LITHUANIAN UNIVERSITY OF HEALTH SCIENCES

VETERINARY ACADEMY

Faculty of Veterinary Medicine

Julia Kempen

Ultrasound evaluation of Canine and Feline lymphoma

Šunų ir kačių limfomos vertinimas ultragarsinio tyrimo metu

MASTER THESIS

Of Integrated Studies of Veterinary Medicine

Supervisor: Ieva Šeibokaitė

Kaunas, 2021

2

THE WORK WAS DONE IN THE DEPARTMENT OF THE SMALL ANIMAL CLINIC.

CONFIRMATION OF THE INDEPENDENCE OF THE DONE WORK:

I confirm that the presented Master Thesis “Ultrasound evaluation of Canine and Feline

lymphoma”

1. has been done by me;

2. has not been used in any other Lithuanian or foreign university;

3. does not contain information from any other sources not indicated in the work and is

presented with a complete list of the used literature.

(date) (author’s name, surname) (signature)

CONFIRMATION ABOUT RESPONSIBILITY FOR THE CORRECTNESS OF THE

ENGLISH LANGUAGE IN THE DONE WORK:

I confirm the correctness of the English language in the done work.

December 11th, 2021 Annamaria Lucia Nevmark

(date) (author’s name, surname) (signature)

CONCLUSION OF THE SUPERVISOR REGARDING DEFENSE OF THE MASTER

THESIS:

(date) (supervisor’s name, surname) (signature)

THE MASTER THESIS HAS BEEN APPROVED IN THE

DEPARTMENT/CLINIC/INSTITUTE

(date) (name, surname of the head of the (signature)

clinic/department/institute)

Reviewer of the Master Thesis

(name, surname) (signature)

Evaluation of the Defense Commission of the Master Thesis:

(date) (name, surname of the secretary of the (signature)

Defense Commission)

3

TABLE OF CONTENTS

SUMMARY 5

SANTRAUKA 6

ABBREVIATIONS 7

INTRODUCTION 8

1. LITERATURE REVIEW 9

1.1. DEFINITION OF LYMPHOMA 9

1.2. CLASSIFICATION OF LYMPHOMA 10

1.2.1. Multicentric lymphoma 10

1.2.2. Alimentary lymphoma 10

1.2.3. Mediastinal lymphoma 11

1.2.4. Extra nodal lymphoma 12

1.2.5. Indolent lymphoma 12

1.3. LESIONS CAUSED BY LYMPHOMA 12

1.4. DIAGNOSTIC METHODS 13

1.5. ULTRASONOGRAPHY IN THE DIAGNOSIS OF LYMPHOMA 14

1.5.1. Ultrasonographic imaging 14

1.5.2. Ultrasound of the urinary and genital system and the adrenal glands 15

1.5.3. Ultrasound of the spleen 16

1.5.4. Ultrasound of the liver and gallbladder 16

1.5.5. Ultrasound of the gastrointestinal tract and pancreas 16

1.5.6. Ultrasound of the lymph nodes 17

1.6. POSSIBLE TREATMENT METHODS OF LYMPHOMA 17

2. MATERIALS AND METHODS 19

2.1. OBJECT OF THE RESEARCH 19

2.2. STUDY DESIGN 19

2.3. DATA PROCESSING 21

3. RESULTS 22

3.1. POPULATION ANALYSIS 22

3.2. ANAMNESIS AND CLINICAL SIGNS 23

4

3.3. BLOOD TESTING 23

3.3.1. Blood morphology 24

3.3.2. Blood biochemistry 25

3.4. ULTRASOUND 27

3.4.1. Ultrasound of the urinary tract 27

3.4.2. Ultrasound of the liver and gall bladder 32

3.4.3. Ultrasound of the spleen 34

3.4.4. Ultrasound of the lymph nodes 36

3.5. OTHER DIAGNOSTIC METHODS OF LYMPHOMA 38

3.6. MAIN ULTRASONOGRAPHIC FINDINGS AND OUTCOME OF THE CASES 39

4. DISCUSSION OF THE RESULTS 41

CONCLUSIONS 43

ACKNOWLEDGEMENTS 44

REFERENCES 45

5

SUMMARY

Ultrasound evaluation of Canine and Feline lymphoma

Julia Kempen

Ultrasonography remains a useful, non-invasive tool for the diagnosis and staging of lymphoma

in dogs and cats. This study was carried out with the objective to determine its meaning in the

diagnostic process as well as its limitations in comparison with other diagnostic tools such as blood

sampling, FNA sampling for cytology and biopsy sampling for histopathology.

The study was conducted in the L. Kriaučeliūnas Small Animal Clinic, Veterinary Academy,

LSMU Kaunas, Lithuania. 61 cases were reviewed in the documentation system of the clinic,

encompassing the past 5 years. Thirty-one (31) of these cases were chosen for the study. The patient

owners were asked to give detailed anamneses and blood samples were taken from the patients prior

to the ultrasound examination including FNA/biopsy sampling of suspicious organs and tissues. Not

all aspects of all the examinations could be executed on all the patients.

It was found that the majority of dogs and cats with lymphoma showed changes in the blood

morphology and biochemistry that coincided with the changes found in ultrasonographic

examinations or the clinical signs described in the anamnesis of the patients. Animals commonly

presented with lethargy, inappetence and weight loss, which corresponded with the non-regenerative

anaemia and elevated white blood cell levels that many of the patients displayed. Organic changes

caused by lymphoma could be seen both in the blood results and the ultrasound views. Changes in

hepatic echotexture, parenchymal lesions and gall bladder sludge or stones were common

ultrasonographic findings along with splenomegaly, changes in splenic homogeneity and echotexture,

increased lymph node size or altered lymph node shape and homogeneity. Other characteristic

changes of lymphoma could not be visualised in the course of this study, but displayed in the blood

results, nevertheless.

It could be concluded that ultrasonography is useful to express the changes caused by

lymphoma and an effective guide for FNA sampling to be used for cytology. However, ultrasound

cannot be used as the only diagnostic tool for lymphoma. Despite the fact that it can visualize many

of the organs involved, the quality of the pictures is limited as well as the perception and skills of the

veterinarian. Because of this, ultrasonography is subject to bias at all times.

Key words: Ultrasound, lymphoma, diagnosis

6

SANTRAUKA

Šunų ir kačių limfomos vertinimas ultragarsinio tyrimo metu

Julia Kempen

Ultragarsinis tyrimas yra neinvazyvus bei naudingas diagnozuojant šunų ir kačių limfomą ir jos

stadijas. Šio tyrimo tikslas yra išsiaiškinti ar ultragarsinis tyrimas gali būti patikimas siekiant įvertinti

limfomą ir jos stadijas, palyginti diagnostinį tikslumą su kitais tyrimais: aspiraciniais mėginiais ir

citologija, kraujo tyrimais, biopsija ir histopatologija.

Tyrimas buvo atliekamas Dr. L. Kriaučeliūno smulkiųjų gyvūnų klinikoje, Veterinarijos

akademijoje, LSMU, Kaunas, Lietuva. Tyrimo metu buvo išanalizuotas 61 atvejis, iš jų 31 atvejis

buvo atrinktas kaip tinkamas tolimesniems tyrimams atlikti. Atrinktųjų gyvūnų savininkai turėjo

pateikti detalią anamnezę. Kraujo mėginiai buvo surinkti prieš atliekant pilvo ertmės organų

ultragarsinį tyrimą. Aspiracijos ir biopsijos mėginiai surinkti iš audinių, kurie atitiko būdingus

pažeidimus. Tyrimo metu daliai pacientų visi numatytieji tyrimai nebuvo atlikti.

Tyrimo metu nustatytas ryšys tarp kačių ir šunų, sergančių limfoma, kraujo biocheminių ir

morfologinių tyrimų rezultatų nuokrypių, ultragarsinio tyrimo metu rastų pokyčių ir savininkų

pateiktos anamnezės duomenų. Gyvūnams pasireiškė letargija, apetito sumažėjimas, svorio kritimas,

šie pokyčiai siejami su limfomos metu matoma neregeneruojančia anemija ir padidėjusiu baltųjų

kraujo kūnelių kiekiu. Tyrimo metu nustatytas ryšys tarp gautų kraujo tyrimų rezultatų bei specifinių

organų pokyčių diagnozuotų ultragarsinio tyrimo metu. Dažniausiai rasti ultragarsiniai pokyčiai:

kepenų echotekstūros ar parenchimos pažeidimai, sedimentai tulžies pūslėje ar cholelitai,

splenomegalija, blužnies echotekstūros bei homogeniškumo pokyčiai, padidėję limfiniai mazgai, jų

struktūros ir formos pokyčiai. Dalis specifinių, limfomai būdingų pokyčių ultragarsinio tyrimo metu

nebuvo įvertinta.

Galima daryti išvadą,jog ultragarsinis tyrimas yra naudingas vertinant struktūrinius limfomos

sukeltus pokyčius vidaus organuose, taip pat reikšmingas atliekant audinių aspiraciją. Tačiau,

ultragarsinis tyrimas negali būti naudojamas kaip vienintelis diagnostinis metodas limfomai

diagnozuoti, nepaisant galimybės įvertinti vidaus organų struktūrinius pokyčius, svarbu atsižvelgti į

dirbančio specialisto gebėjimus, ribotą echogramų panaudojimą bei topografines organų sąvybes.

Raktažodžiai: Ultragarsinis tyrimas, limfoma, diagnozė

7

ABBREVIATIONS

FeLV – Feline Leukaemia Virus

WHO – World Health Organisation

PARR – PCR for antigen receptor rearrangements

FNA – Fine needle aspiration

CD antigens – Cluster of differentiation antigens

MOPP – a cancer chemotherapy drug consisting of Mustargen, Oncovin, Procarbazine

Hydrochloride and Prednisone

DMAC - Dimethylacetamide

8

INTRODUCTION

Lymphoma is the neoplasm that is most commonly treated by chemotherapy (1). The proper

diagnosis and staging can be crucial to treatment success. In lymphoma treatment, the goal is not to

eliminate the disease from the body, but rather to drive the disease into remission which in turn, buys

vital time for the patient. (2). Lymphoma is a complex type of malignant neoplasm, often spreading

to multiple organs and causing a variety of symptoms and complications (3). Because of the multiple

changes that can be caused by lymphoma, it is possible to visualize them in ultrasonography (4) (5).

Advanced ultrasound techniques such as doppler and contrast-enhanced ultrasonography have

recently gained popularity and meaning in the diagnosis of various diseases (6). Ultrasound is a non-

invasive imaging technique, requiring no sedation of the animal and not causing it any pain which

has made it a prime choice for investigating changes of the abdominal organs and heart (7) (8).

Even though ultrasonography has become increasingly meaningful as a diagnostic tool,

cytology and histopathology examinations are often required to confirm the diagnosis. Even in this

case, ultrasound might be useful to provide visual guidance for fine needle aspiration (FNA)

techniques or to point out the site of biopsy sampling (9) (8).

The purpose of this research was to investigate the meaningfulness of ultrasonography as a

diagnostic tool for lymphoma and the possibility to locate lesions specific to lymphoma or a certain

type of lymphoma. Other diagnostics of lymphoma were investigated along with ultrasonographic

findings to be able to compare their meanings in the diagnostic process.

Tasks of the work:

1. To determine the efficiency of ultrasound examination in the diagnostic process of Canine

and Feline lymphoma

2. To evaluate the efficiency of pulmonary ultrasound examination for the diagnosis of

lymphoma

3. To analyse blood test results of dogs and cats with suspected lymphoma

4. To establish the expressiveness of FNA for lymphoma diagnostics

5. To create a relation between ultrasonographic views and diagnosis and prognosis

9

1. LITERATURE REVIEW

1.1. Definition of lymphoma

Lymphoma is a cancer derived from the hematopoietic system or the pathologic clonal

expansion of B – or T – cells. These malignant lymphocytes are the potential cause for lymphoma in

any place in which they migrate or reside (10). The prevalence of B-cell derived lymphoma in dogs

is higher than that of T-cell lymphoma, which only accounts for between 10 and 38% of all Canine

lymphoma cases. In Feline lymphoma however, T-cell derived cases are more prevalent since they

occur due to the transformation of Feline Leukemia Virus (FeLV). Only Feline alimentary

lymphomas are more often B-cell derived and not related to FeLV (11). Generally, lymphoma is the

most frequently diagnosed hematopoietic neoplasm of dogs and cats (10), (11). It commonly occurs

in the primary and secondary lymphoid tissues but expands to many other tissues in the body. This

expansion is not metastasis, but rather disease progression. Lymphoma can originate in one site and

progress to others as well as developing in multiple places simultaneously (11).

The response of lymphoid tissues to damage or stimuli is limited and includes hyperplasia,

hypertrophy, atrophy, necrosis, inflammation, and neoplasia (12). Some of those changes may be

normal immune reactions and therefore, it can be challenging to differ between lymphoid physiology

and pathology (12). It is important to understand the functions of the immune system and the

pathogenesis of lymphoma to determine its type adequately and provide the best possible treatment

and an accurate prognosis.

The primary lymphoid tissues are the bone marrow and thymus. Stem cells of both T –

lymphocytes and B – lymphocytes are formed in the bone marrow. Migration to other organs of the

lymphoid system leads to differentiation of those common stem cells into the different types of

lymphocytes. Lymphocytes that mature in the bone marrow will later become B – lymphocytes while

lymphocytes maturing in the thymus will be T – lymphocytes. In the secondary lymphoid organs, B

– lymphocytes proliferate into plasma cells and memory B – lymphocytes, T – lymphocytes

proliferate into cytotoxic T – cells and memory T – lymphocytes (13).

The secondary lymphoid tissues are the lymph nodes and the spleen. They are not involved in

lymphocyte maturation, but proliferation and differentiation and play an important role in lymphocyte

storage as well as cell-mediated and humoral-mediated immune response (12).

10

1.2. Classification of lymphoma

Tissues and organs commonly affected by lymphoma include the skin, the gastrointestinal tract,

liver, eyes, central nervous system, and bones (10). Clinically, lymphoma can be classified into five

stages according to the World Health Organization (WHO) system for the clinical staging for tumors

of domestic animals. Stage I expresses the involvement of a single lymph node. If multiple regional

lymph nodes are involved, the lymphoma is classified as stage II. Stage III lymphoma shows general

lymph node involvement, in stage IV, liver and spleen are affected as well. Stage V is the final stage

where the lymphoma has manifested itself in the blood, bone marrow and possibly other organs and

systems. Additionally, all these stages can be subdivided into subtype a which describes cases without

clinical signs of disease and subtype b where clinical signs of disease are present (14). Lymphoma

can be classified into four anatomical forms according to its location, extend, morphologic subtype,

immune competence and the clinical signs it causes in both dogs and cats with the incidence varying

between species (10).

1.2.1. Multicentric lymphoma

Multicentric lymphoma encompasses 80 – 85% of all Canine lymphoma cases (10) and the is

considered the second-most common Feline lymphoma case in cats diagnosed with FeLV. Cats that

are FeLV negative are 60 times less likely to develop lymphoma than cats that are FeLV positive

(15). In cats without a FeLV diagnosis, a diffuse gastrointestinal form of lymphoma is the most

common.

Multicentric lymphoma concerns the lymph nodes, liver, spleen, kidneys, and thymus. It is

characterized by the rapid and non-painful development of a generalized lymphadenopathy and

particularly peripheral lymphadenopathy. Using flow cytometry or PARR, malignant lymphocytes

can be detected. Animals with a significant tumor burden will show lethargy, weakness, fever,

anorexia, and dehydration (10).

1.2.2. Alimentary lymphoma

Alimentary lymphoma makes up for less than 10% of Canine lymphoma cases (10), whereas in

cats, it is the most prevalent anatomical form of lymphoma (16). It often affects the gastrointestinal

tract, spleen, liver, and the lymph nodes (10). In dogs with focal intestinal lesions, clinical signs

consistent with partial or complete intestinal luminal obstruction can be found, including vomiting,

constipation, and abdominal pain. In cases with diffuse involvement of the intestines, animals will

11

suffer from anorexia, vomiting, diarrhea, hypoproteinemia, maldigestion and malabsorption which

will eventually lead to weight loss. These signs appear with diffuse intestinal involvement and are

much more significant and debilitating than those that are caused by focal intestinal lesions (10). In

cats however, the different types of lymphoma can be presented with various clinical signs that differ

between the histological grades almost as if they were different diseases overall. Feline alimentary

lymphoma is subdivided in to three histological grades: Low-grade, intermediate-grade and high-

grade alimentary lymphoma of which low grade alimentary lymphoma accounts for only about 10%

of all those cases. Additionally, large granular lymphocyte lymphoma of felines can present with any

one of the three histologically grade severities and is described as a separate subclassification which,

makes up for 28% of lymphoma cases in cats. Clinical signs of low-grade feline alimentary lymphoma

are often chronic (lasting longer than a month) and include weight loss in more than 80% of cases,

vomiting in over 70%, diarrhea in 60% or more and anorexia in about 50% of the animals. Polyphagia

can be a sign of the low-grade form as well as less frequently lethargy and polydipsia. In about a third

to more than half of the cats with a low-grade alimentary lymphoma diagnosis, abnormalities can be

found on abdominal palpation. Those abnormalities can be thickened intestinal loops and one or more

abdominal masses which are usually the enlarged mesenteric lymph nodes or, less commonly, a focal

intestinal mass. Acute and more severe clinical signs have been reported in cats with intermediate-

grade, high-grade and large granular lymphocyte lymphoma. In many of these cases, a palpable

abdominal mass can be found. As a result of this mass, animals will often suffer from focal intestinal

thickening as well as extraintestinal lesions which can include hepatomegaly, renomegaly, and

mesenteric lymph adenomegaly. In some intermediate-grade and high-grade lymphoma cases, cats

will have intestinal obstruction, intussusception, and even intestinal perforation. Rarely, these

problems will occur in low-grade lymphoma cases (16; 17).

1.2.3. Mediastinal lymphoma

The third form according to the anatomical classification is mediastinal lymphoma. Arising

from highly malignant T – lymphocytes in the thymus, it exclusively involves the cranial mediastinal

lymph nodes, the thymus, and the thorax (10). Noticeable on palpation is the sternal lymph node

enlargement. The cranial mediastinal lymph nodes occupy the cranial mediastinum, just ventral to

the trachea. They line the cranial vena cava and the brachiocephalic artery, left subclaviculan artery

and the cost cervical arteries (18). Mediastinal lymphoma can lead to severe problems including

pleural fluid accumulation which can cause respiratory distress, direct compression of the adjacent

lung lobes and caval syndrome. Humoral hypercalcemia, a paraneoplastic syndrome seen in 10-40%

of Canine mediastinal lymphoma, can cause polyuria which in turn will lead to polydipsia. This

12

humoral hypercalcemia of malignancy can be confirmed with the help of ionized calcium, parathyroid

hormone and parathyroid hormone peptide parameters that are measured in the circulating blood (10).

1.2.4. Extra nodal lymphoma

Extra nodal lymphoma refers to a type of mostly cutaneous lymphoma which can be

epitheliotropic or non-epitheliotropic. It is present as solitary, raised, ulcerative nodules or

generalized, diffuse, scaly lesions on the skin. The peripheral lymph nodes and mucocutaneous

junctions are frequently involved, as well as potentially the lungs, kidneys, eyes, central nervous

system, and bone. Depending on the organs and tissues involved, the clinical presentation may differ

between animals, which makes thorough diagnosis more complex and difficult to achieve.

Involvement of the lungs can lead to respiratory distress; involvement of the kidneys might show as

different degrees of renal failure. Animals whose eyes are affected could suffer from impaired vision

or blindness, those with central nervous system lesions might show symptoms as bad as seizures. If

the bones are involved in extra nodal lymphoma, there is a potential for skeletal pain and pathologic

fractures (10; 19).

1.2.5. Indolent lymphoma

A slowly progressive and often asymptomatic type of lymphoma which is not included in the

classification according to anatomical forms is the so-called low grade or indolent lymphoma.

Occurring in connection with follicular lymphoid hyperplasia, it is a molecular variant of Canine

lymphoma and makes up for around 30% of lymphoma diagnoses in dogs (20). Four histopathological

subtypes can be differentiated: Marginal zone lymphoma (mostly involving lymph nodes and spleen),

follicular lymphoma (involving only the lymph nodes), mantle cell lymphoma (occurring as solitary

splenic masses), all three derived from the B – lymphocytes. T – zone lymphomas are the only group

that derive from T – lymphocytes (10; 20). Indolent lymphoma is often not recognized as a disease

as such due to the low grade of tissue invasion and the lack of clinical signs and suffering in many

patients (20).

1.3. Lesions caused by lymphoma

Histopathologic lesions occurring due to lymphoma can differ between the anatomical types of

the disease but can generally be described as a swelling of the peripheral and internal lymph nodes to

three to ten times their normal size. This is especially significant in the multicentric form of

13

lymphoma. Lymph nodes that show signs of lymphadenopathy are however usually non – painful on

palpation, freely movable and firm. Their color – if extracted for pathohistological analysis – is grey-

tan and they swell up locally if cut but show no change in cortical-medullary composition. Frequently,

hepatosplenomegaly can be found. It occurs either as a diffuse organ enlargement or multiple pale

nodules that can differ in size and are spread throughout the parenchyma of the liver and spleen. The

alimentary form of lymphoma may affect any part of the gastrointestinal tract or the mesenteric lymph

nodes. Involvement of the bone marrow, central nervous system, kidneys, heart, tonsils, pancreas,

and the eyes can be found, but it is less common than other lesions mentioned above (10; 21).

1.4. Diagnostic methods

Lymphoma in dogs and cats can be diagnosed by cytologic or histopathologic evaluation of the

affected organ or system (17). To be able to obtain a tissue sample suitable for these methods,

ultrasound guided FNA can be performed. In cytology, a monomorphic population of either large,

intermediate, or small lymphoid cells becomes evident in case of a lymphoma diagnosis. Cytologic

examination of tissue samples as a diagnostic tool for lymphoma is limited regarding differentiation

and categorization of the heterogenous spectrum of lymphomas. This concerns the morphologic

subtype of the neoplasm. It could be diffuse or follicular and cleaved or non-cleaved, both of which

categories cannot be determined in cytology. It is also not possible to categorize the lymphoma

regarding the histologic grade, which might be high or low. The gold standard of lymphoma diagnosis

is currently the histopathologic analysis of tissue samples. This method provides additional

pathologic information to help classify the lymphoma and make important therapeutic decisions (10;

17). Especially the classification is crucial to ensure a good quality therapy and the right choice of

medication and action.

Other special diagnostic methods for lymphoma include immunophenotyping by flow

cytometry for specific cell surface markers. Those markers are the so-called CD antigens, cluster of

differentiation antigens. Moreover, PARR can be used as a diagnostic tool to show the difference

between lymphocyte expansion and inflammation. Expansion is a consequence of cancer while

inflammation is just a reactive or hyperplastic lymphocytosis. PARR is thus a means of distinguishing

neoplasm from other lymphadenopathies. However, these methods are barely used in practice and

remain in use for laboratory diagnostics without reference to actual cases (10; 22).

14

1.5. Ultrasonography in the diagnosis of lymphoma

The organs and tissues that are potentially affected by lymphoma can be evaluated with the

help of ultrasound as a diagnostic tool for the determination of involvement of an organ and the

damage done to it (23). The lymph nodes, spleen, and liver in particular show changes that can be

seen in ultrasound when lymphoma is present (24). It can also be used as a biopsy guidance for

internal masses and is therefore vital for the use of further diagnostic methods. Thus, ultrasound is an

important tool in the process of visualizing, diagnosing, and classifying lymphoma in dogs and cats

(23).

1.5.1. Ultrasonographic imaging

Ultrasonography is a non-invasive imaging method that uses ultrasonic sound waves to create

a live image of tissues and structures by visualizing the pattern of echoes that are reflected when

meeting different textures (25). Therefore, ultrasound enables the recognition and analysis of changes

within the shape, size, density, or elasticity of structures (23). Ultrasonic waves can have a frequency

range of 1.5-15 MHz (megahertz) and can be displayed in several types of formats. The most common

one is the B-mode grayscale scanning where transmission gel is used to create contact between the

animal body and the transducer that creates the ultrasonic sound waves. Due to the change in velocity

of the sound beam when traveling through different tissue densities, an echo occurs and is received

by the transducer, converted back into electrical impulses, and then shows as a real-time black and

white image on the screen that is an actual reflection of what the pictured surfaces would look like if

anatomically cut. Bones and air absorb the sound beams while soft tissues reflect them. Therefore,

not all body structures can be adequately expressed in ultrasound. Depth of tissue is an additional

limitation to ultrasonographic imaging as the echoes will be reflected many times over on their way

back to the transducer if the body cavity is too deep. Using a low-frequency transducer can increase

image depth but will reduce image quality and increase noise. Higher frequency transducers have a

shorter reach but show better quality images (25).

Ultrasonographic imaging can be used to assess organs and tissues such as muscles, tendons,

ligaments, the heart, and abdominal organs. Following an evaluation pattern can be useful to uphold

a specific order of the organs especially in the abdominal cavity, to guarantee that none are forgotten

and to create reproducibility of results and the possibility to compare them. A good knowledge of the

anatomy and the normal appearance of the organs that are being examined are essential to a successful

15

use of ultrasound. Some organs may be compared to others to detect uniform changes in their

echogenicity that would remain unseen without reference (25).

For preparation of an ultrasound examination, the animal should be fasted if possible and have

the abdomen shaved to avoid air being trapped in the fur and disturbing image quality. Adequate

fixation of the animal is crucial to performing a thorough examination of the organs. Animals can be

placed in special restriction pads to maintain their dorsal positioning throughout the examination or

can be fixated in lateral recumbency. It may be necessary to change the position of the animal and

the probes that are being used several times during a sitting. Since ultrasound is a pain-free and non-

invasive diagnostic method, it can usually be done without sedation if the animal is cooperative (26).

1.5.2. Ultrasound of the urinary and genital system and the adrenal glands

Generally, the urinary bladder is one of the organs that can easily be found because of its

position, size, and echogenicity, so it can be helpful to start evaluating the abdominal organs here. It

should be viewed in sagittal and transverse planes to look for any masses, thickening or other

abnormalities in the wall or in the contents of the bladder. In the same view, the prostate should be

observed in male animals as well as the uterus in unspayed females.

Moving the ultrasound probe along the left abdomen towards cranial, the left kidney is located.

The right kidney is more difficult to visualize. It can be found on the right dorsal aspect of the animal

but is often hidden behind intestines or under the rib cage. It can be especially hard to identify in

large, deep chested dogs. Both kidneys should have a homogenous cortex, anechoic medulla and a

clearly defined corticomedullary junction. Ultrasonographic abnormalities that can be found in the

kidneys if they have been affected by lymphoma are renomegaly, parenchymal lesions, pyelectasis,

loss of corticomedullary junction, nodules, masses and other lesions (27). However, these changes

can be primary or secondary pathologies and might as well be related to other diseases than lymphoma

alone. The normal size of the kidneys in cats is 30-43mm in diameter, in dogs the size varies according

to the breed and thus the size of the dog (28).

When examining a kidney, the same sided adrenal gland should be evaluated too. Changes in

the adrenal glands are often related to metabolic diseases and are not significant for the diagnosis of

lymphoma. The most common adrenal gland pathologies are hyperadrenocorticism,

hypoadrenocorticism and adrenal neoplasia that is not lymphoma (26).

16

1.5.3. Ultrasound of the spleen

Moving along the left abdomen cranially, the spleen can be found. The Canine and Feline spleen

is susceptible to a variety of pathologies and can be a meaningful sonographic indicator for different

diseases, including several types and stages of lymphoma (26). Signs of lymphoma that could be seen

in splenic ultrasound are abnormalities such as hypoechoic and anechoic nodules, diffuse

hypoechogenicity or hyperechogenicity (29). Mixed echotexture, complex masses, discrete nodules

and target lesions or a view that is typically called a “swiss cheese pattern”, meaning that the organ

appears “moth eaten” or diffusely perforated, are more specific ultrasonographic images for a spleen

affected by lymphoma. However, the spleen might appear normal in ultrasound even if

histopathological examination will show that it is indeed affected by lymphoma (24). The area mostly

affected by splenic lymphoma is the head of the spleen, which can be hard to see in deep chested

dogs. Therefore, ultrasound can help to positively identify a spleen affected by lymphoma if it shows

classical patterns, but not to exclude the possibility of lymphoma overall.

1.5.4. Ultrasound of the liver and gallbladder

The liver is a valuable ultrasonographic indicator for many diseases. It is situated in the cranial

part of the abdominal cavity, just caudal to the ribs or – in some animals – underneath the ribs. Its

position and location is dependent on the size and breed of the animal. For example, large, deep

chested dogs usually present a greater challenge due to the liver falling dorasally when they are

positioned on their backs (26).

Ultrasonographic findings in the liver that could show in cases of lymphoma are hepatomegaly,

altered hepatic echotexture, heterogenous parenchyma and parenchymal lesions. More specifically,

target lesions or alteration in liver texture would indicate a positive lymphoma diagnosis (30).

The gall bladder should be evaluated during hepatic ultrasound due to its attachment to the

liver. The wall of the gall bladder should not be visible in a healthy animal and the contents should

be anechoic and homogenous. If there are problems with the liver or the digestive tract, the gall

bladder might appear with changes in the layering of the wall, thickening of the wall, sludge, or

stones. These findings are non-specific and could be primary or secondary (31).

1.5.5. Ultrasound of the gastrointestinal tract and pancreas

The ultrasonographic changes in the gastrointestinal tract that are caused by lymphoma are

highly variable, depending on its type and organ involvement. Generally, the wall thickness and

17

thickening, wall layering, and echogenicity should be assessed in addition to obvious gastric or

intestinal obstruction (32). In the small intestines, all four histologic layers should be visible. Serosa,

muscularis, submucosa and mucosa can be seen and differentiated in ultrasound of a healthy intestine

(26). In case of neoplasia, the layering might become blurry or invisible entirely. The regional lymph

nodes are examined. They should not be enlarged, deformed, or show changes in echogenicity or

structure (32).

Ultrasound is the method of choice for the assessment of the pancreas and especially helpful in

pancreatic tumor detection. Besides neoplasms, pancreatitis, nodular hyperplasia, cysts, oedema, and

abscesses are common ultrasonographic findings when visualizing the pancreas (33).

1.5.6. Ultrasound of the lymph nodes

Due to the fact that generalized and peripheral lymphadenopathy can be a possible sign for

many different processes in the body apart from neoplasm, the ultrasound examination of the lymph

nodes is a good indicator especially for multicentric lymphoma, but not a means of definite diagnosis

(10). While superficial lymph nodes can be examined by palpation as well, the deeper lymph nodes

can only be evaluated with the help of ultrasound unless the animal is under anesthesia. Thus,

ultrasound is an important tool for creating an impression of the lymph nodes and leading to a more

accurate list of differential diagnoses (34).

