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Diagnosis and Management of Gynecological Cancers
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Diagnosis and Management of Gynecological Cancers

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 86678

Special Issue Editor

Prof. Dr. Robert Jach

E-Mail Website
Guest Editor
Division of Gynecologic Endocrinology, Jagiellonian University Medical College, Kopernika 23, 31-501 Krakow, Poland
Interests: gynecologic oncology; cervical cancer; cervical cancer screening; hysterectomy; laparoscopic surgery; cancer prevention; ovary; oncology; cervical cancer prevention
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The coronavirus disease 2019 (COVID-19) pandemic is at its apogee, causing a paradigm shift in the way we perceive health, life, and our somatic, mental, and spiritual needs. We do not yet know the consequences of this pandemic on the health of women with gynecological and breast cancers. Research in the field of oncological gynecology, especially in relation to disease diagnosis and treatment, has been curtailed by the lockdown imposed by the pandemic. On the other hand, the fast progress in COVID-19 vaccines allows us some optimism regarding the possibility to resume research on new strategies for the primary and secondary prevention of gynecological and breast cancers and for more efficacious treatments. I cordially invite you to share your discoveries and observations in the field of oncological gynecology with the scientific community and the medical world. This Special Issue will publish reviews and original papers concerning recent advances in diagnostic (based on AI, radiotracers, SLN mapping, biomarkers, DNA/mRNA agents, molecular biology), imaging (expert ultrasonography, hysteroscopy), and treatment modalities (tips and tricks in surgery, minimally invasive techniques, tailored systemic therapy, immunotherapy, side effects management, complications management, terminal phase of cancer management, oncofertility, cancer treatment during pregnancy) for these types of cancer.

I invite you to a fascinating scientific adventure.

Prof. Dr. Robert Jach
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Gynecologic oncology
  • cervical cancer
  • uterine cancer
  • ovarian cancers
  • breast cancer
  • vulvar cancer
  • surgery
  • systemic therapy
  • radiotherapy
  • anesthesiology and intensive care

Published Papers (31 papers)

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10 pages, 1017 KiB  
Article
Nuclear Expression of β-Catenin Is Associated with Improved Outcomes in Endometrial Cancer
by Valeria Masciullo, Tommaso Susini, Giacomo Corrado, Marina Stepanova, Alessandro Baroni, Irene Renda, Francesca Castiglione, Corrado Minimo, Alfonso Bellacosa, Benito Chiofalo, Enrico Vizza and Giovanni Scambia
Diagnostics 2022, 12(10), 2401; https://doi.org/10.3390/diagnostics12102401 - 03 Oct 2022
Viewed by 1498
Abstract
Beta-catenin is involved in intercellular adhesion and participates in the Wnt signaling pathway. This study evaluated the expression pattern and prognostic value of β-catenin in a series of endometrial carcinoma patients. Immunohistochemical analyses were used to assess the expression and subcellular localization of [...] Read more.
Beta-catenin is involved in intercellular adhesion and participates in the Wnt signaling pathway. This study evaluated the expression pattern and prognostic value of β-catenin in a series of endometrial carcinoma patients. Immunohistochemical analyses were used to assess the expression and subcellular localization of β-catenin from tissue sections of 74 patients with endometrial carcinoma. No correlation was found between beta-catenin expression and clinicopathological parameters. Patients expressing nuclear β-catenin (n = 13; 16%) showed a more favorable prognosis than patients expressing membranous β-catenin; the 5-year disease-related survival rate was 100% for cases expressing nuclear β-catenin, compared with 73.8% (SE 0.08) of cases expressing membranous β-catenin (p = 0.04). Although statistical significance was not reached (p = 0.15), cases expressing nuclear β-catenin showed a 5-year disease-free survival rate of 90.9% (SE 0.08) compared with 67.4% (SE 0.08) of cases expressing membranous β-catenin. Univariate Cox analysis revealed that membranous β-catenin expression was found to be associated with a relative risk of death of 33.9 (p = 0.04). The stage of disease (p = 0.0006), histology (p = 0.003), and grading (p = 0.008) were also significantly correlated with disease-free survival according to univariate Cox analyses. Determining β-catenin expression and localization patterns may predict survival in patients with endometrial cancer and, therefore, should be considered a potential prognostic marker of disease. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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12 pages, 710 KiB  
Article
The Impact of SARS-CoV-2 Pandemic on Patients Undergoing Radiation Therapy for Advanced Cervical Cancer at a Romanian Academic Center: A Four-Year Retrospective Analysis
by Alin Popescu, Stelian Pantea, Daniela Radu, Adrian Gluhovschi, Catalin Dumitru, George Dahma, Adelina Geanina Mocanu, Radu Neamtu, Sorin Dema, Codruta Victoria Tigmeanu, Mirela Loredana Grigoras, Silvius Alexandru Pescariu, Hazzaa Aabed and Marius Craina
Diagnostics 2022, 12(6), 1488; https://doi.org/10.3390/diagnostics12061488 - 17 Jun 2022
Viewed by 1513
Abstract
Background and Objectives: Throughout the COVID-19 pandemic, health systems worldwide adapted to support COVID-19 patients while continuing to provide assistance to patients with other potentially fatal illnesses. While patients with cancer may be at an elevated risk of severe COVID-19-related complications, their [...] Read more.
Background and Objectives: Throughout the COVID-19 pandemic, health systems worldwide adapted to support COVID-19 patients while continuing to provide assistance to patients with other potentially fatal illnesses. While patients with cancer may be at an elevated risk of severe COVID-19-related complications, their oncologic therapies generally cannot be postponed indefinitely without a negative effect on outcomes. Taking this into account, a thorough examination of the therapy management of various cancers is necessary, such as cervical cancer. Therefore, we aimed to develop a retrospective cohort study to measure the impact of the COVID-19 pandemic on the delivery of cancer care services for women diagnosed with cervical cancer staged IB2-IVA, necessitating chemo- and radiotherapy in Romania, as well as determine the difference in cervical cancer staging between the pandemic and pre-pandemic period. Materials and Methods: Using a multicentric hospital database, we designed a retrospective study to compare the last 24 months of the pre-pandemic period to the first 24 months of the SARS-CoV-2 pandemic to evaluate the variation in the proportion of women diagnosed with cervical cancer and the percentage of inoperable cases requiring chemotherapy and radiotherapy, as well as to detail their clinical presentation and other findings. Results: We observed that the likelihood of cervical cancer patients requiring radiation therapy at a later stage than before the pandemic increased by about 20% during the COVID-19 pandemic. Patients at an advanced FIGO stage of cervical cancer had a 3.39 higher likelihood of disease progression after radiotherapy (CI [2.06–4.21], p-value < 0.001), followed by tumor size at diagnosis with a hazard ratio (HR) of 3.12 (CI [2.24–4.00], p-value < 0.001). The factors related to the COVID-19 pandemic, postponed treatment and missed appointments, were also identified as significant risk factors for cervical cancer progression (HR = 2.51 and HR = 2.24, respectively). Conclusions We predict that there will be a considerable rise in cervical cancer cases over the next several years based on existing data and that expanding screening and treatment capacity will attenuate this with a minimal increase in morbidity and fatality. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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11 pages, 1179 KiB  
Article
COVID-19 Pandemic Effects on Cervical Cancer Diagnosis and Management: A Population-Based Study in Romania
by Alin Popescu, Marius Craina, Stelian Pantea, Catalin Pirvu, Veronica Daniela Chiriac, Iosif Marincu, Felix Bratosin, Iulia Bogdan, Samer Hosin, Cosmin Citu, Elena Bernad, Radu Neamtu, Catalin Dumitru, Adelina Geanina Mocanu, Claudiu Avram and Adrian Gluhovschi
Diagnostics 2022, 12(4), 907; https://doi.org/10.3390/diagnostics12040907 - 06 Apr 2022
Cited by 9 | Viewed by 1921
Abstract
The Pap test plays a significant role worldwide in the early diagnosis of and high curability rates for cervical cancer. However, the coronavirus disease 2019 (COVID-19) pandemic necessitated the use of multiple drastic measures to stop the spread of the severe acute respiratory [...] Read more.
