Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases.

Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are intraductal papilloma with usual ductal hyperplasia, encapsulated papillary carcinoma, solid papillary carcinoma and invasive micropapillary carcinoma. We studied nine cases of this special papillary tumor and six of each other types mentioned above. We found that solid papillary carcinoma with reverse polarity harbor specific morphologic features as cuboid or tall cells with abundant eosinophilic cytoplasms located at the basal pole giving the impression of reverse nuclear polarity. Nuclei were sometimes grooved. Immunohistochemistry demonstrated the lack of myoepithelial cells, as in encapsulated papillary carcinoma and solid papillary carcinoma, questioning their invasive nature. Seven of nine solid papillary carcinoma with reverse polarity showed a low Ki67 proliferative index (Ki67 <5%). They showed expression of CK5/6 as in intraductal papilloma with usual ductal hyperplasia. They showed expression of calretinin and a low or lack of hormonal receptor (HR) expression that were not observed in other breast tumors studied. By whole-exome analysis, seven of nine solid papillary carcinomas with reverse polarity (78%) harbored a hotspot mutation in IDH2 (R172) that was totally absent in other groups. Six of nine tumors (67%) also harbored PRUNE2 mutation, including the two IDH2 wild-type cases. We also demonstrated for the first time in this breast tumor, immunostaining with a specific antibody IDH1/2 mutant R132/R172 (7/9) that can highlight IDH2 mutation. Moreover, transcriptomic analysis showed that proteoglycan pathway was significantly enriched. Our findings support the fact that solid papillary carcinoma with reverse polarity is a singular breast neoplasm that can be distinguished from other papillary breast tumors.

[Improving practice in breast pathology: 34-months experience of the regional SENOPATH network and webinars as a tool for diagnosis of difficult lesions of the breast]. / Amélioration des pratiques en pathologie mammaire : bilan à 34 mois du groupe régional de relecture SENOPATH et télépathologie pour les lésions de diagnostic difficile.

Pathologists commonly face breast lesions that are difficult to diagnose. To reduce second opinion delay, erase geographical barrier and provide continuing education, we aimed to develop a telepathology-based regional network of pathologists. With the support of ONCOMIP network, we founded a peer-group named SENOPATH, composed of experienced breast pathologists practising in private laboratories, university hospitals or comprehensive cancer center in the region of Midi-Pyrénées in France. Submitted cases are digitalized at the University Hospital, stored in a shared space with a possible access via Internet prior to the SENOPATH sessions. The group meets monthly, via a synchronized webinar and multihead microscope session. A consensual diagnosis and final pathology report is issued for each case, and sent to the referring clinician via the patient medical file securely hosted by ONCOMIP. Between 2012 and 2014, 142 cases were reviewed, for either diagnostic 'routine' difficulty or rare histological type. The SENOPATH group, also regularly called by oncologists to solve difficult cases, has considerably improved the pathologist network in Southern France. Supported by the webinar tool, its educational impact is prominent, with a considerable progress in the region with regards to standardization of pathology processes, literature review and knowledge sharing.