Peer Reviewed

Pediatrics

What Are These Chronic, Progressive, Bruise-Like Lesions on a Child?

Volume 61 - Issue 8 - August 2021

AUTHORS:
Jessica Frelinger, MD • Matthew Baker, MD

AFFILIATION:
Children’s Hospital Los Angeles, Los Angeles, California

CITATION:
Frelinger J, Baker M. What are these chronic, progressive, bruise-like lesions on a child? Consultant. 2021;61(8):e13-e15. doi:10.25270/con.2021.03.00017

Received November 16, 2020. Accepted January 6, 2021. Published online March 24, 2021.

DISCLOSURES:
The authors report no relevant financial relationships.

CORRESPONDENCE:
Jessica Frelinger, MD, Children’s Hospital Los Angeles, Pediatric Residency Office, 4650 Sunset Boulevard, Los Angeles, CA 90027 (jfrelinger@chla.usc.edu)

 

A 6-year-old boy with obesity presented to our clinic with a 7-month history of worsening “bruising” scattered across his entire body. His mother had initially noted a small purplish-brown lesion on his upper left thigh, which slowly progressed in size. Over the course of several months, new lesions appeared and spread to his face, torso, back, and various parts of the extremities.

Several visits to the patient’s primary doctor and urgent care had not led to a diagnosis. He was referred to a dermatologist but presented to the emergency department (ED) prior to his dermatology appointment, because the lesions had become painful.

The lesions were initially dime-sized, flat, and purplish-brown in color and progressively increased in size and became more firm, elevated, and darker purple in color. The patient reported that the lesions are occasionally pruritic and painful to touch.

There is no history of trauma, easy bleeding or bruising, weight loss, night sweats, lymphadenopathy, travel, or unusual environmental exposures.

In the ED, the patient was noted to be afebrile with normal vital signs. Physical examination findings were significant for diffusely scattered, purpuric-appearing patches and plaques, some with a peau d’orange texture (Figures 1-3).

Figure 1 bruise-like lesion
Figure 1. Physical examination findings were significant for lesions spread diffusely over the patient’s upper back.

Figure 2 lesions on the chest
Figure 2. Physical examination findings were significant for lesions over the patient’s anterior chest.

Figure 3 lesions on the thigh
Figure 3. Physical examination findings were significant for a solitary lesion on the patient’s anterior thigh.

 

The results of laboratory workup showed a normal complete blood cell count, normal chemistry and coagulation panels, a normal C-reactive protein level, and a normal erythrocyte sedimentation rate. A radiography scan was conducted because the patient reported chest pain, results of which showed a possible widened mediastinum. The patient was admitted to the hospital for further workup. A computed tomography scan revealed an anterior mediastinal mass on the thymus.

 

 

Answer and discussion on the next page.

    Correct answer: B. Blastic plasmacytoid dendritic cell neoplasm

    Dermatology was consulted and conducted a punch biopsy of one of the lesions, results of which confirmed the diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN). In our patient’s case, the differential diagnosis revolved around the appearance and characteristics of the cutaneous lesions, because there was a lack of other distinct symptoms or clinical findings. The differential diagnosis primarily included vasculitis, benign lesions such as fibromas, or cutaneous oncologic processes.

    Discussion. BPDCN is a rare oncologic process arising from type 2 dendritic cells. BPDCN comprises less than 1% of cutaneous hematologic malignancies, with a male predominance of about 2.5:1. It is also more common among individuals aged older than 60 years, although there appears to be a bimodal age distribution with a second incidence peak in individuals aged younger than 20 years.1-3

    Cutaneous lesions are the most common clinical finding presenting in approximately 80% of cases, but only 30% of cases have cutaneous-isolated disease.3-6 The characteristic lesions—often plaques or nodules that are brown or purple in color with a bruise-like appearance—matched those on our patient.4,5 More than half of patients have involvement of blood, bone marrow, or lymph nodes with peripheral blood involvement presenting with the following frequency: thrombocytopenia, 78%; anemia, 65%; and neutropenia, 34%.4,6 Central nervous system (CNS) involvement is common at the time of diagnosis, affecting up to 33% of patients.2,6,7

    Diagnosis of BPDCN starts with a skin biopsy demonstrating infiltrative, intermediate-size blasts with poor differentiation that spare the epidermis. However, definitive diagnosis requires immunophenotyping that demonstrates cells expressing CD4 and CD56, as well as one or more plasmacytoid dendritic cell specific antigens.3,8,9,10

    Although there is a lack of consensus on the optimal approach to treating BPDCN in pediatric patients, many review articles have touted the benefits of high-risk acute lymphoblastic leukemia (ALL)-type therapies with CNS prophylaxis compared with other chemotherapy regimens.2,7,11,12 Regular intrathecal prophylaxis has been recommended to maintain remission, primarily because the CNS may serve as a persistent blast cell sanctuary and a common site of relapse.11 Hematopoietic stem cell transplantation (HSCT) is typically reserved for children who relapse, primarily because studies have not demonstrated an increase in survival rates for pediatric populations undergoing HSCT during their first remission, and the toxicity of allogeneic HSCT in the first remission outweighs the potential benefits for longer-term outcomes.6,11 Most recently in adult populations with BPDCN, novel targeted therapies have shown promise with manageable toxicities and durable responses to therapy.2,7,13 Tagraxofusp-erzs is the only US Food and Drug Administration–approved targeted therapy for both adults and children aged older than 2 years.7,14 However, this medication may not always be an option.7,14

