Haematology for Dental Students - WBC Disorders

“Success is going from failure to failure without loss of enthusiasm” !

– Winston Churchill

Pathology ofWBC disorders

Dr. Shashidhar Venkatesh MurthyA/Prof. & Head of Pathology

2013: MB2-HRM-Week 7

Diseases of WBC: Learning Objectives:

Normal WBC. Reactive changes: (Philia.. / Penia..)

• Neutropenia, Agranulocytosis, Leukemoid reaction.• Lymphadenitis, Lymphadenopathy.

Neoplastic / Cancers: • Leukemia – Acute, Chronic, Myeloid & Lymphoid.• Lymphomas – Hodgkins & Non Hodgkins.• Precancers: MPD, MDS.

Books/Ref:

TOP 5 WBC disorders.1. Reactive changes.2. Leukemia.3. Lymphoma.4. MPD.5. MDS.

Less More

Small minds discuss people

Average minds discuss events

Great minds discuss solution

Genius silently acts!

5

Normal Blood Cells:

Neutrophil

Basophil

Eosinophil

Band

Lymphocyte

Monocyte

Plt

Non granular, Mononuclears

Specific Immunity

Granulocytes, Polymorphs

Non-Specific Immunity

Normal WBC Production:

Left Shift

Whatever you think, that you will be. If you think yourselves weak,

weak you will be. If you think yourselves strong,

strong you will be!

-- Swami Vivekananda

Leukocytosis: Neutrophilia Increased granulocytes:

• Trauma, Acute Infections, inflammation, Bacterial*

When severe with immature forms – Leukemoid reaction. Clinical features:

• Fever, Fatigue, Inflammation.

Lymphocytosis: Infectious Mononucleosis

Increased Lymphocytes: (Activated)• Chronic Inf., Viral, fungal, TB etc.

Large lymphocytes, more cytoplasm. Irregular, indented by RBC – also known as atypical lymphocyte or virocyte

Clinical features: fever, lymphadenopathy.

Leukopenia: Neutropenia Reduction in granulocytes:

• Decreased Production – Marrow aplasia, drugs, • Increased destruction – drugs, immune, • Congenital: CGD, Idiopathic, cyclical, Benign ethnic (common)

When severe – Agranulocytosis (drugs, immune)

Clinical features:• Infections, oral ulcers with white thick pus (pseudo membrane) of

bacteria or fungus (candida common)

WBC Absolute counts in disease:Penia PhiliaNeutro

Penia PhiliaEosino

Penia cytosisMono

Penia cytosisLympho

WBC counts:

When your thinking is brilliant, you will be

brilliant, but if your thinking is not brilliant

you will not be brilliant, no matter how

brilliant you may think you are….! -- Christian D. Larson

Fake it until you make it…! -- Mohd. Ali. Boxer.

Lymphadenitis: Acute (painful) or Chronic

(painless) Infections, Immune & Cancers. Increased, large follicles with

pale germinal centre & mantle zones (B cell proliferation* & apoptosis*)

Lymphadenitis: Enlarged reactive lymphnodes due to stimulation (inflammation). (Painful)

Lymphadenopathy – any enlargement, but commonly used for Cancer spread. (Painless)

Reactive lymphadenitis

Dark zone

Light zone

Mantle zone

Macrophage

Tingible bodyMacrophage

B Lymphocyte proliferation* & apoptosis*

“When you see a good person, learn from her/him. When you see someone not so good, reflect on your own weak points.” 

― Confucius.

Hemato-oncology: Blood Cancer - Summary

Cancer of immature Blast cells. (Bone marrow common)

Leukemia: • ‘White’ ‘blood’ – excess WBC, Starts in bone marrow extends to

blood & hemopoietic Organs - Liver, Spleen & lymphnodes* • Two Major types: Myeloid & Lymphoid. • Two presentation: Acute / Chronic. (AML, ALL, CML CLL) • Many subtypes* – different mutations personalized medicine*(MB3)

Lymphoma: • Solid tumour of lymphoid tissue – where ever lymphoid tissue.• Hodgkins & Non-Hodgkins lymphoma. B cell type common.• Many subtypes – clinically Low, Intermediate & High grade.

Premalignant Disorders:• MPD Myelo-Proliferative Dis: Excess proliferation, more abnormal cells.• MDS Myelo-Dysplastic Syn.: Dysplastic (abnormal cells) pancytopenia.

Leukemia: Clinical Features Cancer of Bone marrow Blasts – Excess WBC. Decreased Haemopoiesis:

• Erythropoiesis – Anemia - RBC• Leukopoiesis – Infections - WBC• Thrombopoiesis – Bleeding. PLT

Bone marrow expansion/destruction:• Bone pains.

Extraneous hemopoiesis / spread:• Splenomegaly• Hepatomegaly• Lymphadenopathy (more in lymphatic malignancy)

Leukemia Clinical features:

Bleeding - Petechiae

Lymphadenopathy

HepatosplenomegalyInfections - Candidiasis

Leukemia Classification Acute Leukemias: weeks to months.

