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Gynecologic Oncology Jun 2020Cancer complicates 1 in 1000 pregnancies. Multidisciplinary consensus comprised of Gynecologic Oncology, Pathology, Neonatology, Radiology, Anesthesiology, Maternal... (Review)
Review
Cancer complicates 1 in 1000 pregnancies. Multidisciplinary consensus comprised of Gynecologic Oncology, Pathology, Neonatology, Radiology, Anesthesiology, Maternal Fetal Medicine, and Social Work should be convened. Pregnancy provides an opportunity for cervical cancer screening, with deliberate delays in treatment permissible for early stage carcinoma. Vaginal delivery is contraindicated in the presence of gross lesion(s) and radical hysterectomy with lymphadenectomy at cesarean delivery is recommended. Women with locally advanced and metastatic/recurrent disease should commence treatment at diagnosis with chemoradiation and systemic therapy, respectively; neoadjuvant chemotherapy to permit gestational advancement may be considered in select cases. Most adnexal masses are benign and resolve by the second trimester. Persistent, asymptomatic, benign-appearing masses can be managed conservatively; surgery, if indicated, is best deferred to 15-20 weeks, with laparoscopy preferable over laparotomy whenever possible. Benign and malignant germ cell tumors and borderline tumors are occasionally encountered, with unilateral adnexectomy and preservation of the uterus and contralateral ovary being the rule. Epithelial ovarian cancer is exceedingly rare. Ultrasonography and magnetic resonance imaging lack ionizing radiation and can be employed to evaluate disease extent. Tumor markers, including CA-125, AFP, LDH, inhibin-B, and even CEA and ßhCG may be informative. If required, chemotherapy can be administered following organogenesis during the second and third trimesters. Because platinum and other anti-neoplastic agents cross the placenta, chemotherapy should be withheld after 34 weeks to avoid neonatal myelosuppression. Bevacizumab, immune checkpoint inhibitors, and PARP inhibitors should be avoided throughout pregnancy. Although antenatal glucocorticoids to facilitate fetal pulmonary maturation and amniotic fluid index assessment can be considered, there is no demonstrable benefit of tocolytics, antepartum fetal heart rate monitoring, and/or amniocentesis. Endometrial, vulvar, and vaginal cancer in pregnancy are curiosities, although leiomyosarcoma and the dreaded twin fetus/hydatidiform mole have been reported. For gynecologic malignancies, pregnancy does not impart aggressive clinical behavior and/or worse prognosis.
Topics: Female; Humans; Pregnancy; Genital Neoplasms, Female; Pregnancy Complications, Neoplastic
PubMed: 32268951
DOI: 10.1016/j.ygyno.2020.03.015 -
International Journal of Molecular... Aug 2022Uterine fibroids (UFs) are the most common benign tumors of female genital diseases, unlike uterine leiomyosarcoma (LMS), a rare and aggressive uterine cancer. This... (Review)
Review
Uterine fibroids (UFs) are the most common benign tumors of female genital diseases, unlike uterine leiomyosarcoma (LMS), a rare and aggressive uterine cancer. This narrative review aims to discuss the biology and diagnosis of LMS and, at the same time, their differential diagnosis, in order to distinguish the biological and molecular origins. The authors performed a Medline and PubMed search for the years 1990-2022 using a combination of keywords on the topics to highlight the many genes and proteins involved in the pathogenesis of LMS. The mutation of these genes, in addition to the altered expression and functions of their enzymes, are potentially biomarkers of uterine LMS. Thus, the use of this molecular and protein information could favor differential diagnosis and personalized therapy based on the molecular characteristics of LMS tissue, leading to timely diagnoses and potential better outcomes for patients.
