Vulvar biopsy: Punch biopsy or cervical forceps biopsy?

OBJECTIVES: The primary objective of our study is to investigate the rate of non-contributory biopsies between punch biopsy(PB) and cervical forceps biopsy(CFB) for a vulvar lesion seen in consultation. The secondary objective of our study is to evaluate the rate of underestimation of a more severe lesion for patients who have undergone vulvar excision. MATERIAL AND METHOD: This is a retrospective, descriptive, and comparative study conducted at three centers. The study population consisted of patients who underwent vulvar biopsy between 2017 and 2022 in a gynecological surgery consultation at two French hospitals, as well as a city office. The biopsy techniques used were punch or cervical forceps biopsy. Quantitative variables were analyzed using the Mann-Whitney test, while Pearson's or Fisher's Xi2 tests were used for qualitative variables. The significance level was set at 5%. RESULTS: We conducted a retrospective study of 179 vulvar biopsies, of which 100 were punch biopsies and 79 were cervical forceps biopsies, from a total of 107 patients. There was no significant difference in the rate of non-contributory biopsies between the PB and CB groups (p = 1). When analyzing the secondary endpoint of our study, which included 68 patients who underwent vulvectomy after vulvar biopsy, we found that 66 patients (97%) had a good correlation between the pathology of the vulvar biopsy and that of the vulvectomy specimen. CONCLUSION: Vulvar biopsy techniques using punch or cervical forceps appear to have similar diagnostic performance and are associated with comparable and low rates of underestimation of invasive lesions.

Value of high-resolution full-field optical coherence tomography and dynamic cell imaging for one-stop rapid diagnosis breast clinic.

BACKGROUND: Full-field optical coherence tomography combined with dynamic cell imaging (D-FFOCT) is a new, simple-to-use, nondestructive, quick technique that can provide sufficient spatial resolution to mimic histopathological analysis. The objective of this study was to evaluate diagnostic performance of D-FFOCT for one-stop rapid diagnosis breast clinic. METHODS: Dynamic full-field optical coherence tomography was applied to fresh, untreated breast and nodes biopsies. Four different readers (senior and junior radiologist, surgeon, and pathologist) analyzed the samples without knowing final histological diagnosis or American College of Radiology classification. The results were compared to conventional processing and staining (hematoxylin-eosin). RESULTS: A total of 217 biopsies were performed on 152 patients. There were 144 breast biopsies and 61 lymph nodes with 101 infiltrative cancers (49.27%), 99 benign lesions (48.29%), 3 ductal in situ carcinoma (1.46%), and 2 atypias (0.98%). The diagnostic performance results were as follow: sensitivity: 77% [0.7;0.82], specificity: 64% [0.58;0.71], PPV: 74% [0.68;0.78], and NPV: 75% [0.72;0.78]. A large image atlas was created as well as a diagnosis algorithm from the readers' experience. CONCLUSION: With 74% PPV and 75% NPV, D-FFOCT is not yet ready to be used in clinical practice to identify breast cancer. This is mainly explained by the lack of experience and knowledge of this new technic by the four lectors. By training with the diagnosis algorithm and the image atlas, radiologists could have better outcomes allowing quick detection of breast cancer and lymph node involvement. Deep learning could also be used, and further investigation will follow.

Residual Microscopic Peritoneal Metastases after Macroscopic Complete Cytoreductive Surgery for Advanced High-Grade Serous Ovarian Carcinoma: A Target for Folate Receptor Targeted Photodynamic Therapy?

Despite conventional treatment combining complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy, residual microscopic peritoneal metastases (mPM) may persist as the cause of peritoneal recurrence in 60% of patients. Therefore, there is a real need to specifically target these mPM to definitively eradicate any traces of the disease and improve patient survival. Therapeutic targeting method, such as photodynamic therapy, would be a promising method for such a purpose. Folate receptor alpha (FRα), as it is specifically overexpressed by cancer cells from various origins, including ovarian cancer cells, is a good target to address photosensitizing molecules. The aim of this study was to determine FRα expression by residual mPM after complete macroscopic CRS in patients with advanced high-grade serous ovarian cancer (HGSOC). A prospective study conducted between 1 June 2018 and 10 July 2019 in a single referent center accredited by the European Society of Gynecological Oncology for advanced EOC surgical management. Consecutive patients presenting with advanced HGSOC and eligible for complete macroscopic CRS were included. Up to 13 peritoneal biopsies were taken from macroscopically healthy peritoneum at the end of CRS and examined for the presence of mPM. In case of detection of mPM, a systematic search for RFα expression by immunohistochemistry was performed. Twenty-six patients were included and 26.9% presented mPM. In the subgroup of patients with mPM, FRα expression was positive on diagnostic biopsy before neoadjuvant chemotherapy for 67% of patients, on macroscopic peritoneal metastases for 86% of patients, and on mPM for 75% of patients. In the subgroup of patients with no mPM, FRα expression was found on diagnostic biopsy before neoadjuvant chemotherapy in 29% of patients and on macroscopic peritoneal metastases in 78% of patients. FRα is well expressed by patients with or without mPM after complete macroscopic CRS in patients with advanced HGSOC. In addition to conventional cytoreductive surgery, the use of a therapeutic targeting method, such as photodynamic therapy, by addressing photosensitizing molecules that specifically target FRα may be studied.

