● VPTH 131 Report Format

LYMPHOSARCOMA

I. Introduction

Lymphosarcoma is the malignant transformation of lymphoid cells into solid tumors.

Lymphosarcomas develop in lymphoid tissues, including lymph nodes, the spleen,
the thymus, and other lymphoid organs.

Lymphosarcoma are categorized into three types based on their distribution:

(i) Multicentric form, in which they affect the majority of lymph nodes as well as other
organs. This applies to around 65% of canine instances.

(ii) Thymic form: Lymphosarcoma replaces and enlarges the thymus. This happens in
approximately 20% of feline instances and also in cattle, dogs, pigs, and sheep.
cattle with thymic lymphoma and haematoma

(iii) Alimentary form: The tumors appear to originate in Peyer's patches but spread to
the submucosa and muscularis. Occasionally, a leukemic variant appears. The
lymphocytic tumor cells replace bone marrow and accumulate in many organs.In cattle,
walls of the forestomachs and heart are the frequent locations.

(a) Ileocaecocolic high-grade alimentary lymphoma (HGAL) and (b) a cut surface from the same specimen. Diagnosis
of HGAL can often be based on cytology of ultrasound-guided fine-needle aspirates from a focal intestinal mass or an
enlarged mesenteric lymph node. (c) Diff Quik cytology of a concurrent abdominal effusion, showing neoplastic round
cells and a mitotic figure. Image (c) courtesy of Dr Patricia Martin, Veterinary Pathology Diagnostic Services,
University of Sydney

Lymphosarcoma are also broadly classified into:

● Hodgkin lymphoma (HL)

-Hodgkin's disease is lymphoid neoplasm. It is distinguished by its distinctive
histology. Tumor in the lymph Lymphocytic hyperplasia precedes lymph node
 formation. This is followed by a Replacement of lymphocytes causes a gradual
deterioration of normal architecture. As the disease worsens. It is distinguished
by the existence of Reed-Sternberg (RS) cells are unique multinuclear or
binuclear cells. cells are intermingled with inflammatory cells. RS cells are
pathogenic for diagnosis. Typical Hodgkin's disease has not been discovered in
animals. However, some cases of suspected Hodgkin's disease have been
reported in the dog. Additionally, Hodgkin's disease has been diagnosed. A
nine-year-old female cat. A necropsy indicated splenomegaly. The diagnosis was
based on the presence of many cells Properties of RS cells.

● Non- Hodgkin lymphoma (NHL)

- Non- Hodgkin lymphoma is more common than Hodgkin lymphoma,
though both types of cancer are relatively rare. It arises from cells
of the immune system and infection, immune deficiency, and
autoimmunity are among the strongest established risk factors

LYMPHOMA AND LYMPHOSARCOMA

A common contraction of the term “malignant lymphoma,” lymphoma is the
conventional human nomenclature for lymphoid neoplasms arising as solid tissue
masses in organs outside the bone marrow. The term “lymphoma” is a misnomer in that
the suffix oma typically denotes a benign neoplasm. However, a benign form of this
lymphoid neoplasm does not occur in either human or veterinary medicine. For this
reason, the “malignant” portion of malignant lymphoma is understood, and the
abbreviated lymphoma is often used alone. Lymphosarcoma is a term used in veterinary
literature to denote malignant lymphoma. Therefore the terms lymphoma, malignant
lymphoma, and lymphosarcoma are synonymous. Because of its acceptance within
human literature, the term lymphoma is be used throughout this text
In further explanation,the Suffix "-oma" typically denotes "tumor" and is
frequently connected with benign tumors, such as "lipoma" (a benign fatty tumor).
However, there are also cases when "-oma" refers to malignant disorders, such as
"lymphoma". These exceptions are primarily due to historical usage and customs that
predate contemporary classification. Although the term "lymphoma" includes the "-oma"
suffix, it refers to a malignant cancer. This word was coined before there was a clear
differentiation between benign and malignant tumors based solely on suffixes.
Therefore, "lymphoma" signifies malignant malignancies of lymphatic tissue,
despite the benign suggestion that "-oma" may imply. In contrast, "sarcoma" always
refers to a malignant tumor that arises from connective tissues such as bone, muscle,
and fat.
This is why "lymphosarcoma" has historically been used to describe an
aggressive or high-grade lymphoma, specifically one that behaves similarly to other
sarcomas in terms of rapid growth and invasiveness. In conclusion, lymphoma is
malignant because it involves cancerous, unregulated lymphocyte development that
can spread throughout the body. Due to past pathological name traditions, the naming
deviates from the "-oma" convention.