The Pap test plays a significant role worldwide in the early diagnosis of and high curability rates for cervical cancer. However, the coronavirus disease 2019 (COVID-19) pandemic necessitated the use of multiple drastic measures to stop the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, limiting women’s access to essential invasive and non-invasive investigations for cervical cancer diagnosis. Therefore, we aimed to determine the impact the COVID-19 pandemic had on cancer diagnosis and management in western Romania. A retrospective study design allowed us to compare the last 24 months of the pre-pandemic period with the first 24 months of the COVID-19 pandemic to determine the change in volume of cervical screening tests, the number of newly diagnosed cases and their severity, and the access to cancer care. A drastic 75.5% decrease in the volume of tests was observed in April 2020 during the first lockdown, after which the volume of cases decreased by up to 36.1% in December 2021. The total volume loss of tests during the first 24 months of the pandemic was 49.9%. The percentage of late-stage cervical cancers (III–IV) rose by 17%, while the number of newly diagnosed cancers in our outpatient clinic was significantly lower than the baseline, with a 45% drop. The access to cancer care was negatively influenced, with 9.2% more patients waiting longer to receive test results over four weeks, while taking longer to seek cancer care after diagnosis (6.4 months vs. 4.1 months pre-pandemic) and missing significantly more appointments. The COVID-19 pandemic had a significantly negative impact on cervical cancer diagnosis and management during the first 24 months compared with the same period before the pandemic. Although the numbers are now recovering, there is still a big gap, meaning that many cervical cancer cases were potentially missed. We recommend further interventions to reduce the gap between the pre-pandemic and pandemic period. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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15 pages, 834 KiB  
Article
Predictive and Prognostic Significance of mRNA Expression and DNA Copies Aberrations of ERCC1, RRM1, TOP1, TOP2A, TUBB3, TYMS, and GSTP1 Genes in Patients with Breast Cancer
by Matvey M. Tsyganov, Marina K. Ibragimova, Evgeniy Yu. Garbukov, Irina A. Tsydenova, Kseniya A. Gaptulbarova, Daria S. Dolgasheva, Ekaterina A. Zdereva, Anastasia A. Frolova, Elena M. Slonimskaya and Nikolai V. Litviakov
Diagnostics 2022, 12(2), 405; https://doi.org/10.3390/diagnostics12020405 - 04 Feb 2022
Cited by 2 | Viewed by 1790
Abstract
Increasingly, many researchers are focusing on the sensitivity in breast tumors (BC) to certain chemotherapy drugs and have personalized their research based on the assessment of this sensitivity. One such personalized approach is to assess the chemotherapy’s gene expression, as well as aberrations [...] Read more.
Increasingly, many researchers are focusing on the sensitivity in breast tumors (BC) to certain chemotherapy drugs and have personalized their research based on the assessment of this sensitivity. One such personalized approach is to assess the chemotherapy’s gene expression, as well as aberrations in the number of DNA copies—deletions and amplifications with the ability to have a significant effect on the gene’s activity. Thus, the aim of this work was to study the predictive and prognostic significance of the expression and chromosomal aberrations of eight chemosensitivity genes in breast cancer patients. Material and methods. The study involved 97 patients with luminal B breast cancer IIB–IIIB stages. DNA and RNA were isolated from samples of tumor tissue before and after treatment. Microarray analysis was performed for all samples on high-density microarrays (DNA chips) of Affymetrix (USA) CytoScanTM HD Array and Clariom™ S Assay, human. Detection of expression level of seven chemosensitivity genes—RRM1, ERCC1, TOP1, TOP2a, TUBB3, TYMS, and GSTP1—was performed using PCR real-time (RT-qPCR). Results. The expression of the RRM1 (AC scheme), TOP2α, TYMS, and TUBB3 genes in patients with an objective response to treatment (complete and partial regression) is higher than in patients with stabilization and progression (p < 0.05). According to our results, the presence of a high level of GSTP1 in a tumor biopsy is associated with the low efficiency of the NAC CP scheme (p = 0.05). The presence of RRM1 deletion is associated with complete and partial regression, as for the TOP1 and TUBB3 genes (p < 0.05). Higher rates of metastatic survival are associated with a high level of expression and amplification of the GSTP1 gene (log-rank test p = 0.02 and p = 0.05). Conclusion. Thus, a complex assessment of the chemotherapy’s gene expression is important not only for understanding the heterogeneity and molecular biology of breast cancer but also to obtain a more accurate disease prognosis. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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23 pages, 9937 KiB  
Article
Mesonephric-like Adenocarcinoma of the Ovary: Clinicopathological and Molecular Characteristics
by Hyun Hee Koh, Eunhyang Park and Hyun-Soo Kim
Diagnostics 2022, 12(2), 326; https://doi.org/10.3390/diagnostics12020326 - 27 Jan 2022
Cited by 17 | Viewed by 4387
Abstract
Mesonephric-like adenocarcinoma (MLA) arising in the ovary is a rare malignant tumor of the female genital tract. Although the clinicopathological and molecular characteristics of uterine MLA have been accumulated, those of ovarian MLA have not been firmly clarified. In this study, we investigated [...] Read more.
Mesonephric-like adenocarcinoma (MLA) arising in the ovary is a rare malignant tumor of the female genital tract. Although the clinicopathological and molecular characteristics of uterine MLA have been accumulated, those of ovarian MLA have not been firmly clarified. In this study, we investigated the clinicopathological, immunohistochemical, and genetic features of five ovarian MLAs. A review of electronic medical records and pathology slides, immunostaining, and targeted sequencing was performed. On imaging, ovarian MLA presented as either a mixed solid and cystic mass or a purely solid mass. One, three, and one patient were diagnosed as having FIGO stage IA, IC, and II MLA, respectively. Four patients with stage IC–II tumor underwent post-operative adjuvant chemotherapy. Three of the four patients whose follow-up information was available did not experience recurrence. In contrast, the remaining patient with stage IA tumor who did not receive any adjuvant treatment developed multiple metastatic recurrences at post-operative 13 months. Histologically, ovarian MLAs characteristically displayed architectural diversity, compactly aggregated small tubules, and eosinophilic intraluminal secretions. Four tumors were found to be associated with endometriotic cysts. Two cases showed some areas of high-grade nuclear atypia, brisk mitotic activity, and necrosis. Immunohistochemically, all cases showed positive immunoreactivities for at least three of the four examined mesonephric markers (GATA3, PAX2, TTF1, and CD10), lack of WT1 expression, non-diffuse p16 immunoreactivity, and wild-type p53 immunostaining pattern. Targeted sequencing analysis revealed that all four examined cases harbored pathogenic KRAS mutations: p.G12V (2/4); p.G12D (1/4); and p.G12C (1/4). In addition, we reviewed the previous literature reporting 60 cases of ovarian MLA. Our findings corroborate those of the previous data regarding the clinical presentation, histological features, immunophenotypes, and molecular alterations. Our observations should encourage pathologists to recognize and accurately diagnose this rare but distinct entity. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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9 pages, 569 KiB  
Article
Validation and Clinical Utility of the Korean Version of the Obstetric Quality-of-Recovery Score (ObsQoR-11) Following Elective Cesarean Section: A Prospective Observational Cohort Study
by RyungA Kang, Seungwon Lee, Eunkyung Lee, Yoon Jee Cho, Ji Seon Jeong, Soo Joo Choi, Mi Sook Gwak, Woo Seog Sim, Duk Kyung Kim and Justin Sangwook Ko
Diagnostics 2022, 12(2), 291; https://doi.org/10.3390/diagnostics12020291 - 24 Jan 2022
Cited by 5 | Viewed by 2162
Abstract
The Obstetric Quality of Recovery (ObsQoR-11) score is a new scoring tool that assesses maternal recovery after cesarean section (CS). We aimed to validate the translated Korean version of ObsQoR-11 (ObsQoR-11K) after elective CS. We validated ObsQoR-11K between March 2021 to August 2021. [...] Read more.
The Obstetric Quality of Recovery (ObsQoR-11) score is a new scoring tool that assesses maternal recovery after cesarean section (CS). We aimed to validate the translated Korean version of ObsQoR-11 (ObsQoR-11K) after elective CS. We validated ObsQoR-11K between March 2021 to August 2021. Validity (convergent, discriminant, and construct), reliability (Cronbach’s α, inter-item, split-half, and test-retest correlation), responsiveness, and clinical feasibility (recruitment rate and time for ObsQoR-11K completion) of ObsQoR-11K were evaluated. One hundred and twenty women completed the ObsQoR-11K 24 h after CS, and 24 women repeated it 25 h after CS. We found good convergent validity between the ObsQoR-11K score and the global health numerical rating scale (NRS) (ρ = 0.73 (95% CI 0.64 to 0.81); p < 0.001). The ObsQoR-11K score discriminated well between good (NRS ≥ 70 mm, n = 68, 69.6 ± 13.7) and poor recovery (NRS < 70 mm, n = 52, 50.6 ± 12.6, p < 0.001). The ObsQoR-11K score showed acceptable internal consistency (Cronbach’s α = 0.78), split-half reliability (0.89), intra-class correlation > 0.4, and no floor or ceiling effect. Of the participants, 100% completed the ObsQoR-11K and median (IQR) time for ObsQoR-11K completion was 81 s (66–97.5 s). ObsQoR-11K is a valid and reliable scoring tool for assessing maternal recovery after elective CS in Korean women. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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14 pages, 868 KiB  
Article
Clinical Significance of BTLA, CD27, CD70, CD28 and CD80 as Diagnostic and Prognostic Markers in Ovarian Cancer
by Janina Świderska, Mateusz Kozłowski, Maria Gaur, Ewa Pius-Sadowska, Sebastian Kwiatkowski, Bogusław Machaliński and Aneta Cymbaluk-Płoska
Diagnostics 2022, 12(2), 251; https://doi.org/10.3390/diagnostics12020251 - 20 Jan 2022
Cited by 6 | Viewed by 1716
Abstract
It is very important to find new diagnostic and prognostic biomarkers. A total of 79 patients were enrolled in the study. The study group consisted of 37 patients with epithelial ovarian cancer, and the control group consisted of 42 patients with benign ovarian [...] Read more.
