Generalized lymphadenopathy in a dog
SIGNALMENT AND HISTORY
A 6 year old female French Bulldog presented to the veterinarian with moderate generalized lymphadenopathy which did not respond to a two-week course of antibiotics. No other abnormalities were reported by the owner. Her vaccination status was up-to-date. The patient had good appetite and was not losing weight.
PHYSICAL EXAMINATION
On clinical examination, the presence of submandibular, prescapular and popliteal lymphadenomegaly was confirmed. The dog was otherwise bright, alert and responsive. There was no pyrexia, cardiac or respiratory signs.
INVESTIGATION
Haematology, biochemistry and urinalysis
Minimum database included haematology, biochemistry panel and urinalysis. Haematology revealed mild leukocytosis (16.74x10^9/L, reference interval, RI: 6-12x10^9/L) due mild to moderate lymphocytosis (9.87x10^9/L, RI: 1-3.6x10^9/L). Blood smear was also examined in order to evaluate cellular morphology (Figure 1). Other results were unremarkable.
Cytology
Fine needle aspiration (FNA) cytology of palpable peripheral lymph nodes was undertaken (Figure 2).
Figure 2. FNA cytology of a popliteal lymph node – 20x objective (A), 50x objective (B) (Hemacolor stain).
Imaging
Abdominal ultrasound revealed moderate enlargement of the iliac lymph nodes. Chest radiographs were unremarkable.
Molecular diagnostics
Clonality testing (PCR for antigen receptor rearrangements, PARR) was requested to confirm the cytological diagnosis. The test revealed the presence of a monoclonal T-cell population and a polyclonal B-cell population (Figure 3).
Figure 3. Clonality testing (PCR for antigen receptor rearrangements, PARR) of a popliteal lymph node showing a monoclonal T-cell population and a polyclonal B-cell population.
Flow cytometry
Flow cytometry was performed on the peripheral blood in order to characterize the lymphocyte population and further refine the diagnosis. An antigenically homogeneous population of CD3+, CD4+, CD5+ lymphocytes was identified. The cells lost expression of the pan-leukocyte marker – CD45 (Figure 4).
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INTERPRETATION OF THE RESULTS
The presence of lymphocytosis with the predominance of small to intermediate lymphocytes most likely reflected the presence of lymphoid neoplasia given other laboratory findings.
The cytology of the lymph nodes showed a high number of lymphocytes which were small to intermediate in size. A high number of these cells displayed a hand-mirror shape with single cytoplasmic projections extending in different directions. The cytoplasm was scant to moderately abundant and light blue. The nuclei were small, round and paracentrally or eccentrically-located. The chromatin was finely stippled to condensed. In summary, a monomorphic population of small to intermediate lymphocytes with no evidence of reactive lymphoid hyperplasia was detected. Given the presence of lymphadenomegaly, this cytological picture was most consistent with a small cell lymphoma.
A monoclonal T-cell PARR result confirmed the cytological diagnosis of lymphoma without the need of histopathological examination and indicated that the neoplastic cells were of T-cell origin.
The pattern of antigen expression detected in peripheral blood lymphocytes by flow cytometry was consistent with an indolent T-cell neoplasia – T-zone lymphoma (stage V). Chronic lymphocytic leukaemia with secondary lymph node involvement could not be totally ruled out.
DIAGNOSIS: SMALL T-CELL LYMPHOMA (T-ZONE LYMPHOMA) – stage Va
TREATMENT AND FOLLOW-UP
The dog was treated with prednisolone. After initiation of the therapy the lymph nodes decreased in size but did not return to normal. Three months later the patient was well in herself. The observed weight gain and the increase in hepatobiliary enzymes were considered secondary to glucocorticoid treatment.
SUMMARY
Small cell lymphoma is a low-grade malignancy with an indolent clinical course. Its cytological diagnosis frequently requires confirmation with adjunct diagnostic tests, such as histopathology (Figure 5), PARR or flow cytometry. The latter ones are minimally invasive methods which allow definitive diagnosis of lymphoma and determination of the origin of the cells (T versus B-cell). Recent studies have shown that flow cytometry can also accurately identify a specific indolent subtype of canine T-cell lymphoma, called T-zone lymphoma. The diagnosis is based on unique immunophenotypic features: mainly the lack of CD45 expression.
Depending on the clinical picture patients with small cell lymphoma may or may not require treatment at the time of presentation. The recommended treatment protocols are usually less aggressive than the ones used for other types of lymphoma. Glucocorticoids and chlorambucil are the most often used drugs.
