Fallopian tube cytology as a diagnostic tool for adnexal malignancy: the CytoSaLPs score.

INTRODUCTION: During the past decade, the theory that high-grade extrauterine pelvic tumors originate from the fallopian tube has been strongly suggested. Our study aims to illuminate the possible role of tubal cytology as an accessory identification tool for gynecologic extrauterine malignancies, allowing in the long term the implementation of population-level cytologic tube evaluation during all benign gynecologic surgeries that do not result in salpingectomy. MATERIALS AND METHODS: We ex vivo collect salpingeal epithelial cells from the fibria directly from fresh fallopian tube specimens from women undergoing salpingectomy for any indication. The cytomorphologic characteristics of the salpingeal cells are subsequently evaluated and categorized into malignant and non-malignant. Finally, the ipsilateral adnexa are examined with the SEE-FIM (Sectioning and Extensively Examining the FIMbriated End) protocol and the pathology reports are corelated with the cytologic findings. Our research protocol is ongoing and is designed to include a total of 300 patients in order to confirm the sensitivity and specificity of salpingeal cytology as a method in the early diagnosis of extrauterine gynecologic malignancies. RESULTS: So far, we have obtained 343 salpingeal brushings from a total of 214 patients. The sensitivity of cytology regarding distinguishing malignant from non-malignant tumors is 69.64% (95% CI: 55.90%-81.22%), and its specificity 75.96% (95% CI: 70.59%-80.79%). Cytology's positive predictive value (PPV) is 16.33% (95% CI: 12.57%-20.67%), while the negative predictive value (NPP) reached 92.77% (95% CI: 89.56%-95.04%). In general, the diagnostic accuracy of the cytologic evaluation reaches 74.93% (95% CI: 66.99%-79.43%). CONCLUSIONS: Salpingeal cytomorphologic evaluation appears to be a promising method for early detection of adnexal cancer.

Follow the River to the Lake: Sentinel Lymph Node Identification Using the Robotic Platform in Endometrial Cancer Patients.

Sentinel lymph node biopsy for the management of endometrial cancer patients has been introduced into surgical staging of these patients. Several articles and guidelines have evaluated and found sentinel lymph node biopsy as an efficient and oncological safe procedure. The aim of this article is to highlight the most important tips and tricks in order to optimize sentinel lymph node identification and dissection based on our experience. Each step of sentinel lymph node identification technique is analyzed. Tips and tricks, such as site and time of indocyanine green dye injection are essential in optimal identification of sentinel lymph node in patients with endometrial cancer. The standardization of the technique and the recognition of anatomic landmarks are essential as they lead to an improved and effective identification of sentinel lymph node.

The Utility of Fallopian Tube Cytology in the Early Detection of Extrauterine Serous Gynecological Malignancies: A Narrative Literature Review.

INTRODUCTION: The aim of the study was to analyze the published evidence for the use of fallopian tube brush cytology for the early detection of extrauterine serous gynecological cancer. METHODS: We systematically searched the literature and, additionally, cross-checked on the bibliographies of selected articles. The inclusion criteria involved studies assessing the utility of fallopian tube brush cytology and its applications in the diagnosis, screening, or follow-up of extrauterine serous gynecological cancer. RESULTS: The search strategy resulted in 21 abstracts or full-text articles, 5 of which met the inclusion criteria. The year of publication ranged from 2016 to 2022, and a total of 193 fallopian tube samples were investigated. Cytobrush, Tubebrush©, and Cytuity™ were used to obtain salpingeal samples for liquid-based cytology evaluation. CONCLUSIONS: Our findings indicate that, at present, there is a lack of satisfying evidence-based data in the literature which would support the implementation of fallopian tube brush cytology as an adjunctive tool for early detection of extrauterine serous gynecological cancer. Thus, we believe that there is need for well-designed clinical studies to assess the effectiveness and diagnostic accuracy of the method as well as to validate the cytological criteria for the diagnosis and prediction of gynecological malignancies.

Does Obesity Forbid Robotic Gynecological Surgeries? An Urban Legend.

