Laryngeal, Laryngotracheal, and Tracheal Masses in Cats: 27 Cases (1998–2003)
Medical records of 27 cats with masses of the larynx and trachea were examined. Six cats had inflammatory masses, and 21 cats had neoplastic lesions. A definitive diagnosis was reached in 22 cats with a single biopsy. The median age of the cats was 12.0 years (range 6 to 20 years). Dyspnea was the most common clinical sign. Accurate diagnoses were best obtained through direct laryngeal or tracheal examination combined with histological examination of tissue biopsies. Kaplan-Meier survival data for all inflammatory and neoplastic lesions showed a median survival of 5 days, with 7.4% of cats alive at 1 year.
Introduction
Inflammatory and neoplastic laryngeal and tracheal masses are uncommon in cats.1–9 Squamous cell carcinoma and lymphoma have been described as the most common tumors of the larynx in the domestic cat.1,9 Carcinomas and lymphoma have been reported in the feline trachea.1–3,9,10 Cats that are presented with laryngeal and tracheal neoplasia commonly have advanced disease and poor survival rates.9 Conversely, inflammatory laryngeal and tracheal masses causing upper airway obstruction have a good prognosis.5–8,11 Cats with laryngeal and tracheal masses may be presented with dyspnea, dysphonia, wheezing, or coughing.1–9
In contrast to feline nasopharyngeal inflammatory and neoplastic masses, feline laryngeal and tracheal masses have not been evaluated in a single paper. Similar historical and radiographic findings and diagnostic techniques are used to identify all these masses.12
The purpose of this study was to evaluate inflammatory and neoplastic masses involving the larynx and trachea in 27 cats, with emphasis on the signalment, clinical signs, radiographic findings, cytological and/or histopathological findings, treatments, and outcomes.
Materials and Methods
A computer search of the medical records of the Bay Area Veterinary Specialists, San Leandro, California was performed from June 1998 through June 2003 to identify cats with laryngeal, tracheal, and laryngotracheal masses diagnosed by fine-needle aspirate (FNA) cytology or histopathological examination of a tissue biopsy. In all cases, the diagnoses were confirmed by histopathological examination of tissue biopsy.
Information obtained from the medical records included breed, sex, age, presenting complaint, feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) status, mass location, radiographic findings, histopathology/FNA cytology results, treatment, and outcome. Masses were statistically evaluated collectively and by anatomical location (i.e., laryngeal, tracheal, laryngotracheal). Histologically, lymphoid hyperplasia and lymphoplasmacytic inflammation were categorized as inflammatory masses. Masses initially diagnosed as inflammatory that were subsequently identified as neoplastic upon histopathology were only included in the neoplastic category for data analysis.
A single radiologist (Matteucci) interpreted all radiographs. Radiographic findings were identified as one or more of the following: soft-tissue opacity, decreased margination of laryngeal structures, stenosis of the airway, or no radiographic findings. Margination is a roentgen sign describing the ability to discern a structure’s radiographic silhouette contour. Cats were assigned to one of the following treatment groups: tube tracheostomy, chemotherapy, multiple therapies, miscellaneous therapy, or no treatment.
Statistical Analysis
Survival time was defined as the time from diagnosis until death. Median survival time was calculated by the Kaplan-Meier product limit method using statistical analysis software.a,13 Because of the small number of cases available for review, appropriate nonparametrical statistical tests (e.g., Mann-Whitney U test, Spearman’s rank correlation, Kendall’s rank correlation, Wilcoxon’s signed rank test, and chi-square test) were used to compare all recorded variables (i.e., age, gender, breed, mass location, radiographic findings, mass diagnosis, treatment type). All recorded variables were evaluated for their effects on survival time with a Kaplan-Meier life table analysis and Cox proportional hazards analysis. Cats were censored if they were lost to follow-up or died from diseases other than their laryngeal or tracheal mass. In addition, all recorded variables were evaluated statistically for potential correlations and associations. A two-tailed P<0.05 was considered statistically significant.
