Publications by authors named "Angela Santoro"

106 Publications

Current Prognostic and Predictive Biomarkers for Endometrial Cancer in Clinical Practice: Recommendations/Proposal from the Italian Study Group.

Front Oncol 2022 8;12:805613. Epub 2022 Apr 8.

Pathology Unit, "Cannizzaro" Hospital, Catania, Italy.

Endometrial carcinoma (EC) is the most common gynecological malignant disease in high-income countries, such as European countries and the USA. The 2020 edition of the World Health Organization (WHO) Classification of Tumors of the Female Genital Tract underlines the important clinical implications of the proposed new histomolecular classification system for ECs. In view of the substantial genetic and morphological heterogeneity in ECs, both classical pthological parameters and molecular classifiers have to be integrated in the pathology report. This review will focus on the most commonly adopted immunohistochemical and molecular biomarkers in daily clinical characterization of EC, referring to the most recent published recommendations, guidelines, and expert opinions.
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http://dx.doi.org/10.3389/fonc.2022.805613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024340PMC
April 2022

Expression of Beta-Catenin, Cadherins and P-Runx2 in Fibro-Osseous Lesions of the Jaw: Tissue Microarray Study.

Biomolecules 2022 04 16;12(4). Epub 2022 Apr 16.

Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy.

Fibrous dysplasia (FD) and hyperparathyroidism-jaw tumor syndrome (HPT-JT) are well-characterized benign bone fibro-osseous lesions. The intracellular mechanism leading to excessive deposition of fibrous tissue and alteration of differentiation processes leading to osteomalacia have not yet been fully clarified. Tissue Microarray (TMA)-based immunohistochemical expression of β-catenin, CK-AE1/AE3, Ki-67, cadherins and P-Runx2 were analyzed in archival samples from nine patients affected by FD and HPT-JT and in seven controls, with the aim of elucidating the contribution of these molecules (β-catenin, cadherins and P-Runx2) in the osteoblast differentiation pathway. β-catenin was strongly upregulated in FD, showing a hyper-cellulated pattern, while it was faintly expressed in bone tumors associated with HPT-JT. Furthermore, the loss of expression of OB-cadherin in osteoblast lineage in FD was accompanied by N-cadherin and P-cadherin upregulation ( < 0.05), while E-cadherin showed a minor role in these pathological processes. P-Runx2 showed over-expression in six out of eight cases of FD and stained moderately positive in the rimming lining osteoblasts in HPT-JT syndrome. β-catenin plays a central role in fibrous tissue proliferation and accompanies the lack of differentiation of osteoblast precursors in mature osteoblasts in FD. The study showed that the combined evaluation of the histological characteristics and the histochemical and immunohistochemical profile of key molecules involved in osteoblast differentiation are useful in the diagnosis, classification and therapeutic management of fibrous-osseous lesions.
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http://dx.doi.org/10.3390/biom12040587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024991PMC
April 2022

Malignant phyllodes tumor of the breast: a systematic review.

Pathologica 2022 Apr 13;114(2):111-120. Epub 2022 Apr 13.

Division of Anatomic Pathology and Histology Catholic University Rome, Italy.

Phyllodes tumors (PT) are fibroepithelial neoplasms of the breast showing a peculiar leaf-like appearance. They account for 0.3 to 1% of all primary breast tumors and 2.5% of all fibroepithelial breast tumors. PT are classified into benign, borderline and malignant based upon their stromal morphology with a distribution of 60%, 20%, and 20%, respectively. Malignant PT of the breast constitute an uncommon challenging group of fibroepithelial neoplasms. They have a relatively high tendency to recur, although distant metastasis is uncommon, and nearly exclusive to malignant PT. Adequate surgical resection remains the standard approach to achieve maximal local control. Giant malignant PT are rare and a pose a diagnostic dilemma for pathologists, especially when comprised of sarcomatous elements. This review highlights the morphological features of PT detected in cytology and histology specimens and discusses diagnostic pitfalls and differential diagnosis.
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http://dx.doi.org/10.32074/1591-951X-754DOI Listing
April 2022

Accuracy of cytological examination of Tao brush endometrial sampling in diagnosing endometrial premalignancy and malignancy.

Int J Gynaecol Obstet 2022 Apr 1. Epub 2022 Apr 1.

Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, Italy.

Although Tao brush has become one of the most studied and used endometrial cytological samplers, concerns remain about the adequacy of the cytological sample compared with definitive histology. We aimed to assess accuracy of cytological examination from Tao brush sampling in diagnosing endometrial premalignancy and malignancy through a systematic review and meta-analysis. Seven electronic databases were searched from January 2000 to July 2021 for all studies which allowed assessment of accuracy of Tao brush in diagnosing endometrial premalignancy and malignancy. We calculated sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on summary receiver operating characteristic (SROC) curve. Five studies with 774 patients were included. In diagnosing endometrial premalignancy and malignancy, cytological examination from Tao brush endometrial sampling showed pooled sensitivity of 0.95 (95% CI, 0.90-0.98), specificity of 0.92 (95% CI, 0.90-0.94), LR+ of 12.73 (95% CI, 3.94-41.18), LR- of 0.09 (95% CI, 0.05-0.18), DOR of 184.84 (95% CI, 24.37-1401.79), AUC of 0.9757 (standard error: 0.013). In conclusion, cytological examination from Tao brush seems to have a high diagnostic accuracy and might be proposed as both screening and diagnostic tool. However, further studies are necessary to confirm these findings.
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http://dx.doi.org/10.1002/ijgo.14204DOI Listing
April 2022

Prognostic Value of Chemotherapy Response Score (CRS) Assessed on the Adnexa in Ovarian High-Grade Serous Carcinoma: A Systematic Review and Meta-Analysis.

Diagnostics (Basel) 2022 Mar 4;12(3). Epub 2022 Mar 4.

Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Roma, Italy.