BENIGN VS. MALIGNANT

Benign tumors are not invasive, do not spread to other areas of the body, and are
easy to remove surgically. Malignant tumors can spread and cause harm to the animal.
Malignant tumors can invade surrounding tissue and spread to distant organs.
Distinguishing a benign tumor from a cancerous tumor requires specialized knowledge
and laboratory equipment.
Benign lymphoma is a rare, noncancerous tumor arising from lymphocytes, a
type of white blood cell that fights infection. It is not cancerous and occurs when many
lymphocytes accumulate in one area, usually outside the lymphatic system. Benign
lymphoma cells may appear similar to lymphoma but do not cause as much harm. It can
occur in various parts of the body, including the skin, mouth, tongue, throat, lungs,
gastrointestinal system, and breasts.
Malignant lymphoma is a quite typical malignancy in dogs. It is a progressive,
fatal disease caused by the abnormal proliferation of lymphocytes. Lymphoma typically
develops from lymphoid tissues in the bone marrow, thymus, lymph nodes, or spleen.
Other common sites are the skin, eye, central nervous system, and bone. Despite its
prevalence, the disease's causes and genesis are poorly understood. Possible causes
or contributory factors include viral infection, pesticide contamination in the
environment, magnetic field exposure, genetic anomalies, and immune system
dysfunction.

II. Histology
Microscopically, the typical architecture of the lymphoid tissues disappears. Aside
from normal lymphocytes, there are countless anaplastic cells of various sizes. A total
leukocyte count may show increases up to 5 times the average number for horses and
up to 15 for cattle and pigs, and up to 60 dogs. The predominant cells include
Lymphocytes and lymphoblasts. The number has decreased erythrocytes, neutrophils,
and platelets, as the infiltrating Leukocytes cause atrophy of bone's haematopoietic
tissue marrow.
Histological features of lymphoma of the mucosa-associated lymphoid tissue of the salivary
gland (Hematoxylin-eosin staining). (A) The normal structure of the parotid gland is destroyed
by the diffuse hyperplasia of lymphoid tissue, forming lymphoepithelial lesions (magnification
×400). Immunohistochemistry for the mucosa-associated lymphoid tissue lymphoma. The
tumor cells are positive for CD20 (B), CD43 (C), PAX-5 (D) (magnification ×400).

Lymphosarcoma in domestic animals are categorized into four cytological kinds based
on lymphocyte maturity.

1. Lymphocytic type: Lymphosarcoma cells resemble mature lymphocytes.

2. Lymphoblastic type: These cells are immature and resemble lymphoblasts.
3. Reticulum (or histiocytic) type: Lymphocytes are still young, and
 4. Stem cell (or weakly differentiated kind): The most anaplastic form of
cell.These histological types may not be consistently separate, and in rare
circumstances, both types may exist simultaneously.

III. Pathogenesis

Lymphosarcoma develops as a cancerous proliferation of lymphocytes occurs, or white

blood cells that normally function in the immune system.It might originate in any area of
the body.They also live longer as they should.Lymphoma comprises heterogeneous
malignancies that arise from the clonal proliferation of lymphocytes.

Development Process

I. INTERACTION
-Genetic alterations occurs

II. ACTIVATION AND PROLIFERATION

The Lymphosarcoma cells, particularly the ones that are derived from
B-lymphocytes are activated as they recognize specific antigens through their
B-cell receptors (BCRs). T -lymphocytes can be activated as well in response to
antigens presented by other cells.

III. CLONAL EXPANSION

Continuous division of cells results to clonal expansion that causes accumulation
of Lymphosarcoma cells into the Lymphoid Tissue.

IV. APOPTOSIS EVASION

 The Lymphosarcoma cells avoid programmed cell death.

V. MICROENVIRONMENTAL INTERACTIONS
The interaction between Lymphosarcoma cells and their microenvironment
That helps them to grow and survive.

Complications observed

Gross complications

● Lymphadenopathy- Enlargement of lymph nodes due to the accumulation of

neoplastic cells.