It is very important to find new diagnostic and prognostic biomarkers. A total of 79 patients were enrolled in the study. The study group consisted of 37 patients with epithelial ovarian cancer, and the control group consisted of 42 patients with benign ovarian lesions. Five proteins involved in the immune response were studied: BTLA, CD27, CD70, CD28, CD80. The study material was serum and peritoneal fluid. The ROC curve was plotted, and the area under the curve was calculated to characterize the sensitivity and specificity of the studied parameters. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. The cut-off level of CD27 was 120.6 pg/mL, with the sensitivity and specificity of 66 and 84% (p = 0.014). Unfavorable prognostic factors determined in serum were: CD27 (for PFS: HR 1.26, 95% CI 1.21–1.29, p = 0.047; for OS: HR 1.20, 95% CI 1.15–1.22, p = 0.014). Unfavorable prognostic factors determined in peritoneal fluid were: BTLA (for OS: HR 1.26, 95% CI 1.25–1.31, p = 0.033). We conclude that CD27 should be considered as a potential biomarker in the diagnosis of ovarian cancer. BTLA and CD27 are unfavorable prognostic factors for ovarian cancer. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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15 pages, 1270 KiB  
Article
Clinical Relevance of Soluble Forms of Immune Checkpoint Molecules sPD-1, sPD-L1, and sCTLA-4 in the Diagnosis and Prognosis of Ovarian Cancer
by Janina Świderska, Mateusz Kozłowski, Katarzyna Nowak, Małgorzata Rychlicka, Dorota Branecka-Woźniak, Sebastian Kwiatkowski, Ewa Pius-Sadowska, Bogusław Machaliński and Aneta Cymbaluk-Płoska
Diagnostics 2022, 12(1), 189; https://doi.org/10.3390/diagnostics12010189 - 13 Jan 2022
Cited by 5 | Viewed by 1612
Abstract
It is crucial to find new diagnostic and prognostic biomarkers. A total of 80 patients were enrolled in the study. The study group consisted of 37 patients with epithelial ovarian cancer, and the control group consisted of 43 patients with benign ovarian cystic [...] Read more.
It is crucial to find new diagnostic and prognostic biomarkers. A total of 80 patients were enrolled in the study. The study group consisted of 37 patients with epithelial ovarian cancer, and the control group consisted of 43 patients with benign ovarian cystic lesions. Three proteins involved in the immune response were studied: PD-1, PD-L1, and CTLA-4. The study material was serum and peritoneal fluid. The ROC curve was plotted, and the area under the curve was calculated to characterize the sensitivity and specificity of the studied parameters. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. The cut-off level of CTLA-4 was 0.595 pg/mL, with the sensitivity and specificity of 70.3% and 90.7% (p = 0.000004). Unfavorable prognostic factors determined in serum were: PD-L1 (for PFS: HR 1.18, 95% CI 1.11–1.21, p = 0.016; for OS: HR 1.17, 95% CI 1.14–1.19, p = 0.048) and PD-1 (for PFS: HR 1.01, 95% CI 0.91–1.06, p = 0.035). Unfavorable prognostic factors determined in peritoneal fluid were: PD-L1 (for PFS: HR 1.08, 95% CI 1.01–1.11, p = 0.049; for OS: HR 1.14, 95% CI 1.10–1.17, p = 0.045) and PD-1 (for PFS: HR 1.21, 95% CI 1.19–1.26, p = 0.044). We conclude that CTLA-4 should be considered as a potential biomarker in the diagnosis of ovarian cancer. PD-L1 and PD-1 concentrations are unfavorable prognostic factors for ovarian cancer. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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10 pages, 24811 KiB  
Article
Endometrial Metaplastic/Reactive Changes Coexistent with Endometrial Hyperplasia and Carcinoma: A Morphological and Immunohistochemical Study
by Antonio Travaglino, Frediano Inzani, Angela Santoro, Damiano Arciuolo, Alessia Piermattei, Sandra Pasquini, Giulia Scaglione, Nicoletta D’Alessandris, Michele Valente, Antonio Raffone, Francesco Fanfani and Gian Franco Zannoni
Diagnostics 2022, 12(1), 63; https://doi.org/10.3390/diagnostics12010063 - 28 Dec 2021
Cited by 3 | Viewed by 2867
Abstract
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 [...] Read more.
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 (n = 12), atypical endometrial hyperplasia (n = 3), serous carcinoma (n = 2), and clear cell carcinoma (n = 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 (p < 0.001) and higher p16 expression (p < 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 (p = 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. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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13 pages, 2948 KiB  
Article
Menopausal Status Combined with Serum CA125 Level Significantly Predicted Concurrent Endometrial Cancer in Women Diagnosed with Atypical Endometrial Hyperplasia before Surgery †
by Yaochen Lou, Jiongbo Liao, Weiwei Shan, Zhiying Xu, Xiaojun Chen and Jun Guan
Diagnostics 2022, 12(1), 6; https://doi.org/10.3390/diagnostics12010006 - 21 Dec 2021
Cited by 2 | Viewed by 2526
Abstract
About 10–66% of patients with atypical endometrial hyperplasia diagnosed before surgery (preoperative-AEH) are found to have concurrent endometrial cancer (EC) at definitive hysterectomy, leading to incomplete primary surgery and delayed adjuvant treatment. This study aims to investigate the potential risk factors of concurrent [...] Read more.
About 10–66% of patients with atypical endometrial hyperplasia diagnosed before surgery (preoperative-AEH) are found to have concurrent endometrial cancer (EC) at definitive hysterectomy, leading to incomplete primary surgery and delayed adjuvant treatment. This study aims to investigate the potential risk factors of concurrent EC in preoperative-AEH patients in a clinical setting with a gynecological pathology review. All patients diagnosed with AEH by endometrial biopsy or curettage that then underwent definitive hysterectomy from January 2016 to December 2019 in a tertiary hospital were retrospectively analyzed. All diagnoses were reviewed by gynecological pathologists. A total of 624 preoperative-AEH patients were included, 30.4% of whom had concurrent EC. In multivariate analysis, postmenopausal status and CA125 ≥ 35 U/mL significantly correlated with concurrent EC (OR = 3.57; 95% CI = 1.80–7.06; OR = 2.15; 95% CI = 1.15–4.03). This risk was remarkably increased in patients with both postmenopausal status and CA125 ≥ 35 U/mL (OR = 16.20; 95% CI = 1.73–151.44). Notably, concurrent EC seemed to occur more frequently in women with postmenopausal time ≥ 5 years (OR = 4.04, 95% CI = 1.80–5.85). In addition, CA125 ≥ 35 U/mL seemed to be an independent risk factor (OR = 5.74; 95% CI = 1.80–18.27) for concurrent intermediate-high-risk EC. Intermediate-high-risk EC was also more commonly seen in preoperative-AEH women with postmenopausal time ≥ 5 years (OR = 5.52, 95% CI = 1.21–25.19, p = 0.027). In conclusion, preoperative-AEH patients with postmenopausal status or elevated level of CA125 might have a high risk of concurrent EC. Adequate pre-surgical evaluation might be suggested for such patients. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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25 pages, 2945 KiB  
Article
Accuracy of Ultrasonography and Magnetic Resonance Imaging for Preoperative Staging of Cervical Cancer—Analysis of Patients from the Prospective Study on Total Mesometrial Resection
by Maciej Stukan, Paul Buderath, Bartosz Szulczyński, Jacek Gębicki and Rainer Kimmig
Diagnostics 2021, 11(10), 1749; https://doi.org/10.3390/diagnostics11101749 - 23 Sep 2021
Cited by 3 | Viewed by 4938
Abstract
We aimed to evaluate the accuracy of ultrasonography with gynecologic examination performed by a gynecological oncologist and magnetic resonance imaging (MRI) interpreted by a radiologist for the local and regional staging of patients with early-stage cervical cancer. The study was a single-site sub-analysis [...] Read more.
We aimed to evaluate the accuracy of ultrasonography with gynecologic examination performed by a gynecological oncologist and magnetic resonance imaging (MRI) interpreted by a radiologist for the local and regional staging of patients with early-stage cervical cancer. The study was a single-site sub-analysis of the multi-institutional prospective, observational Total Mesometrial Resection (TMMR) Register Study, which included all consecutive study patients from Gdynia Oncology Center. Imaging results were compared with pathology findings. A total of 58 consecutive patients were enrolled, and 50 underwent both ultrasonography and MRI. The accuracy of tumor detection and measurement errors was comparable across ultrasonography and MRI. There were no significant differences between ultrasonography and MRI in the accuracy of detecting parametrial involvement (92%, confidence interval (CI) 84–100% vs. 76%, CI 64–88%, p = 0.3), uterine corpus infiltration (94%, CI 87–100% vs. 86%, CI 76–96%, p = 0.3), and vaginal fornix involvement (96%, CI 91–100% vs. 76%, CI 64–88%, p = 0.3). The importance of uterine corpus involvement for the first-line lymph node metastases was presented in few cases. The accuracy of ultrasonography was higher than MRI for correctly predicting tumor stage: International Federation of Gynecology and Obstetrics (FIGO)–2018: 69%, CI 57–81% vs. 42%, CI 28–56%, p = 0.002, T (from TNM system): 79%, CI 69–90% vs. 52%, CI 38–66%, p = 0.0005, and ontogenetic tumor staging: 88%, CI 80–96% vs. 70%, CI 57–83%, p = 0.005. For patients with cervical cancer who are eligible for TMMR and therapeutic lymphadenectomy, the accuracy of ultrasonography performed by gynecological oncologists is not inferior to that of MRI interpreted by a radiologist for assessing specific local parameters, and is more accurate for local staging of the disease and is thus more clinically useful for planning adequate surgical treatment. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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21 pages, 12270 KiB  
Article
Accuracy of Pretreatment Ultrasonography Assessment of Intra-Abdominal Spread in Epithelial Ovarian Cancer: A Prospective Study
by Agnieszka Tomasińska, Maciej Stukan, Michał Badocha and Aleksandra Myszewska
Diagnostics 2021, 11(9), 1600; https://doi.org/10.3390/diagnostics11091600 - 02 Sep 2021
Cited by 4 | Viewed by 3317
Abstract
The aim of this study was to test the accuracy of ultrasonography performed by gynecological oncologists for the preoperative assessment of epithelial ovarian cancer (EOC) spread in the pelvis and abdominal cavity. A prospective, observational cohort study was performed at a single tertiary [...] Read more.
The aim of this study was to test the accuracy of ultrasonography performed by gynecological oncologists for the preoperative assessment of epithelial ovarian cancer (EOC) spread in the pelvis and abdominal cavity. A prospective, observational cohort study was performed at a single tertiary cancer care unit. Patients with suspected EOC were recruited and underwent comprehensive transvaginal and abdominal ultrasonography performed by a gynecological oncologist. Sixteen intra-abdominal localizations and parameters were assessed using ultrasonography and compared with surgical-pathological status (reference standard). Sensitivity, specificity, positive and negative predictive values, and overall accuracy were calculated. Differences were analyzed using Fisher’s exact and chi-square tests. Ultimately, we included 132 patients (median age 62 years), of whom 67% were in stage IIIC–IVB and 72% had serous cancer. Overall prediction accuracies for the involvement of the omentum, small bowel mesentery root, and frozen pelvis, and detecting ascites were >90%. Detecting the involvement of the pelvis peritoneum, liver and spleen hilum, and rectosigmoid colon, and predictions of disease stage and residual disease had overall accuracies of 80–90%. The lowest accuracy was for involvement of the abdominal peritoneum (69%) and diaphragm peritoneum (right 71%; left 75%) and surgical complexity prediction (77%). Stratification of results by presence or absence of ascites revealed significantly higher specificity of ultrasonography (clinically meaningful) for assessments of the abdominal/pelvic peritoneum, spleen hilum, and rectum wall, if there were ascites. A gynecological oncologist, experienced in surgery and sonology, performing comprehensive ultrasonography on patients with EOC can accurately detect intraperitoneal lesions and recognize critical disease manifestations and predict stage, surgical complexity, and residual disease, which allow accurate qualification of patients for primary debulking surgery or neoadjuvant chemotherapy. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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12 pages, 3233 KiB  
Article
Metabolic Changes in Maternal and Cord Blood in One Case of Pregnancy-Associated Breast Cancer Seen by Fluorescence Lifetime Imaging Microscopy
by Li Zhou, Yawei Kong, Junxin Wu, Xingzhi Li, Yiyan Fei, Jiong Ma, Yulan Wang and Lan Mi
Diagnostics 2021, 11(8), 1494; https://doi.org/10.3390/diagnostics11081494 - 19 Aug 2021
Viewed by 1968
Abstract
Pregnancy-associated breast cancer (PABC) is a rare disease, which is frequently diagnosed at an advanced stage due to limitations in current diagnostic methods. In this study, fluorescence lifetime imaging microscopy (FLIM) was used to study the metabolic changes by measuring maternal blood and [...] Read more.
Pregnancy-associated breast cancer (PABC) is a rare disease, which is frequently diagnosed at an advanced stage due to limitations in current diagnostic methods. In this study, fluorescence lifetime imaging microscopy (FLIM) was used to study the metabolic changes by measuring maternal blood and umbilical cord blood via the autofluorescence of coenzymes, reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), and flavin adenine dinucleotide (FAD). The NAD(P)H data showed that a PABC case had significant differences compared with normal cases, which may indicate increased glycolysis. The FAD data showed that both maternal and cord blood of PABC had shorter mean lifetimes and higher bound-FAD ratios. The significant differences suggested that FLIM testing of blood samples may be a potential method to assist in PABC non-radiative screening. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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15 pages, 1074 KiB  
Article
Ultrasound Measurement of Tumor-Free Distance from the Serosal Surface as the Alternative to Measuring the Depth of Myometrial Invasion in Predicting Lymph Node Metastases in Endometrial Cancer
by Marcin Liro, Marcin Śniadecki, Ewa Wycinka, Szymon Wojtylak, Michał Brzeziński, Agata Stańczak and Dariusz Wydra
Diagnostics 2021, 11(8), 1472; https://doi.org/10.3390/diagnostics11081472 - 14 Aug 2021
Cited by 6 | Viewed by 3880
Abstract
Background: Ultrasonography’s usefulness in endometrial cancer (EC) diagnosis consists in its roles in staging and prediction of metastasis. Ultrasound-measured tumor-free distance from the tumor to the uterine serosa (uTFD) is a promising marker for these diagnostic and prognostic variables. The aim of the [...] Read more.
Background: Ultrasonography’s usefulness in endometrial cancer (EC) diagnosis consists in its roles in staging and prediction of metastasis. Ultrasound-measured tumor-free distance from the tumor to the uterine serosa (uTFD) is a promising marker for these diagnostic and prognostic variables. The aim of the study was to determine the usefulness of this biomarker in locoregional staging, and thus in the prediction of lymph node metastasis (LNM). Methods: We conducted a single-institutional, prospective study on 116 consecutive patients with EC who underwent 2D transvaginal ultrasound examination. The uTFD marker was compared with the depth of ultrasound-measured myometrial invasion (uMI). Univariable and multivariable logit models were evaluated to assess the predictive power of the uTFD and uMI in regard to LNM. The reference standard was a final histopathology result. Survival was assessed by the Kaplan–Meier method. Results: LNM was found in 17% of the patients (20/116). In the univariable analysis, uMI and uTFD were significant predictors of LNM. The accuracy was 70.7%, and the NPV was 92.68% (OR 4.746, 95% CI 1.710–13.174) for uMI (p = 0.002), and they were 63.8% and 89.02% (OR 0.842, 95% CI 0.736–0.963), respectively, for uTFD (p = 0.01). The cutoff value for uTFD in the prediction of LNM was 5.2 mm. The association between absence of LNM and biomarker values of uMI < 1/2 and uTFD ≥ 5.2 mm was greater than that between the presence of metastases and uMI > 1/2 and uTFD values <5.2 mm. In the multivariable analysis, the accuracy of the uMI–uTFD model was 74%, and its NPV was 90.24% (p = non-significant). Neither uMI nor uTFD were surrogates for overall and recurrence-free survivals in endometrial cancer. Conclusions: Both uMI and uTFD, either alone or in combination, were valuable tools for gaining additional preoperative information on expected lymph node status. Negative lymph nodes status was better described by ultrasound biomarkers than a positive status. It was easier to use the uTFD rather than the uMI measurement as a biomarker of EC invasion, and the former still maintained a similar predictive value for lymph node metastases to the latter at diagnosis. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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13 pages, 1463 KiB  
Article
iPMI: Machine Learning-Aided Identification of Parametrial Invasion in Women with Early-Stage Cervical Cancer
by Phasit Charoenkwan, Watshara Shoombuatong, Chalaithorn Nantasupha, Tanarat Muangmool, Prapaporn Suprasert and Kittipat Charoenkwan
Diagnostics 2021, 11(8), 1454; https://doi.org/10.3390/diagnostics11081454 - 12 Aug 2021
Cited by 7 | Viewed by 2353
Abstract
Radical hysterectomy is a recommended treatment for early-stage cervical cancer. However, the procedure is associated with significant morbidities resulting from the removal of the parametrium. Parametrial cancer invasion (PMI) is found in a minority of patients but the efficient system used to predict [...] Read more.
