Leukocytosis - Some Learning Points

Koh Liang Piu

Department of Hematology-Oncology

National University Cancer Institute

National University Health System

Objectives of this talk:

1. To provide some useful practical diagnostic algorithms when confronted with abnormal FBC.

2. To help the non-haematologist to decide when you can circumvent yourself and when haematology consult is necessary.

Simple Approach to Abnormal FBC results

High White Blood Counts

Causes:

1. Central:

• Myeloproliferative/lymphoproliferative disease

• Leukaemia

2. Peripheral:

• ‘Stress’’ ,

• Infection, inflammation,

• Malignancy, splenectomy

Simple Approach to Abnormal FBC results High White Blood Counts

Important Clues to look for

1. History

2. Physical Exam: Liver/Spleen, , Lymphadenopathy etc

3. Peripheral Blood Film (Most Important)

4. WBC: Differentials

5. Biochemisry: ESR/CRP, LDH

6. PT/PTT/DIC screen.

7. Septic/ Malignancy screen

Important Questions for Leucocytosis :

• Is this Reactive ?

• Is this Neoplastic (Clonal) ?

• Which subset of WBC is elevated ?

Reactive Neoplastic

Neutrophil ? ++ +

Lymphocytes ? ++ +

Monocytes ? ++ +

Eosinophil ? ++ +

Basophil ? +

Blast ? - +++

Important Questions for Leucocytosis :

• Is this affecting the other 2 cell lines

(lineages), i.e. RBC/Hb and platelet count ?

- If yes, this is probably neoplastic

(although not absolute)

42 Male Abnormal FBC during health screen

42 Male Abnormal FBC during health screen

1. Take good history 2. Look for

Hepatosplenomegaly 3. Look at PBF

MPD ??

PBF of a patient with severe

postoperative sepsis due to a Gram-

negative organism.

WBC 92 x 109/L

- Neutrophil count of 74 × 109/l (80%)

- Monocyte count of 16 × 109/l (17%)

Hb 12g/dL

Platelet 100 x 109/L

Leukemoid Reaction

PBF shows a band form, a

macropolycyte and monocytes with

increased cytoplasmic basophilia.

Neutrophilia • Reactive (Leukemoid Reaction)

• Infection • Inflammation • Malignancy • Drugs

- Steroids, GCSF, Psychiatric Medications

• Myeloid Malignancy • CML • MPD • Chronic Neutrophilic Leukemia (rare)

band forms showing vacuolation and marked toxic granulation

Reactive Neutrophilia

45 / Chinese/ female Presenting Complaints: -Vague epigastric discomfort x few months. Clinical Examinations: - Massive splenomegaly

45 / Chinese/ female Presenting Complaints: -Vague epigastric discomfort x few months. Clinical Examinations: - Massive splenomegaly

45 / Chinese/ female Presenting Complaints: -Vague epigastric discomfort x few months. Clinical Examinations: - Massive splenomegaly

Chronic Myeloid Leukaemia

Peripheral Blood Film

Marrow Aspirate

Normal Hematopoiesis

CML

In CML myelocytes and neutrophils being the most frequent cells.

FBC of a patient with Acute Leukemia

AML CML

Peripheral Blood Film

Differentiating acute versus chronic myeloid leukemia based on FBC

AML • Leucocytosis.

• Predominant population of blasts.

• Anemia and thrombocytopenia more sig.

• Eosinophilia/ basophilia unusual.

CML • Leukocytosis.

• Mixture of blasts amd immature cells.

• Anemia usually mild. Plts may be mildly low, normal or even high.

• Eosinophilia and basophilia common.

A 56 year old man with epistaxis. Clinically: Small cervical Lymphadenopathy Massive splenomegaly

Lymphocytosis

PBF and Flow Cytometry

Reactive causes present (infection, postsplenectomy)

Clonal disorder present

No Clonal disorder (Reactive Lymphocytosis)

Exclude Infectious etiologies • Viral (HIV, EBV, Hepatitis). • Other Infections (TB,

Toxoplasmosis)

CLL

Hairy Cell Leukemia Mantle Cell Lymphoma Follicular Lymphoma

Cell Surface Markers of Lymphocytes in B/T LPD

34 / Male Presenting Complaints: -LHC fullness for many months, a/w LOW Clinical Examination: - Massive splenomegaly

34 / Male Presenting Complaints: -LHC fullness for many months, a/w LOW Clinical Examination: - Massive splenomegaly

Monocytosis

• “Reactive” • Chronic Infectious/ Inflammatory/

Granulomatous • Metastatic Cancer • Lymphoma • Follow AMI

• “Relative” • Recovery from Chemotherapy or drug-

induced neutropenia

• Neoplastic • Marker of MPD (eg: Chronic

Myelomonocytic Leukemia, CMMoL)

Eosinophilia

• “Primary” • Clonal • Hypereosinophilic Syndrome (HES) •

• “Secondary” • Parasite • Drugs • Allergic conditions • Vasculitides • Lymphoma (T-NHL, Hodgkin) • Metastatic Cancer

Eosinophilia

1. Obtaining a good patient history 2. Stool test for ova and parasites In patients with “primary eosinophilia” - Bone marrow biopsy recommended - distinguish between clonal eosinophilia and HES In patients with suspected HES - Cytogenetic studies, - FISH for FIP1L1-PDGFRA mutation, - Immunohistochemical stains for tryptase - Mast cell immunophenotyping.

Basophilia

• Rare

• Seen in CML and Chronic Basophilic

Leukemia (extremely rare)

• Refer Hematology • Bone Marrow Biopsy

59 / Chinese/ Male Presenting Complaints: -LHC fullness for many months, a/w LOW Clinical Examination: - Massive splenomegaly

Tear Drop Cells

Leukoerythroblastic Reaction

Malignancy Metastasis Myelofibrosis Marble Bone Disease (metabolic disease) Mycobacterial Tuberculosis (infection)

Bone Marrow Infiltration (the ‘M’s)

Peripheral Stress/ Destruction/ Loss

Infection Hemolysis Hemorrhage

Conclusions

Simple Approach to Leukocytosis High White Blood Cells: Which subtype

Important Clues to look for

1. Obtain good history

2. Physical Exam: Liver/Spleen, , Lymphadenopathy etc

3. Peripheral Blood Film (Most Important)

4. WBC: Differentials

5. Biochemisry: ESR/CRP, LDH

6. PT/PTT/DIC screen.

7. Septic/ Malignancy screen

Any doubt, ask a haematologist

Thank you for your attention

Email : liang_piu_koh@nuhs.edu.sg