● Splenomegaly- is defined as the enlargement of the spleen measured by size or

weight.

● Hepatomegaly- is a clinical state of abnormal liver enlargement.

 ● Gastrointestinal involvement- Grossly, affected regions may appear thickened
or have masses, which can be identified during endoscopy or surgery.

Microscopic observations

● Hyperplasia- Increased number of Lymphocytes.

● Atypical Lymphocyte Morphology- Lymphoma cells often exhibit atypical

features.

● Tumor infiltration- Lymphoma cells infiltrate lymph nodes, spleen, and other
lymphoid tissues.
 ●
● Mitotic Activity- Increased mitotic activity is a hallmark of lymphoma, indicating
aggressive behavior.

● Loss of Follicular Structure- loss of normal follicular architecture, leading to a

more diffuse appearance.

IV. Risk Factors and Causes

1. Genetic Predisposition

● Certain dog breeds, such as Boxers, Golden Retrievers, Basset Hounds, and
Rottweilers, are more prone to developing lymphosarcoma, indicating a genetic
predisposition.
● In cats, Siamese and Oriental breeds may have a slightly higher risk.
 ● Genetic mutations or hereditary factors in these animals could affect immune
function or cell regulation, making them more susceptible.

2. Viral Infections

● Feline Leukemia Virus (FeLV): In cats, FeLV is a major risk factor for lymphoma,
particularly mediastinal and multicentric types. FeLV suppresses the immune
system and promotes abnormal lymphocyte proliferation.
● Feline Immunodeficiency Virus (FIV): FIV is also associated with an increased
risk of lymphoma in cats, due to its immune-suppressing effects.
● Bovine Leukemia Virus (BLV): In cattle, BLV infection is a well-established cause
of lymphosarcoma, particularly in dairy cattle. BLV can be transmitted via blood,
milk, and other bodily fluids, leading to lymphoma in the lymph nodes, digestive
tract, and other organs.

3. Immune System Suppression

● Animals with compromised immune systems, whether due to disease, chronic

illness, or medication, have an increased risk of lymphoma. For example, dogs
and cats on immunosuppressive drugs for autoimmune diseases may be more
prone to lymphosarcoma.
● In cattle, genetic mutations or stressors that weaken the immune system may
exacerbate the effects of BLV infection, increasing cancer risk.

4. Environmental Exposures

● Exposure to pesticides, herbicides, and other environmental toxins has been

suggested as a potential risk factor for lymphosarcoma in dogs, particularly in
agricultural or heavily landscaped areas.
● Similarly, in cats, household chemicals and certain types of tobacco smoke
exposure may have some correlation with lymphoma, though studies are limited.

5. Chronic Inflammation and Infections

 ● Chronic inflammatory conditions, such as inflammatory bowel disease (IBD) in
cats and dogs, may predispose them to lymphoma in the gastrointestinal tract.
Long-term inflammation could drive abnormal cell growth, leading to cancer.
● Chronic infections, though not well-studied in all species, may also contribute to
immune dysregulation and increased lymphoma risk.

6. Age and Gender

● In both dogs and cats, middle-aged to older animals are more likely to develop
lymphosarcoma, although the disease can occur at any age.
● Gender-specific risks are not strongly established, but some studies suggest a
slight predisposition in male animals for certain types of lymphoma.

7. Lifestyle and Diet

● Diets high in certain preservatives, low-quality ingredients, or lacking in variety

may contribute to inflammatory processes that could elevate cancer risk in pets,
though this area is still under research.
● Overweight or obese pets may also be at increased risk due to the potential role
of chronic inflammation associated with obesity in promoting cancerous growths.

V. Diagnosis

Samples Taken for Diagnosis:

1. Tissue Biopsy
○ Fine Needle Aspiration (FNA): A minimally invasive method to collect
cells from a tumor or lymph node for cytological examination.
○ Core Needle Biopsy: Obtains a larger tissue sample, providing better
histopathological detail.
○ Excisional Biopsy: Involves the surgical removal of a tumor for
comprehensive analysis.
Biopsy Type Fine Needle Core Needle Excisional Biopsy
Aspiration Biopsy

Definition A technique that uses a A technique that uses a Surgical removal of an

thin needle to extract larger needle to obtain entire lump or lesion.
cells from a mass. a core of tissue.