Background: chemotherapy response score (CRS) is widely used to assess the response of ovarian high-grade serous carcinoma (HGSC) to chemotherapy and is based on pathological examination of omental specimens. We aimed to assess the prognostic value of CRS assessed on the uterine adnexa.

Methods: a systematic review and meta-analysis were performed by searching three electronic databases from 2015 inception to September 2021. We included all studies reporting either hazard ratio (HR) with 95% confidence interval (CI) for progression-free survival (PFS) or primary PFS data, for both adnexal and omental CRS in HGSC. HRs with 95% CI were extracted and pooled by using a significant -value < 0.05. Statistical heterogeneity was assessed by using Higgins' I2.

Results: six studies with 691 HGSC patients were included. Adnexal CRS3 vs. CRS1-2 significantly stratified PFS, with a HR of 0.572 (0.447-0.733; < 0.001). Omental CRS3 vs. CRS1-2 significantly stratified PFS with a similar HR (HR = 0.542; 95% CI 0.444-0.662; < 0.001). Statistical heterogeneity was 0% in both analyses.

Conclusions: adnexal CRS significantly stratifies PFS in HGSC and might be used when omental CRS is not assessable.
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http://dx.doi.org/10.3390/diagnostics12030633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946962PMC
March 2022

TLR4 Expression in Ex-Lichenoid Lesions-Oral Squamous Cell Carcinomas and Its Surrounding Epithelium: The Role of Tumor Inflammatory Microenvironment.

Biomolecules 2022 02 28;12(3). Epub 2022 Feb 28.

Pathological Anatomy Unit, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.

Toll-like receptors (TLRs) regulate innate and adaptive immune responses. Moreover, TLRs can induce a pro-survival and pro-proliferation response in tumor cells. This study aims to investigate the expression of TLR4 in the epithelium surrounding oral squamous cell carcinomas (OSCC) in relation to its inflammatory microenvironment. This study included 150 human samples: 30 normal oral control (NOC), 38 non-lichenoid epithelium surrounding OSCC (NLE-OSCC), 28 lichenoid epithelium surrounding OSCC (LE-OSCC), 30 OSCC ex-non oral lichenoid lesion (OSCC Ex-NOLL), and 24 OSCC ex-oral lichenoid lesion (OSCC Ex-OLL). TLR4 expression was investigated by immunohistochemistry and the percentage of positive cells was quantified. In addition, a semiquantitative analysis of staining intensity was performed. Immunohistochemical analysis revealed that TLR4 is strongly upregulated in LE-OSCC as compared to normal control epithelium and NLE-OSCC. TLR4 expression was associated with the inflammatory environment, since the percentage of positive cells increases from NOC and NLE-OSCC to LE-OSCC, reaching the highest value in OSCC Ex-OLL. TLR4 was detected in the basal third of the epithelium in NLE-OSCC, while in LE-OSCC, TLR4 expression reached the intermediate layer. These results demonstrated that an inflammatory microenvironment can upregulate TLR4, which may boost tumor development.
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http://dx.doi.org/10.3390/biom12030385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945442PMC
February 2022

Endometrial giant cell carcinoma: new insights from a morphological, immunohistochemical, and molecular analysis of three cases.

Virchows Arch 2022 Mar 19. Epub 2022 Mar 19.

Gynecopathology and Breast Pathology Unit, Department of Woman and Child's Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Herein, we present a morphological, immunohistochemical, and molecular analysis of three cases of endometrial giant cell carcinoma (EGCC) with a literature review. Patient age was 55 to 76 years. The tumors were limited to the uterus and showed dyshesive, bizarre giant cells with numerous atypical mitoses. Minor components were low-grade endometrioid, spindled/myxoid (case nos. 1 and 2), serous (case no. 3), and undifferentiated (all cases). The giant cells were e-cadherin-, cytokeratins/EMA + (focal/multifocal), hormone receptors + (focal/multifocal), vimentin + , p16 + (diffuse), CD68-, α-FP-, β-HCG-, muscle markers-, CD10-, and ERG-. Case no. 3 was p53-abnormal. All cases were mismatch repair-proficient and microsatellite-stable. No POLE mutations were detected. Based on our and previous reports, EGCC is often accompanied by a conventional carcinomatous component (mostly endometrioid) and shows partial loss epithelial markers and negativity for specific differentiation markers. EGCC shows evident similarities to both undifferentiated/dedifferentiated carcinoma and carcinosarcoma and should be managed similarly. Unlike the latter two, EGCC might preferentially derive from "no-specific-molecular-profile" carcinomas.
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http://dx.doi.org/10.1007/s00428-022-03310-xDOI Listing
March 2022

Editorial: Future Perspectives of Sentinel Node Mapping in Gynecological Oncology.

Front Oncol 2022 25;12:809765. Epub 2022 Feb 25.

Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.

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http://dx.doi.org/10.3389/fonc.2022.809765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8913892PMC
February 2022

Clinicopathological Features Associated with Microsatellite Instability/Mismatch Repair Deficiency in Uterine Carcinosarcoma: A Quantitative Systematic Review.

Pathobiology 2022 Mar 1:1-7. Epub 2022 Mar 1.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.

Introduction: Recent studies suggested that microsatellite instability/mismatch repair deficiency (MSI/MMR-d) might define a clinicopathologically distinct subset of uterine carcinosarcomas (UCSs).

Objective: The aim of this study was to compare clinicopathological features between MSI/MMR-d and microsatellite-stable/mismatch repair-proficient (MSS/MMR-p) UCSs.

Methods: A quantitative systematic review was performed by searching electronic databases from January 2000 to January 2021. All studies assessing MSI/MMR status in UCS were included. Odds ratio (OR) with a significant two-tailed p value <0.05 was used to assess the association of MSI/MMR-d with clinicopathological features.