• Acute Myeloid Leukemia – AML - Adults • Many Subtypes: M0, M1 to M7

• Acute Lymphoid Leukemia – ALL - Children • Many Subtypes: L1, L2 & L3

Chronic Leukemias: Years, late age.• Chronic Myeloid Leukemia- CML- Adults

• Chronic Lymphoid Leukemia - CLL –Old age.

ALL children - AML adults

Leukemia Morphology:Normal Acute Leukemia AML/ALL

CML: Chronic Myeloid LeukemiaCLL: Chronic Lymphatic Leukemia

Leukemia Case:

JK 12y, Boy Presents to ED: “Very Sick, fever, back pain, nothing helping it”.

History: • Feels unwell? - Very• Fever? Yes, intermittent• Easy bruising -Yes,

Examination:• Slim, unwell, pale, Multiple Bruises• Liver & Spleen enlarged – mild.• Lymph nodes enlarged neck & axilla.

Any fool can know. The point is to understand !

-- Albert Einstein

Without Pathology, Medicine is quackery…!

Lymphoma Definition: Solid cancer of lymphoid tissue Clinical: Painless, immobile, Lymphadenopathy,

weight loss, Fever. Two Major Types: & many subtypes. Hodgkins lymphoma (HL) – Reed-Sternberg cells.

• B cell only. Types: Lymph. rich Mixed Ly. Poor. Non-Hodgkins lymphoma (NHL) – no RS cells.

• B cell, T cell & Histiocytic lymphoma.

Hodgkins Non Hodgkins

NHL: Diffuse Small Cell

NHL: Follicular Mixed Small & Large CellHL: Nodular Sclerosis (common)

Only RS cell Malignant All cells Malignant

"Creativity is inventing, experimenting, growing, taking risks, breaking rules, making

mistakes, and having fun. -- Mary Lou Cook

Burkitt’s lymphoma: large B cell NHL Endemic in Africa Epstein Barr Virus (EBV) B Cell Lymphoma. Dark large B lymphocytes

(malignant) with plenty of pale macrophages. (Starry sky pattern).

Multiple Myeloma: Malignancy of Plasma cells (Mature B

lymph, Ab) - Old age, males. Marrow, LN, Blood. Multiple, punched out Lytic bone

lesions (Osteolysis) Hyper gammaglobulinemia Monoclonal antibody peak – serum

protein electrophoresis. Immunodeficiency infections.

“The future belongs to those who believe in the beauty of their dreams.”

–Eleanor Roosevelt

Myelo Proliferative Disorders.Myelo Dysplastic Syndromes.

(Pre-canceraous stage of blood cancers)

MPD MDS

Marrow Proliferation with maturation.

Increased abnormal cells in blood – Leukocytosis.

4 major types (mixed types common). • Polycythemia Vera (RBC)• Chronic Myeloid Leuk. (WBC)• Essential Thrombocythemia

(PLT)• Myelofibrosis (Fibrosis)

Old age, Neoplastic proliferation of stem cells. Reduced normal marrow (RBC, WBC & PLT - anemia, infections & bleeding. Liver & Spleen enlarged.Usually transform to Acute leukemia at the end.

Marrow Proliferation with no maturation.

Decreased abnormal cells in blood. – Leukopenia.

4 major types.• RA (Refractory Anemia)• RARS• RAEB• RAEB in transformation.

Polycythemia Rubra Vera (PV)

Hypercellular Marrow, Red skin & Hepatosplenomegaly

Essential thrombocythemia

Plenty of

Platelets in blood

But clinical bleeding (abnormal platelets)

The goal of mankind is knowledge, which is inherent in man. No knowledge comes from outside: it is all inside. What man

'learns' is really what he “discovers” by taking the cover off his own soul.

- - Swami Vivekananda

‘Education’… from Eduse (latin) to bring out..!‘Doctor’ … from Dokere’ (latin) to teach…!

Summary: Reactive Leukocytosis:

• Neutrophilia, Eosinophilia, Lymphocytosis. Reactive Leukopenia:

• Neutropenia, lymphopenia, pancytopenia. Leukemia: – Blood Cancer (of Blasts in marrow)

• AML / ALL, CML / CLL Lymphoma: – solid Tumor of lymphoid tissue.

• Hodgkins & Non- Hodgkins Precancerous conditions:

• MPS (Leukocytosis) & MDS (leukopenia):

I am here for you….

Discussion Board: Questions & Answer others Q.Email: venkatesh.shashidhar@jcu.edu.au Need personal guidance? Email me for an appointment.

Office Tel: 4781 4566Office location – DB39-136 (Townsville)

The only person who never makes

a mistake is a person who

never does anything…!

- Theodore Roosevelt

38

3 R’s of success:

Respect for self, Respect for others &Responsibility for your actions.

Aspire to become good, not great.... Greatness is like a passing cloud, temporary. - Sai Baba - Divine Discourse, July 16, 2001.

Normal Blood Cells:

Normal Blood Cells: