COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation.

COL1A1::PDGFB fusion uterine sarcoma is a rare uterine mesenchymal tumor with some clinicopathological features that overlap with those of soft tissue dermatofibrosarcoma protuberans. However, the varied clinicopathologic and genetic characteristics have not been fully revealed, which may be a potential pitfall for diagnosis. Here, we present a case of COL1A1::PDGFB fusion-positive uterine sarcoma in a 49-years-old female. Histologically, the tumor from the initial marginal excision predominantly exhibited high-grade fibrosarcomatous and myxofibrosarcoma-like appearances, while a low-grade focal area displaying storiform growth was identified in the residual tumor after subsequently extended resection. Immunohistochemically, the high-grade components mainly exhibited focal positivity for CD34 and mutated-type p53 immunoreactivity, whereas the low-grade component showed diffuse positivity for CD34 and wild-type p53 staining. The COL1A1::PDGFB fusion was confirmed by fluorescence in situ hybridization and next-generation sequencing. In addition, the TERT-124 C > T mutation was further identified in this lesion's fibrosarcomatous and classic storiform components. To the best of our knowledge, this is the first described case of COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation, which might be a novel genetic finding associated with tumorigenesis of this rare tumor.

Disruption of precise regulation of αPKC expression and cellular localization is associated with cervical cancer progression.

PURPOSE: To understand the pathogenesis of cervical cancer (CC) associated with polarity protein αPKC and the potential roles of αPKC in clinical management of CC. METHODS: Tissue samples were collected from women who received colposcopy biopsy or hysterectomy surgery, including 9 CIN1, 8 CIN2, 15 CIN3, and 12 invasive cervical squamous cancer (ICC). 16 normal controls were from the normal region of tumor samples, HE and immunofluorescence staining of αPKC were performed on these samples. ANOVA and Kruslal-wallis test were used to quantitate the abnormal distribution and expression level of αPKC among different cervical lesions. RESULTS: Disruption of polarized apical localization and increased cytoplasmic accumulation of αPKC were identified in cervical lesions. In normal cervical epithelium, αPKC was detected on the apical membrane of endocervical columnar epithelial cells and of exocervical epithelial cells located at basal layer of squamous epithelium. While in squamous metaplasia, a precancerous lesion of cervical neoplasia, the polarized apical membrane localization of αPKC was disrupted, and intensed cytoplasmic accumulation was identified in the immature squamous metaplastic cells. Compared with normal cervix, number of epithelial cells with abnormal αPKC distribution was progressively increased in CINs and ICC (P < 0.05), and cytoplasmic accumulation of αPKC was increased in CIN2, CIN3, and ICC compared with CIN1 (P < 0.05). CONCLUSIONS: Disruption of polarized apical localization and increased cytoplasmic accumulation of αPKC were associated with CC progression, indicating that precise regulation of αPKC may play important roles in CC progression, and αPKC may be a potential molecular target for clinical diagnoses and treatment of CC.

Perivascular epithelioid cell tumor of the uterine cervix identified on the liquid-based cytology: a case report.

BACKGROUND: Perivascular epithelioid cell tumor (PEComa) occurring in the female genital tract are rare, and typically found in the uterine corpus. PEComa occurring in the cervix is extremely rare, and very few cases have been reported till now. Cytological diagnosis of cervical PEComa is even rarer. So far, only two cases of PEComa diagnosed by conventional cervical smears have been reported. CASE PRESENTATION: A 55-year-old postmenopausal woman presented with abnormal vagina discharge for 3 months. A liquid-based cytology test was performed. Microscopically, some loosely cohesive epithelioid cells were uniform with abundant clear cytoplasm, showing predominantly round or oval nuclei with finely stippled chromatin. Distinct round nucleoli were visible in some cells, notably with numerous melanin pigments in the cytoplasm. The cytopathological features were well correlated with cell block and histopathological findings. Upon immunohistochemistry (IHC), the tumor cells were positive for HMB45 and TFE3, focally positive for MelanA, while negative for muscle marker. Fluorescence in situ hybridization (FISH) confirmed TFE3 gene rearrangement. The final pathological diagnosis was PEComa identified by the liquid-based cytology, cell block, cervical biopsy, IHC and FISH result. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy and was followed up for 2 years with no evidence of disease. CONCLUSION: The cytologic characteristics of the tumor can provide sufficient clues for PEComa diagnosis, which includes loosely cohesive, epithelioid morphology with abundant clear or eosinophilic cytoplasm, low-grade nuclear atypia, cytoplasmic melanin pigments. This will help cytopathologists to recognize this rare tumor that occurred in the cervix, and the combination of predictive morphology evaluation, immunophenotype, and molecular testing can achieve the definitive diagnosis of PEComa.

Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines.

BACKGROUND: Astrocyte elevated gene 1 (AEG-1), an important oncogene, has been shown to be overexpressed in several types of cancers. In colorectal cancer (CRC), the protein level of AEG-1 is up-regulated in tumour tissue compared to normal mucosa, showing prognostic significance. Since little is known about the transcriptional level of AEG-1 expression and its biological pathway in CRC the aim of the present study was to examine the relationship of AEG-1 mRNA expression, the protein level and clinicopathological variables as well as its biology pathway in CRC. MATERIAL AND METHODS: The mRNA expression of AEG-1 was analysed by qPCR in fresh frozen patient samples including 156 primary tumours, along with the corresponding normal mucosa, and in five colon cancer cell lines, SW480, SW620, KM12C, KM12SM and KM12L4a. AEG-1 protein expression was investigated by immunohistochemistry in paraffin-embedded materials from 74 distant normal mucosa, 107 adjacent mucosa, 158 primary tumour, 35 lymph node metastasis and 9 liver metastasis samples. In addition, the AEG-1 protein expression was elucidated in the cell lines by Western blot. RESULTS: The lymph node metastatic cell line SW620 had a significantly higher AEG-1 mRNA (0.27 ± 0.02) expression compared to the primary tumour cell line SW480 (0.17 ± 0.04, p = 0.026). AEG-1 expression at the mRNA level and/or the protein level was significantly up-regulated gradually from normal mucosa to primary CRC, and then to lymph node metastasis and finally to liver metastasis (p < 0.05). There were significant associations of AEG-1 mRNA expression with tumour location (p = 0.047), as well as mRNA and protein expression with the tumour stage (p < 0.03). Furthermore AEG-1 protein expression was positively related to biological variables including NF-κB, p73, Rad50 and apoptosis (p < 0.05). CONCLUSION: AEG-1 is up-regulated, at the mRNA and the protein level, during CRC development and aggressiveness, and is related to tumour location and stage. It may play its role in CRC through the NF-κB signaling pathway.

Enhanced anti-glioma efficacy of doxorubicin with BRD4 PROTAC degrader using targeted nanoparticles.

Current treatment of glioma is hampered due to the physical blood-brain barrier (BBB) and the resistance to traditional chemotherapeutic agents. Herein, we proposed a combined treatment strategy based on Cyclo (Arg-Gly-Asp-d-Phe-Lys) (cRGDfk) peptides-modified nanoparticle named cRGD-P in a self-assembly method for the co-delivery of doxorubicin (DOX) and BRD4 PROTAC degrader ARV-825 (ARV). Molecular dynamics simulations showed that cRGD-P could change its conformation to provide interaction sites for perfectly co-loading DOX and ARV. The cRGD-P/ARV-DOX exhibited an average size of 39.95 â€‹nm and a zeta potential of -0.25 â€‹mV. Increased expression of BRD4 in glioma cells was observed after being stimulated by cRGD-P/DOX, confirming one of the possible mechanisms of DOX resistance and the synergistic tumor inhibition effect of BRD4 degrading ARV combined with DOX. In the study, the combination of DOX and ARV in the cRGD-P nanoparticle system exhibited synergistic suppression of tumor growth in glioma cells on account of cell cycle arrest in the G2/M phase and the activation of tumor cells apoptosis-related pathways including triggering caspase cascade and downregulating Bcl-2 as well as upregulating Bax. The cRGD-P/ARV-DOX system could effectively suppress the heterotopic and orthotopic growth of glioma by increasing tumor apoptosis, inhibiting tumor proliferation, and decreasing tumor angiogenesis in vivo. Therefore, the cRGD-modified nanoparticle to co-deliver DOX and ARV provides a potential platform for exploiting a more effective and safer combination therapy for glioma.

Primary dedifferentiated Liposarcoma of vagina: a first case report.

