Cat Mast Cell tumor grade - removal no effect on reocurrence

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Cat Mast Cell tumor grade - removal no effect on reocurrence

Postby guest » Mon Sep 29, 2003 12:10 pm

Cutaneous Mast Cell Tumors in Cats: 32 Cases (1991– 1994)

Heather Molander-McCrary, DVM; Carolyn J. Henry, DVM, MS; Kathleen Potter, DVM, PhD; Jeff W. Tyler, DVM, PhD; Michael S. Buss, DVM, MS
Journal of the American Animal Hospital Association
July 1, 1998




Case records of 32 cats with cutaneous mast cell tumors (CMCTs) were reviewed. Using the Patnaik system for grading canine mast cell tumors, the relationships between histopathological grade and patient survival time and tumor recurrence were examined. Tumor histopathological grade had no prognostic significance. One-, two-, and three-year tumor recurrence rates following surgical excision were 16%, 19%, and 13%, respectively. Incomplete excision was not associated with a higher rate of tumor recurrence.

J Am Anim Hosp Assoc 1998;34:281–4.


Introduction

The reported incidence of mast cell tumors varies from 2% to 15% of all tumors in cats.1–3 Feline mast cell tumors are observed most commonly on the head, neck, and trunk, but they also may occur in the visceral organs.4 Siamese cats are predisposed to the development of mast cell tumors.1,4 Canine mast cell tumors are graded histopathologically to permit prediction of patient survival time and prognosis. In dogs, the most frequently used histopathological grading system for mast cell tumors was proposed by Patnaik in 1984.5 In this grading system, grade I tumors are well differentiated and confined to the dermis; grade II tumors are moderate to highly cellular with neoplastic cells infiltrating the lower dermal tissue with indistinct cell borders; and grade III tumors are cellular and pleomorphic with undifferentiated boundaries and mitotic figures. Using this grading system, Patnaik, et al. observed an association between mast cell tumor histopathological grade and survival time in dogs.5

Although several histopathological grading schemes have been proposed for use in feline mast cell tumors, none has gained widespread acceptance.2,6,7 Feline mast cell tumors have been classified generally as well differentiated (i.e., compact), poorly differentiated (i.e., anaplastic), or histiocytic.7–9 Well-differentiated tumors are circumscribed, nonencapsulated masses consisting of solid sheets of uniform, round cells.9,10 Poorly differentiated (or anaplastic) mast cell tumors account for 5% to 10% of mast cell tumors in cats and are characterized by pleomorphism, increased mitotic activity, and infiltration of surrounding tissues.9,10 Histiocytic mast cell tumors are small, nonencapsulated, deep dermal or subcutaneous masses often grouped as papulonodular lesions on the head.6,9,10 These masses comprise 10% to 20% of all feline mast cell tumors and are most common in young (i.e., less than four years of age) Siamese cats.6,9,10

To the authors’ knowledge, only one prior study with a limited number (n=14) of cats examined the relationship between histopathological grade and patient survival time or disease-free interval (DFI).2 This previous study did not examine completeness of surgical excision as a risk factor for recurrence or survival. The purpose of this study was to examine a larger independent population of cats with cutaneous mast cell tumors (CMCTs) in order to determine whether histopathological grade and completeness of surgical excision are useful predictors of survival and prognosis.




...
Materials and Methods

Archived biopsy samples (from 1991 to 1994) from cats with CMCTs were obtained for review. Case inclusion criteria included a histopathological diagnosis of CMCT at least one year prior to the beginning of the study, and survival and follow-up more than one month after the initial diagnosis. The histiocytic form of mast cell tumor was excluded, as were cases with systemic mastocytosis. Practitioners who had submitted biopsy specimens were contacted by letter and phone to obtain information regarding tumor location, size, lymph-node involvement, presence of distant metastasis, treatment type, local recurrence, date of recurrence, and the cause and date of death, if applicable. Complete information was obtained for 32 cases. In each case, the diagnosis of CMCT was confirmed, and tumors were assigned a histopathological grade.

