Difference between revisions of "Lymphoma"

From WikiVet English
Jump to navigation Jump to search
(127 intermediate revisions by 7 users not shown)
Line 1: Line 1:
−
{{OpenPagesTop}}
+
{{dog}}
−
Also known as: '''''Lymphosarcoma — Malignant Lymphoma'''''
+
{{cat}}
 +
[[Image:tonguelymphoma.gif|right|thumb|125px|<small><center>Tongue Lymphoma - a recognised entity (Courtesy of Alun Williams (RVC))</center></small>]][[Category:Tongue_-_Pathology]]
 +
==Gastric==
 +
* Diffuse infiltration of [[Lymphocytes|lymphocytes]].
 +
* Seen primarlity in dogs and cattle, but also in the pig and cat.
  
−
==Introduction==
+
==Intestinal==
−
[[Image:tonguelymphoma.gif|right|thumb|125px|<small><center>Tongue Lymphoma - a recognised entity (Courtesy of Alun Williams (RVC))</center></small>]]
+
* Lymphoma occurs in both the small and [[Large Intestine - Anatomy & Physiology|large intestine]]s.
−
[[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>]]
+
* Is a relatively common neoplasm of the cat and dog.
−
[[File:Lymphoma in golden.JPG|right|thumb|200px| Lymphoma in a Golden Retriever (Wikimedia Commons)]]
+
* Causes a diffuse spread of neoplastic lymphocytes through the mucosa and the rest of the wall.
−
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.  
+
** Leads to malabsorption and therefore [[Diarrhoea|diarrhoea]] and the development of a protein losing enteropathy.
  
−
'''Classification'''
+
=Alimentary Lymphoma=
−
:'''Cytological classification'''
+
Intestinal tumours are uncommon accounting for less than 10% of all tumours in dogs and cats and 22% of gastrointestinal tumours in dogs and 35% in cats. Intestinal tumours in dogs and cats are usually malignant, alimentary lymphoma (AL) being the most common type of intestinal malignancy in cats and the second most frequent malignancy to affect the intestine in dogs. Primary AL may be differentiated from widespread multicentric lymphoma by the fact that the lymph nodes are not affected with AL. AL must also be distinguished from localised lymphoma that affects the mesenteric lymph node only with no intestinal involvement, which should be classified in the miscellaneous lymphoma group.  
−
::Well differentiated (lymphocytic) - The malignant cells represent normal lymphocytes, although in excessive numbers.
 
−
::Poorly differentiated (lymphoblastic) - The malignant cells represent atypical lymphocytic cells with lymphoblastic characteristics.
 
−
:'''Tumour distribution'''
 
−
::Nodular/ follicular - A well organised pattern of slow growth, no metastasis, they are of the B-lymphocyte type
 
−
::Diffuse - Result in effacement of normal lymphoid architecture by a very homogeneous population of lymphoid cells.
 
−
:'''Anatomical classification'''
 
−
::Thymic - Only the [[Thymus - Anatomy & Physiology|thymus]] is affected.
 
−
::Alimentary - Gut and associated lymphoid tissue affected.
 
−
::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.
 
−
:'''Type of lymphocyte''' - [[T cells|T-cell]], [[B cells|B-cell]] or [[Natural Killer cells|NK-cell]]
 
−
:'''Time scale''' - Acute or Chronic
 
  
−
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.
 
−
 
−
===Dog===
 
−
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.
 
−
 
−
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.
 
−
 
−
===Cat===
 
−
[[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.
 
−
Only 10% of lymphoma cases in cats are now associated with FeLV, whereas it used to be 70%.
 
−
 
−
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.
 
−
 
−
===Horse===
 
−
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.
 
−
 
−
===Cattle===
 
−
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.
 
−
 
−
===Pig===
 
−
Porcine disease is mainly multicentric affecting lymph nodes, liver and spleen.
 
−
 
−
===Sheep===
 
−
Ovine lymphoma is uncommon. It may be multicentric or thymic.
 
  
 
==Signalment==
 
==Signalment==
−
===Dog===
+
* Cats:
−
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.
+
** Usually over 5 years of age
 +
** Oriental breeds may be predisposed
 +
* Dogs:
 +
** Wide age range, most are middle-aged though young can be affected
 +
** There may be a male predilection
  
−
===Cat===
 
−
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.
 
