Hematology & immune disorders

Peripheral blood smear morphology

Neoplastic

Neoplastic WBC


Resident / Fellow Advisory Board: Frido Bruehl, M.D.
Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.
Jingwei Li, M.D., Ph.D.
Olga Pozdnyakova, M.D., Ph.D.

Last author update: 28 March 2023
Last staff update: 28 March 2023

Copyright: 2020-2024, PathologyOutlines.com, Inc.

PubMed Search: Peripheral blood smear neoplastic white blood cells

Jingwei Li, M.D., Ph.D.
Olga Pozdnyakova, M.D., Ph.D.
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Cite this page: Li J, Pozdnyakova O. Neoplastic WBC. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/hematologyneoplasticWBC.html. Accessed March 29th, 2024.
Definition / general
  • Neoplastic hematolymphoid cells circulating in the peripheral blood
Essential features
  • Morphologic identification of neoplastic hematolymphoid cells on peripheral blood smears
Small lymphocytes
  • Chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma
  • Mantle cell lymphoma
    • Mature B cell neoplasm
    • Monomorphic small - intermediate sized lymphocytes
    • Irregular nuclear contours (indented, folded or cleaved)
    • Moderately clumped chromatin
    • Scant amount of pale blue cytoplasm
    • Morphologically indistinguishable from CLL cells
    • Prolymphocytic-like morphology is common during leukemic phase
    • CD5+, CD19+, CD20+, cyclin D1+, SOX11+, CD200-, CD23-, FMC7+
    • Associated with t(11;14)(q13;q32) / CCND1::IGH translocation (95%)
    • See figure 2
  • Follicular lymphoma
    • Mature B cell neoplasm
    • Irregular nuclear contour with frequent indentations, folding, angulations and cleaved nuclei
    • Moderately clumped chromatin
    • Occasional small nucleoli
    • Scant amount of basophilic cytoplasm
    • CD19+, CD20+, CD79a+, CD10+, FMC7+, CD5-, CD23-
    • Genetically characterized by t(14;18)(q32;q21), a translocation resulting in fusion of the IGH and BCL2 genes
    • See figure 3
  • Hairy cell leukemia
    • Mature B cell neoplasm
    • Monomorphic small to intermediate sized lymphocytes
    • Smooth chromatin with inconspicuous nucleoli
    • Moderate amount of pale blue cytoplasm classically seen with fine, hair-like projections
    • CD19+, CD20+ (bright), TRAP+, CD11c+, CD25+, CD103+, CD200+, annexin A1+ (most specific), CD5-, CD10- (80 - 90%), CD23-
    • Splenic B cell lymphoma / leukemia with prominent nucleoli (WHO 5th edition) and hairy cell leukemia variant (ICC 2022), a chronic lymphoproliferative disorder whose morphologic characters resemble hairy cell leukemia; neoplastic cells have prominent nucleoli and are negative for HCL markers (CD25, annexin A1 and TRAP)
    • BRAF V600E mutation is found in most (> 90%) classic hairy cell leukemia cases
    • Associated with pancytopenia and splenomegaly
    • See figure 4
  • Reference: Leuk Lymphoma 2015;56:2000, Leukemia 2022;36:1720, Blood 2022;140:1229
Intermediate sized cells
  • T cell prolymphocytic leukemia
    • Mature T cell neoplasm
    • Small to intermediate sized lymphocytes
    • Round to irregular nuclei
    • Distinct nucleoli
    • Basophilic cytoplasm with cytoplasmic blebs
    • CD2+, CD3+, CD5+, CD7+, TdT-, CD4+/-, CD8+/-, TCL1+
    • Most cases are found with inv(14)(q11q32) and TCL1 gene rearrangement detectable by FISH, while deletion or mutations in ATM have also been observed
    • Aggressive disease
    • See figure 5
  • Sézary syndrome
    • Mature T cell neoplasm
    • Medium sized to larger lymphocytes
    • Irregular nuclear contour, often described as cerebriform pattern
    • Condensed chromatin
    • Inconspicuous nucleoli
    • Abundant basophilic cytoplasm
    • CD2+, CD3+, CD5+, TCRαβ+, CLA+, usually CD4+, CD8-, CD7- and CD26-
    • T cell receptor gene rearrangements are present; recurrent balanced chromosomal translocations have not been identified
    • Aggressive form of mycosis fungoides
    • See figure 6
  • Adult T cell leukemia / lymphoma
    • Mature T cell neoplasm, caused by human retrovirus HTLV1
    • Several morphological variants have been identified: small, medium, large cell and anaplastic variants
