Bone marrow neoplastic
Bone marrow - plasma cell and lymphoid neoplasms
NK and T cell precursor lymphoid neoplasms
NK lymphoblastic leukemia / lymphoma
Board of reviewers: Carlos A. Murga-Zamalloa, M.D.
Editorial Board Member: Alexa J. Siddon, M.D.
Last author update: 19 November 2024
Last staff update: 19 November 2024
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PubMed Search: NK lymphoblastic leukemia / lymphoma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Peripheral smear description | Peripheral smear images | Positive stains | Negative stains | Flow cytometry description | Flow cytometry images | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Atiq A, Raza M, Minhas MK. NK lymphoblastic leukemia / lymphoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomaNKlymphoblastic.html. Accessed December 17th, 2024.
Definition / general
- NK lymphoblastic leukemia / lymphoma is a rare tumor that is characterized by the proliferation of immature natural killer (NK) cells; the World Health Organization (WHO) still classifies it as a provisional entity because of a lack of clear cut and reliable diagnostic criteria and lack of published information on expression of NK cell associated antigens
Essential features
- Characterized by the neoplastic proliferation of precursor NK cells
- Associated with a poor prognosis
- NK lymphoblastic leukemia / lymphoma share similar immunophenotype and molecular features with T cell acute lymphoblastic leukemia / lymphoma (T ALL); therefore, it is difficult to distinguish and remains a provisional entity
Terminology
- Blastic NK cell leukemia / lymphoma
- Precursor NK cell lymphoblastic leukemia / lymphoma (Indian J Hematol Blood Transfus 2014;30:283)
ICD coding
Epidemiology
- Detailed epidemiological data specific to NK cell lymphoblastic leukemia / lymphoma are limited
Sites
- Bone marrow
- Peripheral blood
- Can exhibit generalized lymphadenopathy (Case Rep Oncol 2017;10:588)
Pathophysiology
- Exact pathophysiology is not fully understood due to the rarity of disease
Etiology
- Not much known
Clinical features
- Fever
- Fatigue
- Bleeding
- Bone pain (Mod Pathol 2021;34:1358)
- Hepatosplenomegaly
- Lymphadenopathy
- Neurological symptoms
Diagnosis
- Peripheral blood: morphology and flow cytometry
- Bone marrow: morphology and immunophenotyping (flow cytometry and IHC)
- Imaging test(s) can help in evaluating the extent of disease but are not required to establish a diagnosis
Laboratory
- Pancytopenia
- Elevated lactate dehydrogenase (LDH)
- Hyperuricemia
- Hypofibrinogenemia
Radiology description
- Radiographs may show diffuse osteopenia and osteoporosis due to marrow replacement by leukemic cells
- MRI or CT scan may reveal diffuse bone marrow signal alterations
- Lymphadenopathy on imaging indicating lymphatic involvement by leukemic cells
- MRI may reveal soft tissue masses or hepatosplenomegaly (Case Rep Oncol 2017;10:588)
Prognostic factors
- Clinical stage at the time of diagnosis is a crucial prognostic factor
- Performance status of the patient reflecting their overall health is a prognostic factor; poor performance status may correlate with worse treatment tolerance and outcomes
Case reports
- 1 year old boy presented with a skin nodule (Int J Hematol 2010;91:525)
- 19 year old Saudi Arabian man presented with extensive cervical and axillary lymphadenopathy (Case Rep Oncol 2017;10:588)
- 23 year old man presented with history of intermittent fever, body ache, fatigue and weakness of 1 month duration (Indian J Hematol Blood Transfus 2014;30:283)
- 24 year old woman with relapsing brainstem manifestations and multiple focal brain lesions (Brain Pathol 2015;25:115)
Treatment
- Chemotherapy: there are specific induction and consolidation schemes for T ALL that are also used for the treatment of NK lymphoblastic leukemia
- Stem cell transplantation: allogeneic stem cell transplantation can be considered as a therapy (Cureus 2022;14:e22537)
- Supportive care
- Clinical trials
Frozen section description
- Diffuse infiltration of leukemic cells
- Large granular lymphocyte morphology (Int J Hematol 2003;78:18)
Microscopic (histologic) description
- Bone marrow shows extensive infiltration of immature mononuclear NK blasts
- NK blasts are intermediate to large in size, with variable cytoplasm and vesicular chromatin
- NK blasts display nuclear indentation and clearing
- Abnormal cell morphology or reduced cell counts (Int J Lab Hematol 2010;32:239)
Microscopic (histologic) images
Contributed by Muhammad Khurram Minhas, M.B.B.S.
NK lymphoblastic lymphoma involving bone marrow
CD56
TdT
CD3
CD20
Cytology description
- Large immature cells with high mitotic activity
- High N:C ratio
- Prominent nucleoli
- Scant cytoplasm
- Hyper chromatic nuclei
- Lymphoblastic appearance (J Pathol Transl Med 2023;57:196)
Cytology images
Contributed by Muhammad Khurram Minhas, M.B.B.S.
Lymphoblasts
with nuclear
indentations
and clefting
Peripheral smear description
- Pleomorphic
- Medium to large sized atypical cells
- Irregularly shaped nuclei
- Nuclear convolutions
- High N:C ratio
- Immature, blastic chromatin with multiple nucleoli (Indian J Hematol Blood Transfus 2022;38:434)
Peripheral smear images
Contributed by Muhammad Khurram Minhas, M.B.B.S.
