This is a case of a 54-year-old, perimenopausal, Asian, woman, who presented with an enlarging left breast mass associated with whitish to bloody nipple discharge. A core needle biopsy, done in another institution, showed histologic findings of a mucinous carcinoma with triple negative “basal-like” biomarker status (ER, PR, HER2/neu). Six cycles of neoadjuvant chemotherapy were given after which the subsequent modified radical mastectomy revealed a centrally located, 10.0 cm, well-circumscribed, nodular, ovoid mass on gross examination. Microscopic findings showed tall columnar cells in stratification, tufts and papillary formations, with surrounding abundant extracellular mucin. The individual tumor cells exhibit enlarged, hyperchromatic, basally located nuclei with prominent nucleoli, abundant amphophilic and occasionally oncocytic cytoplasm which contains intracytoplasmic mucin. Based on the histologic features, “basal-like” biomarker expression, and additional immunohistochemical studies (positive CK7, negative CK20 and CDX2), this case demonstrates a pure mucinous cystadenocarcinoma of the breast. In addition to the rare histologic type, this case is exceptional since, despite multiple cycles of neoadjuvant chemotherapy, presence of extensive lymphovascular invasion and axillary lymph node involvement with extranodal extension remain evident.
Cystadenocarcinoma, Mucinous ; Breast Neoplasms

Objective: To investigate the cytomorphological and immunocytochemical features of tumor cells in the ascites of ovarian plasmacytoma (SOC). Methods: Specimens of serous cavity effusions were collected from 61 tumor patients admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2015 to July 2021, including ascites from 32 SOC, 10 gastrointestinal adenocarcinomas, 5 pancreatic ductal adenocarcinomas, 6 lung adenocarcinomas, 4 benign mesothelial hyperplasia and 1 malignant mesothelioma patients, pleural effusions from 2 malignant mesothelioma patients and pericardial effusion from 1 malignant mesothelioma. Serous cavity effusion samples of all patients were collected, conventional smears were made through centrifugation, and cell paraffin blocks were made through centrifugation of remaining effusion samples. Conventional HE staining and immunocytochemical staining were applied to observe and summarize cytomorphological characteristics and immunocytochemical characteristics. The levels of serum tumor markers carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected. Results: Of the 32 SOC patients, 5 had low-grade serous ovarian carcinoma (LGSOC) and 27 had high-grade serous ovarian carcinoma (HGSOC). 29 (90.6%) SOC patients had elevated serum CA125, but the difference was not statistically significant between them and patients with non-ovarian primary lesions included in the study (P>0.05); The serum CEA was positive in 9 patients with gastrointestinal adenocarcinoma and 5 patients with lung adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.001); The serum CA19-9 was positive in 5 patients with gastrointestinal adenocarcinoma and 5 patients with pancreatic ductal adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.05). The serum CA125, CEA and CA19-9 were within the normal range in 4 patients with benign mesothelial hyperplasia. LGSOC tumor cells were less heterogeneous and aggregated into small clusters or papillary pattern, and psammoma bodies could be observed in some LGSOC cases. The background cells were fewer and lymphocytes were predominant; the papillary structure was more obvious after making cell wax blocks. HGSOC tumor cells were highly heterogeneous, with significantly enlarged nuclei and varying sizes, which could be more than 3-fold different, and nucleoli and nuclear schizophrenia could be observed in some cases; tumor cells were mostly clustered into nested clusters, papillae and prune shapes; there were more background cells, mainly histiocytes. Immunocytochemical staining showed that AE1/AE3, CK7, PAX-8, CA125, and WT1 were diffusely positively expressed in 32 SOC cases. P53 was focally positive in all 5 LGSOCs, diffusely positive in 23 HGSOCs, and negative in the other 4 HGSOCs. Most of adenocarcinomas of the gastrointestinal tract and lung had a history of surgery, and tumor cells of pancreatic ductal adenocarcinoma tend to form small cell nests. Immunocytochemistry can assist in the differential diagnosis of mesothelial-derived lesions with characteristic "open window" phenomenon. Conclusion: Combining the clinical manifestations of the patient, the morphological characteristics of the cells in the smear and cell block of the ascites can provide important clues for the diagnosis of SOC, and the immunocytochemical tests can further improve the accuracy of the diagnosis.
Female ; Humans ; Carcinoembryonic Antigen ; Ascites ; CA-19-9 Antigen ; Mesothelioma, Malignant/diagnosis* ; Hyperplasia ; Adenocarcinoma/pathology* ; Cystadenocarcinoma, Serous/diagnosis* ; Biomarkers, Tumor ; Carcinoma, Ovarian Epithelial ; Diagnosis, Differential ; Ovarian Neoplasms/pathology* ; Carbohydrates