Needle Type Thin, hollow needle Larger, hollow needle Scalpel cutting
(22-25 gauge) (14-18 gauge)

Sample Size Small cellular sample Larger tissue sample Entire lesion or tumor

Indications Used for diagnosing Used for deeper or For definitive diagnosis
masses (e.g., tumors, more solid lesions. and treatment.
cysts).

Procedure Time Quick (few minutes) Quick (few minutes) Longer (depends on the
lesion size)

Sedation Required Often not required, but Mild sedation may be Usually requires
may be used needed general anesthesia

Complications Minimal (bruising, Moderate (bleeding, Higher risk (infection,

bleeding) infection) anesthesia risks)

Advantages -Minimal invasiveness - Larger sample for -Provides complete

- Quick and easy histology removal
- Low risk - Better for deeper - Definitive diagnosis
- Can be done in an lesions - Therapeutic benefits
outpatient setting - Can be done under
sedation

Disadvantages - Limited information Slightly invasive More invasive

- May require follow-up - May still require - Longer recovery time
procedures surgical follow-up - Higher costs

2. Blood Samples
○ Complete Blood Count (CBC): Can reveal anemia or leukocytosis, which
may indicate malignancy.
○ Serum Chemistry Panel: Assesses organ function and detects
abnormalities related to lymphosarcoma.
3. Bone Marrow Aspirate

This procedure helps determine if the cancer has spread to the bone marrow.
 4. Lymph Node Aspiration

Evaluating enlarged lymph nodes can provide critical information about disease
spread.

Diagnostic Imaging

1. Radiography (X-rays):
○ Can identify enlarged lymph nodes, mediastinal masses, and bone
involvement, showing potential lytic lesions.
2. Ultrasound:
○ Useful for assessing abdominal lymph nodes and organ involvement,
determining mass characteristics (size, shape, consistency).
3. Computed Tomography (CT) Scans:
○ Provides detailed cross-sectional images, helping to evaluate the extent of
the disease and any lymphatic involvement.
4. Magnetic Resonance Imaging (MRI):
○ Particularly effective for assessing soft tissue masses and central nervous
system involvement.

Imaging Modality Differences Advantages Disadvantages

Radiography Uses ionizing - Quick and - Limited soft tissue

(X-rays) radiation; good for accessible contrast
bones and larger - Useful for - May miss smaller
masses. identifying bone lesions.
involvement and
obvious masses.

Ultrasound Uses sound waves - Non-invasive; no Operator-

for soft tissue radiation dependent results
imaging; real-time. - Excellent for - Limited reach for
assessing lymph deep structures.
nodes and guiding
biopsies.

Computed Combines X-rays - High-resolution - Higher radiation

Tomography (CT for cross-sectional images exposure
Scan) imaging; high - Better soft tissue - More expensive
 detail. and anatomical and less
detail for staging. accessible.

Magnetic Uses magnetic - Excellent soft - Expensive; longer

Resonance fields and radio tissue contrast scan times
Imaging (MRI) waves; superior - No ionizing - Less effective for
soft tissue radiation. bone evaluation.

Practitioner Considerations

● Mass Appearance

Lymphosarcoma often appears as irregular soft tissue masses on imaging.

Practitioners should note any associated lymphadenopathy.

● Differential Diagnosis

It’s crucial to distinguish lymphosarcoma from other conditions such as infections

or reactive lymphadenopathy.

● Clinical Signs

Systemic signs (e.g., weight loss, fever, lethargy) may accompany

lymphosarcoma, guiding diagnostic efforts.

● Staging Importance

Proper staging is essential for treatment planning, requiring assessment of

localized versus disseminated disease.

VI. Treatment

Antineoplastics for Lymphosarcoma/Lymphoma

1. Chemotherapy Drugs:
○ Cyclophosphamide
○ Doxorubicin (Adriamycin)
○ Vincristine
 ○ L-asparaginase
○ Prednisone (often part of multi-drug protocols)

Other Medications

● Steroids: Prednisone and dexamethasone can help reduce inflammation and

improve quality of life.
● Immunotherapy:
○ Monoclonal antibodies (e.g., tocilizumab) targeting specific tumor
markers.
● Supportive Care: Antiemetics (e.g., maropitant), pain management (e.g.,
NSAIDs), and appetite stimulants.