    • Convoluted and polylobated nuclei, often described as flower cells
    • Condensed chromatin
    • Small or inconspicuous nucleoli
    • Moderate amount of basophilic cytoplasm
    • CD2+, CD3+, CD5+, CD4+/- and CD8-/+, CD25+, CD7-
    • Clonal T cell receptor gene rearrangement
    • Associated with hypercalcemia
    • See figure 7
  • Reference: Am J Hematol 2019;94:1027
Plasma cells
  • Multiple myeloma - plasma cell leukemia (primary or secondary)
    • Plasma cell neoplasm
    • Medium sized neoplastic cells
    • Eccentric round nucleus
    • Coarse chromatin, often seen in a clockface pattern
    • Abundant amount of pale to basophilic cytoplasm with perinuclear clearing
    • According to the 2021 International Myeloma Working Group recommendation, primary plasma cell leukemia is defined as "5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma" (Blood Cancer J 2021;11:192)
    • CD38+, CD138+, CD56+ (80%), CD45-, CD19- (95%)
    • Immunoglobulin heavy and light chain gene rearrangement
    • Associated with Rouleaux formation of RBCs and monoclonal gammopathy
    • See figure 8
  • Reference: Blood Rev 2011;25:107
Large lymphocytes
  • Diffuse large B cell lymphoma (example: CLL status post-Richter transformation)
    • Mature B cell neoplasm
    • Large sized neoplastic cells
    • Irregular nuclei
    • Dispersed chromatin
    • Inconspicuous to prominent nucleoli
    • Abundant amount of cytoplasm
    • CD19+, CD20+, CD79a+, CD10+ (30 - 60%), BCL6+ (60 - 90%), MUM1+ (35 - 65%)
    • See figure 9
  • T cell large granular lymphocytic leukemia
    • Mature cytotoxic T cell neoplasm
    • Large sized lymphocytes
    • Irregular nuclear contour
    • Coarse chromatin
    • Indistinct nucleoli
    • Abundant clear cytoplasm with azurophilic granules; cytologically indistinguishable from natural killer cells (CD3-)
    • CD2+, CD3+, CD4-, CD8+, CD57+, CD56 variable, CD16+ (variable), loss of CD5 or CD7 is common
    • Clonal T cell receptor gene rearrangement
    • Indolent disease; associated with cytopenia, particularly neutropenia, and rheumatoid arthritis
    • See figure 10
  • Reference: Autops Case Rep 2016;6:41
Blasts
  • Myeloid: acute myeloid leukemia (example: AML with inv(16))
    • Immature myeloid neoplasm
    • Medium to large sized myeloblasts
    • Round to irregular or folded nuclei
    • Dispersed chromatin
    • Distinct nucleoli
    • Moderately abundant cytoplasm
    • Auer rods present in some cases, abundant in acute promyelocytic leukemia
    • Typically, CD34+ and CD117+, may exhibit granulocytic lineage (positive for CD13, CD33, CD15, CD65 and MPO) or monocytic lineage (positive for CD14, CD4, CD11c, CD64, CD36 and lysozyme)
    • See figure 11 showing an AML with inv(16)(p13.1;q22)
  • Lymphoid: B lymphoblastic leukemia / lymphoma (example: B ALL with KMT2A rearrangement)
    • Immature lymphoid neoplasm
    • Intermediate sized lymphoblasts
    • Round to irregular nuclei
    • Dispersed chromatin
    • Distinct nucleoli
    • Scant amount of basophilic cytoplasm
    • Typically, CD19+, CD22+, CD79a+, CD10+, CD45 (moderate intensity) and variable expression of TdT and CD34
    • Recurrent genetic abnormalities include t(9;22)(q34.1;q11.2) BCR::ABL1, t(v;11q23.3) KMT2A rearranged, t(12;21)(p13.2;q22.1) ETV::RUNX1, t(5;14)(q31.1;q32.1) IGH::IL3 or t(1;19)(q23;p13.3) TCF3::PBX1
    • See figure 12
  • Blast equivalents (promonocytes) (example: acute myelomonocytic leukemia)
    • Immature monocytic precursors that are counted towards the total blast count in monocytic and myelomonocytic neoplasms
    • Irregular and convoluted nuclear contours with fine folds
    • Fine chromatin
    • Distinct nucleoli
    • Moderate amount of gray to pale blue cytoplasm with occasional small vacuoles
    • Immature monocytic precursor cells are usually CD14+/-, CD64+, CD15+, CD11b+, CD11c+, CD4+, CD36+, CD68+, CD163+ and lysozyme+
    • Nonspecific cytogenetic abnormalities
    • See figure 13
    • Reference: StatPearls: Leukemia [Accessed 11 January 2023]
Diagrams / tables