  
−
==Clinical Signs==
+
==Description==
−
===Dogs===
+
* Localised lymphoma: can be intramural or extend intraluminally. The lesion may be focal or multifocal. The tumour can be of a variety of shapes namely nodular, plaque-like or circumferential. Circumferential transmural or intramural tumours often bulge outward since the diseased muscle atrophies so that rows of lymphocytes remain supported by parallel bands of reticulum fibers only. The circumferential intramural form is the most frequently seen in the feline intestine.
−
'''Multicentric Lymphoma'''
+
* Diffuse lymphoma: with these tumours there is a granular or cobblestone appearance to the mucosa. The mesenteric lymph nodes are often affected.
−
: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.
+
* In cats the most frequent sites are the jejunum, ileocaecocolic junction, duodenum, colon and stomach (in decreasing order of frequency).
 +
* In dogs focal lesions most frequently occur in the small intestine. Multifocal tumours are rarer and affect various sites.
 +
* At the time of diagnosis in cats tumour nodules are often already apparent in the liver, kidney, spleen and abdominal and sternal lymph nodes. Differentiating AL and multicentric lymphoma may be difficult at this point.
 +
* In most cats AL is not associated with FeLV and aetiololgy is idiopathic.
  
−
For other types of lymphoma affecting dogs the clinical signs will demonstrate the anatomical site affected.
+
==Diagnosis== 
 +
===Clinical Signs===
 +
The following may be seen:
 +
* Vomiting
 +
* Diarrhoea
 +
* Weight loss
 +
* Anorexia
 +
* Tenesmus
 +
* Dyschezia
 +
* (Peritonitis - following complete intestinal obstruction and rupture)
  
−
'''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.
+
===Physical Examination===
 +
* An abdominal mass may be palpable
 +
* Bowel loops may feel thickened
 +
* Enlarged mesenteric lymph nodes may be palpable
  
−
'''Alimentary''' forms may present with signs such as [[Vomiting|vomiting]], [[Diarrhoea|diarrhoea]], anorexia and thickened loops of intestine or mass lesions on abdominal palpation.
+
===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 include:
 +
* For those with bone marrow involvement:
 +
** Lymphocytosis
 +
** Thrombocytopenia
 +
** Neutropenia
 +
** Presence of immature lymphoid precursors
 +
* Affected cats are not usually leukemic
 +
* Hypoproteinaemia
 +
* Elevated hepatic enzymes
 +
* Elevated BUN/creatinine
  
−
'''Cutaneous''' lymphoma can also occur with a varied presentation but often present as cutaneous nodules or plaques.
+
===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.
  
−
===Cats===
+
===Paraneoplastic Syndromes===
−
In contrast to dogs, cats are more likely to present unwell. Again the clinical signs will depend on the anatomical location affected.
+
* Dogs may present with hypercalcaemia, affected cats are not usually hypercalcaemic
−
 
+
* (Hypergammaglobulinaemia)
−
'''Alimentary''' cats often present with vomiting, diarrhoea, weight loss and anorexia.
 
−
 
 
−
'''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]].
 
−
 
 
−
'''Nasal''' lymphoma cases may present with any of dyspnoea, nasal discharge, epistaxis, facial pain or distortion and loss of airflow.
 
−
 
 
−
===Horse===
 
−
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]]'''.
 
−
 
 
−
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.
 
−
 
 
−
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===
 
−
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.
 
−
 
 
−
===Horse===
 
−
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.
 
−
 
 
−
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). 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'''
 
−
Dogs may present with [[hypercalcaemia]], this is due to the release of parathyroid hormone - related protein (PTHrp) released by the tumor, which produces these effects by acting like parathyroid hormone. Affected cats are not usually hypercalcaemic.
 
  
 
===Radiography===
 
===Radiography===
−
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.
+
A mass may be visible via plain or contrast abdominal radiography. Both abdominal and thoracic imaging is required in assessing the surrounding structures.
  
 
===Ultrasonography===
 
===Ultrasonography===
−
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.
+
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.
−
 
 
−
===Cytology===
 
−
[[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)]]
 
−
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''',
 
−
'''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.
 
