Invasive micropapillary carcinoma of the dog mammary gland: a case report

Carcinoma micropapilar invasivo na glândula mamária da cadela: relato de caso

Invasive micropapillary carcinoma of the dog mammary gland. A case report

[Carcinoma micropapilar invasivo na glândula mamária da cadela. Relato de caso]

G.D. Cassali¹, R. Serakides², F. Gärtner³, F.C. Schmitt³

¹Laboratório de Patologia Comparada

Depto. Patologia Geral - ICB/UFMG - Caixa Postal 486

³1270-901 – Belo Horizonte, MG

2Escola de Veterinária – UFMG

3Instituto de Patologia e Imunologia Molecular da Universidade do Porto - Portugal

Recebido para publicação em 8 de junho de 2001.

Recebido para publicação, após modificações, em 29 de abril de 2002

email: [e-mail]

ABSTRACT

This report describes the morphological and immunohistochemical findings of two cases of breast invasive micropapillary carcinoma occurring in dogs. Histologically, the tumors are characterized by the presence of numerous irregular cystic formations filled out with nests of epithelial cells that exhibit a micropapillary pattern. These morphological features are characteristic of invasive micropapillary carcinoma in woman, a breast tumor not previously described in dogs.

Keywords: Dog, mammary carcinoma, mammary gland, invasive micropapillary carcinoma

RESUMO

São descritos os aspectos morfológico e imunoistoquímico de dois casos de carcinoma micropapilar invasivo da glândula mamária na espécie canina. Histologicamente, os tumores eram caracterizados pela presença de numerosas formações císticas irregulares contendo grupamentos de células epiteliais exibindo um padrão micropapilar. Essa morfologia é característica do carcinoma micropapilar invasivo descrito na mulher, porém ainda não mencionado na cadela.

Palavras-chave: Cão, carcinoma, glândula mamária, carcinoma micropapilar invasivo

INTRODUCTION

The morphologic spectrum of mammary neoplasms in canine species is generally quite different from those seen in humans (Hampe & Misdorp, 1974; Nerurkar et al., 1989). However, there are some histologic types of breast tumors occurring in canines with a striking similarity with their human counterpart. The purpose of this report is to describe the morphological and immunohistochemical features of two cases of an unusual type of breast neoplasm, the invasive micropapillary carcinoma, not yet described in the bitch.

CASE DESCRIPTIONS

Case 1: A 10-year-old Doberman bitch was referred to the hospital with a tumor mass involving all mammary glands, with the exception of two cranial and right caudal thoracic glands. Due to the fact that the dog had been previously submitted to a surgery for excision of a mammary tumor 20 months ago, the owner decided to euthanize the animal. Tissue samples were obtained and fixed in 10% buffered formalin. The fixed tissue was embedded in paraffin, sectioned at 4mm and stained with haematoxylin and eosin. For immunostaining, the avidin-biotin-peroxidase complex (ABC) method was used. The monoclonal antibodies for epithelial membrane antigen (EMA) diluted at 1:25 (Dakopatts, Denmark), progesterone receptor (PR) diluted at 1:40 (Immunotech, France), and MIB-1 diluted at 1:100², and a polyclonal antibody for c-erbB2 diluted 1:200 25 ¹ were used.

The histological sections revealed an infiltrating carcinoma with numerous irregular cystic spaces, distributed diffusely through the mammary tissue. Some cystic spaces had an architecture lymphatic-like channels and were filled out with nests of epithelial cells that exhibited a micropapillary pattern (Fig.1- A and B). The epithelial cells showed large eosinophilic cytoplasm and a vesicular pleomorphic nucleus with a prominent nucleoli. Numerous mitotic figures were depicted. Metastasis were observed in the axillary and internal iliac lymph nodes. The neoplastic cells were positive for EMA and c-erbB2 and presented a high proliferative index when immunostained for MIB-1 (55.09%) (Fig.1- C). PR was negative.