NK lymphoblasts with nuclear indentations
Positive stains
- Neoplastic cells typically show
- CD2
- CD7
- CD56 (can be dim or bright) (Cytometry A 2013;83:702)
- CD3 (partial staining)
- TdT (50% of the cases)
- CD16
- Other NK markers: NKp46, NKG2D, KIR, HLA-DR (Front Immunol 2021;12:616853)
Negative stains
Flow cytometry description
Flow cytometry images
Images hosted on other servers:
Analysis of bone marrow
Electron microscopy description
- Blastic cytologic features
- Various abnormalities in cell structure
- Presence of granule-like structures (Cancer 1996;77:2592)
Electron microscopy images
Images hosted on other servers:
Lymphoma cells and granule-like structures
Molecular / cytogenetics description
- FISH analysis confirmed that the TP53 gene was deleted in 14% of the studied cells and was negative for ALL panel specific abnormalities
- Typically lacks the recurrent molecular abnormalities observed in B cell acute lymphoblastic leukemia / lymphoma (B ALL) and T ALL; however, in some cases, mutations in genes associated with the JAK::STAT pathway may be present, indicating the involvement of similar signaling pathways as seen in other NK / T cell malignancies (Hematol Oncol Clin North Am 2009;23:991)
Sample pathology report
- Bone marrow, right posterior iliac crest, core biopsy:
- NK lymphoblastic leukemia / lymphoma (see comment)
- Comment: Microscopic examination reveals a hypercellular bone marrow with infiltration of large atypical lymphoid cells. These cells exhibit high N:C ratio, irregular nuclear contours and prominent nucleoli. The cells are positive for CD56, CD3 (partial), CD7 and TdT immunohistochemical stains and negative for CD4, CD8, CD5, CD20, PAX5, CD79a, BCL6 and MPO, consistent with a diagnosis of NK lymphoblastic leukemia. No evidence of granulocytic or erythroid hyperplasia is noted.
Differential diagnosis
- Acute lymphoblastic leukemia (ALL), including T ALL and precursor B ALL:
- Coexpression of CD56 in ETP ALL or T ALL is identified in a percentage of these cases and the distinction with NK lymphoblastic leukemia / lymphoma is difficult
- Mutations in NOTCH1 and DNMT3A are shared between T ALL / ETP ALL and NK lymphoblastic leukemia / lymphoma; however, coexpression of myeloid markers and early age of presentation is more frequent in T ALL cases than in NK lymphoblastic leukemia / lymphoma (Haematologica 2009;94:224, Br J Haematol 2018;183:96, Mod Pathol 2021;34:1358)
- Pre-T ALL / pre-B ALL is much more common than NK lymphoblastic leukemia / lymphoma
- NK lymphoblastic lymphoma is characterized by the presence of CD56, a marker of NK cell differentiation (Mediterr J Hematol Infect Dis 2014;6:e2014073)
- Coexpression of CD56 in ETP ALL or T ALL is identified in a percentage of these cases and the distinction with NK lymphoblastic leukemia / lymphoma is difficult
- Acute myeloid leukemia with coexpression of CD56:
- Frequently involves the gums, skin and CNS, whereas NK lymphoblastic leukemia / lymphoma presents with general features of leukemia with lymph node involvement and involvement of extra medullary sites (Leuk Res 1999;23:615)
- Positive for myeloid markers such as CD13, CD33 and monocytic markers like CD14 and CD11b, whereas NK lymphoblastic lymphoma / leukemia is positive for NK markers like CD56
- Neuroblastoma:
- Usually presents as a mass in abdomen as compared to NK lymphoblastic lymphoma which is associated with lymphadenopathy (Front Immunol 2014;5:56)
- Positive for NSE, CD56, CD57, synaptophysin and chromogranin, whereas NK lymphoblastic lymphoma is positive for CD45, CD56 and TdT
- Ewing sarcoma:
- Originates from neuroectodermal cells and second most common sarcoma of bone in children, whereas NK lymphoblastic lymphoma is characterized by an immature proliferation of precursor lymphoid cells
- Positive for CD99, FLI1 and BCOR, whereas NK lymphoblastic lymphoma is positive for CD56 and TdT (Am J Clin Pathol 2001;115:11)
- Aggressive NK cell leukemia:
- Associated with EBV infection
- Can also express CD56 but lacks immaturity markers seen in NK lymphoblastic lymphoma (Mod Pathol 2017;30:1100)
- Has a worse prognosis as compared to NK lymphoblastic lymphoma
Board review style question #1
A 15 year old boy presented with extensive cervical and axillary lymphadenopathy. As a part of the workup, staging bone marrow aspirate and a trephine biopsy were performed. The positivity of which of the following stains raises the possibility of NK lymphoblastic lymphoma?
- CD30
- CD56
- CD79a
- MPO
Board review style answer #1
B. CD56. Positivity of CD56, either bright or dim, is associated with NK lymphoblastic lymphoma. Answer A is incorrect because CD30 is usually negative in NK lymphoblastic lymphoma. Answer D is incorrect because MPO is a myeloid marker. Answer C is incorrect because CD79a is a B cell marker, usually negative in NK lymphoblastic lymphoma.
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Board review style question #2
A 10 year old girl presented with generalized lymphadenopathy. Bone marrow aspirate has been done as a part of diagnostic workup, as shown in the figure above. Which of the following combinations is suggestive of the diagnosis of NK lymphoblastic lymphoma?
- CD56-, TdT+, CD20+
- CD56-, TdT-, CD3+
- CD56+, TdT+, HLA-DR+
- CD56-, TdT-, MPO+
Board review style answer #2
C. CD56+, TdT+, HLA-DR+. This immunohistochemical panel is suggestive for the diagnosis of NK lymphoblastic lymphoma. Answers A, B and D are incorrect because positivity of CD20, along with negativity of CD56 and TdT, rules out NK lymphoblastic leukemia / lymphoma.
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