The most consistently visualized abdominal lymph nodes are the medial iliac lymph nodes and

they should present with a homogenous texture (26). The shape, echogenicity, hilar tissue definition

and contour should also be evaluated as well as the perinodal fat which could have a changed

echogenicity and therefore indicate pathologies (35).

1.6. Possible treatment methods of lymphoma

Treatment of lymphoma depends on many factors, including the age and general condition of

the animal, stage and grade of the disease and the organs and tissues involved. The prognosis for

lymphoma patients is always guarded, though there are cases that receive complete reduction of tumor

burden with certain types of lymphoma (10).

There are multi-agent chemotherapy protocols for aggressive, high grade multicentric Canine

lymphoma that can lead to more than 90% of the dogs receiving complete healing. These protocols

commonly comprise the use of Vincristine, Doxorubicin, Cyclophosphamide, L-asparaginase and

Prednisone. If the patient fails to respond to treatment or relapses, certain rescue protocols are used

18

to improve their response. Rescue protocols may consist of Lomustine, MOPP and DMAC. It is also

commonly advised to follow the Madison Wisconsin protocol for multicentric lymphoma (10).

Despite all efforts, the expected lifetime of dogs with B-cell multicentric lymphoma is only

about 12 months with adequate treatment and sufficient response. The life expectancy for dogs with

T-cell lymphoma is limited to only about 6 months or less (10).

Alimentary Canine lymphoma often requires resection and chemotherapy if it is of the focal

type. Nevertheless, animals often survive only about 3 months due to the high grade of

gastrointestinal involvement, their low constitutional reserves, nutrient malabsorption, and protein

loss (10).

Cases of mediastinal lymphoma have shown good survival times and quality of life with

chemotherapy occasionally combined with palliative radiation therapy.

Single-agent systemic Lomustine or a combination of systemic chemotherapies (for example

the CHOP protocol) can be used to treat extra nodal lymphoma.

Low-grade indolent lymphoma is usually treated with low intensity oral chemotherapy

protocols that lead to a good clinical prognosis and a survival time of potentially more than two years.

Chemotherapy protocols can include chlorambucil and prednisone. If there is a low grade of organ

specific involvement (commonly regarding the spleen), removal of that organ without the use of

chemotherapeutic drugs is recommended (10).

For cats, treatment protocols can differ because of the high prevalence of FeLV diagnosed cats

with lymphoma. Cats are commonly treated with cytotoxic drugs, but the prognosis heavily depends

on the FeLV test results (15).

About 50% of cats with lymphoma given cytotoxic medication obtain complete remission.

Those tested negative for FeLV have a life expectancy of 9 months while those tested positive for

FeLV have a life expectancy of only 6 months. With no treatment whatsoever, all cats can live

between two and six weeks from the moment of diagnosis, regardless of their FeLV test (15).

19

2. MATERIALS AND METHODS

2.1. Object of the research

The study was conducted on 31 dogs and cats that were presented to the L. Kriaučeliūnas

Small Animal Clinic of the Veterinary Faculty of LSMU Kaunas between July 2015 and May

2021. Data of the cases were extracted from the university small animal clinic’s patient

documentation system during May and June of 2021. Three of the cases were seen in-person by the

author of the thesis, the other cases were analyzed based on the information obtained from the written

documentation of the veterinary doctors in the clinic. Sixty-one (61) cases from 2015-2021 were

reviewed, but only 31 cases met the criteria to be included in the study. Criteria for the inclusion of

the study were a lymphoma diagnosis, suspected (probable) lymphoma or clinical signs and

symptoms characteristic for lymphoma, even without diagnosis. In some cases, the animals died or

were euthanized before a diagnosis could be made. These cases were included in the “suspected

lymphoma” group. The focus of the study was on the comparison of diagnostic tools and their relation

to the diagnosis of the cases. The treatment of the patients was not an object of the research.

The aim of the work was to establish the meaning of ultrasound examination in the diagnosis

of Canine and Feline lymphoma. This was planned to be achieved by determining the efficiency of

ultrasound examination of lymphoma patients, analyzing the blood results of dogs and cats with

suspected lymphoma and ultimately, comparing the results to the cytology and histopathology

examination results. Therefore, a relation between ultrasonographic views and diagnosis should be

created with the help of statistical analysis of the data.

Fig.1 Research scheme

2.2. Study design

The group of animals tested consisted of 22 dogs and 9 cats, adding up to 31 animals in total.

The owners of the animals were questioned for a thorough anamnesis and the animals were clinically

examined by a veterinary doctor. Scientific research has been conducted in observation of the

Data extraction from the clinic

documentation system

Review of 61 cases, choosing 31 cases

Grouping of data in Excel

Collection of literature and visual material about ultrasound of

lymphoma

Statistical analysis of the data (SPSS) in

relation to the theoretical material

20

requirements for animal care, keeping, usage and veterinary requirements. Blood samples were taken

from the animals and processed for morphological and biochemical examination.

Ultrasound was done on the animals with the three ultrasound machines available in the small

animal clinic, the Mindray DP-7, the Philips Affinity 70, and the Mindray DC-70. All the ultrasound

pictures presented in this thesis were taken with the Mindray DC-70 by veterinarians in the small

animal clinic.

Organs evaluated in ultrasound included the urinary bladder, spleen, kidneys, liver and gall

bladder, stomach and intestines, the lymph nodes and in some cases the pancreas and adrenal glands.

Since the amount of data about the ultrasound of the pancreas and adrenal glands was so small, these

organs were excluded from the analysis. The ultrasound of the urinary bladder and the gastrointestinal

tract brought up no relevant information, so this data was also neglected and not included in the

description of the results, although they were quantitatively and qualitatively analyzed and mentioned

in the literature as relevant information.

Fig.2 left: An ultrasound picture of the right kidney taken with the convex probe of the Mindray DC-

70; right: An ultrasound picture of the same kidney taken with the linear probe of the Mindray DC-

70

Fig.3 A picture taken with the Doppler in use on the convex probe of the Mindray DC-70

21

In some cases, FNA samples were taken from the animals for cytology. Other cases had

biopsies taken for histopathology. Not all the analyzed diagnostic tools were used on all animals,

which was according to the individual decisions of the patient owners and the veterinary doctors

working on the cases.

2.3. Data processing

For data processing, Excel and SPSS were used. All the information was collected in the form

of text and transferred as number format to Excel. Blood samples were entered as the numbers that

they were while ultrasound protocols and cytology and histopathology samples had to be transferred

into yes-and-no-questions with numerals as answers to be able to process the data in SPSS.

Animals were grouped according to their species, gender, and breed. However, with a small

sample size, many of the ultrasound protocols were analyzed for all animals as a collective. Blood

parameter norms differ between the species, but for the ultrasound examination, this was a small bias.

If an examination had been done on an animal, but parameters were missing from the protocol,

it was assumed that the missing parameters were normal. For missing blood parameters, the mean

value of the normal range was entered and for missing ultrasound –, cytology or histopathology

examinations, the value for “normal” was entered.

To statistically analyze the data, SPSS was used to create frequencies, crosstabs, binomial

distributions, correlations between values and to evaluate the significance of the calculations. Graphs

were created with SPSS and Excel.

X-ray pictures, treatment methods and other medications or anamneses not related to the current

presentation at the clinic as well as previous diseases of the patients were neglected during the

analysis of the data. Pulmonary ultrasound was done on none of the patients and was therefore

excluded from the list of tasks for this thesis.

22

3. RESULTS

The anamnesis, clinical examinations, blood samples, ultrasound examinations and cytology

and histopathology samples of cats and dogs were evaluated for the presence or absence of signs of

lymphoma over a six-year time period between 2017 and 2021. The study population consisted of 31

animals.

Diagnosis of lymphoma was defined as the certain knowledge that an animal suffered from

lymphoma. Suspected lymphoma was defined as a high probability for lymphoma, but no

confirmation of the diagnosis, either because the animal was euthanized before or because it did not

return to the clinic for various reasons.

3.1. Population analysis

Of the dogs, (n = 22), 9 were male and 13 were female. 17 dogs were purebred, 5 dogs were

mixed breeds. 15 of the dogs turned out to suffer from lymphoma at the end of their diagnostics, 7

had suspected lymphoma and none of the dogs ended up healthy (without lymphoma).

Of the cats (n = 9), 2 were male and 7 were female. 3 cats were purebred, 6 were mixed breeds.

6 of the cats were diagnosed with lymphoma, 2 were suspected to have lymphoma and 1 turned out

to have no lymphoma.

Fig.4 Lymphoma diagnoses in the study population

The relations between the lymphoma diagnosis and gender and breed were analysed in both

study populations. In the dog population (n = 22), there was no statistical relation between the gender

of the animals and the diagnosis. Females had more lymphoma (n = 9) and suspected lymphoma (n

Lymphoma68%

No lymphoma3%

Suspected lymphoma

29%

23

= 4) diagnoses than males (n = 6 for lymphoma and n = 3 for suspected lymphoma), but the total

number of females in the population is also considerably higher (n = 13) than the number of males (n

= 9). This could be shown in crosstabs in SPSS.

The same was shown in the crosstabs for the relation between breed and diagnosis in the Canine

group. More purebred dogs were diagnosed with lymphoma or suspected to have lymphoma than

mixed breed dogs, but the number of purebred dogs in the study population was also significantly

higher (n = 17) than the number of mixed breeds (n = 5).

The partial correlations between gender, breed and diagnosis are statistically significant with a

one-sided significance of p<0,05, but they are negative correlations.

Since the Feline population consists of a very small number of animals (n = 9), the correlations

between gender and diagnosis or breed and diagnosis were not statistically significant. The animal

that turned out to have no lymphoma, was a female mixed breed cat. Males had only suspected

lymphoma (n = 2), while females had no lymphoma (n = 1) or lymphoma (n = 6). Purebred cats had

lymphoma (n = 1) or suspected lymphoma (n = 2), mixed breeds had no lymphoma (n = 1) or

lymphoma (n = 5).

24 animals (77,4%) received ultrasound, but not for all 24 animals every organ in the abdominal

cavity was viewed. 7 animals (22,6%) received no ultrasound.

