Canine Indolent Lymphoma – Why Do We Need to Know About
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IN THE LAB FIGURE 1: T-zone lymphoma fine needle aspirate cytology showing ‘hand mirror’ cells – small to intermediate lymphocytes that frequently have a unipolar cytoplasmic extension (red arrows). (Bar = 10um.) of lymphoma is made based on cell morphology only, without assessment Canine indolent of architecture or immunophenotype. Specific therapy based on a specific subset of lymphoma type is therefore largely lymphoma – why lacking in the veterinary world, compared with the tailored treatment regimens implemented in human oncology. do we need to know The most common indolent lymphomas include T-cell lymphoma and the B-cell indolent lymphomas, including marginal about it? cell lymphoma, mantle cell lymphoma, and follicular lymphoma (Flood-Knapik et al., 2013; Valli et al., 2006). Other, less Clinical and Anatomic Veterinary Pathologist Michelle common, indolent lymphomas in dogs include small lymphocytic lymphoma, Lepherd of Gribbles Veterinary Christchurch highlights lymphoplasmacytic lymphoma, and T-cell a potentially underdiagnosed subset of lymphomas. rich B-cell lymphoma. A dog with an indolent lymphoma may present with one or more enlarged lymph WHILE THE MOST common types as important to differentiate aggressive nodes or a solitary splenic nodule (found of lymphoma in dogs are of the high- versus indolent lymphoma, in addition on palpation, ultrasound, or subsequent grade, large cell, B- or T-cell type that to B- versus T-cell lymphoma, as low- to haemoabdomen), and is, more often most of us would be familiar with, grade, indolent lymphomas can have than not, clinically well. In some dogs, there is a significant subset of indolent a long survival time and often require the lymph nodes may have been enlarged lymphomas that may account for up to conservative or no therapy. for several months or years prior to 30% of canine lymphoma cases and are Canine lymphoma is a heterogeneous presentation (Valli et al., 2006). probably underdiagnosed (Flood-Knapik disease with highly variable clinical Indolent lymphomas are typically et al., 2013; Valli et al., 2013). In terms presentation, progression, and prognosis. composed of small- to intermediate-sized of survival and prognosis, it may be just In many instances, a generic diagnosis lymphocytes that have a low mitotic rate. 50 – VetScript November 2017 IMAGERY: SUPPLIED IN THE LAB They can be mistaken for lymphoid In fact, many dogs can do well without hyperplasia or a reactive lymph node WHILE THE CLUED- treatment, and ‘watchful waiting’ may on fine needle aspirate (FNA) cytology, be a reasonable approach, particularly in as they lack the significant numbers UP PATHOLOGIST the earlier phases of disease. However, of large lymphocytes that help to CAN OFTEN GET it appears that some indolent B-cell cytologically diagnose the more lymphomas can behave like, or transform common large cell lymphomas. A SUSPICION OF into, high-grade lymphomas. There is While the clued-up pathologist can INDOLENT LYMPHOMA no established consensus about when to often get a suspicion of indolent treat dogs with indolent lymphoma. For lymphoma from cytology findings and FROM CYTOLOGY asymptomatic TZL, Moore (2016) suggests detailed clinical history, histopathology FINDINGS AND DETAILED watchful waiting with careful monitoring is essential for confirmation. Whole of peripheral nodes and haematology. node or large wedge-shaped biopsies that CLINICAL HISTORY, Further therapy should be considered incorporate capsule, cortex and medulla HISTOPATHOLOGY if dogs develop clinical signs, have are required, as most indolent lymphomas rapid progression (defined as a tumour have a characteristic pattern of follicular IS ESSENTIAL FOR doubling time of less than six months), a expansion and effacement. CONFIRMATION. circulating lymphocyte count greater than Tru-cut and narrow core biopsies are 9.2 x 109/L, multiple sites of lymphoma often unrewarding, as they