Radical hysterectomy is a recommended treatment for early-stage cervical cancer. However, the procedure is associated with significant morbidities resulting from the removal of the parametrium. Parametrial cancer invasion (PMI) is found in a minority of patients but the efficient system used to predict it is lacking. In this study, we develop a novel machine learning (ML)-based predictive model based on a random forest model (called iPMI) for the practical identification of PMI in women. Data of 1112 stage IA-IIA cervical cancer patients who underwent primary surgery were collected and considered as the training dataset, while data from an independent cohort of 116 consecutive patients were used as the independent test dataset. Based on these datasets, iPMI-Econ was then developed by using basic clinicopathological data available prior to surgery, while iPMI-Power was also introduced by adding pelvic node metastasis and uterine corpus invasion to the iPMI-Econ. Both 10-fold cross-validations and independent test results showed that iPMI-Power outperformed other well-known ML classifiers (e.g., logistic regression, decision tree, k-nearest neighbor, multi-layer perceptron, naive Bayes, support vector machine, and extreme gradient boosting). Upon comparison, it was found that iPMI-Power was effective and had a superior performance to other well-known ML classifiers in predicting PMI. It is anticipated that the proposed iPMI may serve as a cost-effective and rapid approach to guide important clinical decision-making. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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15 pages, 1732 KiB  
Article
The Correlation of the IETA Ultrasound Score with the Histopathology Results for Women with Abnormal Bleeding in Western Romania
by Alexandru Marius Furau, Mirela Marioara Toma, Cringu Ionescu, Cristian Furau, Simona Bungau, Mihai Dimitriu, Delia Mirela Tit, Gheorghe Furau, Izabella Petre and Marius Craina
Diagnostics 2021, 11(8), 1342; https://doi.org/10.3390/diagnostics11081342 - 26 Jul 2021
Cited by 4 | Viewed by 3179
Abstract
In the early differential diagnosis of endometrial cancer (EC), decisive and mandatory histological aspects are considered, in addition to obvious clinical manifestations. In addition, sonographic aspects are characteristic in relation to the stage, degree, and histological types of identified cancer. This bi-center retrospective [...] Read more.
In the early differential diagnosis of endometrial cancer (EC), decisive and mandatory histological aspects are considered, in addition to obvious clinical manifestations. In addition, sonographic aspects are characteristic in relation to the stage, degree, and histological types of identified cancer. This bi-center retrospective observational study included 594 women with abnormal uterine bleeding outside pregnancy, for which a biopsy was performed in the Obstetrics and Gynecology Departments of the Emergency County Hospitals of Arad and Timis Counties, Romania, between 2015 and 2019. Most of the cases were represented by EC or endometrial hyperplasia (EH). Of the 594 cases, 25.5% (n = 153) were EC at women aged between 41 and 85 years. High International Endometrial Tumor Analysis (IETA) scores (3, 4) were associated with a relative risk of 2.9335 compared with other endometrial lesions (95% CI 2.3046 to 3.734, p < 0.0001, NNT 1.805). Histological aspects and pelvic ultrasound using IETA scores represent valuable noninvasive assets in diagnosing and differentiating endometrial cancer from benign uterine pathology. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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21 pages, 3159 KiB  
Article
Assessment of Potential Risk Factors and Skin Ultrasound Presentation Associated with Breast Cancer-Related Lymphedema in Long-Term Breast Cancer Survivors
by Khairunnisa’ Md Yusof, Kelly A. Avery-Kiejda, Shafinah Ahmad Suhaimi, Najwa Ahmad Zamri, Muhammad Ehsan Fitri Rusli, Rozi Mahmud, Suraini Mohd Saini, Shahad Abdul Wahhab Ibraheem, Maha Abdullah and Rozita Rosli
Diagnostics 2021, 11(8), 1303; https://doi.org/10.3390/diagnostics11081303 - 21 Jul 2021
Cited by 9 | Viewed by 3698
Abstract
Breast cancer has been reported to have the highest survival rate among various cancers. However, breast cancer survivors face several challenges following breast cancer treatment including breast cancer-related lymphedema (BCRL), sexual dysfunction, and psychological distress. This study aimed to investigate the potential risk [...] Read more.
Breast cancer has been reported to have the highest survival rate among various cancers. However, breast cancer survivors face several challenges following breast cancer treatment including breast cancer-related lymphedema (BCRL), sexual dysfunction, and psychological distress. This study aimed to investigate the potential risk factors of BCRL in long term breast cancer survivors. A total of 160 female breast cancer subjects were recruited on a voluntary basis and arm lymphedema was assessed through self-reporting of diagnosis, arm circumference measurement, and ultrasound examination. A total of 33/160 or 20.5% of the women developed BCRL with significantly higher scores for upper extremity disability (37.14 ± 18.90 vs. 20.08 ± 15.29, p < 0.001) and a lower score for quality of life (103.91 ± 21.80 vs. 115.49 ± 16.80, p = 0.009) as compared to non-lymphedema cases. Univariate analysis revealed that multiple surgeries (OR = 5.70, 95% CI: 1.21–26.8, p < 0.001), axillary lymph nodes excision (>10) (OR = 2.83, 95% CI: 0.94–8.11, p = 0.047), being overweight (≥25 kg/m2) (OR = 2.57, 95% CI: 1.04 – 6.38, p = 0.036), received fewer post-surgery rehabilitation treatment (OR = 2.37, 95% CI: 1.05–5.39, p = 0.036) and hypertension (OR = 2.38, 95% CI: 1.01–5.62, p = 0.043) were associated with an increased risk of BCRL. Meanwhile, multivariate analysis showed that multiple surgeries remained significant and elevated the likelihood of BCRL (OR = 5.83, 95% CI: 1.14–29.78, p = 0.034). Arm swelling was more prominent in the forearm area demonstrated by the highest difference of arm circumference measurement when compared to the upper arm (2.07 ± 2.48 vs. 1.34 ± 1.91 cm, p < 0.001). The total of skinfold thickness of the affected forearm was also significantly higher than the unaffected arms (p < 0.05) as evidenced by the ultrasound examination. The continuous search for risk factors in specific populations may facilitate the development of a standardized method to reduce the occurrence of BCRL and provide better management for breast cancer patients. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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17 pages, 3165 KiB  
Article
Dendritic Cells Are Associated with Prognosis and Survival in Breast Cancer
by Joanna Szpor, Joanna Streb, Anna Glajcar, Paulina Frączek, Aleksandra Winiarska, Katarzyna E. Tyrak, Paweł Basta, Krzysztof Okoń, Robert Jach and Diana Hodorowicz-Zaniewska
Diagnostics 2021, 11(4), 702; https://doi.org/10.3390/diagnostics11040702 - 14 Apr 2021
Cited by 22 | Viewed by 2392
Abstract
Dendritic cells (DCs) constitute a part of the tumour microenvironment, but we are still far from understanding their complex role in immune response to the tumour. This study aimed to investigate the density of DCs expressing CD1a, CD83, CD123, DC-LAMP3 (CD208) and DC-SIGN [...] Read more.
