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Also known as: '''''Lymphosarcoma — Malignant Lymphoma'''''
Also known as: '''''Lymphosarcoma — Malignant Lymphoma'''''
::Multicentric - Widespread involvement of lymph nodes.
::Multicentric - Widespread involvement of lymph nodes.
::Cutaneous lymphoma - Usually presents as generalised skin disease, but is a malignant transformation of T cells with a propensity for epithelial sites.
::Cutaneous lymphoma - Usually presents as generalised skin disease, but is a malignant transformation of T cells with a propensity for epithelial sites.
:'''Type of lymphocyte''' - [[T cells|T-cell]], [[B cells|B-cel]] or [[Natural Killer cells|NK-cell]]
:'''Type of lymphocyte''' - [[T cells|T-cell]], [[B cells|B-cell]] or [[Natural Killer cells|NK-cell]]
:'''Time scale''' - Acute or Chronic
:'''Time scale''' - Acute or Chronic
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.
'''Alimentary''' cats will present with vomiting, diarrhoea, weight loss and anorexia.
'''Alimentary''' cats often present with vomiting, diarrhoea, weight loss and anorexia.
'''Mediastinal''' cats will present with signs of compression of structures in the cranial thorax. These include dyspnoea, coughing and tachypnoea due to compression of the trachea. Weight loss and regurgitation may also occur secondary to compression of the oesophagus. On auscultation lung sounds are displaced caudally and lung sounds are decreased ventrally. There may be a loss of compressibility ('rib spring') over the cranial thorax. There may be pleural effusion present. Differential diagnoses for a cranial mediastinal mass are: thymoma, thyroid adenocarcinoma, a mediastinal abscess, or a branchial cyst.
'''Mediastinal''' cats may present with signs of compression of structures in the cranial thorax or with dyspnoea from an associated pleural effusion. Signs include dyspnoea, coughing and tachypnoea due to compression of the trachea. Weight loss and regurgitation may also occur secondary to compression of the oesophagus though these are rare. On auscultation, lung sounds are displaced caudally and lung sounds are decreased ventrally. There may be a loss of compressibility ('rib spring') over the cranial thorax. Differential diagnoses for a cranial mediastinal mass include: thymoma, thyroid adenocarcinoma, a mediastinal abscess, or a branchial cyst.
'''Renal''' lymphoma also occurs in cats and affected animals will present with signs similar to [[:Category:Renal Failure|renal failure]].
'''Renal''' lymphoma also occurs in cats and affected animals will typically present with bilateral renomegally and signs similar to [[:Category:Renal Failure|renal failure]].
'''Nasal''' lymphoma cases will present with dyspnoea, nasal discharge, epistaxis, facial pain or distortion and loss of airflow.
'''Nasal''' lymphoma cases may present with any of dyspnoea, nasal discharge, epistaxis, facial pain or distortion and loss of airflow.
===Horse===
===Horse===
===Cat and Dog===
===Cat and Dog===
Findings will depend on the anatomic region affected as described above. For example, 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, [[Regenerative and Non-Regenerative Anaemias|anaemia]] and [[icterus]] may also be present in any form of lymphoma.
Petechiae, [[Regenerative and Non-Regenerative Anaemias|anaemia]] and [[icterus]] may also be present in any form of lymphoma.
'''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.
'''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 and dogs are not usually leukemic.
On '''biochemistry''' abnormalities may include hypoproteinaemia, elevated hepatic enzymes and elevated [[Urea|Blood Urea Nitrogen]] /[[Creatinine|creatinine]].
On '''biochemistry''' abnormalities may include hypoproteinaemia, elevated hepatic enzymes and elevated [[Urea|Blood Urea Nitrogen]] /[[Creatinine|creatinine]], but again these will depend on the area affected. A percentage of dogs will present with hypercalcemia of malignancy (see below), affecting both total and ionized calcium and in some cases causing a secondary azotaemia.
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). False negatives are very rare but false positives can be seen depending on the sensitivity and specificity of the assay and if the diagnosis does not fit with the clinical picture, a confirmatory test should be performed such as viral isolation. Vaccination for FeLV does not lead to false positive results on the ELISA as the test looks for antigen. However, the current FIV vaccines available in the USA do not have a marker and so can lead to false positive FIV antibody SNAP tests.
'''Paraneoplastic Syndrome'''
'''Paraneoplastic Syndrome'''
===Radiography===
===Radiography===
Nodal or organomegally may be visible radigraphically depending on the area affected. Other imaging modalities such as CT or MRI may be more appropriate for investigating nasal or CNS lymphoma, where available.
