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Pathology Oncology Research : POR Jan 2020Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as... (Review)
Review
Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insufficiency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women's Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude definitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Therefore, the denial of HRT also needs to be supported by evidence and should be weighed againts the risks of HRT. Yet, the oncologic risk of HRT is extremely difficult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies, regarding HRT in survivors of gynecologic and non-gynecologic cancers. Based on our literature research, we group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: 'HRT is advanageous' (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); 'HRT is neutral' (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); 'HRT is relatively contraindicated' for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); 'HRT is diasadvantageous and thus contraindicated' (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).
Topics: Breast Neoplasms; Cancer Survivors; Estrogens; Female; Genital Neoplasms, Female; Hormone Replacement Therapy; Humans; Neoplasms; Neoplasms, Second Primary; Progesterone
PubMed: 30617760
DOI: 10.1007/s12253-018-00569-x -
Journal of Clinical Pathology Aug 2006A major proportion of the workload in many histopathology laboratories is accounted for by endometrial biopsies, either curettage specimens or outpatient biopsy... (Review)
Review
A major proportion of the workload in many histopathology laboratories is accounted for by endometrial biopsies, either curettage specimens or outpatient biopsy specimens. The increasing use of pipelle and other methods of biopsy not necessitating general anaesthesia has resulted in greater numbers of specimens with scant tissue, resulting in problems in assessing adequacy and in interpreting artefactual changes, some of which appear more common with outpatient biopsies. In this review, the criteria for adequacy and common artefacts in endometrial biopsies, as well as the interpretation of endometrial biopsies in general, are discussed, concentrating on areas that cause problems for pathologists. An adequate clinical history, including knowledge of the age, menstrual history and menopausal status, and information on the use of exogenous hormones and tamoxifen, is necessary for the pathologist to critically evaluate endometrial biopsies. Topics such as endometritis, endometrial polyps, changes that are induced by hormones and tamoxifen within the endometrium, endometrial metaplasias and hyperplasias, atypical polypoid adenomyoma, adenofibroma, adenosarcoma, histological types of endometrial carcinoma and grading of endometrial carcinomas are discussed with regard to endometrial biopsy specimens rather than hysterectomy specimens. The value of ancillary techniques, especially immunohistochemistry, is discussed where appropriate.
Topics: Algorithms; Artifacts; Biopsy; Curettage; Diagnosis, Differential; Endometrial Hyperplasia; Endometrial Neoplasms; Endometritis; Endometrium; Estrogen Replacement Therapy; Female; Humans; Precancerous Conditions
PubMed: 16873562
DOI: 10.1136/jcp.2005.029702 -
Archives of Pathology & Laboratory... Mar 2016Müllerian adenosarcoma is an uncommon biphasic tumor composed of malignant stromal and benign epithelial components. Morphologically, adenosarcoma is characterized by a...
Müllerian adenosarcoma is an uncommon biphasic tumor composed of malignant stromal and benign epithelial components. Morphologically, adenosarcoma is characterized by a broad leaflike architecture, reminiscent of phyllodes tumors of the breast. Periglandular cuffing of the stromal cells around the compressed or cystically dilated glands is characteristic. The mesenchymal component is typically a low-grade spindle cell sarcoma, whereas the epithelial counterpart is commonly endometrioid with frequent squamous or mucinous metaplasia and may, in some circumstances, show mild to moderate atypia. In all cases, it is important to assess for the presence of sarcomatous overgrowth and myometrial invasion, which are the prognostic factors. In this brief review, we present the clinical, histopathologic, and immunohistochemical features of adenosarcoma, as well as updates on the molecular biology of this neoplasm.
Topics: Adenosarcoma; DNA Helicases; Diagnosis, Differential; Female; Gene Amplification; Humans; Immunohistochemistry; Mixed Tumor, Mullerian; Molecular Diagnostic Techniques; Mutation; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Staging; Nuclear Proteins; Practice Guidelines as Topic; Prognosis; Proto-Oncogene Proteins; Stromal Cells; Trans-Activators; Uterine Neoplasms; Uterus; X-linked Nuclear Protein
PubMed: 26927725
DOI: 10.5858/arpa.2014-0523-RS -
Nature Communications Jun 2022The genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification of therapeutic targets, clinical research, and advancing patient...
The genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification of therapeutic targets, clinical research, and advancing patient care. Because there are > 100 sarcoma subtypes, in-depth genetic studies have focused on one or a few subtypes. Herein, we report a comparative genetic analysis of 2,138 sarcomas representing 45 pathological entities. This cohort is prospectively analyzed using targeted sequencing to characterize subtype-specific somatic alterations in targetable pathways, rates of whole genome doubling, mutational signatures, and subtype-agnostic genomic clusters. The most common alterations are in cell cycle control and TP53, receptor tyrosine kinases/PI3K/RAS, and epigenetic regulators. Subtype-specific associations include TERT amplification in intimal sarcoma and SWI/SNF alterations in uterine adenosarcoma. Tumor mutational burden, while low compared to other cancers, varies between and within subtypes. This resource will improve sarcoma models, motivate studies of subtype-specific alterations, and inform investigations of genetic factors and their correlations with treatment response.