BACKGROUND: Dedifferentiated liposarcoma, one of the most deadly types of soft tissue sarcoma, is an aggressive and high-grade form of liposarcoma. Liposarcoma occurs most commonly in the retroperitoneum, extremities and trunk, but less frequently in the female genital tract. The vagina is a very rare site of origin. Herein we report the first case of dedifferentiated Liposarcoma deriving from vagina and discuss its clinical course. CASE PRESENTATION: A 38-year-old female patient presented to our institution with a painless vaginal mass. Abdominal computed tomography showed a 17.6 cm× 10.4 cm solid mass originating from the right lateral wall of her vagina. Then she underwent complete surgical resection of the tumor mass, and postoperative pathological result confirmed the diagnosis of dedifferentiated liposarcoma deriving from vagina. Six courses of combination chemotherapy with pirarubicin plus ifosfamide were performed after surgery. The patient remains with no evidence of disease recurrence with 13 months of follow-up. CONCLUSIONS: Liposarcoma is very rare in female genital tract, and more rare for dedifferentiated liposarcoma in gynecologic field. Little is known about the clinical characteristics, pathological diagnosis, prognosis and optimal management strategy of vaginal dedifferentiated liposarcoma. Complete surgical resection followed by systemic chemotherapy is suggested to be standard treatment for dedifferentiated liposarcoma. Combination chemotherapy with pirarubicin and ifosfamide may be effective for treating vaginal dedifferentiated liposarcoma.

Mesonephric adenocarcinomas in female genital tract: A case series.

ABSTRACT: Mesonephric adenocarcinoma (MNAC) is a very rare tumor that originates from mesonephric duct remnants of the female genital tract. Only a few cases were reported in the literature, and most of them occurred in the cervix, extremely rare in the uterine body and ovary. MNAC was rarely reported to arise in the uterine corpus, but never was reported in the ovary. Mesonephric-like adenocarcinomas are recently suggested to describe these neoplasms arising from the uterine corpus and ovary. Due to the rareness of the disease, little is known regarding clinical characteristics, pathological diagnosis, prognosis, and optimal management strategy of MNAC in the female reproductive system. We report a series of MNACs arising from the vagina, cervix, uterine corpus, ovary, and fallopian tube, to summarize the clinical characteristics, pathological diagnosis, treatment, and prognosis.We retrospectively analyzed all MNACs in the female genital tract derived from our institute from January 2010 till January 2020. Patients' clinical details and follow-up were obtained from hospital records and scans were obtained from picture archiving and communication system.A total of 11 patients were included. The median age of onset of symptoms was 52 years. All patients underwent total hysterectomy and bilateral salpingo-oophorectomy, and lymph node dissections were performed in 7/11 (63.6%) patients. Two/eleven (18.2%) received neoadjuvant chemotherapy before surgery and 7/11 (63.6%) received adjuvant chemotherapy after primary surgery. Of the 11 patients, only 1 patient received adjuvant radiation therapy. One patient died at the end point of this study, 9 patients (81.8%) survived and 1 patient was lost to follow-up. The mean follow-up duration was 33.5 months.Although there is no consensus for the optimal treatment of this rare disease, radical surgery is considered to be the initial choice for localized lesion. Given the high malignancy, the majority of MNAC or mesonephric-like adenocarcinoma patients who underwent adjuvant chemotherapy received 4 to 8 cycles of carboplatin/paclitaxel as a first-line treatment after primary surgery with a median progression-free survival of 12 months. Treatment for recurrent disease in these patients included gemcitabine, carboplatin, and paclitaxel. Radiation was very limited in the treatment of the disease.

Recurrent and metastatic female adnexal tumor of probable Wolffian origin: A case report and review of the literature.

