Lymphoma is one of the most common neoplasms in cats; however, cutaneous lymphoma comprises only a small fraction of cases and remains poorly understood.1 Previous reports have documented cases of cutaneous lymphoma in cats as a primary disease process or secondary to systemic involvement of other primary sites. To date, the etiology remains unknown, with no consistent correlation with prior trauma or retroviral status.1
In cats and dogs, histologic evaluation differentiates cutaneous lymphoma into epitheliotropic or nonepitheliotropic forms.2 Both forms can have a similar clinical appearance, with solitary, multifocal, or diffuse lesions that are most commonly described as superficial lesions consisting of alopecia, erythema, crusting, papules, nodules, ulcers, or plaques.2–12 Cutaneous lymphoma is well described in dogs, and the epitheliotropic form is most common.13 In contrast, data regarding the prevalence of epitheliotropic versus nonepitheliotropic lymphoma in cats are limited to case reports and a few small case series. In a case series6 of 9 cats, 8 cats were classified as having nonepitheliotropic and 1 as having epitheliotropic lymphoma. Feline epitheliotropic cutaneous lymphoma has also been reported in a recent case series7 and several case reports.3,9,10,12,14
Generally, epitheliotropic cutaneous lymphoma is considered to be a disease of T lymphocytes, and nonepithelioptropic cutaneous lymphoma may be of either T- or B-cell phenotype.3,5,7,9,12,14 Prior reviews of nonepitheliotropic cutaneous lymphoma in cats indicate a slight predominance of T-cell over B-cell immunophenotype.2,5,11,15–19
Nonepitheliotropic cutaneous lymphoma in dogs is also more frequently of T-cell immunophenotype.2,13
A syndrome of cutaneous lymphocytosis, which can have a similar appearance to cutaneous lymphoma, has been reported in cats. These cats have superficial skin lesions consisting most commonly of alopecia, erythema, and scaling with or without crusting. Other less frequently reported lesions include alopecic erythematous plaques, single or multiple nodular lesions, solitary ulcers, and miliary papules. Histologically, lymphocytes are well differentiated (low grade), with no mitotic figures observed, and of mostly T-cell phenotype.20 This is thought to be a nonneoplastic disease. However, it may be difficult to separate cutaneous lymphocytosis from well-differentiated cutaneous lymphoma without further diagnostic testing such as PCR assay for antigen receptor rearrangement.21
Although cutaneous lymphoma is most commonly described as superficial dermal lesions, several reports2,6,14,15,17,19,22–24 describe it as having a subcutaneous, mass-like appearance. It was the authors' experience that this subcutaneous form had a predilection for the tarsal region. The purpose of the study reported here was to determine the features of lymphoma of the tarsus in cats.
Materials and Methods
Case selection—Veterinary oncologists from North America were requested to submit cases fitting the following criteria: histologically or cytologically confirmed lymphoma with a location at or near the tarsus and described as subcutaneous or mass-like (Figure 1). Cases were excluded if lesions were multifocal, extended beyond the tarsus, or were described as superficial without the appearance of an underlying mass.
Representative photograph of the right hind limb of a cat with lymphoma surrounding the right tarsus.
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
Representative photograph of the right hind limb of a cat with lymphoma surrounding the right tarsus.
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
Representative photograph of the right hind limb of a cat with lymphoma surrounding the right tarsus.
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
Medical records review—Data regarding breed, sex, age, FeLV and FIV status, and reason for evaluation were collected. Results of staging tests including CBC, serum biochemical profile, thoracic and abdominal radiography, ultrasonography, bone marrow aspiration, lymph node or organ cytologic or histologic evaluation, location of the tumor, immunophenotype, and histopathologic description were recorded when available. Types of treatments, outcome, survival time, presence or absence of progressive disease (local or systemic at time of death), and cause of death or reason for euthanasia were also recorded. Survival time was defined as the time from diagnosis until death or euthanasia. Cats were censored for survival analysis at the point of last contact if they were lost to follow-up or were still alive. Cause of death was determined as reported by the submitting veterinarian when necropsy was not performed.
Tumor histologic reevaluation was performed by a pathologist (JHK) in all cases for which samples were available (n = 8). Immunohistochemical analysis by use of antibodies against CD3, CD18, and CD79 was performed and reviewed in all cases for which samples were available and in which immunophenotyping had not previously been performed. A Congo Red stain was also performed in select cases that were suspicious for the presence of amyloid on routine H&E preparations.