Topics: Bone Neoplasms; Genomics; Humans; Osteosarcoma; Sarcoma; Soft Tissue Neoplasms
PubMed: 35705560
DOI: 10.1038/s41467-022-30453-x -
International Journal of Women's Health 2017Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for... (Review)
Review
Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade), undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases.
PubMed: 28919822
DOI: 10.2147/IJWH.S117754 -
Modern Pathology : An Official Journal... Nov 2022Mullerian adenosarcoma is an uncommon mesenchymal tumor of the gynecologic tract. Most cases are low-grade, while high-grade adenosarcomas are rare and not well studied....
Mullerian adenosarcoma is an uncommon mesenchymal tumor of the gynecologic tract. Most cases are low-grade, while high-grade adenosarcomas are rare and not well studied. Herein, we characterize the clinicopathologic and molecular features of 27 adenosarcomas of gynecologic origin, enriched for high-grade tumors subjected to targeted panel sequencing. Sarcomatous overgrowth was more frequently seen in high-grade compared to low-grade tumors (12/17, 71%, vs 1/10, 10%, p = 0.004) and heterologous elements were exclusive to high-grade cases (n = 7, p = 0.03). All deaths were from high-grade disease (advanced primary, n = 2, or recurrence, n = 5). Genetic alterations specific to high-grade adenosarcomas have known associations with chromosome instability, including TP53 mutations (n = 4) and amplifications of MDM2 (n = 2) and CCNE1 (n = 2). Somatic ATRX frameshift mutations were found in 2 patients with high-grade recurrences following a primary low-grade adenosarcoma and ATRX deletion in 1 high-grade adenosarcoma with an adjacent low-grade component. The fraction of genome altered by copy number alterations was significantly higher in high-grade compared to low-grade adenosarcomas (P = 0.001). Other recurrent genetic alterations across the entire cohort included BAP1 homozygous deletions (n = 4), DICER1 mutations (n = 4), ARID1A mutations (n = 3), TERT promoter mutations (n = 2) and amplification (n = 1), as well as alterations involving members of the PI3K and MAPK signaling pathways. One tumor harbored an ESR1-NCOA3 fusion and another had an MLH1 homozygous deletion. Immunohistochemical analysis for BAP1 revealed loss of nuclear expression in 6/24 (25%) cases, including all four tumors with BAP1 deletions. Notably, out of 196 mesenchymal neoplasms of gynecologic origin, BAP1 homozygous deletion was only found in adenosarcomas (P = 0.0003). This study demonstrates that high-grade adenosarcomas are heterogeneous at the molecular level and are characterized by genomic instability and TP53 mutations; ATRX loss may be involved in high-grade transformation of low-grade adenosarcoma; and BAP1 inactivation appears to be a specific pathogenic driver in a subset of adenosarcomas.
Topics: Humans; Female; Adenosarcoma; Homozygote; Uterine Neoplasms; Sequence Deletion; Phosphatidylinositol 3-Kinases; Ribonuclease III; DEAD-box RNA Helicases; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 36138078
DOI: 10.1038/s41379-022-01160-1 -
Critical Reviews in Oncology/hematology Feb 2018Uterine sarcomas (US) are rare mesenchymal tumours of the uterus and are divided mainly into uterine leiomyosarcoma (uLMS), low grade endometrial stromal sarcoma... (Review)
Review
Uterine sarcomas (US) are rare mesenchymal tumours of the uterus and are divided mainly into uterine leiomyosarcoma (uLMS), low grade endometrial stromal sarcoma (LG-ESS), high grade endometrial stromal sarcoma (HG-ESS), adenosarcomas and high grade undifferentiated sarcoma (HGUS). US are often high-grade tumours with a high local recurrence rate and metastatic risk. We here discuss the current standard of care and knowledge of systemic therapy for adult uterine sarcomas, in particular uLMS, LG-ESS, HG-ESS and HGUS, in both the adjuvant as well as the metastatic setting.
Topics: Adult; Chemotherapy, Adjuvant; Endometrial Neoplasms; Female; Humans; Leiomyosarcoma; Radiotherapy, Adjuvant; Sarcoma; Sarcoma, Endometrial Stromal; Uterine Neoplasms
PubMed: 29458779
DOI: 10.1016/j.critrevonc.2017.12.009 -
Discovery Medicine Sep 2014Uterine sarcomas are a heterologous group of rare malignancies accounting for 8-10% of all uterine malignancies, but are significantly more aggressive and have worse... (Review)
Review
Uterine sarcomas are a heterologous group of rare malignancies accounting for 8-10% of all uterine malignancies, but are significantly more aggressive and have worse prognoses. Management of uterine sarcomas including leiomyosarcoma and endometrial stromal sarcoma are reviewed here, with additional discussions regarding high-grade undifferentiated sarcoma and adenosarcoma. Uterine carcinosarcomas are currently staged and treated similar to high-grade epithelial endometrial carcinomas, thus will not be discussed in this review. Gemcitabine/docetaxel with adriamycin holds promise for the treatment of leiomyosarcoma, but currently, limited advancements have been made in discovering targeted therapies to these tumors. Continued translational research in both medical oncology and gynecologic oncology is necessary to forward the development of novel and targeted therapeutic agents in the treatment of sarcoma. Enrollment of these patients in clinical trials is encouraged, and will allow for the development of safer and more effective therapies.
