Clinical presentation
Clinically, the malignancy presents with variable involvement of the skin, bone marrow, lymph nodes, peripheral blood, and central nervous system. “Patients may have one or all of these,” she said. Because 80% of patients have skin lesions, “dermatologists should be aware of this entity in order to communicate with our pathologists to understand that maybe one biopsy isn’t enough. Several biopsies may be required.”
The most common dermatologic presentation of BPDCN is erythematous to deeply violaceous nodules. Other patients may present with infiltrated ecchymotic plaques or petechial to hyperpigmented macules, patches, and plaques. Biopsy reveals a diffusely infiltrated dermis of markedly atypical large cells, but occasionally can be more subtle. “Early lesions may only be perivascular in nature, so going on high power on anything that looks atypical on low power is important in these cases,” Dr. DeClerck said.
The recommended histochemical stains for suspected BPDCN include CD123, CD4, and CD56. “We need to have other stains to rule out other things, such as negative stains that are going to exclude other T cell and B cell processes, and Merkel cell carcinoma, which can express CD56. We also want to have another confirmatory stain because other things can express CD123, CD4, and CD56. Commonly we use TCL1 or TCF4.”
The differential diagnosis of cutaneous findings includes leukemia cutis, mycosis fungoides, NK/T-cell lymphoma, and cutaneous gamma-delta T-cell lymphoma, while the differential diagnosis of biopsy findings includes AML, acute lymphoblastic leukemia, and NK/T-cell lymphoma.
Treatment of BPDCN
Historically, BPDCN was treated with multiagent high-dose chemotherapy. “Patients would frequently respond early but would relapse quickly, progress, and have a poor outcome,” Dr. DeClerck said. Now, first-line therapy is tagraxofusp-erzs (Elzonris) or multiagent chemotherapy based on where the patient is in the course of disease. Tagraxofusp-erzs is an IL-3 conjugated diphtheria toxic fusion protein which binds to CD123, which was approved by the Food and Drug Administration in 2018 for treating BPDCN. After that initial therapy, it is determined whether the patient has a complete response or failed response, she said. “If they have a complete response, they frequently go on to bone marrow transplantation, which is the only curative therapy at this point for these patients.”
According to Dr. DeClerck, an anti-BCL-2 therapy, venetoclax, can be used for patients with BPDCN as well. National Comprehensive Cancer Network (NCCN) guidelines for the treatment of BPDCN can be found on the NCCN website.
Dr. DeClerck emphasized the importance of reviewing biopsy results with a hematopathologist, “because there are complex leukemias that are beyond what dermatopathologists have been trained in.” Once a patient is diagnosed with BPDCN, she recommends rapid referral to a large center for treatment and possible bone marrow transplantation.
Dr. DeClerck disclosed that she is an adviser for tagraxofusp-erzs manufacturer Stemline Therapeutics.