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Also know as: '''''Lymphosarcoma'''''
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Also known as: '''''Lymphosarcoma'''''
    
==Introduction==   
 
==Introduction==   
 
[[Image:tonguelymphoma.gif|right|thumb|125px|<small><center>Tongue Lymphoma - a recognised entity (Courtesy of Alun Williams (RVC))</center></small>]]
 
[[Image:tonguelymphoma.gif|right|thumb|125px|<small><center>Tongue Lymphoma - a recognised entity (Courtesy of Alun Williams (RVC))</center></small>]]
 
[[Image:Lymphoma in nasal cavity.jpg|right|thumb|125px|<small><center>Lymphoma in nasal cavity (Image sourced from Bristol Biomed Image Archive with permission)</center></small>]]
 
[[Image:Lymphoma in nasal cavity.jpg|right|thumb|125px|<small><center>Lymphoma in nasal cavity (Image sourced from Bristol Biomed Image Archive with permission)</center></small>]]
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[[File:Lymphoma in golden.JPG|right|thumb|200px| Lymphoma in a Golden Retriever (Wikimedia Commons)]]
 
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.  
 
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.  
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===Horse===
 
===Horse===
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A '''thoracic effusion''' may occur in the alimentary and multicentric forms of the disease, which usually has the characteristics of a '''[[Modified Transudate|modified transudate]]'''.
    
==Physical Examination==
 
==Physical Examination==
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===Cytology===
 
===Cytology===
For cytology findings in lymphoma cases, please refer to [[Lymphoma - Cytology|this]] article.
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[[File:Canine lymphoma 1.JPG|right|thumb|200px|Cytology from an FNA of a lymph node of a dog with lymphoma. The predominant cells are lymphoblasts (Wikimedia Commons)]]
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Cytology is a necessary tool in the work-up of a lymphoma case. It provides both a '''diagnosis''' and a '''prognosis''' when combined with the '''entire clinical picture'''. Lymphoma produces a cell
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population which is both distinct and recognisable, allowing identification and classification of the type of lymphoma by cytology. '''Fine needle aspiration''' is a '''quick''', '''cheap''',
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'''non-invasive''' and '''effective''' method for collecting cells for cytology, and should always be considered a '''first-line test'''. Ideally cytology should always be supported by histology.  
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Cytology can also be used to examine pleural fluid samples if there is a suspicion of neoplasia.
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Smears should be '''stained''' and examined microscopically.
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Cytological criteria for lymphoma:
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* '''Large amounts of lymphoblasts'''
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* '''Large nuclei and prominent nucleoli'''
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* '''High mitotic rate - bizarre mitotic figures may be present'''
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* '''Small volume of basophilic cytoplasm'''
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* '''Coarse chromatin'''
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These features can be assessed to determine the '''grade''' of tumour and therefore the likely '''treatment response''' and '''progression of disease'''. Small well-differentiated lymphocytes normally suggest a low-grade lymphoma, and large, poorly differentiated lymphoid cells suggest a higher grade of lymphoma.
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'''Dogs'''
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:Canine lymphoma is normally '''multicentric''', therefore the ideal method for collecting a sample for cytological examination is '''fine needle aspiration of the lymph nodes'''. Ideally samples should come from '''multiple nodes''' to give a representative sample. '''Popliteal''' and '''prescapular lymph nodes''' are easily accessible and therefore ideal for sampling. Submandibular lymph nodes should be avoided where possible as they are commonly enlarged and reactive as a
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result of dental disease. It should be noted that canine lymphoma can occur in any organ containing lymphoid tissue.
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'''Cats'''
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:Feline lymphoma is more '''variable''' in its presentation, with the three types  ('''mediastinal''', '''alimentary''' and '''multicentric''') common in general practice. The
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sample taken for cytological examination should be appropriate for the type of lymphoma:
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::'''Ultrasound guided aspirates''', '''partial thickness endoscopic grab biopsies''' or '''full thickness biopsies''' via '''exploratory laparotomy''' for intenstinal lymphoma
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::'''Pleural fluid aspirate''' with or without supporting '''ultrasounded-guided aspirate or core biopsy''' of the mass (which will differentiate it from thymoma) with mediastinal lymphoma
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::'''Peripheral lymph node aspirates''' for multicentric lymphoma
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:Lymphoma can occur in any tissue containing lymphoid tissue, for example the '''eye''', '''kidney''', '''CNS''', '''liver''', '''upper respiratory tract''', '''lungs''' and '''skin'''. Cytology is an essential tool for diagnosis in these cases, as the lymphoma can present with variable clinical signs and diagnosis can only be confirmed using cytology. As mentioned above, the cytological diagnosis should be supported by histopathology if possible, particularly if the cytological sample is equivocal.
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:'''NB'''. Lymphoma should not be confused with [[Lymph Node Abnormalities#Reactive Lymph Nodes|
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reactive lymphoid hyperplasia]] in the healthy cat. Generalised lymphadenopathy may present like multicentric lymphoma but is infact a natural immune response in the healthy cat. The same should be
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considered in other types of lymphoma, for example hepatic lymphoma looks cytologically identical to lymphocytic periportal hepatitis, and it is necessary to incorporate the entire clinical picture when making a diagnosis. Histopathological sampling is ideal for confirming the diagnosis.
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'''Horse'''
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:In equine lymphoma, neoplastic cells are not always present, but when they are this may allow diagnosis.
    
