Association between lymphocyte antigen receptor gene rearrangements and histopathological evaluation in canine chronic enteropathy

Hiyoshi, Saaya; Ohno, Koichi; Uchida, Kazuyuki; Goto‐Koshino, Yuko; Nakashima, Ko; Fukushima, Kenjiro; Kanemoto, Hideyuki; Maeda, Shingo; Tsujimoto, Hajime

doi:10.1016/j.vetimm.2015.03.009

Cited by 12 publications

(17 citation statements)

References 32 publications

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“…25 A clonal IgH rearrangement or absence of clonal TCR rearrangement could be attributed to inconsistencies resulting from differences in biopsy sites between PARR and histopathological evaluation, or the limited coverage of the primers. 26 The current canine study showed an association between tumour cell morphology and prognosis. Our finding was consistent with that of a previous study, 27 which showed that LCL cases had a poorer prognosis than did SCL cases.…”

Section: Discussionmentioning

confidence: 58%

“…It should be noted that dual TCR and IgH rearrangements were documented in both T‐ and B‐cell lymphomas and that final determination should be based on immunohistochemical phenotypes . A clonal IgH rearrangement or absence of clonal TCR rearrangement could be attributed to inconsistencies resulting from differences in biopsy sites between PARR and histopathological evaluation, or the limited coverage of the primers . The current canine study showed an association between tumour cell morphology and prognosis.…”

Section: Discussionmentioning

confidence: 69%

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Pathological features of intestinal T‐cell lymphoma in Shiba dogs in Japan

Matsumoto

Uchida

Nakashima

et al. 2018

Vet Comparative Oncology

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Intestinal T-cell lymphoma is being more frequently diagnosed in dogs owing to the wide availability of endoscopy and clonality analysis in veterinary medicine. However, no epidemiological study on intestinal T-cell lymphoma has been previously performed, and hence, information about dog breed, age and sex distributions of intestinal T-cell lymphoma has largely remained unclear. In this study, breed predisposition to canine intestinal T-cell lymphoma was determined by calculating odds ratios and 95% confidential intervals. Of the 43 breeds identified, 7 appeared to have an increased risk of developing intestinal T-cell lymphoma, including Shiba dogs, German shepherds, Cairn terriers, Boston terriers, Papillons, Pugs and Maltese. Immunohistochemistry of representative Shiba cases revealed ubiquitous cytotoxic immunophenotype in both large and small cell lymphomas. Interestingly, CD20 co-expression was observed in 11% of cases. It could potentially be aberrant expression of CD20 or neoplastic transformation of a normal subset of CD20-positive T-cells. A comparison of mean age between representative breeds revealed that Shiba dogs were slightly younger than Miniature Dachshunds (P < .05). However, there was no difference in survival between the 2 breeds. As Shiba dogs are predisposed to chronic enteropathy, there may be underlying inflammatory process contributing to lymphomagenesis of intestinal T-cell lymphoma in this breed. Our findings provide insights into the underlying pathogenesis of breed-specific canine intestinal T-cell lymphoma.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 69%

Pathological features of intestinal T‐cell lymphoma in Shiba dogs in Japan

Matsumoto

Uchida

Nakashima

et al. 2018

Vet Comparative Oncology

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“…Furthermore, lymphoma was diagnosed based on histopathology and not immunohistochemistry and PARR in our study. Considering the limitations of histopathology for the diagnosis of lymphoma, lymphoma could not be completely excluded especially in 3 dogs that were PARR positive, although 51% of dogs with chronic enteritis showed positive results for PARR in a previous study . In addition, functional biomarkers for enteropathy in dogs, such as fecal and serum concentrations of alpha‐1 proteinase inhibitor, folate, and cobalamin, which are possibly useful for determining responsiveness to ULFD, were not measured in most dogs in our study.…”

