Establishing cell lines for canine tonsillar and non-tonsillar oral squamous cell carcinoma and identifying characteristics associated with malignancy.

Canine tonsillar squamous cell carcinoma (TSCC) shows a higher metastasis rate than non-tonsillar oral SCC (NTSCC). The mechanisms of metastasis for TSCC have been less studied, because both TSCC and NTSCC cell lines are few. In this study, 6 cloned TSCC (TSCCLN#1-#6), which were from a metastatic lymph node, and 2 cloned NTSCC (oSCC-1 and -4) cell lines, which were from the primary lesion, were established, and their characteristics were evaluated in vitro and in vivo. Results showed that increased expression level of Vimentin in TSCC cell lines and increased expression levels of mesenchymal markers including Vimentin, Snail, and Slug in NTSCC cell lines corelated with the malignant phenotypes such as the cell growth and colony formation abilities in vitro. However, expression levels of mesenchymal markers and in vitro characteristics were unrelated to tumorigenic ability in nude mice. Additionally, the expression levels of E-cadherin and Vimentin were also evaluated by immunohistochemistry using the formalin-fixed paraffin embedded canine oral SCC tissues, and the results show that the expression level of Vimentin in TSCC was higher than in NTSCC. In conclusion, the cell lines established in this study might contribute to elucidating the mechanisms involved in TSCC metastasis.

Canine tonsillar neoplasia and tonsillar metastasis from various primary neoplasms.

Tonsillar metastasis from distant primary tumours has not been described in dogs, and reports are rare in humans. The aims of this study were to determine whether tumour metastasis occurs to the canine palatine tonsils and evaluate whether afferent lymphatics drain to the palatine tonsils via skull indirect computed tomography lymphangiography (ICTL). Retrospective review of the diagnostic laboratory tonsillar histopathology submissions was performed. ICTL studies (n = 53) were retrospectively reviewed by a single radiologist. Of 882 total tonsil histopathology samples, 492 (56%) were considered neoplastic, with 8% of them benign. Of the primary malignant neoplasms of the tonsil, squamous cell carcinoma (55%), lymphoma (17%) and melanoma (12%) were most common. Tonsillar metastasis was confirmed in 41 cases; histopathologic evaluation revealed melanoma (25), carcinoma (10), hemangiosarcoma (2) and one each of fibrosarcoma, malignant histiocytosis, basal cell tumour and undifferentiated sarcoma. A total of 53 tonsillar melanoma cases were identified, of which 25 represented metastasis from a known distant primary tumour and 28 were solely tonsillar, with 9 of these cases having concurrent lymph node metastasis. No ICTL cases had lymphatic contrast drainage to the palatine tonsil. The palatine tonsil is an important site of metastasis for a variety of primary tumour types from many locations. ICTL did not reveal lymphatics draining to the palatine tonsil, which is highly supportive of hematogenous route of metastasis to the tonsil. Tonsillar metastasis may be more common than previously thought. It is recommended to perform a thorough oral examination, including the tonsils, for all oral tumours and melanoma cases.

Hypoglycemia associated with disseminated metastatic tonsillar squamous cell carcinoma producing insulin-like growth factor-I in a Pomeranian dog.

A 13-year-old spayed female Pomeranian dog was presented for persistent, severe hypoglycemia (37 mg/dL; reference interval [RI] 75-128 mg/dL). Progressive nonregenerative anemia (hematocrit 23.3%-15.9%; RI 37.0%-55.0%) and severe thrombocytopenia (36 000/µL; RI 200-500 000/µL) were also noted. The serum insulin concentration was low (0.24 ng/mL; RI 0.302-1.277 ng/mL). Computed tomography revealed multiple splenic nodules (1-6 mm in diameter) and several hepatic nodules (7.6, 12 mm in diameter). Ultrasound-guided fine-needle aspiration of the splenic and hepatic nodules revealed low numbers of epithelial cells with mild cellular atypia, suggestive of a metastatic epithelial tumor, but the primary site was unknown at that time. On careful oral examination under general anesthesia, an enlarged right tonsil was noted grossly, and histopathologic examination of the tonsil diagnosed squamous cell carcinoma. Bone marrow aspirates and biopsies of the splenic and hepatic nodules were performed; all samples were diagnosed as metastatic carcinoma on histopathologic examination. No nodules were present in the pancreas, despite careful palpation during exploratory laparotomy. On immunohistochemistry, the neoplastic cells were positive for cytokeratin AE1/3 and insulin-like growth factor (IGF)-I but were negative for chromogranin A, PGP9.5, insulin, and inconclusive for IGF-II. This is the first report of a primary IGF-I-producing squamous cell carcinoma in the tonsil of a dog with metastases to bone marrow, liver, and spleen, resulting in hypoglycemia.

