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Haematological Neoplasia:

Leukemias - Acute & Chronic Lymphomas - Hodgkins & Non-Hodgkins

(T cell, B cell, histiocytic & others) Premalignant Conditions: Myeloproliferative syndromes (MPS) Myelodysplastic syndromes (MDS)

Lymphomas

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Introduction:

Neoplastic lymphoid proliferation Two types – Hodgkins & Non-Hodgkins. Fever, lymphadenopathy, Immunodeficiency / autoimmune syndrome Viral, genetic, unknown etiology. Lack of programmed cell death - Apoptosis

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Lymphoma’sWhere They Begin

Lymphomas are a cancer of the lymphatic system

– Lymphatic vessels– Lymph nodes

(underarms, groin, neck, spleen, tonsils and bone marrow)

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Lymphoma’sWhere They Begin

The Lymphatic system is our bodies main fight against infection

Lymphocytes (B-cell and T-cell)– Carried through our lymphatic system and help our

bodies fight infection– Lymphocytes are carried through the lymph vessels

as well as the blood stream, so cancer can start in nodes and spread anywhere throughout the body.

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Lymphatic System

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Lymphoma Row of enlarged lymph nodes

Lymphoma - Gross

Lymphoma Intestine

Lymphoma Intestine

Mediastinal Lymphnodes-NHL

Hodgkins Lymphoma (HL)

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Hodgkin’s Disease

Is a malignant lymphoma characterized by the presence of atypical, multinucleated giant cell (Reed-Sternberg cell)

The disease is slightly more common in men Most patients have asymptomatic lymphadenopathy

at the time of diagnosis– The initial site of nodal involvement is:

Cervical (65-80%) Axillary (10-15%) Inguinal (6-12%)

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Reed-Sternberg Cell

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Hodgkins lymphoma

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Hodgkins lymphoma cells

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Hodgkins Lymphoma

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Causes/Risk Factors

The exact cause of Hodgkin’s disease is unknown. Also, a virus called Epstein-Barr may be involved

with an increased risk of Hodgkin’s. Also, Agent Orange, used during the Vietnam War is

linked with the development of Hodgkin’s. Siblings of a Hodgkin’s victim are more at risk for

developing the disease. It is more common for men to have the disease. Hodgkin’s occurs most often in those between 15

and 34 or over the age of 55.

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Classification of Hodgkin’s Disease

Treatment depends on – The anatomic distribution of the disease and the

presence or absence of specific symptoms– The stage of the disease– The histopathologic subtype

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Classification of Hodgkin’s Disease

The Rye classification– Based on four histopathologic subtypes

Lymphocytes predominanceNodular sclerosisMixed cellularityLymphocytes depletion

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Classification of Hodgkin’s Disease

Histopathologic diagnosis– Is made by lymph node biopsy– Nodes from the lower cervical or axillary areas provide the

best tissue for evaluation

Ann Arbor staging classification– A classification based on anatomic distribution of the

disease Stage I disease – Stage IV disease

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Splenic Involvement

The probability of splenic involvement increases with increasing spleen size

The absence of splenomegaly does not exclude splenic involvement

Upon gross examination of the spleen a grayish white nodule ranging from several millimeters to several centimeters is apparent with Hodgkin’s disease

Liver involvement with Hodgkin’s disease rarely occurs in the absence of splenic disease

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Classifications

Classic Hodgkin’s divisions– Nodular Sclerosing– Mixed Cellularity– Lymphocyte rich– Lymphocyte depleted

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Nodular Sclerosing

>60% of cases Connective tissue RS cells Lacunar cells other cells

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Mixed Cellularity

15 – 30% cases Mixed cells

– Lymphocytes– Histocytes– Eosinophils– Plasma cells– RS cells– Variants– +Necrosis

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Lymphocyte rich

<5% cases Large numbers of Lymphocytes May suppress other cells RS cells Not to be confused with LP Hodgkin’s

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Lymphocyte depleted

<1% cases Lymphocytes rare RS cells predominate

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Symptoms & Presentation

Swollen, painful lymph nodes Fatigue, etc. Generalized iching Appetite, weight loss Neck %/or back pain Hair loss Night sweats