Results: Eleven studies with 783 patients were included. MSI/MMR-d was directly associated with endometrioid (pure: p < 0.001; pure + mixed: p < 0.001), undifferentiated/dedifferentiated (p < 0.001), and clear cell carcinoma component (p = 0.046), and inversely associated with age >60 (p = 0.034), serous carcinoma component (pure: p < 0.001; pure + mixed: p < 0.001), heterologous sarcoma component (p = 0.027), TP53-mutation/p53-abnormal expression (p < 0.001), and recurrence (p < 0.001). MSI/MMR-d showed no significant association with advanced FIGO stage (OR = 1.259; p = 0.517), low-grade carcinoma component (pure: p = 0.596; pure + mixed: p = 0.307), mixed carcinoma component (p = 1), and proportion of patients "dead of disease" (p = 0.352), "alive with disease" (p = 1) or with "no evidence of disease" (p = 0.458).

Conclusion: MSI/MMR-d UCSs show younger age, more common endometrioid, undifferentiated or clear cell carcinoma component, and less common serous carcinoma component, heterologous sarcoma component, and TP53 mutation than MSS/MMR-p UCSs. Given the discrepancy between recurrence rate and oncologic outcomes at the last follow-up, further studies are necessary to define whether MSI/MMR-d UCSs have better prognosis.
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http://dx.doi.org/10.1159/000521876DOI Listing
March 2022

Assessing Post-Treatment Pathologic Tumor Response in Female Genital Tract Carcinomas: An Update.

Front Oncol 2022 10;12:814989. Epub 2022 Feb 10.

Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

In the last decades, several new therapeutic strategies have been introduced in the field of gynecologic oncology. These include neoadjuvant chemotherapy for high-grade serous tubo-ovarian carcinoma, hormonal fertility-sparing strategies for endometrial cancer, pressurized intraperitoneal aerosol chemotherapy (PIPAC) for surgically incurable peritoneal metastasis, and neoadjuvant treatments for locally advanced cervical carcinomas. All these recent advances lead to the development of novel scoring systems for the evaluation of pathological response related to specific treatments. In this regard, pathological evaluation of the morphological modifications related to these treatments and the definition of a tumor regression grading score have been introduced in clinical practice in order to achieve a more efficient prognostic stratification of patients affected by gynecological malignancies. The aim of the present paper is to provide a detailed review on the post-treatment pathological scoring systems in patients affected by gynecological malignancies.
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http://dx.doi.org/10.3389/fonc.2022.814989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866564PMC
February 2022

Pilomatrix-like High-grade Endometrioid Carcinoma is a Morphologically and Immunophenotypically Distinct Entity and May Show Mismatch Repair Deficiency.

Int J Gynecol Pathol 2022 Feb 18. Epub 2022 Feb 18.

Gynecopathology and Breast Pathology Unit Department of Woman and Child's Health and Public Health Sciences, Agostino Gemelli University Polyclinic (D.A., A.T., A.S., P.R., F.I., G.F.Z.). Department of Life health and Public Health, Catholic University of the Sacred Hearth, Rome. (D.A., G.F.Z.). Pathology Unit, Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples (A.T.) Division of Gynecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC), IRCCS Azienda Ospedaliero-Univeristaria di Bologna, S. Orsola-Malpighi Hospital University of Bologna, Bologna, Italy (A.R.).

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http://dx.doi.org/10.1097/PGP.0000000000000859DOI Listing
February 2022

SATB2 is expressed in neuroendocrine carcinoma of the uterine cervix.

Virchows Arch 2022 Apr 29;480(4):873-877. Epub 2022 Jan 29.

Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy.

Neuroendocrine carcinoma (NEC) of the uterine cervix is less characterized than neuroendocrine neoplasms of other sites such as of the digestive system and the lung. Special AT-rich sequence-binding protein 2 (SATB2) recently emerged as a marker of well-differentiated neuroendocrine tumors of the lower gastrointestinal (GI) tract. Among NECs, SATB2 is more frequently expressed in cutaneous Merkel cell carcinoma than in NEC of other anatomical sites. In our study, we performed an immunohistochemical study of SATB2 in 16 NECs of the uterine cervix, where the expression of these markers is still undefined. SATB2 was expressed in 12/16 cervical NECs (75%), with 7/16 cases (44%) showing SATB2 positivity in ≥ 50% of cells. In 7 cervical NECs associated with a non-neuroendocrine component, the expression of SATB2 was restricted to the neuroendocrine component. SATB2 was positive in all cases that expressed CDX2 (n = 7) and TTF1 (n = 5), with no evident association with p16 and p53. Our study demonstrated that SATB2 is often expressed in NECs of the uterine cervix. This information should be taken into account when assessing the origin of a NEC.
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http://dx.doi.org/10.1007/s00428-021-03255-7DOI Listing
April 2022

"Clock mapping" prior to excisional surgery in vulvar Paget's disease: tailoring the surgical plan.

Arch Gynecol Obstet 2022 Jan 27. Epub 2022 Jan 27.

Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Introduction: Paget disease is a rare neoplasm of the skin that mainly involves the vulvar region. Vulvar Paget's disease (VPD) can spread beyond the apparent edges of the lesion resulting in a high risk of involved surgical margins. Our aim is to verify the efficacy of a preoperative vulvo-vaginal intensive clock mapping in the prediction of the invasiveness and the extension of VPD.

Materials And Methods: All consecutive patients with primary VPD referred to our institution from July 2005 to December 2018 were subjected to a preoperative intensive biopsy mapping (clock mapping) of the vulvo-vaginal area: inside and outside the vulvar skin visible lesion, according to o'clock positions, and in the vagina. Patients with positive biopsies "only inside" or "also beyond" the visible lesion were included, respectively, in Group A and B. Surgical excision was drawn passing by the points with negative histology. Pathological findings of mapping biopsies were compared with those from radical surgery.

Results: A total of 28 women were enrolled. After clock mapping definitive histology: 17 (60.7%) and 11 (39.3%) patients were included in Group A and B. Definitive histology showed non-invasive, micro-invasive and invasive VPD, respectively, in 13 (46.4%), 11 (39.3%) and 4 (14.3%) patients, with 4 patients further upstaged. Overall, negative margins were found in 14 (50%) patients: 9 (32.1%) from Group A and 5 (17.9%) from Group B. In 23 cases (82.1%), clock mapping identified free surgical margins along the vulvo-perineal skin excision front.