Topics: Female; Humans; Leiomyoma; Leiomyosarcoma; Pelvic Neoplasms; Uterine Neoplasms; Uterus
PubMed: 36077127
DOI: 10.3390/ijms23179728 -
Diagnostic and Interventional Imaging Oct 2019Uterine leiomyomas, the most frequent benign myomatous tumors of the uterus, often cannot be distinguished from malignant uterine leiomyosarcomas using clinical... (Review)
Review
Uterine leiomyomas, the most frequent benign myomatous tumors of the uterus, often cannot be distinguished from malignant uterine leiomyosarcomas using clinical criteria. Furthermore, imaging differentiation between both entities is frequently challenging due to their potential overlapping features. Because a suspected leiomyoma is often managed conservatively or with minimally invasive treatments, the misdiagnosis of leiomyosarcoma for a benign leiomyoma could potentially result in significant treatment delays, therefore increasing morbidity and mortality. In this review, we provide an overview of the differences between leiomyoma and leiomyosarcoma, mainly focusing on imaging characteristics, but also briefly touching upon their demographic, histopathological and clinical differences. The main indications and limitations of available cross-sectional imaging techniques are discussed, including ultrasound, computed tomography, magnetic resonance imaging (MRI) and positron emission tomography/computed tomography. A particular emphasis is placed on the review of specific MRI features that may allow distinction between leiomyomas and leiomyosarcomas according to the most recent evidence in the literature. The potential contribution of texture analysis is also discussed. In order to help guide-imaging diagnosis, we provide an MRI-based diagnostic algorithm which takes into account morphological and functional features, both individually and in combination, in an attempt to optimize radiologic differentiation of leiomyomas from leiomyosarcomas.
Topics: Algorithms; Contrast Media; Diagnosis, Differential; Diagnostic Imaging; Female; Humans; Leiomyoma; Leiomyosarcoma; Neoplasm Staging; Radiopharmaceuticals; Uterine Neoplasms
PubMed: 31427216
DOI: 10.1016/j.diii.2019.07.007 -
Journal of the Advanced Practitioner in... Jan 2022Leiomyosarcoma (LMS) is the most common soft tissue sarcoma in adults and can occur in any part of the body. Uterine leiomyosarcoma (uLMS) is the most common location...
Leiomyosarcoma (LMS) is the most common soft tissue sarcoma in adults and can occur in any part of the body. Uterine leiomyosarcoma (uLMS) is the most common location for LMS, making up 2% to 5% of all uterine malignancies. It is an aggressive tumor that is challenging to treat because of its resistance to standard therapy. The majority of patients (60%) are diagnosed with early-stage disease. However, regardless of the stage, uLMS has a poor prognosis. Surgical resection is the cornerstone of treatment for patients with localized LMS independent of the site of origin. Adjuvant chemotherapy for early-stage disease remains controversial as multiple clinical trials have failed to demonstrate benefit on overall survival. Progress has been made in therapy for advanced and recurrent disease. This case study will highlight the current and emerging data regarding novel therapies for women with uLMS.
PubMed: 35173990
DOI: 10.6004/jadpro.2022.13.1.6 -
Modern Pathology : An Official Journal... Apr 2023The morphologic assessment of uterine leiomyosarcoma (LMS) may be challenging, and diagnostic immunohistochemical (IHC) analysis is currently lacking. We evaluated the...
The morphologic assessment of uterine leiomyosarcoma (LMS) may be challenging, and diagnostic immunohistochemical (IHC) analysis is currently lacking. We evaluated the genomic landscape of 167 uterine LMS by targeted next-generation sequencing (NGS) to identify common genomic alterations. IHC analyses corresponding to these genomic landmarks were applied to a test cohort of 16 uterine LMS, 6 smooth muscle tumors of uncertain malignant potential (STUMP), and 6 leiomyomas with NGS data and a validation cohort of 8 uterine LMS, 12 STUMP, 21 leiomyomas and leiomyoma variants, 7 low-grade endometrial stromal sarcomas, and 2 diagnostically challenging uterine smooth muscle tumors. IHC results were individually interpreted by 3 pathologists blinded to NGS data. Overall, 94% of LMS showed ≥1 genomic alteration involving TP53, RB1, ATRX, PTEN, CDKN2A, or MDM2, with 80% showing alterations in ≥2 of these genes. In the test cohort, an initial panel of p53, Rb, PTEN, and ATRX was applied, followed by a panel of DAXX, MTAP, and MDM2 in cases without abnormalities. Abnormal p53, Rb, PTEN, and ATRX IHC expression was seen in 75%, 88%, 44%, and 38% of LMS, respectively, in the test cohort. Two or more abnormal IHC results among these markers were seen in 81% of LMS. STUMPs demonstrated only 1 IHC abnormality involving these markers. No IHC abnormalities were seen in leiomyomas. In the validation cohort, abnormal p53, Rb, and PTEN IHC results were seen in LMS, whereas rare STUMP or leiomyomas with bizarre nuclei showed IHC abnormalities involving only 1 of the markers. Abnormalities in ≥2 markers were present in both diagnostically challenging smooth muscle tumors, confirming LMS. Concordance was excellent among pathologists in the interpretation of IHC (κ = 0.97) and between IHC and NGS results (κ = 0.941). Uterine LMS exhibit genomic landmark alterations for which IHC surrogates exist, and a diagnostic algorithm involving molecular-based IHC may aid in the evaluation of unusual uterine smooth muscle tumors.