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Hodgkin’s Disease

Symptoms such as fever, night sweats, weight loss and pruritus are indicative of widespread involvement and are unfavorable prognostic signs

– A typical fever pattern is a high-temperature alternating for a few days with an afebrile period

Many patients have a mild normochromic, normocytic anemia

– 1/3 have a leukocytosis due to a neutrophil increase– Eosinophilia is frequently present

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Prognosis

Staging Nodular or Diffuse Anatomical Staging

– Stage I- one region– Stage II- two regions, same side diaphragm– Stage III- two regions, both sides of diaph– Stage IV- spread outside of lymph system

I & II- >10 years III & IV - < 6 years

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Current Treatment of Hodgkin’s Disease

Integrates radiation therapy and combination chemotherapy to achieve the maximum potential for cure

Untreated Hodgkin’s has a five-year survival rate of 5%

The Stanford experience-patients at all stages have survival rate of 86%

– Patients in stage IV have a generally poor prognosis

Non-Hodgkins Lymphoma (NHL)

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NON- Hodgkin’s Lymphoma

Absence of Reed-Sternberg Cells May result from damage to DNA that controls

growth of cells in immune system Increased incidence in immunodeficiency

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Associated with Non-H lymphoma

SLE Celiac Disease AIDS Organ transplant patients Rheumatoid Arthritis

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Causes and Risk Factors

The Exact causes are still unknown– Higher risk for individuals who:

Exposed to chemicals such as pesticides or solvents Infected w/ Epstein-Barr Virus Family history of NHL (although no hereditary pattern

has been established) Infected w/ Human Immunodeficiency Virus (HIV)

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Classifications

Based on cell type and location(s) Non symptomatic -> Aggressive

– Worst prognosis < 1 year

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Non-Hodgkin’s Lymphoma (NHL)

A diverse group of primary malignancies of lymphoreticular tissue

The clinical course and natural history is more variable than Hodgkin’s disease

The pattern of spread is irregular and more patients have leukemic features

Current histologic classifications utilize electron microscopic morphology, histochemical studies and selected cell surface antigens.

– For our purposes NHL is classified according to nodular (favorable) and diffuse (unfavorable) types

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NHL

In contrast to Hodgkin’s disease, about two-thirds of patients initially have asymptomatic lymphadenopathy

In addition to peripheral and mediastinal lymphadenopathy NHL is commonly found initially as an abdominal mass or as hepatic or splenic enlargement

Fever, weight loss and night sweats are frequently present

The median age at diagnosis is 50 No sex preference is noted

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NHL

Patients below 35 or over 65 are more likely to have diffuse histology

As with Hodgkin’s, chemotherapy and / or radiation therapy are the primary forms of treatment

Staging laparotomy is seldom required Significant therapeutic benefit can be achieved by

splenectomy in 80-90 % of patients with advanced lymphomas (including Hodgkin’s disease)

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Classification

Usually classified by how the cells look under a microscope and how quickly they grow and spread– Aggressive lymphomas (high-grade lymphomas)

– Indolent Lymphomas (low-grade lymphomas)

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Classification of Malignant Lymphomas

Low Grade: small lymphoid cells, nodular growth

Intermediate Grade: large cells, follicular and diffuse patterns

High Grade: immunoblastic, lymphoblastic, Burkitt’s disease

T-cell lymphomas: peripheral, cutaneous

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Non-Hodgkin’s LymphomaStaging

Stage is the term used to describe the extent of tumor that has spread through the body( I and II are localized where as III and IV are advanced.

Each stage is then divided into categories A, B, and E

– A: No systemic symptoms– B: Systemic Symptoms such as fever, night sweats and

weight loss– E: Spreading of disease from lymph node to another organ

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Staging

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Non-Hodgkin’s Lymphoma

Two main types of Non-Hodgkin’s Lymphoma:

B-Cell and T-Cell Lymphomas– B-Cell lymphomas (80%)– T-Cell lymphomas (15%)

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NHL – Classification:

According to cell type – T cell, B cell, Histiocytic & Misc. NHL

According to Clinical grade – Low grade, Intermediate & High grade NHL.