3.2. Anamnesis and clinical signs

Animals in the study commonly presented with inappetence, lethargy, unknown masses or

swelling in various sites and gastrointestinal signs such as vomiting or diarrhoea. One animal suffered

from melena when presented to the clinic. General signs such as bad skin and fur or extreme weight

loss were also commonly seen. Neurological pathologies could be seen in one case, including head

tilt, tetraparesis, lateral recumbency, no reaction to light, slow withdrawal reflexes in all four limbs,

hyperreflexes in the patella, tibia, and extensor carpi radialis and respiratory distress. Some animals

were presented in such bad condition that they died.

3.3. Blood testing

Twenty-one (21) animals had blood samples taken and analysed, 6 of which were cats and 15

were dogs. When values were missing or recorded to be “normal” without any parameters, the median

of the normal range was entered for these values. The groups were divided in dogs and cats and

animals with lymphoma and suspected lymphoma.

24

3.3.1. Blood morphology

In the dog-group with lymphoma diagnosis, it was particularly outstanding how many animals

presented with abnormalities in the red blood cells (mostly anaemia). Changes in the white blood

cells were also evident and, in many cases, the lymphocytes and neutrophiles were elevated. Animals

with anaemia often did not show reticulocytosis.

Blood morphology Blood values

(Canine)

Number of cases

(Canine)

Blood values

(Feline)

Number of cases

(Feline)

RBCs x10^12/L

<4,95 5 <5,0 1

4,95-7,87 (norm) 5 5,0-7,06 (norm) 1

>7,87 1 >7,06 2

WBCs x10^9/L

<5,0 1 <5,5 0

5,0-14,10 (norm) 3 5,5-19,50 (norm) 2

>14,10 6 >19,50 2

Lymphocytes x10^9/L <2,90 (norm) 6 <7,0 (norm) 2

>2,90 5 >7,0 2

Neutrophiles x10^9/L

<2,90 1 <2,5 0

2,90-12,0 (norm) 6 2,5-12,5 (norm) 3

>12,0 4 >12,5 1

Table 1. An overview of the blood morphology values with the most changes in the study

Fig.5 Red blood cells (p > 0,05) and White blood cells (p > 0,05) in dogs with lymphoma

The normal range of the red blood cells for dogs is 4,95-7,78x10^12/L, the normal range of the white blood cells for dogs

is 5,0-14,10x10^9/L.

25

Fig.6 Elevated lymphocytes (p > 0,05) and neutrophiles (p > 0,05) in dogs with lymphoma

The normal range of the lymphocytes for dogs is 0,40-2,90x10^9/L, the normal range of the neutrophiles for dogs is 2,9-

12,9x10^9/L.

In the group of cats with lymphoma, the blood tests showed changes in the same parameters,

but they shifted differently than the parameters in the dog group. The cat group of cats with lymphoma

consisted of only 4 animals and was thus considerably smaller than the group of dogs with lymphoma

(n = 11).

3.3.2. Blood biochemistry

While analyzing the biochemistry blood values, it became evident that the most commonly

abnormal values concern the liver, particularly in dogs. Kidney values were more clearly changed in

the cat group with lymphoma than the dog group with lymphoma. Glucose was particularly low in

the dogs with lymphoma, while total protein was elevated in 7 of the 11 Canine cases. The cases of

cats with suspected lymphoma and no lymphoma were neglected in this comparison, because there

was only 1 case for each category and the sample size was thus too small.

26

Blood biochemistry Blood values

(Canine

Number of cases

(Canine)

Blood values

(Feline)

Number of cases

(Feline)

ALP U/L

<1,0 0

1,0-114,9 (norm) 3

>114,9 8

ALT U/L

<10,0 0

10,0-109,0

(norm) 7

>109,0 4

BUN mmol urea/L

<4,20 1 <3,3 0

4,20-6,60 (norm) 7 3,3-6,70 (norm) 2

>6,60 3 >6,70 2

Creatinine 𝜇mol/L

<2,90 2 <6,8 0

2,90-10,0 (norm) 2 6,8-12,1 (norm) 1

>10,0 7 >12,1 3

Glucose mmol/L

<54,0 6

54,0-75,0 (norm) 3

>75,0 2

Total protein g/L

<27,0 1

27,0-44,0 (norm) 3

>44,0 7

Table 2. An overview of the blood biochemistry values with the most changes in the study

BUN was elevated in 50% and creatinine in 75% of the cats with lymphoma. Both values were

also increased in the dog group with lymphoma, but also decreased in some cases.

Glucose and total protein values were altered in 50% of the cats with lymphoma. Dogs with

lymphoma displayed a drop in glucose in 54% of the cases and a rise in total protein in 63% of the

cases.

Fig.7 Glucose (p > 0,05) and total protein (p > 0,05) values in dogs with lymphoma

The normal range of glucose in dogs is 54,0-75,0mmol/L, the normal range of total protein in dogs is 27,0-44,0g/L.

27

3.4. Ultrasound

The ultrasound results were analysed with crosstabs and correlation statistics to show how they

were related to the diagnosis of lymphoma. The relations between ultrasound findings and species of

the animals were also determined to see if there would be a prevalence of Canines or Felines for

certain ultrasound results.

3.4.1. Ultrasound of the urinary tract

Of the 31 animals that were included in the study, 24 received ultrasound of the urinary tract.

Out of those, 18 were Canine and 6 were Feline.

The left kidney size was measured in 7 of the 24 animals. Renomegaly of the left kidney could

be seen in 2 dogs and 1 cat. The mean left kidney size of all the measures was 4,45x3,12cm. Three

animals with lymphoma or suspected lymphoma also showed signs of left renomegaly in ultrasound.

21 animals did not have renomegaly, 20 of which had a lymphoma diagnosis or suspected lymphoma.

Fig.8 Left sided renomegaly in relation to lymphoma diagnosis

Renomegaly of the right kidney could be seen in 1 dog and 1 cat. The size of the right kidney

was measured in 7 animals and was 6,62x3,53 cm on average. 2 of the animals with right sided

renomegaly had lymphoma, none were suspected to have lymphoma and none had no lymphoma. 14

of the animals with no renomegaly had lymphoma, 7 were suspected to have lymphoma and the

animal that had no lymphoma also had no right sided renomegaly.

1

13

7

3

0 2 4 6 8 10 12 14

No lymphoma

Lymphoma

Suspected lymphoma

Number of cases

Dia

gnosi

s

Left sided renomegaly

Yes No

28

Fig.9 Right sided renomegaly in relation to lymphoma diagnosis

The relation between animals with homogenous left kidney parenchyma and heterogenous left

kidney parenchyma was the same in both species’ groups. Out of 18 dogs, 15 showed kidneys with

homogenous parenchyma and 3 had heterogenous parenchyma in their left kidney. There were 5 cats

with homogenous – and 1 cat with heterogenous left kidney parenchyma.

Left kidney parenchymal

homogeneity Homogenous Heterogenous Total

Species Canine 15 3 18

Feline 5 1 6

Total 20 4 24

Table 3. The homogeneity of the left kidney parenchyma in relation to the animal species

The homogeneity of the left kidney parenchyma did not show a positive correlation to the

diagnosis of lymphoma. 19 animals had homogenous parenchyma, but lymphoma or suspected

lymphoma. 4 animals had lymphoma or suspected lymphoma and heterogenous parenchyma. The

animal without lymphoma had homogenous left kidney parenchyma in ultrasound.

1

14

7

2

0 2 4 6 8 10 12 14 16

No lymphoma

Lymphoma

Suspected lymphoma

Number of cases

Dia

gnosi

sRight sided renomegaly

Yes No

29

Left kidney parenchymal

homogeneity Homogenous Heterogenous Total

Diagnosis

No

lymphoma 1 0 1

Lymphoma 13 3 16

Suspected

lymphoma 6 1 7

Total 20 4 24

Table 4. The left kidney parenchyma homogeneity in relation to the diagnosis of lymphoma

The right kidney was homogenous in 16 dogs and 4 cats and heterogenous in 2 dogs and 2

cats. Thus, the left and right kidney did not show the same homogeneity of parenchyma in all animals.

The right kidney parenchyma homogeneity had no relation with the diagnosis of lymphoma. 4

animals with suspected lymphoma or lymphoma had a heterogenous right kidney parenchyma. Out

of the 20 animals with a homogenous parenchyma, 14 were diagnosed with lymphoma, 5 had

suspected lymphoma and 1 had no lymphoma.

Right kidney parenchymal

homogeneity Homogenous Heterogenous Total

Species Canine 16 2 18

Feline 4 2 6

Total 20 4 24

Table 5. The homogeneity of the right kidney parenchyma in relation to the animal species

Right kidney parenchymal

homogeneity Homogenous Heterogenous Total

Diagnosis

No

lymphoma 1 0 1

Lymphoma 14 2 16

Suspected

lymphoma 5 2 7

Total 20 4 24

Table 6. The homogeneity of the right kidney parenchyma in relation to the diagnosis of lymphoma

30

The left kidney’s cortical lesions differed between species. In the Canine group, there was 1

animal with anechoic lesions and 3 animals with hyperechoic lesions, while 14 animals had no

cortical left kidney lesions. 5 Felines had no cortical lesions, while one had hypoechoic lesions.

Fig.10 Left sided renal cortical lesions in relation with the animal species

In the right kidney, the anechoic (n = 1) and hyperechoic (n = 1) lesions were also prevalent in

the Canine group, while hypoechoic renal cortical lesions (n = 1) were only seen in the Felines.

Fig.11 Right sided renal cortical lesions in relation with the animal species

However, the cortical lesions of both Canines and Felines were not related to the diagnosis of

lymphoma. Left sided renal cortical lesions were absent in the animal without lymphoma (n = 1) and

of the animals that had lymphoma, only 4 had cortical lesions in the left kidney, whereas 12 had none.

Only one animal with suspected lymphoma had anechoic lesions in the left kidney, 6 animals had no

14

51 13

0

5

10

15

Canine Feline

Num

ber

of

case

s

Species

Left renal cortical lesions

None Anechoic Hypoechoic Hyperechoic

16

5

1 110

2

4

6

8

10

12

14

16

18

Canine Feline

Num

ber

of

case

s

Species

Right renal cortical lesions

None Anechoic Hypoechoic Hyperechoic

31

lesions. 14 animals with lymphoma had no right sided renal cortical lesions, 2 did. Out of the group

of animals with suspected lymphoma that received urinary tract ultrasound (n = 7), 6 had no lesions

and 1 did. The animal without lymphoma also had no right sided renal cortical lesions.