Topics: Female; Humans; Algorithms; Immunohistochemistry; Leiomyosarcoma; Molecular Diagnostic Techniques; Reproducibility of Results; Uterine Neoplasms
PubMed: 36788080
DOI: 10.1016/j.modpat.2022.100084 -
Radiology Feb 2023Laparoscopic myomectomy, a common gynecologic operation in premenopausal women, has become heavily regulated since 2014 following the dissemination of unsuspected... (Review)
Review
Laparoscopic myomectomy, a common gynecologic operation in premenopausal women, has become heavily regulated since 2014 following the dissemination of unsuspected uterine leiomyosarcoma (LMS) throughout the pelvis of a physician treated for symptomatic leiomyoma. Research since that time suggests a higher prevalence than previously suspected of uterine LMS in resected masses presumed to represent leiomyoma, as high as one in 770 women (0.13%). Though rare, the dissemination of an aggressive malignant neoplasm due to noncontained electromechanical morcellation in laparoscopic myomectomy is a devastating outcome. Gynecologic surgeons' desire for an evidence-based, noninvasive evaluation for LMS is driven by a clear need to avoid such harms while maintaining the availability of minimally invasive surgery for symptomatic leiomyoma. Laparoscopic gynecologists could rely upon the distinction of higher-risk uterine masses preoperatively to plan oncologic surgery (ie, potential hysterectomy) for patients with elevated risk for LMS and, conversely, to safely offer women with no or minimal indicators of elevated risk the fertility-preserving laparoscopic myomectomy. MRI evaluation for LMS may potentially serve this purpose in symptomatic women with leiomyomas. This evidence review and consensus statement defines imaging and disease-related terms to allow more uniform and reliable interpretation and identifies the highest priorities for future research on LMS evaluation.
Topics: Female; Humans; Leiomyosarcoma; Leiomyoma; Uterine Neoplasms; Uterine Myomectomy; Hysterectomy; Laparoscopy; Magnetic Resonance Imaging
PubMed: 36194109
DOI: 10.1148/radiol.211658 -
European Journal of Nuclear Medicine... Nov 2021Ga-FAPI (fibroblast activation protein inhibitor) is a novel and highly promising radiotracer for PET/CT imaging. The aim of this retrospective analysis is to explore...
PURPOSE
Ga-FAPI (fibroblast activation protein inhibitor) is a novel and highly promising radiotracer for PET/CT imaging. The aim of this retrospective analysis is to explore the potential of FAPI-PET/CT in gynecological malignancies. We assessed biodistribution, tumor uptake, and the influence of pre- or postmenopausal status on tracer accumulation in hormone-sensitive organs. Furthermore, a comparison with the current standard oncological tracer F-FDG was performed in selected cases.
PATIENTS AND METHODS
A total of 31 patients (median age 59.5) from two centers with several gynecological tumors (breast cancer; ovarian cancer; cervical cancer; endometrial cancer; leiomyosarcoma of the uterus; tubal cancer) underwent Ga-FAPI-PET/CT. Out of 31 patients, 10 received an additional F-FDG scan within a median time interval of 12.5 days (range 1-76). Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean, and tumor-to-background ratio (TBR) was calculated (SUVmax tumor/ SUVmean organ). Moreover, a second cohort of 167 female patients with different malignancies was analyzed regarding their FAPI uptake in normal hormone-responsive organs: endometrium (n = 128), ovary (n = 64), and breast (n = 147). These patients were categorized by age as premenopausal (<35 years; n = 12), postmenopausal (>65 years; n = 68), and unknown menstrual status (35-65 years; n = 87), followed by an analysis of FAPI uptake of the pre- and postmenopausal group.