Histopathological– Diffuse/Follicular NHL, – Small, Intermediate & Large cell NHL

Ex: Lennert’s lymphoma is a low grade Tcell NHL. Burkitt’s lymphoma is a high grade B cell NHL

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Kiel Classification of NHL

B Cell NHL:– Low Grade: lymphocytic, plasmacytic, centrocytic,

mixed centrocytic centroblastic.– High Grade: Centroblastic, Immunoblastic, Burkitts,

lymphoblastic.

T Cell NHL:– Low Grade: lymphocytic, mycosis, Lennerts– High Grade: immunoblastic, lymphoblastic etc.

Rare types:

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NCI – Working Formulation

Low-grade NHL:– Small lymphocytic– Follicular small cleaved

Intermediate-grade NHL:– Follicular large cell– Diffuse small cleaved

High-grade NHL:– Immunoblastic– Lymphoblastic

Miscellaneous: Histiocytic, Mycosis etc.

Diffuse - & - Follicular

NHL- Histologic types

Small – Intermed. – Large

NHL- Histologic typesNHL- Histologic types

Staging of Lymphoma

Lymphoma spread to Spleen

Lymphoma spread to Spleen

Laboratory Diagnosis:

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Laboratory Diagnosis:

Haematological: – Normocytic normochromic anemia, High ESR*– Leucocytosis, Eosinophilia, lymphopenia– Leukoerythroblastic picture - BM infiltration*

Bone marrow:– Normal, or late involvement.– Trephine biopsy- diffuse or follicular infiltration

Biochemical:– High serum LDH – poor prognosis– Hypercalcemia, Alkaline phosphatase, Uric acid.– Serum transaminases & Bilirubin – Liver

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Laboratory Diagnosis:

Immunological:– Monoclonal gammopathy –B cell NHL, Myeloma– Low normal gammaglobulins– Autoimmune hemolytic anemia – auto ab.

Karyotypic/Genetic:– t(14;18) – B cell follicular (14* heavy chain)– t(11;14) – diffuse NHL

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Diagnosis

X-Rays CT scans Magnetic Resonance Imaging (MRI) Biopsy Lymphangiogram

– Pictures of the lymphatic system taken w/ x-ray after a special dye is injected to illuminate lymph nodes and vessels

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Treatment

Non-Hodgkin’s Lymphoma is usually treated by a team of physicians including hematologists, medical oncologists and a radiation oncologist.

In some cases such as for Indolent lymphomas, the Doctor may wait to start treatment until the patient starts showing symptoms, known as “watchful waiting”

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Treatment Options

Chemotherapy Radiation Bone Marrow Transplantation Surgery Bortezomib (Velcade) Immunotherapy

Using the bodies own immune system combined with material made in a lab.

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Treatment:

Staging & grading

Chemotherapy – CHOP, MCHOP.. Radiotherapy – Local/regional/TBI Combination – Intensive Chemo/Radio-TBI with Autologous bone marrow rescue.

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Survival Rates

Survival Rates vary widely by cell type and staging.

– 1 Year Survival Rate: 77%

– 5 Year Survival Rate: 56%

– 10 Year Survival Rate: 42%

Burkitt’s Lymphoma

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Burkitt’s Lymphoma

Unusual, B-Lymphoblastic high grade Young african children, jaw bones Isolated histiocytes, starry sky pattern EBV infection related. t(8;14) Chemotherapy – good response But relapse usual, 30% cure.

Burkitt’s Lymphoma

Burkitt’s Lymphoma L.N.

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Lymphoma Summary:

Solid malignancy of lymphoid tissue. Lymphadenopathy, fever, anemia. Hodgkins & Non-Hodgkins (NHL) types. RS-Cells, eosinophilia – Hodgkins. Low-grade, Intermediate & High grade. Blood, Biochemical, BM, LN - biopsy Immunological & Genetic tests. Chemotherapy, Radiotherapy, combination