Risks and Side Effects

● Chemotherapy:
○ Side Effects: Vomiting, diarrhea, myelosuppression (low blood cell
counts), alopecia, and increased risk of infections.
○ Contraindications: Pregnant or nursing animals, severe pre-existing
health conditions (like liver or kidney disease).
● Steroids:
○ Side Effects: Increased thirst and urination, weight gain, potential for
diabetes mellitus.
○ Contraindications: Active infections, diabetes, certain gastrointestinal
conditions.
● Immunotherapy:
○ Side Effects: Allergic reactions, immune-mediated conditions.
○ Contraindications: Autoimmune diseases, hypersensitivity to the drug.

Alternative Therapies
 ● Nutritional Support: Specialized diets can help support overall health and
immune function.
● Herbal Supplements: Some veterinarians may recommend certain
supplements, but these should be used cautiously and under veterinary
guidance.

Radiation Therapy

● Though not a medication, it can be used to target specific tumors or lymph

nodes, especially if they are causing pain or other issues.

Medication Type Risks/Side Effects Contraindications

Cyclophosphamide Chemotherapy Vomiting, diarrhea, Pregnant/nursing,
myelosuppression, severe liver/kidney
alopecia disease

Doxorubicin Chemotherapy Cardiotoxicity, vomiting, Pregnant/nursing, heart

myelosuppression disease

Vincristine Chemotherapy Neuropathy, vomiting, Pregnant/nursing,

myelosuppression severe liver disease

L-asparaginase Chemotherapy Allergic reactions, Previous

vomiting hypersensitivity

Prednisone Steroid Increased Active infections,

thirst/urination, weight diabetes
gain

Tocilizumab Immunotherapy Allergic reactions, Autoimmune diseases,

immune-mediated hypersensitivity
diseases

Antiemetics (e.g., Supportive Care Sedation, diarrhea Hypersensitivity, certain

maropitant) drug interactions
The duration of medication or therapy for lymphosarcoma and lymphoma in veterinary
patients varies based on several factors, including the specific treatment used, the type
and stage of cancer, and the individual response of the animal. Here’s a general
overview:

1. Chemotherapy

● Typical Duration: Chemotherapy protocols often last from 6 months to 1 year,

with treatments typically administered every 2 to 3 weeks. The exact schedule
depends on the specific drugs used and the treatment protocol.
● Monitoring: Regular follow-up visits are necessary to monitor blood counts and
assess the response to treatment.

2. Steroids

● Typical Duration: Steroids can be used for varying lengths of time, often starting
with a high dose that is gradually tapered. This might last from a few weeks to
several months, depending on the response and side effects.
● Monitoring: Regular check-ups to assess side effects and adjust dosages are
important.

3. Immunotherapy

● Typical Duration: Immunotherapy treatments can vary widely; some may be

given for a few months, while others might be longer-term, depending on the
drug and the animal’s response.
● Monitoring: Frequent assessments to evaluate efficacy and potential side
effects.

4. Supportive Care Medications

 ● Typical Duration: Supportive care medications, like antiemetics or pain
management, are typically given as needed and can be part of a long-term
management plan based on the pet’s condition.
● Monitoring: Ongoing evaluation of the animal's quality of life and adjustment of
medications accordingly.

5. Radiation Therapy

● Typical Duration: Radiation treatment usually involves multiple sessions (often 3

to 5 days a week) over a period of 2 to 4 weeks, depending on the treatment
plan.
● Monitoring: Follow-up visits to assess response to therapy and manage any
side effects

Treatment Type Typical Duration Monitoring/Notes

Chemotherapy 6 months to 1 year Treatments every 2 to 3

weeks; regular blood
monitoring.

Steroids A few weeks to several Starting with high doses,

months tapering as needed;
regular check-ups.

Immunotherapy Varies widely (months to Frequent assessments to

longer-term) evaluate response and
side effects.

Supportive Care As needed, potentially Adjust based on quality of

Medications long-term life and specific symptoms.

Radiation Therapy 2 to 4 weeks (multiple Follow-up to assess

sessions) response and manage side
effects.

VII. Advances in Treatment, Control and Diagnosis

● Molecular Diagnostics
 Techniques like PCR (Polymerase Chain Reaction) and flow cytometry allow for
more precise identification of lymphoma subtypes, aiding in treatment plans

● Advanced Imaging

High-resolution imaging modalities, such as MRI and CT scans, provide detailed

information about tumor location, size, and potential spread, enabling more
accurate staging and treatment planning.