Introduction: Obesity is a worldwide problem that considered to be a challenge in optimal surgical management. A breakthrough in the technologies of minimal invasive surgery over the last ten years has turned robotic approach into the widespread method for surgical management of obese population. Aim: In this study we emphasize the benefits of the robotic assisted laparoscopy versus open laparotomy and conventional laparoscopy in obese women with gynecological disorders. Methods: We conducted a single center experience retrospective study of obese women (BMI 30 Kg/m2) that underwent robotic assisted gynecologic procedures from January 2020 till January 2023. "Iavazzo" score was used in order to predict preoperatively the feasibility of robotic approach as well as the overall operative time. The perioperative management a well as the postoperative course of obese patients were documented and analyzed. Results: 93 obese women underwent robotic surgical management for benign and malignant gynecological disorders. 62 of these women had BMI between 30 and 35 kg/m2 and 31 had BMI 35 kg/m2. None of them was converted into laparotomy. All of the patients had a smooth postoperative course without any complications and were discharged at the first postoperative day. Mean operative time was 150 min. Conclusions: Our 3-year experience in robotic-assisted gynecologic surgery in obese patients has revealed numerous benefits concerning perioperative management and postoperative rehabilitation.

CytoSaLPs score: a promising new tool for the detection and screening of extrauterine high grade serous carcinoma.

BACKGROUND: A recent theory supports that high-grade serous epithelial ovarian cancer derives from the fimbrial end of the fallopian tube and during the last decade, a few studies have examined the fallopian tube cytology. Our study aims to determine the cytomorphological characteristics of both benign and non-benign salpingeal samples, in order to establish fallopian cytology as a valuable diagnostic test for women with high risk for development of ovarian/fallopian/peritoneal cancer. METHODS: Our study included patients undergoing salpingoophorectomy or total hysterectomy and salpingoophorectomy for any gynecological pathology. Using a soft brush, fallopian tube smears from the fimbrial end were collected ex vivo. The Cytologists of our Institution described the morphological characteristics of the fallopian cells by adopting a proposed Table, which had a calibration system ranging from 3 to 29. This Table is referred to as the CytoSaLPs Score. Our study compared the two diagnostic cytological methods, the one of the conventional cytology and the other using the CytoSaLPs Score, having as gold standard the tubal's pathological findings. RESULTS: A total of 230 tubal specimens from 144 patients were included in this study. The Score's mean for the benign and non-benign arm was 12.8 and 18.7 respectively. The cut-off point for both arms was 16.5. The CytoSaLPs Score tool showed significantly higher specificity (87.50% vs. 75.96, p-value < 0.001) and positive predictive value PPV (40.91% vs. 26.47%, p-value < 0.001) compared to conventional cytology. Regarding the accuracy, the Score's superiority is highlighted (86.96% vs. 76.52%, p-value < 0.001). CONCLUTIONS: The evaluation of tubal cytology using the CytoSaLPs Score could be used as a reliable diagnostic method. Further evaluation with larger studies is warranted.

High grade neuroendocrine carcinoma of the breast, first line and maintenance immunotherapy.

Small cell carcinomas (SCCs) are poorly differentiated neuroendocrine tumors that arise predominantly in the lung and gastrointestinal tract (GIT). Neuroendocrine carcinomas can occur in a variety of extrapulmonary sites throughout the body, including breast, larynx, GIT, prostate, urinary bladder, ovary and cervix. This is a case report of a 55-year-old Asian female patient with metastatic high-grade neuroendocrine carcinoma of unknown origin that responded notably to off-label nivolumab maintenance treatment after first-line carboplatin - etoposide chemotherapy and radiation. After 2 years of nivolumab after platinum-based chemotherapy results from PET-CT showed no residual disease and we proceeded to mastectomy.

Tall cell carcinoma with reversed polarity: A case report of a very rare breast tumor entity and mini-review.

