Lymphadenopathy in Cats (Felis) | Vetlexicon
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Lymphadenopathy

ISSN 2398-2950


Introduction

  • Enlargement of lymph nodes is a common clinical finding in cats with a wide range of underlying disease states, but may sometimes be the primary presenting complaint. 
  • Technically, the term lymphadenomegaly is the correct description for lymph node enlargement, but lymphadenopathy (lymph node pathology) is generally used synonymously. 
  • Lymphadenopathy may involve peripheral (palpable) lymph nodes and/or internal visceral lymph nodes (as determined by imaging examination). 
  • Lymphadenopathy may be localized (solitary or regional) or generalized in distribution. The differential diagnosis of lymphadenopathy is important. Not all lymph node enlargement is attributed to neoplastic change, and there are numerous causes of relatively benign lymphadenopathy. Finally, there are some exceptions to these general comments:
  • 'Lymphadenopathy' might also encompass situations where lymph nodes are reduced in size, for example in senility, cachexia or with viral infection or immunosuppression that depletes lymphoid tissue.  Further, lymph nodes might display pathological change (eg the presence of metastatic tumor) without necessarily being enlarged.
Follow the diagnostic trees for Lymphadenopathy (single node) and Lymphadenopathy (multiple nodes).

Presenting signs

  • By definition, lymphadenopathy/lymphadenomegaly implies that lymph nodes are enlarged, as determined by palpation of external nodes or imaging examination of internal/visceral nodes.
  • Lymphadenopathy may be accompanied by changes in the tissue that is drained by the particular lymph node, eg  neoplastic, inflammatory, hemorrhagic or edematous change.

Acute presentation

  • Lymphadenopathy is generally a chronic rather than acute change. The pathology that underlies lymph node enlargement is generally of insidious onset and the changes occur slowly over time. However, in general terms lymphadenopathy associated with neoplasia may be of longer duration than enlargement due to inflammation or infection.

Geographic incidence

  • Some infectious causes of lymphadenopathy, for example,histoplasma capsulatum Histoplasma capsulatum, have specific geographic localizations. There is no clear evidence that neoplastic causes of lymphadenopathy have a particular geographic distribution.

Age predisposition

  • Lymphadenopathy can occur at any age, but there may be some age predilections. Lymph node enlargement post vaccination (draining the site of vaccine administration) might be more commonly observed in kittens.
  • Lymphadenopathy in young cats is more likely to be due to infectious or inflammatory diseases.
  • Lymphadenopathy in older cats is more likely to be due to neoplastic infiltration, most commonly lymphoma Lymphoma.

Breed/Species predisposition

  • There is no significant breed predisposition for lymphadenopathy in cats.

Public health considerations

  • Some infectious causes of feline lymphadenopathy have zoonotic implications particularly mycobacterial disease and sporotrichosis Sporotrichosis.

Cost considerations

  • The diagnostic approach to lymphadenopathy is relatively inexpensive - the two most relevant techniques include cytology (fine needle aspiration Fine-needle aspirate) and histopathology (biopsy  Biopsy: overview).

Pathogenesis

Pathophysiology

  • Lymphadenopathy is not generally considered a specific disease entity, but is an important clinical finding, the cause for which should be ascertained whenever it is recognized. There are numerous differential diagnoses for canine lymphadenopathy. The investigation of lymphadenopathy is generally one part of an overall clinical examination, and the interpretation of lymphadenopathy should always be made in light of all that is known about other local or systemic disease in the patient. 
  • The first distinction that is made in the investigation of lymphadenopathy is whether the change is localized or generalized. Enlargement of a single lymph node, or unilateral enlargement of paired lymph nodes, most likely reflects pathological change in the tissue drained by that node, eg oral infectious or neoplastic disease will often result in uni- or bilateral submandibular lymphadenopathy.  Enlargement of multiple lymph nodes, particularly at distant sites not directly related to each other, is a potentially more significant clinical finding and suggests a multisystemic or multifocal disease process.
  • The single most common cause of lymphadenopathy in the cat is primary lymphoid neoplasia (lymphoma) affecting the node. In contrast to the situation in dogs, generalized lymph node enlargement is a very rare manifestation of lymphoma in cats and should trigger consideration of an infectious or autoimmune disease process.
  • The pathogenesis of lymphoma Lymphoma is discussed elsewhere. 
  • Reactive hyperplasia is the most common cause of benign lymphadenopathy, and simply reflects activity of the node as part of a local or general immune response. Hyperplasia (increased cell number) involves the cortical (follicular) and paracortical B and T lymphocytes respectively, and the plasma cells of the medullary cords. Reactive lymph nodes have increased lymphatic flow and there is evidence of this increased drainage from tissue from the presence of numerous phagocytic cells (macrophages and dendritic cells) within the medullary sinuses (sinus histiocytosis).
  • Lymphadenitis is inflammation of the lymph node. Most commonly, this is a sequel to an inflammatory/infectious process in the tissue drained by the node with the node becoming secondarily involved in the same process.  Some such processes will however have a primary focus within the node in the absence of local tissue changes.  There is a wide range of infectious causes of lymph node enlargement, but in general pathogens that induce chronic inflammation (particularly intracellular pathogens) are most likely to induce this type of lymph node pathology. Mycobacterial infection and feline infectious peritonitis Feline infectious peritonitis are good examples of this type of pathology. Increasingly, pathologists recognize a syndrome of 'sterile granulomatous lymphadenopathy' where there is inflammatory change in an enlarged lymph node, but conventional methodology fails to demonstrate an infectious cause. This syndrome most likely represents infection with an unconventional pathogen that might require more sensitive molecular diagnostic approaches.
  • Lymph node enlargement secondary to metastatic spread of neoplasia can involve any lymph node draining malignant neoplastic tissue. Lymph node enlargement due to a range of other causes (hemorrhage, infarction, edema) might occur - but again often reflects changes in local or surrounding tissues.
  • Methimazole Methimazole administration for hyperthyroidism has been associated with an atypical lymphoid hyperplasia characterized by B and T cell proliferation. Resolution follows withdrawal of the inciting cause.