● Genetic Profiling

By analyzing the genetic makeup of a tumor, veterinarians can identify specific

genetic alterations that drive cancer growth. This information can help select the
most effective targeted therapies.

● Monoclonal Antibodies

These target specific proteins on cancer cells, leading to their destruction.

● Immunotherapy

This approach stimulates the pet's immune system to recognize and attack
cancer cells.

● Tyrosine Kinase Inhibitors

These drugs block specific signaling pathways involved in cancer cell growth and
survival.

MAREK’S DISEASE

I. Introduction
 Marek's disease (MD) is a lymphoproliferative illness with A cell-associated
herpesvirus that causes the disease in chickens. It is distinguished by a mononuclear
infiltration of the peripheral nervous system and, to a lesser degree, other tissues and
visceral organs. In other words, the condition is linked to the development of lymphoid
tumors (lymphoma). MD affects chickens as early as 6 weeks of age, with the majority
of cases occurring between 12 and 24 weeks.

Marek's disease is named after Hungarian veterinarian Jozsef Marek, who first
described the disease in the 1900s. The virus responsible for the disease is known as
Marek's disease virus (MDV), which is classified into several strains, including the most
common: MDV serotype 1, and other strains like MDV serotype 2 and 3.

1. MDV Serotype
● Characteristics:
○ The most pathogenic strain, responsible for causing Marek's disease in
chickens.
○ Associated with severe clinical signs, including tumors and
immunosuppression.
● Common Vaccines:
○ Vaccines like HVT and Rispens target this serotype effectively.
● Virulence:
○ Highly virulent and can cause significant economic losses in poultry.
U S 3 of MDV-1, MDV-2, and HVT differentially regulate virus replication in lymphoid organs. At
six days postinoculation, lymphoid organs (spleen, thymus, and bursa) were collected from
virus-inoculated or uninoculated (negative control) chickens, fixed in 10% neutral buffered
formalin solution for 48 h, and stored in 70% ethanol until used. Tissue sections were prepared
and subjected to immunostaining with anti-pp38 monoclonal antibody and VECTASTAIN ABC kit
according to the manufacturer's instructions, using DAB (3,3'-diaminobenzidine) as the
substrate. A representative image of three independent samples from each group is presented;
the scale bar is the same for every panel (scale bar = 50 µm).

2. MDV Serotype 2

● Characteristics:
○ Considered less virulent compared to serotype 1.
○ Primarily used in vaccine production to create a level of immunity against
more virulent strains.
● Common Vaccines:
○ Some vaccines use serotype 2 as a component to enhance protection
when combined with other strains.
● Virulence:
○ Generally associated with mild clinical disease and lower tumor incidence.

3. MDV Serotype 3
 ● Characteristics:
○ Also known as the turkey herpesvirus (HVT), primarily affects turkeys but
can infect chickens.
○ Less pathogenic in chickens compared to serotype 1.
● Common Vaccines:
○ HVT vaccines are derived from this strain and are widely used for Marek's
disease prevention in chickens.
● Virulence:
○ Non-pathogenic to chickens; mainly serves as a vaccine strain to provide
cross-protection against serotype 1.

Serotype Pathogenicity Common Uses Typical Vaccines

Serotype 1 Highly pathogenic Causes Marek’s HVT, Rispens

disease

Serotype 2 Less pathogenic Used in vaccine Combines with

production other vaccines

Serotype 3 Non-pathogenic Primarily in turkeys HVT vaccines for

chicken

Tissues Involved

Marek's disease primarily affects:

● Nervous System: Tumors can form in nerves, leading to paralysis and

neurological symptoms.
● Lymphoid Tissues: Lymphomas can develop in various organs, including the
spleen, liver, and kidneys.
 ● Skin: Cutaneous lesions, such as nodules, can occur.

Benign vs. Malignant Form

● Benign Form: This form is characterized by localized tumors that may not
significantly affect the health of the bird. These tumors are often less aggressive
and may resolve without treatment.
● Malignant Form: This form is more severe and involves aggressive tumor
growth that can spread to multiple organs. It typically leads to serious health
issues, including severe weight loss, paralysis, and often results in death if not
managed.