Results
Clinical Data
Twenty-seven cats met the criteria for inclusion in this study and included 10 castrated males and 17 spayed females. Of the 27 cats, 18 (67%) were domestic shorthairs, six (22%) were domestic longhairs, two (7%) were Siamese, and one (4%) was a Himalayan [Table 1]. Median age at diagnosis was 12.0 years (mean 12.7 years; range 6 to 20 years). Results of whole blood or serum enzyme-linked immunosorbent assay (ELISA) tests for FeLV antigen were negative in all cats. Two (7%) cats were positive for FIV upon ELISA testing. Positive FIV results were confirmed with Western blot analysis.b
The most common presenting complaints were dyspnea (n=17, 63.0%) and voice change (n=15, 55.6%) [Figure 1]. Coughing (n=10, 37%), gagging (n=10, 37%), weight loss (n=9, 33.3%), anorexia (n=8, 29.6%), wheezing (n=7, 25.9%), vomiting (n=5, 18.5%), tachypnea (n=2, 7.4%), and lethargy (n=1, 3.7%) were also noted.
Mass Location
Nineteen masses were located in the larynx [Table 1]. Eighteen of these involved the arytenoids. Unilateral arytenoid masses were found equally distributed between the left (n=7) and right (n=7) arytenoids. Four masses involved both arytenoids. One cat had a mass involving the epiglottis. Seven masses were located in the trachea. Of these, five involved the cervical trachea and two involved the intrathoracic trachea. One laryngotracheal mass extended from the left arytenoid into the proximal trachea.
Cytology and Histology
Tissue biopsy and histopathological examination were definitive in 22 cats. Five cats had a cytological or histopathological diagnosis of lymphoid hyperplasia that was subsequently changed to neoplastic disease upon further histopathological examination [Table 2]. Three of these five cats (case nos. 1, 2, 4) were initially diagnosed by FNA cytology as having lymphoid hyperplasia, and they were subsequently diagnosed with neoplasia by tissue biopsy and histopathology. One cat (case no. 3) was initially diagnosed with lymphoid hyperplasia by tissue biopsy, and a second tissue biopsy and histopathology revealed neoplasia. Case no. 5 was diagnosed with lymphoid hyperplasia via FNA cytology and concurrent tissue biopsy, but examination of a second tissue biopsy revealed neoplasia. In this last cat, the time interval between biopsies was 1109 days, so both biopsies may have been correct.
Twenty-one (77.8%) masses were neoplastic, and six (22.2%) masses were inflammatory in nature. Histopathological diagnoses are summarized in Table 1. The most common diagnoses were lymphoma (n=9, 33.3%) and squamous cell carcinoma (n=8, 29.6%). Other diagnoses included adenocarcinoma (n=4, 14.8%), lymphoplasmacytic inflammatory disease (n=4, 14.8%), and lymphoid hyperplasia (n=2, 7.4%). When masses were examined by anatomical location, the most common diagnoses for laryngeal masses were squamous cell carcinoma (n=7, 25.9%) and lymphoma (n=6, 22.2%). The most common tracheal mass was lymphoma (n=3, 11.1%). The cat with a laryngotracheal mass was diagnosed with adenocarcinoma.
The two cats that were FIV positive were diagnosed with laryngeal lymphoma and laryngeal squamous cell carcinoma, respectively. Another cat had a concurrent upper respiratory tract infection and tested positive on an oral swab for feline herpesvirus-1 using a polymerase chain reaction (PCR) assay.c No other cats or tissues were tested for herpesvirus.
Breeds of cats were statistically compared by tissue diagnosis. Significant correlations were found for Siamese cats with lymphoma (P=0.006), for domestic longhair cats with adenocarcinoma (P=0.006), and for domestic longhair cats with lymphoma (P=0.006).
Radiographic Findings
Twenty-four of the 27 cats had radiographs available for review, and radiographic abnormalities were identified in 21 (88%) cats. A total of 27 radiographic findings were seen and included a soft-tissue opacity in 13 (43.3%) cats, decreased margination of the laryngeal structures in seven (23.3%) cats, and stenosis of the airway in seven (23.3%) cats. Three (10%) cats had no defined lesions. Some cats had more than one radiographic finding.
Radiographic abnormalities found in cats with laryngeal masses included soft-tissue opacities (n=10), decreased margination of the laryngeal structures (n=6), and stenosis of the airway (n=4). Three cats had no defined lesions. Radiographic abnormalities found in cats with tracheal masses included soft-tissue opacities (n=3) and stenosis (n=3). The one cat with a laryngotracheal mass had decreased margination of the laryngeal structures.
