Case of the month #4
by Eric Fish (DipACVP)
A Scottish Terrier dog presented to the Internal Medicine service at a large, multi-specialty referral hospital for evaluation of decreased energy and appetite. This patient had a prior medical history of multiple episodes of acute pancreatitis, a hepatoid gland tumor, and T Zone Lymphoma diagnosed 1.5 years prior. On physical exam, the patient had mild peripheral lymphadenopathy and hepatosplenomegaly, which was confirmed on abdominal ultrasound.
A Complete Blood Count (CBC) revealed the following abnormalities: Mild anemia (HCT 30.5%, RI: 38.7-59.%) without reticulocytosis or changes to MCV/MCHC/RDW, moderate to marked thrombocytopenia (48,000/uL, RI: 152,000-518,000/uL) with minimal clumping, and marked leukocytosis (72,740/uL, RI: 5,090-17,410/uL) characterized by marked lymphocytosis with a mild neutrophilia, significant left-shift, and monocytosis.
Multiple photomicrographs from the peripheral blood smear are provided (Figures 1-4). FNA cytology was also collected from the spleen and liver.
What is your interpretation of the CBC data and blood smear?
What additional tests would you recommend?
Fig 1A-B Peripheral blood from a dog with severe leukocytosis Wright Giemsa, 50x.
Concurrent TZL and high-grade B cell lymphoma.
Fig 2 Peripheral blood from a dog with leukemic TZL and high-grade B cell lymphoma, Wright Giemsa, 50x.
Fig 3 A-B Liver and spleen aspirates from a dog TZL and high-grade B cell lymphoma, Wright Giemsa, 20-50x.
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Evaluation of the blood film revealed at least two distinct populations of lymphocytes. Approximately 70% were small to intermediate in size with irregular margins, expanded pale blue cytoplasm, rare faint pink granules, moderate N:C, and rounded nuclei about the same diameter as a neutrophil with finely clumped chromatin without visible nucleoli. However, 20-30% of lymphocytes were larger in size with less cytoplasm that was medium blue, with a high N:C ratio, and pleomorphic nuclei ~1.5x the diameter of a neutrophil with fine chromatin and prominent nucleoli. Rare small “mature” lymphocytes were also noted.
The conclusion was that the lymphocytosis was composed of a mix of many cells that appeared consist with indolent lymphoproliferative disease (i.e. the previously diagnosed TZL vs T-CLL) and larger, atypical lymphocytes that were concerning for a more aggressive hematopoietic neoplasm.
The neutrophilia with a left-shift and monocytosis was interpreted as most consistent with inflammation. There was also a mild, normocytic normochromic, non-regenerative anemia, with considerations including anemia of chronic/inflammatory disease vs myelophthisis vs other causes of decreased bone marrow production. Rare ovalocytes were noted, which supported the possibility of bone marrow injury and myelofibrosis. The moderate thrombocytopenia was accompanied by increased MPV, which could suggest an active bone marrow response to peripheral thrombocytopenia, although given the other findings in this case, decreased bone marrow production could not be ruled out.
Based on the suspicion of aggressive lymphoid neoplasia and the enlarged liver and spleen on ultrasound, FNA cytology of both organs was performed. Each site contained abundant large neoplastic lymphocytes similar in appearance to the population of the large lymphocytes on the peripheral blood smear. The working diagnosis was multicentric large cell lymphoma, and the owners elected humane euthanasia.
The original diagnosis of T-Zone Lymphoma was confirmed by flow cytometry ~18 months prior. While no additional diagnostics were performed after the liver and spleen cytology, given the radically different morphology of lymphoid populations and the fact that TZL is generally indolent with prolonged survival, this patient most likely had two different forms of lymphoid neoplasia, rather than transformation of TZL into a high grade neoplasm.
Matsuyama A, Bienzle D, Richardson D, Deravi N, Hwang MH, Darzentas N, Keller SM. Composite lymphoma of concurrent T zone lymphoma and large cell B cell lymphoma in a dog. BMC Vet Res. 2019 Nov 16;15(1):413.
Rosenbaum CS, Seelig DM, Burton EN, Gwynn AD, Granick J, Able HR. Monitoring of large B-cell lymphoma and T-zone lymphoma in a dog via flow cytometry. J Vet Diagn Invest. 2021 Sep;33(5):1008-1012.