Tall cell carcinoma with reversed polarity (TCCRP) is a very rare variant of carcinoma of the breast, resembling the tall cell variant of papillary thyroid carcinoma, first described in 2003, recently recognized as a separate entity in the 5th edition of the WHO (World Health Organization) Blue Book Classification of breast tumors with alternative terminology of tall cell variant of papillary breast carcinoma and solid papillary carcinoma with reversed polarity. Here, we report an additional case of this rare tumor in a 71-year-old woman, and the problems correlating with its diagnosis.

gamma-H2AX: A potential biomarker in breast cancer.

Histone H2AX undergoes phosphorylation as an answer to DNA double-strand breaks, which in turn are part of the oncogenic procedure. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. The aim of this study was to evaluate the clinical significance of gamma-H2AX expression in breast cancer. Gamma-H2AX expression in tissues from 110 breast cancer patients was analyzed by immunohistochemistry and correlated with clinicopathological variables. Greater tumor size, higher grade, and the number of affected lymph nodes are significantly associated with greater values of gamma-H2AX. In addition, gamma-H2AX differs significantly among patients' International Federation of Gynecology and Obstetrics stage. Higher values of estrogen receptor and progesterone receptor are significantly associated with lower gamma-H2AX values. In conclusion, a positive association between gamma-H2AX expression and infaust histopathological parameters was observed.

Coexistence of Gastric Cancer and Multiple Small Gastrointestinal Stromal Tumors: Report of a Unique Case and Review of the Literature.

BACKGROUND: In recent years, the synchronous occurrence of tumors of different histotypes arising in the same organ has been reported more frequently in the literature. The simultaneous development of adenocarcinoma and gastrointestinal stromal tumor (GIST) has been documented rarely. SUMMARY: The coexistence of primary gastric adenocarcinoma and GIST has been detected incidentally on gastric mucosa, serosa or occasionally intramurally, at surgery, or gastroscopy for other reasons. We present a case of a 79-year-old male patient who underwent surgery for an advanced gastric carcinoma, where multiple nodules of GIST were incidentally discovered during the work-up of his gastrectomy specimen. KEY MESSAGE: GISTs range from small "low-risk" tumors to sarcomas. Small GISTs are found incidentally during unrelated surgery or autopsy. Multiple GISTs are extremely rare and usually associated with hereditary diseases. PRACTICAL IMPLICATIONS: In any case of gastrointestinal neoplasm, the surgeon and pathologist should be alert to perform a thorough investigation. Our case could provide further awareness and insight into the entity of concurrent tumors.

Primary Alveolar Rhabdomyosarcoma of the Breast in an Adult: An Extremely Rare Case.

Sarcomas of the breast constitute less than 1% of all malignant breast tumors and primary rhabdomyosarcoma (RMS) is a very rare entity with limited case reports in the literature. RMS is common in children and adolescents and rare in adults. Primary RMS arising from the breast is exceedingly rare in adults. We report a case of a primary RMS of the breast in a 60-year-old woman, who presented in an early stage, mimicking invasive ductal carcinoma clinically and is in complete remission after three years of diagnosis and one year of treatment.

A very rare case of renal cell carcinoma metastasis to spermatic cord and a condensed literature review.

INTRODUCTION: Renal cell carcinoma (RCC) is proved to be the ninth most common malignancy. Two-third of the patients suffering from RCC will present metastases. Secondary metastases of RCC to spermatic cord are very rare. PRESENTATION OF CASE: In this report we present the case of a patient with renal cell carcinoma with metachronous metastasis to the spermatic cord occurring two years after the initial diagnosis of the disease. DISCUSSION: Our patient was treated according to EAU guidelines. The metastatic tumor was diagnosed accidentally, in contrast to the previous follow-up exams which show no disease in the meantime. Moreover, the histological examination of the spermartic cord tumor illustrated tumor thrombus. The former examination results along with the anatomical and embryological relations of renal and spermatic cord structures indicate a hypothesis about the mechanism of this metastasis' route. CONCLUSION: Our case is of great interest, since such cases are very few in the international literature. Therefore the presentation of this case as well as its implications should be made to the global surgery community.

Protein expression patterns of cell cycle regulators in operable breast cancer.

