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Journal of Biomolecular Structure &... May 2024Proto-oncogene tyrosine-protein kinase ROS (ROS1) is a member of the sevenless receptor, which affects epithelial cell differentiation and is highly expressed in a...
Proto-oncogene tyrosine-protein kinase ROS (ROS1) is a member of the sevenless receptor, which affects epithelial cell differentiation and is highly expressed in a variety of tumor cells. The elevated expression and dysfunction of ROS1 have been involved in various malignancies, such as non-small cell lung cancer (NSCLC), stomach cancer, ovarian, breast cancer, cholangiocarcinoma, colorectal cancer, adenosarcoma, oesophageal cancer, etc. ROS1 has been postulated as a potential drug target in anticancer therapeutics. In this study, we carried out a virtual screening of phytochemicals against ROS1 to identify its potential inhibitors. The virtual screening process was performed on the ROS1 structure, where two phytochemicals, Helioscopinolide C and Taiwanin C, were identified. These compounds resulted from filters like Lipinski rule of five, PAINS filter, binding affinities values, and all-atom molecular dynamics (MD) simulations followed by principal component analysis (PCA) and essential dynamics. The findings of this study highlight the role of ROS1 in multiple physiological candidates and its therapeutic targeting using phytochemicals. This study suggests Helioscopinolide C and Taiwanin C as potential compounds for therapeutic development targeting ROS1-associated non-small cell lung cancer for clinical applications. Further and experiments are required to validate these findings.Communicated by Ramaswamy H. Sarma.
Topics: Humans; Antineoplastic Agents; Binding Sites; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Molecular Docking Simulation; Molecular Dynamics Simulation; Phytochemicals; Protein Binding; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Proto-Oncogene Mas; Proto-Oncogene Proteins; Structure-Activity Relationship; Tyrosine Kinase Inhibitors; Lactones; Lignans
PubMed: 37254309
DOI: 10.1080/07391102.2023.2217450 -
Translational Cancer Research May 2024Endometrial adenosarcoma is an unusual type of uterine tumor that features a seemingly benign epithelial component, paired with a low-grade sarcomatous component,...
BACKGROUND
Endometrial adenosarcoma is an unusual type of uterine tumor that features a seemingly benign epithelial component, paired with a low-grade sarcomatous component, usually similar in appearance to endometrial stromal sarcoma. To our knowledge, no image of endometrial adenocarcinoma in the cesarean scar diverticulum has been reported previously.
CASE DESCRIPTION
We present a rare case of endometrial adenocarcinoma located in the cesarean scar diverticulum of a 44-year-old patient. The patient was admitted to our hospital complaining of irregular vaginal bleeding that had lasted for over two months. Both B-ultrasound and magnetic resonance imaging confirmed a mass at the junction of the corpus uteri and cervix. After the initial curettage failed to confirm the disease, a hysteroscopy was subsequently performed. Upon further pathological analysis, a diagnosis of endometrial adenosarcoma was confirmed. The patient underwent hysterectomy and salpingo-oophorectomy. The patient was discharged home four days after the surgery and remained recurrence-free for one year after follow-up.
CONCLUSIONS
Hysteroscopy can serve as a valuable diagnostic tool to identify the lesion in this unique scenario, particularly when curettage fails to diagnose this uncommon condition. We hope that this case would bring awareness of this potential scenario, enabling clinicians in the future to identify similar cases more readily.
PubMed: 38881921
DOI: 10.21037/tcr-23-2155 -
International Journal of Gynecological... May 2024Endometrial and endocervical polyps not uncommonly exhibit focal benign "hobnail" change/metaplasia within the glandular epithelium, sometimes in association with...