Dendritic cells (DCs) constitute a part of the tumour microenvironment, but we are still far from understanding their complex role in immune response to the tumour. This study aimed to investigate the density of DCs expressing CD1a, CD83, CD123, DC-LAMP3 (CD208) and DC-SIGN (CD209) in breast cancer. The correlations between DC density and molecular subtype of breast cancer, its hormone receptor status, spatial location and their associations with clinical and pathological prognostic factors were evaluated. We have shown that intratumoural CD1a+ cells were significantly associated with progression-free survival. For LAMP3+ and CD123+ DCs, higher cell densities were associated with non-luminal as compared to luminal cancer phenotype. In contrast, dense CD83+ DC infiltrate was observed in luminal tumours. The number of CD1a+ DCs in both locations was the highest in luminal B/HER2+ cancers. The highest positive cell count of LAMP3+ cells was observed in the triple-negative subtype in both locations. We found higher numbers of LAMP3+ DCs both intratumourally and at the invasive margin, as well as CD123+ DCs intratumourally in tumours with negative expression of oestrogen or progesterone receptors. Our study demonstrates associations between DC subpopulations and histological and clinical characteristics, as well as molecular subtypes in breast carcinoma. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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Review

Jump to: Research, Other

12 pages, 1742 KiB  
Review
Diagnostically Challenging Subtypes of Invasive Lobular Carcinomas: How to Avoid Potential Diagnostic Pitfalls
by Nektarios Koufopoulos, Ioannis S. Pateras, Alina Roxana Gouloumis, Argyro Ioanna Ieronimaki, Andriani Zacharatou, Aris Spathis, Danai Leventakou, Panagiota Economopoulou, Amanda Psyrri, Nikolaos Arkadopoulos and Ioannis G. Panayiotides
Diagnostics 2022, 12(11), 2658; https://doi.org/10.3390/diagnostics12112658 - 01 Nov 2022
Viewed by 2054
Abstract
Invasive lobular carcinoma is the most common special breast carcinoma subtype, with unique morphological (discohesive cells, single-cell files, targetoid pattern) and immunohistochemical (loss of E-cadherin and β-catenin staining) features. Moreover, ILC displays a poor response to neoadjuvant therapy, a different metastatic pattern compared [...] Read more.
Invasive lobular carcinoma is the most common special breast carcinoma subtype, with unique morphological (discohesive cells, single-cell files, targetoid pattern) and immunohistochemical (loss of E-cadherin and β-catenin staining) features. Moreover, ILC displays a poor response to neoadjuvant therapy, a different metastatic pattern compared to invasive breast carcinoma of no special type, as well as unique molecular characteristics. In addition to the classic variant of invasive lobular carcinoma, several other well-recognized variants exist, including classic, alveolar, tubulolobular, solid, pleomorphic, signet-ring, and mixed. Furthermore, three novel variants of invasive lobular carcinoma, i.e., with extracellular mucin production, papillary features, and tubular elements, have been described during the last decade. We herewith focus on the unique morphological and immunohistochemical characteristics of these novel varieties of invasive lobular carcinoma, as well as differential diagnostic considerations and potential diagnostic pitfalls, especially when dealing with biopsy specimens. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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25 pages, 2989 KiB  
Review
An Update on the General Features of Breast Cancer in Male Patients—A Literature Review
by Sinziana Ionescu, Alin Codrut Nicolescu, Marian Marincas, Octavia-Luciana Madge and Laurentiu Simion
Diagnostics 2022, 12(7), 1554; https://doi.org/10.3390/diagnostics12071554 - 26 Jun 2022
Cited by 4 | Viewed by 3268
Abstract
Male breast cancers are uncommon, as men account for less than 1 percent of all breast carcinomas. Among the predisposing risk factors for male breast cancer, the following appear to be significant: (a) breast/chest radiation exposure, (b) estrogen use, diseases associated with hyper-estrogenism, [...] Read more.
Male breast cancers are uncommon, as men account for less than 1 percent of all breast carcinomas. Among the predisposing risk factors for male breast cancer, the following appear to be significant: (a) breast/chest radiation exposure, (b) estrogen use, diseases associated with hyper-estrogenism, such as cirrhosis or Klinefelter syndrome, and (c) family health history. Furthermore, there are clear familial tendencies, with a higher incidence among men who have a large number of female relatives with breast cancer and (d) major inheritance susceptibility. Moreover, in families with BRCA mutations, there is an increased risk of male breast cancer, although the risk appears to be greater with inherited BRCA2 mutations than with inherited BRCA1 mutations. Due to diagnostic delays, male breast cancer is more likely to present at an advanced stage. A core biopsy or a fine needle aspiration must be performed to confirm suspicious findings. Infiltrating ductal cancer is the most prevalent form of male breast cancer, while invasive lobular carcinoma is extremely uncommon. Male breast cancer is almost always positive for hormone receptors. A worse prognosis is associated with a more advanced stage at diagnosis for men with breast cancer. Randomized controlled trials which recruit both female and male patients should be developed in order to gain more consistent data on the optimal clinical approach. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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10 pages, 3446 KiB  
Review
Patterns of Myometrial Invasion in Endometrial Adenocarcinoma with Emphasizing on Microcystic, Elongated and Fragmented (MELF) Glands Pattern: A Narrative Review of the Literature
by Svetlana Mateva, Margarita Nikolova and Angel Yordanov
Diagnostics 2021, 11(9), 1707; https://doi.org/10.3390/diagnostics11091707 - 18 Sep 2021
Cited by 3 | Viewed by 4955
Abstract
Endometrioid endometrial adenocarcinoma (EEC) is the most common malignancy of the female genital tract. According to the 2009 FIGO staging system, the depth of myometrial invasion (MI), and tumor spread to adjacent organs or tissues are the staging criteria for endometrial carcinoma (EC). [...] Read more.
Endometrioid endometrial adenocarcinoma (EEC) is the most common malignancy of the female genital tract. According to the 2009 FIGO staging system, the depth of myometrial invasion (MI), and tumor spread to adjacent organs or tissues are the staging criteria for endometrial carcinoma (EC). Therefore, assessment of the depth of MI is of great importance. There is a spectrum of morphological patterns of MI. Still, their number and features vary according to the scientific literature, with a certain overlap that creates difficulties and controversies in the precise assessment of MI depth. The purpose of this review is to present and discuss the most important and recent information about patterns of MI, focusing on the more aggressive and the elongated and fragmented glands (MELF) pattern in particular. Assessment of MI depth and correct staging of EC is possible only after the precise recognition of each MI pattern. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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Other

Jump to: Research, Review

13 pages, 2536 KiB  
Case Report
Genomic Breakpoints’ Characterization of a Large CHEK2 Duplication in an Italian Family with Hereditary Breast Cancer
by Aldo Germani, Daniele Guadagnolo, Valentina Salvati, Caterina Micolonghi, Rita Mancini, Gioia Mastromoro, Soha Sadeghi, Simona Petrucci, Antonio Pizzuti and Maria Piane
Diagnostics 2022, 12(7), 1520; https://doi.org/10.3390/diagnostics12071520 - 22 Jun 2022
Viewed by 1622
Abstract
CHEK2 (checkpoint kinase 2; MIM# 604373) is a tumor suppressor gene that encodes a serine threonine kinase involved in pathways such as DNA repair, cell cycle arrest, mitosis, and apoptosis. Pathogenic variants in CHEK2 contribute to a moderately increased risk of breast and [...] Read more.
CHEK2 (checkpoint kinase 2; MIM# 604373) is a tumor suppressor gene that encodes a serine threonine kinase involved in pathways such as DNA repair, cell cycle arrest, mitosis, and apoptosis. Pathogenic variants in CHEK2 contribute to a moderately increased risk of breast and other cancers. Several variant classes have been reported, either point mutations or large intragenic rearrangements. However, a significant portion of reported variants has an uncertain clinical significance. We report an intragenic CHEK2 duplication, ranging from intron 5 to intron 13, identified in an Italian family with hereditary breast cancer. Using long range PCR, with duplication-specific primers, we were able to ascertain the genomic breakpoint. We also performed a real-time PCR to assess a possible loss-of-function effect. The genomic characterization of large intragenic rearrangements in cancer susceptibility genes is important for the clinical management of the carriers and for a better classification of rare variants. The molecular definition of breakpoints allows for the prediction of the impact of the variant on transcripts and proteins, aiding in its characterization and clinical classification. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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9 pages, 2358 KiB  
Case Report
Metaplastic Matrix-Producing Carcinoma and Apocrine Lobular Carcinoma In Situ Associated with Microglandular Adenosis: A Unique Case Report
by Nektarios Koufopoulos, Dionysios Dimas, Foteini Antoniadou, Kyparissia Sitara, Dimitrios Balalis, Ioannis Boutas, Alina Roxana Gouloumis, Adamantia Kontogeorgi and Lubna Khaldi
Diagnostics 2022, 12(6), 1458; https://doi.org/10.3390/diagnostics12061458 - 13 Jun 2022
Cited by 5 | Viewed by 1609
Abstract
Microglandular adenosis is a non-lobulocentric haphazard proliferation of small round glands composed of a single layer of flat to cuboidal epithelial cells. The glandular structures lack a myoepithelial layer; however, they are surrounded by a basement membrane. Its clinical course is benign, when [...] Read more.