Histopathological criteria that were evaluated included nuclear pleomorphism, mitosis, and invasion of surrounding tissue [see Table]. Eosinophils also were evaluated but not included in the grading scheme. At least 10 fields at 400X magnification were examined to categorize results. Nuclear pleomorphism was characterized as none (0); one (1) for up to one cell per 400X field; two (2) for two-to-five cells per 400X field; or three (3) for more than five cells per 400X field. Mitosis was defined as none (0); one (1) for up to one mitotic figure per 400X field; two (2) for two-to-three mitotic figures per 400X field; or three (3) for more than three mitotic figures per 400X field. Extension of neoplastic cells outside the dermis was defined as absent (0) or present (1). Eosinophils were categorized as none (0); one (1) for one-to-two cells per 400X field; two (2) for three-to-five cells per 400X field; or three (3) for more than five cells per 400X field. Histological grades were assigned based upon the criteria described for canine CMCTs by Patnaik, et al.5 Briefly, grade I was assigned to tumors that were small, superficial infiltrates of well-differentiated mast cells [Figure 1]. Category scores for nuclear pleomorphism and mitoses were both 0 in grade I tumors. Grade II was assigned to larger tumors that often extended into the deep dermis [Figure 2]. Anisokaryosis and multinucleated cells were common, but mitoses usually were rare. Grade II assignment was considered appropriate when nuclear pleomorphism category scores ranged from 1 to 3, with a mitosis category score of 0 to 3. Grade III was assigned to deep dermal or subcutaneous tumors composed of anaplastic cells, which often stained poorly with toluidine blue [Figure 3]. Category score criteria for grade III assignment included a nuclear pleomorphism score of at least 3 and a mitosis score of at least 1.

Survival time was defined as the time between tumor diagnosis and death. Cases that died due to causes unrelated to CMCT or that were lost to follow-up were classified as censored. Disease-free interval was defined as the time from surgical excision to tumor recurrence or metastasis. Median survival times and DFIs were compared between older (more than 10 years of age) and younger (less than 10 years of age) cats, sex groups (male, castrated male, female, spayed female), breed groups (domestic shorthair, domestic medium hair, domestic longhair, Siamese, Himalayan), nuclear pleomorphism grades, mitotic grades, eosinophilic grades, and histopathological grades using the Kaplan-Meier method. Group medians were deemed to differ significantly when p was less than 0.05. Proportions of cases with tumor recurrence, death due to tumor, and death due to any cause also were reported. The recurrence rates were compared between cases with complete and incomplete excision using the chi-square test.

Results

The case records of 32 cats had adequate information available for review and complete responses to questionnaires by referring veterinarians. Four (12.5%) cases had more than one lesion at presentation, and 28 (87.5%) cases had single lesions. Of the four cases with multiple lesions, two had histopathological confirmation of CMCTs for all masses and two cases had only one of the masses submitted for histopathogical examination. Local lymph-node or distant metastasis was not detected in any case. Histopathological examination of excised tissues indicated complete excision in 10 (31%) of 32 cases and incomplete excision in 20 (63%) of 32 cases. In two cases, completeness of surgical margins could not be determined because all excised tissue was not submitted for examination. Five cases (complete excision, n=3; incomplete excision, n=2) had local tumor recurrences. These recurrence rates did not differ significantly. Eleven (34%) of the tumors were grade I, 18 (56%) were grade II, and three (9%) were grade III. Four cases died due to causes unrelated to CMCT, and no cases died due to the tumor. Median survival times and DFI could not be determined because 28 of 32 cases were alive at the end of the study and 27 of 32 had no tumor recurrence.

None of the examined historical risk factors, age, sex, breed group, histopathological indices listed in the Table, or tumor grade were associated significantly with either survival time or DFI. All cases were treated with surgical excision only. The ages at time of diagnosis ranged from one to 18 years. The mean and median ages at the time of initial diagnosis were nine and 9.6 years, respectively. The number of male cases was 12 (all castrated), and the number of female cases was 20, 15 of which were spayed. The breeds represented were domestic shorthair (66%), domestic medium hair (3%), domestic longhair (13%), Siamese (16%), and Himalayan (3%). Of cases (n=32) followed for at least one year, five (16%) had tumor recurrences, none died due to tumor complications, and four (13%) died due to unrelated causes. Of cases (n=27) followed for at least two years, five (19%) had tumor recurrences, none died due to tumor complications, and three (11%) died due to unrelated causes. Of cases (n=16) followed for at least three years, two (13%) had tumor recurrences, none died due to tumor complications, and two (13%) died due to unrelated causes.

Discussion

Cutaneous mast cell tumor was not the cause of death for any case in this study. The cases lived long lives despite tumor recurrence in 16% of cases. A correlation between histopathological grade and survival time could not be established because of the apparent benign nature of this tumor.