RATIONALE: Female adnexal tumors of probable Wolffian origin (FATWOs) are rare gynecologic neoplasms arising from the mesonephric duct remnants. Less than 90 cases have been reported in the English literature. Although most cases of FATWO are considered benign, recurrence and metastasis may occur in very few cases during the course of the disease. Due to the small number of recurrent and metastatic FATWO cases, there are no clear recommendations regarding optimal treatment. PATIENT CONCERNS: A 75-year-old postmenopausal woman, who underwent a mass excision of the right broad ligament three years ago, was found to have a right adnexal mass during a regular postoperative physical examination. DIAGNOSES: Vaginal ultrasound examination revealed a cystic and solid mass approximately 3.6 × 4.4 × 3.8 cm on the right side of the uterus. Three years ago, the mass of the right broad ligament was diagnosed with FATWO in the local hospital. Following extensive immunohistochemistry analysis and after reviewing the histology slides from the primary tumor, the final diagnosis of the mass on the right side of the uterus was recurrent and metastatic FATWO. INTERVENTIONS: The patient underwent laparoscopic mass excision, hysterectomy and resection of the metastatic lesion in the small intestine, and then she received 6 cycles of docetaxel and carboplatin-based chemotherapy. OUTCOMES: The disease has recurred three years after the first surgery in the local hospital. After the second surgery followed by systemic chemotherapy, there is no evidence of recurrence with 24 months of follow-up till now. LESSONS: FATWO is considered a benign entity. However, a few FATWOs have been shown to behave aggressively. Due to only a few reported cases, there are no comprehensive recommendations regarding the optimal clinical management of recurrent and metastatic FATWOs. Complete surgical resection followed by combination chemotherapy is considered to be the most effective therapy for recurrent and metastatic FATWOs. Chemotherapy with docetaxel plus carboplatin, which is most commonly used in malignant cases, may be effective in the treatment of recurrent and metastatic FATWOs.

Primary mesonephric adenocarcinoma of the fallopian tube: A case report.

BACKGROUND: Mesonephric adenocarcinoma (MNAC) is an extremely rare malignancy in the female genital tract. Only a few cases have been reported in the literature, and most of them occurred in the cervix, with extremely rare cases in the uterine body and ovary. MNAC has never been reported to arise in the fallopian tube. CASE SUMMARY: A 45-year-old woman was referred to our institution with a history of abdominal pain. Ultrasound revealed a cystic and solid mass in left adnexal region. The patient underwent complete staging surgery when intraoperative pathological examination demonstrated that the mass was malignant. The final histological and immunohistochemical results confirmed the diagnosis of MNAC originating from the fallopian tube. Then she received four cycles of combination chemotherapy with carboplatin plus paclitaxel. The tumor recurred with hepatic metastases 4 mo after initial surgery, and second resection of the tumors in the liver plus partial hepatectomy was performed. She was supplemented with five courses of a new combination chemotherapy with gemcitabine plus carboplatin, and there was no evidence of recurrence within the 22-mo follow-up period after the second surgery. CONCLUSION: MNAC originating from the fallopian tube is an extremely rare and high malignancy with a poor prognosis. It can be very aggressive, even at early stage. Little is known about the clinical characteristics, pathological diagnosis, prognosis, and optimal management strategy of MNAC originating from the fallopian tube. Herein we report the first case of primary MNAC deriving from the fallopian tube.

Malignant mixed müllerian tumor of the fallopian tube: report of two cases and review of literature.

PURPOSE: Malignant mixed müllerian tumors (MMMT) of the female genital tract is rare and it is extremely rare in the fallopian tube, with fewer than 53 cases reported in the literature. METHODS: We had experienced two cases of MMMT of the fallopian tube. The clinical features, pathologic findings, diagnosis, therapy, and outcome were reviewed. RESULTS: The clinical features and diagnosis were similar to those of primary carcinoma of the fallopian tube. Histologically, the two patients had homologous and heterologous elements mixed müllerian tumors. Treatment has focused on surgery with postoperative chemotherapy. Prognosis is poor, with fewer than half of patients surviving 2 years. CONCLUSIONS: MMMT of fallopian tube is an uncommon carcinoma in the female genital tract. Cervical cytology and endometrial curettage could raise the suspicion of a tubal malignancy, but diagnosis is not usually made until the time of surgery. The patient survival will improve after surgery and postoperative chemotherapy.

Mesonephric-like adenocarcinoma of the ovary: A case report and a review of the literature.

