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Simple Summary: The rate of positive parametrial lymph nodes in a series of apparent early-stage cervical cancer patients undergoing bilateral sentinel lymph node mapping was 3.1%. After ultrastaging of parametrial tissue, no occult micrometastasis was detected. Occult parametrial involvement in apparent early-stage cervical cancer might be overlooked with standard pathologic assessment. The primary endpoint of the present study was to assess the rate of positive parametrial lymph nodes and of microscopic continuous or discontinuous parametrial involvement. This is a retrospective, single-center, observational study including patients with FIGO 2018 stage IA1–IIA1 and IIIC1p in whom bilateral sentinel lymph node (SLN) detection and ultrastaging of SLN were performed according to institutional protocol, with surgery as primary treatment performed between May 2017 and February 2021, as well as type B2/C1/C2 (Querleu–Morrow) radical hysterectomy and usual histology (squamous cell, adenocarcinoma and adenosquamous carcinoma). Thirty-one patients were included in the study period. Six (18.7%) patients had metastatic lymph nodes, of whom four had only SLN metastasis (two cases of ITC, one case of micrometastasis and one case of macrometastasis). We found a macroscopic deposit of cancer cells in the parametrial lymph node of one patient (3.1%). There was a positive statistical correlation between the incidence of parametrial lymph node involvement and the metastatic pelvic lymph nodes (p = 0.038). When performed per patient, the sensitivity, negative predictive value and accuracy of parametrial lymph node involvement in predicting pelvic lymph node metastasis were 16.7%, 83.3% and 83.9%, respectively. Ultrastaging of parametrial tissue did not identify any occult continuous or discontinuous parametrial metastasis. In conclusion, the incidence of lymph node parametrial involvement in a retrospective series of early-stage cervical cancer was 3.1% of all included patients. Lymph node involvement of the parametrium was associated with lymph node metastasis. The sensitivity of parametrial lymph node involvement to predict pelvic lymph node metastasis was low. The lack of parametrial involvement revealed by parametrial ultrastaging could be related to the number of patients with tumors with a pathologic diameter < 2 cm (54.8%). Further prospective studies are needed to analyze the role of parametrial ultrastaging in early-stage cervical cancer and to assess whether it can be considered the "sentinel" of the sentinel lymph node. [ABSTRACT FROM AUTHOR]

Background. Gynecological neuroendocrine neoplasms (NENs) are extremely rare, accounting for 1.2–2.4% of the NENs. The aim of this study was to test cervical NENs for novel markers of potential utility for differential diagnosis and target therapy. Methods. All cases of our center (n = 16) were retrieved and tested by immunohistochemistry (IHC) for 12 markers including markers of neuroendocrine differentiation (chromogranin A, synaptophysin, CD56), transcription factors (CDX2 and TTF1), proteins p40, p63, p16INK4a, and p53, somatostatin receptors subtypes (SST2-SST5) and the proliferation marker Ki67 (MIB1). Results. All cases were poorly differentiated neuroendocrine carcinomas (NECs), 10 small cell types (small cell–neuroendocrine carcinomas, SCNECs) and 6 large cell types (large cell–neuroendocrine carcinomas, LCNECs); in 3 cases a predominant associated adenocarcinoma component was observed. Neuroendocrine cancer cells expressed at least 2 of the 3 tested neuroendocrine markers; p16 was intensely expressed in 14 (87.5%) cases; SST5 in 11 (56.25%, score 2–3, in 9 cases); SST2 in 8 (50%, score 2–3 in 8), CDX2 in 8 (50%), TTF1 in 5 (31.25%), and p53 in 1 case (0.06%). P63 and p40 expressions were negative, with the exception of one case that showed moderate expression for p63. Conclusions. P40 is a more useful marker for the differential diagnosis compared to squamous cell carcinoma. Neither CDX2 nor TTF1 expression may help the differential diagnosis versus potential cervical metastasis. P16 expression may suggest a cervical origin of NEC; however, it must be always integrated by clinical and instrumental data. The expression of SST2 and SST5 could support a role for SSAs (Somatostatin Analogues) in the diagnosis and therapy of patients with cervical NECs. [ABSTRACT FROM AUTHOR]