Statistical analysis—Statistical analyses were performed with a commercial software package.a Cats were categorized on the basis of treatment: corticosteroids alone (group 1; n = 2), chemotherapy alone (group 2; 9), radiation and chemotherapy (group 3; 7), or surgery with or without chemotherapy (group 4; 5). One-way ANOVA was used to evaluate differences in mean survival time among treatment types. Cats were also categorized as receiving corticosteroids or chemotherapy alone (groups 1 and 2) or surgery or radiation with or without chemotherapy (groups 3 and 4). A Student t test was used to evaluate differences in mean survival time between these categories. A Kaplan-Meier survival plot was generated for the 4 treatment groups. Comparison of survival curves was performed with log-rank and Wilcoxon rank sum tests. For all comparisons, P < 0.05 was considered significant.
Results
Patient characteristics—Thirty-seven cases were submitted for consideration. Of the 37 cases, 14 were excluded because of the following: lesion described as plaque-like (n = 1), mass occurring in an area other than the tarsal region (9), multiple masses in locations other than tarsus (1), single mass encompassing the limb and extending into the inguinal region (2), or tumor not confirmed as lymphoma after histologic review (1). Twenty-three cases met the inclusion criteria.
Most cats were older, with a median age of 12 years (range, 7 to 18 years) at diagnosis. Breeds included 19 domestic shorthairs, 2 domestic longhairs, and 2 Maine Coons. There were 12 (52%) castrated males, 2 (9%) sexually intact males, and 9 (39%) spayed females.
Reason for evaluation was recorded for 21 cats and included a hind limb mass or swelling. In addition, 2 cats had limping and 3 cats had evidence of self-trauma associated with the mass. The duration of clinical signs prior to initial evaluation (n = 20 cats) ranged from 1 day to 6 months. None of the cats were described as having systemic signs of illness such as anorexia, vomiting, or diarrhea. The right hind limb was affected in 15 (65%) cats and the left in 8 (35%) cats. Twenty-two cats had a solitary cutaneous lesion. One cat had 3 masses, all associated with the same limb, with 2 of the masses located on the medial and lateral aspects of the tarsus and 1 smaller mass located proximal to the tarsus.
Seventeen cats were tested for FeLV antigen, and all results were negative. Eighteen cats were tested for antibodies against FIV, and 1 cat had positive results. Complete blood counts and serum biochemical profiles were available for review in 22 cats. At initial evaluation, 5 cats were anemic (Hct < 30%; range, 19% to 24%). There were no other consistent abnormalities of blood analyses.
In 18 cats, thoracic radiographs were performed for staging purposes. One cat had a possible pulmonary mass as determined from review of radiographic images by a veterinary radiologist; this finding was not evaluated further and was of uncertain importance. The remaining 17 cats had no radiographic evidence of lymphadenopathy or pulmonary involvement as reported by the submitting veterinarian. In 15 cats, abdominal ultrasonography was performed, and 4 cats had findings suggestive of systemic disease, including mesenteric (n = 1) or iliac (2) lymph node enlargement or nodules in the liver (2), spleen (1), and kidney (1). Ultrasonographically guided fine-needle aspiration was performed in 2 cats. Cytologic evaluation in 1 cat (liver and iliac lymph nodes) was consistent with anaplastic metastatic neoplasia, which was not confirmed as lymphoma; the other had a cytologically normal mesenteric lymph node. No other major abnormalities were detected in the remaining 10 cats. In 4 cats, bone marrow aspirates were obtained as part of routine staging, and no evidence of lymphoma was found in any of the samples. Ten cats underwent popliteal lymph node needle aspiration (n = 7) or biopsy by lymph node removal (3), and in 5, findings were consistent with lymphoma (3 by needle aspiration and 2 by biopsy). Three additional cats were reported to have popliteal lymph node enlargement; however, fine-needle aspiration or biopsy was not performed.
Histologic evaluation and immunophenotyping—Initial histologic evaluation was performed at various laboratories. Additional histologic slides of the 20 cases in which a diagnosis was obtained by use of biopsy were requested for review by a pathologist. Of these 20 cases, additional slides were received for 8 cases. Seven were classified as large cell lymphoma and 1 as intermediate cell lymphoma. All cases were nonepitheliotropic. Some specimens were obtained by needle core biopsy, allowing only a small area for microscopic examination and limited evaluation of tissue architecture. Additionally, necrosis was a common feature of many of the specimens. Mitotic index was evaluable in 5 specimens, with 4 having > 25 mitoses in 10 hpfs. In 2 smaller samples, > 5 mitoses/hpf were observed. Neoplastic cells were arranged in sheets rather than in nodular or follicular arrangements in all samples evaluated (Figures 2 and 3).