don’t include larger than 3cm in diameter or a single enough architecture for diagnosis. In site greater than 7cm in diameter, many cases, routine histopathology of an development of myelosuppression due to adequately sized biopsy will be sufficient lymphoma (MZL), which is of B-cell origin, myelophthisis, or organ dysfunction due to diagnose the subtypes of indolent and occurs in either lymph nodes or, more to infiltration. Chemotherapy for indolent lymphoma. However, in more advanced commonly, the spleen. It is characterised lymphoma ranges from prednisone alone, cases, where there is greater effacement of by coalescing perifollicular proliferation combination prednisone and chlorambucil, architecture and obscure residual follicles, of marginal cells and paracortical atrophy. or CHOP-based chemotherapy protocols, immunophenotyping for B- and T-cell Splenic MZL often has a good response to similar to those used for aggressive markers can be enormously helpful in splenectomy alone (Valli et al., 2006). lymphoma (Flood-Knapik et al., 2013). recognising the follicle-related heritage Interestingly, 10-50% of dogs with In the future, better characterisation and fading follicles that characterise most indolent lymphoma also have demodicosis and more precise diagnoses of lymphoma, indolent lymphomas. The detection of (Flood-Knapik et al., 2013; Mizutani et al., alongside the documentation of responses clonality is a useful adjunct to histology 2016). Demodex spp. infestation is usually to specific treatments, will hopefully allow and immunohistochemistry, particularly associated with immunosuppression and for more accurate prognostications and in those cases with an ambiguous the presence of indolent lymphoma may lymphoma-specific therapy. morphology and immunophenotype. predispose to immune dysregulation T-zone lymphoma (TZL) is the most and subsequent demodicosis. Also, common type of indolent lymphoma demodicosis itself may cause further REFERENCES: and, as the name suggests, is of T-cell immunosuppression. Further work-up for Flood-Knapik KE, Durham AC, Gregor TP, origin, developing as an expansion of the lymphoma may be warranted in older dogs Sánchez MD, Durney ME, Sorenmo KU. Clinical, histopathological and immunohistochemical paracortical areas between fading follicles. with generalised demodicosis, and should characterization of canine indolent lymphoma. A clue to diagnosis can often be seen include lymph node biopsy, rather than Veterinary and Comparative Oncology 11, 272–86, 2013 on FNA of affected lymph nodes, due to just FNA, to ensure indolent lymphoma Mizutani, N, Goto-Hoshino Y, Takahashi the presence of large numbers of small to can be detected. M, Uchida K, Tsujimoto H. Clinical and histopathological evaluation of 16 dogs with T-zone intermediate lymphocytes that frequently Median lymphoma-specific survival lymphoma. Journal of Veterinary Medicine and Surgery have a unipolar cytoplasmic extension time for indolent lymphoma has been 78, 1237–44, 2016 (hand mirror cells – Figure 1). reported to be as long as 4.4 years and Moore AS. Treatment of T-cell lymphoma in dogs. Dogs with TZL often have generalised the median overall survival time (OST) Veterinary Record 179, 277–81, 2016 lymphadenopathy, and therapy does not as 21.2 months, and is longest for TZL Valli VE, Vernau W, de Lorimier L-P, Graham appear to positively influence survival (median OST of 33.5 months) (Flood- PS, Moore PF. Canine indolent nodular lymphoma. Veterinary Pathology 43, 241–56, 2006 or quality of life (Valli et al., 2006; Valli Knapik et al., 2013). Dogs with solitary Valli VE, Kass PH, San Myint M, Scott F. Canine et al., 2013). splenic nodules are reported to do well lymphomas: association of classification type, disease The second most common type of with splenectomy alone (Flood-Knapik stage, tumor subtype, mitotic rate, and treatment with indolent lymphoma is marginal zone et al., 2013; Valli et al., 2006). survival. Veterinary Pathology 50, 738–48, 2013 VetScript November 2017 – 51.