Uterine perivascular epithelioid cell tumors (PEComa) and the accuracy of proposed classification systems in predicting the malignant versus non-malignant behavior.

OBJECTIVE: To compare the accuracy of available classification systems (Folpe, modified Folpe, Bennet, and Schoolmester) in predicting the behavior of uterine Perivascular Epithelioid Cell tumors (PEComas). METHODS: We reviewed the pathology registry to identify all uterine PEComas treated at our center. We conducted a systematic literature review searching electronic databases from inception to November 2023. We included all references reporting at least one case of uterine PEComa; cases associated with tuberous sclerosis complex were excluded. Patient-level data were extracted by identified records. Survival analysis was used to assess the accuracy of all proposed classification systems to classify uterine PEComas as malignant versus non-malignant. RESULTS: Six uterine PEComas were treated at our center. The literature search identified 101 uterine PEComas from 32 studies. Eighty-five out of 107 PEComas (28 studies and our series) reported enough follow-up data and details to apply all four classifications. The modified Folpe classification demonstrated the highest hazard ratio (HR) for relapse (HR:8.63; 95% confidence interval [CI] 2.06-36.1) and death due to PEComa (HR:6.8, 95%CI:0.89-51.6) for malignant versus non-malignant PEComas. Changing the cut-off of PEComa size to ≥8 cm and mitotic figures per 50 high power fields to ≥5, the HR for recurrence lowered (HR:6.26; 95% CI 2.20-17.80), but HR for death increased (HR:10.3; 95% CI 1.35-77.80). CONCLUSIONS: The modified Folpe classification was the most accurate in predicting the PEComa behavior. Changing the cut-off of PEComa size and number of mitotic figures may improve the accuracy in predicting death due to disease.

BRCA somatic and germline mutation detection in paraffin embedded ovarian cancers by next-generation sequencing.

BRCA mutated ovarian cancers respond better to platinum-based therapy and to the recently approved PARP-inhibitors. There is the need for efficient and timely methods to detect both somatic and germline mutations using formalin-fixed paraffin-embedded (FFPE) tissues and commercially available technology. We used a commercial kit exploring all exons and 50bp exon-intron junctions of BRCA1 and BRCA2 genes, and semiconductor next-generation sequencing (NGS) on DNA from 47 FFPE samples of high-grade serous ovarian cancers. Pathogenic mutations were found in 13/47 (28%) cancers: eight in BRCA1 and five in BRCA2. All BRCA1 and two BRCA2 mutations were germline; three BRCA2 mutations were somatic. All mutations were confirmed by Sanger sequencing. To evaluate the performance of the NGS panel, we assessed its capability to detect the 6,953 variants described for BRCA1 and BRCA2 in ClinVar and COSMIC databases using callability analysis. 6,059 (87.1%) variants were identified automatically by the software; 829 (12.0%) required visual verification. The remaining 65 (0.9%) variants were uncallable, and would require 15 Sanger reactions to be resolved. Thus, the sensitivity of the NGS-panel was 99.1%. In conclusion, NGS performed with a commercial kit is highly efficient for detection of germline and somatic mutations in BRCA genes using routine FFPE tissue.

A rare case of extrauterine adenosarcoma arising in endometriosis of the rectovaginal septum.

OBJECTIVE: To present a rare case of endometrial stromal sarcoma arising in endometriosis of the rectovaginal septum. DESIGN: Case report. SETTING: Academic tertiary referral center for endometriosis treatment. PATIENT(S): A 50-year-old woman with a history of endometriosis presented with catamenial rectal pain and deep dyspareunia. Imaging findings suggested new endometriotic lesions in the rectovaginal space. INTERVENTION(S): Total hysterectomy, salpingo-oophorectomy, and excision of the lesion in the rectovaginal septum were performed. Although extemporary pathology confirmed endometriosis, the final histologic diagnosis was extrauterine adenosarcoma in the rectovaginal septum. Two years later, recurrence of the malignancy occurred and was treated by resecting the new perirectal mass. Subsequent radiotherapy and chemotherapy were administered. MAIN OUTCOME MEASURE(S): Imaging findings at follow-up evaluation. RESULT(S): The patient was in good health for 2 years after the initial surgery, when she developed a new lesion at the site of the previous resection. The histologic appearance of the lesion was consistent with recurrence of the tumor. After postoperative therapy, the patient is now without evidence of disease. CONCLUSION(S): Malignant transformation of endometriosis should be considered in the differential diagnosis of a new pelvic lesion in a patient with a history of endometriosis.

Benign breast lesions at risk of developing cancer--a challenging problem in breast cancer screening programs: five years' experience of the Breast Cancer Screening Program in Verona (1999-2004).

