Difference between revisions of "Lymphoma"

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Also known as: '''''Lymphosarcoma — Malignant Lymphoma'''''
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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]]
  
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==Introduction==   
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==Description==   
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[[Image:tonguelymphoma.gif|right|thumb|125px|<small><center>Tongue Lymphoma - a recognised entity (Courtesy of Alun Williams (RVC))</center></small>]]
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Lymphoma is caused by malignant clonal expansion of lymphoid cells and most commonly arises from lymphoid tissues including the [[Bone Marrow|bone marrow]], [[Thymus|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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[[Image:Lymphoma in nasal cavity.jpg|right|thumb|200px|<small><center>Lymphoma in nasal cavity (Image sourced from Bristol Biomed Image Archive with permission)</center></small>]]
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In the dog, multicentric lymphoma is most common representing 80% of cases. [[Alimentary - 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.  
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[[File:Lymphoma in golden.JPG|right|thumb|200px| Lymphoma in a Golden Retriever (Wikimedia Commons)]]
 
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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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'''Classification'''
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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.
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:'''Cytological classification'''
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Only 10% of lymphoma cases in cats are now associated with FeLV.
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::Well differentiated (lymphocytic) - The malignant cells represent normal lymphocytes, although in excessive numbers.
 
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::Poorly differentiated (lymphoblastic) - The malignant cells represent atypical lymphocytic cells with lymphoblastic characteristics.
 
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:'''Tumour distribution'''
 
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::Nodular/ follicular - A well organised pattern of slow growth, no metastasis, they are of the B-lymphocyte type
 
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::Diffuse - Result in effacement of normal lymphoid architecture by a very homogeneous population of lymphoid cells.
 
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:'''Anatomical classification'''
 
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::Thymic - Only the [[Thymus - Anatomy & Physiology|thymus]] is affected.
 
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::Alimentary - Gut and associated lymphoid tissue affected.
 
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::Multicentric - Widespread involvement of lymph nodes.
 
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::Cutaneous lymphoma - Usually presents as generalised skin disease, but is a malignant transformation of T cells with a propensity for  epithelial sites.
 
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:'''Type of lymphocyte''' - [[T cells|T-cell]], [[B cells|B-cell]] or [[Natural Killer cells|NK-cell]]
 
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:'''Time scale''' - Acute or Chronic
 
−
 
 
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Order of '''prevalence''' in UK is cats, dogs, cattle, pigs and sheep. In the cat and ox, viral agents have been identified as the causal agents.
 
−
 
 
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===Dog===
 
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Lymphoma is one of the prevalent neoplasms in the dog. The incidence is about 28 per 100,000 dogs. Blood of affected dogs shows neither a relative nor absolute increase in the number of lymphocytes until the late stages of the disease. When this stage is reached, poorly differentiated cells may appear in the blood.
 
−
 
 
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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.
 
−
 
 
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===Cat===
 
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[[FeLV]] is an important cause of lymphoma in the cat. 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.
 
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Only 10% of lymphoma cases in cats are now associated with FeLV, whereas it used to be 70%.
 
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The alimentary form arises from the mesenteric lymph nodes or intestine, [[Liver - Anatomy & Physiology|liver]]. The thymic form presents as a thymic mass. The bronchial, cranial mediastinal and pre-sternal lymph nodes may potentially be affected. The multicentric form is rare in the cat. This form originates in the peripheral lymph nodes, later involving liver, spleen and other organs, eventually bone marrow in some cases. Cats can also develop extra-nodal lymphoma in several sites including the CNS and kidneys. A leukaemic form affecting the bone marrow alone is rare.
 
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===Horse===
 
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In horses, lymphoma is the most common haemopoietic neoplasm. It has been characterised into four main forms: '''alimentary, cutaneous, mediastinal and multicentric''', however, it takes mainly the alimentary form.
 
−
 
 
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===Cattle===
 
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Cattle suffer both lymphosarcoma and leukosis in a variety of cytological forms. Bovine lymphoma is caused by [[Bovine Leukaemia Virus]] (BLV). There is a [[Sporadic Bovine Leukosis|juvenile form of bovine lymphoma]] seen in young cattle which is not associated with BLV.
 