    Data demonstrates a difference in prognosis between pediatric and adult patients. The overall prognosis for adult BPDCN is poor, with a reported average survival median of less than 2 years.7,15 In comparison, pediatric patients fare better than their adult counterparts on multiple prognostic measures. Children are more likely to achieve complete remission, have lower rates of relapse, and have higher survival rates at follow-up.11 In a 2010 review article, pediatric patients on chemotherapy, without HSCT, had an overall survival of 74%, with a median follow-up of 30 months.6 Older age is the primary negative predictive prognostic factor for BPDCN; clinical presentation, aside from cutaneous lesions, does not have prognostic significance in pediatric populations.11 It is unclear whether the presence of cutaneous lesions at diagnosis affects the prognosis in children. Some studies have shown that pediatric patients presenting without cutaneous lesions can be expected to fare better, but this may be due to a higher proportion of patients with noncutaneous symptoms receiving ALL treatment.6,11

    Patient Outcome. After biopsy results returned, the patient was admitted to the oncology service and underwent further workup, including peripheral smear and cytometry, bone marrow aspirate, and lumbar puncture, results of which showed no signs of malignancy. The patient was started on a regimen of induction high-risk ALL, including vincristine, doxorubicin, pegasparaginase, and dexamethasone with intrathecal methotrexate and cytarabine.

    At the end of induction, the patient had significant fading or resolution of all skin lesions without evidence of disease metastasis on repeat imaging. He underwent consolidation phase treatment with 6-mercaptopurine and cytarabine with intrathecal triple therapy, including vincristine, methotrexate, and 6-mercaptopurine. Now, he is on a maintenance therapy regimen of vincristine, high-dose methotrexate, and 6-mercaptopurine without significant complications or signs of disease relapse.

    References

    1. Guru Murthy GS, Pemmaraju N, Atallah E. Epidemiology and survival of blastic plasmacytoid dendritic cell neoplasm. Leuk Res. 2018;73:21-23. https://doi.org/10.1016/j.leukres.2018.08.014
    2. Khoury JD. Blastic Plasmacytoid dendritic cell neoplasm. Curr Hematol Malig Rep. 2018;13(6):477-483. https://doi.org/10.1007/s11899-018-0489-z
    3. Petrella T, Bagot M, Willemze R, et al. Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review. Am J Clin Pathol. 2005;123(5):662-675. https://doi.org/10.1309/GJWNPD8HU5MAJ837
    4. Julia F, Petrella T, Beylot-Barry M, et al. Blastic plasmacytoid dendritic cell neoplasm: clinical features in 90 patients. Br J Dermatol. 2013;169(3):579-586. https://doi.org/10.1111/bjd.12412
    5. Rauh MJ, Rahman F, Good D, et al. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation, lacking cutaneous involvement: case series and literature review. Leuk Res. 2012;36(1):81-86. https://doi.org/10.1016/j.leukres.2011.07.033
    6. Jegalian AG, Buxbaum NP, Facchetti F, et al. Blastic plasmacytoid dendritic cell neoplasm in children: diagnostic features and clinical implications. Haematologica. 2010;95(11):1873-1879. https://doi.org/10.3324/haematol.2010.026179
    7. Venugopal S, Zhou S, El Jamal SM, Lane AA, Mascarenhas J. Blastic plasmacytoid dendritic cell neoplasm-current insights. Clin Lymphoma Myeloma Leuk. 2019;19(9):545-554. https://doi.org/10.1016/j.clml.2019.06.002
    8. Feuillard J, Jacob MC, Valensi F, et al. Clinical and biologic features of CD4+CD56+ malignancies. Blood. 2002;99(5):1556-1563. https://doi.org/10.1182/blood.v99.5.1556
    9. Marafioti T, Paterson JC, Ballabio E, et al. Novel markers of normal and neoplastic human plasmacytoid dendritic cells. Blood. 2008;111(7):3778-3792. https://doi.org/10.1182/blood-2007-10-117531
    10. Shi Y, Wang E. Blastic plasmacytoid dendritic cell neoplasm: a clinicopathologic review. Arch Pathol Lab Med. 2014;138(4):564-569. https://doi.org/10.5858/arpa.2013-0101-rs
    11. Kim MJ, Nasr A, Kabir B, et al. Pediatric blastic plasmacytoid dendritic cell neoplasm: a systematic literature review. J Pediatr Hematol Oncol. 2017;39(7):528-537. https://doi.org/10.1097/mph.0000000000000964
    12. Tomé A, Pragosa H, Caldas G, Lacerda A, Pereira F. Pediatric blastic plasmacytoid dendritic cell neoplasm: how to treat? J Pediatr Hematol Oncol. 2017;39(4):323. https://doi.org/10.1097/mph.0000000000000812
    13. Kerr D 2nd, Zhang L, Sokol L. Blastic plasmacytoid dendritic cell neoplasm. Curr Treat Options Oncol. 2019;20(1):9. https://doi.org/10.1007/s11864-019-0605-x
    14. FDA approves tagraxofusp-erzs for blastic plasmacytoid dendritic cell neoplasm. News release. US Food and Drug Administration. December 21, 2018. Accessed March 8, 2021. https://www.fda.gov/drugs/fda-approves-tagraxofusp-erzs-blastic-plasmacytoid-dendritic-cell-neoplasm
    15. Pagano L, Valentini CG, Pulsoni A, et al. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study. Haematologica. 2013;98(2):239-246. https://doi.org/10.3324/haematol.2012.072645