Chapter 27 Lymphoid Neoplasia
The lymphoproliferative disorders presented here are characterized by neoplasia involving cells or cell lines of lymphoid origin, including lymphoma, lymphoid leukemia, multiple myeloma, and plasmacytoma. Because of differences in diagnosis, therapy, and prognosis among these conditions, they are discussed here as separate entities.
Lymphoma (lymphosarcoma) is defined as a lymphoid neoplasm primarily affecting lymph nodes or other solid visceral organs such as the liver or spleen. It is the most common of the lymphoproliferative disorders in small animals. Middle-aged to older dogs primarily are affected without sex predilection. Although lymphoma can occur in any purebred or mixed-breed dog, it may be more prevalent in golden retrievers, German shepherds, boxers, poodles, bassets, and Saint Bernards.
No breed predilection exists for cats; however, several reports have observed a 1.5:1 male-to-female ratio. Affected cats that are feline leukemia virus (FeLV) antigenemic tend to be younger (median age 3–5 years) than FeLV-negative cats (median age 7–10 years).
A retroviral etiology for certain forms of lymphoma has been demonstrated in a variety of species, including cats, chickens, and humans. In the cat, evidence exists for direct induction of lymphoma by FeLV and indirect induction by the feline immunodeficiency virus (FIV). Before 1985, most cats with lymphoma (>70%) were FeLV antigenemic. Since then, the general availability of FeLV vaccination and testing has increased and FeLV-positive cats currently make up a minority of lymphoma cases (<25%). This shift is likely due directly to vaccination and to FeLV antigen testing before vaccination, which allowed separation of potentially infective cats from the susceptible population. In either situation, the result is a reduction in the number of FeLV-associated lymphomas. Conclusive evidence of a viral etiology has not been established in the dog.
Classification and Clinical Signs
Traditionally, lymphoma is classified based on anatomic site. Clinical signs vary with the sites involved. In cats, the frequency of anatomic forms associated with FeLV antigenemia (i.e., mediastinal and multicentric forms) has declined along with the declining frequency of FeLV-associated lymphomas. Whereas these sites made up the bulk of cases observed in cats before 1985, they are now in the minority. Currently, the alimentary form, which only rarely is associated with FeLV antigenemia, makes up the bulk of lymphomas in cats. Other less common forms occurring in cats include renal, hepatic, and miscellaneous extranodal sites.
World Health Organization (WHO) clinical staging of lymphoma also can be used to classify the extent of the disease (Table 27-1).
|I||Involvement limited to single lymph node or lymphoid tissue in a single organ (excluding bone marrow)|
|II||Involvement of many lymph nodes in regional area (with or without tonsils)|
|III||Generalized lymph node involvement|
|IV||Liver and/or spleen involvement (with or without stage III)|
|V||Manifestations in blood and involvement of bone marrow and/or other organ systems (with or without stages I–IV)|
* Reprinted with permission from World Health Organization: Owen LN: TNM Classification of Tumors in Domestic Animals. Geneva: WHO, 1980.
† Each stage is subclassified into (a) without systemic signs and (b) with systemic signs.
This is the most common form in the dog. It usually manifests as increased lymph node size with non-specific signs such as inappetence, weight loss, polyuria or polydipsia, and lethargy. Hepatic and splenic involvement, manifested as diffuse organ enlargement, also is common in multicentric lymphoma.
This type of lymphoma often is associated with vomiting, diarrhea, and nonspecific signs such as weight loss and lethargy.
This form of lymphoma often causes respiratory signs secondary to pleural effusion, the mass effect of the tumor, or precaval syndrome (i.e., facial and forelimb edema caused by reduced venous and/or lymphatic drainage). Approximately 40% to 50% of mediastinal lymphomas in the dog are associated with hypercalcemia, which can cause polyuria or polydipsia, anorexia, and weakness.
Cutaneous lymphoma involves single or multiple skin lesions that can vary greatly in appearance. It may mimic other skin disorders such as seborrhea, pemphigus, and pyoderma. The cutaneous lesions can begin as a mild eczematous pruritic plaque and progress to nodular tumors. Approximately half of the reported cases of cutaneous lymphoma are pruritic.
Miscellaneous extranodal forms of lymphoma include lymphoma of the eyes, central nervous system (CNS), bones, heart, kidneys, urinary bladder, and nasal cavity. Their presentations vary with respect to the site of involvement.
Classification by Immunophenotype
Lymphomas also can be classified by immunophenotype, that is, whether they are of B lymphocyte or T lymphocyte origin. Most (70–80%) lymphomas in dogs are composed of B cells. T cell origin lymphoma in dogs is associated more commonly with hypercalcemia and cranial mediastinal involvement. In cats, most FeLV-associated lymphomas are T cell in origin. The breakdown of B versus T cell lymphoma is less clear cut in cats.
The diagnosis of lymphoma is based on a complete history, physical examination, tissue diagnosis, and clinical staging. Clinical staging should include a complete blood count (CBC), platelet count, bone marrow aspiration or core biopsy, biochemistry profile, and thoracic and abdominal radiographs. Abdominal ultrasound can be added to the workup if indicated based on presentation.
The history should include an evaluation of past and present water intake and urination frequency because they may reflect hypercalcemia of malignancy and subsequent renal disease.
Perform a complete physical examination for all animals with lymphoma.
Serum calcium is elevated in 15% to 20% of dogs with lymphoma. The likelihood of hypercalcemia is greatest in dogs with the mediastinal form.
Radiography and Ultrasonography
Radiography and ultrasonography (see Chapter 4), although not diagnostic for lymphoma, are often useful for staging or determining the extent of disease.
Histopathology and Cytology
Histopathologic and cytologic evaluation of affected tissues is necessary for confirmation of lymphoma.
Additional Diagnostic Tests
Additional tests may be necessary to confirm the diagnosis of the extranodal forms of lymphoma.