Lymphoid Neoplasia


Table 27-2 UNIVERSITY OF WISCONSIN-MADISON LYMPHOMA PROTOCOL

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Chapter 27 Lymphoid Neoplasia



David M. Vail


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


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).



Etiology



Retrovirus


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.



Genetic


A genetic predisposition for the development of certain forms of lymphoma may exist.



Carcinogenic Agents


Exposure to chemical, physical, and viral carcinogens may play a role in the development of many tumor types. Weak associations with herbicide use and exposure to high tension wires have been reported.



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).


Table 27-1 WORLD HEALTH ORGANIZATION CLINICAL STAGING FOR LYMPHOMA*





















Stage† Criteria
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.



Multicentric Lymphoma


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.



Alimentary Lymphoma


This type of lymphoma often is associated with vomiting, diarrhea, and nonspecific signs such as weight loss and lethargy.



Mediastinal Lymphoma


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


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.



Extranodal Forms


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.



Diagnosis


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.



History


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.



Physical Examination


Perform a complete physical examination for all animals with lymphoma.


• Palpate all lymph nodes (including rectal palpation of sublumbar nodes) and abdominal viscera.

• Because bone marrow involvement can result in hematologic abnormalities, closely examine mucous membranes for signs of pallor or petechiae.

• Visceral involvement can lead to organ failure; therefore, look for any physical signs that may be indicative of liver or kidney disease (e.g., icterus and uremic ulcers).

• Ophthalmic abnormalities are present in more than one-third of dogs with lymphoma and include uveitis, hemorrhage, and ocular infiltration. Therefore, optic and fundic examinations should be conducted.



Key Point


Canine lymphoma usually is a disease of middle-aged and older animals; thus, it is essential to perform a complete examination to identify concomitant problems in other systems.



Laboratory Evaluations



Hematologic Abnormalities



• Hematologic abnormalities occur in most dogs and cats with multicentric lymphoma. Common abnormalities, in decreasing frequency, include atypical immature lymphocytes in the circulation, thrombocytopenia, eosinopenia, anemia, and nucleated erythrocytes.

• The anemia is usually that of chronic disease (normocytic, normochromic, and nonregenerative); however, a small percentage of animals have indices compatible with blood loss or hemolysis. FeLV-positive cats are more likely to be anemic than cats that are not infected.

• Bone marrow aspirate or core biopsy may reveal an altered bone marrow myeloid-to-erythroid ratio and bone marrow infiltration with neoplastic lymphocytes.


Biochemical Abnormalities




Key Point


Serum calcium is elevated in 15% to 20% of dogs with lymphoma. The likelihood of hypercalcemia is greatest in dogs with the mediastinal form.



• Paraneoplastic hypercalcemia (i.e., elevated serum calcium) may serve as a marker for response to therapy and, although uncommon, may cause hypercalcemic nephropathy, a potentially irreversible cause of renal failure (see Chapters 32 and 77).

• Elevations in blood urea nitrogen and serum creatinine may result from neoplastic infiltration of the kidneys, hypercalcemic nephrosis, or dehydration.

• Increased serum concentration of liver enzymes or bilirubin may indicate neoplastic infiltration of the liver.

• Abnormally elevated serum globulins may be noted in some B cell lymphomas.


Feline Leukemia Virus Status


Approximately 80% of cats with mediastinal and multicentric lymphoma are FeLV-positive, in contrast to 50% with renal lymphoma, 5% to 10% with alimentary lymphoma, and a minority with cutaneous forms.



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.


• Half of all dogs with lymphoma have evidence of enlarged sternal and sublumbar lymph nodes, spleen, and liver.

• Thoracic radiographs are important for identification of thoracic masses that are due to mediastinal lymphoma and are recommended for any dog with hypercalcemia of unknown etiology.

• Abdominal ultrasonography and contrast studies of the upper gastrointestinal (GI) tract are abnormal in most animals with GI lymphoma.


Histopathology and Cytology


Histopathologic and cytologic evaluation of affected tissues is necessary for confirmation of lymphoma.


• Fine-needle aspiration cytology of lymph nodes, visceral organs, and other involved sites can be suggestive of neoplastic disease; however, conclusive histologic diagnosis is often recommended.



Key Point


In the cytologic evaluation of lymph nodes in cats, neoplastic involvement is difficult to distinguish from benign lymphadenopathy syndromes. For this reason, only histopathologic examination is definitive.


• Avoid sampling lymph nodes draining reactive areas of the body (e.g., submandibular lymph nodes in the presence of periodontal disease) because reactive lymphoid hyperplasia can mask (or mimic) the true neoplastic condition.

• In addition to confirming a diagnosis of lymphoma, histologic and cytologic samples can be analyzed by various immunohistochemical and histochemical techniques to determine immunophenotype (B vs. T cell), tumor proliferation rates, and histologic subtype (high-, intermediate-, or low-grade tumors). The availability of such analysis is growing; however, at present only immunophenotype is consistently predictive of prognosis in dogs.


Additional Diagnostic Tests


Additional tests may be necessary to confirm the diagnosis of the extranodal forms of lymphoma.


• Stage the disease by performing a CBC, bone marrow evaluation, and thoracic and abdominal radiography. Staging is important in animals with extranodal lymphoma to ensure that the disease is not a sequela of the more common multicentric forms and to determine whether the disease is localized to a solitary extranodal site.

• Perform exploratory laparotomy and full-thickness biopsy or fine-needle aspiration to diagnose most cases of alimentary lymphoma. Endoscopic biopsies of the mucosa may be too superficial to diagnose GI lymphoma because lymphoma usually originates in the submucosa. In addition, GI lymphoma often is accompanied by lymphocytic/plasmacytic mucosal infiltrations that may be misdiagnosed as a benign condition. However, improved endoscopic sampling techniques may reduce the likelihood of misdiagnosis.

Related posts:

  1. Feline Infectious Peritonitis (Feline Coronavirus)
  2. Borreliosis (Lyme Disease)
  3. Immune-Mediated Dermatoses
  4. Canine and Feline Demodicosis

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Aug 27, 2016 | Posted by in SMALL ANIMAL | Comments Off on Lymphoid Neoplasia

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