Conclusions: Preoperative clock mapping emerged as potentially useful workup tool to predict invasiveness and extension of VPD, to tailor surgical excision.
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http://dx.doi.org/10.1007/s00404-022-06408-4DOI Listing
January 2022

Lymphovascular space invasion in endometrial carcinoma: A prognostic factor independent from molecular signature.

Gynecol Oncol 2022 04 23;165(1):192-197. Epub 2022 Jan 23.

Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.

Background: The 2020 ESGO/ESTRO/ESP guidelines stratify the prognosis of endometrial carcinoma (EC) patients combining The Cancer Genome ATLAS (TCGA) molecular signature and pathological factors, including lymphovascular space invasion (LVSI). However, little is known about the prognostic independence of LVSI from molecular signature.

Aim: To assess whether the prognostic value of LVSI is independent from the TCGA signature.

Material And Methods: A systematic review and meta-analysis was performed by searching 5 electronic databases from their inception to March 2021. All peer-reviewed studies reporting assessing LVSI as a prognostic factor independent from the TCGA groups in EC were included. Multivariate HRs with 95% confidence interval (CI) were pooled separately for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). The absence of LVSI was considered as a reference. In DFS analyses, locoregional and distant recurrence were separately considered for one study.

Results: Six studies with 3331 patients were included in the systematic review and three studies with 2276 patients in the meta-analysis. LVSI showed a pooled multivariate HR of 1.818 (CI 95%, 1.378-2.399) for OS, 1.849 (CI 95%, 1.194-2.863) for DSS, 1.377 (CI 95%, 1.008-1.880) for DFS excluding one study, 1.651 (CI 95%, 1.044-2.611) for DFS additionally considering locoregional recurrence from one study, and 1.684 (CI 95%, 1.05-2.701) for DFS additionally considering distant recurrence from the same study.

Conclusion: LVSI has a prognostic value independent of TCGA signature, as well as age and adjuvant treatment, increasing the risk of death of any cause, death due to EC and recurrent or progressive disease by 1.5-2 times.
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http://dx.doi.org/10.1016/j.ygyno.2022.01.013DOI Listing
April 2022

Endometrial Metaplastic/Reactive Changes Coexistent with Endometrial Hyperplasia and Carcinoma: A Morphological and Immunohistochemical Study.

Diagnostics (Basel) 2021 Dec 28;12(1). Epub 2021 Dec 28.

Gynecopathology and Breast Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.

The aim of this study was to assess the relationship between endometrial metaplastic/reactive changes (EMRCs) and endometrial neoplastic lesions. Twenty cases of "simple" (without architecture complexity) EMRCs coexistent with endometrial malignant/premalignant lesions, twenty cases of neoplasia-unassociated EMRCs, and eight cases of complex metaplastic lesions were assessed by immunohistochemistry. EMRCs coexisted with endometrioid carcinoma ( = 12), atypical endometrial hyperplasia ( = 3), serous carcinoma ( = 2), and clear cell carcinoma ( = 3). Neoplasia-associated EMRCs showed a mean Ki67 labeling index of 12.6% (range 0-30%); with nuclear atypia in 16/20 (80%) cases; diffuse p16 expression in 15/20 (75%) cases; and heterogeneous ER, PR, and vimentin expression. Compared to the associated neoplasia, EMRCs showed a lower Ki67 expression ( < 0.001) and higher p16 expression ( < 0.001). No EMRC case showed mitotic activity, PTEN loss, MMR deficiency, nuclear β-catenin, p53-mutant pattern, Napsin A, or AMACR expression. No significant differences were found between neoplasia-associated and neoplasia-unassociated EMRCs. Complex metaplastic lesions showed a lower Ki67 expression than EMRCs ( = 0.044) and PTEN loss in 5/8 cases, even in the absence of nuclear atypia. In conclusion, neoplasia-associated simple EMRCs may show evident atypia and a worrisome immunophenotype, but no data support their involvement in endometrial carcinogenesis. Architectural complexity appears as a crucial factor to identify precancerous lesions.
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http://dx.doi.org/10.3390/diagnostics12010063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774443PMC
December 2021

Histological Prognostic Factors of Endometrial Cancer in Patients with Adenomyosis: A Systematic Review and Meta-Analysis.

Pathobiology 2022 Jan 20:1-8. Epub 2022 Jan 20.

Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, Italy.

Background: A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been hypothesized based on a different prevalence of favorable EC histological prognostic factors. However, pooled risk of EC unfavorable histological prognostic factors in patients with adenomyosis has never been calculated.

Objectives: We aimed to assess the risk of EC unfavorable histological prognostic factors in patients with adenomyosis.

Methods: All studies with data about histological prognostic factors of EC in patients with and without adenomyosis were included. Relative risk for each unfavorable histological prognostic factor of EC, such as nonendometrioid histotype, FIGO grade 3, FIGO stage II-IV, lymphovascular space invasion (LVSI), and deep myometrial invasion, was calculated in patients with adenomyosis compared to patients without adenomyosis.

Results: Seven studies with 4,439 patients were included in the quantitative analysis. EC patients with adenomyosis showed a pooled RR of 0.77 (p = 0.05) for nonendometrioid histotype, 0.55 (p < 0.00001) for FIGO grade 3, 0.60 (p = 0.005) for FIGO stage II-IV, 0.75 (p = 0.004) for LVSI, and 0.65 (p = 0.001) for deep myometrial invasion.

Conclusion: EC patients with adenomyosis have a significantly decreased risk for unfavorable histological prognostic factors of EC compared to EC patients without adenomyosis. Such findings might explain the supposed better EC prognosis in patients with adenomyosis.
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http://dx.doi.org/10.1159/000521105DOI Listing
January 2022

The Vulvar Immunohistochemical Panel (VIP) Project: Molecular Profiles of Vulvar Squamous Cell Carcinoma.