===Biopsy===
 
===Biopsy===
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A '''biopsy''' may be required if diagnosis cannot be made from FNA's.  This may occur if; the aspirate provided a '''low number of cells'''; the '''cells were badly preserved'''; the disease is in its '''early stages''' or the neoplastic '''cells''' are '''small'''.  If the lymph node is biopsied, it is best to remove the entire node in an '''excisional biopsy''' so the '''tissue architecture remains intact'''.
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Biopsy may also be indicated it the neoplasia is '''localised''' to a '''specific organ''' which is not amenable to ultrasound guided FNA, for example the gastrointestinal tract.
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Nasal lymphoma can be diagnosed by rhinoscopic or blind biopsy using a suction-catheter or grab-forceps technique.
 
Nasal lymphoma can be diagnosed by rhinoscopic or blind biopsy using a suction-catheter or grab-forceps technique.
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'''Bone Marrow Aspirate/Biopsy''' should be taken ideally for all cases as part of the staging procedure.
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'''Bone marrow aspiration or biopsy is needed to stage the disease'''.
    
===Staging===
 
===Staging===
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==Treatment==
 
==Treatment==
===Surgery===
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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).
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===Radiotherapy===
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===Cats and Dogs===
Lymphoma is highly radiosensitive and in theory should be efficient in treating all forms of lymphoma, however, surrounding tissues often have a low tolerance.
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'''Surgery'''
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: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. Should relapse occur, or if there is systemic progression, chemotherapy will be required (multimodal treatment).
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===Chemotherapy===
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'''Radiotherapy'''
Combination chemotherapy is the most frequent method of treatment and the most commonly used protocols include:
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:Lymphoma is highly radiosensitive and in theory radiotherapy should be efficient in treating all forms of lymphoma, however, surrounding tissues often have a low tolerance.
* COP which consists of Cyclophosphamide, Vincristine and Prednisolone. It is frequently used in cats and can be used for induction therapy (8 weeks) as well as a long term maintenance protocol.
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* COAP consists of Cyclophosphamide, Vincristine, Prednisolone and Cytosine arabinoside
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* CHOP consists of Cyclophosphamide, Vincristine, Prednisolone and Doxorubicin.
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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.
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The aim is to induce remission and then continue with a maintenance regime, adjusting the dose as required with rescue therapy should relapse occur.
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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.
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===Supportive Therapy===
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'''Chemotherapy'''
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.
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:Combination chemotherapy is the most frequent method of treatment and the most commonly used protocols include:
Additionally [[Principles of Fluid Therapy|fluid therapy]], laxatives and [[Systemic Analgesia|analgesia]] may be required.
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:* COP which consists of Cyclophosphamide, Vincristine and Prednisolone. It is frequently used in cats and can be used for induction therapy (8 weeks) as well as a long term maintenance protocol.
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:* COAP consists of Cyclophosphamide, Vincristine, Prednisolone and Cytosine arabinoside
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:* CHOP consists of Cyclophosphamide, Vincristine, Prednisolone and Doxorubicin.
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: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.
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: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.
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'''Supportive Therapy'''
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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.
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Additionally, [[Principles of Fluid Therapy|fluid therapy]], laxatives and [[Systemic Analgesia|analgesia]] may be required.
    