Immunophenotyping was performed in 13 of the 23 cats. Immunohistochemical analysis was performed in 4 cases at the time of pathology review. Eight cats were classified as having B-cell lymphoma (7 via immunohistochemical analysis). Six samples were CD79a positive, and 1 sample was CD20 positive. One cat was classified as having B-cell lymphoma on the basis of PCR assay for antigen receptor rearrangement (performed at Colorado State University). Four cats were classified as having T-cell lymphoma (CD3 positive) via immunohistochemical analysis. Two of the cats classified as having T-cell lymphoma also had a small population of neoplastic cells that were positive for CD79a. One cat had negative results for CD18, CD3, and CD79a.
Three samples were evaluated with a Congo red stain, of which 2 samples yielded positive results, indicating the presence of amyloid. The cat that had negative results for CD18, CD3, and CD79a had positive results of staining with Congo red, which suggested a B-cell phenotype.19
Representative photomicrograph of tissue obtained from a cat with lymphoma of the tarsus. H&E stain; bar = 200 μm.
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
Representative photomicrograph of tissue obtained from a cat with lymphoma of the tarsus. H&E stain; bar = 200 μm.
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
Representative photomicrograph of tissue obtained from a cat with lymphoma of the tarsus. H&E stain; bar = 200 μm.
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
Representative photomicrograph of tissue obtained from a cat with lymphoma of the tarsus. H&E stain; bar = 25 μm.
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
Representative photomicrograph of tissue obtained from a cat with lymphoma of the tarsus. H&E stain; bar = 25 μm.
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
Representative photomicrograph of tissue obtained from a cat with lymphoma of the tarsus. H&E stain; bar = 25 μm.
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
Treatment and outcome—Two cats were treated with corticosteroids alone (group 1). One was euthanized 22 days following diagnosis because of local progressive disease. The second cat was euthanized 190 days following diagnosis because of local and metastatic progressive disease.
Nine cats were treated with chemotherapy alone. The most common treatment was a CHOP-based protocol, with or without l-asparaginase (n = 4). Other protocols included a 25-week CHOP administration with the addition of lomustine, vincristine given in combination with cyclophosphamide, cyclophosphamide as a single agent, or lomustine as a single agent. One cat achieved complete remission and survived 328 days. Two cats had a partial remission as reported by the attending clinician and survived 207 and 384 days. Five cats initially had stable disease, surviving a median of 95 days (range, 17 to 201 days). One cat had progressive disease and survived 80 days. Three cats received rescue chemotherapy consisting of lomustine (n = 3); mustargen, vincristine, procarbazine, and prednisone (1); or mustargen, vinblastine, procarbazine, and prednisone (1). The overall median survival time for all cats that received chemotherapy alone (group 2) was 136 days (range, 17 to 384 days).
Seven cats were treated with a combination of radiation therapy and chemotherapy. Two cats received a definitive radiation protocol. One of the cats treated with 12 fractions of 3 Gy achieved partial remission, which was followed by chemotherapy (vincristine and cyclophosphamide), with stable disease maintained for approximately 60 days. A second cat received definitive radiation therapy (15 fractions of 3.2 Gy) after developing progressive disease following chemotherapy (CHOP and lomustine). Radiation therapy was started 146 days after diagnosis and 124 days after starting chemotherapy. A complete response following radiation therapy was noted for a period of 58 days. Four cats received hypofractionated radiation therapy because of a lack of response to chemotherapy or progressive disease during chemotherapy. Three cats received 4 once-weekly fractions of 8 Gy, and 1 cat received 5 daily fractions of 4 Gy. Chemotherapy protocols for cats receiving hypofractionated radiation therapy consisted of CHOP (n = 3) or single-agent lomustine (1). Responses to hypofractionated radiation therapy were variable, with 1 complete remission, 1 partial remission, 1 stable disease, and 1 progressive disease. For 1 cat, chemotherapy (l-asparaginase, vincristine, cyclophosphamide, and methotrexate) and radiation therapy were performed simultaneously. The radiation protocol used in this case was not known, and stable disease was achieved for 117 days before development of new metastatic lesions. The overall median survival time for cats receiving radiation and chemotherapy (group 3) was 216 days (range, 167 to 1,011 days).