Cancers (Basel) 2021 Dec 19;13(24). Epub 2021 Dec 19.

Dipartimento Scienze della Vita e Sanità Pubblica, Sezione Ginecologia e Ostetricia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Introduction: The study's aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC).

Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N.

Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14-15.87, = 0.03) and 2.68 (CI 95% = 1.0-7.19, < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases.

Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression.
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http://dx.doi.org/10.3390/cancers13246373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699435PMC
December 2021

The role of fat grafting on contracted breast implant capsules: A retrospective comparative histological and immunohistochemical study.

J Plast Reconstr Aesthet Surg 2022 03 19;75(3):1083-1093. Epub 2021 Oct 19.

Fondazione Policlinico Universitario A. Gemelli IRCSS, Dipartimento Scienze della Salute della Donna e del Bambino, Unità di Chirurgia Plastica, Largo Francesco Vito 1, Roma 00168, Italy.

Capsular contracture, a common complication of breast implant reconstruction following postmastectomy radiotherapy (PMRT), represents a challenge for plastic surgeons. Regenerative surgery with multiple autologous fat grafts (lipobed) before replacing the implant has been proven to be a satisfactory approach in the radio-damaged breast. Currently, in literature, there are no data available on the histological features of irradiated capsules after regenerative surgery. We enrolled 80 patients after immediate subpectoral alloplastic breast reconstruction, with indication for revision surgery due to grade IV capsular contracture developed after PMRT. Forty patients were undergoing multiple fat grafting (lipobed group, mean age 48) and 40 patients were not undergoing multiple fat grafting (non-regenerative surgery (NRS) group, mean age 49). The removed capsules were addressed to histological and immunohistochemical assessment. The capsules of the lipobed group patients compared with NRS group patients showed: a lower mean thickness (602.17 versus 670.43 µm; P = 0.013), a lower collagen fiber alignment (median value of angle deviation: 30.34 versus 18.38; P = 0.001), a lower immunohistochemical positivity for myofibroblasts (α-smooth muscle actin [α-SMA] expression: 12.5% versus 52.5%; P = 0.00), a higher immunohistochemical positivity for estrogen receptor-β (ER-β; 80% versus 20%; P = 0.00), and a lower immunohistochemical positivity for estrogen receptor-α (ER-α; 53.3% versus 16.7%; P = 0.00). The histological and immunohistochemical differences found are possibly due to alterations in the extracellular microenvironment determined by grafted fat.
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http://dx.doi.org/10.1016/j.bjps.2021.09.035DOI Listing
March 2022

Prognostic predictors in recurrent adult granulosa cell tumors of the ovary: a systematic review and meta-analysis.

Arch Gynecol Obstet 2021 Nov 19. Epub 2021 Nov 19.

Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Roma, Italy.

Background: Ovarian adult granulosa cell tumours are low-grade malignant sex cord-stromal neoplasm with a low recurrence rate. Prognostic factors for recurrence include tumor stage, tumor rupture in Stage I neoplasms and the presence of residual tumors after surgery. However, in recurrent tumors, prognostic factors for overall survival (OS) are lacking. In the present paper, we conducted a systematic meta-analysis with the aim to assess prognostic factors for OS in patients with recurrent GCT.

Methods: Electronic databases were searched for all studies assessing prognostic factors in recurrent adult granulosa cell tumor of the ovary. Student T test, Fisher's exact test and Kaplan-Meier survival analysis with long-rank test were used to assess differences among groups; a p value < 0.05 was considered significant.

Results: Eleven studies analyzing 102 recurrent tumors were included in the systematic review. Tumor stage and localization of recurrent tumors were significantly associated with OS on Kaplan-Meier analysis; Cox regression analysis showed a HR of 0.879 for the stage II, of 3.052 for the stage III, and of 2.734 for stage IV tumor was significantly associated with OS (p = 0.037); observed HRs for abdominal and thoracic locations were of 2.405 and of 4.024, respectively.

Conclusions: In conclusion, the present article emphasizes the prognostic significance of tumor stage > II and extrapelvic anatomic sites of recurrences in patients with recurrent granuolase cell tumors of the ovary.
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http://dx.doi.org/10.1007/s00404-021-06305-2DOI Listing
November 2021

Risk of Recurrence in Uterine Leiomyoma with Bizarre Nuclei: a Systematic Review and Meta-Analysis.

Geburtshilfe Frauenheilkd 2021 Nov 4;81(11):1217-1223. Epub 2021 Nov 4.

Division of Gynaecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC), IRCCS Azienda Ospedaliero-Univeristaria di Bologna, S. Orsola Hospital, University of Bologna, Bologna, Italy.

Leiomyoma with bizarre nuclei (LBN) is a variant of uterine leiomyoma, which has replaced the previous category of "atypical leiomyoma" and must be distinguished from smooth muscle tumors of uncertain malignant potential (STUMP). However, previously published series of "atypical leiomyoma" might have included both LBN and STUMP, due to the lack of strict diagnostic criteria. Based on such hypothesis, we aimed to define the risk of recurrence in LBN. A systematic review and meta-analysis was performed by searching 4 electronic databases for all studies assessing the outcome of patients with "atypical leiomyoma" or LBN. The pooled absolute risk of recurrence was calculated. The included studies were subdivided into two subgroups based on the criteria used: "LBN + STUMP" or "LBN-only". Twelve studies with 433 patients were included. The pooled risk of recurrence was 5.5% overall. The funnel plot showed two cluster of studies which superimposed to the two subgroups. In the LBN + STUMP cluster/subgroup, the pooled risk of recurrence was 7.7%. In the LBN-only cluster/subgroup, the pooled risk of recurrence was 1.9%. Statistical heterogeneity was null in all analyses. Our results show a risk of recurrence of 1.9% for LBN; higher recurrence rates in older studies are likely due to the inclusion of STUMPs.
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http://dx.doi.org/10.1055/a-1533-1651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568503PMC
November 2021

Clear cell endometrial carcinoma precursors: presentation of two cases and diagnostic issues.

