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[[Image:tonguelymphoma.gif|right|thumb|125px|<small><center>Tongue Lymphoma - a recognised entity (Courtesy of Alun Williams (RVC))</center></small>]][[Category:Tongue_-_Pathology]]

[[Image:tonguelymphoma.gif|right|thumb|125px|<small><center>Tongue Lymphoma - a recognised entity (Courtesy of Alun Williams (RVC))</center></small>]]

Lymphoma is caused by malignant clonal expansion of lymphoid cells and most commonly arises from lymphoid tissues including the [[Bone Marrow|bone marrow]], [[Thymus - Anatomy & Physiology|thymus]], [[Lymph Nodes - Anatomy & Physiology|lymph nodes]] and [[Spleen - Anatomy & Physiology|spleen]]. Lymphoma is documented to be the most common haematopoietic [[Neoplasia - Pathology|neoplasm]] in dogs.

In the '''dog''', multicentric lymphoma is most common representing 80% of cases. Alimentary, cutaneous, mediastinal and extranodal sites are less common. Additionally the majority of lymphoma cases in dogs are of the B-cell immunophenotype.  

In the dog, multicentric lymphoma is most common representing 80% of cases. [[Alimentary System Overview - Anatomy & Physiology|Alimentary]], cutaneous, [[Mediastinum - Anatomy & Physiology|mediastinal]] and extranodal sites are less common. Additionally the majority of lymphoma cases in dogs are of the B-cell immunophenotype.  

In cats following the inroduction of widespread [[Feline Leukaemia Virus|FeLV]] testing and [[vaccines|vaccination]] the most common type of lymphoma affecting cats is alimentary when previously it had been mediastinal and multicentric forms.

In '''cats''' following the introduction of widespread [[Feline Leukaemia Virus|FeLV]] testing and [[vaccines|vaccination]] the most common type of lymphoma affecting cats is alimentary when previously it had been mediastinal and multicentric forms.

Only 10% of lymphoma cases in cats are now associated with FeLV.

Only 10% of lymphoma cases in cats are now associated with FeLV.

==Signalment==

==Signalment==

The median age of affected cats is 9-10 years and oriental [[Feline Breeds - WikiNormals|cat breeds]] may be predisposed.

The median age of affected cats is 9-10 years and oriental [[Feline Breeds - WikiNormals|cat breeds]] may be predisposed.

Affected dogs have a wide age range, most are middle-aged however young animals can be affected. There may also be a male predilection.

Affected dogs have a wide age range, most are middle-aged however young animals can be affected. There may also be a male predilection.

The most common presenting sign in dogs is a lymphadenopathy, with only 10-20% of dogs presenting clinically unwell. Dogs that do present with clinical signs may be anorexic, lethargic and have lost weight.

The most common presenting sign in dogs is a lymphadenopathy, with only 10-20% of dogs presenting clinically unwell. Dogs that do present with clinical signs may be anorexic, lethargic and have lost weight.

For other types of lymphoma affecting dogs the clinical signs will demonstrate the anatomical site affected.

For other types of lymphoma affecting dogs the clinical signs will demonstrate the anatomical site affected.

Dogs with mediastinal lymphoma can also have pitting [[Oedema - Pathology|oedema]] of the head and neck due to compression of the cranial vena cava.

Dogs with mediastinal lymphoma can also have pitting [[Oedema - Pathology|oedema]] of the head and neck due to compression of the cranial vena cava.

'''Alimentary''' forms will present with [[Vomiting|vomiting]], [[Diarrhoea|diarrhoea]], anorexia and thickened loops of [[Small Intestine Overview - Anatomy & Physiology|intestine]] on abdominal palpation.

'''Alimentary''' forms will present with [[Vomiting|vomiting]], [[Diarrhoea|diarrhoea]], anorexia and thickened loops of intestine on abdominal palpation.

'''Cutaneous''' lymphoma can also occur with a varied presentation but often present as cutaneous nodules.

'''Cutaneous''' lymphoma can also occur with a varied presentation but often present as cutaneous nodules.

====Feline Lymphoma====

===Cats===

In contrast to dogs, cats are more likely to present unwell.  Again the clinical signs will depend on the anatomical location affected.

In contrast to dogs, cats are more likely to present unwell.  Again the clinical signs will depend on the anatomical location affected.

'''Mediastinal''' cats will present with respiratory signs and may be in respiratory distress.

'''Mediastinal''' cats will present with respiratory signs and may be in respiratory distress.

'''Renal''' lymphoma also occurs in cats and affeted animals will present with signs similar to [[Kidney Renal Failure - Pathology|renal failure]].

'''Renal''' lymphoma also occurs in cats and affected animals will present with signs similar to [[Kidney Renal Failure - Pathology|renal failure]].

===Physical Examination===  

==Physical Examination==

An abdominal mass may be palpable and bowel loops may feel thickened in alimentary lymphoma. Additionally enlarged mesenteric [[Lymph Nodes - Anatomy & Physiology|lymph nodes]] and enlarged abdominal organs may be palpable . Muffled [[ Heart - Anatomy & Physiology|heart]] sounds and a non-compressible thoracic region may be found in mediastinal lymphoma.