Table 1: B cell lymphoproliferative disorders and markers
CD45RA CD19 CD20 CD79a CD5 CD10 CD23 Cyclin D1 SOX11 LEF1 CD200 CD103 CD11c CD25
Follicular lymphoma + + + + - + - - -/+ Unknown - - -/+ -/+
Chronic lymphocytic leukemia / small lymphocytic lymphoma + + + + + - + - - +/- + - -/+ -/+
Diffuse large B cell lymphoma + + + + - +/- - - -/+ -/+ +/- -/+ -/+ -/+
Mantle cell lymphoma + + + + + - - + + - - - - -/+
Marginal zone lymphoma + + + + - - - - -/+ - - - -/+ -
Lymphoplasmacytic lymphoma + + + + - - - - Unknown - +/- - +/- +/-
Hairy cell leukemia + + + + - - - + +/- - + +/- + +
+: positive; -: negative; +/-: majority positive; -/+: majority negative


Table 2: T cell lymphoproliferative disorders and markers
CD4 / CD8 Pan-T cell markers (CD2, CD3, CD5, CD7) CD30 T cell receptor
T cell prolymphocytic leukemia CD4+ / CD8- > CD4+ / CD8+ All expressed - Alpha / beta
Sézary syndrome CD4 CD7 loss +/- Alpha / beta
Adult T cell leukemia / lymphoma CD4 CD7 loss -/+ Alpha / beta
T cell large granular lymphocytic / leukemia CD8 CD2, CD5 and CD7 variably loss - Alpha / beta
+: positive; -: negative; +/-: majority positive; -/+: majority negative
Peripheral smear images

Contributed by Jingwei Li, M.D., Ph.D., Olga Pozdnyakova, M.D., Ph.D. and Karry Charest, MT (ASCP)
Clumped chromatin, smudge cells

Clumped chromatin, smudge cells

Moderately clumped chromatin

Moderately clumped chromatin

Cleaved nuclei

Cleaved nuclei

Fine, hair-like cytoplasmic projections

Fine, hair-like cytoplasmic projections

Round to irregular nuclei

Round to irregular nuclei


Irregular, cerebriform nuclear contour

Irregular, cerebriform nuclear contour

Polylobed nuclei, flower cells

Polylobed nuclei, flower cells

Eccentric, round nuclei

Eccentric, round nuclei

Large sized neoplastic cells

Large sized neoplastic cells

Abundant cytoplasm, azurophilic granules

Abundant cytoplasm, azurophilic granules


Dispersed chromatin, distinct nucleoli Dispersed chromatin, distinct nucleoli

Dispersed chromatin, distinct nucleoli

Irregular, convoluted nuclear contours

Irregular, convoluted nuclear contours

Board review style question #1
Which of the following lymphoproliferative disorders is associated with human retrovirus HTLV1?

  1. Adult T cell leukemia / lymphoma
  2. Hairy cell leukemia
  3. Sézary syndrome
  4. T cell large granular lymphocytic leukemia
  5. T cell prolymphocytic leukemia
Board review style answer #1
A. Adult T cell leukemia / lymphoma

Comment Here

Reference: Neoplastic WBC
Board review style question #2

Which of the following lymphoproliferative disorders is associated with BRAF V600E mutation?

  1. Chronic lymphocytic leukemia / small lymphocytic lymphoma
  2. Classic hairy cell leukemia
  3. Mantle cell lymphoma
  4. Multiple myeloma
  5. Sézary syndrome
Board review style answer #2
B. Classic hairy cell leukemia

Comment Here

Reference: Neoplastic WBC
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