The 13 cats with radiographic soft-tissue opacities were diagnosed with laryngeal squamous cell carcinoma (n=5), laryngeal lymphoma (n=3), tracheal lymphoma (n=2), tracheal adenocarcinoma (n=1), laryngeal adenocarcinoma (n=1), and laryngeal lymphoid hyperplasia (n=1). The seven cats with decreased margination of the laryngeal structures were diagnosed with laryngeal lymphoma (n=3) and one each of a laryngotracheal adenocarcinoma, laryngeal squamous cell carcinoma, laryngeal lymphoid hyperplasia, and laryngeal lymphoplasmacytic inflammation. The seven cats with upper airway stenosis were diagnosed with laryngeal squamous cell carcinoma (n=3) and one each of a laryngeal lymphoma, tracheal squamous cell carcinoma, tracheal lymphoid hyperplasia, and tracheal lymphoplasmacytic inflammation. The three cats with no defined lesions on radiographs were diagnosed with laryngeal lymphoplasmacytic inflammation (n=2) and a laryngeal squamous cell carcinoma (n=1). There was a statistically significant correlation in finding a soft-tissue opacity and a diagnosis of neoplasia (P=0.0002). Inflammatory masses had a variety of radiographic findings.
Treatment and Survival
Seven cats had a tube tracheostomy as their sole form of treatment. Tracheostomies were performed in four cats with laryngeal squamous cell carcinoma and in one cat each with a tracheal lymphoplasmacytic inflammatory mass, tracheal adenocarcinoma, and tracheal lymphoid hyperplasia. These cats had a median survival time of 3 days (mean 3.3 days; range 1 to 6 days). All cats died from the severity or rapid progression of their disease.
Four cats received multiple therapies for their masses. One cat with tracheal lymphoma had a tube tracheostomy, radiation therapy, and chemotherapy (i.e., L-asparaginase, cyclophosphamide, vincristine, and prednisone). A cat with a laryngeal adenocarcinoma had a tube tracheostomy, laryngectomy, and chemotherapy (i.e., methotrexate and doxorubicin). A cat with laryngeal lymphoma received radiation therapy and chemotherapy (i.e., L-asparaginase, cyclophosphamide, vincristine, prednisone, and lomustine). A cat with laryngeal lymphoma had a tube tracheostomy and chemotherapy (i.e., L-asparaginase, cyclophosphamide, vincristine, and prednisone). This last cat was previously diagnosed with lymphoid hyperplasia and was treated with prednisone and amoxicillin/clavulanic acid initially. These four cats had a median survival time of 134.5 days (mean 133 days; range 80 to 183 days).
Five cats received chemotherapy as their sole treatment modality. The diseases that were treated with chemotherapy included two laryngeal lymphomas (treated with L-asparginase, prednisone, doxorubicin, vincristine, chlorambucil, cyclophosphamide, and dactinomycin), two laryngeal squamous cell carcinomas (treated with piroxicam), and one laryngeal lymphoplasmacytic inflammatory mass (treated with prednisone). These five cats had a median survival time of 141 days (mean 171.6 days; range 59 to 370 days). The cat that survived the longest (370 days) had laryngeal lymphoplasmacytic inflammation and was still alive at the time of data analysis.
Two cats received miscellaneous therapies. One cat with laryngeal lymphoplasmacytic inflammation was treated with interferon-α-2ad (30 units per os q 24 hours for 5 days) for a concurrent herpesvirus-positive upper respiratory tract infection. This cat survived 5 days and then died from progression of its disease. One cat was initially diagnosed with laryngeal lymphoid hyperplasia and was treated with antibiotics. This cat was subsequently diagnosed with a laryngeal adenocarcinoma at the site of the original inflammatory mass 1109 days later.
Nine cats were euthanized or died without treatment. These cats were diagnosed with laryngeal lymphoma (n=2), tracheal lymphoma (n=2), and one each of a laryngotracheal adenocarcinoma, tracheal squamous cell carcinoma, laryngeal lymphoid hyperplasia, laryngeal lymphoplasmacytic inflammation, and laryngeal squamous cell carcinoma. The median survival time for these nine cats was only 1 day (mean 7 days; range 1 to 30 days).
By the end of the study period, 26 cats had died or were euthanized because of the severity or progression of their disease. The remaining cat was lost to follow-up at 370 days. Cats with inflammatory masses had a median survival time of 5 days (range 1 to 370 days). Cats with neoplastic masses had a median survival time of 15.5 days (range 1 to 1109 days). Kaplan-Meier survival data for all cats revealed a median survival time of 5 days, with 7.4% alive at 1 year [Figure 2]. Kaplan-Meier survival data for cats treated with chemotherapy, multiple therapies, and miscellaneous therapies revealed a median survival time of 121 days. Kaplan-Meier survival time was not significantly associated with any of the examined variables (i.e., age, gender, breed, mass location, radiographic findings, mass diagnosis, and treatment type).
