherapy, higher rates of complete remission and lower rates of relapse,” writes Rivas‐Calderón MK, Cheirif‐Wolosky O, Rosas‐Romero ME, et al.

The authors report the pediatric patient is currently receiving treatment and has displayed a positive response devoid of complications after 18 months’ follow-up.

Diagnosis

In most BPDCN cases, both children and adults present skin lesions as the initial finding (76% and 85%, respectively), presenting as nodules, bruise-like macules or disseminated lesions. However, the study authors state not all cases present skin manifestations at the time of diagnosis, making it more difficult to diagnose.

Additionally, BPDCN is extremely rare in children, primarily affecting elderly males. One review found 283 total cases of BPDCN, with 74 cases being patients 18 years and younger and only 15 of those cases demonstrated skin only involvement.3

Most pediatric cases (80%) also present extracutaneous organ involvement at initial staging, including bone marrow involvement, hepatosplenomegaly and lymphadenopathy. Also, central nervous system involvement (CNS) is also reported more frequently in children than adults (47% versus 30%, respectively).

When diagnosing BPDCN, physicians should examine histolopathological morphology, as well as immunophenotype markers for dense monomorphous infiltrate of medium-sized blasts within the dermis ranging to the subcutaneous fat. The authors also note that due to the broad spectrum possibility of affected organs, PET/CT scans, BM biopsy and CSF analysis should also be included for assessment of suspected cases of BPDCN.

Management

When it comes to management of BPDCN, possible options include cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), a non-Hodgkin lymphoma regimen; or high-risk ALL chemotherapy regimens such as hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (hyper-CVAD) alternating with methotrexate and cytarabine, or AML induction regimens.

Of these management options, ALL-type regimens were seen as the most beneficial and successful, according to the authors.

If a relapse occurs, it is suggested pediatric patients receive a hematopoietic stem cell transplant (HSCT), which has demonstrated improved overall survival (OS) and disease-free survival (DFS) compared with chemotherapy alone.

“Management of patients with cutaneous BPDCN, like ours, is extremely challenging due to the indolent clinical picture and the potential lethality associated with the treatment,” writes the study authors. “However, BPDCN localized to skin should be treated as systemic, as recommended by current evidence about risk-benefit and outcomes of the disease. Scarce reports of children with skin-only involvement BPDCN showed good outcomes after treatment, but further evidence is needed.”

References:

1. Rivas‐Calderón MK, Cheirif‐Wolosky O, Rosas‐Romero ME, et al. Primary cutaneous blastic plasmacytoid dendritic cell neoplasm in a child: A challenging diagnosis and management. Pediatr Dermatol. Published online December 4, 2020:pde.14473.

2. Hilton L. Tagraxofusp: efficacy, safety and unanswered questions. Dermatology Times. https://www.dermatologytimes.com/view/tagraxofusp-efficacy-safety-and-unanswered-questions. Published July 29, 2020. Accessed December 7, 2020.

3. Kim MJ, Nasr A, Kabir B, et al. Pediatric blastic plasmacytoid dendritic cell neoplasm. J Pediatr Hematol Oncol. 2017;39(7):528-537.

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