==Prognosis==
 
==Prognosis==
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===Cats and Dogs===
 
The mean survival times for dogs and cats without therapy is 6-8 weeks. For those receiving 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.
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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).
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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 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.
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==Literature Search==
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===Horse===
[[File:CABI logo.jpg|left|90px]]
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The prognosis is '''poor''' and definitive diagnosis is usually achieved on post-mortem examination.
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{{Learning
Use these links to find recent scientific publications via CAB Abstracts (log in required unless accessing from a subscribing organisation).
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|flashcards = [[Feline Medicine Q&A 12]]<br>[[Cytology Q&A 03]]<br>[[Cytology Q&A 10]]
<br><br><br>
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|literature search = [http://www.cabdirect.org/search.html?q=title%3A%28lymphoma%29+AND++od%3A%28dogs%29 Lymphoma in dogs publications]
[http://www.cabdirect.org/search.html?q=title%3A%28lymphoma%29+AND++od%3A%28dogs%29 Lymphoma in dogs publications]
      
[http://www.cabdirect.org/search.html?q=title%3A%28lymphoma%29+AND+od%3A%28cats%29 Lymphoma in cats publications]
 
[http://www.cabdirect.org/search.html?q=title%3A%28lymphoma%29+AND+od%3A%28cats%29 Lymphoma in cats publications]
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}}
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{{Learning
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|flashcards = [[Feline Medicine Q&A 12]]
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}}
      
==References==
 
==References==
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Cowell, R. (2002) '''Diagnostic cytology and haematology of the horse''' ''Elsevier Health Sciences''
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Freeman, KP (2007) '''Self-Assessment Colour Review of Veterinary Cytology - Dog, Cat, Horse and Cow''' ''Manson''
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Gear, R (2009) '''Practical update on canine lymphoma : 1. Classification and Diagnosis''' ''In Practice 2009 31: 380-384''
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Hayes A. (2006) '''Feline lymphoma 1. Principles of diagnosis and management''', ''In Practice'', 28, pp 516-524
 
Hayes A. (2006) '''Feline lymphoma 1. Principles of diagnosis and management''', ''In Practice'', 28, pp 516-524
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Sparks, AH & Caney, SMA (2005) '''Self-Assessment Colour Review Feline Medicine''' ''Manson''
 
Sparks, AH & Caney, SMA (2005) '''Self-Assessment Colour Review Feline Medicine''' ''Manson''
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Stell, A (2009) '''Haemopoetic Neoplasia - Lymphoreticular and Haemopoetic System''' RVC Intergrated BVetMed Course, ''Royal Veterinary College''
    
White, R. A. S, (2003), '''Tumours of the intestines, in BSAVA Manual of Canine and Feline Oncology''', second edition, Eds Dobson J. M, Lascelles B. D. X, Gloucester, ''British Small Animal Veterinary Association'', pp 229-233
 
White, R. A. S, (2003), '''Tumours of the intestines, in BSAVA Manual of Canine and Feline Oncology''', second edition, Eds Dobson J. M, Lascelles B. D. X, Gloucester, ''British Small Animal Veterinary Association'', pp 229-233
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