Case 2: A 7-year-old Poodle bitch presented with a history of cardiac failure with pleural effusion for approximately one year. Ascitic effusion had also developed in the last three months. A tissue mass was found in the cranial and caudal thoracic left glands in the clinical examen. The diagnosis of mammary cancer was established by cytological examination of the pleural effusion and fine needle aspiration of the mammary gland. Thirty days after the diagnosis the owner decided to euthanize the animal and necropsy was performed. A tumor mass weighing 52g and measuring 11.5 x 5.0 x 1.5cm was found in the cranial and caudal thoracic left glands. There was no gross indication of tumor in other organs, but in the right kidney was found an area of infarction measuring 1.2 x 0.7cm. Formalin fixed tissues from the tumor mass and from the other organs were paraffin embedded and sections 4mm thick were cut and stained with haematoxylin and eosin. Immunostaining was performed according to the avidin-biotin-peroxidase complex method. The monoclonal antibodies for EMA, PR and MIB-1 and a polyclonal antibody for c-erbB2 were used in the same dilutions previously mentioned.

Histologically, similar aspects described for case one were observed. Micrometastasis were observed in lymph nodes, lung, epicardium, pericardium and kidneys. The right kidney contained neoplastic emboli in the cortico-medullary arteries with coagulative necrosis consistent with infarction. The neoplastic cells were positive for EMA, c-erbB2 and focally for PR (Fig.1- D). The proliferative index detected by MIB-1 was 17.9%.

DISCUSSION

Invasive micropapillary carcinoma is a morphologically distinctive form of invasive ductal carcinoma of the breast, characterized by the diffuse presence of groups of tumor cells in morule-like clusters inside cystic spaces. These tumors have a low incidence in the human species, however it is important to recognize them because they have a high lymphotropism and lymph node metastases are frequent in these cases (Luna-Moré et al., 1994). Although the tumor had a sponge-like pattern of growing, most of these spaces are not true lymphatic vessels. In fact, the identification of true lymphatic tumor emboli in the vicinity of the primary tumor is difficult (Rosen, 1997). The tumor cells showed immunoreactivity with epithelial membrane antigen (EMA), which stained the apical cell membrane in morula nests and tubules. The peripheral pattern of immunostaining observed in these cases is similar to those described in human cases by Luna-Moré et al. (1994) and Rosen (1997), and confirmed the micropapillary nature of the neoplastic cell nests.

Luna-Moré et al. (1994) reported in their series a diagnosis age range from 36 to 81 years (mean of 54 years) in women. In these cases, using the age conversion table, postulated by Lebeau (1953), the animal of the case 1 should be compared to a 56-year-old woman and case 2 to a woman of 44-year-old. In humans, patients with a predominant pattern of invasive micropapillary carcinoma tend to be older than those with ordinary breast carcinomas (Luna-Moré et al., 1994; Rosen, 1997).

Information about the clinical course of invasive micropapillary carcinoma is very limited (Rosen, 1997). In one study, 50% of the patients died of disease (Luna-Moré et al., 1994). Another study reported one patient with a local recursion 2.8 years after mastectomy(Siriaunkgul & Tavassoli, 1993). In this respect, c-erbB2 can play a key role in these groups of tumors. The neu-protein is overexpressed in about 20% of invasive ductal carcinomas of the breast (Schmitt et al., 1995). The overexpression of c-erbB2 is correlated with decreased of overall survival and disease free survival, due to increased metastatic activity of neu-overexpressing tumor cells. This increased metastatic potential is a consequence of the motility enhancing activity of the neu-protein, which is exclusively expressed on pseudopodia and, to a lesser extent of its growth stimulating effect (Schmitt et al., 1995). In fact, Luna-Moré et al. (1996) observed in their series of invasive micropapillary carcinomas of the breast, 36.3% of cases positive for c-erbB2, and these cases had lower survival rates in comparison with the negative cases. Our results are in agreement with these findings, since both micropapillary carcinomas exhibited c-erbB2 overexpression, and in case 2 it was found generalized metastasis.

CONCLUSION

The histological and immunohistochemical findings observed in these cases were similar with previous observations for this rare human breast tumor and agree with the diagnosis of invasive micropapillary carcinoma. These are the first cases of this tumor described in dogs. Although there are well established differences between canine and human breast tumors, veterinary pathologists should be prepared to diagnose rare cases of mammary tumors similar to those observed in humans, as described in this paper.

ACKNOWLEDGEMENTS

This work was partially supported by grants from CAPES/ICCTI (035/98; 423 CAPES; BEX0013/98-6), FAPEMIG (CBS838/96) and CNPq.

References

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Publication Dates

• Publication in this collection
  16 Dec 2002
• Date of issue
  Aug 2002

History

• Accepted
  29 Apr 2002
• Received
  08 June 2001