Blastic Plasmacytoid Dendritic Cell Neoplasm

Wesley O. Greaves, MD

L. Jeffrey Medeiros, MD

Key Facts

Clinical Issues

Median age: ˜ 65 years
- Wide age range: 8-96 years
Male to female ratio: ˜ 2-3:1
Skin is most common initial site of disease
Other common sites of disease at initial diagnosis
- Lymph nodes
- Bone marrow and blood
No established standard therapy
Very aggressive clinical course; median survival 12-14 months

Microscopic Pathology

Skin: Diffuse dermal infiltrate
Lymph nodes: Paracortical or diffuse replacement
Bone marrow: Interstitial pattern
Neoplastic cells can exhibit spectrum of findings
- Small/intermediate size resembling lymphoblasts
- Intermediate size and resembling myeloblasts

Ancillary Tests

Characteristic immunophenotype
- CD123(+), TCL1(+), CD303(+), bcl-11A(+)
- CD4(+), CD56(+)
TdT expressed in ˜ 50% of cases
CD45/LCA(+), CD99(+/-)
Conventional cytogenetics
- Complex karyotype common

Top Differential Diagnoses

Myeloid/monocytic sarcoma or leukemia
T lymphoblastic leukemia/lymphoma
PDC proliferations associated with myeloid neoplasms

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) involving lymph node. The neoplasm incompletely replaces the lymph node in a paracortical pattern. Uninvolved areas

can be appreciated.

BPDCN involving lymph node. The neoplasm has a “starry sky” pattern in this field, indicating a high cell turnover rate. The neoplastic cells are blast-like.

TERMINOLOGY

Abbreviations

Blastic plasmacytoid dendritic cell neoplasm (BPDCN)
- Current term in 4th edition of World Health Organization (WHO) classification

Synonyms

CD4(+), CD56(+) hematodermic neoplasm/tumor
CD4(+), CD56(+) blastic tumor of skin
Blastic NK-cell lymphoma (3rd edition of WHO classification)

Definitions

Highly aggressive neoplasm derived from precursors of plasmacytoid dendritic cells

ETIOLOGY/PATHOGENESIS

Normal Plasmacytoid Dendritic Cells (PDCs)

Other terms used for PDCs
- Type 2 dendritic cells (DC2)
- Plasmacytoid monocytes (obsolete)
- Plasmacytoid T cells (obsolete)
Mostly located in T-zones of lymphoid tissues
Also present in bone marrow and blood
PDCs are characterized by
- High expression of IL-3α chain receptor
- Production of interferon-γ
- Differentiate into dendritic cells in culture after treatment with IL3 and CD40 ligand
PDCs are increased in a number of diseases including
- Lymph nodes
  - Chronic granulomatous inflammation
  - Kikuchi-Fujimoto disease, Castleman disease
  - Classical Hodgkin lymphoma
- Skin
  - Psoriasis
  - Lupus erythematosus
Immunophenotype of normal PDCs
- CD4(+), CD123(+), HLA-DR(+)
- CD303/BDCA-2(+), CLA(+), TCL1(+)
- GZM-B(+), CD43(+, dim), CD68(+, dim)
- CD11c(-), CD56(-), TIA1(-), perforin(-)

Etiology & Pathogenesis of BPDCN Unknown

Associated with myelomonocytic leukemia in ˜ 10-20% of cases
- With or without underlying myelodysplasia

CLINICAL ISSUES

Epidemiology

Incidence
- Rare
  - < 1% of all lymphomas that involve skin
Age
- Median age: ˜ 65 years
- Wide age range: 8-96 years
Gender
- Male to female ratio: ˜ 2-3:1
Ethnicity
- No known ethnic predilection

Site

Skin is most common initial site of disease
Other common sites of disease at time of initial diagnosis
- Lymph nodes
- Bone marrow and blood
  - Usually low-level involvement
Staging studies can show involvement of
- Spleen, liver, other viscera
Other rare sites of disease
- Tonsils, nasopharynx, gums
- Lacrimal gland, conjunctiva
- Kidneys, gynecologic tract
Central nervous system involvement is rare at diagnosis
- Involved in ˜ 33% of patients at time of relapse
Mediastinum is rarely involved

Presentation

Solitary or multiple skin lesions
- Nodules, patch-like, or plaques
- ± erythema, ± purpura
- Can be asymptomatic
- Disease restricted to skin in ˜ 50% of patients
Regional lymph nodes positive in ˜ 50% of patients
Low-level blood and bone marrow involvement
Systemic B symptoms are uncommon

Laboratory Tests

Complete blood count
- ± cytopenias
- ± monocytosis
BPDCN can progress to full-blown leukemic phase
- Neoplastic cells may be either BPDCN or myelomonocytic leukemia

Treatment

No established standard therapy; options usually employed
- Combination chemotherapy
- Allogeneic stem cell transplantation at first relapse
Localized radiotherapy has limited utility

Prognosis

Very aggressive clinical course
Median survival: 12-14 months
- Patients often have good initial response to chemotherapy
- Relapse and disease progression very common
Skin lesions respond to radiotherapy, but this modality has limited utility
Few patients enter long-term remission after stem cell transplantation
Prognosis is relatively better for patients < 40 years
- Median survival: ˜ 3 years

IMAGE FINDINGS

Radiographic Findings

Increased uptake by [18F] fluorodeoxyglucose positron emission tomography

MACROSCOPIC FEATURES

General Features

Nodules, plaques, or bruise-like lesions of skin
- ± ulcer

MICROSCOPIC PATHOLOGY

Histologic Features

Skin
- Monomorphous infiltrate predominantly involving dermis
  - Perivascular and periadnexal pattern in lesions with minimal involvement
  - Diffuse pattern with extensive involvement
  - Grenz zone usually present between infiltrate and epidermis
  - No or minimal epidermotropism
- Erythrocyte extravasation is common
- Modest inflammatory infiltrate associated with neoplasm
  - Small number of T cells
  - Usually no plasma cells or eosinophils
Lymph node
- Diffuse effacement of lymph node architecture
- In cases with partial involvement
  - Preferential paracortical replacement
  - Sinuses can be involved
Bone marrow
- Mild to marked interstitial infiltration
- Dysplasia in residual hematopoietic cells
  - Can be prominent in megakaryocytes