Introduction

• Enlargement of lymph nodes is a common clinical finding in dogs 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.

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 dog is primary lymphoid neoplasia (lymphoma Lymphoma ) affecting the node. However, approximately one third of enlarged lymph nodes in one large series of dogs presenting with primary lymphadenopathy were not due to lymphoma.
• The second most common cause of lymphadenopathy is reactive hyperplasia, reflecting immunological activity in the node. Other important differentials include:
  • Primary or secondary inflammation of the node (lymphadenitis).
  • Mineral-associated lymphadenopathy.
  • Metastatic neoplasia.
  • Lymph node hemorrhage, infarction or edema.
• The pathogenesis of lymphoma Lymphoma is discussed elsewhere.
• Lymph node involvement might occur in most of the various anatomical forms of lymphoma in the dog, and lymphoma might be more likely to induce multiple or generalized lymphadenopathy.
• 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. Leishmania and the range of systemic mycoses 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.
• Mineral-associated lymphadenopathy (mineral-associated disease, MAD) was first documented in the UK in the late 1980s, and is now commonly recognized in that country as a significant cause of canine lymph node enlargement. Affected dogs present with a range of non-specific clinical signs (eg malaise, pyrexia, inappetence) in conjunction with multiple lymphadenopathy. The diagnosis is made histopathologically, and is characterized by granulomatous lymphadenitis with the accumulation of large quantities of crystalline, mineral material within the node. Electronmicroprobe analysis of this mineral reveals it to comprise a complex mixture of elements. Many of these comprise extraneous environmental elements (eg aluminium, silicon, titanium, nickel) that sometimes collect together to form unique mineral species that are not known in nature. This process of biomineralization involves the aggregation of these elements within the unique chemical matrix of mammalian tissue. It is presumed that these elements have an environmental origin, but the precise source and means of entry to the body and deposition within peripheral lymph nodes has not yet been determined.
• 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.

Diagnosis

Treatment