II. Histology
Microscopically, The lesion is composed of proliferating lymphoid cells,
lymphoblasts,lymphocytes can be small, medium, or big. The most prevalent lesions in
visceral organs are lymphoid tumors, showing comparable cellular infiltration.
Malignantly altered cells are thymus-dependent lymphocytes (T-cells), and lymphoma is
a combination of malignant T-cells, reactive, bursa-dependent lymphocytes (Bcells),
T-cells, and macrophages.

Muscle tumour, Marek’s disease. Focal pleomorphic cell proliferation. H/E, Bar
= 35 µm.
Diffuse pleomorphic cell proliferation in the proventriculus mucous coat
(arrow), hen. Compression and atrophy of glandular acini. H/E, Bar = 40 µm.

Lymphoid cell proliferations in the iris and ciliary muscles in the ocular form
of Marek’s disease. H/E, Bar = 50 µm.

Peripheral nerve, B-type lesion (mostly inflammatory type). Interneuritic

inflammatory oedema and slight to moderate proliferation of lymphocytes
and plasmatic cells, rarely lymphoblasts. The mild version of B-type lesions is
called C-type. H/E, Bar = 25 µm.
 III. Pathogenesis

Marek's disease tumors primarily develop due to the transformation of T-lymphocytes

infected by the Marek's disease virus (MDV). The virus integrates into the host genome,
leading to uncontrolled cell proliferation and the formation of lymphoid tumors. Initially,
the virus induces a state of immune suppression, allowing for the unchecked growth of
transformed cells.

Development Process

I.Infection and Initial Replication- MDV enters the host primarily through the
respiratory tract via inhalation of dust particles containing the virus.

II.Immune Evasion- DV has developed mechanisms to evade the host immune

response, including downregulation of major histocompatibility complex (MHC)
molecules and the induction of immunosuppressive factors.

IV.Tumor Development- The virus causes transformation of T-lymphocytes, leading to

uncontrolled proliferation and the development of lymphomas.

V.Clinical Manifestation- Exhibit a range of clinical signs, including lethargy, loss of

appetite, weight loss, and neurological symptoms due to nerve infiltration.

Complications Observed

Gross Observations:

● Tumor Masses: Enlarged organs, especially the liver, spleen, and kidneys, may
present with visible tumor masses.
 Tumors found in mice with Marecks Disease

● Nerve Enlargement: Thickening and swelling of peripheral nerves can be

observed, often leading to paralysis.

●
● Cutaneous Lesions: Nodular lesions can appear on the skin.

Microscopic Observations:

● Lymphoid Hyperplasia: An increase in lymphocyte numbers is noted, often with

atypical morphology.
● Tumor Infiltration: Tumors infiltrate surrounding tissues, displacing normal cells.
● Nuclear Pleomorphism: Neoplastic cells exhibit variability in size and shape,
often with prominent nucleoli.
IV. Risk factors and Causes
-Lifestyle or congenital factors that may increase the risk of having the type of
cancer?
Lifestyle Factors:

1. High-Density Housing: Chickens raised in crowded conditions are more

susceptible to Marek's disease due to increased stress and the potential for
greater viral transmission.
2. Poor Biosecurity Practices: Inadequate sanitation and lack of vaccination can
heighten the risk of infection.
3. Nutritional Deficiencies: Suboptimal nutrition can weaken the immune system,
making birds more susceptible to MDV infection and subsequent tumor
development.

Congenital Factors:

1. Genetic Predisposition: Certain breeds of chickens may have a genetic

susceptibility to Marek's disease, impacting their immune response to MDV.
2. Age of Infection: Younger birds, especially those under 16 weeks of age, are
more likely to develop severe forms of the disease.

V. Diagnosis

Samples Taken

1. Tissue Biopsies: Samples from affected organs (e.g., liver, spleen, nerves) can
be taken to examine for neoplastic changes.
2. Blood Samples: These can help assess the overall health of the bird and detect
any signs of immunosuppression.
3. Swabs: Samples from skin lesions may be collected for cytological examination.

Diagnostic Imaging
 ● Radiography: X-rays can reveal enlarged organs and abnormal masses.
● Ultrasound: This modality can be used to visualize internal organs for signs of
tumor presence, such as mass lesions or abnormalities in organ structure.
● CT Scans: Computed tomography may provide detailed images of internal
structures, helping to identify the extent of tumor spread.