RATIONALE: Mesonephric-like adenocarcinoma (MLA) from ovary is a very rare tumor which derives from mesonephric duct remnant of the female genital tract. Only six cases have been reported so far in the English literature. PATIENT CONCERNS: A 29-year-old female patient was referred to the local hospital with a 20-day history of abdominal discomfort. DIAGNOSES: Pelvic ultrasound examination revealed a solid and cystic mass measuring 10 cm in diameter in the right adnexal area and a cystic mass measuring 5 cm in the left adnexal area. Postoperative pathology in the local hospital revealed suspected malignancy of the right ovary, and she was then transferred to our institution for definite diagnosis. The tumor mass was finally diagnosed as a primary MLA arising from the right ovary by histological and immunohistochemical examination in our institution. INTERVENTIONS: The patient underwent laparoscopic right adnexectomy and removal of left ovarian cyst in the local institution. Then, she underwent a complete staging surgery including a total hysterectomy, left adnexectomy, pelvic plus para-aortic lymphadenectomy, and omentectomy in our hospital. In addition, she received four cycles of combination chemotherapy with carboplatin plus paclitaxel. OUTCOMES: There is no evidence of recurrence with 13 months of follow-up till now, and we are still following-up this patient. LESSONS: MLA is an extremely uncommon malignancy with difficult diagnosis, unclear treatment and poor prognosis. Familiarizing with the clinical features and optimal management of this rare tumor may increase awareness of the disease among clinicians and pathologists, thus avoiding the misdiagnosis and mistreatment.

miR-29b inhibits non-small cell lung cancer progression by targeting STRN4.

Non-small cell lung cancer (NSCLC) is a malignant tumor with a high fatality, low overall cure, and survival rates worldwide. When only palliative therapy is available, the disease leads to malignant proliferation. Previous studies showed miR-29b serves as an NSCLC suppressor by inhibiting cells proliferation, migration, and invasion. However, the mechanism underlying NSCLC progression remains elusive. In this study, we identified Striatin 4 (STRN4), a target of miR-29b, which serves as a pro-oncogenic protein by promoting cells proliferation, migration, and invasion in NSCLC. Besides, the STRN4 was highly expressed in NSCLC and negatively regulated by miR-29b. Down-regulation of STRN4 inhibits NSCLC cells proliferation, migration, invasion, and promotes apoptosis in vitro, whereas overexpression-induced enhanced cell migration and invasion could be reverved by miR-29b. Notably, overexpression of miR-29b and down-regulation of STRN4 by shRNA suppressed cellular proliferation and delayed tumor progression in vivo. Together, these findings identify a miR-29b/STRN4 regulatory pathway in NSCLC progression, which may provide a new sight for the treatment of NSCLC.

Sclerosing stromal tumor of the ovary with masculinization, Meig's syndrome and CA125 elevation in an adolescent girl: A case report.

BACKGROUND: Sclerosing stromal tumor (SST) is an extremely rare sex cord stromal tumor of the ovary. It was first reported and named in 1973. These tumors typically present with pelvic/abdominal pain and tenderness, a mass, and/or abnormal menses, but rarely present with masculinity in children and adolescents. Only 2 cases of these tumors have been reported in premenarchal girls, who demonstrated hormonal activity, with a history of the development of a virilizing female due to hyperandrogenism. Here, we report a case of a giant SST with obvious masculinity combined with Meig's syndrome and CA125 elevation. CASE SUMMARY: A 17-year-old female presented with a 7-year history of the development of masculinity and a 2-year history of amenorrhea. She had hirsutism, acne, obvious laryngeal prominence, and voice deepening. Physical examination showed a male suprapubic hair pattern and a 4.0 cm × 1.5 cm enlarged clitoris. Laboratory tests showed that the testosterone level was > 15.00 ng/mL (normal range: 0.14-0.76 ng/mL), and androstenedione level was > 10.00 ng/mL (normal range: 0.3-3.3 ng/mL). A computed tomography scan of the abdomen and pelvis was carried out and showed a large, solid and cystic, partly calcified pelvic mass in the right ovary measuring 27.1 cm × 20.0 cm × 11.0 cm, 15 cm above the umbilicus (to the level of the upper part of L1). Intraoperative findings at laparotomy revealed a large tumor arising from the right ovary. Approximately, 500 mL of pale-yellow clear liquid was found in the pelvic cavity. A right salpingo-oophorectomy was performed. Microscopic examination and immunohistochemical staining of the surgical specimen showed an SST of the ovary. CONCLUSION: This report is remarkable as our patient was not only diagnosed with an SST of the ovary, which is extremely rare in this age group, but was the largest and most obvious reported patient with this tumor who presented with virilization. Therefore, gynecologists should be aware of this potential complication in adolescent girls with a mass in the ovary.

Improving the Anti-Ovarian Cancer Activity of Docetaxel by Self-Assemble Micelles and Thermosensitive Hydrogel Drug Delivery System.