Discussion
It is interesting to note that spayed female cats were diagnosed with laryngeal and tracheal masses more frequently in this study. This finding contrasted previous reports of equal distribution between the sexes or an increased incidence in male cats.1,9 The median age of cats that were presented for all masses in this study was 12.0 years, which was consistent with that (>8 years) previously reported.1,9
Some previous retrospective studies of laryngeal or tracheal masses have not identified a breed predisposition for mass types.1,9 The current study found that Siamese cats had a significant association with lymphoma and that domestic longhair cats had a statistical correlation with adenocarcinomas and lymphoma. These breed correlations were based on a small number of cats, so whether a true association exists or not is unknown.
In the current study, the most common clinical sign reported for laryngeal and tracheal masses was dyspnea. Previous reports listed dysphonia as the most common clinical sign, and dysphonia was also common in the current study.1,8
In previous reports of laryngeal and tracheal masses, radiographic findings were not statistically correlated with a specific mass type.1,5,6,9 In the current study, soft-tissue opacities were found to be significant indicators of neoplasia (P<0.002). While a statistical significance was found, radiographic findings were absent or variable with some neoplastic and inflammatory masses. Based on these results, a definitive diagnosis as to mass type should not be made solely upon radiographic findings. Further diagnostic tests, such as direct laryngeal or tracheal examination, should be performed in every case of a suspected mass. If a mass or abnormal-looking tissue is identified on direct examination, a tissue biopsy is indicated.
Inflammatory masses causing airway obstruction have been reported in the larynx and trachea of cats.5–7 No underlying causes of these inflammatory masses have been identified in previous studies; however, infectious etiologies and laryngeal trauma have been proposed as possible causes.5,6 In the current study, no special stains or bacterial or viral cultures were performed, so no causative agents were identified. One cat had concurrent rhinotracheitis at the time the laryngeal mass was identified and was positive for feline herpesvirus-1. This cat’s laryngeal mass did not respond to interferon-α-2a therapy, and the cat subsequently died. Further investigation into the possible role of feline herpesvirus-1 in upper airway lymphoplasmacytic inflammation may be warranted.
One previous case of chronic polypoid laryngitis with inflammatory infiltrates of primarily lymphocytes and scattered neutrophils has been reported in the larynx of a cat.5 Whether this histopathological finding was truly lymphoid hyperplasia was difficult to determine from the data provided.5 No retrospective reports of lymphoid hyperplasia in the trachea of cats have been published. Seven cases of lymphoid hyperplasia were found in this study, but five of these cats were subsequently diagnosed with neoplasia. Two of the cats had lymphoid hyperplasia diagnosed by a single tissue biopsy of their masses (one tracheal, one laryngeal), and it is not known whether these cats also had underlying neoplastic diseases that were masked by inflammation. Regardless, laryngeal or tracheal lymphoid hyperplasia as a sole diagnosis in cats appears to be very rare.
Laryngeal and tracheal lymphoid hyperplasia has been well described in humans.14–17 A diagnosis of lymphoid hyperplasia in the larynx and trachea of humans has been associated with concurrent neoplasia and precancerous findings associated with chronic inflammation.14–16,23 In people, laryngeal lymphoid hyperplasia associated with neoplasia and chronic laryngitis has been related to smoking, viral infections, and other environmental factors.18–20 The suspicion exists that chronic inflammation leads to neoplastic transformation in inflammatory bowel disease (e.g., intestinal lymphoma) in cats.24 Chronic inflammation progressing to neoplastic transformation has also been experimentally demonstrated in mice.25 Other studies have reported lymphoid hyperplasia as a mechanism of host resistance to neoplasia.16,21–23 Some human studies have attempted to define histological criteria for benign versus malignant lymphoid hyperplasia, and similar studies in animals are warranted.14,15,21
In the study reported here, a definitive diagnosis was obtained with one biopsy attempt in 22 of 27 cats. The remaining five cats were initially diagnosed with lymphoid hyperplasia and then subsequently diagnosed with neoplasia, which was consistent with reports of laryngeal lymphoid hyperplasia in humans.14–16,21 One cat with biopsy and concurrent FNA had a revised diagnosis of neoplasia 1109 days later. Both the initial FNA and concurrent tissue biopsy and the subsequent tissue biopsy may have provided accurate diagnoses. Possibly the underlying inflammation was responsible for neoplastic changes, as it is unlikely this cat would have survived 1109 days with no specific treatment of a laryngeal adenocarcinoma. A second cat was initially diagnosed by FNA with laryngeal lymphoid hyperplasia and was subsequently diagnosed with laryngeal lymphoma 102 days later. Both diagnoses may also have been accurate. Based upon results of this study, a second biopsy of cats with lymphoid hyperplasia may be indicated. If lymphoid hyperplasia is confirmed again, close monitoring of the lesion is warranted.
