Georgia Karpathiou

The Premetastatic Lymph Node Niche in Gynecologic Cancer

It has been suggested that a primary tumor can “prepare” the draining of lymph nodes to “better accommodate” future metastatic cells, thus implying the presence of a premetastatic lymph node niche. However, this phenomenon remains unclear in gynecological cancers. The aim of this study was to evaluate lymph-node draining in gynecological cancers for premetastatic niche factors, such as myeloid-derived suppressor cells (MDSCs), immunosuppressive macrophages, cytotoxic T cells, immuno-modulatory molecules, and factors of the extracellular matrix. This is a monocentric retrospective study of patients who underwent lymph-node excision during their gynecological-cancer treatment. In all, 63 non-metastatic pelvic or inguinal lymph nodes, 25 non-metastatic para-aortic lymph nodes, 13 metastatic lymph nodes, and 21 non-cancer-associated lymph nodes (normal controls) were compared for the immunohistochemical presence of CD8 cytotoxic T cells, CD163 M2 macrophages, S100A8/A9 MDSCs, PD-L1+ immune cells, and tenascin-C, which is a matrix remodeling factor. PD-L1-positive immune cells were significantly higher in the control group, in comparison to the regional and distant cancer-draining lymph nodes. Tenascin-C was higher in metastatic lymph nodes than in both non-metastatic nodes and control lymph nodes. Vulvar cancer-draining lymph nodes showed higher PD-L1 values than endometrial cancer and cervical cancer-draining lymph nodes. Endometrial cancer-draining nodes had higher CD163 values and lower CD8 values, compared to vulvar cancer-draining nodes. Regarding regional draining nodes in low- and high-grade endometrial tumors, the former showed lower S100A8/A9 and CD163 values. Gynecological cancer-draining lymph nodes are generally immunocompetent, but vulvar cancer draining nodes, as well as high-grade endometrial cancer draining nodes, are more susceptible to harboring premetastatic niche factors.

Brain Metastases from Gynecologic Malignancies

Background and Objectives: To present a series of brain metastases from gynecologic primaries and provide a summary of the relevant literature. Materials and Methods: We retrospectively review 18 patients with histologically confirmed brain metastases from gynecologic primaries and summarize the largest series of relative reports. Results: Six brain metastases were of endometrial primary and 12 of ovarian primary. In 3 cases (16.7%), diagnosis of brain metastases was made at presentation of the gynecologic primary; in the others, median time to development of brain metastasis was 34 (range, 6–115) months. Median survival after brain metastasis diagnosis was 5 (range, 1–89) months. Favorable prognostic factors were better performance status (p = 0.04) and, marginally, smaller metastasis size (p = 0.06). No differences in brain metastases between endometrial and ovarian primaries were found, except for the time interval from primary to brain metastases diagnosis, which was shorter for endometrial tumors (p = 0.05). A comprehensive summary of previous studies is provided. Conclusions: Performance status and smaller brain metastases size are good prognostic factors. Endometrial cancer brain metastases develop earlier than ovarian cancer brain metastases.

Molecular Analysis of an Abdominal Wall Cesarean Section Endometrioid Carcinoma

Malignant transformation of endometriosis is rare, and most cases concern the ovaries, while extraovarian cases are mostly found in the rectovaginal septum. Incisional adenocarcinoma is extremely rare, with only few cases reported in the literature, while their molecular profile remains unknown. Thus, we report on an abdominal wall cesarean section scar endometrioid adenocarcinoma studied by next-generation sequencing and microsatellite instability analysis.

Performance of Indocyanine Green Compared to 99mTc-Nanocolloids for Sentinel Lymph Node Detection in Early Vulvar Cancer

Study objective: The aim of this study was to evaluate the performance of indocyanine green (ICG) compared to that of the gold standard 99mtechnetium (99mTc-nanocolloids) in detecting sentinel lymph nodes (SLN) in early vulvar cancer. Material and Methods: A single-center retrospective cohort study comparing SLN detection by 99mTc-nanocolloids and ICG was performed in patients presenting early vulvar cancer (T1/2), with clinically negative nodes. All SLN showing a radioactive and/or fluorescent signal were resected. The primary endpoints were the sensitivity, positive predictive value (PPV) and false negative (FN) rate of ICG in detecting SLN compared to 99mTc-nanocolloids. Results: Thirty patients were included and 99 SLN were identified in 43 groins. Compared to 99mTc-nanocolloids, ICG had a sensitivity of 80.8% (95% CI [72.6; 88.6%]), a PPV of 96.2% (95% CI [91.8; 100%]) and a FN rate of 19.1% in detecting SLN. Seventeen (17.1%) infiltrated (positive) SLN were identified out of the 99 SLN detected. Compared to 99mTc-nanocolloids, ICG showed a sensitivity of 82.3% (95% CI [73.1; 91.5%]), a PPV of 100% and a FN rate of 17.6% (3/17) in detecting infiltrated SLN. Conclusion: Despite its many advantages, ICG cannot be used as the sole tracer for the detection of SLN in early vulvar cancer and should be employed in conjunction with 99mTc-nanocolloids.

Clinical correlation of lymphovascular invasion and Silva pattern of invasion in early-stage endocervical adenocarcinoma: proposed binary Silva classification system

Silva invasion pattern can help predict lymph node metastasis risk in endocervical adenocarcinoma. We analysed Silva pattern of invasion and lymphovascular invasion to determine associations with clinical outcomes in stage IA and IB1 endocervical adenocarcinomas. International Federation of Gynecology and Obstetrics (FIGO; 2019 classification) stage IA-IB1 endocervical adenocarcinomas from 15 international institutions were examined for Silva pattern, presence of lymphovascular invasion, and other prognostic parameters. Lymph node metastasis status, local/distant recurrences, and survival data were compared using appropriate statistical tests. Of 399 tumours, 152 (38.1%) were stage IA [IA1, 77 (19.3%); IA2, 75 (18.8%)] and 247 (61.9%) were stage IB1. On multivariate analysis, lymphovascular invasion (p=0.008) and Silva pattern (p<0.001) were significant factors when comparing stage IA versus IB1 endocervical adenocarcinomas. Overall survival was significantly associated with lymph node metastasis (p=0.028); recurrence-free survival was significantly associated with lymphovascular invasion (p=0.002) and stage (1B1 versus 1A) (p=0.002). Five and 10 year overall survival and recurrence-free survival rates were similar among Silva pattern A cases and Silva pattern B cases without lymphovascular invasion (p=0.165 and p=0.171, respectively). Silva pattern and lymphovascular invasion are important prognostic factors in stage IA1-IB1 endocervical adenocarcinomas and can supplement 2019 International Federation of Gynecology and Obstetrics staging. Our binary Silva classification system groups patients into low risk (patterns A and B without lymphovascular invasion) and high risk (pattern B with lymphovascular invasion and pattern C) categories.