Abstract

Invasive mammary carcinomas with neuroendocrine differentiation are rare in women and were reported only once in female dogs. For the present study, ten cases of solid mammary carcinoma positive for chromogramin A in immunohistochemistry were selected. Histopathological characteristics of these tumors were described and immunohistochemical evaluation was performed with chromogranin A, synaptophysin, CD56, NSE, PGP 9.5, pancitokeratin, Ki67, estrogen receptor (ER), and progesterone receptor (PR). The average animal age was 13.2 years old and the average tumor size was 4.8 cm. In total, 70% of the neoplasms were classified as grade III and 30% as grade II by the Nottingham histological grade system. High mitotic index was observed with a mean of 27.5 mitoses in 10 high magnification fields. Only one case showed typical carcinoid tumor characteristics. In addition, vascular invasion was shown in 3 tumors. All carcinomas were positive for chromogran A, while only two cases were reactive to synaptophysin. For PGP 9.2, NSE and CD56, we observed positivity of 100, 90, and 70%, respectively, in the samples, being that no tumor was positive for all the neuroendocrine markers. All neoplasms showed ER and PR in at least 10% of neoplastic cells, while Ki67 varied from 29 to 95%, with mean mitotic index of 67%. Four of the ten animals died within 1 year of the tumor diagnosis. Neuroendocrine neoplasms occur in the canine mammary gland and are propably underdiagnosed. This is due to their non-specific morphological characteristics and the low use of neuroendocrine immunohistochemistric markers the diagnostic routine. More studies are necessary to determine the prognosis of this new histological type.

Highlights

  • Neuroendocrine tumors are a group of biologically and clinically heterogeneous neoplasms that originate most commonly in lungs, gastrointestinal tract and pancreas [1, 2]

  • We aimed to investigate the presence of neuroendocrine differentiation in 10 cases of solid mammary carcinoma of female dogs, in order to promote a greater recognition and appropriate classification of this histological type in this species

  • Invasive carcinomas with neuroendocrine differentiation of the human breast are under-recognized in the practical routine and represent 0.5–1% of all breast cancers [11, 12, 15]

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Summary

Introduction

Neuroendocrine tumors are a group of biologically and clinically heterogeneous neoplasms that originate most commonly in lungs, gastrointestinal tract and pancreas [1, 2]. Their occurrence is rare, pure neuroendocrine tumors and invasive breast carcinomas with neuroendocrine features have already been reported in women [3,4,5], while only one case has been reported in a female dog [6]. The 2012 classification included a chapter on “Carcinomas with neuroendocrine features,” in which the minimum cut-off of tumor cells with positive labeling for neuroendocrine markers was removed [9, 14]

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