Microglandular adenosis is a non-lobulocentric haphazard proliferation of small round glands composed of a single layer of flat to cuboidal epithelial cells. The glandular structures lack a myoepithelial layer; however, they are surrounded by a basement membrane. Its clinical course is benign, when it is not associated with invasive carcinoma. In around 30% of cases, there is a gradual transition to atypical microglandular adenosis, carcinoma in situ, and invasive breast carcinoma of several different histologic subtypes, including an invasive carcinoma of no special type, metaplastic matrix-producing carcinoma, secretory carcinoma, metaplastic carcinoma with squamous differentiation, acinic cell carcinoma, spindle cell carcinoma, and adenoid cystic carcinoma. Recent molecular studies suggest that microglandular adenosis is a non-obligate precursor of triple-negative breast carcinomas. In this manuscript, we present a unique case of microglandular adenosis associated with metaplastic matrix-producing carcinoma and HER-2 neu oncoprotein positive pleomorphic lobular carcinoma in situ with apocrine differentiation in a 79-year-old patient. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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9 pages, 1459 KiB  
Case Report
Desmoplastic Small Round Cell Tumor of the Uterus: A Report of Molecularly Confirmed Case with EWSR1-WT1 Fusion
by Pavel Dundr, Jana Drozenová, Radoslav Matěj, Michaela Bártů, Kristýna Němejcová, Helena Robová, Lukáš Rob, Jan Hojný and Ivana Stružinská
Diagnostics 2022, 12(5), 1184; https://doi.org/10.3390/diagnostics12051184 - 10 May 2022
Cited by 2 | Viewed by 1723
Abstract
We report a case of a 49-year-old female with desmoplastic small round cell tumor of the uterus (DSRCT). Histologically, in some areas the tumor showed typical features with ample desmoplastic stroma, while in other areas the tumor cells diffusely infiltrated myometrium with only [...] Read more.
We report a case of a 49-year-old female with desmoplastic small round cell tumor of the uterus (DSRCT). Histologically, in some areas the tumor showed typical features with ample desmoplastic stroma, while in other areas the tumor cells diffusely infiltrated myometrium with only focal desmoplastic reaction. Immunohistochemically, the tumor cells showed diffuse positivity for desmin, CD56, CD57, EMA and cyclin D1. Focal positivity was present for antibodies against cytokeratin AE1/3, BerEP4, NSE, IFITM1 and CD10. The WT-1 antibody (against the N-terminus) showed cytoplasmic positivity in some tumor cells, while the nuclei were negative. P53 expression was wild-type. The Ki-67 index (MIB1 antibody) was about 55%. Other markers examined including transgelin, myogenin, synaptophysin, chromogranin, h-caldesmon, PAX8, and CD117 were all negative. NGS analysis revealed a fusion transcript of the EWSR1 and WT1 genes. DSRCT of the uterus is a rare neoplasm, as only two cases have been reported so far. However, only one of these cases was examined molecularly with a confirmation of the characteristic EWSR1-WT1 fusion. We report a second case of molecularly confirmed DSRCT of the uterus and discuss its clinical features, differential diagnosis and the significance of molecular testing. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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13 pages, 3896 KiB  
Case Report
Alveolar Soft Part Sarcoma of the Uterus: Clinicopathological and Molecular Characteristics
by Yurimi Lee, Kiyong Na, Ha Young Woo and Hyun-Soo Kim
Diagnostics 2022, 12(5), 1102; https://doi.org/10.3390/diagnostics12051102 - 27 Apr 2022
Cited by 2 | Viewed by 2100
Abstract
Alveolar soft part sarcoma (ASPS) is a rare malignant mesenchymal tumor mainly affecting adolescents and young adults, with a predilection for the deep soft tissues of extremities. ASPS arising in the female genital tract is extremely rare and poses a significant diagnostic challenge. [...] Read more.
Alveolar soft part sarcoma (ASPS) is a rare malignant mesenchymal tumor mainly affecting adolescents and young adults, with a predilection for the deep soft tissues of extremities. ASPS arising in the female genital tract is extremely rare and poses a significant diagnostic challenge. We herein present two rare cases of ASPS, one occurring in the uterine corpus of a 27-year-old woman, and the other in the uterine cervix of a 10-year-old girl. We described the clinical, histological, immunophenotypical, and molecular characteristics of primary uterine ASPS. We performed immunostaining for transcription factor E3 (TFE3), human melanoma black 45 (HMB45), melan-A, desmin, pan-cytokeratin (CK), paired box 8 (PAX8), CD10, hormone receptors, and S100, and targeted RNA and DNA sequencing using commercially available cancer gene panel. In case 1, a 27-year-old woman was referred to our hospital after laparoscopic uterine myomectomy at an outside hospital. Imaging studies revealed a residual tumor in the uterine corpus. In case 2, a 10-year-old girl underwent surgical excision for the cervical mass and was diagnosed as having ASPS. She was then referred to our hospital for further management. Both patients received total hysterectomy. Histologically, they displayed characteristic histological features of ASPS. Strong nuclear TFE3 immunoreactivity, periodic acid-Schiff-positive, diastase-resistant intracytoplasmic rod-shaped crystalloids or granules, and the identification of ASPSCR1–TFE3 fusion confirmed the diagnosis of ASPS in both cases. Lack of immunoreactivity for HMB45, melan-A, desmin, pan-CK, PAX8, and S100 excluded the possibility of perivascular epithelioid cell tumor, clear cell sarcoma, metastatic renal cell carcinoma, granular cell tumor, and paraganglioma. Our observations can help pathologists make an accurate diagnosis of uterine ASPS and suggest that pathologists should include primary uterine ASPS in the differential diagnosis of uterine mesenchymal tumors. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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7 pages, 2616 KiB  
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Dissecting Gonadoblastoma of the Ovary Coexistent with an Atypical Endometriotic Cyst: Incidental Detection in Cystectomy Specimen of a Woman with 46,XX Karyotype
by Hera Jung, Bo Seong Yun, Yoon Yang Jung and Hyun-Soo Kim
Diagnostics 2022, 12(3), 660; https://doi.org/10.3390/diagnostics12030660 - 09 Mar 2022
Cited by 2 | Viewed by 3373
Abstract
Dissecting gonadoblastoma (DGB) of the ovary, a recently described terminology, defines a unique distribution of neoplastic germ cells. Here, we report a case of incidental DGB coexistent with an atypical endometriotic cyst occurring in a 23-year-old woman. The ovarian cyst was lined by [...] Read more.
Dissecting gonadoblastoma (DGB) of the ovary, a recently described terminology, defines a unique distribution of neoplastic germ cells. Here, we report a case of incidental DGB coexistent with an atypical endometriotic cyst occurring in a 23-year-old woman. The ovarian cyst was lined by endometrial-like glands and stroma. Some glands displayed nuclear enlargement and hyperchromasia, and abundant eosinophilic cytoplasm with occasional intracytoplasmic hemosiderin and mucin vacuoles. The neoplastic germ cells resembled those of ovarian dysgerminoma and were diffusely distributed within the ovarian stroma, which was stretched around the wall of the endometriotic cyst. These cells were arranged in nests and cords, possessing clear cytoplasm and centrally located round nuclei with prominent nucleoli and occasional mitoses. Chromosomal analysis revealed a 46,XX karyotype. We describe the clinical, histological, immunophenotypical, and genetic features of ovarian DGB incidentally detected in the ovarian cystectomy specimen of a woman with normal female karyotype. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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6 pages, 2100 KiB  
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Extraskeletal Mesenchymal Chondrosarcoma of the Uterus
by Yurimi Lee, Sangjoon Choi and Hyun-Soo Kim
Diagnostics 2022, 12(3), 643; https://doi.org/10.3390/diagnostics12030643 - 05 Mar 2022
Cited by 3 | Viewed by 1877
Abstract
Mesenchymal chondrosarcoma is an uncommon malignant mesenchymal tumor with an aggressive behavior. Diagnoses of mesenchymal chondrosarcoma are established based on histomorphological, immunohistochemical, and molecular findings. Only one case of extraskeletal mesenchymal chondrosarcoma (EMC) of the uterus has been reported. This article presents the [...] Read more.