Occult tonsillar squamous cell carcinoma in 2 dogs presenting for treatment of primary oral squamous cell carcinoma.

Canine non-tonsillar oral squamous cell carcinoma (OSCC) is generally regarded as locally invasive with low rates of metastasis. Two cases of canine non-tonsillar OSCC with occult tonsillar squamous cell carcinoma (TSCC) detected with tonsillar biopsies are reported. Tonsillar biopsies and detection of occult TSCC changed the therapeutic plan and may have contributed to long-term tumor control.

Carcinome squameux tonsillaire occulte chez 2 chiens présentés pour le traitement d'un carcinome squameux buccal primaire. Le carcinome squameux buccal (CSB) non tonsillaire canin est généralement considéré comme localement invasif avec de faibles taux de métastase. Deux cas de CSB non tonsillaire canin avec un carcinome squameux tonsillaire (CST) occulte détectés lors de biopsies tonsillaires ont été signalés. Les biopsies tonsillaires et la détection du CST occulte ont modifié le régime thérapeutique et peuvent avoir contribué au contrôle de la tumeur à long terme.(Traduit par Isabelle Vallières).

Tonsillar plasmacytoma in a dog.

A 10-year-old greyhound dog was presented because of an incidental finding of a tonsillar mass. Excisional surgical biopsy was performed and the dog was diagnosed with an incompletely resected plasma cell tumor. Adjuvant therapy was declined. One year later there was no local recurrence or distant metastasis of the mass or clinical signs associated with the tonsillar plasmacytoma.

Plasmacytome tonsillaire chez un chien. Un chien Greyhound âgé de 10 ans a été présenté en raison de la découverte fortuite d'une masse tonsillaire. Une biopsie par excision chirurgicale a été réalisée et le chien a été diagnostiqué avec une tumeur à plasmocytes avec résection incomplète. Le traitement avec adjuvant a été refusé. Une année plus tard, il n'y avait aucune récurrence locale ou de métastase distante de la masse ou de signes cliniques associés au plasmacytome tonsillaire.(Traduit par Isabelle Vallières).

Primary tonsillar mast cell tumour in a dog.

CASE REPORT: A 6-year-old speyed female Bull Arab-cross dog was found to have a small tonsillar nodule. Histological examination revealed a well-differentiated mast cell tumour (MCT). At initial staging, no evidence of concurrent cutaneous or visceral MCTs was found on a complete blood count, a single lateral thoracic radiograph, abdominal ultrasound or cytology of the spleen and regional lymph nodes. A diagnosis of primary tonsillar MCT was made. At 40 months postoperatively, the dog is alive with no evidence of gross tumour progression, in contrast to some previous reports of rapid disease progression and metastasis in dogs with primary oral MCTs. CONCLUSION: To the authors' knowledge, no previous reports of a primary MCT of the tonsil in dogs exist in the veterinary literature.

Computed tomographic appearance of canine tonsillar neoplasia: 14 cases.