BACKGROUND-AIM: To evaluate the prognostic role of elaborate molecular clusters encompassing cyclin D1, cyclin E1, p21, p27 and p53 in the context of various breast cancer subtypes. METHODS: Cyclin E1, cyclin D1, p53, p21 and p27 were evaluated with immunohistochemistry in 1077 formalin-fixed paraffin-embedded tissues from breast cancer patients who had been treated within clinical trials. Jaccard distances were computed for the markers and the resulted matrix was used for conducting unsupervised hierarchical clustering, in order to identify distinct groups correlating with prognosis. RESULTS: Luminal B and triple-negative (TNBC) tumors presented with the highest and lowest levels of cyclin D1 expression, respectively. By contrast, TNBC frequently expressed Cyclin E1, whereas ER-positive tumors did not. Absence of Cyclin D1 predicted for worse OS, while absence of Cyclin E1 for poorer DFS. The expression patterns of all examined proteins yielded 3 distinct clusters; (1) Cyclin D1 and/or E1 positive with moderate p21 expression; (2) Cyclin D1 and/or E1, and p27 positive, p53 protein negative; and, (3) Cyclin D1 or E1 positive, p53 positive, p21 and p27 negative or moderately positive. The 5-year DFS rates for clusters 1, 2 and 3 were 70.0%, 79.1%, 67.4% and OS 88.4%, 90.4%, 78.9%, respectively. CONCLUSIONS: It seems that the expression of cell cycle regulators in the absence of p53 protein is associated with favorable prognosis in operable breast cancer.

Peritoneal Keratin Granulomatosis Associated with Endometrioid Adenocarcinoma of the Uterine Corpus in a Woman with Polycystic Ovaries: A Potential Pitfall-A Case Report and Review of the Literature.

Peritoneal keratin granulomatosis is a rare condition included under granulomatous lesions of the peritoneum. It can be secondary to neoplasms of the female genital tract and can mimic carcinomatosis intraoperatively. A case of a 40-year-old woman with a history of polycystic ovaries and a chief complaint of vaginal bleeding is presented. She was diagnosed with endometrioid adenocarcinoma with squamous differentiation in endometrial curettings. Intraoperatively, many peritoneal nodules were found, interpreted as peritoneal carcinomatosis. The woman underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, bilateral pelvic lymphadenectomy, and appendicectomy. Multiple biopsies were taken, as well as peritoneal washings. Microscopic examination revealed multiple keratin granulomas on the serosal surface of the ovaries, fallopian tubes, appendix, and omentum. Lymph node metastasis was not found. Peritoneal keratin granulomas (PKGs) have been reported in cases of endometrioid adenocarcinoma with squamous differentiation of the uterine corpus, ovary, and atypical adenomyoma. It should be noted that the prognosis of cases of peritoneal keratin granulomas without viable tumor cells is favourable and that the histologic examination is essential for its diagnosis. We report a case of PKG in a patient with endometrial carcinoma with squamous differentiation, being the first in a woman with polycystic ovaries.

Differential response of immunohistochemically defined breast cancer subtypes to anthracycline-based adjuvant chemotherapy with or without paclitaxel.

