Background: Preferentially expressed antigen in melanoma (PRAME) is a cancer testis antigen (CTA) identified in 1997 through analysis of the specificity of tumor-reactive T-cell clones derived from a patient with metastatic cutaneous melanoma. Although at first it seemed even more specific, various studies have shown that PRAME can also be expressed in the context of atypical lesions that do not correspond solely to the definition of malignant melanoma. Methods: A systematic review of English articles was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: 126 records were identified in the literature search, of which 9 were duplicates. After screening for eligibility and inclusion criteria, 53 publications were included. Conclusions: The advent of a new marker such as PRAME is surely a step forward not only in the diagnostic approach, but also in the immunotherapeutic approach to MM. However, various studies have shown that PRAME can also be expressed in the context of atypical lesions apart from MM and, for this reason, the diagnostic sensitivity and specificity (hence accuracy) are clearly lower. Further studies with larger case series will be necessary to understand better what possibilities are offered in terms of diagnostic reliability by PRAME.

The presence of stromal osteoclast-like giant cells is a distinctive feature of some rare breast tumors, accounting for less than 1% of all breast cancer cases. Although the presence of stromal osteoclast-like giant cells may be encountered in different breast tumors, some authors still describe them as a specific tumor type. Usually, a histological diagnosis of breast carcinoma is made by a pathologist through a biopsy, which is then confirmed through a surgical specimen: it is rare for the two to differ, particularly when there are pathognomonic morphological markers, such as osteoclast-like giant cells. Herein, we report a case of a 45-year-old pre-menopausal woman, who was found to have a single solid mass in her right breast on screening mammogram. She underwent a core biopsy, which showed a malignant epithelial lesion arranged in tubules, glands, and papillae, intermingled with numerous stromal osteoclast-like giant cells. Therefore, a diagnosis of breast cancer with osteoclast-like giant cells was rendered. Curiously, these cells were no longer detectable in the surgical specimen.