The palatine tonsil is an uncommon site of oral canine neoplasia. For affected tonsils, squamous cell carcinoma is the most frequent type of neoplasia, followed by melanoma and lymphoma. Computed tomography (CT) is increasingly used for investigation of canine oropharyngeal pathology; however, limited information is available on the CT appearance of tonsillar neoplasms. Objectives of this retrospective descriptive case series were to characterize the CT features of canine tonsillar neoplasia and determine whether specific CT features differentiate nonneoplastic from neoplastic tonsils. Computed tomographic studies of 14 dogs diagnosed with tonsillar neoplasia were retrieved from two referral hospitals and reviewed by two observers. Diagnosis was based on histology or cytology. Carcinoma was diagnosed in 11 dogs, melanoma in two and lymphoma in one dog. Specific CT features of the tonsil and regional lymph nodes did not differentiate neoplastic from nonneoplastic tonsillar diseases, but regional lymph node CT features were useful for diagnosis in some cases. Marked enlargement (width ≥ 18 mm, 12/18), heterogeneity (16/18), and loss of the hypoattenuating hilus (18/18) of the medial retropharyngeal lymph node were common concomitant features of tonsillar neoplasia. The medial retropharyngeal and mandibular lymphadenomegaly was ipsilateral to the neoplastic tonsil in 8/12 and 6/9 dogs, respectively. Five dogs demonstrated little or no enlargement of the tonsil despite the associated metastatic lymphadenomegaly. Tonsillar neoplasia should therefore be considered as a differential diagnosis for dogs with CT evidence of isolated medial retropharyngeal lymphadenomegaly (regardless of normally sized tonsils), or of any enlarged tonsil with no associated lymphadenomegaly.

Evaluation of the factors contributing to long-term survival in canine tonsillar squamous cell carcinoma.

OBJECTIVES: To identify any prognostic factors that may be associated with the long-term survival of dogs diagnosed with tonsillar squamous cell carcinoma (TSCC). METHODS: The medical records of 15 dogs treated for TSCC were reviewed retrospectively. The signalment, presenting signs, clinical stage, treatments and outcome were documented. RESULTS: The overall median survival time (MST) of the dogs in the study was 243 days. There was a 1-and 2-year survival of 40% and 20%, respectively. The results of initial staging had a significant effect on survival, as dogs with only one tonsil affected and no evidence of metastatic disease had a longer MST (637.5 days) than the dogs with local (MST: 134 days) or distant (MST: 75 days) metastatic disease or bilateral tonsillar involvement at the time of initial presentation. Prolonged survival times were reported for dogs undergoing surgery and adjunctive chemotherapy (MST: 464.5 days) for treatment of their TSCC. CLINICAL SIGNIFICANCE: This is the first veterinary study demonstrating an association between prognosis of patients with TSCC and stage at the time of presentation, with long survival times demonstrated for dogs with early-stage disease following an initial treatment protocol that included surgery and chemotherapy. There was no clear association between long survival and additional surgeries for progressive disease; however; further investigation is warranted.

Detection of carcinoma micrometastases in bone marrow of dogs and cats using conventional and cell block cytology.

BACKGROUND: The presence of human breast carcinoma micrometastases in bone marrow is associated with poor overall survival, poor breast-cancer-specific survival, poor disease-free survival, and poor distant disease-free survival. In veterinary practice, the detection of micrometastases as a component of clinical staging is a routine practice for lymphomas and mast cell tumors, but not for carcinomas. OBJECTIVES: This prospective study evaluated whether the identification of micrometastases from various carcinomas in dogs and cats in bone marrow using cell block cytology is technically feasible and whether it correlates with routine cytologic examination. METHODS: Thirteen dogs and 4 cats with various types of carcinomas were available for analysis. Routine and cell block cytologic evaluation combined with immunocytochemical staining with antibodies to CKAE1/AE3 and CK7 were performed on all bone marrow samples. RESULTS: Bone marrow micrometastasis was demonstrated by both methods in 2 dogs with advanced disease. In one case cells were immunoreactive for both CKAE1/AE3 and CK7. CONCLUSIONS: This study demonstrates that cell block cytology is a practical and useful method for bone marrow evaluation and is suitable for cytokeratin immunocytochemical analysis.

