Multiple tongue lesions in a dog with lymphadenopathy

Francesco Cian DVM, Dip. ECVCP, FRCPath, MRCVS, RCVS and EBVS Specialist in Veterinary Clinical Pathology. BattLab, UK.

SIGNALMENT, CLINICA HISTORY AND CLINICAL EXAMINATION

A 12-year-old mixed breed dog was referred to the veterinarian for the presence of multiple lesions on the tongue and enlarged submandibular and prescapular lymph nodes. At clinical examination, the tongue lesions were multiple and measured up to 1cm in diameter. They were lightly pink in colour, raised, with distinct borders. The veterinarian performed fine needle aspirates of both tongue lesions and enlarged lymph nodes and submitted the slides to an external laboratory for cytological examination. Complete blood count and serum biochemistry analyses results were also performed and were within the reference limits, except for a mild non-specific elevation in ALP and albumin and a mild lymphopenia, the latter likely steroid-stress related.

Fig 1. Multiple raised lesions on the tongue of a dog. Photo courtesy of Fitzpatrick Referrals Ltd.

CYTOPATHOLOGY


Multiple aspirates of the tongue lesions and enlarged lymph nodes were taken under sedation. The following pictures show the most relevant cytological findings of these samples.

Fig 2. Enlarged submandibular lymph node, dog. Wright Giemsa, 50x.
Fig 3. Lingual mass, dog. Wright Giemsa, 50x.

What is your diagnosis based on these clinical and cytological findings?

INTERPRETATION OF THE RESULTS


Cytology. The aspirate from the submandibular lymph node was highly cellular and contained a main population of lymphoid cells on a lightly basophilic background. These cells appeared small to intermediate in size and had scant to moderately expanded pale blue cytoplasm, which often formed a small tail, giving the cells a typical “hand mirror” shape. Nuclei were small to intermediate in size, round in shape, with coarse nuclear chromatin and occasionally poorly visible nucleoli. Rare mature plasma cells were also noted. Cytological findings in the tongue lesions were similar, except for the aspirates being less cellular. There was a prevalence of small lymphocytes, only occasionally showing a hand mirror shape, on a clear and haemodiluted background. The cytological findings were overall highly suggestive of small cell lymphoma.


Further investigations and follow-up Further investigations to confirm the suspicion of lymphoma were recommended. These included flow cytometry, histopathology and/or PARR assay. The veterinarian requested PARR testing in order to avoid a second sedation for collecting a new sample. A clonal T-cell receptor rearrangement was identified, giving further support to the initial diagnosis and confirming small cell lymphoma. In particular, given the size and shape of most cells (small lymphoid cells with hand-mirror appearance) and the PARR results (clonal rearrangement of the T cell receptor), a T zone lymphoma (TZL) was considered very likely. The dog was referred to a specialist oncologist centre. Clinical staging was performed and liver and spleen aspirates were collected. Both samples harvested an increased numbers of small lymphoid cells, similar to those observed in the tongue. PARR assay was performed on the splenic aspirate and confirmed the presence of monoclonal population of lymphoid cells. The patient received lomoustine (CCNU) (70mg/m2, PO, every 3 weeks). Peripheral lymph nodes showed a mild decrease in size, whereas the tongue lesions persisted. At two months from the initial presentation, the disease is stable.


Discussion. Neoplasms of the tongue in dogs are rare and account for about 4% of all tumours that involve the oropharynx. The most commonly tumours found in the tongue are squamous cell carcinoma and melanoma. Lymphoma in the tongue rarely occurs in dogs and has been recently documented in a case series study in Veterinary Comparative Oncology Journal. All these twelve cases were TZL. This is a relatively common subtype of indolent small cell lymphoma, most often involving lymph nodes. Cytologically, it is characterised by an expansion of main population of hand mirror shape small lymphocytes originating from the paracortical area of lymphoid follicles. These neoplastic cells have a distinctive immunophenotype characterised by loss of expression of the pan-leukocyte marker CD45 and variable expression of other T-cell markers (e.g. CD3, CD4, CD8). Therefore, it is possible to diagnose this form of lymphoma based on cytology and flow cytometry only, and histopathology and immunohistochemistry may not be necessary. From a clinical point of view, TZL is a slowly progressive and indolent disease. The cases of the aforementioned publication were treated with a variety of therapeutic options, from surgical excision to multi-agent chemotherapy to palliative radiation. All but one achieved complete remission or stable disease. Median survival time (MST) was not provided because only two dogs died during the study period. However, ten of 12 dogs were still alive at publication (27-893 days post diagnosis).


Useful tips Histopathology, PARR and flow cytometry are all diagnostic tests that are often requested to confirm and/or to refine a diagnosis of lymphoma. Flow cytometry and PARR have the advantage of being less invasive than histopathology, not requiring any solid biopsy to be taken.

  • Flow cytometry is considered one of the tests of choice to confirm the diagnosis of lymphoma and to establish its immunophenotype. However, this technique requires a new fresh sample to be submitted to a dedicated external laboratory and this should be ideally analysed within 24 hours from collection.

  • PARR assay has the advantage that can be performed on almost any sample (including pre-stained cytology smears), and therefore it does not require additional sampling. It is a valid test to confirm / rule out lymphoma, when a cytological diagnosis is not possible. However, false negative and occasionally false positive results may occur. Therefore, it should not be used as a first line but only as a confirmatory test. It is not the preferred test for immunophenotyping purposes. In fact, it may happen that clonality results are not reflective of a cell’s true immunophenotype. This may be seen in cross-lineage rearrangements of T-cell receptor in diffuse large B cell lymphomas or plasma cell neoplasms.



Further reading

  • Harris LJ, Rout ED, Hughes KL et al. Clinicopathologic features of lingual canine T-zone lymphoma. Vet Comp Oncol, 2018. 16(1), 131-139.

  • Martini V, Marconato L, Poggi A et al. Canine small clear cell/T-zone lymphoma: clinical presentation and outcome in a retrospective case series. Vet Comp Oncol, 2015. 14(S1), 117-125.

  • Raposo-Ferreira TMM, Cesar Jarl P, Rossi Varallo G et al. T-cell lymphoma in the tongue of a dog with cutaneous and striated forelimb muscle involvement. Acta Sci Vet, 2014. 42(1), 60.

  • Seelig DN, Avery P, Webb T et al. Canine T-zone lymphoma; unique immunophenotypic features, outcome and population characteristics. J Vet Intern Med, 2014. 28(3), 878-886.