Of the 5 cats treated initially with surgery, 2 cats had microscopic residual disease and received adjuvant chemotherapy. Adjuvant chemotherapy consisted of CHOP (n = 2). One cat developed local disease recurrence at 173 days. The second cat developed regional lymph node involvement at 119 days following surgery. Three cats had complete excision via hind limb amputation. One cat was treated with adjuvant l-asparaginase and vincristine and developed lymphoma in the contralateral tarsus at 350 days. A second cat developed lymphoma at a different site (ie, distant disease) in the inguinal lymph node 56 days after amputation, at which time chemotherapy was initiated. Chemotherapy consisted of a single dose of l-asparaginase followed by approximately 3 weeks of chlorambucil administered every other day. Stable disease was initially achieved, and lomustine was administered at the time of progression. The cat died of progressive disease and anemia 10 days after lomustine administration. The third cat treated with amputation did not receive adjuvant chemotherapy and subsequently developed lymphoma of the liver and omentum 525 days following diagnosis. Median survival time for cats that received surgery with or without chemotherapy (group 4) was 410 days (range, 126 to 525 days).
Kaplan-Meier survival curve of 23 cats with lymphoma of the tarsus classified on the basis of treatment with corticosteroids alone (group 1; n = 2), chemotherapy alone (group 2; 9), radiation and chemotherapy (group 3; 7), or surgery with or without chemotherapy (group 4; 5).
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
Kaplan-Meier survival curve of 23 cats with lymphoma of the tarsus classified on the basis of treatment with corticosteroids alone (group 1; n = 2), chemotherapy alone (group 2; 9), radiation and chemotherapy (group 3; 7), or surgery with or without chemotherapy (group 4; 5).
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
Kaplan-Meier survival curve of 23 cats with lymphoma of the tarsus classified on the basis of treatment with corticosteroids alone (group 1; n = 2), chemotherapy alone (group 2; 9), radiation and chemotherapy (group 3; 7), or surgery with or without chemotherapy (group 4; 5).
Citation: Journal of the American Veterinary Medical Association 244, 12; 10.2460/javma.244.12.1429
No significant (P = 0.245) differences were detected in mean survival time among treatment groups. However, a significant (P = 0.04) difference was detected in mean survival time between combined groups 1 and 2 (mean, 155 days) and groups 3 and 4 (mean, 316 days). A Kaplan-Meier survival plot (Figure 4) revealed no significant differences among survival curves for the 4 groups.
All 23 cats died or were euthanized. Overall median survival time was 190 days, and the 1- and 2-year survival rates were 21% and 4%, respectively. Thirteen cats had reported metastatic disease at the time of death. Sites of metastatic disease confirmed by cytologic evaluation or evaluation of a biopsy specimen included popliteal lymph node, inguinal lymph node, iliac lymph node, omentum, liver, spleen, other cutaneous sites, and conjunctiva. The cause of death was thought to be secondary to lymphoma in 17 cats (8 died of local disease, 4 died of metastatic disease, and 5 died of local and metastatic disease), unrelated to lymphoma in 2 cats, and unknown in 4 cats. Eleven cats were reported to have developed metastatic disease after diagnosis despite chemotherapy.
Discussion
The cats in this report had a distinct form of cutaneous lymphoma that originated near or around the tarsal joint and clinically appeared as a subcutaneous mass. In humans, the European Organization for the Research and Treatment of Cancer has developed a classification scheme for primary cutaneous lymphomas.25 The World Health Organization–European Organization for the Research and Treatment of Cancer classification recognizes 3 main types of primary cutaneous B-cell lymphoma: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, and primary cutaneous large B-cell lymphoma (leg type). Primary cutaneous large B-cell lymphoma (leg type) most commonly occurs on the lower portions of the legs and is associated with diffuse nonepidermotropic infiltrates. Lymphomas of this group frequently disseminate to extracutaneous sites and have a more unfavorable prognosis than lymphomas of the other 2 groups.26 In domestic species, lymphoma affecting the tarsal region has been described as part of a more disseminated disease process in cattle27 and in 2 case reports28,29 in horses. There is also a case report30 of a sheep with bilateral tarsal involvement. Previous reports2,6,14,15,17,19,22–24 of cutaneous lymphoma in cats have described an apparent subcutaneous form of lymphoma in sites other than near the tarsal joint. We elected to focus on the tarsal location in an attempt to define whether there were any discernible similarities among cats with this disease in tumor characteristics or behavior.