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===Pig===
 
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Porcine disease is mainly multicentric affecting lymph nodes, liver and spleen.
 
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===Sheep===
 
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Ovine lymphoma is uncommon. It may be multicentric or thymic.
 
  
 
==Signalment==
 
==Signalment==
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===Dog===
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The median age of affected cats  is 9-10 years and oriental [[Feline Breeds - WikiNormals|cat breeds]] may be predisposed.
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Affected dogs have a wide age range, most are middle-aged however young animals can be affected, 80% of cases affect the 5 to 11 year old age group. There may also be a male predilection.
 
  
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===Cat===
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Affected dogs have a wide age range, most are middle-aged however young animals can be affected. There may also be a male predilection.
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The median age of affected cats is 9-10 years and oriental [[Feline Breeds - WikiNormals|cat breeds]] may be predisposed.
 
−
 
−
===Horse===
 
−
There are no sex, age or breed predilections.
 
  
 +
==Diagnosis== 
 
==Clinical Signs==
 
==Clinical Signs==
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===Dogs===
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====Dogs: Multicentric Lymphoma====
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'''Multicentric Lymphoma'''
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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.
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: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.
  
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'''Mediastinal''' forms may present with dyspnoea due to compression of the trachea and lungs. Dogs with mediastinal lymphoma can also have pitting [[Oedema|oedema]] of the head and neck due to compression of the cranial vena cava, called caval syndrome. On ausculatation there is often an absence of lung sounds cranially and caudal displacement of the normal cardiac sounds, and dullness on percussion of the cranial thorax. Polyuria and polydypsia may be present due to paraneoplastic hypercalcaemia. Differential diagnoses for a cranial mediastinal mass include: thymoma, thyroid adenocarcinoma, a mediastinal abscess, or a branchial cyst.
+
'''Mediastinal''' forms will present with decreased [[Heart - Anatomy & Physiology|heart]] sounds, [[Dyspnoea|dyspnoea]] and polyuria and polydypsia due to paraneoplastic hypercalcaemia.
−
 
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Dogs with mediastinal lymphoma can also have pitting [[Oedema - Pathology|oedema]] of the head and neck due to compression of the cranial vena cava.
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'''Alimentary''' forms may present with signs such as [[Vomiting|vomiting]], [[Diarrhoea|diarrhoea]], anorexia and thickened loops of intestine or mass lesions on abdominal palpation.
 
−
 
 
−
'''Cutaneous''' lymphoma can also occur with a varied presentation but often present as cutaneous nodules or plaques.
 
−
 
 
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===Cats===
 
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In contrast to dogs, cats are more likely to present unwell. Again the clinical signs will depend on the anatomical location affected.
 
−
 
 
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'''Alimentary''' cats often present with vomiting, diarrhoea, weight loss and anorexia.
 
−
 
 
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'''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 typically present with bilateral renomegally and signs similar to [[:Category:Renal Failure|renal failure]].
 
−
 
 
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'''Nasal''' lymphoma cases may present with any of dyspnoea, nasal discharge, epistaxis, facial pain or distortion and loss of airflow.
 
−
 
 
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===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]]'''.
 
−
 
 
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Mediastinal lymphoma also produces clinical signs such as pointing of the forelimb, tachycardia, distension of the jugular vein and caudal displacement of the heart - it may be confused with [[:Category:Colic in Horses|colic]]. It should be differentiated from mediastinal abscessation by ultrasound of the mass and cytology of pleural fluid.
 
−
 
 
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Intra-abdominal neoplasia (which can be multicentric or alimentary) may presents with a history of chronic weight loss and inappetance, recurring colic and intermittant pyrexia.
 
−
 
 
−
==Physical Examination==
 
−
 
 
−
===Cat and Dog===
 
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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.
 
−
 
 
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===Horse===
 
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Mediastinal masses can sometimes be palpable externally at the base of the jugular groove, due to the mass extending through the thoracic inlet.
 
−
 
 
−
==Diagnosis==
 
−
===Laboratory Tests===
 
−
'''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 and dogs are not usually leukemic.
+
'''Alimentary''' forms will present with [[Vomiting|vomiting]], [[Diarrhoea|diarrhoea]], anorexia and thickened loops of [[Small Intestine - Anatomy & Physiology|intestine]] on abdominal palpation.
  