In recent decades, a large number of research studies have been conducted to improve the treatment strategy against epithelial ovarian cancer, but women in advanced stage still have poor outcomes. The development of advanced treatments must be continued to overcome the limitation. Docetaxel, a semi-synthetic product derived from the Pacific Taxus extract, has been studied for many years for its potent anticancer applications. Aiming to solve the problems of its highly lipophilicity, insolubility and adverse side effects, nanocarriers were applied. Relying on the integration of nanoparticles which had optimized sizes, shapes, and surface properties, the effect of docetaxel was enhanced. In this study, we designed a novel drug loaded gel-forming nanoparticle system (Doc-NMs-hydrogel composites), which acted as a sustained drug depot for docetaxel. Docetaxel was encapsulated into MPEG-PCL and then into blank thermosensitive hydrogel Pluronic F-127. Characterization showed that the prepared Doc-NMs had high drug loading (7%), minor particle size (37 nm), relatively good water solubility. Moreover, the cytotoxicity, apoptosis induction and the antitumor effects of Doc-NMs-hydrogel composites on mice abdominal SKOV-3 ovarian cancer model were investigated in vivo. Compared with other groups, at the same dosage, Doc-NMs-hydrogel composites show better apoptosis induction and cell growth inhibition. In conclusion, the prepared Doc-NMs-hydrogel composites enhanced anti-tumor activity by increasing local docetaxel concentration, maintaining stable and sustained drug release, prolonging drug retention time in tumors, and reducing toxicity to normal tissues. Doc-NMs-hydrogel composites might have great potential clinical application in anti-ovarian cancer activity.

Ovarian endometrioid adenocarcinoma a with yolk sac tumor in a 41-year-old woman: a case report.

BACKGROUND: Yolk sac tumors (YSTs) are the second most common germ cell malignancy of the ovaries generally present in children and young women. YSTs arising in combination with epithelial ovarian carcinoma (EOC) in older women are rarely reported. The YST components in such cases often show a marked morphological and immunophenotypic overlap with epithelial neoplasms, making diagnosis difficult. CASE REPORT: A 41-year-old woman presented with irregular vaginal bleeding and a bilateral adnexal mass. The postoperative pathology confirmed a poorly differentiated adenocarcinoma and YST of the left ovary. The short tandem repeat (STR) analysis further indicated that the YST component was probably derived from an epithelial precursor neoplasm. CONCLUSION: This case improves our ability to detect and diagnose YST coexisting with epithelial tumors in older patients by summarizing its histopathologic characteristics and immunohistochemical stains. Molecular analysis should be used to further identify such mixed neoplasms.

Correction: Enhancing the anti-ovarian cancer activity of quercetin using a self-assembling micelle and thermosensitive hydrogel drug delivery system.

[This corrects the article DOI: 10.1039/C8RA03274B.].

Atypical carcinoid of the uterine cervix accompanying adenocarcinoma in situ.

