Clinical staging in bitches with mammary tumors: Influence of type and histological grade

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Previous studies have reported tumor metastases in less than 50% of dogs, which corresponds with the findings of this study. A retrospective study of 99 dogs in the United States reported 25% of the animals at stage I, 12% at stage II, and 15% at stage III of the disease (13). However, a study in Brazil that examined 36 dogs described 22.2% of the animals as stage I and 75% as stage II of the disease; none of the animals were classified as stage III (14).

Given that the differentiation between stages I, II, and III is based only on the tumor size, another study conducted in Brazil reported that 35% of malignant tumors were smaller than 5.0 cm (11), while other studies have reported that neoplasms measured less than 3.0 cm [48.81% (15) and 44.7% (16), respectively].

A study involving human female subjects reported that 55.3% of patients presented tumors smaller than 3 cm and that the tumor diameter negatively affected the chance of survival despite resection (7). The smaller tumor size in these female subjects might have been due to early diagnosis. A similar correlation was observed herein which might be due, in part, to the owners seeking medical attention for swelling in the breasts sooner than usual.

With regard to the bitches diagnosed with the lymph node invasion in the present study (29.7%), previous studies conducted in Portugal and Colombia showed similar frequencies of occurrence [298% (16) and 30% (17), respectively]. Another study, however, had classified only 15.46% of the animals as stage IV (13).

The frequency of distant metastases in the present study was 7.9%. Previous studies have also reported similarly low frequencies of bitches at this stage of the disease; Ribas et al (18) and Gomes et al (17) reported that 8.3% and 16.7% of dogs were diagnosed with pulmonary metastasis, respectively. However, a negative radiological finding does not prove the absence of metastases, since the detection of tumors is challenging owing to their smaller sizes (19). Moreover, highly accurate diagnostic methods such as magnetic resonance imaging (MRI) and positron emission tomography (PET) scans are rarely practiced in veterinary medicine. Another reason for the fewer number of dogs at stage V of the disease is the fact that these animals are often already at advanced stages of the disease without having received any surgical treatment.

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With regard to the frequency of tumors according to histological type, previous studies have reported that tubular carcinoma is the most common (20,21), which corresponds to the findings in this study. However, the incidences of other types of tumors reported by different studies vary. The different histological classification systems used for the canine mammary tumors makes it difficult to compare the results of the various studies. The solid carcinoma has been reported as the second most frequent type of carcinoma in a previous study (20); however, another study reported the complex carcinoma as being the second most frequent (21). Carcinoma in mixed tumors also appears as one of the more frequent types of carcinomas (22), and in the present study, it was found to be the third most frequent.

The simple carcinomas were found to have the highest frequency of occurrence in this study when the tumors were grouped on the basis of their histological origin. The simple carcinomas have also been reported as the most frequent type of tumors in studies conducted in Japan (23), Brazil (24), and Iran (21).

Several authors have reported that simple carcinomas are more aggressive and have a worse prognosis than complex carcinomas (25,26). Therefore, the clinical staging of simple carcinomas in the present study was unexpected and can be attributed to the fewer number of the animals at the stages II, III, and V.

However, the staging of the carcinomas in mixed tumors in this study revealed the lower aggressiveness of these tumors, as has previously been described by Cassali et al (26), who also reported that these tumors have a better prognosis compared to other carcinomas. However, in the present study, the statistical corroboration of this fact was hindered because none of the animals with carcinomas in mixed tumors were at stage V.

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With regard to the complex carcinomas, we did not expect a large number of the animals to present lymph node invasions (stage IV) since Rasotto et al (27) had previously shown that 66.6% of the simple carcinomas in their study had metastasized to the lymph nodes and in 81.01% of the cases, invasion of the lymphatic vessels was observed; whereas, among the complex carcinomas, only 11.11% had metastasized to the lymph nodes and 20% showed lymphatic invasion.

The time-evolution of the tumor might affect the occurrence of the metastases. The larger tumors usually have a longer development duration, which increases the likelihood of metastasis (28). Unfortunately, the determination of the duration of tumor progression depends on the owner’s observation of the condition and is therefore often unclear.

In the histological grading findings, complex carcinomas showed less differentiation compared to simple carcinomas, as has been reported previously (27,10). The degree of differentiation of simple carcinomas is a matter of debate; it has been reported that this histological type of carcinoma has no association with the degree of differentiation (27) and that their classification as grade III (10) is frequent. The discrepancies between the results of the various studies might be because of the subjectivity of the gradation method, which can vary according to the reviewer. Another hypothesis is that a greater number of tubular tumors were classified as carcinomas in this study since tubule formation is one of the parameters considered for gradation, and tubular carcinomas tend to attain lower scores in the evaluation.

Histological grade is a factor that can influence the clinical staging of a tumor. A study in Slovenia reported that 64.71% of animals had stage I and grade I tumors, a result that is comparable to what we presented in this study (29). Similarly, a study conducted in Madrid described a significant association between the histological grade and the clinical staging of tumors (30). Other previous studies have also correlated the type and histological grade of the tumors with the overall survival rate (16).

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A limitation of the present study was the fewer number of animals at stage V of the disease. Although mixed tumor carcinomas typically show less aggression, fewer metastases, and lower cell differentiation, whereas simple carcinomas are more aggressive, this association could not be proven statistically because of the fewer number of animals at stage V. It can, however, be concluded that the histological grading proved to be the best parameter for the prognostic evaluation of breast carcinomas.


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About the Author: Tung Chi