RESULTS
In 8 out of 31 patients, the primary tumor was present, and all 31 patients showed lesions suspicious for metastasis (n = 81) demonstrating a high mean SUVmax in both the primary (SUVmax 11.6) and metastatic lesions (SUVmax 9.7). TBR was significantly higher in Ga-FAPI compared to F-FDG for distant metastases (13.0 vs. 5.7; p = 0.047) and by trend for regional lymph node metastases (31.9 vs 27.3; p = 0.6). Biodistribution of Ga-FAPI-PET/CT presented significantly lower uptake or no significant differences in 15 out of 16 organs, compared to F-FDG-PET/CT. The highest uptake of all primary lesions was obtained in endometrial carcinomas (mean SUVmax 18.4), followed by cervical carcinomas (mean SUVmax 15.22). In the second cohort, uptake in premenopausal patients differed significantly from postmenopausal patients in endometrium (11.7 vs 3.9; p < 0.0001) and breast (1.8 vs 1.0; p = 0.004), whereas no significant difference concerning ovaries (2.8 vs 1.6; p = 0.141) was observed.
CONCLUSION
Due to high tracer uptake resulting in sharp contrasts in primary and metastatic lesions and higher TBRs than F-FDG-PET/CT, Ga-FAPI-PET/CT presents a promising imaging method for staging and follow-up of gynecological tumors. The presence or absence of the menstrual cycle seems to correlate with FAPI accumulation in the normal endometrium and breast. This first investigation of FAP ligands in gynecological tumor entities supports clinical application and further research in this field.
Topics: Adult; Female; Gallium Radioisotopes; Genital Neoplasms, Female; Humans; Middle Aged; Positron Emission Tomography Computed Tomography; Retrospective Studies; Tissue Distribution
PubMed: 34050777
DOI: 10.1007/s00259-021-05378-0 -
Proceedings of the National Academy of... Apr 2021Uterine leiomyosarcomas (uLMS) are aggressive tumors arising from the smooth muscle layer of the uterus. We analyzed 83 uLMS sample genetics, including 56 from Yale and...
Uterine leiomyosarcomas (uLMS) are aggressive tumors arising from the smooth muscle layer of the uterus. We analyzed 83 uLMS sample genetics, including 56 from Yale and 27 from The Cancer Genome Atlas (TCGA). Among them, a total of 55 Yale samples including two patient-derived xenografts (PDXs) and 27 TCGA samples have whole-exome sequencing (WES) data; 10 Yale and 27 TCGA samples have RNA-sequencing (RNA-Seq) data; and 11 Yale and 10 TCGA samples have whole-genome sequencing (WGS) data. We found recurrent somatic mutations in TP53, MED12, and PTEN genes. Top somatic mutated genes included TP53, ATRX, PTEN, and MEN1 genes. Somatic copy number variation (CNV) analysis identified 8 copy-number gains, including 5p15.33 (TERT), 8q24.21 (C-MYC), and 17p11.2 (MYOCD, MAP2K4) amplifications and 29 copy-number losses. Fusions involving tumor suppressors or oncogenes were deetected, with most fusions disrupting RB1, TP53, and ATRX/DAXX, and one fusion (ACTG2-ALK) being potentially targetable. WGS results demonstrated that 76% (16 of 21) of the samples harbored chromoplexy and/or chromothripsis. Clinically actionable mutational signatures of homologous-recombination DNA-repair deficiency (HRD) and microsatellite instability (MSI) were identified in 25% (12 of 48) and 2% (1 of 48) of fresh frozen uLMS, respectively. Finally, we found olaparib (PARPi; = 0.002), GS-626510 (C-MYC/BETi; < 0.000001 and = 0.0005), and copanlisib (PIK3CAi; = 0.0001) monotherapy to significantly inhibit uLMS-PDXs harboring derangements in C-MYC and PTEN/PIK3CA/AKT genes (LEY11) and/or HRD signatures (LEY16) compared to vehicle-treated mice. These findings define the genetic landscape of uLMS and suggest that a subset of uLMS may benefit from existing PARP-, PIK3CA-, and C-MYC/BET-targeted drugs.
Topics: Animals; Antineoplastic Agents; Female; Genotype; Humans; Leiomyosarcoma; Metabolic Networks and Pathways; Mice; Mice, Inbred C57BL; Molecular Targeted Therapy; Mutation; Oncogene Fusion; Phthalazines; Piperazines; Pyrimidines; Quinazolines; Uterine Neoplasms
PubMed: 33876771
DOI: 10.1073/pnas.2025182118