−
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.  
+
'''Cutaneous''' lymphoma can also occur with a varied presentation but often present as cutaneous nodules.
  
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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.  
+
====Feline Lymphoma====
 +
In contrast to dogs, cats are more likely to present unwell. Again the clinical signs will depend on the anatomical location affected.
  
−
'''Paraneoplastic Syndrome'''
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'''Alimentary''' cats will present with vomiting, diarrhoea, weight loss and anorexia.
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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.
 
  
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===Radiography===
+
'''Mediastinal''' cats will present with respiratory signs and may be in respiratory distress.
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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===
+
'''Renal''' lymphoma also occurs in cats and affeted animals will present with signs similar to [[Kidney Renal Failure - Pathology|renal failure]].
−
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===
+
===Physical Examination===  
−
[[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)]]
+
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.
−
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
+
Petechiae, [[Anaemia - Introduction|anaemia]] and icterus may also be present in any form of lymphoma.
−
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 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.
+
==Laboratory Tests==
 +
===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.
 +
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]].
  
−
Smears should be '''stained''' and examined microscopically.
+
===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.
  
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Cytological criteria for lymphoma:
+
===Paraneoplastic Syndromes===
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* '''Large amounts of lymphoblasts'''
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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
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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''' 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.
+
==Radiography==
 +
A mass may be visible via plain or contrast abdominal radiography. Both abdominal and thoracic imaging is required in assessing the surrounding structures.
  
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'''Dogs'''
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==Ultrasonography==
−
: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.
+
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.
  
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'''Cats'''
+
==Bone Marrow Aspirate/Biopsy==
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: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:
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Should be taken ideally for all cases as part of the staging procedure.
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::'''Ultrasound guided aspirates''', '''partial thickness endoscopic grab biopsies''' or '''full thickness biopsies''' via '''exploratory laparotomy''' for intestinal lymphoma
 
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::'''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)
 
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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 result 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 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.
 
−
 
 
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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.
 
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:A sample of pleural or peritoneal fluid may be taken and examined cytologically if it is present. Otherwise a direct fine needle aspirate of the mass of lymph nodes may be performed. The fluid should be a modified transudate and contain a mixed cell population. Neoplastic lymphocytes are pleomorphic round cells that demonstrate anisocytosis and anisokaryosis and have very basophilic cytoplasm. If these cells are present then the diagnosis of lymphoma can be confirmed, otherwise surgical biopsy may be necessary.
 
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===Biopsy===
 
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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'''.
 
−
 
 
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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.
 
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'''Bone marrow aspiration or biopsy is needed to stage the disease'''. 
 
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====Pathology====
 
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'''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.
 
−
 
 
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'''Splenomegaly''' occurs in multicentric lymphosarcoma.  Splenic enlargement may be marked if any form of lymphosarcoma is in leukaemic phase.
 
  
 
===Staging===
 
===Staging===
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A staging system is used for multicentric lymphoma (Owen, 1980):
+
A staging system is used for 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)
Line 175: Line 69:
 
* Stage IV - Liver and/or 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. Other lymphomas such as primary hepatic are typically automatically classed as a grade V.
 
  
 
==Treatment==
 
==Treatment==
 +
===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).
  
−
===Cats and Dogs===
+
===Radiotherapy===
−
 
+
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'''
 
−
: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'''
 
−
: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'''
 
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: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.
 
−
:* COAP consists of cyclophosphamide, vincristine, prednisolone and cytosine arabinoside
 
−
:* 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.
 
−
: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'''
 
−
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'''
+
===Chemotherapy===
−
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.
+
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.
 +
* COAP consists of Cyclophosphamide, Vincristine, Prednisolone and Cytosine arabinoside
 +
* CHOP consists of Cyclophosphamide, Vincristine, Prednisolone and Doxorubicin.
 +
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.
  
−
===Horses===
+
===Supportive Therapy===
−
Treatment is symptomatic and euthanasia may be required with the progression of clinical signs.
+
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 antiemetics if vomiting occurs.
 +
Additionally fluid therapy, laxatives and analgesia may be required.
  