Diagnosis

Presenting problems

  • The clinical presentation of cats with lymphadenopathy is highly variable. Most commonly, cats present with intra-abdominal lymphadenopathy due to alimentary lymphoma Alimentary tract: neoplasia . Typical presenting signs include weight loss, reduced appetite, lethargy and the presence of a palpable abdominal mass.

Client history

  • Important historical information for the investigation of lymphadenopathy would include the duration of the process, recent vaccination, trauma, infection or travel to areas endemic for particular infectious diseases.

Clinical signs

  • By definition a cat with lymphadenopathy will have enlargement of one or more lymph nodes. 
  • External nodes should be palpably enlarged, and internal lymph node enlargement will be visualized by imaging examinations or identified on laparotomy/laparoscopy. Palpation of most enlarged lymph nodes reveals them to be firm to touch, mobile within surrounding tissues, painless and of normal temperature.   
  • Lymph nodes affected by lymphadenitis, or where neoplastic cells infiltrate through the node capsule, are more likely to be adherent to surrounding tissue than mobile within it. 
  • The size of the enlarged lymph nodes might also be informative. Extreme enlargement (five to ten times greater than normal) is more likely to occur with lymphoma, metastatic neoplasia or lymphadenitis, than a benign reactive process.
  • Cats presenting with lymphadenopathy as a primary clinical problem will often display a range of non-specific clinical signs such as pyrexia, inappetence/anorexia, malaise. 
  • The effect of gross lymphadenomegaly will be to compromise adjacent structures, eg enlargement of retropharyngeal nodes might lead to dysphagia, or of cervical/bronchial nodes might cause dyspnea or a cough.
  • Lymphadenopathy which disrupts the flow of afferent lymph from tissues will be associated with edema of the upstream tissue.

Diagnostic investigation

  • The diagnostic approach to lymphadenopathy should always involve a consideration of the entire animal, with a view to the identification of any underlying primary disease. 
  • Routine diagnostic procedures such as hematology, serum biochemistry, urinalysis and imaging (survey radiography and ultrasound) may provide valuable diagnostic information that help to refine a differential diagnosis list for lymphadenopathy. 
  • Possible infectious etiologies might be confirmed by culture, serology or PCR PCR (Polymerase chain reaction) testing.  Similarly, note should be taken of serum calcium concentration Blood biochemistry: total calcium, as lymphoma is rarely associated with the 'hypercalcemia of malignancy'.
  • A specific diagnosis of lymphadenopathy will require either (or both) cytological and histopathological examination of the lymph node. 
  • Fine needle aspiration of peripheral nodes Cytology: lymph node aspirate (or internal nodes by ultrasound guidance) is simply performed. 
  • Multiple smears should be prepared and stained for cytological examination. Artifacts are common in such aspirates, as there is often contamination by blood and adipose tissue. Lymph node aspirate samples yield very fragile cellular material and cells can therefore be easily disrupted during the samplaing process.
  • Cytological examination may provide a definitive diagnosis, but a greater chance of achieving a diagnosis would be obtained by taking a tissue sample for histopathology. 
  • Biopsy of a lymph node might be restricted to a needle core of tissue, a partial incisional biopsy, or an excisional biopsy of the entire enlarged node might be considered. The greater the quantity of tissue submitted to the pathologist, the more likely it is that a diagnosis will be achieved. Needle core or incisional biopsies might still only sample a small portion of a node in which  pathological change is not uniform. An excisional biopsy permits assessment of the entire nodal structure, and whether there is involvement or infiltration of extranodal tissue. Diagnosis might be refined by the application of panels of special histochemical stains (eg for detection of infectious agents) or immunohistochemical stains (eg for infectious agents or tumor types). Where an infectious cause for lymphadenopathy is possible, a portion of the lymph node biopsy might be submitted freshly for culture.  Where a patient has multiple lymphadenopathy, sampling of more than one node is appropriate - the popliteal and axillary nodes are often chosen for their relative accessibility. In general, the single largest node should not be sampled through choice as such nodes may have a necrotic center and not provide a representative sample.  Similarly, the submandibular node should not be sampled through choice as these nodes will often be reactive if a cat has any evidence of oral pathology.