Histologic evaluation revealed that most cases were nonepitheliotropic, of high grade, and of B-cell phenotype. However, only a limited number of tumor samples were available for pathologist review and immunophenotyping. The high prevalence of the B-cell lymphoma phenotype in this series of cases was in contrast to the previously reported cases of feline cutaneous lymphoma in which the T-cell lymphoma phenotype was more frequent.2,5,11,15–19 In the largest compilation of cases evaluating immunophenotype of feline cutaneous lymphoma, 5 of 6 cats were found to have T-cell lymphoma. All 6 of these cases were considered nonepitheliotropic.2 Currently, the prognostic and clinical importance of immunophenotype in feline lymphoma is not well-defined. Previously, an evaluation of 130 cats with lymphoma of variable anatomic locations for CD3 immunoreactivity found no prognostic value for CD3-positive cats. However, it was determined that FeLV-positive cats had a higher prevalence of CD3 immunoreactivity and worse overall survival time, whereas FeLV-negative cats expressing CD3 had some of the longest survival times. Only response to treatment, clinical substage, and FeLV status were found to be prognostic.31 Likewise, a pilot study32 evaluating immunophenotype for alimentary lymphoma found no prognostic value in a small number of cats. Another study33 evaluating the histologic features of feline gastrointestinal lymphoma found that cell size, transmural location of cancer cells, or lymphoma confined to the mucosa was more prognostic than immunophenotype. In our case series, 1 biopsy specimen was negative for CD18 (panleukocyte marker; strong staining seen with histiocytic tumors), CD3 (T-cell lymphocyte marker), and CD79 (B-cell lymphocyte or plasma cell marker) but positive for Congo red. Congo red staining was performed on specimens that were suspicious for the presence of amyloid with routine H&E stains (presence of hyaline or eosinophilic material in the intralesional interstitium). Amyloid is an extracellular proteinaceous material that can result from neoplastic or nonneoplastic proliferation or activity of B cells and plasma cells.19 Because the number of specimens was limited, further subtyping of the amyloid was not performed. The presence of amyloid in 2 of 3 tested specimens was notable; however, the clinical relevance was unknown. Of these 2 cats, 1 cat was treated with chemotherapy alone (vincristine and cyclophosphamide) and survived 384 days after diagnosis. The second cat was treated with surgery and chemotherapy (25-week CHOP protocol) and survived 410 days after diagnosis.
There is a paucity of information on the treatment of feline cutaneous lymphoma in the veterinary literature. One case report9 of epitheliotropic cutaneous lymphoma described the disease as indolent, with the cat having prolonged survival time without treatment. In contrast, other reports6,8,9,14,15,22 evaluating both epitheliotropic and nonepitheliotropic cutaneous lymphoma describe the disease process as more rapid and aggressive. The cats described in those reports6,8,9,14,15,22 had highly variable disease. In our cases series, cutaneous tarsal lymphoma appeared to be an aggressive disease in most cats, with an overall median survival time of 190 days and 1- and 2-year survival rates of 21% and 4%, respectively. Interestingly, the cat with the longest survival time (euthanized at 1,011 days; treated with chemotherapy and radiation) had a nonepitheliotropic lymphocytic form of cutaneous lymphoma (histologic slides not available for review). Although this was a single case, it is possible that a lymphocytic form of lymphoma associated with the tarsus may have a less aggressive disease course than large cell lymphoma associated with the tarsus. This cat had popliteal lymph node involvement at the time of diagnosis, and a nonmalignant disease, such as cutaneous lymphocytosis, was considered less likely but cannot be excluded.20
Treatments described for feline cutaneous lymphoma include fibronectin,5,6 placental lysate,9 corticosteroids alone,6,8,18 chemotherapy,9,11,14,15,17,22,24,34 surgery,3,6,14,17–19 or radiation therapy.9,14,22 Some success has been reported with each of these modalities; however, there are no case series that describe response rates and survival times with a set treatment protocol. As a result, there is no standard of care for the treatment of feline cutaneous lymphoma.