 
==Prognosis==
 
==Prognosis==
−
===Cats and Dogs===
+
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 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).
  
−
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 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.
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===Horse===
 
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The prognosis is '''poor''' and definitive diagnosis is usually achieved on post-mortem examination.
 
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{{Learning
 
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|Vetstream = [https://en.wikivet.net/Lymphoma, Canine lymphoma]
 
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|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]]
 
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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]
 
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[http://www.cabdirect.org/search.html?q=title%3A%28lymphoma%29+AND+od%3A%28cats%29 Lymphoma in cats publications]
 
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}}
 
  
 
==References==
 
==References==
−
Copas, V (2011) '''Diagnosis and treatment of equine pleuropneumonia''' ''In Practice 2011 33: 155-16''
+
−
 
 
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Cowell, R. (2002) '''Diagnostic cytology and haematology of the horse''' ''Elsevier Health Sciences''
 
−
 
 
−
Freeman, KP (2007) '''Self-Assessment Colour Review of Veterinary Cytology - Dog, Cat, Horse and Cow''' ''Manson''
 
−
 
 
−
Gear, R (2009) '''Practical update on canine lymphoma : 1. Classification and Diagnosis''' ''In Practice 2009 31: 380-384''
 
−
 
 
 
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
−
 
−
Hayes, A (2006) '''Feline lymphoma 2. Specific Disease Presentations''' ''In Practice 2006 28, pp 578-585''
 
  
 
Head K. W, Else R. W, Dubielzig R.R, (2002)''' Tumours of the Alimentary Tract, in Tumours in Domestic Animals''', 4th edition, Ed Menten D. J, Iowa State Press, ''Blackwell Publishing'', Iowa, pp 471-472
 
Head K. W, Else R. W, Dubielzig R.R, (2002)''' Tumours of the Alimentary Tract, in Tumours in Domestic Animals''', 4th edition, Ed Menten D. J, Iowa State Press, ''Blackwell Publishing'', Iowa, pp 471-472
−
 
−
Hewetson, M (2006) '''Investigation of false colic in the horse''' ''In Practice 2006 28: 326-33''
 
−
 
−
Milne, E (2004) '''Peritoneal fluid analysis for the differentiation of medical and surgical colic in horses''' ''In Practice 2004 26: 444-44''
 
  
 
Morris J, Dobson J (2001) '''Gastrointestinal Tract, in Small Animal Oncology''', ''Blackwell Science'', pp 228-239
 
Morris J, Dobson J (2001) '''Gastrointestinal Tract, in Small Animal Oncology''', ''Blackwell Science'', pp 228-239
  
 
Selting K. A, (2007), '''Intestinal Tumours, Cancer of the Gastrointestinal Tract, in Withrow and MacEwen's Small Animal Clinical Oncology''', fourth edition, Eds Withrow S.J, Vail D.M, Missouri, ''Saunders Elsevier'', pp 491-501  
 
Selting K. A, (2007), '''Intestinal Tumours, Cancer of the Gastrointestinal Tract, in Withrow and MacEwen's Small Animal Clinical Oncology''', fourth edition, Eds Withrow S.J, Vail D.M, Missouri, ''Saunders Elsevier'', pp 491-501  
−
 
−
Sparks, AH & Caney, SMA (2005) '''Self-Assessment Colour Review Feline Medicine''' ''Manson''
 
−
 
−
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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[[Category:Stomach_and_Abomasum_-_Proliferative_Pathology]][[Category:Lymphoreticular and Haemopoietic Diseases]]
 
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[[Category:Neoplasia]][[Category:Intestines_-_Proliferative_Pathology]][[Category:Tongue_-_Pathology]]
 
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[[Category:Intestinal Diseases - Dog]]
 
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[[Category:Gastric Diseases - Dog]][[Category:Lymphoreticular and Haematopoietic Diseases - Dog]]
 
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[[Category:Intestinal Diseases - Cat]][[Category:Gastric Diseases - Cat]][[Category:Lymphoreticular and Haematopoietic Diseases - Cat]]
 
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[[Category:Alimentary Diseases - Horse]]
 
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[[Category:Nasal Cavity - Hyperplastic/Neoplastic Pathology]]
 