An abdominal mass may be palpable and bowel loops may feel thickened in alimentary lymphoma. Additionally enlarged mesenteric lymph nodes and enlarged abdominal organs may be palpable. Muffled heart sounds and a non-compressible thoracic region may be found in mediastinal lymphoma.

Petechiae, [[Anaemia - Introduction|anaemia]] and icterus may also be present in any form of lymphoma.

Petechiae, [[Anaemia - Introduction|anaemia]] and icterus may also be present in any form of lymphoma.

==Laboratory Tests==

==Laboratory Tests==

===Haematology and Biochemistry===

===Haematology and Biochemistry===

Haematological analysis should always be performed with suspected lymphoma for staging purposes and for the recording of base-line parameters prior to the initiation of any treatment to assess the severity of any future myelosuppression. Potential abnormalities for those patients with [[Bone Marrow|bone marrow]] involvement may include [[Lymphocytosis|lymphocytosis]], [[Platelet Abnormalities#Thrombocytopaenia|thrombocytopenia]], [[Neutropenia|neutropenia]] and the presence of immature lymphoid precursors.

Haematological analysis should always be performed with suspected lymphoma for staging purposes and for the recording of base-line parameters prior to the initiation of any treatment to assess the severity of any future myelosuppression. Potential abnormalities for those patients with bone marrow involvement may include [[Lymphocytosis|lymphocytosis]], [[Platelet Abnormalities#Thrombocytopaenia|thrombocytopenia]], [[Neutropenia|neutropenia]] and the presence of immature lymphoid precursors.

 

Affected cats are not usually leukemic.

Affected cats are not usually leukemic.

On biochemistry abnormalities may include hypoproteinaemia, elevated hepatic enzymes and elevated [[Blood urea nitrogen|Blood Urea Nitrogen]] /[[Creatinine|creatinine]].

On biochemistry abnormalities may include hypoproteinaemia, elevated hepatic enzymes and elevated [[Blood urea nitrogen|Blood Urea Nitrogen]] /[[Creatinine|creatinine]].

===FeLV/FIV===

===FeLV/FIV===

All cats with suspected lymphoma should be tested for FeLV and [[Feline Immunodeficiency Virus|FIV]], usually performed via enzyme-linked immunosorbent assay ([[ELISA testing|ELISA]]) available in general practice in kit form (CITE test). Virus isolation would be required for a definitive result, however this is not only more time consuming but is more expensive. An ELISA is also frequently used for the diagnosis of FIV.

All cats with suspected lymphoma should be tested for [[FeLV]] and [[Feline Immunodeficiency Virus|FIV]], usually performed via enzyme-linked immunosorbent assay ([[ELISA testing|ELISA]]) available in general practice in kit form (CITE test). Virus isolation would be required for a definitive result, however this is not only more time consuming but is more expensive. An ELISA is also frequently used for the diagnosis of FIV.

===Paraneoplastic Syndromes===

===Paraneoplastic Syndromes===

Dogs may present with hypercalcaemia, this is due to the release of Parathyroid hormone- related protein (PTHrp) released by the tumor, which produces these effects by acting like parathyroid hormone. Affected cats are not usually hypercalcaemic

Dogs may present with hypercalcaemia, this is due to the release of parathyroid hormone - related protein (PTHrp) released by the tumor, which produces these effects by acting like parathyroid hormone. Affected cats are not usually hypercalcaemic.

==Radiography==

==Radiography==

* Stage II - Involvement of many lymph nodes in a regional area (+/- tonsils)

* Stage II - Involvement of many lymph nodes in a regional area (+/- tonsils)

* Stage III - Generalised lymph node involvement

* Stage III - Generalised lymph node involvement

* Stage IV - [[Liver - Anatomy & Physiology|Liver]] and/or [[Spleen - Anatomy & Physiology|spleen]] involvement (+ stage III)

* Stage IV - Liver and/or spleen involvement (+ stage III)

* Stage V - Manifestations in the blood and involvement of bone marrow and/or other organ systems (+/-stages I-IV)

* Stage V - Manifestations in the blood and involvement of bone marrow and/or other organ systems (+/-stages I-IV)

Each stage is then subclassifed as a) without systemic signs or b) with systemic signs.

Each stage is then subclassifed as a) without systemic signs or b) with systemic signs.

==Treatment==

==Treatment==

===Surgery===

===Surgery===

Firstly, a laparotomy is required for many cases of Alimentary lymphoma to obtain biopsy material. For solitary masses without systemic disease resection and anastomosis of the intestine is advised (single modality treatment). Local resection in cats has occasionally been curative. Other focal lyphoma may also be resected, however surgery alone may be insufficient for long-term control of the disease and if not all the tumour is able to be resected, or should relapse occur, or if there is systemic progression, chemotherapy will be required   (multimodal treatment).