===Ultrasonography===
===Ultrasonography===
Superior to radiography in assessing infiltration or abnormalities of tissue architecture and assessing the surrounding structures for [[Neoplasia - Pathology#The Process of Metastasis|metastasis]]. Guided aspirates or biopsies may also be taken at this time, including lymph node sampling, to evaluate degree of systemic involvement.
Superior to radiography in some areas for assessing abnormalities of tissue architecture and assessing the surrounding structures for [[Neoplasia - Pathology#The Process of Metastasis|metastasis]]. Guided aspirates or biopsies may also be taken at this time, including lymph node sampling, to evaluate degree of systemic involvement.
===Cytology===
===Cytology===
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
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
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''',
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''',
'''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.
'''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 for immunophenotyping to distinguish B and T cell forms. Hyperplastic or reactive lymph nodes can be difficult to interpret and a second opinion from a qualified cytologist should always be taken when available prior to commencing treatment.
Cytology can also be used to examine pleural fluid samples if there is a suspicion of neoplasia.
Cytology can also be used to examine pleural fluid samples if there is a suspicion of neoplasia.
* '''Coarse chromatin'''
* '''Coarse chromatin'''
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.
These features can be assessed to determine the '''grade''' of tumour and therefore the likely '''treatment response''' and '''progression of disease''' though the prognostic ability of cytology remains poor. Small well-differentiated lymphocytes normally suggest a low-grade lymphoma, and large, poorly differentiated lymphoid cells suggest a higher grade of lymphoma and with that a poorer prognosis.
'''Dogs'''
'''Dogs'''
: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 result of dental disease. It should be noted that canine lymphoma can occur in any organ containing lymphoid tissue.
:Canine lymphoma is most commonly '''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 result of dental disease. It should be noted that canine lymphoma can occur in any organ containing lymphoid tissue.
'''Cats'''
'''Cats'''
:Feline lymphoma is more '''variable''' in its presentation, with the three types ('''mediastinal''', '''alimentary''' and '''multicentric''') common in general practice. The sample taken for cytological examination should be appropriate for the type of lymphoma:
:Feline lymphoma is more '''variable''' in its presentation, with extra-nodal forms being the commonest in general practice in the UK. The sample taken for cytological examination should be appropriate for the type of lymphoma:
::'''Ultrasound guided aspirates''', '''partial thickness endoscopic grab biopsies''' or '''full thickness biopsies''' via '''exploratory laparotomy''' for intenstinal lymphoma
::'''Ultrasound guided aspirates''', '''partial thickness endoscopic grab biopsies''' or '''full thickness biopsies''' via '''exploratory laparotomy''' for intestinal lymphoma
::'''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
::'''Pleural fluid aspirate''' with or without supporting '''ultrasound-guided aspirate or core biopsy''' of a mediastinal mass (which will in most cases differentiate it from thymoma though for some flow cytometry is necessary to make this distinction)
::'''Peripheral lymph node aspirates''' for multicentric lymphoma
::'''Peripheral lymph node aspirates''' for multicentric lymphoma
: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.
: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 result is equivocal.
:'''NB'''. Lymphoma should not be confused with [[Lymph Node Abnormalities#Reactive Lymph Nodes|
:'''NB'''. Lymphoma should not be confused with [[Lymph Node Abnormalities#Reactive Lymph Nodes|
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 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.
reactive lymphoid hyperplasia]] in the healthy cat. Generalised lymphadenopathy may present like multicentric lymphoma but is in fact a natural immune response in the healthy cat. The same should be considered in other types of lymphoma, for example hepatic lymphoma looks cytologically very similar 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.
'''Horse'''
'''Horse'''
===Biopsy===
===Biopsy===
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'''.
A '''biopsy''' may be required if diagnosis cannot be made from fine needle aspirates. This may occur if; the aspirate provided a '''low number of cells'''; the '''cells were badly preserved''' or the disease is in its '''early stages'''. If the lymph node is biopsied, it is best to remove the entire node in an '''excisional biopsy''' so the '''tissue architecture remains intact'''.
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.
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.
'''Secondary liver tumours''' are the most common secondary malignancy. They can be present as nodules or as diffuse infiltration along the portal tracts. Grossly, the liver is enlarged, turgid and friable with many minute pale foci. The whole organ is diffusely pale. Microscopically, tumour cells are seen to spread diffusely through the sinusoids.
'''Secondary liver tumours''' are the most common secondary malignancy. They can be present as nodules or as diffuse infiltration along the portal tracts. Grossly, the liver is enlarged, turgid and friable with many minute pale foci. The whole organ is diffusely pale. Microscopically, tumour cells are seen to spread diffusely through the sinusoids.