BACKGROUND: The aim of the present study was to investigate the efficacy of adjuvant dose-dense sequential chemotherapy with epirubicin, paclitaxel, and CMF in subgroups of patients with high-risk operable breast cancer, according to tumor subtypes defined by immunohistochemistry (IHC). MATERIALS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 1,039 patients participating in two adjuvant dose-dense sequential chemotherapy phase III trials were centrally assessed in tissue micro-arrays by IHC for 6 biological markers, that is, estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, cytokeratin 5 (CK5), and EGFR. The majority of the cases were further evaluated for HER2 amplification by FISH. Patients were classified as: luminal A (ER/PgR-positive, HER2-negative, Ki67(low)); luminal B (ER/PgR-positive, HER2-negative, Ki67(high)); luminal-HER2 (ER/PgR-positive, HER2-positive); HER2-enriched (ER-negative, PgR-negative, HER2-positive); triple-negative (TNBC) (ER-negative, PgR-negative, HER2-negative); and basal core phenotype (BCP) (TNBC, CK5-positive and/or EGFR-positive). RESULTS: After a median follow-up time of 105.4 months the 5-year disease-free survival (DFS) and overall survival (OS) rates were 73.1% and 86.1%, respectively. Among patients with HER2-enriched tumors there was a significant benefit in both DFS and OS (log-rank test; p = 0.021 and p = 0.006, respectively) for those treated with paclitaxel. The subtype classification was found to be of both predictive and prognostic value. Setting luminal A as the referent category, the adjusted for prognostic factors HR for relapse for patients with TNBC was 1.91 (95% CI: 1.31-2.80, Wald's p = 0.001) and for death 2.53 (95% CI: 1.62-3.60, p<0.001). Site of and time to first relapse differed according to subtype. Locoregional relapses and brain metastases were more frequent in patients with TNBC, while liver metastases were more often seen in patients with HER2-enriched tumors. CONCLUSIONS: Triple-negative phenotype is of adverse prognostic value for DFS and OS in patients treated with adjuvant dose-dense sequential chemotherapy. In the pre-trastuzumab era, the HER2-enriched subtype predicts favorable outcome following paclitaxel-containing treatment.

Primary osteogenic sarcoma of the breast: cytomorphologic study of 3 cases with histologic correlation.

BACKGROUND: Primary osteogenic sarcomas of the breast are extremely rare neoplasms. The histologic and cytologic features are comparable to those of their soft tissue and skeletal counterparts. To assess the utility of fine needle aspiration (FNA) in preoperative identification of osteogenic sarcomas, we retrospectively reviewed the FNA findings of 3 cases diagnosed in our hospital over 2 1/2 years. CASES: Three women, aged 48, 55 and 76 years, presented with a palpable lump of a few months' duration in their breasts. FNA was indicative of malignancy, and mastectomy with ipsilateral axillary lymph node dissection was performed. The cytologic features were of hypocellular or hypercellular smears with pleomorphic cells; scarce or abundant metachromatic amorphous material, suggestive of osteoid; osteoclast-like giant cells; and stromal fragments. CONCLUSION: Although cytologic features can be suggestive of osteosarcoma in the appropriate clinical setting, prompt preoperative diagnosis of malignancy in FNA samples of these tumors can avoid undertreatment, because mammographic and clinical findings are in many cases confused with the features of a benign lesion, more specifically calcified fibroadenoma.

Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors--a surrogate marker?

BACKGROUND: The number of mitoses and, thus, the proliferative capacity of a tumor is one of the most crucial variables for tumor grading. The Ki-67 nuclear antigen may be considered as an alternative to mitotic counts in grading schemes and as a single parameter that can be used in fine-needle aspirates and small biopsies. METHODS: Immunohistochemistry using the anti-Ki-67 antibody MIB-1 was performed on 434 breast carcinoma specimens from the International Breast Cancer Study Group (formerly Ludwig) Trial V. Three groups based on Ki-67 percent were used to replace the mitotic counts component in the Nottingham grade (NHG) to produce the Nottingham/Ki-67 grade (NKG) and to assess Ki-67 as a single parameter. RESULTS: In both the lymph node positive subgroup and the lymph node negative subgroup, the NKG and Ki-67 group was correlated significantly with Bloom-Richardson grade (BRG), NHG, and Nottingham type. Tumor size in the lymph node negative cohort and estrogen receptor status, progesterone receptor status, and c-erbB-2 expression in the lymph node positive cohort also were correlated significantly with NKG. Ki-67 percentage was correlated significantly with c-erbB-2 expression in the lymph node positive cohort only. NKG was similar to BRG and NHG when it was evaluated for prognostic significance. Patients with higher categoric Ki-67 percentages had worse overall and disease free survival in all groups except for the untreated, lymph node negative group. CONCLUSIONS: Ki-67 detection represents a valuable tool and is a good objective substitute for mitotic counts when used in a grading system. When it is used alone, Ki-67 detection provides valuable information, although it is necessary to combine this with other parameters in the study of core biopsies and fine-needle aspirates.