−
 
 
−
Smears should be '''stained''' and examined microscopically.
 
−
 
 
−
Cytological criteria for lymphoma:
 
−
* '''Large amounts of lymphoblasts'''
 
−
* '''Large nuclei and prominent nucleoli'''
 
−
* '''High mitotic rate - bizarre mitotic figures may be present'''
 
−
* '''Small volume of basophilic cytoplasm'''
 
−
* '''Coarse chromatin'''
 
−
 
 
−
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'''
 
−
: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'''
 
−
: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 intestinal 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
 
−
 
 
−
: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|
 
−
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'''
 
−
:In equine lymphoma, neoplastic cells are not always present, but when they are this may allow diagnosis.
 
−
: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.
 
  
−
===Biopsy===
+
===Bone Marrow Aspirate/Biopsy===
−
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'''.
+
Should be taken ideally for all cases as part of the staging procedure.  
−
 
 
−
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.
 
−
 
 
−
Nasal lymphoma can be diagnosed by rhinoscopic or blind biopsy using a suction-catheter or grab-forceps technique.
 
−
 
 
−
'''Bone marrow aspiration or biopsy is needed to stage the disease'''. 
 
−
 
 
−
====Pathology====
 
−
'''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.
 
  
 
===Staging===
 
===Staging===
−
A staging system is used for multicentric lymphoma (Owen, 1980):
+
A group 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 84:
 
* 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, celiotomy is required for many cases of AL 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. 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.
−
'''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'''
+
===Chemotherapy===
−
: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.  
+
* Combination chemotherapy is the most frequent method of treatment
 +
* Commonly used protocols include:
 +
** COP -  Cyclophosphamide, Vincristine, Prednisolone. Frequently used in cats and can be used for induction therapy (8weeks) as well as a long term maintenance protocol
 +
** COAP - Cyclophosphamide, Vincristine, Prednisolone, Cytosine arabinoside
 +
** CHOP - Cyclophosphamide, Vincristine, Prednisolone, Doxorubicin, (potentiated sulphonamides)
 +
* 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 degree of effects of drugs.
  
−
'''Chemotherapy'''
+
===Supportive Therapy===
−
:Combination chemotherapy is the most frequent method of treatment and the most commonly used protocols include:
+
For those receiving chemotherapy:  
−
:* 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.
+
* High quality, palatable diet
−
:* COAP consists of cyclophosphamide, vincristine, prednisolone and cytosine arabinoside
+
* Appetite stimulation in cats e.g Cyproheptadine (Periactin)
−
:* CHOP consists of cyclophosphamide, vincristine, prednisolone and doxorubicin.
+
* Antiemetics
−
:* Prednisolone and chlorambucil can provide good long term palliation in low grade lymphomas, for example feline small cell gastrointestinal lymphoma.
+
* Assisted (tube) feeding
−
: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.
+
* Fluid therapy
−
: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.
+
* Laxatives
−
 
+
* Analgesia
−
'''Supportive Therapy'''
+
* Treatment for and monitoring of:
−
Whilst receiving chemotherapy. patients should receive a high quality, palatable diet to maintain calorific intake. If animals become anorexic, the cause should be investigated.
+
** Azotaemia
−
 
+
** Neutropenia/sepsis
−
''' Prognosis'''
+
** Hypercalcaemia
−
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.
+
** Pyrexia
−
 
 
−
===Horses===
 
−
Treatment is symptomatic and euthanasia may be required with the progression of clinical signs.
 
  
 
==Prognosis==
 
==Prognosis==
−
===Cats and Dogs===
+
* Mean survival times for dogs and cats:
−
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.
+
** Without therapy: 6-8 weeks.  
−
 
+
** For those receiving cortocosteroids only: 3 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).  
+
** For those receiving chemotherapy: 6-9 months.
−
Local canine lymphoma responds better to chemotherapy than the diffuse form of disease.  
+
* Local canine lymphoma responds better to chemotherapy than the diffuse form of disease.  
−
Immunophenotype (T cell versus B cell lymphoma) does not appear to be associated with prognosis in cats as it can be in dogs. Factors indicating a better prognosis (overall survival) in '''cats''' include: '''an early presentation, a complete initial response to treatment and a clinically well patient''' (‘substage a’ disease).
+
* Immunophenotype (T cell versus B cell lymphoma)does not appear to be associated with prognosis in cats as it can be in dogs. Factors indicating a better prognosis (overall survival) in cats include:
−
 