Objective To investigate the expression of long non-coding RNA ubiquitin-specific peptidase 30 antisense RNA 1 (lncRNA USP30-AS1) and its relationship with immune infiltration in ovarian serous cystadenocarcinoma (OSC), and to determine its prognostic role in OSC. Methods The Cancer Genome Atlas (TCGA) database was utilized to retrieve the expression of USP30-AS1 and clinical information of 384 OSC patients. Wilcoxon rank-sum test was employed to compare the expression of USP30-AS1 between OSC and normal ovarian tissues. Logistic regression analysis was conducted to assess the relationship between clinical pathological features and USP30-AS1. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate enrichment pathways and functions and quantify the degree of immune cell infiltration in USP30-AS1. Based on the expression level of long non-coding RNA (lncRNA) USP30-AS1, the samples were divided into high and low expression groups according to the expression mean. Log-rank tests, univariate and multivariate proportional hazards model (Cox) were used to compare prognostic differences between different USP30-AS1 expression groups. The impact of lncRNA USP30-AS1 expression on other genomic analyses was also analyzed. Results High expression of USP30-AS1 was significantly associated with the International Federation of Gynecology and Obstetrics (FIGO) stage of the tumor. Multivariate survival analysis indicated that USP30-AS1 expression level served as an independent prognostic marker for OSC. GSEA data showed that high expression of USP30-AS1 might activate programmed death 1 (PD-1) signaling pathway, cytotoxic T lymphocyte-associated protein 4 (CTLA4) pathway, B-cell receptor signaling pathway, cell apoptosis, fibroblast growth factor receptor (FGFR) signaling pathway, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. The expression of USP30-AS1 was negatively correlated with immune cell infiltration, including B cells, CD4⁺ T cells, dendritic cells, CD8⁺ T cells, and neutrophils. Conclusion USP30-AS1 may be used as a prognostic molecular marker for OSC.
Female ; Humans ; Pregnancy ; CD8-Positive T-Lymphocytes ; Computational Biology ; Cystadenocarcinoma, Serous/genetics* ; RNA, Antisense ; RNA, Long Noncoding/genetics* ; Ubiquitin-Specific Proteases/genetics*

Humans ; Breast/pathology* ; Cystadenocarcinoma/pathology* ; Cystadenocarcinoma, Mucinous/pathology* ; Female

To develop a survival time prediction model for patients with ovarian serous cystadenocarcinoma after surgery. A retrospective analysis of 5906 postoperative patients with ovarian serous cystadenocarcinoma in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015 was performed. The independent risk factors for long-term survival were analyzed with multivariate Cox proportional hazard regression model. The nomogram of 3-year and 5-year survival was developed by using R language. The receiver operator characteristic (ROC) curve and were used to test the discrimination of the model and the calibration diagram was used to evaluate the degree of calibration of the prediction model. The survival curves was conducted by the risk factors. Cox proportional hazard regression model showed that age, race, histological grade (poorly differentiated and undifferentiated), stage T (T2a, T2b, T2c, T3a, T3b and T3c), and stage M (M1) were independent factors for the prognosis of patients with ovarian serous cystadenocarcinoma after surgery. A nomogram was developed by the R language tool for predicting the 3-year and survival of patients through age, race, histological classification, stage T and stage M. The C-index was 0.688 and the areas under ROC curve of the nomogram for predicting 3-year and 5-year survival were 0.708 and 0.716, respectively. The results of the calibration indicated that the predicted values were consistent with the actual values in the prediction models. The survival time of patients with high-risk factors was shorter than that of patients with low-risk factors (<0.05). The developed nomogram in this study can be used to predict 3-year and 5-year survival of postoperative patients with ovarian serous cystadenocarcinoma, and it may be beneficial to guide clinical treatment.
Cystadenocarcinoma, Serous/surgery* ; Humans ; Neoplasm Staging ; Nomograms ; Prognosis ; ROC Curve ; Retrospective Studies ; SEER Program ; Survival Rate