Histological subtypes of oral non-tonsillar squamous cell carcinoma in dogs.

Several histological subtypes and grades of oral squamous cell carcinoma (SCC) are described in human literature and these subtypes have distinct morphological features and biological behaviour. This retrospective study (1990-2010) included 84 dogs diagnosed with SCC of the oral cavity and oropharynx, excluding the tonsils. Sixty-nine of the SCCs (82.1%) were further diagnosed as conventional SCC (CSCC) (33 [47.8%] well-differentiated, 31 [44.9%] moderately-differentiated and five [7.3%] poorly-differentiated), five (5.95%) each as papillary SCC and basaloid SCC, three (3.6%) as adenosquamous carcinoma and two (2.4%) as spindle cell carcinoma. Compared with the general hospital population, neutered female dogs, dogs aged 10 to <15 years, English springer spaniels and Shetland sheepdogs were overrepresented. The majority (78.1%) of SCCs were proliferative with or without associated ulceration, although no significant association was observed between the gross appearance and different SCC subtypes. 71.4% of SCCs were located in dentate jaws; however, well-differentiated CSCC more often affected the tongue and other non-dentate mucosal surfaces (P=0.0022). No significant association was found between any of the SCC subtypes and tumour-associated inflammation (TAI), perineural and lymphovascular invasion (PNI, LVI), or between gross appearance of the tumour and tumour location, PNI, LVI or TAI or PNI, LVI, TAI and tumour location.

Canine tonsillar squamous cell carcinoma -- a multi-centre retrospective review of 44 clinical cases.

OBJECTIVES: To review the presenting clinical signs, treatment and survival of dogs with tonsillar squamous cell carcinoma and, if possible, to identify useful prognostic indicators. METHODS: Medical records of 44 dogs were reviewed retrospectively. Clinical signs, clinical stage, time of diagnosis, treatment and outcome were recorded. Data were analysed using the Kaplan-Meier, log-rank, Student's t test, Kruskal-Wallis test and Chi-square/Fisher Exact test as appropriate. RESULTS: The most frequent clinical signs were cough (12 dogs, 27%), enlarged lymph nodes (11 dogs, 25%) and dysphagia (11 dogs, 25%). Anorexia and lethargy were less common but were significantly associated with a poor outcome. No matter what treatment modalities were used, survival times were short and median survival time for all the dogs in the study was 179 days. However, there were a small number of long-term survivors. CLINICAL SIGNIFICANCE: Dogs with tonsillar squamous cell carcinoma that suffered anorexia and lethargy had shorter survival times than patients without these clinical signs. Although surgery, chemotherapy and radiotherapy seem to increase the median survival time of dogs diagnosed with tonsillar squamous cell carcinoma, there is no highly effective treatment for canine tonsillar squamous cell carcinoma.

Tonsillar lymphangiomatous polyp in an adult dog.

A female spayed cocker spaniel dog, aged 8 years, developed a large, smooth pedunculated mass arising from the right palatine tonsil. Histology revealed that the mass was composed of many, variably dilated, thin-walled lymphatic channels filled with pale eosinophilic fluid lacking red blood cells and embedded in a dense, fibrovascular stroma. The dilated lymphatic channels were lined by a single layer of flattened, discontinuous endothelium with scattered intraluminal valves. Periodic acid-Schiff staining highlighted the discontinuous basement membrane and immunohistochemistry revealed strong cell membrane and cytoplasmic immunoreactivity for CD31 and von Willebrand factor, respectively. The clinical and histological findings were consistent with a tonsillar lymphangiomatous polyp - an uncommon, benign tumour of the tonsil in man that has previously been unrecognized in veterinary medicine.

Role of carboplatin in multi-modality treatment of canine tonsillar squamous cell carcinoma--a case series of five dogs.