What Practitioners Look Out For

● Presence of Tumors: Identification of abnormal masses in lymphoid

organs or nerves.
● Enlarged Organs: Significant swelling of the liver, spleen, or kidneys.
● Nerve Involvement: Signs of nerve enlargement, which may indicate
tumor infiltration.
● Fluid Accumulation: Abnormal fluid levels in body cavities, which may
suggest complications from tumors.

VI. Treatment
Marek's disease primarily relies on prevention, as there is no definitive cure once
the disease is established. However, certain management strategies can help
mitigate its impact:

1. Vaccination

Vaccination is the most effective method to prevent Marek's disease. Vaccines

are typically administered to chicks at one day old and can significantly reduce
the incidence and severity of the disease.

Several vaccines are used to protect against Marek's disease in poultry. Some of the
most commonly used vaccines include:

● HVT (Herpesvirus of Turkeys) Vaccine: This is the most widely used vaccine
and offers broad protection against various strains of Marek's disease virus.
 Provides effective protection for the life of the bird, typically for several months to
a year, with some studies suggesting immunity may last longer.
● SB-1 Vaccine: A live attenuated vaccine derived from the serotype 1 MDV
strain, providing good protection, particularly in commercial poultry. Usually
provides effective immunity for about 6 to 12 months, although some birds may
retain protection longer.
● Rispens Vaccine: A more recent vaccine that is effective against a broader
range of MDV strains, including more virulent strains. Offers robust protection for
at least a year and may provide long-term immunity against various strains.

Vaccine Pros Cons Duration/Schedule

HVT Strong protection May not cover all Day 1; lifelong

strains immunity

SB-1 Effective;combinable Slightly lower efficacy Day 1; 6-12 months

vs. some strains immunity

Rispens Broad protection Higher cost;potential Day 1; at least 1 year

adverse reactions immunity

2. Supportive Care

● Nutritional Support: Providing a balanced diet can help bolster the immune
system of affected birds.
● Stress Reduction: Minimizing stress through proper housing, management
practices, and reducing overcrowding can improve overall health and potentially
reduce the severity of the disease.

3. Culling
 ● Severe Cases: Infected birds that exhibit severe clinical signs or tumors may
need to be culled to prevent further spread of the virus within the flock.

4. Management Practices

● Biosecurity: Implementing strict biosecurity measures can help prevent the

introduction and spread of Marek's disease in poultry populations.
● Environmental Control: Maintaining clean and dry living conditions can help
reduce the viral load in the environment.

VII. Advances on the Diagnosis, Treatment and Control

1. Advances in Diagnosis

● Molecular Techniques: The use of polymerase chain reaction (PCR) and

real-time PCR has improved the ability to detect Marek's disease virus (MDV) in
tissue samples and blood. These methods allow for rapid and specific
identification of the virus.
● Serological Tests: Advances in serological assays, such as enzyme-linked
immunosorbent assays (ELISA), have improved the detection of antibodies
against MDV, helping to assess the immune status of the flock.
● Imaging Technologies: Enhanced imaging techniques like ultrasound and
computed tomography (CT) provide detailed insights into tumor presence and
organ involvement, aiding in accurate diagnosis.

2. Advances in Treatment

● Genetic Research

Ongoing research into genetic resistance in certain chicken breeds may lead to
the development of more resilient poultry. Breeding programs focused on
enhancing immune responses to MDV are being explored.
 ● Immunotherapy

Although still in early stages, approaches that enhance the immune response to
the virus are being investigated, potentially leading to new therapeutic options.

● Supportive Care Protocols

Improved management practices, including stress reduction and nutritional

support, can help affected birds cope with the disease more effectively.

3. Advances in Control

● Vaccination Strategies

Continuous improvements in vaccine formulations and administration techniques

are being developed. New vaccines may provide broader protection against
various strains of MDV and may include recombinant vaccines that enhance
immunity.

● Biosecurity Measures

Advances in biosecurity protocols, including better sanitation practices and

monitoring systems, help prevent the introduction and spread of MDV in poultry
farms.

● Monitoring and Surveillance

Enhanced surveillance systems and data analytics are being used to track
outbreaks, assess risk factors, and implement control measures more effectively.

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