Section: Discussionmentioning

confidence: 78%

Clinical characteristics of dogs with food‐responsive protein‐losing enteropathy

Nagata

Ohta

Yokoyama

et al. 2020

Veterinary Internal Medicne

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Background In dogs with protein‐losing enteropathy (PLE), data on the clinical characteristics of food‐responsive PLE (FR‐PLE) remain scarce. Objective To determine the clinical characteristics of FR‐PLE in dogs responsive to ultralow‐fat diet (ULFD) management. Animals Thirty‐three dogs diagnosed with PLE based on standard diagnostic criteria. Methods Retrospective review of medical records. Clinical findings were compared between dogs with FR‐PLE (FR‐PLE group) and those with immunosuppressant‐responsive PLE (IR‐PLE) or nonresponsive PLE (NR‐PLE) (IR/NR‐PLE group). The area under the curve (AUC) of a receiver operating characteristic curve was used to evaluate the ability of factors to differentiate the FR‐PLE and IR/NR‐PLE groups. Survival time was compared between the FR‐PLE and IR/NR‐PLE groups. Results Twenty‐three dogs responded to ULFD management and were diagnosed with FR‐PLE. The canine chronic enteropathy clinical activity index (CCECAI) was significantly lower in the FR‐PLE group than in the IR/NR‐PLE group (P < .001). The AUC of CCECAI for differentiating the FR‐PLE group was 0.935 (95% confidence interval [CI], 0.845‐1.000) with an optimal cutoff value of 8 (sensitivity, 0.826; specificity, 0.889). Survival times were significantly longer in the FR‐PLE group (median, not reached) than in the IR/NR‐PLE group (median, 432 days; P < .001). Conclusions and Clinical Importance Dogs that respond to ULFD management and are diagnosed with FR‐PLE are expected to have a favorable prognosis. Clinical scores, specifically the CCECAI, could be useful for differentiating FR‐PLE from IR‐PLE or NR‐PLE.

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“…A lymphocytosis due to increased LGLs in dogs is proposed to be, according to the etiology, as either a reactive lymphocytosis including infectious and inflammatory diseases or malignant transformation of lymphoid neoplasia . It has been reported that PARR analysis is useful for neoplastic clonal detection, but some infectious diseases, including Ehrlichia and inflammatory diseases, were not completely ruled out . As a result of PARR analysis, a clonal TCRɤ gene rearrangement was detected in the BM smears, and a reactive lymphocytosis secondary to a systemic bacterial infection was less likely after culture and real‐time PCR of the peripheral blood.…”

Section: Discussionmentioning

confidence: 99%

“…However, the dog was not definitively diagnosed with lymphoid neoplasia because the lymphocyte ratio was less than 30% in the BM and no lymphocytosis was found in the peripheral blood . A clonal lymphocytosis secondary to infection was considered unlikely given the negative blood culture and the real‐time PCR results, though other inflammatory diseases, such as immune‐mediated disease, was not excluded . Therefore, the dog was diagnosed with hemophagocytic syndrome (HPS) based on a report by Weiss, using a cutoff >2% hemophagocytic macrophages in the BM to make a diagnosis .…”

Section: Case Presentationmentioning

confidence: 99%

A case of hemophagocytic syndrome progressing into large granular lymphoma in a dog

Akiyoshi

Hisasue

Neo

et al. 2019

Veterinary Clinical Pathol

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A 12-year-old castrated male mixed breed dog was presented with anorexia, lethargy, intermittent vomiting, diarrhea, and weight loss. Clinicopathologic and imaging abnormalities included pancytopenia, icterus, and splenomegaly with multiple minute hypoechogenic nodules. Bone marrow (BM) smears revealed 2.5% hemophagocytic macrophages. In addition, an increased number of small to intermediate lymphocytes (16.3%) and plasma cells (3.2%) were recognized in the BM smears. More than 80% of the lymphocytes contained multiple small intracytoplasmic magenta granules.Histopathologic findings of the spleen revealed hemophagocytosis. Large granular lymphocytes (LGLs) were not found on the liver cytology or splenic histopathology at this time. PCR for antigen receptor rearrangement (PARR) analysis showed a clonal reaction in the T-cell receptor ɤ (TCRɤ) gene in the BM sample. The dog was diagnosed with hemophagocytic syndrome (HPS). The dog was maintained in good condition with immunosuppressive therapy. However, the dog developed hepatic LGL lymphoma 7 months later. At this time, PARR analysis showed a clonal TCRɤ gene rearrangement in the hepatic LGL lymphoma samples. The BM and liver sample clonal rearrangements showed 100% homology, indicating that the small to intermediate granular lymphocytes in the BM at the HPS stage had progressed to hepatic LGL lymphoma. To our knowledge, this is the first report of canine secondary HPS caused by the occurrence of a BM LGL lymphoma clone that progressed to hepatic LGL lymphoma.

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Association between lymphocyte antigen receptor gene rearrangements and histopathological evaluation in canine chronic enteropathy

Cited by 12 publications

References 32 publications

Pathological features of intestinal T‐cell lymphoma in Shiba dogs in Japan

Pathological features of intestinal T‐cell lymphoma in Shiba dogs in Japan

Clinical characteristics of dogs with food‐responsive protein‐losing enteropathy

A case of hemophagocytic syndrome progressing into large granular lymphoma in a dog

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