Diagn Pathol 2021 Oct 25;16(1):95. Epub 2021 Oct 25.

Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Roma, Italy.

Background: The precursors of clear cell endometrial carcinoma (CC-EC) are still undefined. Here, we deal with the diagnostic issues related to CC-EC precursors by presenting a morphological, immunophenotypical and molecular study of two representative cases and discussing the relevant literature.

Case Presentation: Our and previous cases suggest that clear cell endometrial intraepithelial carcinoma (CC-EIC) is a real entity, which may be distinguished from metaplastic/reactive changes and from its serous counterpart. CC-EIC appears associated with atrophic polyps and may be diagnosed based on morphological and immunophenotypical features of CC-EC in the absence of invasive disease. We described a p53-mutant putative precursor characterized by high-grade nuclei in the absence of other distinctive features. Two putative low-grade precursors resembled atypical tubal metaplasia and endometrial intraepithelial neoplasia, although immunohistochemistry could not support their relationship with CC-EC.

Conclusions: In conclusion, pathologists should be aware of the existence of CC-EIC, since its correct diagnosis may be crucial for a correct patient management. Although several putative earlier precursors have been described, they does not show univocal features that allow their recognition in the common practice. Further studies are necessary in this field.
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http://dx.doi.org/10.1186/s13000-021-01154-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543890PMC
October 2021

Depth of Stromal Invasion as the Most Prognostically Relevant Regression System in Locally Advanced Cervical Cancer after Neoadjuvant Treatment: A Systematic Review and Meta-Analysis Grading.

Diagnostics (Basel) 2021 Sep 26;11(10). Epub 2021 Sep 26.

Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo A. Gemelli 8, 00168 Roma, Italy.

several different criteria have been proposed to categorize the pathological response in cervical cancer after neoadjuvant therapy; although it is unclear what the most prognostically valuable one is. to assess the prognostic value of pathological criteria for categorizing the response in cervical cancer after neoadjuvant therapy, through a systematic review and meta-analysis. four electronic databases were searched from January to December 2020 for all studies, assessing the prognostic value of pathological response in cervical cancer after neoadjuvant therapy. Hazard ratio (HR) for overall survival (OS) was calculated with a significant -value < 0.05. A meta-analysis was performed for each criteria assessed in at least three studies. sixteen studies were included. Criteria for pathological response included (i) residual stromal invasion < vs. >3 mm; (ii) complete response vs. any residual; (iii) proportion of viable cells; (iv) residual tumor diameter; and (v) intracervical vs. extracervical residual. Criteria (i) and (ii) were suitable for meta-analysis. The presence of a residual tumor with stromal invasion > 3 mm showed a HR of 4.604 (95% CI; 3.229-6.565; < 0.001), while the presence of any residual showed a HR of 1.610 (95% CI; 1.245-2.081; < 0.001); statistical heterogeneity was absent in both analyses. dichotomizing the pathological response in cervical cancer after neoadjuvant therapy as < vs. >3 mm stromal invasion is more prognostically valuable than dichotomizing as complete response vs. any residual. Further studies are necessary to evaluate other systems.
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http://dx.doi.org/10.3390/diagnostics11101772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534824PMC
September 2021

Clinical Characteristics of Patients with Endometrial Cancer and Adenomyosis.

Cancers (Basel) 2021 Sep 30;13(19). Epub 2021 Sep 30.

Division of Gynaecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC), IRCCS Azienda Ospedaliero-Univeristaria di Bologna, S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy.

A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been reported. Unfortunately, it is still unclear if this better prognosis is related to a more favorable clinical profile of adenomyosis patients. We aimed to evaluate differences in the clinical profiles of EC patients with and without adenomyosis. A systematic review and meta-analysis was performed by searching seven electronics databases for all studies that allowed extraction of data about clinical characteristics in EC patients with and without adenomyosis. Clinical characteristics assessed were: age, Body Mass Index (BMI), premenopausal status, and nulliparity. Mean difference in mean ± standard deviation (SD) or odds ratio (OR) for clinical characteristics between EC patients with and without adenomyosis were calculated for each included study and as a pooled estimate, and graphically reported on forest plots with a 95% confidence interval (CI). The Z test was used for assessing the overall effect by considering a value < 0.05 as significant. Overall, eight studies with 5681 patients were included in the qualitative analysis, and seven studies with 4366 patients in the quantitative analysis. Pooled mean difference in mean ± SD between EC women with and without adenomyosis was -1.19 (95% CI: -3.18 to 0.80; = 0.24) for age, and 0.23 (95% CI: -0.62 to 1.07; = 0.60) for BMI. When compared to EC women without adenomyosis, EC women with adenomyosis showed a pooled OR of 1.53 (95% CI: 0.92 to 2.54; = 0.10) for premenopausal status, and of 0.60 (95% CI: 0.41 to 0.87; = 0.007) for nulliparity. In conclusion, there are not significant differences in clinical characteristics between EC patients with and without adenomyosis, with the exception for nulliparity. Clinical features seem to not underlie the better EC prognosis of patients with adenomyosis compared to patients without adenomyosis.
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http://dx.doi.org/10.3390/cancers13194918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508080PMC
September 2021

Prognostic value of the TCGA molecular classification in uterine carcinosarcoma.

Int J Gynaecol Obstet 2021 Sep 18. Epub 2021 Sep 18.

Gynecopathology and Breast Pathology Unit, Department of Woman's Health Science, Agostino Gemelli University Polyclinic, Rome, Italy.

Background: The TCGA molecular groups of endometrial carcinoma are "POLE-mutated" (POLEmut), "microsatellite-instable/mismatch repair-deficient" (MSI/MMRd), "TP53-mutated/p53-abnormal" (TP53mut/p53abn), and "no specific molecular profile" (NSMP).