Firstly, a laparotomy is required for many cases of alimentary lymphoma to obtain biopsy material. For solitary masses without systemic disease resection and anastomosis of the intestine is advised (single modality treatment). Local resection in cats has occasionally been curative. Other focal lyphoma may also be resected, however surgery alone may be insufficient for long-term control of the disease and if not all the tumour is able to be resected, or should relapse occur, or if there is systemic progression, chemotherapy will be required (multimodal treatment).

===Radiotherapy===

===Radiotherapy===

Corticosteroids must not be administered prior to initiation of chemotherapy as they can cause resistance to cytotoxics and hence reduce the rate of response and the survival time.

Corticosteroids must not be administered prior to initiation of chemotherapy as they can cause resistance to cytotoxics and hence reduce the rate of response and the survival time.

The aim is to induce remission and then continue with a maintenance regime, adjusting the dose as required with rescue therapy should relapse occur.  

The aim is to induce remission and then continue with a maintenance regime, adjusting the dose as required with rescue therapy should relapse occur.  

Response to treatment can be monitored via reduction in tumour mass and size of lymph nodes. Haematological values should be frequently monitored to assess the effects of the drugs. In particular animals should be monitored for the presence of [[Azotaemia|Azotaemia]], neutropenia/sepsis, hypercalcaemia and pyrexia.

Response to treatment can be monitored via reduction in tumour mass and size of lymph nodes. Haematological values should be frequently monitored to assess the effects of the drugs. In particular animals should be monitored for the presence of [[Azotaemia|azotaemia]], neutropenia/sepsis, hypercalcaemia and pyrexia.

===Supportive Therapy===

===Supportive Therapy===

Whilst receiving chemotherapy patients should recieve a high quality, palatable diet to maintain calorific intake. If animals become anorexic they should recieve appetite stimulation in cats e.g Cyproheptadine (Periactin) or [[Emetics and Anti-Emetic Drugs|antiemetics]] if vomiting occurs.

Whilst receiving chemotherapy patients should receive a high quality, palatable diet to maintain calorific intake. If animals become anorexic they should receive appetite stimulation in cats e.g Cyproheptadine (Periactin) or [[Emetics and Anti-Emetic Drugs|antiemetics]] if vomiting occurs.

Additionally [[Principles of Fluid Therapy|fluid therapy]], laxatives and [[Systemic Analgesia|analgesia]] may be required.

Additionally [[Principles of Fluid Therapy|fluid therapy]], laxatives and [[Systemic Analgesia|analgesia]] may be required.

==Prognosis==

==Prognosis==

The mean survival times for dogs and cats without therapy is 6-8 weeks. For those recieving corticosteroids alone is 3 months.

The mean survival times for dogs and cats without therapy is 6-8 weeks. For those receiving corticosteroids alone is 3 months.

If chemotherapy is administered then the mean survival time increases to 6-9 months.

If chemotherapy is administered then the mean survival time increases to 6-9 months.

Local canine lymphoma responds better to chemotherapy than the diffuse form of disease.  

Local canine lymphoma responds better to chemotherapy than the diffuse form of disease.  

Immunophenotype (T cell versus B cell lymphoma) does not appear to be associated with prognosis in cats as it can be in dogs. Factors indicating a better prognosis (overall survival) in cats include: an early presentation, a complete initial response to treatment and a clinically well patient(‘substage a’ disease).

Immunophenotype (T cell versus B cell lymphoma) does not appear to be associated with prognosis in cats as it can be in dogs. Factors indicating a better prognosis (overall survival) in cats include: an early presentation, a complete initial response to treatment and a clinically well patient(‘substage a’ disease).

In cats, response rate to induction chemotherapy is 26-79% and thus there is an apparently a poorer response rate in cats compared with dogs, however, 30-40% of cats that do have complete remission and will maintain complete remission for two years or more and long-term maintenance chemotherapy can frequently be stopped and many will then live free of disease. Hence, dogs may have higher remission rates but are less likely than cats to be able to maintain remission without chemotherapy.

In cats, response rate to induction chemotherapy is 26-79% and there is an apparently a poorer response rate in cats compared with dogs, however, 30-40% of cats that do have complete remission and will maintain complete remission for two years or more and long-term maintenance chemotherapy can frequently be stopped and many will then live free of disease. Hence, dogs may have higher remission rates but are less likely than cats to be able to maintain remission without chemotherapy.

 

 

 

 

==References==

==References==

[[Category:Stomach_and_Abomasum_-_Proliferative_Pathology]][[Category:Dog]][[Category:Cattle]]

[[Category:Stomach_and_Abomasum_-_Proliferative_Pathology]][[Category:Dog]][[Category:Cat]]

[[Category:Intestines_-_Proliferative_Pathology]]

[[Category:Intestines_-_Proliferative_Pathology]][[Category:Tongue_-_Pathology]]

[[Category:To Do - Caz]][[Category:Lymphoreticular and Haemopoietic Diseases]]

[[Category:Lymphoreticular and Haemopoietic Diseases]]

[[Category:Neoplasia]]

[[Category:Neoplasia]]

[[Category:To Do_-_Review]]

[[Category:Expert_Review]]