On-line version ISSN 1678-4162
Arq. Bras. Med. Vet. Zootec. vol.55 no.1 Belo Horizonte Feb. 2003
Protocol for the anatomopathological examination of canine mammary tumors
[Protocolo para exame anatomopatológico de tumores mamários em cães]
E. FerreiraI; G.C. BregunciI; F.C. SchmittII; G.D. CassaliI
ILaboratório de Patologia Comparada - Departamento de Patologia Geral Instituto Ciências Biológicas da UFMG Caixa Postal 486 31270-901, Belo Horizonte, MG
IIInstituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal
Foi elaborado um protocolo para exame anatomopatológico de tumores de mama em cães, constituído de três partes: requisição, exame clínico e laudo histopatológico. O exame clínico contém dados sobre a descrição macroscópica da lesão. O laudo histopatológico constituiu-se de campos para descrição microscópica pormenorizada das lesões e classificação da principal lesão observada. A elaboração do protocolo tem como objetivo estabelecer critérios para estudos e pesquisas sobre neoplasias mamárias em animais e auxiliar no diagnóstico e prognóstico de lesões mamárias.
Palavras-chave: neoplasia, glândula mamária, histopatologia, protocolo, cão
Keywords: neoplasia, mammary gland, histopathology, protocol, dog
Mammary gland neoplasias usually occur in dogs, and more rarely in cats. The incidence in dogs is around 198 for each 1000 animals, representing about 50% of all neoplasias observed in this species (Moulton, 1990).
According to the World Health Organization (Misdorp et al., 1999), classification of tumors is done based on its descriptive morphology in accordance with the malignancy degree. It is known that, according to the malignancy degree, a considerable reduction in the survival rate of the animal is observed.
It has been described, that the order of malignancy increases from the "in situ" carcinoma (noninfiltrating), simple or complex carcinoma (with myoepithelial involvement), to tubulopapillary, solid and anaplastic carcinoma. Among the benign neoplasms, benign mixed tumor represents 50% of all mammary neoplasms (Moulton, 1990; Cassali, 2000). Other malignant neoplasms, such as spindle cell carcinoma, squamous cell carcinoma, mucinous carcinoma, lipid-rich carcinoma, carcinoma in benign tumor, carcinosarcoma, fibrosarcoma, chondroosteosarcoma and liposarcoma are less frequent (Misdorp et al., 1999).
Histopathological analysis of a tumor is essential in order to obtain consistent information on the prognostic factors of mammary cancer, and should be considered as a basic step for the therapeutic orientation of these lesions (Schmitt, 2000). Immunohistochemical techniques for detection of estrogen receptors, progesterone, epidermal growth factor, oncogenes, among others, are of great value in order to get a more accurate prognosis in mammary neoplasms (Cassali, 2000). However, these techniques are very expensive and, consequently, prohibit their routine use in veterinary medicine. Histopathological analysis is a more viable alternative for attaining a meaningful and cost effective prognosis of malignant tumors in dogs.
The main elements to be evaluated by microscopic analysis are the following: histological type of the tumor, presence of vascular or soft tissue infiltration; grading (pleomorphism, mitotic rate, differentiation), presence of necrosis and verification of surgical edges (Schmitt, 2000).
Tumors must be categorized according to the TNM system, where T means the maximum diameter of the tumor, N the involvement of regional lymph nodes and M distant metastasis (Brody et al., 1983). Usually, size of the tumor (larger than 5 cm), involvement of lymph nodes and presence of distant metastasis reduce, significantly, the survival rate of animals one year after the diagnosis (Yamagami et al., 1996).
Scoring of a cancer is based on the degree of differentiation of neoplastic cells and on the number of mitotic figures of the tumor, these characteristics correlate to the aggressiveness of the tumor. Criteria for scoring mammary tumors is not systematically used in veterinary pathology (Cassali, 2002).
Two to three new cases of female canine mammary tumors are diagnosed each week at the Veterinary Hospital of the Veterinary College of Federal University of Minas Gerais (Brazil). In the majority of these cases, the tumor is surgically removed and, sometimes, the regional lymph node is also excised (Cassali, 1998).
The use of a protocol to collect data facilitates the communication between clinical and diagnostic branches. Protocols for studing mammary neoplasms are used routinely in human medicine. These protocols are an important component of the process for reaching a final diagnosis and prognostics based mainly on clinical and histopathological findings (Gobbi et al., 1993).
Since these protocols are not currently used in veterinary medicine, the elaboration of such protocols for analyses of alterations of the mammary gland, specially neoplasms, is necessary. These protocols will provide solid bases for future studies on mammary cancer in domestic animals and assist in the diagnosis and prognosis of mammary lesions.
The anatomo-histopathological protocol was divided into three parts. First, the request, containing identification of the animal and its clinical history with all the factors that could be associated to mammary alterations.
The second part of the protocol consists of clinical examination, containing data on the macroscopic description of the lesion. It should contain up to three alterations considering all the five pairs of glands, information on size and weight, localization of the lesion, collection procedure (biopsy, surgical or necropsy) and if surgically removed, whether it has cutaneous and muscular involvement. In addition, it should supply information on characteristics of the tumor and lymphatic involvement.
The third part consists of identification of the tumor and tumor data supplying information on the detailed microscopic characterization of the lesions. This could be used for the classification of the lesions either as benign lesions or else benign or malignant neoplasias.
The malignant neoplasia item contains several subdivisions to be filled out considering the determining aspects of the prognostic of the mammary cancer.
In the item "tubular arrangement", percentage of occurrence of tubules formation must be quantified. The cytological degree evaluates the nuclear pleomorphism. Mitotic figures must be counted in a 10 HPF (High Power Field), selected in the proliferative active periphery of the tumor in the 4m m tissue sections stained with hematoxylin and eosin, as emphasized by Elston and Ellis (1991, 1998).
The histological degree is obtained by the sum of the values of three items: tubular arrangement, cytological degree and mitotic activity. It varies from 3 to 9, and will be evaluated as degree I when the sum varies 3 to 5, degree II, 6 to 7 and degree III, 8 to 9 (Elston and Ellis, 1991; Elston, Ellis, 1998).
The approach proposed in this protocol emphasizes general quantitative and qualitative aspects of the tumor. The pathological staging item must be filled in cases of malignant tumors, according to TNM criteria. Classification of tumors smaller than 3 cm will be T1, between 3 and 5 cm, T2 and larger than 5 cm, T3. As for extent of the involvement of regional lymph nodes, it will be N0 when there is no involvement, N1 when there is ipsilateral involvement and N2, when bilateral. Presence of metastasis is classified as absent (M0) or present (M1) (Brody et al., 1983).
In conclusion, the protocol summarizing clinical and anatomo-histopatological data guides to the final diagnosis of the main pathological process in the examined surgical specimen.
We are grateful to Leonor B. Guerra for critically reviewing the English manuscript and suggestions and to Conselho Nacional de Desenvolvimento Cientifico e Tecnólogico (CNPq).
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Recebido para publicação em 31 de maio de 2002
Recebido para publicação, após modificações, em 29 de janeiro de 2003