+
** Early presentation
−
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.
+
** A complete initial response to treatment
−
 
+
** A clinically well patient(‘substage a’ disease)
−
===Horse===
+
** Whether doxorubicin is included in the treatment protocol may also affect prognosis
−
The prognosis is '''poor''' and definitive diagnosis is usually achieved on post-mortem examination.
+
* In cats, response rate to induction chemotherapy is 26-79%
−
 
+
* Thus there is an apparently a poorer response rate in cats compared with dogs, however, 30-40% of cats that do have complete remission 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.
−
{{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]]
 
−
|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%28cats%29 Lymphoma in cats publications]
 
−
}}
 
  
 
==References==
 
==References==
−
Copas, V (2011) '''Diagnosis and treatment of equine pleuropneumonia''' ''In Practice 2011 33: 155-16''
+
−
 
+
* Hayes A. (2006) Feline lymphoma 1. Principles of diagnosis and management, In Practice, 28, pp 516-524
−
Cowell, R. (2002) '''Diagnostic cytology and haematology of the horse''' ''Elsevier Health Sciences''
+
* 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
−
Freeman, KP (2007) '''Self-Assessment Colour Review of Veterinary Cytology - Dog, Cat, Horse and Cow''' ''Manson''
+
* 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
−
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 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
 
−
 
 
−
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
 
−
 
 
−
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
 
−
 
 
−
 
 
−
{{review}}
 
−
 
 
−
{{OpenPages}}
 
−
[[Category:Stomach_and_Abomasum_-_Proliferative_Pathology]][[Category:Lymphoreticular and Haemopoietic Diseases]]
 
−
[[Category:Neoplasia]][[Category:Intestines_-_Proliferative_Pathology]][[Category:Tongue_-_Pathology]]
 
−
 
 
−
[[Category:Intestinal Diseases - Dog]]
 
−
[[Category:Gastric Diseases - Dog]][[Category:Lymphoreticular and Haematopoietic Diseases - Dog]]
 
  
−
[[Category:Intestinal Diseases - Cat]][[Category:Gastric Diseases - Cat]][[Category:Lymphoreticular and Haematopoietic Diseases - Cat]]
 
  
−
[[Category:Alimentary Diseases - Horse]]
 
−
[[Category:Nasal Cavity - Hyperplastic/Neoplastic Pathology]]
 
−
[[Category:Respiratory System - Hyperplastic/Neoplastic Pathology]]
 
−
[[Category:Liver,_Secondary_Tumours]]
 
  
 +
[[Category:Stomach_and_Abomasum_-_Proliferative_Pathology]][[Category:Dog]][[Category:Cattle]]
 +
[[Category:Intestines_-_Proliferative_Pathology]]
 +
[[Category:To Do - Blood]][[Category:Lymphoreticular and Haemopoietic Diseases]]
 
[[Category:Neoplasia]]
 
[[Category:Neoplasia]]
−
[[Category:Splenic Neoplasia]]
 
−
[[Category:Expert Review]]
 

Revision as of 13:22, 11 August 2010

Category:WikiClinical CanineCow
Category:WikiClinical FelineCow
Tongue Lymphoma - a recognised entity (Courtesy of Alun Williams (RVC))

Gastric

  • Diffuse infiltration of lymphocytes.
  • Seen primarlity in dogs and cattle, but also in the pig and cat.

Intestinal

  • Lymphoma occurs in both the small and large intestines.
  • Is a relatively common neoplasm of the cat and dog.
  • Causes a diffuse spread of neoplastic lymphocytes through the mucosa and the rest of the wall.
    • Leads to malabsorption and therefore diarrhoea and the development of a protein losing enteropathy.