Canine tonsillar squamous cell carcinoma is an aggressive disease with a poor prognosis. A retrospective study was undertaken of all dogs that were presented between January 1999 and January 2004 to the Animal Health Trust for the treatment of tonsillar squamous cell carcinoma. Five cases were identified, and their median survival time was 211 days (95 per cent confidence interval 80 to 352) with two of the five dogs remaining alive at the end of the study, 826 and 1628 days from diagnosis with no clinical signs of disease. The protocol was well tolerated with only one of the five dogs showing toxicity associated with carboplatin and all dogs that started radiotherapy completing it. Compared with results of previous studies, these cases suggest that surgical cytoreduction followed by coarse fractionated radiotherapy together with carboplatin may be a useful way to treat this tumour. Carboplatin alone caused partial remission in the two cases where it was used as neo-adjunctive therapy.

Tp53 expressing squamous cell carcinoma of the tonsil in a captive polar wolf (Canis lupus arctos).

The gross and histopathologic findings for a primary tonsillar squamous cell carcinoma in a captive 11-yr-old male polar wolf (Canis lupus arctos) are described. The carcinoma had metastasized to regional lymph nodes of the pharynx, the precardial mediastinum, and the lungs. Tumor suppressor protein TP53 was detected by immunohistochemistry in the nuclei of poorly differentiated, cytokeratin-positive cells of the primary neoplasm and the metastases. Canine oral papillomavirus DNA was not detectable by polymerase chain reaction (PCR).

Early-onset leukopenia and severe thrombocytopenia following doxorubicin chemotherapy for tonsillar squamous cell carcinoma in a dog.

Doxorubicin is reported to cause myelosuppression, with a white blood cell count nadir occurring between day 7 and day 10. Thrombocytopenia is less severe and occurs between days 3 and 8. This report presents an early onset of leukopenia (day 5) and a severe thrombocytopenia (4000 platelets/microliter) (day 6) associated with doxorubicin administration for treatment of recurrent tonsillar squamous cell carcinoma in a dog.

Surgery of the tonsils.

The palatine tonsils are paired aggregates of lymphoid tissue that are surgically removed as a result of primary tonsillar disease, or are extirpated in an effort to decrease upper airway resistance in conjunction with other procedures of the oropharynx. Complications from tonsillectomy can arise for three reasons: 1) the effects of tonsil disease on the function of the oropharyngeal regions; 2) surgical dissection in the region; or 3) postoperative complication of the insult to tissue. Thorough preoperative patient evaluation, gentle tissue handling plus meticulous hemostasis, and careful observation during the postoperative period are stressed in this discussion of problems in tonsillar surgery.

Tonsillar granular cell tumour in a cat.

Granular cell tumour was diagnosed in a cat based on light and electron microscopic findings. Immunohistochemical findings for S-100 protein and neuron-specific enolase were negative, unlike its human counterpart.

Chemotherapy versus chemotherapy plus radiotherapy in the treatment of tonsillar squamous cell carcinoma in the dog.

The effect of adjuvant chemotherapy and combined chemotherapy and radiotherapy in 22 dogs with advanced canine tonsillar carcinoma (World Health Organization [WHO], T2-3 primary tumor with infiltration into surrounding tissues) was evaluated. There were four treatment groups of at least five dogs each. Combinations of chemotherapeutic drugs reported to have activity against squamous cell carcinoma in humans and dogs (doxorubicin, cisplatin, vinblastine, and cyclophosphamide) were administered after tonsillectomy. Radiation therapy (orthovoltage type, external beam) was combined with chemotherapy in one treatment group. The dogs that had combination radiation therapy and chemotherapy had higher response rates and significantly longer survival times. However, most dogs died of progression of disease.

Comparison of canine oropharyngeal malignancy in various geographical locations.

The variation in prevalence of neoplasms over time and location has been of value in identifying environmental carcinogens. Studies on the relative frequency of the different histological types of canine oropharyngeal malignant neoplasm have shown that squamous cell carcinoma of the tonsil occurs four times more commonly in south east England, and twice as frequently in the United States of America as in Melbourne, Australia. The prevalence of tonsillar squamous cell carcinoma in London in 1950 was 15 times greater than that currently experienced in Melbourne and four times greater than that now found in other areas of south east England.