Endometrial and endocervical polyps not uncommonly exhibit focal benign "hobnail" change/metaplasia within the glandular epithelium, sometimes in association with inflammation or infarction. In most cases, this is readily recognized as benign but occasionally, especially in endometrial polyps, this change prompts consideration of a premalignant or malignant lesion, including early serous or clear cell carcinoma. Herein we highlight the previously unreported phenomenon of positive staining of this hobnail epithelium with Napsin A which has the potential to exacerbate concern for clear cell carcinoma. Endometrial (n = 22) and endocervical (n = 17) polyps showing hobnail change were stained with Napsin A. Six cases were positive (4 of 22 endometrial and 2 of 17 endocervical polyps). In all cases, Napsin A positivity was confined to the hobnail epithelium. The hobnail epithelium was positive with estrogen receptor and hepatocyte nuclear factor 1- beta and exhibited wild-type immunoreactivity with p53 in all cases where these markers were performed. In addition, in 2 of 3 uterine adenosarcomas with focal hobnail change the epithelium was Napsin A positive. Pathologists should be aware that Napsin A may be expressed in benign/reactive hobnail epithelium in endometrial and endocervical polyps and should not consider positivity with this marker as a diagnostic of clear cell carcinoma.
PubMed: 38781161
DOI: 10.1097/PGP.0000000000001037 -
Gynecologic Oncology Reports Jun 2024•Non-puerperal uterine inversion can be associated with uterine sarcomas.•Adenosarcoma is a tumor composed of benign epithelium and malignant stroma.•If malignancy...
•Non-puerperal uterine inversion can be associated with uterine sarcomas.•Adenosarcoma is a tumor composed of benign epithelium and malignant stroma.•If malignancy is suspected or confirmed treatment of uterine inversion with hysterectomy is advised.
PubMed: 38681981
DOI: 10.1016/j.gore.2024.101398 -
Frontiers in Oncology 2024Polypoid lesions in the uterus are very common. There are a lot of benign lesions and malignant tumor should be considered. Adenosarcoma, one of the differential...
Polypoid lesions in the uterus are very common. There are a lot of benign lesions and malignant tumor should be considered. Adenosarcoma, one of the differential diagnoses, is a rare mixed epithelial and mesenchymal tumor consisting of benign epithelial components and sarcoma stroma. Here, we present a case of atypical adenosarcoma that has never been reported. This tumor was composed of benign endometrial epithelium and hyperplastic stroma with extensive bizarre stromal cells. But the cleft-like spaces and papillary stomal fronds which were the typical histological images of adenosarcoma were absent. These stomal cells, including bizarre cells, were positive for vimentin, CD10, ER, PR, cyclin D1 and P16 but were immunonegative for caldesmon. Furthermore, this tumor harbored amplification of MDM2, as revealed by fluorescence hybridization testing (FISH) and next-generation DNA sequencing (NGS).
PubMed: 38549925
DOI: 10.3389/fonc.2024.1351646 -
Case Reports in Oncology 2023Uterine adenosarcoma (AS) is a rare biphasic neoplasm composed of a malignant, usually low-grade stromal component and benign epithelial component, usually endometrioid....
Uterine adenosarcoma (AS) is a rare biphasic neoplasm composed of a malignant, usually low-grade stromal component and benign epithelial component, usually endometrioid. Pathogenesis is unknown; some cases are undoubtably associated with tamoxifen use. Endometrial clear cell carcinoma (CCC) is an aggressive subtype of endometrial cancer, accounting for less than 10% of all uterine carcinomas. The etiology is unknown but can rarely be associated with Lynch syndrome and tamoxifen administration. The development of a composite neoplasm consisting of adenocarcinoma in AS is extremely rare. Endometrioid carcinoma typically represents the epithelial component of the composite tumor. Here we present the very first case of composite tumor, namely, AS with CCC in which next-generation sequencing was performed. Patient was an 85-year-old woman treated with tamoxifen for 5 years. To better understand the pathobiology of two tumors, a targeted genomic analysis of both components was performed. We found seven identical somatic variants in the samples of both tumors, indicating that the tumors have a high probability of having the same origin. Dual amplification of CDK4 and MDM2 was the most likely primary cause of tumor formation, but also one driver variant in the DHX15 gene that was present in both tumor components, suggesting that DHX15 may play an important role in the initiation and development of sarcoma and carcinoma. The patient is followed by regular clinical controls and is alive without signs of disease recurrence 18 months after surgery.