Alimentary Lymphoma

Intestinal tumours are uncommon accounting for less than 10% of all tumours in dogs and cats and 22% of gastrointestinal tumours in dogs and 35% in cats. Intestinal tumours in dogs and cats are usually malignant, alimentary lymphoma (AL) being the most common type of intestinal malignancy in cats and the second most frequent malignancy to affect the intestine in dogs. Primary AL may be differentiated from widespread multicentric lymphoma by the fact that the lymph nodes are not affected with AL. AL must also be distinguished from localised lymphoma that affects the mesenteric lymph node only with no intestinal involvement, which should be classified in the miscellaneous lymphoma group.


Signalment

  • Cats:
    • Usually over 5 years of age
    • Oriental breeds may be predisposed
  • Dogs:
    • Wide age range, most are middle-aged though young can be affected
    • There may be a male predilection


Description

  • Localised lymphoma: can be intramural or extend intraluminally. The lesion may be focal or multifocal. The tumour can be of a variety of shapes namely nodular, plaque-like or circumferential. Circumferential transmural or intramural tumours often bulge outward since the diseased muscle atrophies so that rows of lymphocytes remain supported by parallel bands of reticulum fibers only. The circumferential intramural form is the most frequently seen in the feline intestine.
  • Diffuse lymphoma: with these tumours there is a granular or cobblestone appearance to the mucosa. The mesenteric lymph nodes are often affected.
  • In cats the most frequent sites are the jejunum, ileocaecocolic junction, duodenum, colon and stomach (in decreasing order of frequency).
  • In dogs focal lesions most frequently occur in the small intestine. Multifocal tumours are rarer and affect various sites.
  • At the time of diagnosis in cats tumour nodules are often already apparent in the liver, kidney, spleen and abdominal and sternal lymph nodes. Differentiating AL and multicentric lymphoma may be difficult at this point.
  • In most cats AL is not associated with FeLV and aetiololgy is idiopathic.

Diagnosis

Clinical Signs

The following may be seen:

  • Vomiting
  • Diarrhoea
  • Weight loss
  • Anorexia
  • Tenesmus
  • Dyschezia
  • (Peritonitis - following complete intestinal obstruction and rupture)

Physical Examination

  • An abdominal mass may be palpable
  • Bowel loops may feel thickened
  • Enlarged mesenteric lymph nodes may be palpable

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 include:

  • For those with bone marrow involvement:
    • Lymphocytosis
    • Thrombocytopenia
    • Neutropenia
    • Presence of immature lymphoid precursors
  • Affected cats are not usually leukemic
  • Hypoproteinaemia
  • Elevated hepatic enzymes
  • Elevated BUN/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, affected cats are not usually hypercalcaemic
  • (Hypergammaglobulinaemia)

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 group 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, celiotomy is required for many cases of AL 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. 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
  • Commonly used protocols include:
    • COP - Cyclophosphamide, Vincristine, Prednisolone. Frequently used in cats and can be used for induction therapy (8weeks) as well as a long term maintenance protocol
    • COAP - Cyclophosphamide, Vincristine, Prednisolone, Cytosine arabinoside
    • CHOP - Cyclophosphamide, Vincristine, Prednisolone, Doxorubicin, (potentiated sulphonamides)
  • 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 degree of effects of drugs.

Supportive Therapy

For those receiving chemotherapy:

  • High quality, palatable diet
  • Appetite stimulation in cats e.g Cyproheptadine (Periactin)
  • Antiemetics
  • Assisted (tube) feeding
  • Fluid therapy
  • Laxatives
  • Analgesia
  • Treatment for and monitoring of:
    • Azotaemia
    • Neutropenia/sepsis
    • Hypercalcaemia
    • Pyrexia

Prognosis

  • Mean survival times for dogs and cats:
    • Without therapy: 6-8 weeks.
    • For those receiving cortocosteroids only: 3 months.
    • For those receiving chemotherapy: 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:
    • Early presentation
    • A complete initial response to treatment
    • A clinically well patient(‘substage a’ disease)
    • Whether doxorubicin is included in the treatment protocol may also affect prognosis
  • In cats, response rate to induction chemotherapy is 26-79%
  • Thus there is an apparently a poorer response rate in cats compared with dogs, however, 30-40% of cats that do have complete remission 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
Retrieved from "https://en.wikivet.net/index.php?title=Lymphoma&oldid=83375"