Historically, investigators described feline CMCT as highly malignant and likely to metastasize to regional lymph nodes and viscera within months.11 This belief was challenged by a retrospective study of 14 cases in which a benign behavior was noted,2 similar to the findings of the current study. Of 160 cats with CMCTs in the literature, only four had visceral metastasis.6,7,12


Buerger and Scott reported tumor grades, survival times, and recurrence rates for 14 feline CMCT cases.2 Similar to this study, they reported low mortality figures and a lack of lymph-node involvement. However, in their study, a greater percentage (36%) of cats had recurrent tumors. Although completeness of surgical excision was not evaluated as a risk factor in Buerger and Scott’s study,2 none of the recurrences they reported occurred at the site of original excision. The data in the authors’ study indicates no significant difference in survival time or recurrence rate for cats with complete versus incomplete surgical excision. In the previously reported study, multiple lesions occurred in 64% of cases2 as compared to 13% in the present study, and high grades (II or III) occurred in a proportion of cases (64%) similar to the present study (66%). The small number of cases with multiple lesions is a limitation of this study. In the two cases with multiple lesions confirmed to be CMCTs, one had grade I tumors and the other had grade II tumors. With this small number of cases, it is not possible to predict the relationship between histopathological grade and the presence of multiple tumors.


In dogs, recurrence, advanced stage, and high grades are all factors that decrease survival times.5,8,13 In this study, recurrence rates at one, two, and three years were 16%, 19%, and 13% respectively, but deaths due to tumor did not occur. The sex predilection of male cats that has been reported previously2,12 was not noted in this study. This finding correlates well with Holzinger7 and Miller, et al.14 who also found no sex predilection.


Conclusion

Histopathological grade does not provide useful prognostic information for solitary feline CMCTs. These tumors should be considered benign and warrant a good prognosis, provided visceral or systemic disease is not identified. Incomplete tumor excision was not associated with decreased survival time or a higher rate of tumor recurrence.


References

1. Macy DW, MacEwen EG. Mast cell tumors. In: Withrow SJ, MacEwen EG, eds. Clinical veterinary oncology. Philadelphia: JB Lippincott, 1989:156–66.

2. Buerger RG, Scott DW. Cutaneous mast cell neoplasia in cats: 14 cases (1975–1985). J Am Vet Med Assoc 1987;190:1440–4.

3. Pulley LT, Stannard AA. Tumors of the skin and soft tissues. In: Moulton JE, ed. Tumors in domestic animals. 3rd ed. Berkeley: Univ Calif Press, 1990:23–87.

4. Madewell BR, Theilen GH. Mast cell and melanocytic neoplasms. In: Theilen GH, Madewell BR, eds. Veterinary cancer medicine. 2nd ed. Philadelphia: Lea & Febiger, 1987:310–5.

5. Patnaik AK, Ehler WJ, MacEwen EG. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet Path 1984;21:469–74.

6. Wilcock BP, Yager JA, Zink MC. The morphology and behavior of feline cutaneous mastocytomas. Vet Path 1986;23:320–4.

7. Holzinger EA. Feline cutaneous mastocytomas. Cornell Vet 1973;63: 87–93.

8. Vail DM. Mast cell tumors. In: Withrow SJ, MacEwen EG, eds. Small animal clinical oncology. 2nd ed. Philadelphia: WB Saunders, 1996: 192–210.

9. Gross TL, Ihrke PJ, Walder EJ. Histiocytic and mast cell tumors. In: Gross TL, Ihrke PJ, Walder EJ, eds. Veterinary dermatopathology. St. Louis: Mosby-Year Book, 1992:467–73.

10. Yager JA, Wilcock BP. Round cell tumors. In: Yager JA, Wilcock BP, eds. Colour atlas and text of surgical pathology of the dog and cat. London: Mosby-Year Book Europe Limited, 1994:273–86.

11. Scott EW. Feline dermatology 1900–1978: a monograph. J Am Anim Hosp Assoc 1980;16:331–459.

12. Garner FM, Lingeman CH. Mast cell neoplasms of the domestic cat. Pathologia Veterinaria 1970;7:517–30.

13. Turrel JM, Kitchell BE, Miller LM, et al. Prognostic factors for radiation treatment of mast cell tumor in 85 dogs. J Am Vet Med Assoc 1988;193:936–40.

14. Miller MA, Nelson SL, Turk JR, et al. Cutaneous neoplasia in 340 cats. Vet Path 1991;28:389–95.
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Postby Guest » Mon Oct 13, 2003 9:11 am

I just wanted to comment that the study you have on your site is specifically referring to cutaneous mast cell tumours
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