Blastic NK cell lymphoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Agranular CD4+CD56+ hematodermic neoplasm; CD4+CD56+ hematodermic neoplasm; HDT; Blastic plasmacytoid dendritic cell neoplasm; BPDCN; Blastic natural killer cell lymphoma

Overview

Blastic natural killer cell lymphoma was first discovered by Adachi, an American hematologist, in 1994 following an unusual presentation of cutaneous lymphoma that express CD4 and CD56 antigens but no other T cell and B cell antigens. The deletion in 5q has been associated with the development of blastic natural killer cell lymphoma. Blastic natural killer cell lymphoma must be differentiated from other malignancies such as acute myeloid leukemia, human T-cell lymphotropic virus 1 associated adult T-cell leukemia/lymphoma, cutaneous NK/T-cell lymphoma, primary and secondary cutaneous pleomorphic T-cell lymphomas, undifferentiated carcinoma, and malignant melanoma. Blastic NK cell lymphoma is more commonly observed among middle-aged or elderly patients. The mean age at diagnosis is 66 years.[1]Males are more commonly affected with blastic natural killer cell lymphoma than females. Prognosis is generally poor, and the median survival rate is 15 months. Symptoms of blastic natural killer cell lymphoma may include nodules, plaques and patches of variable sizes on skin. Immunohistochemical staining is positive for r CD4 and CD56, with variable positivity for CD43, TdT, and CD68. The mainstay of therapy for blastic natural killer cell lymphoma is chemotherapy with CHOP or COP-like regimens.

Historical Perspective

Pathophysiology

Differentiating Blastic NK cell Lymphoma from other Diseases

ABBREVIATIONS

N/A: Not available, NL: Normal, FISH: Fluorescence in situ hybridization, PCR: Polymerase chain reaction, LDH: Lactate dehydrogenase, PUD: Peptic ulcer disease, EPO: Erythropoietin, LFTs: Liver function tests, RFTs: Renal function tests, LAP: Leukocyte alkaline phosphatase, LAD: Leukocyte alkaline dehydrgenase, WBCs: White blood cells.

Myeloproliferative neoplasms (MPN) Clinical manifestations Diagnosis Other features
Symptoms Physical examination CBC & Peripheral smear Bone marrow biopsy Other investigations
WBCs Hb Plat-
elets
Leuko-cytes Blasts Left
shift
Baso-
phils
Eosino-
phils
Mono-
cytes
Others
Chronic myeloid leukemia
(CML), BCR-ABL1+[9][10]
<2% + N/A NL
Chronic neutrophilic leukemia (CNL)[11][12][13] Minimal + NL NL NL
Polycythemia vera
(PV)[14][15][16][17]
  • Constitutional
NL or ↑ None - ↑ or ↓ NL or ↑ NL ↑↑ NL
  • Hypercellularity for age with tri-lineage growth
Primary myelofibrosis (PMF)[18][19][20][21] Erythroblasts - Absent NL NL
  • Variable with fibrosis or hypercellularity
Essential thrombocythemia (ET)[22][23][24]

NL or ↑

None

-

↓ or absent

NL

NL

  • N/A

↑↑

  • Normal/Hypercellular
Chronic eosinophilic leukemia,
not otherwise specified
(NOS)[25][26][27][28]
Present + ↑↑
MPN,
unclassifiable
Variable ± ↑ or ↓ ↑ or ↓ ↑ or ↓
  • N/A
Mastocytosis[29][30][31][32]
  • Constitutional
None - NL NL ↓ or ↑
Myeloid/lymphoid neoplasms
with eosinophilia and rearrangement
of PDGFRA, PDGFRB, or FGFR1,
or with PCM1-JAK2[33][34][35][36]
NL - NL
  • None
NL
  • FISH shows t(8;13) and t(8;22)
B-lymphoblastic leukemia/lymphoma[37][38] NL or ↑ >25% N/A ↑ or ↓ ↑ or ↓ ↑ or ↓
Myelodysplastic syndromes
(MDS)[39][40]
Variable -
  • Leukemia transformation
  • Acquired pseudo-Pelger-Huët anomaly
Acute myeloid leukemia (AML)
and related neoplasms[41][42]
NL or ↑ N/A ↑ or ↓ ↑ or ↓ ↑ or ↓

with dysplasia

Blastic plasmacytoid
dendritic cell neoplasm
[43][44][45][46]
NL NL NL NL
Myelodysplastic
/myeloproliferative
neoplasms
(MDS/MPN)
Chronic myelomonocytic leukemia (CMML)[47]
[48][49]
< 20% NL ↑↑
  • Overlapping of both, MDS and MPN
  • Absolute monocytosis > 1 × 109/L (defining feature)
  • MD-CMML:WBC ≤ 13 × 109/L (FAB)
  •  MP-CMML:WBC > 13 × 109/L (FAB)
Atypical chronic myeloid leukemia (aCML), BCR-ABL1-[50][51] <20% + <2% of WBCs N/A N/A
  • N/A
Juvenile myelomonocytic leukemia (JMML)[52][53] N/A N/A N/A
MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)[54][55][56]
  • Variable
NL or ↑ NL - NL N/A N/A
T-lymphoblastic leukemia/
lymphoma
T-lymphoblastic leukemia/
lymphoma
[57][58][59]
>25% blasts (Leukemia)

<25% blasts (Lymphoma)

± ↑ or ↓ ↑ or ↓ ↑ or ↓
  • LDH
  • Positive for TdT
  • Hypercelluarity with increased T cells precursors
Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymph[60] ± ↑ or ↓ ↑ or ↓ ↑ or ↓
  • N/A
Provisional entity: Early T-cell precursor lymphoblastic leukemia[61][62] ± ↑ or ↓ ↑ or ↓ ↑ or ↓
  • Hypercelluarity with increased T cells precursors

Epidemiology and Demographics

  • The prevalence of blastic natural killer cell lymphoma is unknown as it is an extremely rare disorder.[63]

Age

  • Blastic natural killer cell lymphoma is more commonly observed amongmiddle-aged or elderly patients. The mean age at diagnosis is 66 years.[1]

Gender

  • Males are more commonly affected with blastic natural killer cell lymphoma than females.

Natural History, Complications and Prognosis

  • The majority of patients with blastic natural killer cell lymphoma have an aggressive clinical course.
  • Prognosis is generally poor, and the median survival rate is 15 months.[8]

Diagnosis

Symptoms

  • Symptoms of blastic natural killer cell lymphoma may include:
  • Nodules, plaques and patches of variable sizes on skin

Physical Examination

  • Physical examination may be remarkable for:
  • Nodules, plaques and patches of variable sizes on skin
A plaque-like pigmented bruised rash over the patient’s trunk (A) and face (B)[63]

Laboratory Findings

  • There are no specific laboratory findings associated with blastic natural killer cell lymphoma.

Imaging Findings

  • There are no imaging study findings associated with blastic natural killer cell lymphoma

Other Diagnostic Studies

  • Blastic natural killer cell lymphoma may also be diagnosed using immunochemistry.
  • Immunohistochemical staining is positive for r CD4 and CD56, with variable positivity for CD43, TdT, and CD68.

Treatment

Medical Therapy

  • The mainstay of therapy for blastic NK cell lymphoma is chemotherapy with CHOP or COP-like regimens.
  • Immunomodulation or immunotherapy with IL-3 or with antiCD123 antibody is also being considered for chemotherapy-resistant patients.

Prevention

  • There are no primary preventive measures available for blastic natural killer cell lymphoma.

References

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