Objective: Prognostic assessment of the TCGA groups in uterine carcinosarcoma (UCS).

Search Strategy: Systematic review from January 2000 to January 2021.

Selection Criteria: Studies assessing the TCGA groups in UCS.

Data Collection And Analysis: Progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan-Meier and Cox analyses (reference: TP53mut/p53abn group) and compared with endometrioid and serous carcinomas (original TCGA cohort), with a significant P < 0.050.

Main Results: Five studies with 263 UCS were included. Compared with TP53mut/p53abn UCS, MSI/MMRd UCS showed significantly better PFS (P < 0.001) but similar OS (P = 0.788), whereas NSMP UCS showed similar PFS (P = 0.936) and OS (P = 0.240). Compared with their endometrioid/serous counterparts, NSMP and TP53mut/p53abn UCS showed significantly worse PFS (P < 0.001 and P = 0.004) and OS (P < 0.001 and P < 0.001), while MSI/MMRd UCS showed similar PFS (P = 0.595) but significantly worse OS (P < 0.001). The POLEmut group showed neither recurrences nor deaths in both the UCS and the endometrioid/serous carcinoma cohorts.

Conclusion: POLEmut UCS show excellent prognosis, whereas TP53mut/p53abn and NSMP UCS show a prognosis even worse than that of TP53mut/p53abn endometrioid/serous carcinomas. The prognosis of MSI/MMRd UCS remains to be defined.
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http://dx.doi.org/10.1002/ijgo.13937DOI Listing
September 2021

TCGA molecular subgroups of endometrial carcinoma in ovarian endometrioid carcinoma: A quantitative systematic review.

Gynecol Oncol 2021 11 24;163(2):427-432. Epub 2021 Aug 24.

Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bam-bino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Roma, Italy; Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italy. Electronic address:

Background: Ovarian endometrioid carcinoma (OEC) shares morphological and molecular features with endometrial endometrioid carcinoma (EEC). Several studies assessed the four TCGA groups of EEC, i.e. POLE-mutated (POLEmut), mismatch repair-deficient (MMRd), no specific molecular profile (NSMP) and p53-abnormal (p53abn), in OEC; however, it is unclear whether the TCGA groups have the same distribution and clinicopathological features between OEC and EEC.

Objective: To assess the distribution and clinicopathological features of the TCGA groups in OEC.

Methods: A systematic review and meta-analysis was carried out by searching 7 electronic databases from January 2013 to April 2021 for studies assessing the TCGA classification in OEC. Prevalence of each TCGA group in OEC and of FIGO grade 3 and stage>I was pooled using a random-effect model. Prevalence of TCGA groups was compared between OEC and EEC, extracting EEC data from a previous meta-analysis. Kaplan-Meier and Cox regression survival analyses were performed for progression-free survival (PFS). A significant p-value<0.05 was adopted.

Results: Four studies with 785 patients were included. The frequency of the TCGA groups in OEC vs EEC was: POLEmut = 5% vs 7.6% (p = 0.594); MMRd = 14.6% vs 29.2% (p < 0.001); p53abn = 14% vs 7.8% (p = 0.097); NSMP = 66.4% vs 55.4% (p = 0.002). The pooled prevalence of FIGO grade 3 was: POLEmut = 19.2%; MMRd = 18.3%; p53abn = 38.1%; NSMP = 14.5%. The pooled prevalence of FIGO stage >I was: POLEmut = 31.6%; MMRd = 42.8%; p53abn = 48.5%; NSMP = 24.6%. Two-, 5- and 10-year PFS was: POLEmut = 100%, 100%, and 100%; MMRd = 89.1%, 82.2% and 73.3%; p53abn = 61.7%, 50.2% and 39.6%; NSMP = 87.7%, 79.6% and 65.5%. The hazard ratio for disease progression (reference = NSMP) was: POLEmut = not estimable (no events); MMRd = 0.825 (p = 0.626); p53abn = 2.786 (p = 0.001).

Conclusion: The prognostic value of the TCGA groups was similar between OEC and EEC, despite the differences in the frequency and pathological features of each group.
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http://dx.doi.org/10.1016/j.ygyno.2021.08.011DOI Listing
November 2021

Diagnostic impact of safety protocols for processing peritoneal washing specimens during the global pandemic of coronavirus disease 2019: A comparative study from 195 cytological samples.

Cytopathology 2022 01 13;33(1):93-99. Epub 2021 Oct 13.

Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Unità Operativa Complessa di Gineco-patologia e Patologia Mammaria, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background: The global pandemic of the coronavirus disease 2019 represents a major concern for health services worldwide, and has also induced major changes in cytopathology practice.

Aim: We aimed to verify the diagnostic performance of cytological evaluation under a new safety protocol during the pandemic compared to the standard pre-pandemic procedure. We also aimed to assess how cytological diagnoses and sampling were impacted during the pandemic period compared to the pandemic-free period in 2019.

Materials And Methods: Cytological samples of peritoneal washings taken during the first 10 months of the pandemic emergency in Italy (March 11, 2020 to January 11, 2021) were compared to samples from the preceding 10-month time frame (May 11, 2019 to March 10, 2020).

Results: One hundred ninety-five specimens were analysed in the present study. We observed no noticeable differences in cytological diagnoses during the pandemic period compared to the pre-pandemic period. The case numbers by diagnostic category for the pre-pandemic vs pandemic periods, respectively, were as follows: non-diagnostic, 0 vs 0 cases; negative for malignancy, 86 vs 52 cases; atypia of uncertain significance, 7 vs 1 cases; suspicious for malignancy, 0 vs 2 cases; malignant, 42 vs 4 cases.

Conclusion: While a consistent reduction in the number of cytological examinations has been observed during the COVID-19 period, our institutional safety protocol for processing cytological samples did not affect the diagnostic reliability of peritoneal washing cytology.
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http://dx.doi.org/10.1111/cyt.13053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420544PMC
January 2022

Clear cell endometrial carcinomas with mismatch repair deficiency have a favorable prognosis: A systematic review and meta-analysis.