PubMed: 37946747
DOI: 10.1159/000531988 -
BMC Women's Health May 2024Cervical mullerian adenosarcoma is a rare uterine sarcoma, especially in young women. Its pathological features are low-grade malignant tumors with bidirectional...
BACKGROUND
Cervical mullerian adenosarcoma is a rare uterine sarcoma, especially in young women. Its pathological features are low-grade malignant tumors with bidirectional differentiation, and the degree of malignancy is similar to that of low-grade endometrial stromal sarcoma. This paper reports the case of a young asexual patient who has been closely followed up after tumor resection and has not had any recurrences.
CASE PRESENTATION
A 20-year-old, young asexual woman was diagnosed with cervical mullerian adenosarcoma with sarcomatous overgrowth (MASO). Cervical tumor resection was performed after admission, and the resection margin was negative. After the operation, she refused to undergo secondary surgery due to fertility requirements and did not receive adjuvant treatment. The patient was closely followed up after the operation and has not yet relapsed.
CONCLUSION
A young woman with cervical MASO did not receive adjuvant treatment after cervical tumor resection. For women with fertility requirements, close follow-ups should be conducted after the operation to guard against tumor recurrence and radical tumor resection should be performed as early as possible after the patient no longer requires their fertility.
Topics: Humans; Female; Adenosarcoma; Young Adult; Uterine Cervical Neoplasms; Uterine Neoplasms; Sexual Behavior
PubMed: 38783282
DOI: 10.1186/s12905-024-03140-w -
International Journal of Gynecological... Jul 2024Mesonephric-like adenocarcinoma (MLA) of the ovary is a recently recognized, rare malignancy with aggressive clinical behavior, and is thought to originate from...
Mesonephric-like adenocarcinoma (MLA) of the ovary is a recently recognized, rare malignancy with aggressive clinical behavior, and is thought to originate from Mullerian epithelium with mesonephric transdifferentiation. Emerging evidence suggests that MLA may be classified as an endometriosis-associated neoplasm. The presence of a sarcomatous component within MLA is extremely rare, with common differential diagnoses including the spindle cell component of MLA, carcinosarcoma, as well as mixed Mullerian adenocarcinoma and adenosarcoma. Herein, we report a 58-year-old Chinese woman with bilateral ovarian solid-cystic masses. The left ovarian mass comprised a biphasic tumor with a predominantly high-grade sarcomatous component displaying heterologous mesenchymal differentiation, including liposarcoma, rhabdomyosarcoma and chondrosarcoma-like areas, with a null-type p53 expression. The epithelial component ranged from a bland appearance in areas diagnostic of adenosarcoma to a clearly invasive carcinoma, both with mesonephric-like phenotype, being negative for estrogen receptor, progesterone receptor, and Wilms' tumor 1, variably positive for paired box gene 8, GATA binding protein 3, and thyroid transcription factor 1, with a wild-type p53 expression. The differing p53 expression between the epithelial and sarcomatous elements mitigated against a diagnosis of carcinosarcoma. The right ovarian mass showed endometriosis with focal direct evidence of the development of malignancy within a benign endometriotic cyst, exhibiting the identical immunoprofile of MLA but originating as another malignancy. To the best of our knowledge, this case represents the first reported case of synchronous bilateral ovarian MLAs with separate origins, from high-grade Mullerian adenosarcoma and endometriosis respectively, which broadens the morphologic spectrum of MLA and provides further evidence supporting the Mullerian origin theory.
Topics: Humans; Female; Endometriosis; Middle Aged; Adenosarcoma; Ovarian Neoplasms; Adenocarcinoma; Ovary; Diagnosis, Differential; Mixed Tumor, Mullerian
PubMed: 37922943
DOI: 10.1097/PGP.0000000000000997 -
International Journal of Gynecological... Sep 2023MEIS1-NCOA1/2 fusions are recently described gene rearrangements found in rare sarcomas, mainly involving the genitourinary and gynecologic tracts, with 3 cases reported...