Successful outcomes have been described for inflammatory laryngeal and tracheal masses in cats.5–8,11 In contrast, a Kaplan-Meier median survival time of 5 days was found in the current study. However, two cats in the study with laryngeal inflammatory masses survived long-term. At the time of data analysis, one cat with laryngeal lymphoplasmacytic inflammation was alive at 370 days on prednisone therapy. A second cat initially diagnosed with lymphoid hyperplasia lived 1109 days prior to subsequent diagnosis of laryngeal adenocarcinoma. The remaining cats with tracheal and laryngeal inflammation were euthanized shortly after diagnosis.
The prognoses of cats with laryngeal and tracheal neoplastic masses were also poor in the current study (Kaplan-Meier survival time of 5 days). Although some cats were still alive at 186 days postdiagnosis, most were euthanized upon diagnosis. Since most affected cats were presented with severe clinical signs and advanced disease, a selection bias likely existed in this population of cats. A comparison to a control population was not performed; therefore, caution is necessary in comparing treatment groups.
In the study reported here, tube tracheostomy alone had the shortest median survival time (3 days) of any of the treatment groups. The cats with tube tracheostomies died before other intended therapies could be initiated. One possible reason for this poor survival was that cats requiring tube tracheostomies had advanced disease at presentation and probably would have died with or without treatment. Multiple therapies and chemotherapy as a sole treatment increased median survival times to 134.5 days and 141 days, respectively. These results suggested that only a short-term response to therapy occurred in cats with masses of the larynx and/or trachea.
Although this study provided important clinical information, there were also inherent limitations. The retrospective nature of the study did not allow a single pathologist to review all tissue biopsies; therefore, criteria to distinguish between benign and malignant lymphoid proliferative diseases were not established. A review of cytological and histopathological discrepancies was also not performed. It is important to note that survival times are often subjective endpoints, which are impacted by a variety of factors independent of the disease. The inclusion of various mass types and variation in treatment protocols did not allow for clear interpretation of survival data. A selection bias likely existed for more advanced cases, because the study was performed at a specialty referral hospital. However, the Kaplan-Meier survival data are still useful in that they provide the clinician with survival information at the time the animal is presented to the hospital. The small number of cats in this study made interpretation of some comparisons difficult (e.g., breed associations with diagnoses). While the results were significant for a small number of cats, a larger study population would help substantiate breed correlations or other comparisons. Also, because of the observational nature of the study, conclusions were limited by the lack of randomizations of treatment groups.
Conclusion
Despite therapies offered, most cats with laryngeal, tracheal, and laryngotracheal masses did not survive long-term. Laryngeal and tracheal masses may have confounding cytological or histological findings that complicate the clinician’s ability to give accurate prognostic information and treatment recommendations. Multiple biopsies may be necessary to accurately diagnose the underlying pathology. Further investigation of risk factors associated with carcinogenesis in the cat larynx and trachea is warranted.
Statview statistical software; SAS Institute Inc., Cary, NC 27513
IDEXX, West Sacramento, CA 95605
IDEXX, West Sacramento, CA 95605
Roferon-A; Roche, Nutley, NJ 07110
Citation: Journal of the American Animal Hospital Association 41, 5; 10.5326/0410310
Citation: Journal of the American Animal Hospital Association 41, 5; 10.5326/0410310
Percentage of cats with each presenting complaint for masses involving the larynx and/or trachea.
Kaplan-Meier survival times for cats with masses involving the larynx and/or trachea. The dot indicates a cat that was still alive at the time of data analysis. The overall Kaplan-Meier survival times were 5 days for cats with either neoplasia or inflammatory lesions. On the Y-axis, each 0.1 represents 10% of the cats in the study.