Topics: Adenosarcoma; Chemotherapy, Adjuvant; Clinical Trials as Topic; Combined Modality Therapy; Endometrial Neoplasms; Female; Humans; Leiomyosarcoma; Receptors, Estrogen; Receptors, Progesterone; Sarcoma; Sarcoma, Endometrial Stromal; Translational Research, Biomedical; Uterine Neoplasms
PubMed: 25227754
DOI: No ID Found -
Gynecologic Oncology Reports Feb 2022To examine clinicopathologic characteristics and oncologic outcomes of patients diagnosed with Mullerian adenosarcoma and to evaluate ovarian preservation as a practical...
OBJECTIVE
To examine clinicopathologic characteristics and oncologic outcomes of patients diagnosed with Mullerian adenosarcoma and to evaluate ovarian preservation as a practical management option in early-stage disease.
METHODS
A retrospective review was performed of 31 patients treated for uterine, ovarian, or cervical adenosarcoma at our institution between 1/2000-3/2020. Recurrence-free survival (RFS) and overall survival (OS) were analyzed with Kaplan-Meier estimates, the log-rank test, and Cox proportional hazards regression.
RESULTS
Median age was 51 years (IQR: 41-68). Primary sites included uterine corpus (n = 23, 74.2%), uterine cervix (n = 7, 22.6%), and ovary (n = 1, 3.2%). Surgical management primarily consisted of total hysterectomy +/- bilateral adnexectomy +/- lymph node dissection. Fifteen (48.1%) patients underwent lymph node dissection; no patients had positive nodes. Ovaries were preserved in 6 (19.4%). Twenty-two (71.0%) patients received no adjuvant therapy, 4 (12.9%) received chemotherapy, 1 (3.2%) received chemoradiation, and 3 (9.7%) received hormonal therapy. Sarcomatous overgrowth (p = 0.04), high grade histology (p = 0.002), and greater depth of myometrial invasion (p = 0.001) were associated with decreased RFS. None of the 6 patients with ovarian preservation had recurrences. At last follow up, 21 patients (67.7%) had no evidence of disease, 7 (22.6%) were deceased due to disease, and 3 (9.7%) were deceased due to non-cancerous reasons.
CONCLUSIONS
Uterine adenosarcoma appears to have a relatively good prognosis, especially in the absence of risk factors, such as sarcomatous overgrowth, high grade histology, and deep myometrial invasion. Ovarian preservation may be a feasible management option with non-inferior outcomes for premenopausal women with early-stage disease. Future studies including larger patient cohorts are needed for this rare disease.
PubMed: 35005157
DOI: 10.1016/j.gore.2021.100913 -
Diagnostic and Interventional Radiology... 2015Uterine sarcomas are a rare heterogeneous group of tumors of mesenchymal origin, accounting for approximately 8% of uterine malignancies. They comprise leiomyosarcoma,... (Review)
Review
Uterine sarcomas are a rare heterogeneous group of tumors of mesenchymal origin, accounting for approximately 8% of uterine malignancies. They comprise leiomyosarcoma, endometrial stromal sarcoma, undifferentiated endometrial sarcoma, and adenosarcoma. Compared with the more common endometrial carcinomas, uterine sarcomas behave more aggressively and are associated with a poorer prognosis. Due to their distinct clinical and biological behavior, the International Federation of Gynecology and Obstetrics introduced a new staging system for uterine sarcomas in 2009, categorizing uterine carcinosarcoma as a variant of endometrial carcinoma, rather than a pure sarcoma. Magnetic resonance imaging (MRI) has a developing role in the assessment of these malignancies. Features such as tumor localization, irregular or nodular margins, necrosis, rapid growth, intense contrast enhancement, and restriction at diffusion-weighted imaging can suggest the diagnosis and help differentiate from more common leiomyomas and endometrial carcinoma. MRI is therefore extremely useful in preoperative detection and staging and, consequently, in determination of appropriate management. This pictorial review aims to discuss the clinical features of uterine sarcomas, as well as their most common appearances and distinct characteristics in MRI.
Topics: Adenosarcoma; Adult; Diagnosis, Differential; Female; Humans; Leiomyosarcoma; Magnetic Resonance Imaging; Middle Aged; Neoplasm Staging; Prognosis; Sarcoma; Sarcoma, Endometrial Stromal; Uterine Neoplasms
PubMed: 25347940
DOI: 10.5152/dir.2014.14053