OBJECTIVE: To investigate the relationship between the precursors of high grade serous ovarian cancer (HGSOC) and the characteristics of patients with a low HGSOC risk in terms of the effects of pregnancy. METHODS: We prospectively examined consecutive cases in which the bilateral fallopian tubes were removed during benign gynecological or obstetric surgery and assessed the relationship between the patient characteristics, including parity and pregnancy, and the incidence of HGSOC precursors. All the fallopian tubes were examined by applying the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) Protocol. RESULTS: Of the 113 patients enrolled, 67 were gynecological and 46 were obstetric. The p53 signature was identified in 21 patients. No other precursors were identified. In a comparison of the p53 signature-positive and negative groups, parous women and pregnant women were significantly fewer in the p53 signature-positive group (53% vs. 86%, p=0.002, 10% vs. 47%, p=0.001, respectively). Current pregnancy was also associated with a significantly lower incidence of the p53 signature after multivariate adjustment (odds ratio [OR]=0.112; 95% confidence interval [95% CI]=0.017–0.731; p=0.022). Among gynecological patients, parous women were fewer in the p53 signature-positive group on univariate (47% vs. 73%, p=0.047) and multivariate analysis (OR=0.252; 95% CI=0.069–0.911; p=0.036). No other characteristics were associated with p53 signature positivity. CONCLUSIONS: The incidence of the p53 signature was significantly lower in parous women and pregnant women. This decreased incidence of early phase serous carcinogenesis may be one of the possible mechanisms underlying HGSOC risk reduction among parous women.
Carcinogenesis ; Cystadenocarcinoma, Serous ; Fallopian Tube Neoplasms ; Fallopian Tubes ; Female ; Humans ; Incidence ; Multivariate Analysis ; Obstetric Surgical Procedures ; Ovarian Neoplasms ; Parity ; Pregnancy ; Pregnant Women ; Prospective Studies ; Risk Reduction Behavior ; Tumor Suppressor Protein p53

Schistosomiasis has been established as a causative factor in urinary bladder, liver, colorectal and cervical cancer. However, its role in ovarian malignancy has not been described. With the premise that long-standing inflammation secondary to chronic infection predisposes to cancer by promoting an environment that cultivates genomic lesions and tumor initiation, we are left with an open question: Does chronic infection with schistosomiasis also predispose to ovarian cancer? In this paper, we presented a case of a 54-year-old diagnosed with high grade serous carcinoma of the ovary and fallopian tube with a history of chronic infection with Schistosomiasis. In this case, the infection caused neoplastic lesions in the right fallopian tube with subsequent seeding of malignant cells to the right ovary, indirectly causing the high grade serous ovarian carcinoma of the patient.
Fallopian Tubes ; Cystadenocarcinoma, Serous ; Ovarian Neoplasms ; Schistosomiasis

OBJECTIVE: Ovarian needle aspiration and biopsy (ONAB) may be employed for pretreatment diagnosis of ovarian malignancies or intraoperatively to facilitate removal of ovarian masses. However, there is reluctance to utilize this procedure due to potential cyst rupture or seeding of malignant cells. The objective of this study was to examine the efficacy of ONAB over a 13-year period at our institution. METHODS: Between 2000 and 2013, all ONAB specimens were identified from the Queen's Medical Center Pathology Department database. All cytologic specimens were reviewed and correlated with histopathologic findings. A retrospective chart review was conducted to retrieve data on clinical course and treatment. RESULTS: This study identified 144 cases of ovarian masses sampled by aspiration or needle biopsy between 2000 and 2013. Ninety-two (64%) cases had corresponding histopathology, 84 (91%) of which were obtained concomitantly. On histology, 12 (13%) cases were malignant and 80 (87%) benign. Three false negative cases were noted; 2 serous borderline tumors and 1 mucinous cystadenocarcinoma. These were sampling errors; no diagnostic tumor cells were present in the aspirates. Sensitivity and specificity of ONAB in the detection of malignancy were 75% and 100%, respectively. The positive and negative predictive values were 100% and 96%, respectively. CONCLUSION: ONAB represents a valuable tool in the diagnosis of malignancy and treatment of ovarian masses. In our study, it was highly specific, with excellent positive and negative predictive value.
Biopsy ; Biopsy, Needle ; Cystadenocarcinoma, Mucinous ; Diagnosis* ; Needles* ; Ovarian Neoplasms ; Pathology ; Retrospective Studies ; Rupture ; Selection Bias ; Sensitivity and Specificity

BACKGROUNDOvarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the differences in the PH domain leucine-rich repeat protein phosphatase (PHLPP), forkhead homeobox type O 3a (FoxO3a), and RAD51 protein expressions, and their associations with prognosis in patients with low- and high-grade ovarian serous adenocarcinomas.