Gross autopsy findings

  • At gross necropsy examination any enlarged lymph node should be investigated. The adherence of the node to surrounding soft tissue should be assessed. The node should be hemisected longitudinally and both cut surfaces examined. The primary gross observation is whether there is evidence of cortico-medullary structure or whether this has been obliterated by a diffuse cellular infiltration. In a normal node, the cortex and medulla should be visible. The follicles within the cortex of a reactive node might be visible to the naked eye. 
  • Lymph nodes affected by lymphoma will generally have a diffuse, cream to white cut surface that obliterates normal structure. 
  • Chronic lymphadenitis might appear similar if there is granulation tissue formation, and in both cases the node will be firm in texture. A necrotic center might be present in markedly enlarged neoplastic nodes, but necrosis might also occur in lymphadenitis. 
  • Bronchial lymph nodes might appear pigmented due to the accumulation of carbon, and nodes draining melanomata may accumulate melanin pigment.

Histopathology findings

  • The histopathological features of the main causes of lymphadenopathy are distinctive. 
  • Lymph nodes affected by lymphoma will characteristically have loss of normal microarchitecture, and replacement of this by a diffuse sheet of neoplastic lymphocytes.  Reactive lymph nodes will have prominent secondary follicle formation, paracortical hyperplasia, subcapsular and medullary sinus dilation and often sinus histiocytosis (increased numbers of macrophages within the medullary sinuses). 
  • Lymphadenitis will be characterized by inflammatory change replacing normal lymph node structure. This is often granulomatous or involves distinct, coalescing microgranulomas. Infectious agents might be located within these lesions.  
  • In nodes affected by metastatic neoplasia, there will be focal obliteration of structure by neoplastic tissue that should bear resemblance to that of the primary neoplasm.

Differential diagnosis

  • The main differential diagnoses for feline lymphadenopathy are described above.

Treatment

Initial symptomatic treatment

  • As lymphadenopathy is not a diseaseper se, there is no specific treatment applicable to all cases. Cats with lymphadenopathy secondary to lymphoma or other metastatic neoplasia might respond to chemotherapy, radiotherapy or surgical excision of affected tissue and draining nodes. 
  • Cats with lymphadenopathy secondary to a specific infectious disease will respond to appropriate antimicrobial therapy. 
  • Reactive hyperplasia does not require specific therapy. The underlying disease may require treatment, in which case, the lymphadenopathy would be expected to resolve in parallel with the concurrent lymphadenopathy would be expected to resolve in parallel with the concurrent clinical signs.

Subsequent management

Treatment

  • The approach to monitoring a cat with lymphadenopathy will depend upon the diagnosis made.

Prevention

Outcomes

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Addie D, Belák S, Boucraut-Baralon C et al (2009) Feline infectious peritonitis. ABCD guidelines on prevention and management. J Feline Med Surg 11 (7), 594-604 PubMed.
  • Niessen S J, Voyce M J, de Villiers L et al (2007) Generalised lymphadenopathy associated with methimazole treatment in a hyperthyroid cat. J Small Anim Pract 48 (3), 165-168 PubMed.
  • Brömel C, Sykes J E (2005) Histoplasmosis in dogs and cats. Clin Tech Small Anim Pract 20 (4), 227-232 PubMed.
  • Ruiz de Gopegui R, Peñalba B & Espada Y (2004) Causes of lymphadenopathy in the dog and cat. Vet Rec 155 (1), 23-24 PubMed.
  • Fan T M (2003) Lymphoma updates. Vet Clin North Am Small Anim Pract 33 (3), 455-471 PubMed.
  • Rogers K S, Barton C L & Landis M (1993) Canine and feline lymph nodes.  Part I.  Anatomy and function. Comp Contin Educ Pract Vet 15 (3), 397-408 VetMedResource.
  • Rogers K S, Barton C L & Landis M (1993) Canine and feline lymph nodes. Part II.  Diagnostic evaluation of lymphadenopathy. Comp Contin Educ Pract Vet 15 (11), 1493-1503 VetMedResource.

Other sources of information

  • Day M J (1999) Diseases of lymphoid tissue. In: M J Day. Clinical Immunology of the Dog and Cat. Manson Publishing, London. pp. 250-265.