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[[Category:Respiratory System - Hyperplastic/Neoplastic Pathology]]
 
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[[Category:Liver,_Secondary_Tumours]]
 
  
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[[Category:Stomach_and_Abomasum_-_Proliferative_Pathology]][[Category:Dog]][[Category:Cattle]]
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[[Category:Intestines_-_Proliferative_Pathology]]
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[[Category:To Do - Caz]][[Category:Lymphoreticular and Haemopoietic Diseases]]
 
[[Category:Neoplasia]]
 
[[Category:Neoplasia]]
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[[Category:Splenic Neoplasia]]
 
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[[Category:Expert Review]]
 

Revision as of 21:28, 19 August 2010


 This article is still under construction.


Tongue Lymphoma - a recognised entity (Courtesy of Alun Williams (RVC))

Description

Lymphoma is caused by malignant clonal expansion of lymphoid cells and most commonly arises from lymphoid tissues including the bone marrow, thymus, lymph nodes and spleen. Lymphoma is documented to be the most common haematopoietic 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 cats following the inroduction of widespread FeLV testing and 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.

Signalment

The median age of affected cats is 9-10 years and oriental 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.

Diagnosis

Clinical Signs

Dogs: Multicentric Lymphoma

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.

Mediastinal forms will present with decreased heart sounds, dyspnoea and polyuria and polydypsia due to paraneoplastic hypercalcaemia. Dogs with mediastinal lymphoma can also have pitting oedema of the head and neck due to compression of the cranial vena cava.

Alimentary forms will present with vomiting, 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.

Feline Lymphoma

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.

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 renal failure.

Physical Examination

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 and icterus may also be present in any form of lymphoma.

Laboratory Tests

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 involvement may include lymphocytosis, thrombocytopenia, neutropenia and the presence of immature lymphoid precursors. Affected cats are not usually leukemic. On biochemistry abnormalities may include hypoproteinaemia, elevated hepatic enzymes and elevated Blood Urea Nitrogen /creatinine.

FeLV/FIV

All cats with suspected lymphoma should be tested for FeLV and FIV, usually performed via enzyme-linked immunosorbent assay (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

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

A mass may be visible via plain or contrast abdominal radiography. Both abdominal and thoracic imaging is required in assessing the surrounding structures.

Ultrasonography

Superior to radiography in assessing infiltration or abnormalities of tissue architecture and assessing the surrounding structures for metastasis. Guided aspirates or biopsies may also be taken at this time, including lymph node sampling, to evaluate degree of systemic involvement.

Bone Marrow Aspirate/Biopsy

Should be taken ideally for all cases as part of the staging procedure.

Staging

A staging system is used for lymphoma (Owen, 1980):

  • 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 III - Generalised lymph node involvement
  • 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)

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

Treatment

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).

Radiotherapy

Lymphoma is highly radiosensitive and in theory should be efficient in treating all forms of lymphoma, however, surrounding tissues often have a low tolerance.

Chemotherapy

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.
  • COAP consists of Cyclophosphamide, Vincristine, Prednisolone and Cytosine arabinoside
  • CHOP consists of Cyclophosphamide, Vincristine, Prednisolone and Doxorubicin.

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, neutropenia/sepsis, hypercalcaemia and pyrexia.

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 antiemetics if vomiting occurs. Additionally fluid therapy, laxatives and analgesia may be required.

Prognosis

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

References

Hayes A. (2006) Feline lymphoma 1. Principles of diagnosis and management, In Practice, 28, pp 516-524

Head K. W, Else R. W, Dubielzig R.R, (2002) Tumours of the Alimentary Tract, in Tumours in Domestic Animals, 4th edition, Ed Menten D. J, Iowa State Press, Blackwell Publishing, Iowa, pp 471-472

Morris J, Dobson J (2001) Gastrointestinal Tract, in Small Animal Oncology, Blackwell Science, pp 228-239

Selting K. A, (2007), Intestinal Tumours, Cancer of the Gastrointestinal Tract, in Withrow and MacEwen's Small Animal Clinical Oncology, fourth edition, Eds Withrow S.J, Vail D.M, Missouri, Saunders Elsevier, pp 491-501

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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