CLINICAL QUESTION: A 45-year-old woman presented with painless vaginal bleeding for 2 months. A biopsy was taken from the uterine cervix, and poorly differentiated adenocarcinoma was suspected. After three cycles of neoadjuvant chemotherapy treatment, the patient underwent radical hysterectomy with bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy.Review the high quality, interactive digital Aperio slide at http://virtualacp.com/JCPCases/jclinpath-2018-205081-1/ and consider your diagnosis. WHAT IS YOUR DIAGNOSIS?: Typical carcinoid.Poorly differentiated adenocarcinoma.Atypical carcinoid.Small cell neuroendocrine carcinoma.Sex cord-stromal tumours of the uterine cervix.-The correct answer is after the discussion. DISCUSSION: Neuroendocrine tumours of the uterine cervix are a rare cancer of the female reproductive system, accounting for approximately 1% of all female cervical malignancies.1 2 In 1997, a consensus workshop suggested four types of neuroendocrine tumours of the uterine cervix: typical and atypical carcinoid tumours, small cell neuroendocrine carcinomas, and large cell carcinomas.1 Among all the categories, small cell neuroendocrine carcinomas are of the highest incidence. A PubMed search revealed that only 15 cases of atypical carcinoid tumours of the uterine cervix have been reported.3 4 Because of infrequency, the clinical and pathological features of atypical carcinoid tumours of the uterine cervix remain unknown.Atypical carcinoids are characterised by great cytological atypia, which means abundant or scanty cytoplasm and visible nucleoli with granular chromatin. Tumour cells lined up in insular, trabecular, columnar and nested organoid patterns; they are epithelioid in appearance, but can be spindled (figure 1A). Necrosis could be observed in some areas and mitotic activity is up to 10 mitotic figures/10 high-power field (figure 1B). On immunohistochemistry, atypical carcinoids are diffuse and positive for Syn, CgA and CD56 (figure 2). An electron microscopic test was done, and several neuroendocrine granules were distributed in the tumour cell plasma (figure 3).jclinpath;71/11/1030/F1F1F1Figure 1(A) Insular, trabecular and columnar patterns of tumour cells were focally observed in the deep stroma of the cervix (H&E ×200). (B) Tumour cells showed small-sized, scanty cytoplasm, enlarged and deeply stained nuclei with condensed chromatin, obvious atypia, and increased mitotic activity (H&E ×400). (C) The cervical gland has shown atypical hyperplasia and adenocarcinoma in situ (H&E ×200).jclinpath;71/11/1030/F2F2F2Figure 2Immunohistochemical study findings: (A-C) The neuroendocrine markers Syn, CgA and CD56 were diffuse with strong expression in the tumour cell plasma. (D-E) P63 and CK5/6 for the squamous cell carcinomas showed no expression. (F-G) P16 for atypical carcinoid and adenocarcinoma in situ, respectively, had strong diffuse expression. (H-I) Ki67 had low expression in both atypical carcinoid and adenocarcinoma in situ (×200).jclinpath;71/11/1030/F3F3F3Figure 3Several neuroendocrine granules were distributed in the tumour cell plasma.Neuroendocrine tumours of the uterine cervix are sometimes combined with adenocarcinoma (figure 1C); their cytological and immunohistochemical features showed the neuroendocrine and adenomatous components shared the same origin.

Inhibition of cervical cancer cells by co-culturing with mesenchymal stem cells.

Background: The effect of mesenchymal stem cells (MSCs) on tumors remains controversial and requires further exploration. In this study, we isolated MSCs from umbilical cord (UC) and co-cultured with cervical cancer HeLa cells. Flow cytometry was conducted to detect apoptosis and cell cycle. CCK8 and Matrigel-transwell were performed to assay cell proliferation and invasion ability, respectively. Results: Our results indicated that UCMSCs inhibited proliferation of HeLa cells 72 hours post co-culture but had no obvious effect on apoptosis and cell cycle. UCMSCs dramatically suppressed invasion of HeLa cells in transwell detection. In mechanism study, we found that UCMSCs could inhibit expression of AKT/PI3K/STAT3/mTOR pathway and influence epithelial-mesenchymal transition markers. Conclusion: Our study clearly confirms that UCMSCs could inhibit biological functions of cervical cancer cells.

Enhancing the anti-ovarian cancer activity of quercetin using a self-assembling micelle and thermosensitive hydrogel drug delivery system.

Ovarian cancer, as one of the killers that threaten women's health, has been studied extensively. As a natural bioflavonoid with prospective effects, quercetin is highly recognized for its anti-cancer applications. However, one of the major challenges that quercetin faces is its poor water solubility, instability in physiological media, and subsequent poor bioavailability. Thus, optimizing the ideal drug delivery options is necessary to facilitate the harnessing of the maximum benefits from quercetin. In this study, a quercetin-loaded thermosensitive injectable hydrogel system (Qu-M-hydrogel composites) was constructed based on nanotechnology. Quercetin was encapsulated into MPEG-PCL (with a high drug loading of 7% and minor particle size of 32 nm) and then added into the blank thermosensitive hydrogel Pluronic F-127. The Qu-M-hydrogel composites showed a much slower release than Qu-M in vivo. Moreover, the cytotoxicity, apoptosis induction, and anti-tumor effects of the Qu-M-hydrogel composites on the abdominal SKOV-3 ovarian cancer mouse models were investigated in vivo. Compared with other groups, the Qu-M-hydrogel composites exhibited improved apoptosis induction and cell growth inhibition effects and in vivo trials showed a better balance between the anti-tumor efficacy in the Qu-M-hydrogel composite group than in other groups at an equal drug dose. In conclusion, the prepared Qu-M-hydrogel composites enhanced the anti-tumor activity by providing a high local quercetin concentration, sustained and stable drug release, extended drug retention inside the tumor, and low toxicity to normal tissues. The Qu-M-hydrogel composites might have great potential for clinical application in anti-ovarian cancer activity.