Complete surgical resection of solitary cutaneous lymphoma has been advocated.35 However, given the tarsal location of lymphoma in the present study, complete surgical resection would not be likely unless limb amputation were performed. There are 3 case reports3,18,19 in the literature of cats with cutaneous lymphoma that were treated with amputation of a hind limb. Two of the 3 cats were disease free for > 1 year without adjuvant therapy.3,18 One cat died secondary to widespread systemic disease 2 months following amputation.19 Three cats in our series were treated with hind limb amputation and remained disease free for 56, 350, and 525 days. Results of treatment with amputation must be interpreted with caution, given that few reports exist. It is strongly recommended that all staging tests be completed, including abdominal ultrasonography, before pursuing an aggressive surgery such as amputation. Considering that 56% of cats had reported metastatic disease at the time of death or last follow-up, adjuvant chemotherapy should be considered to address the possibility of disease developing after surgery.
In this case series, 5 cats had confirmed popliteal lymph node involvement, with 3 additional cats suspected of having popliteal lymph node involvement at the time of diagnosis. One cat had cytologically confirmed metastatic round cell neoplasia in the liver and iliac lymph nodes at the time of diagnosis. Thirteen cats were reported to have developed metastatic disease at the time of death or last follow-up. Sites of metastatic disease development included the associated or draining popliteal lymph node, inguinal lymph node, other cutaneous sites, omentum, spleen, liver, and conjunctiva. Because the possibility for development of metastatic disease exists, frequent monitoring is recommended, including a thorough physical examination as well as periodic abdominal ultrasonography.
Determination of an optimal treatment was beyond the scope of this study. Additionally, the limited case numbers and the multi-institutional and retrospective nature of the study limited the ability to speculate on an appropriate treatment course. It is likely that a multimodal approach will give the best chance for control of this disease. Prospective studies with standardized treatment protocols, histologic evaluation, and immunophenotyping are warranted.
ABBREVIATIONS
| CHOP | Cyclophosphamide, doxorubicin, vincristine, and prednisone |
JMP, version 11, SAS Institute Inc, Cary, NC.
References
1. Hardy WD. Hematopoietic tumors of cats. J Am Anim Hosp Assoc 1981; 17: 921–940.
2. Day MJ. Immunophenotypic characterization of cutaneous lymphoid neoplasia in the dog and cat. J Comp Pathol 1995; 112: 79–96.
3. Tobey JC, Houston DM, Breur GJ, et al. Cutaneous T-cell lymphoma in a cat. J Am Vet Med Assoc 1994; 204: 606–609.
4. Dallman MJ, Noxon JO, Stogsdill P. Feline lymphosarcoma with cutaneous and muscle lesions. J Am Vet Med Assoc 1982; 181: 166–168.
5. Caciolo PL, Hayes AA, Patnaik AK, et al. A case of mycosis fungoides in a cat and literature review. J Am Anim Hosp Assoc 1983; 19: 505–512.
6. Caciolo PL, Nesbitt GH, Patnaik AK, et al. Cutaneous lymphosarcoma in the cat: a report of nine cases. J Am Anim Hosp Assoc 1984; 20: 491–496.
7. Fontaine J, Heimann M, Day MJ. Cutaneous epitheliotropic T-cell lymphoma in the cat: a review of the literature and five new cases. Vet Dermatol 2011; 22: 454–461.
8. Dust A, Norris AM, Valli VE. Cutaneous lymphosarcoma with IgG monoclonal gammopathy, serum hyperviscosity and hypercalcemia in a cat. Can Vet J 1982; 23: 235–239.
9. Baker JL, Scott DW. Mycosis fungoides in two cats. J Am Anim Hosp Assoc 1989; 25: 97–101.
10. Schick RO, Murphy GF, Goldschmidt MH. Cutaneous lymphosarcoma and leukemia in a cat. J Am Vet Med Assoc 1993; 203: 1155–1158.
11. Komori S, Nakamura S, Takahashi K, et al. Use of lomustine to treat cutaneous nonepitheliotropic lymphoma in a cat. J Am Vet Med Assoc 2005; 226: 237–239.
12. Wood C, Almes K, Bagladi-Swanson M, et al. Sezary syndrome in a cat. J Am Anim Hosp Assoc 2008; 44: 144–148.
13. Moore PF, Olivry T. Cutaneous lymphoma in companion animals. Clin Dermatol 1994; 12: 499–505.
14. Neta M, Naigamwalla D, Bienzle D. Perforin expression in feline epitheliotropic cutaneous lymphoma. J Vet Diagn Invest 2008; 20: 831–835.