METHODSThe PHLPP, FoxO3a, and RAD51 protein expressions were examined in 94 high- and 26 low-grade ovarian serous adenocarcinomas by immunohistochemistry. The differences in expression and their relationships with pathological features and prognosis were analyzed.

RESULTSIn high-grade serous adenocarcinomas, the positive rates of PHLPP and FoxO3a were 24.5% and 26.6%, while in low-grade tumors, they were 23.1% and 26.9%, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). The positive rates of RAD51 were 70.2% and 65.4% in high- and low-grade serous adenocarcinomas, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). Meanwhile, in high-grade tumors, Stage III/IV tumors and lymph node and omental metastases were significantly associated with lower PHLPP and FoxO3a and higher RAD51 expression. The 5-year survival rates of patients with PHLPP- and FoxO3a-positive high-grade tumors (43.5% and 36.0%) were significantly higher than in patients with PHLPP-negative tumors (5.6% and 7.2%, respectively; P< 0.05). Similarly, the 5-year survival rate of RAD51-positive patients (3.0%) was significantly lower than in negative patients (42.9%; P< 0.05). In low-grade tumors, the PHLPP, FoxO3a, and RAD51 expressions were not significantly correlated with lymph node metastasis, omental metastasis, Federation of Gynecology and Obstetrics stage, or prognosis.

CONCLUSIONSAbnormal PHLPP, FoxO3a, and RAD51 protein expressions may be involved in the development of high- and low-grade ovarian serous adenocarcinomas, suggesting common molecular pathways. Decreased PHLPP and FoxO3a and increased RAD51 protein expression may be important molecular markers for poor prognosis, and RAD51 may be an independent prognosis factor, of high-grade, but not low-grade, ovarian serous adenocarcinomas.

Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Female ; Forkhead Box Protein O3 ; metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Nuclear Proteins ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; Phosphoprotein Phosphatases ; metabolism ; Prognosis ; Rad51 Recombinase ; metabolism

The diagnosis of hepatocellular carcinoma (HCC) is based on imaging studies particularly in high-risk patients without histologic confirmation. This study evaluated the prevalence and characteristics of false-positively diagnosed HCC in a liver resection cohort for HCC. A retrospective review was performed of 837 liver resection cases for clinically diagnosed HCC between 2005 and 2010 at our institute. High-risk patients with tumors > 1 cm with one or two image findings consistent with HCC and tumors < 1 cm with two or more image findings consistent with HCC with persistently increased serum alpha-fetoprotein (AFP) levels above the normal range with underlying inhibited hepatitis activity underwent liver resection. The false-positive rate was 2.2% (n = 18). Of the 18 patients, 7 patients (0.8%) were diagnosed with benign conditions (one each of hemangioma, inflammation, cortical adenoma, dysplastic nodule, angiomyolipoma, bile duct adenoma, and non-neoplastic liver parenchyme) and 11 patients (1.3%) were diagnosed with malignancies (cholangiocarcinoma [n = 6], hepatoblastoma [n = 2], and one each of lymphoepithelioma-like carcinoma, ovarian cystadenocarcinoma, and nasopharynx carcinoma metastasis). The clinical characteristics of pathologically diagnosed HCC patients were similar (P > 0.05) compared to non-HCC patients except for higher rate of history of alcoholism (P < 0.05) observed in non-HCC patients. Four of 18 non-HCC patients (22.2%) showed diagnostic discordance on the dynamic imaging study. Despite the recent progression in diagnostic imaging techniques, 2.2% of cases were false-positively diagnosed as HCC in a liver resection patient cohort; and the final diagnosis was benign disease in 0.8% of liver resection patients clinically diagnosed with HCC.
Adenoma ; Adenoma, Bile Duct ; Alcoholism ; alpha-Fetoproteins ; Angiomyolipoma ; Carcinoma, Hepatocellular* ; Cohort Studies ; Cystadenocarcinoma ; Diagnosis* ; Diagnostic Imaging ; Hemangioma ; Hepatitis ; Hepatoblastoma ; Humans ; Inflammation ; Liver* ; Nasopharynx ; Prevalence ; Reference Values ; Retrospective Studies