Gynecol Oncol 2021 09 12;162(3):804-808. Epub 2021 Jul 12.

Gynecopathology and Breast Pathology Unit, Department of Woman's Health Science, Agostino Gemelli University Polyclinic, Rome, Italy; Catholic University of Sacred Heart, Rome, Italy.

Introduction: In the ESGO/ESTRO/ESP guidelines for endometrial carcinoma management, the risk category of clear cell carcinoma (CCC) is not well defined. In fact, while p53-abnormal (p53abn) CCC are known to be aggressive, the prognosis of mismatch repair-deficient (MMRd) and p53-wild-type (p53wt) CCCs is less clear.

Objective: To assess the prognostic value of the MMRd and p53wt groups in CCC through a systematic review and meta-analysis.

Methods: Electronic databases were searched from their inception to February 2021. All studies reporting p53 expression, MMR proteins expression and survival outcomes in endometrial CCC (either pure or mixed) were included. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) for overall survival (OS) were performed by using the p53abn group as reference; a significant p-value<0.05 was adopted.

Results: Six studies with 136 CCC (114 pure and 22 mixed) were included. Five-year OS was 95.7 ± 4.3% in the MMRd group, 48.4 ± 8.4% months in the p53wt group and 40.6 ± 10.4% in the p53abn group. The hazard of death was significantly lower in the MMRd group than in the p53abn group (HR = 0.062; p = 0.007), while it did not significantly differ between the p53wt and the p53abn group (HR = 0.673; p = 0.222). The POLEmut group could not be analyzed due to the absence of deaths. Similar results were observed in the pure CCC and mixed CCC subgroups.

Conclusion: MMRd CCCs seem to have a favorable prognosis and might be lumped together with MMRd endometrioid carcinoma for management purpose. On the other hand, p53wt CCCs appear prognostically more similar to p53abn CCCs.
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http://dx.doi.org/10.1016/j.ygyno.2021.07.007DOI Listing
September 2021

Impact of adenomyosis on the prognosis of patients with endometrial cancer.

Int J Gynaecol Obstet 2022 May 18;157(2):265-270. Epub 2021 Jul 18.

Division of Gynecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC, IRCCS Azienda Ospedaliero-Univeristaria di Bologna, S. Orsola Hospital, University of Bologna, Bologna, Italy.

Background: Despite the high prevalence of adenomyosis in hysterectomy specimens of endometrial carcinoma (EC) patients, the relationship between adenomyosis and EC prognosis appears unclear.

Objective: To assess the prognostic value of coexistent adenomyosis in patients with EC.

Methods: A systematic review and meta-analysis was performed by searching six electronic databases for studies reporting data on prognosis of EC patients with and without coexistent adenomyosis. Studies with patient selection based on prognostic factors were excluded. Pooled univariate hazard ratio (HR) analyses for overall survival (OS) and disease-free survival (DRF) were performed, using EC patients without adenomyosis as a control group. For DFS, pooled multivariate HR analysis was also evaluable.

Results: Three studies of 2505 EC patients (553 with and 1952 without adenomyosis) were included. Compared with EC patients without adenomyosis, EC patients with coexistent adenomyosis showed a pooled HR of 0.533 (CI 95%, 0.329-0.864) for OS at univariate analysis; 0.536 (CI 95%, 0.334-0.859) for DFS at univariate analysis; and 0.875 (CI 95%, 0.331-2.315) for DFS at multivariate analysis.

Conclusion: In EC patients with coexistent adenomyosis, the risk of death is halved compared with EC patients without adenomyosis. However, the independence of this association needs to be verified in future studies.
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http://dx.doi.org/10.1002/ijgo.13818DOI Listing
May 2022

Prognostic value of myometrial invasion and TCGA groups of endometrial carcinoma.

Gynecol Oncol 2021 08 1;162(2):401-406. Epub 2021 Jun 1.

Division of Gynaecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC)., IRCCS Azienda Ospedaliero-Universitaria di Bologna. S. Orsola Hospital. University of Bologna, Via Massarenti 13, Bologna 40138, Italy.

Background: 2021 ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma (EC) encourage molecular classification and propose a new prognostic risk stratification based on both pathologic and molecular features. Although deep myometrial invasion (DMI) has been considered as a crucial risk factor in EC, it is unclear if its prognostic value is independent from The Cancer Genome ATLAS (TCGA) groups.

Aim: To assess if the prognostic value of DMI is independent from the TCGA groups in EC patients.

Materials And Methods: A systematic review and meta-analysis was performed by searching through 5 electronic databases, from their inception to March 2021, for all studies that allowed to assess DMI as a prognostic factor independent of the TCGA groups in EC patients. Pooled hazard ratio (HR) of DMI for overall survival (OS) and disease-free survival (DFS) was calculated at multivariable analyses including TCGA groups as a variable. Superficial myometrial invasion (<50% of myometrial thickness) was considered as a reference. In DFS analyses, locoregional and distant recurrence were separately considered for one study.

Results: Five studies with 2469 patients were included in the systematic review and 3 studies with 1549 patients in the meta-analysis. Pooled HR of DMI was 1.082 (CI 95% 0.85-1.377; p = 0.524) for OS, 1.709 (CI 95% 1.173-2.491; p = 0.005) for DFS, 1.585 (CI 95% 1.154-2.178; p = 0.004) for DFS additionally considering locoregional recurrence for one study, and 1.701 (CI 95% 1.235-2.344, p = 0.001) for DFS additionally considering distant recurrence for the same study.

Conclusions: DMI does not appear as an independent prognostic factor for OS in EC patients; instead, it seems to affect the risk of recurrence independently from the TCGA groups. Further studies are necessary to confirm these findings and to assess the prognostic impact of DMI separately in each TCGA group.
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http://dx.doi.org/10.1016/j.ygyno.2021.05.029DOI Listing
August 2021
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