Page 719 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 33 Hematopoietic Tumors 697

serum proteins may be evaluated by serum protein electropho- malignancy. Therefore classification of lymphoma into subtypes
resis. Monoclonal gammopathies have been reported to occur in that make up the low-, intermediate-, and high-grade forms can
be attempted using cytologic appearance and immunopheno-
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approximately 6% of dogs with lymphoma.
VetBooks.ir site involved as well as paraneoplastic syndromes, such as hyper- typic analysis of cytologic specimens (Fig. 33.7B), 96,148–150 but
Serum biochemical abnormalities often reflect the anatomic
is performed most accurately on histologic sections. Although
calcemia. In dogs with lymphoma, ionized calcium concentra- cytologic findings identified by an experienced cytopathologist
tions should be obtained, as they may be increased even if the total may suggest a particular subtype of lymphoma, subsequent anal-
calcium concentration is within the reference interval. In cases of ysis that may include flow cytometry, immunocytochemistry,
hypercalcemia of unknown origin, lymphoma should always be biopsy for histologic examination, clonality assays, and cytoge-
considered high on the differential disease list and diagnostic testing netic analysis are required to further subtype the lymphoma or
directed at this possibility should be undertaken (see Chapter 5). to confirm or establish a diagnosis in equivocal cases. Fig. 33.8
In addition, the presence of hypercalcemia can serve as a biomarker presents a diagnostic algorithm for assessing peripheral lymph-
for response to therapy and relapse. Increased urea nitrogen and adenopathy in dogs applying these techniques, beginning with
creatinine concentrations can occur secondary to renal infiltra- initial screening by cytologic examination.
tion with tumor, hypercalcemic nephrosis, or prerenal azotemia For accurate histopathologic evaluation, an entire LN, includ-
from dehydration. Increases in liver-specific enzyme activities or ing the capsule, should be removed, placed in buffered formalin,
bilirubin concentrations may result from hepatic parenchymal and submitted to a pathologist. Needle-core biopsies are generally
infiltration. Increased serum globulin concentrations, usually inadequate to evaluate nodal morphology. Effacement of normal
monoclonal, occur infrequently with B-cell lymphoma. nodal architecture by neoplastic lymphocytes and capsular disrup-
Urinalysis is part of the minimum database used to assess tion are characteristic findings (Fig. 33.7C, D).
renal function and the urinary tract. For example, isosthenuria
and proteinuria in the absence of an active sediment may indi- Histologic and Cytologic Evaluation of Extranodal Sites
cate renal disease, and hematuria may result from a hemostatic Diagnostic ultrasonography and ultrasound-guided FNA or
abnormality. It is important to note that isosthenuria in hyper- needle biopsy have been useful for evaluation of involvement of
calcemic dogs is not necessarily indicative of renal disease, as the liver, spleen, or abdominal LNs. 151–153 Aspiration of ultra-
high calcium concentrations interfere with tubular concentrat- sonographically normal splenic tissue is rarely contributory to a
ing capabilities through impairment of response to antidiuretic diagnosis. If possible, the diagnosis should be made by sampling
hormone; however, clinicians should be aware that there is a risk peripheral nodes, avoiding percutaneous biopsies of the liver and
of renal calcification and subsequent failure with sustained high spleen. However, if there is no peripheral node involvement, it is
calcium concentrations. appropriate to biopsy affected tissues in the abdominal cavity.
When GI lymphoma is suspected, an open surgical wedge
Histologic and Cytologic Evaluation of Lymph Nodes biopsy of the intestine is preferred in most cases to differentiate
Morphologic and phenotypic examination of the tissue and cells lymphoma from lymphocytic enteritis. If associated abdominal
that constitute the tumor is essential to the diagnosis and sub- LNs also appear involved, image-guided biopsies may be obtained
typing of lymphoma. In humans, a combination of histologic, with less morbidity than intestinal biopsies. Multiple samples
immunophenotypic, clinical, and genetic features are used in may be necessary to accurately diagnose segmental disease. Endo-
the diagnosis and subtyping of NHL. An excellent review of scopic biopsies may be inadequate as only a superficial specimen is
the morphologic and immunophenotypic diagnostic features of obtained; however, more aggressive endoscopic biopsy techniques
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canine lymphoma has recently been published. In veterinary combined with more accurate histopathologic, immunopheno-
medicine, care should be taken to avoid sampling LNs from typic, and molecular assessments are improving the diagnostic
reactive areas (e.g., mandibular LNs), unless those nodes are the yield of these less invasive techniques. 125,126,154–162 In many dogs
only ones enlarged; the prescapular or popliteal LNs are prefer- with primary GI lymphoma, an inflammatory nonneoplastic infil-
able if also involved. Also, lymphocytes are fragile, and in pre- trate (i.e., LP-IBD) may be misdiagnosed on biopsy specimens
paring smears of aspirated material only gentle pressure should that are too superficial. The application of assays for clonal expan-
be applied in spreading material on the slides. As the majority sion (e.g., receptor gene rearrangement [PARR]) does not appear
of dogs with nodal lymphomas are presented with multicentric as yet to be as accurate for endoscopically derived intestinal biop-
effacement of peripheral LNs by intermediate or large lympho- sies as it is for other solid lymphoid tumors in dogs.
cytes, cytologic examination of FNAs of affected LNs or other Cytologic examination of cerebrospinal fluid (CSF), thoracic
tissues is a highly sensitive and specific first-line or screening fluid, or mass aspirates is indicated in animals with CNS disease,
diagnostic step. Typically, most of the cells are large lympho- pleural effusion, or an intrathoracic mass, respectively. In two
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cytes (>2 times the diameter of a red blood cell or larger than a studies, CSF analysis was diagnostic of lymphoma in 74% of 27
neutrophil), and they may have visible nucleoli and basophilic samples. 133,136 Characteristics of the CSF in one study included
cytoplasm with or without paranuclear clear zones (Fig. 33.7A) an increased nucleated cell count in seven dogs with 95% to
or fine chromatin with indistinct nucleoli. Because tissue archi- 100% of the cells comprising atypical lymphocytes. 133 CSF pro-
tecture is not maintained in cytologic specimens, effacement of tein concentration was increased in five of the dogs, ranging from
the node or capsular disruption cannot be detected. Therefore 34 to 310 mg/dL (reference interval <25 mg/dL). Flow cytometric
marked reactive hyperplasia characterized by increased numbers and molecular diagnostic procedures may also be applied to CSF
of large lymphocytes may be difficult to distinguish from lym- samples, 136 although cell counts may be a limiting factor as some
phoma. In some forms of lymphoma, intermediate lymphocytes of these assays require at least 10,000 cells.
that are similar in diameter to neutrophils predominate; these For cutaneous lymphoma, dermal punch biopsies (4–8
specimens can be more challenging for novice cytopathologists. mm) should be taken from the most representative and infiltra-
Small-cell lymphomas may have few cytologic clues that point to tive, but not secondarily infected, skin lesions. Application of