Marked hyperphosphatasemia associated with an acute leukemia in a Great Dane

Abstract

This is the report of a 5-year-old male neutered Great Dane with an extreme leukocytosis (544.9 × 10(9) cells/L; RI 5.2-13.9 × 10(9) cells/L) characterized by highly atypical round cells. Cellular morphologic features such as cytoplasmic membrane blebs, a high nuclear-to-cytoplasmic ratio, and nuclear indentations and irregularities and large nucleoli, as well as immunocytochemistry for CD3 and CD79, myeloperoxidase cytochemistry, and clonality testing were not conclusive for myeloid or lymphoid origin. Marked alkaline hyperphosphatasemia was present at the first visit (2783.0 U/L; RI 6-80.0 U/L), followed by a 5-fold increase (14,000 U/L) a week later, identified as being mostly contributed by the bone-ALP isoform (11,062 U/L; RI 0-30 U/L). In addition, the atypical leukocytes were strongly positive for cytoplasmic ALP activity. In vitro lysis of a heparin blood sample resulted in a 1.7-fold increase of ALP activity, supporting the origin of the hyperphosphatasemia at least in part from the leukemic cell population. To the authors' knowledge, this is a unique case of alkaline hyperphosphatasemia, due at least to a leukemic cell population producing a bone-ALP isoform, regardless of the exact nature of the leukemia.

Dogs with Acute Myeloid Leukemia Have Clonal Rearrangements in T and B Cell Receptors

“…We found a similar result in this study, in which tumor cells in dogs with AML expressed B or T cell surface antigens, yet displayed non-clonal, biclonal, or B or T cell receptor clonal rearrangements. Although non-clonal or polyclonal results on clonality testing have been used to support a diagnosis of AML in previous reports (6, 10, 14, 15), false-negative reactions for clonality do occur in lymphoid neoplasms, with reported sensitivities ranging from 67 to 98% (5–7, 10, 20), using similar primer sets to that used herein.…”

“…Clonality testing is primarily used to distinguish between neoplastic and reactive lymphocyte expansions (1, 2, 6–8); however, this testing is also used as a means to phenotype lymphoid neoplasms as B or T in origin, particularly with tumors showing expression of more than one lineage with flow cytometry or immunohistochemical (IHC) staining (2, 5, 6, 8–13). The use of clonality as a phenotyping tool is being extended to myeloid neoplasms, where clonality testing has been used as a means to distinguish between acute myeloid leukemia (AML) and lymphoid neoplasms (lymphoma or leukemia) (6, 14, 15). However, we have observed clonal rearrangements in both B and T cell receptors in cases of AML in dogs and a previous study documented a clonally rearranged B cell receptor in one of three dogs with AML (3).…”