Expression of CD3, PD-L1 and CTLA-4 in mammary and extra-mammary Paget disease

Abstract

Background

Mammary and extra-mammary Paget disease is a rare form of intra-epithelial glandular neoplasm which is characteristically recurrent and necessitates multiple excisions that have an important impact on morbidity. Local immuno-modulating treatments have been applied with promising results, but the local immune markers of Paget disease have not been studied.

Aim of the study

To investigate the local immune micro-environment of Paget disease.

Materials and methods

Sixty-four specimens from 41 patients, including cases with multiple recurrences and underlying primary neoplasm, have been studied for their expression of CD3, PD-L1 and CTLA-4.

Results

Nineteen cases were mammary; 22 were extra-mammary and involved the vulva, the anus, the inguinal region and the lower extremity. PD-L1 was not expressed by any neoplastic lesion or the associated lymphocytes. CTLA-4 expression was found in nine cases. Higher stromal CD3 expression and moderate levels of intra-epithelial CD3 expression were present in most cases. Biopsies, subsequent excision specimens and recurrences showed the same immunohistochemical profile of CD3 and PD-L1, although there were different levels of CTLA-4 in a few cases. The underlying lesions in mammary Paget disease showed the same immunohistochemical profile as the intra-epithelial neoplastic cells. The expression of the markers did not correlate with age, sex, localization or recurrence.

Conclusion

Paget disease is characterized by an intense lymphocytic response, devoid of the immune-suppressive impact of the PD-L1 pathway, but with occasional CTLA-4 expression.

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