'''Splenomegaly''' occurs in multicentric lymphosarcoma. Splenic enlargement may be marked if any form of lymphosarcoma is in leukaemic phase.
'''Splenomegaly''' occurs in multicentric lymphosarcoma. Splenic enlargement may be marked if any form of lymphosarcoma is in leukaemic phase.
===Staging===
===Staging===
A staging system is used for lymphoma (Owen, 1980):
A staging system is used for multicentric lymphoma (Owen, 1980):
* Stage I - Involvement limited to a single node or lymphoid tissue in a single organ (excluding bone marrow)
* Stage I - Involvement limited to a single node or lymphoid tissue in a single organ (excluding bone marrow)
* 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 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. Other lymphomas such as primary hepatic are typically automatically classed as a grade V.
==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. 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 and in some cases to de-bulk and obstructing mass, though owners should be warned of the high potential of dehiscence post-operatively. 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 lymphoma may also be resected, however as there is typically systemic involvement, chemotherapy will be required (multimodal treatment).
'''Radiotherapy'''
'''Radiotherapy'''
: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.
: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. The main site for which radiotherapy is used is in nasal lymphoma, though many oncologists combine this with systemic chemotherapy. Half body radiotherapy is currently being trialled in the USA as part of a multi-modal protocol.
'''Chemotherapy'''
'''Chemotherapy'''
:Combination chemotherapy is the most frequent method of treatment and the most commonly used protocols include:
:Combination chemotherapy is the most frequent method of treatment and the most commonly used protocols include:
:* 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.
:* 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.
:* COAP consists of Cyclophosphamide, Vincristine, Prednisolone and Cytosine arabinoside
:* COAP consists of cyclophosphamide, vincristine, prednisolone and cytosine arabinoside
:* CHOP consists of Cyclophosphamide, Vincristine, Prednisolone and Doxorubicin.
:* CHOP consists of cyclophosphamide, vincristine, prednisolone and doxorubicin.
:* Prednisolone and chlorambucil can provide good long term palliation in low grade lymphomas, for example feline small cell gastrointestinal lymphoma.
: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.
: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.
: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 or 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 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.
Whilst receiving chemotherapy. patients should receive a high quality, palatable diet to maintain calorific intake. If animals become anorexic, the cause should be investigated.
''' Prognosis'''
Unfortunately it is unusual for animals with lymphoma to be cured, and whilst the disease goes into remission in most patients treated with multi-modal chemotherapy, typically they will relapse after a period of weeks to months. At this time, rescue chemotherapy can be performed but often does not provide a long second remission period.
===Horses===
===Horses===
==Prognosis==
==Prognosis==
===Cats and Dogs===
===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 it is thought to be around 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 6-12 months for canine multicentric lymphoma depending on the protocol used and a huge variety of other factors - the median survival of other disease sites and species is less well documented. Documented poor prognostic indicators in the dog include T cell immunophenotype, cranial mediastinal involvement, hypercalcemia, bone marrow involvement and being ill at diagnosis (substage b).
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).
{{Learning
{{Learning
|Vetstream = [https://en.wikivet.net/Lymphoma, Canine lymphoma]
|flashcards = [[Feline Medicine Q&A 12]]<br>[[Feline Medicine Q&A 19]]<br>[[Cytology Q&A 03]]<br>[[Cytology Q&A 10]]<br>[[Equine Internal Medicine Q&A 18]]
|flashcards = [[Feline Medicine Q&A 12]]<br>[[Feline Medicine Q&A 19]]<br>[[Cytology Q&A 03]]<br>[[Cytology Q&A 10]]<br>[[Equine Internal Medicine Q&A 18]]
|literature search = [http://www.cabdirect.org/search.html?q=title%3A%28lymphoma%29+AND++od%3A%28dogs%29 Lymphoma in dogs publications]
|literature search = [http://www.cabdirect.org/search.html?q=title%3A%28lymphoma%29+AND++od%3A%28dogs%29 Lymphoma in dogs publications]
{{review}}
{{review}}
{{OpenPages}}
[[Category:Stomach_and_Abomasum_-_Proliferative_Pathology]][[Category:Lymphoreticular and Haemopoietic Diseases]]
[[Category:Stomach_and_Abomasum_-_Proliferative_Pathology]][[Category:Lymphoreticular and Haemopoietic Diseases]]
[[Category:Neoplasia]][[Category:Intestines_-_Proliferative_Pathology]][[Category:Tongue_-_Pathology]]
[[Category:Neoplasia]][[Category:Intestines_-_Proliferative_Pathology]][[Category:Tongue_-_Pathology]]