Aggressive High-grade Uterine Sarcoma Harboring MEIS1-NCOA2 Fusion and Amplification of Multiple 12q13-15 Genes: A Case Report With Morphologic, Immunohistochemical, and Molecular Analysis.
MEIS1-NCOA1/2 fusions are recently described gene rearrangements found in rare sarcomas, mainly involving the genitourinary and gynecologic tracts, with 3 cases reported in the uterine corpus. Although local recurrence was very common, no death has been reported, and some investigators consider these sarcomas low grade. Amplification of genes located at the 12q13-15 locus, especially MDM2 , is the hallmark genetic abnormality in well-differentiated and dedifferentiated liposarcoma of the soft tissue. Some uterine tumors have also been reported to harbor MDM2 amplification, including a proportion of Müllerian adenosarcomas, BCOR fusion-positive high-grade endometrial stromal sarcoma, BCORL1 -altered high-grade endometrial stromal sarcoma, rare JAZF1 fusion-positive low-grade endometrial stromal sarcoma, rare undifferentiated uterine sarcoma, and a single case of MEIS1-NCOA2 fusion sarcoma. Here, we report a case of high-grade MEIS1-NCOA2 fusion uterine sarcoma which also harbored amplification of multiple 12q13-15 genes, including MDM2 , CDK4 , MDM4 , and FRS2 , that exhibited aggressive clinical course leading to patient's death within 2 yr of the initial diagnosis. To the best of our knowledge, this is the first documented case of fatal MEIS1-NCOA2 fusion uterine sarcoma, and the second case of MEIS1-NCOA2 fusion uterine sarcoma that also harbors MDM2 amplification.
Topics: Humans; Female; Sarcoma, Endometrial Stromal; Uterus; Sarcoma; Myeloid Ecotropic Viral Integration Site 1 Protein; Endometrial Neoplasms; Nuclear Receptor Coactivator 2; Proto-Oncogene Proteins; Cell Cycle Proteins
PubMed: 36811835
DOI: 10.1097/PGP.0000000000000937 -
Clinical Case Reports Mar 2024Rhabdomyosarcoma of the female genital tract often involves the vagina and cervix. It usually occurs in infants and children. Such tumors are uncommon in the uterus,...
KEY CLINICAL MESSAGE
Rhabdomyosarcoma of the female genital tract often involves the vagina and cervix. It usually occurs in infants and children. Such tumors are uncommon in the uterus, especially in adults. Treatment options are based on studies of younger individuals.
ABSTRACT
Rhabdomyosarcoma (RMS) is a malignant mesenchymal neoplasm with a tendency to differentiate into skeletal muscle cells. RMS is an aggressive tumor that tends to develop in children and younger patients. A vast majority of genital tract RMSs occur in the vagina and cervix. Such tumors rarely occur in adults. Usually, these tumors either occur as a component of a biphasic uterine tumor (carcinosarcoma or adenosarcoma) or can be a pure heterologous tumor. Pure uterine RMSs are extremely rare in adult patients and difficult to diagnose. Accurate diagnosis of these tumors depends on precise histopathological evaluation. The present report describes a rare case of embryonal RMS of the uterus in a postmenopausal female and explores the most recent literature. The aim is to strengthen the existing literature and aid clinicians in the management of similar cases. A 64-year-old postmenopausal female presented with a history of abdominal pain associated with abdominal distension, per vaginal bleeding, and foul-smelling discharge for 6 months. A transabdominal ultrasound revealed a bulky uterus with a well-circumscribed heterogeneous lesion. Histopathology confirmed the diagnosis of high-grade embryonal RMS within the corpus region of the uterus. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed, followed by adjuvant chemotherapy to prevent relapse of the disease. Six months after oncological care has passed, the patient remains symptoms-free without evidence of recurrence or metastasis.
PubMed: 38455863
DOI: 10.1002/ccr3.8631