Mesenchymal chondrosarcoma is an uncommon malignant mesenchymal tumor with an aggressive behavior. Diagnoses of mesenchymal chondrosarcoma are established based on histomorphological, immunohistochemical, and molecular findings. Only one case of extraskeletal mesenchymal chondrosarcoma (EMC) of the uterus has been reported. This article presents the second case of primary uterine EMC, occurring in a 33-year-old woman. We describe the histological and immunophenotypical features of EMC. Our observations will help pathologists and clinicians perform accurate histological diagnoses of uterine EMC and plan appropriate treatment strategies for this rare tumor. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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6 pages, 7288 KiB  
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Local and Metastatic Relapses in a Young Woman with Papillary Squamous Cell Carcinoma of the Uterine Cervix
by Ha Young Woo and Hyun-Soo Kim
Diagnostics 2022, 12(3), 599; https://doi.org/10.3390/diagnostics12030599 - 26 Feb 2022
Cited by 3 | Viewed by 3468
Abstract
Papillary squamous cell carcinoma (PSCC) is a rare histological type of cervical carcinoma whose biological behavior has not been fully established. A 33-year-old woman with an exophytic cervical mass underwent radical hysterectomy and bilateral pelvic lymph node dissection. Histological examination of the tumor [...] Read more.
Papillary squamous cell carcinoma (PSCC) is a rare histological type of cervical carcinoma whose biological behavior has not been fully established. A 33-year-old woman with an exophytic cervical mass underwent radical hysterectomy and bilateral pelvic lymph node dissection. Histological examination of the tumor revealed numerous papillary fronds lined by atypical stratified squamous cells, resembling high-grade squamous intraepithelial lesions or urothelium. She was diagnosed with stage IB1 PSCC. Three months postoperatively, a 5.7 cm vaginal stump mass was detected. She received chemoradiotherapy, which helped her achieve a complete response. However, nine months postoperatively, she developed pelvic lymph node metastases. We present a rare case of recurrent cervical PSCC in a young woman. PSCC of the uterine cervix can recur rapidly within just a few months and become aggressive, as in the present case. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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7 pages, 1033 KiB  
Case Report
Diagnostic Framework of Pelvic Massive Necrosis with Peritonitis following Chemoradiation for Locally Advanced Cervical Cancer: When Is the Surgery Not Demandable? A Case Report and Literature Review
by Elisabetta Sanna, Giacomo Chiappe, Fabrizio Lavra, Sonia Nemolato, Sara Oppi, Antonio Macciò and Clelia Madeddu
Diagnostics 2022, 12(2), 440; https://doi.org/10.3390/diagnostics12020440 - 09 Feb 2022
Cited by 1 | Viewed by 2133
Abstract
Concurrent platinum-based chemoradiation (CCRT) is the established treatment for locally advanced cervical cancer and has an acceptable toxicity. Radiation-induced necrosis of the uterus and pelvic tissue is a rare and usually late potential complication. Limited data are available about its management. Here, we [...] Read more.
Concurrent platinum-based chemoradiation (CCRT) is the established treatment for locally advanced cervical cancer and has an acceptable toxicity. Radiation-induced necrosis of the uterus and pelvic tissue is a rare and usually late potential complication. Limited data are available about its management. Here, we describe a case of a patient affected by a locally advanced cervical cancer (stage IVA) who received CCRT, obtaining a partial response with persistence of bladder and rectal infiltration. Unfortunately, after the first brachytherapy dose, the patient developed a worsening clinical picture with fever and altered laboratory data indicative of sepsis; the computed tomography revealed a massive necrosis of the uterus with pelvic abscess and peritonitis. We performed a laparoscopic emergency surgery with removal of the necrotic tissue, supracervical hysterectomy, bilateral-oophorectomy, and abscess drainage. Thereafter, once the severe inflammatory condition was resolved, the patient underwent pelvic exenteration with palliative/curative intent. The postoperative PET/CT was negative for residual disease. However, the patient needed further hospitalization for re-occurrence of peritonitis with multiple abscesses. A careful diagnosis is crucial in locally advanced cervical cancer patients who, after CCRT, present persistent pain and problematic findings at imaging and laboratory parameters. In these cases, radiation-induced necrosis of the pelvis should be suspected. This case helps to clarify the central role of surgery, especially when actinic necrosis leads to complications such as abscess, fistulae, and extensive tissue destruction that cannot be conservatively medically handled. Laparoscopy represents an ideal approach to realizing the correct diagnosis, as well as enabling the performance of important therapeutic surgical procedures. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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12 pages, 14811 KiB  
Case Report
Yolk Sac Tumor of the Omentum: A Case Report and Literature Review
by Daniela Fischerova, Tereza Indrielle-Kelly, Andrea Burgetova, Rosalie Jana Bennett, Maria Gregova, Pavel Dundr, Ondrej Nanka, Giulia Gambino, Filip Frühauf, Roman Kocian, Martina Borcinova and David Cibula
Diagnostics 2022, 12(2), 304; https://doi.org/10.3390/diagnostics12020304 - 25 Jan 2022
Cited by 2 | Viewed by 6027
Abstract
This is a case report of a rare finding of an extragonadal yolk sac tumor in a 37-year-old patient who presented with shortness of breath and abdominal bloating. During imaging and staging surgery, the findings were strongly suggestive of an extragonadal advanced tumor [...] Read more.
This is a case report of a rare finding of an extragonadal yolk sac tumor in a 37-year-old patient who presented with shortness of breath and abdominal bloating. During imaging and staging surgery, the findings were strongly suggestive of an extragonadal advanced tumor presenting with peritoneal dissemination, predominantly affecting omentum, with no clear primary origin. Histology revealed an extragonadal yolk sac tumor in a pure form outside the ovaries. Lacking an obvious origin elsewhere, the tumor was highly suspected to have truly originated from the omentum. The patient underwent surgery and four cycles of chemotherapy consisting of cisplatin, etoposide, and bleomycin. One-year outpatient follow-up thereafter showed no relapse. We herein discuss a possible site of the tumor origin and its development, as well as diagnostic challenges and disease prognosis. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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14 pages, 3141 KiB  
Case Report
Mesonephric Adenocarcinoma of the Vagina Harboring TP53 Mutation
by Hyunjee Lee, Hyunjin Kim and Hyun-Soo Kim
Diagnostics 2022, 12(1), 119; https://doi.org/10.3390/diagnostics12010119 - 05 Jan 2022
Cited by 8 | Viewed by 1852
Abstract
Mesonephric adenocarcinoma (MA) of the female genital tract is a rare but distinct entity, exhibiting unique morphological, immunophenotypical, and molecular characteristics. Vaginal MA is hypothesized to arise from the mesonephric remnants located in the lateral vaginal wall. A 52-year-old woman presented with vaginal [...] Read more.
Mesonephric adenocarcinoma (MA) of the female genital tract is a rare but distinct entity, exhibiting unique morphological, immunophenotypical, and molecular characteristics. Vaginal MA is hypothesized to arise from the mesonephric remnants located in the lateral vaginal wall. A 52-year-old woman presented with vaginal bleeding. Physical examination revealed a protruding mass in the left vaginal wall. Pelvic magnetic resonance imaging revealed a 2.5-cm mass arising from the left upper vagina and extending posterolaterally to the extravaginal tissue. The punch biopsy was diagnosed as poorly differentiated adenocarcinoma. She received radical surgical resection. Histologically, the tumor displayed various architectural patterns, including compactly aggregated small tubules, solid cellular sheets, endometrioid-like glands and ducts, intraluminal micropapillae, cribriform structure, and small angulated glands accompanied by prominent desmoplastic stroma. The tubules and ducts possessed hyaline-like, densely eosinophilic intraluminal secretions. The tumor extended to the subvaginal soft tissue and had substantial perineural invasion. Immunostaining revealed positivity for the mesonephric markers, including GATA3, TTF1, and PAX2, while showing very focal and weak positivity for estrogen receptor and negativity for progesterone receptor. Additionally, we observed a complete absence of p53 immunoreactivity. Targeted sequencing analysis revealed that the tumor harbored both activating KRAS p.G12D mutation and truncating TP53 p.E286* mutation. A thorough review of the previous literature revealed that 4.5% (3/67) of vaginal/cervical MAs and 0.9% (1/112) of uterine/ovarian mesonephric-like adenocarcinomas harbor TP53 mutations, indicating that this is very uncommon in malignant mesonephric lesions. In summary, we presented a rare case of vaginal MA uniquely harboring pathogenic TP53 mutation, resulting in p53 aberration. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers)
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