15. Legendre AM, Becker PU. Feline skin lymphoma: characterization of tumor and identification of tumor-stimulating serum factor(s). Am J Vet Res 1979; 40: 1805–1807.
16. Gabor LJ, Canfield PJ, Malik R. Immunophenotypic and histologic characterization of 109 cases of feline lymphosarcoma. Vet J 1999; 77: 436–441.
17. Fritz D, Freeman KP, Hopfner C, et al. Multilobulated “flower” cells in a subcutaneous mass aspirate from a cat. Vet Clin Pathol 2005; 34: 429–433.
18. Lenard ZM, Zuber RM, Nicoll RG, et al. Evaluation of lymphoma in a cat using 99mTc-sestamibi. Vet Radiol Ultrasound 2005; 46: 533–535.
19. Kagawa Y, Yamashita T, Maetani S, et al. Cutaneous lymphoplasmacytic lymphoma with systemic metastasis in a cat. J Vet Med Sci 2011; 73: 1221–1224.
20. Gilbert S, Affolter VK, Gross TL, et al. Clinical, morphological and immunohistochemical characterization of cutaneous lymphocytosis in 23 cats. Vet Dermatol 2004; 15: 3–12.
21. Kiupel M, Smedley RC, Pfent C, et al. Diagnostic algorithm to differentiate lymphoma from inflammation in feline small intestinal biopsy samples. Vet Pathol 2011; 48: 212–222.
22. Elmslie RE, Ogilvie GK, Gillette EL, et al. Radiotherapy with and without chemotherapy for localized lymphoma in 10 cats. Vet Radiol Ultrasound 1991; 32: 227–280.
23. Kristal O, Lana SE, Ogilvie GK, et al. Single agent chemotherapy with doxorubicin for feline lymphoma: a retrospective study of 19 cases (1994–1997). J Vet Intern Med 2001; 15: 125–130.
24. Simon D, Eberle N, Laacke-Singer L, et al. Combination chemotherapy in feline lymphoma: treatment outcome, tolerability, and duration in 23 cats. J Vet Intern Med 2008; 22: 394–400.
25. Willemze R, Kerl H, Sterry W, et al. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 1997; 90: 354–371.
26. Willemze R. Primary cutaneous B-cell lymphoma: classification and treatment. Curr Opin Oncol 2006; 18: 425–431.
27. Van Pelt RW. Pathologic changes of joint disease associated with malignant lymphoma, in cattle: clinical, gross pathologic, and histopathologic observations. Am J Vet Res 1967; 28: 429–442.
28. Gerard MP, Healy LN, Bowman KF, et al. Cutaneous lymphoma with extensive periarticular involvement in a horse. J Am Vet Med Assoc 1998; 213: 391–393.
29. Held JP, McCracken MD, Toal R, et al. Epididymal swelling attributable to generalized lymphosarcoma in a stallion. J Am Vet Med Assoc 1992; 201: 1913–1915.
30. Pearson GR, Day MJ, Main D, et al. B-cell (CD79a+) lymphoma affecting the tarsal joint synovia in a sheep. J Comp Pathol 1999; 120: 295–299.
31. Vail DM, Moore AS, Ogilvie GK, et al. Feline lymphoma (145 cases): proliferation indices, cluster of differentiation 3 immunoreactivity, and their association with prognosis in 90 cats. J Vet Intern Med 1998; 12: 349–354.
32. Patterson-Kane JC, Kugler BP, Francis K. The possible prognostic significance of immunophenotype in feline alimentary lymphoma: a pilot study. J Comp Pathol 2004; 130: 220–222.
33. Moore PF, Rodriquez-Bertos A, Kass PH. Feline gastrointestinal lymphoma: mucosal architecture, immunophenotype, and molecular clonality. Vet Pathol 2012; 49: 658–668.
34. Peaston AE, Maddison JE. Efficacy of doxorubicin as an induction agent for cats with lymphosarcoma. Aust Vet J 1999; 77: 442–444.
35. Vail DM, Young KM. Hematopoietic tumors. In: Withrow SJ, Vail DM, eds. Withrow and MacEwen's small animal clinical oncology. St Louis: Saunders Elsevier, 2007; 699–784.