Breast carcinomas with osteoclast-like giant cells: a comprehensive clinico-pathological and molecular portrait and evidence of RANK-L expression.

Breast carcinomas (BC) with osteoclast-like giant cells (OGC) are rare. Despite their distinct stromal features, their molecular characteristics remain unknown. Here, we report comprehensive clinico-pathological and molecular findings for 27 patients diagnosed with BC-OGC at Institut Curie between 2000 and 2021. Seventeen (63%) cases were invasive carcinomas of no special type (IC NST) with OGC (OGC-IC NST), four (15%) were mixed or multifocal cases with and without OGC (OGC-Mixed), and six (22%) were metaplastic carcinomas with OGC (OGC-MC). All OGC-IC NST and OGC-Mixed cases were ER+ HER2- tumors (most being luminal A based on transcriptomic subtyping, when available), while all OGC-MC were triple-negative. The median age at diagnosis was 46, 45 and 62 years for OGC-IC NST, OGC-Mixed and OGC-MC, respectively. Three patients developed distant metastases (one OGC-IC NST, two OGC-Mixed), one of whom died of metastatic disease (OGC-Mixed), and one other patient died of locally advanced disease (OGC-MC). Histopathological evaluation comparing 13 OGC-IC NST and 19 control IC NST without OGC confirmed that OGC-IC NST showed significantly higher density of vessels (by CD34 immunohistochemistry (IHC)), iron deposits (Perls stain), and CD68 and CD163-positive cell infiltrates. Genomic findings for nine OGC-IC NST and four OGC-MC were consistent with the underlying histologic subtype, including activating alterations of the PI3K/AKT/mTOR pathway in 7/13 cases. Using RNA-seq data, differential gene expression analysis between OGC-IC NST (n = 7) and control IC NST without OGC (n = 7) revealed significant overexpression of TNFSF11 (RANK-L), TNFRSF11A (RANK), CSF1 (M-CSF), CSF1R, and genes encoding osteoclastic enzymes (MMP9, ACP5, CTSK, CTSB) in OGC-IC NST, while OPG (osteoprotegerin) was underexpressed. We also confirmed for the first time RANK-L expression in BC with OGC by IHC (seen in 15 out of 16 cases, and only in 2 of 16 controls without OGC). These findings could offer a rationale for further investigating RANK-L as a therapeutic target in BC with OGC.

Microscopic Peritoneal Residual Disease after Complete Macroscopic Cytoreductive Surgery for Advanced High Grade Serous Ovarian Cancer.

BACKGROUND: Epithelial ovarian cancers (EOC) are usually diagnosed at an advanced stage and managed by complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy. Peritoneal recurrence occurs in 60% of patients and may be due to microscopic peritoneal metastases (mPM) which are neither eradicated by surgery nor controlled by systemic chemotherapy. The aim of this study was to assess and quantify the prevalence of residual mPM after complete macroscopic CRS in patients with advanced high-grade serous ovarian cancer (HGSOC). METHODS: A prospective study conducted between 1 June 2018 and 10 July 2019 in a single referent center accredited by the European Society of Gynecological Oncology for advanced EOC management. Consecutive patients presenting with advanced HGSOC and eligible for complete macroscopic CRS were included. Up to 13 peritoneal biopsies were taken from macroscopically healthy peritoneum at the end of CRS and examined for the presence of mPM. A mathematical model was designed to determine the probability of presenting at least one mPM after CRS. RESULTS: 26 patients were included and 26.9% presented mPM. There were no differences in characteristics between patients with or without identified mPM. After mathematical analysis, the probability that mPM remained after complete macroscopic CRS in patients with EOC was 98.14%. CONCLUSION: Microscopic PM is systematically present after complete macroscopic CRS for EOC and could be a relevant therapeutic target. Adjuvant locoregional strategies to conventional surgery may improve survival by achieving microscopic CRS.