The loss of renal corticomedullary distinction in the left kidney could be shown in 33,3% of

the cats (n = 2), but only in 22,2% of dogs (n = 4). However, more animals had no loss of

corticomedullary junction in the left kidney. In the right kidney, loss corticomedullary distinction

could be observed in 27,8% of dogs (n = 5) and again, 33,3% of cats (n = 2). More animals had no

loss of corticomedullary junction as well in the Canine – as in the Feline group.

In relation to the diagnosis of lymphoma, the loss of corticomedullary junction in the left

kidney had no statistical relevance with a Pearson-R > 0,05 and a Spearman correlation > 0,05. The

values for loss of corticomedullary junction on the right side in relation to the diagnosis were more

relevant but did not reach statistically significant levels (Pearson-R > 0,05, Spearman correlation >

0,05). 5 animals with lymphoma and 1 animal with suspected lymphoma had loss of corticomedullary

junction on the left side, 6 animals with lymphoma and 1 animal with suspected lymphoma had loss

of corticomedullary junction on the right side, while 18 animals (left side) and 17 animals (right side)

did not even if all except for one were either diagnosed with lymphoma or suspected to have

lymphoma.

Fig.12 Left kidney of an eight-year-old female Maine Coon cat with immunoblastic large – and

medium cell lymphoma, April 29th, 2021

32

Fig.13 Right kidney of the same Maine Coon cat, April 29th, 2021

The cat suffers from bilateral renomegaly. The parenchyma in both kidneys is heterogenous and shows anechoic and

hypoechoic cortical lesions. There is total loss of corticomedullary junction on both sides.

3.4.2. Ultrasound of the liver and gall bladder

Out of the 31 animals in the study, 23 received ultrasound of the liver and gall bladder. There

were no correlations between the parameters measured in ultrasound of the liver and gall bladder and

the species of the animals.

The animal with no lymphoma had no hepatomegaly. Animals diagnosed with lymphoma (n =

15) had no hepatomegaly, except for one case. Those with suspected lymphoma showed 2 cases of

hepatomegaly. 5 had no hepatomegaly. Overall, only 13% (n = 3) animals had hepatomegaly in

ultrasound, which is statistically irrelevant with a Pearson-R > 0,05.

The liver was isoechoic compared to the right kidney cortex in 10 animals with lymphoma

and 6 animals with suspected lymphoma. It was also isoechoic in the case without lymphoma. Only

two lymphoma patients showed hypoechoic liver parenchyma and three had hyperechoic liver

parenchyma. One animal with suspected lymphoma also presented with hyperechoic liver

parenchyma in ultrasound.

33

Fig.14 The hepatic echotexture in relation to the diagnosis of lymphoma

The homogeneity of the liver parenchyma was homogenous in most of the cases (n = 18),

regardless of their diagnosis. The animal with no lymphoma had a homogenous liver parenchyma

and so did 10 animals with lymphoma and 7 animals with suspected lymphoma. Only 5 animals with

lymphoma also had heterogenous parenchyma of the liver in ultrasound.

Parenchymal hepatic lesions could be seen in 8 of the 15 animals with lymphoma, while 7

animals with lymphoma had no parenchymal lesions. The animal with no lymphoma had no lesions

either. Animals with suspected lymphoma had no lesions (n = 6) or only hypoechoic lesions (n = 1).

Lymphoma patients also displayed anechoic (n = 1) and hyperechoic lesions (n = 2) besides the

hypoechoic lesions (n = 5).

Fig.15 Hepatic parenchymal lesions in relation to the diagnosis of lymphoma

1

10

6

23

10

2

4

6

8

10

12

No lymphoma Lymphoma Suspected lymphoma

Num

ber

of

case

s

Diagnosis

Hepatic echotexture

Isoechoic Hypoechoic Hyperechoic

1

7

6

1

5

1

2

0

1

2

3

4

5

6

7

8

No lymphoma Lymphoma Suspected lymphoma

Num

ber

of

case

s

Diagnosis

Hepatic parenchymal lesions

None Anechoic Hypoechoic Hyperechoic

34

The layering of the gall bladder was normal in 19 of the patients, 1 of which had no lymphoma,

12 of which had lymphoma and 6 of which had suspected lymphoma. The wall was thickened in 1

case with suspected lymphoma, hyperechoic in 2 lymphoma cases and had lesions in 1 case of

lymphoma. The relation between gall bladder layering and diagnosis of lymphoma showed no

statistical significance (p > 0,05).

Gall bladder sludge or stones could be seen in 6 animals with lymphoma and 2 animals with

suspected lymphoma. 15 animals had no sludge or stones, 1 with no lymphoma, 9 with lymphoma

and 5 with suspected lymphoma. Although statistically irrelevant (p > 0,05) due to the small number

of cases, sludge and/or stones could only be seen in animals with lymphoma or suspected lymphoma.

3.4.3. Ultrasound of the spleen

22 animals received splenic ultrasound. Splenic changes in general were more prevalent in dogs

than in cats in the study (70,05% of dogs, 40% of cats that received splenic ultrasound).

The cat with no lymphoma also had no splenomegaly (n = 1). 7 of the animals with lymphoma

had splenomegaly in ultrasound, 7 did not. 4 animals with suspected lymphoma had no splenomegaly,

while 3 did. The Pearson-R for splenomegaly showed no statistical significance (p > 0,05).

Nevertheless, 50% of lymphoma cases also had splenomegaly.

Another splenic change that was analysed in the study was the echotexture of the splenic

parenchyma compared to the left renal cortex. The patient with no lymphoma had isoechoic splenic

parenchyma compared to the parenchyma of the left renal cortex. 14 lymphoma patients also had

isoechoic parenchyma of the spleen, none of them had hyperechoic or hypoechoic parenchyma. 6 of

the patients with suspected lymphoma had isoechoic splenic parenchyma, 1 had hyperechoic

parenchyma. The binomial distribution of isoechoic splenic parenchyma shows that p < 0,001.

Fig.16 The echotexture of the splenic parenchyma in relation to the diagnosis of lymphoma

1

14

61

0

5

10

15

No lymphoma Lymphoma Suspected lymphomaNum

ber

of

case

s

Diagnosis

Echotexture of the splenic parenchyma

Isoechoic Hyperechoic

35

The parenchyma of the spleen was homogenous in the animal with no lymphoma, in 4 of the

animals with lymphoma and in 3 of the animals with suspected lymphoma. 14 animals had a

heterogenous parenchyma, with 10 belonging to the group of lymphoma patients and 4 having the

suspicion of lymphoma. The lymphoma – and suspected lymphoma cases showed thus more incidents

of heterogenous splenic parenchyma than homogenous splenic parenchyma (71% of animals with

lymphoma had heterogenous parenchyma and 57,1% of animals with suspected lymphoma had

heterogenous splenic parenchyma).

Fig.17 Ultrasound pictures of the spleen of a six-year-old male Labrador Retriever with diagnosed

B-cell lymphoma, May 20th, 2021

The splenic parenchyma is heterogenous with small hyperechoic and anechoic irregularities.

Fig.18 The homogeneity of the splenic parenchyma in relation to the diagnosis of lymphoma

1

43

10

4

0

2

4

6

8

10

12

No lymphoma Lymphoma Suspected lymphoma

Num

ber

of

case

s

Diagnosis

Splenic parenchyma homogeneity

Homogenous Heterogenous

36

Discrete nodules in the spleen could be found in 5 out of 22 animals, all of which had

lymphoma (n = 14) or suspected lymphoma (n = 7). The animal with no lymphoma had no discrete

splenic parenchymal nodules. One of the lymphoma patients had anechoic nodules in the splenic

parenchyma, one had hypoechoic nodules and one had hyperechoic nodules. The rest had no discrete

nodules (n = 11). Of the animals with suspected lymphoma, 2 had hypoechoic discrete nodules and

five animals had no nodules in the splenic parenchyma.

Target lesions could be ultrasonographically visualised in 5 animals with lymphoma and 2

animals with suspected lymphoma. One animal without target lesions had no lymphoma, 9 had

lymphoma and 5 had suspected lymphoma.

The so-called “swiss cheese pattern” could only be seen in five animals out of the 22 that

received splenic ultrasound. 17 animals had no evidence of “swiss cheese pattern”, 1 of which had

no lymphoma, 9 of which had lymphoma and 7 of which had suspected lymphoma. All animals with

a “swiss cheese pattern” had thus lymphoma, but not all animals with lymphoma also displayed the

“swiss cheese pattern”. According to the Spearman correlation, “swiss cheese pattern” and the

diagnosis of lymphoma are negatively correlated (correlation-coefficient = -0,304) with a one-sided

significance of p > 0,05.

3.4.4. Ultrasound of the lymph nodes

13 animals received ultrasound of the lymph nodes. 11 animals were Canine and 2 animals

were Feline. Abnormalities in lymph nodes were counted, no matter which lymph nodes they were

found in. it could be one lymph node or multiple lymph nodes.

The animal with no lymphoma had normal sized lymph nodes. 2 animals with lymphoma had

normal sized lymph nodes, 9 had lymph nodes that were increased in size. One animal with suspected

lymphoma had increased lymph nodes, too. The Pearson-correlation between the size of the lymph

nodes and the diagnosis was statistically insignificant, where p = 0,054 (one-sided).

The animal with no lymphoma had rounded lymph nodes and was ultimately diagnosed with

an inflammatory lymphadenopathy with the help of histopathological analysis of the abnormal lymph

nodes (it is unknown which lymph nodes). No other animal in the lymph node ultrasound group (n =

13) had rounded lymph nodes. 10 of the lymphoma cases had normal lymph nodes, only one showed

elongated lymph nodes in ultrasound examination. The only suspected lymphoma case in the group

of animals that received ultrasound of the lymph nodes had normal lymph nodes.

The echogenicity of the lymph nodes was changed in all three groups of animals. The animal

without lymphoma had hypoechoic lymph nodes, 6 animals with lymphoma had isoechoic lymph

37

nodes, four had hypoechoic lymph nodes and 1 showed hyperechoic lymph nodes. One suspected

lymphoma case had isoechoic lymph nodes.

The animal without lymphoma also had homogenous lymph nodes. Out of the 11 lymphoma

cases, 6 had homogenous lymph nodes and 5 had heterogenous lymph nodes. The animal with

suspected lymphoma had a heterogenous lymph node as well. The Pearson-correlation between the

homogeneity of the lymph nodes and the diagnosis was statistically insignificant with a one-sided p

= 0,092.