BACKGROUND: Cytology and core-needle biopsies are not always sufficient to exclude malignancy in benign breast lesions (BBL) that are at risk of developing cancer, and open biopsy often is mandatory. In screening programs, open biopsies performed for lesions that are at risk of developing malignancy are considered benign. The authors of this report evaluated the impact of the screen-detected BBL at risk of developing cancer that were counted in the quota of benign breast open biopsies in the Breast Cancer Screening Program of Verona. METHODS: Benign open biopsies were subdivided into 4 groups according to their risk of developing cancer: Histo1, normal histology; Histo2, 'pure' BBL (fibroadenoma, fibrocystic disease, mastitis, adenosis); Histo3, BBL with a low risk of developing cancer (radial scar, papilloma, papillomatosis, phyllodes tumor, mucocele-like lesion); and Histo4, BBL with a high risk of developing cancer (atypical columnar cell hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia). RESULTS: Of 510 open biopsies, 83 biopsies were benign, and the ratio of benign to malignant biopsies was 1:5. Histo1 was observed in 4.8% of all benign open biopsies, Histo2 was observed in 37.4%, Histo3 was observed in 31.3%, and Histo4 was observed 26.5%. CONCLUSIONS: BBL at risk of developing cancer may be numerous in screening programs. It is inappropriate to include BBL at risk of developing cancer in the overall benign open biopsy rate. The authors propose separating pure BBL from lesions at higher risk of developing cancer. To date, there is no evidence to support the premise that detecting high-risk proliferative lesions leads to benefits in terms of reduced mortality; however, these lesions need to be counted separately for future evaluations.

Cancer size, histotype, and cellular grade may limit the success of fine-needle aspiration cytology for screen-detected breast carcinoma.

BACKGROUND: Fine-needle aspiration cytology (FNAC) was adopted as the first-line method to assess breast lesions in the Verona Breast Cancer Screening Program. The radiological and pathological factors relating to the success of FNAC in breast cancer series were evaluated. METHODS: Between July 1999 and June 2004, 418 breast cancers were submitted to FNAC in the Verona Breast Cancer Screening Program. The results of FNAC diagnoses were compared with final histology. The FNAC sensitivity rate, underestimation of malignancy rate, and inadequacy rate were correlated with histotype, size, grading, and radiologic imaging. RESULTS: Of the 418 cancers, 95 were in situ, and 323 were invasive. The sensitivity rate was higher in invasive cancers (P < .001), and the underestimation of malignancy rate was greater in in situ cancers (P = .002). Lobular type cancers had a lower sensitivity rate in invasive and in situ cancers. The sensitivity rate was 100% in medullary, mucinous, and papillary cancers, and no case had inadequate sampling. The underestimation of malignancy rate was higher in tubular carcinoma (18.2%); lobular carcinoma showed a higher inadequacy rate (10.4%). The sensitivity rate was lower and the underestimation of malignancy rate was higher in low-grade carcinomas and in lesions <1 cm (P < .001). The performance of FNAC was not significantly influenced by mammographic imaging of lesions. CONCLUSIONS: Low-grade cancer histotype, cancer size <1 cm, and lobular and tubular histotypes limit the possibility of obtaining positive results by FNAC. Operator experience and multidisciplinary consultation may help in overcoming these limitations. Pathologists must be aware of the limits of FNAC; results must be critically evaluated in light of the triple assessment.

Clinicopathological evaluation of 59 cases of fetal death.

OBJECTIVE: The purpose of this study has been assessing the determinants of stillbirth among the newborns of the Verona University Obstetrics Department. MATERIALS AND METHODS: A total of 59 stillbirth cases, observed between January 2000 and June 2006, were retrospectively studied. WHO definition for stillbirth was adopted as the inclusion criterion. Clinical files, feto-maternal laboratory data, feto-placental pathology findings as well as delivery mode and circumstances were all systematically reviewed. RESULTS: The 59 observed cases correspond to an incidence of 9.8 stillbirths/year, which, considering the institutional delivery rate, correspond to 5.4 cases per 1000 births. Frequent relevant conditions associated with stillbirth were intrauterine growth restriction (15.2%), congenital fetal anomalies (13.5%), various maternal diseases (21.0%); no cause of fetal demise could be found in 10/59 (17.0%) cases, which were classified as unexplained. Most deliveries were successfully induced with prostaglandins except 11 cases (19.0%) which required a C-section due to severe maternal conditions associated with the fetal loss. CONCLUSION: Thorough investigation of each individual stillbirth case, by means of an integrated study protocol, along with the Pathologist's close collaboration, allows identification of a likely cause in the majority of cases. Better knowledge of unexpected fetal loss is the premise for better parental counselling and for prevention of recurrences.