Fig.19 The homogeneity of the lymph nodes in relation to the diagnosis of lymphoma (p > 0,05)

All the 13 cases showed normal hilar tissue definition in ultrasound. The contour of the lymph

nodes was ill defined in one animal with lymphoma and one animal with suspected lymphoma but

was well defined in the rest of the group (n = 11).

The perinodal fat was hyperechoic only in case of the animal with no lymphoma which had

inflammatory lymphadenopathy. All lymphoma and suspected lymphoma cases had normal perinodal

fat in ultrasound (n = 12).

Fig.20 Classical lymphoma view of two different lymph nodes in a six-year-old male Labrador

Retriever, May 20th, 2021

1

6

5

10

1

2

3

4

5

6

7

No lymphoma Lymphoma Suspected lymphoma

Num

ber

of

case

s

Diagnosis

Lymph node homogeneity

Homogenous Heterogenous

38

Left: The lymph node is hypoechoic compared to the surroundings and highly heterogenous with large hypoechoic

cavities.

Right: The surrounding fat is hyperechoic; the lymph node is hypoechoic and heterogenous.

Fig.21 A highly enlarged lymph node at the aortic trifurcation of the same Canine, May 20th, 2021

3.5. Other diagnostic methods of lymphoma

While ultrasound was done on 77,4% (n = 24) of the cases, 74,2% (n = 23) of animals received

FNA, 9,7% (n = 3) received a histopathological examination and in 64,5% (n = 20) of the cases,

cytology was used to determine the diagnosis. Out of all the cases (n = 31), 3,2% (n = 1) had no

lymphoma, 67,7% (n = 21) had lymphoma and 29% (n = 9) were suspected to have lymphoma.

For the analysis of diagnostic methods other than ultrasound, it was assumed that the cases

with no information about the cytology and histopathology did not receive any.

Fig.22 The percentage of diagnostic tools used in the study population

Diagnosis only with

ultrasound19,3%

Diagnosis with

multiple tools 58,1%

Diagnosis without

ultrasound22,6%

39

17 animals received both ultrasound and had an FNA sample taken. Two of the 17 also received

histopathology, but both were cases where FNA and cytology was also done. One patient received

FNA without cytology but was diagnosed with histopathology. This patient also received ultrasound.

One patient had ultrasound and FNA done, but neither cytology nor histopathology. 6 out of 31 cases

required only ultrasound and neither cytology nor histopathology to be diagnosed. 4 were diagnosed

with lymphoma and two were suspected to have lymphoma.

Ultrasound was enough as an only diagnostic tool in 19,3% of the cases. In 22,6% of the cases,

diagnosis was made entirely without the help of ultrasound. A combination of diagnostic tools was

used in most cases (58,1%).

3.6. Main ultrasonographic findings and outcome of the cases

In animals with lymphoma or suspected lymphoma (n = 30), the ultrasonographic changes in

the urinary tract did not seem to be caused – or indicate any kind of lymphoma.

In hepatic ultrasound, the echotexture (p > 0,05), parenchymal lesions (p > 0,05) and sludge

or stones in the gall bladder (p > 0,05) occurred with an increased frequency in case of lymphoma.

The spleen showed ultrasonographic changes such as splenomegaly (p > 0,05) and changes in

echotexture (p > 0,05) and homogeneity (p > 0,05). The characteristic “swiss cheese pattern” (p >

0,05) could not be found as often as expected.

Patients with lymphoma or suspected lymphoma suffered from increased lymph node size (p

> 0,05), changes in the shape of the lymph nodes (p > 0,05) and changes in homogeneity of the lymph

nodes (p > 0,05) that could be pictured in ultrasound.

Other changes investigated in the study could not be found to occur more frequently or

indicate lymphoma.

51,6% of the patients either went to another clinic for treatment or did not come back for more

consultations, so the outcome of the cases remained unknown. 3,2% went into remission after being

treated with chemotherapy. 9,7% of the animals died during the study due to the lymphoma or the

treatment (died in anaesthesia, respiratory failure). 35% of the animals were euthanized.

40

Fig.23 Main ultrasonographic findings

Fig.24 Outcome of the cases

21

30

17

26 25

22 23 23

29

26

10

1

14

5 6

9 8 8

2

5

0

5

10

15

20

25

30

35

Within the norm Changed

35.50%

9.70%

3.20%

51.60%

0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00%

Euthanasia

Died due to lymphoma or treatment

Remission

Unknown

41

4. DISCUSSION OF THE RESULTS

In the study about the meaning of ultrasound in the diagnosis of lymphoma, the main

ultrasonographic features of lymphoma could be visualized in many of the cases that were analysed.

Ultrasound of the urinary tract did not reveal the same changes that are described by Angela J.

Taylor et al. (27). In fact, not many changes were found in the kidneys at all. This could be due to the

small sample size and because most of the cases were dogs, where kidney changes are not as common

in dogs as in cats (10).

The changes seen in hepatic ultrasound of lymphoma patients coincide with what is described

by Amanda C. Crabtree et al. (24) and Thomas G. Nyland (30). The main hepatic changes consisted

of parenchymal lesions and – most likely secondary to the hepatic problems – sludge and/or stones

in the gall bladder. Hepatomegaly was not one of the main changes characterizing the

ultrasonographic view of the liver, which was unexpected according to Thomas G. Nyland (30).

It could be shown in the study that splenic ultrasonographic changes agree with Amanda C.

Crabtree et al. (24). Changes in homogeneity and echogenicity are described V. Nerschbach et al.

(29) as features particular to splenic lymphoma that can be seen in ultrasound examination, which

coincides with the most commonly found splenic changes in the animals in this study. Other splenic

changes described by Amanda C. Crabtree et al. (24), particularly the “swiss cheese pattern”, also

called “moth eaten appearance” could not be found.

Ultrasound examination of the gastrointestinal tract was neglected in the results of this study,

because no characteristic or significant changes could be found. The reason for the lack of data here

could be the small sample size, but also insufficient documentation in the ultrasound protocols that

were viewed for the analysis. Thus, the results of the study regarding the gastrointestinal tract are not

congruent with M. Frances et al. (32) who states that changes in wall layering and thickness vary in

patients with lymphoma or with the article about pancreatic ultrasonography by Michelle L. Avante

et al. (33).

The most striking feature of lymphoma, the swollen peripheral and deep lymph nodes, were

unfortunately not examined in ultrasound sufficiently to make assumptions or conclusions about the

diagnostic value of these results. However, the findings that were made, coincided with Marie de

Swarte et al. (35) and Rochelle M. Salvei (34).

It can thus be concluded that the findings in this study generally meet the contemplations of the

author, but that the sample size was too small to reach significant statistical values and the

documentation of the cases was partly incomplete, so no relevant statements could be made.

42

The blood values showed that many dogs with lymphoma suffered from non-regenerative

anaemia and leukocytosis which was mainly due to elevated lymphocytes and neutrophiles. These

changes could be the cause for many animals presenting to the clinic with lethargy, inappetence and

weight loss. The cats showed changes in the same blood parameters, but more cats had elevated red

blood cells. Leukocytes were elevated mainly because of lymphocytosis, so it can be suggested that

lymphocytosis is a sign for lymphoma in the blood in both cats and dogs.

The blood biochemistry values are consistent with the ultrasonographic findings in the animals.

Elevated liver values could present as parenchymal lesions and gall bladder sludge or stones which

is what was predominantly found and has also been described by Amanda C. Crabtree et al. (24) and

Thomas G. Nyland (30). However, changes in ALP and ALT can be caused by other factors and are

not specific to certain ultrasonographic changes in the liver.

The changes found in the renal blood parameters of both dogs and cats do not correspond with

the ultrasound examinations, because the ultrasonographic findings in the urinary tract were not

conclusive in this study. However, they would agree with the kidney changes that can be expected in

lymphoma patients with kidney involvement according to Angela J. Taylor et al. (27), including

parenchymal lesions, renomegaly, nodules or lesions and changes in homogeneity of the renal cortical

parenchyma. With kidney changes like these, blood parameters could change as they did in some of

the cases in this study.

Interestingly, glucose and total protein values showed significant changes in the group of dogs

with lymphoma. The high total protein does not correspond with the prevalent anaemia. The

decreased glucose values could be related to other clinical signs that the dogs showed, such as

lethargy, inappetence and weight loss. David M. Vail et al. (36) found no such prevalence in their

study on changes of metabolism in Canine patients with lymphoma. It is however known that human

patients with lymphoma display a reduced tissue sensitivity to insulin and thus glucose intolerance

prior to extreme weight loss (36). Glucose intolerance could also be caused by other disorders that

could or could not be concurrent to lymphoma. Further investigations with focus on this question

would be required to investigate if the drop in blood glucose concentration in the dogs with lymphoma

in this study was due to the lymphoma. Since the pancreas was not visualised in ultrasound in most

of the patients at all, it is not possible to relate the glucose levels to an ultrasonographic view in this

case.

43

CONCLUSIONS

1. The efficiency of ultrasound in the diagnostic process of Canine and Feline lymphoma

was determined during the work. It could be manifested that ultrasound is an efficient tool

for visualizing the progress of lymphoma and for staging lymphoma and helps to classify

and stage lymphoma according to the organs affected by metastases and the severity of

their involvement.

2. The efficiency of pulmonary lymphoma is without a doubt high according to the literature.

In this study, it could not be evaluated, because none of the viewed cases received

pulmonary ultrasound.

3. The blood test results of dogs and cats with suspected lymphoma were analysed and

statistically expressed. It could be established that patients with lymphoma generally

present with characteristic changes in the blood. There were limits to the analysis of Feline

blood, because no FeLV testing or testing for other Feline diseases was done even though

outcomes might have played a role in the development of lymphoma. The focus of the

study was not on the blood analysis, but nevertheless changes in the blood could be related

to ultrasonographic changes in many cases.

4. The expressiveness of FNA for lymphoma diagnostics could be established. Ultrasound

guided FNA is an important, minimally invasive tool in lymphoma diagnosis and can help

to confirm or reject the diagnosis. Histopathological examination of biopsies is still

considered the gold standard of lymphoma diagnosis but could not be properly analysed

in this study due to the very small sample size.

5. There is a clear relation between ultrasonographic views and diagnosis. It was not

statistically significant at any point in this study, but various ultrasonographic changes can

be seen in certain types and stages of lymphoma. Ultrasound can display a characteristic

view of lymphoma, especially in the spleen and lymph nodes. However, a lymphoma

diagnosis cannot be made with one diagnostic tool alone and requires blood sampling and

cytology or histopathology examination to be confirmed eventually.

44

ACKNOWLEDGEMENTS

I would like to thank my supervisor, Ieva Šeibokaitė for her support and for always keeping

calm when I felt stressed. For being there when I least expected it and just taking on this dedication

without really knowing what she was in for. Thank you, I appreciate it so much.

To Brigita Zakarevičiūtė. First of all, for teaching me ultrasound in a way that makes me feel

confident about using it in the future. For being a mentor and impersonating the kind of veterinarian

I would like to be one day. For having a never-ending passion for veterinary medicine and for sharing

it with the students. For showing us that we will never stop learning and that mistakes are a part of

the way. For believing in this thesis and for pushing me, for never letting me down. For everything.

Thank you.

To Dr. Valentin Reichle and his team who filled my summer times with veterinary medicine,

taught me so many practical skills and set me up for success. Who reviewed a part of this thesis and

never stopped reminding me to not lose focus. Thank you.

To the team of Tierklinik Dr. Hutter, Vienna. For making me feel at home and for making me

believe that what I do matters. For never letting me fail and always making me want to do better.

To my big little brother, Nikolas. Because you are this much better at statistics and so many

other things than I am. And because I can always count on you. Thank you so much.

To my friend Hannah, who knows me better than I do and always finds a way to sort my

thoughts. Who told me where to start with this thesis and who never tires to hear more about it. Who

motivates me every single day to be my best and believe in myself. And everything else you do.

Thank you for being my friend unconditionally.

I would like to thank my parents and my friends at home and abroad just for being you and

never giving up on me, wherever my paths have led me. For supporting all of my chaos and lending

a helping hand anytime I need it.

And last but not least, this is to Emma, Bo and the Breeze. For all the breaks and all the laughter

and all the happiness in the world. And for always being by my side.

45

REFERENCES

1. V. E. Valli, P. H. Kass, M. San Myint, F. Scott. Canine Lymphomas: Association of

Classification Type, Disease Stage, Tumor Subtype, Mitotic Rate, and Treatment With Survival.

PubMed. [Online] 2013. https://pubmed.ncbi.nlm.nih.gov.

2. Ettinger, Susan N. Principles of Treatment for Canine Lymphoma. Clinical Techniques in Small

Animal Practice. 2003, Vol. 18, 2, pp. 92-97.

3. Tracy Gieger, DVM. Alimentary Lymphoma in Cats and Dogs. Veterinary Clinics: Small Animal

Practice. [Online] 2011. https://www.vetsmall.theclinics.com.

4. Jennifer Kinns, Wilfried Mai. Association Between Malignancy and Sonographic Heterogeneity

in Canine and Feline Abdominal Lymph Nodes. Veterinary Radiology & Ultrasound. 2007, Vol.

48, 6.

5. Suran, Jantra Ngosuwan. General Diagnostic Imaging in Small Animal Oncology. Philadelphia,

PA : s.n.

6. George Mantziaras, Gaia Cecilie Luvoni. Advanced Ultrasound Techniques in Small Animal

Reproduction Imaging. [Article] Milano, Italy : s.n., 2020.

7. Lisciandro, Gregory R. Abdominal and Thoracic Focused Assessment with Sonography for

Trauma, Triage, and Monitoring in Small Animals. Journal of Veterinary Emergency and Critical

Care. 2011, Vol. 21, 2, pp. 104-122.

8. Larson, Martha Moon. Ultrasound Imaging of the Hepatobiliary System and Pancreas. 2015.

9. H. Thiemeyer, L. Taher, J. T. Schille, L. Harder, S. O. Hungerbuehler, R. Mischke, M.

Hewicker-Trautwein, Z. Kielbowicz, B. Brenig, E. Schütz, J. Beck, H. Murua Escobar, I. Nolte.

Suitability of ultrasound-guided fine needle aspiration biopsy for transcriptome sequencing of the

canine prostate. Scientific Reports. [Online] 2019. https://www.nature.com/srep/.

10. Fan, Timothy M. Canine Lymphoma. MSD Veterinary Manual. [Online] 2019.

https://www.msdvetmanual.com/en-au/circulatory-system/canine-lymphoma/canine-lymphoma.

11. Joanna Morris, Jane Dobson. Small Animal Oncology. Cambridge : Blackwell Science, 2001. p.

221.

12. Haley, Patrick J. The lymphoid system: a review of species differences. 2016.

13. Oystein V. Sjaastad, Olav Sand, Knut Hoove. Physiology of Domestic Animals. Oslo, Norway :

Scandinavian Veterinary Press, 2003. pp. 342-343. 978-82-91743-08-3.

14. Alessandra Gavazza, Federico Sacchini, George Lubas, Biancaurora Gugliucci, Elisa Valori.

Clinical, laboratory, diagnostic and prognostic aspects of canine lymphoma: a retrospective study.

Comparative Clinical Pathology. 2009.

46

15. Julie K. Levy, Amanda Burling. Feline Leukemia Virus and Related Diseases in Cats -

Overview. MSD Veterinary Manual. [Online] 2014. https://www.msdvetmanual.com/generalized-

conditions/feline-leukemi...eases/feline-leukemia-virus-and-related-diseases-in-cats-overview.

16. Vanessa Barrs, Julia Beatty. Feline Alimentary Lymphoma 1. Classification, risk factors,

clinical signs and non-invasive diagnostics. Journal of Feline Medicine and Surgery. 2012, 14, pp.

182-190.

17. Couto, C. Guillermo. What is new on feline lymphoma? Journal of Feline Medicine and

Surgery. 2001, Vol. 3, pp. 171-176.

18. Franz-Viktor Salomon, Hans Geyer, Uwe Gille. Anatomie für die Tiermedizin. s.l. : Thieme,

2020. p. 470.

19. Hiroshi Ueno, Kenijro Miyoshi, Sho Fukui, Yumi Kondo, Kazuya Matsuda, Tsuyoshi Uchide.

Extranodal Lymphoma with Peripheral Nervous System Involvement in a Dog. Japan : s.n., 2014.

20. V. E. Valli, W. Vernau, L. P. De Lorimier, P. S. Graham, P. F. Moore. Canine Indolent Nodular

Lymphoma. SagePub. [Online] 2006. https://journals.sagepub.com/home/vet.

21. Fausto Quintavalla, Rosanna Di Lecce, Daniele Carlini, Matteo Zanfabro, Anna M. Cantoni.

Multifocal cutaneous non-epitheliotropic B-cell lymphoma in a cat. Jouranl of Feline Medicine and

Surgery Open Reports. 2020.

22. Davis M. Seelig, Anne C. Avery, E.J. Ehrhart, Michael A. Linden. The Comparative Diagnostic

Features of Canine and Human Lymphoma. Comparative Pathogenesis of Cancers in Animals and

Humans. 2016.

23. Robert E. Cartee, Judith A. Hudson, Susan Finn-Bodner. Ultrasonography. Veterinary Clinics of

America: Small Animal Practice. 1993, Vol. 23, 2.

24. Amanda C. Crabtree, Elizabeth Spangler, Debra Beard, Annette Smith. Diagnostic Accuracy of

Gray-Scale Ultrasonography for the Detection of Hepatic and Splenic Lymphoma in Dogs.

Veterinary Radiology and Ultrasound. 2010, Vol. 51, 6.

25. Lattimer, Jimmy C. Ultrasonography in Animals. MSD Veterinary Manual. [Online] 2019.

https://www.msdvetmanual.com.

26. Albury, Kelly. An Overview of Small Animal Veterinary Sonography. Journal of Diagnostic

Medical Sonography. 2015, Vol. 31, 3, pp. 160-167.

27. Angela J. Taylor, Ana Lara-Garcia, Livia Benigni. Ultrasonographic Characteristics of Canine

Renal Lymphoma. Vet Radiol Ultrasound. 2014, Vol. 55, 4, pp. 441-446.

28. Miyabayashi, Takayoshi. vin.com. [Online]

https://www.vin.com/apputil/content/defaultadv1.aspx?pId=8708&catId=18054&id=3843782.

29. V. Nerschbach, N. Eberle, A. E. Joetzke, R. Hoeinghaus, S. Hungerbuehler, R. Mischke, I.

Nolte, D. Betz. Splenic and hepatic ultrasound and cytology in canine lymphoma: effects of

47

findings on stage migration and assessment of prognosis. Veterinary and Comparative Oncology.

s.l. : John Wiley & Sons Ltd, 2014.

30. Nyland, Thomas G. Ultrasonic Patterns of Canine Hepatic Lymphosarcoma. 1984, Vol. 25, 4,

pp. 167-172.

31. JG Besso, RH Wrigley, JM Gliatto, CRL Webster. Ultrasonographic Appearance and Clinical

Findings in 14 Dogs with Gallbladder Mucocele. 2000, Vol. 41, 3, pp. 261-271.

32. M. Frances, A. E. Lane, Z. M. Lenard. Sonographic features of gastrointestinal lymphoma in 15

dogs. Journal of Small Animal Practice. 2013, 54, pp. 468-474.

33. Michelle L. Avante, Priscila DA da Silva, Marcus AR Feliciano, Marjury C. Maronezi, Ana R.

Simoes, Ricardo AR Uscategui, Julia C. Canola. Ultrasonography of the canine pancreas. Revista

MVZ Cordoba. 2018, Vol. 23, 1.

34. Rochelle M. Salwei, Robert T. O'Brien, Jodi S. Matheson. Characterization of Lymphomatous

Lymph Nodes in Dogs Using Contrast Harmonic and Power Doppler Ultrasound. Madison, WI :

s.n., 2005.

35. Marie De Swarte, Kate Alexander, Benoit Rannou, Marc-Andre D'Anjou, Laurent Blond, Guy

Beauchamp. Comparison of Sonographic Features of Benign and Neoplastic Lymph Nodes in

Dogs. Veterinary Radiology & Ultrasound. 2011, Vol. 52, 4, pp. 451-456.

36. David M. Vail, Gregory K. Ogilvie, Steven L. Wheeler, Martin J. Fettman, Shirley D. Johnston,

Rebecca L. Hegstad. Alterations in Carbohydrate Metabolism in Canine Lymphoma. Journal of

Veterinary Internal Medicine. 1990.

37. Trisha J. Oura, Philip E. Hamel, Samuel H. Jennings, Perry J. Bain, Dennis E. Jennings, John

Berg. Radiographic Differentiation of Cranial Mediastinal Lymphomas from Thymic Epithelial

Tumors in Dogs and Cats. Grafton, Massachussetts : American Animal Hospital Association, 2019.