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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., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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., ((c) 2009 American Cancer Society.)

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.

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.

Cell proliferation and death account for the refinement of the cell number during corticogenesis. These processes have been investigated in the human developing telencephalon (12th-24th week of gestation) and cerebellum (16th-24th week). Only foetal brains, which had normal neuropathological examination, were utilised. Cell proliferation was analysed by classical histology and PCNA immunohistochemistry; cell death was investigated by the TUNEL method, which makes evident the different stages of apoptosis. High figures of mitotic nuclei were seen in the ventricular zone at the 12th-15th week of gestation, before sharply declining. The decrease of the proliferating cells occurs synchronously in both frontal and occipital germinal zones. Conversely, a slow increase of the number of the mitotic cells was observed in the more dorsal regions, probably due to the presence of proliferating glial elements. The amount of apoptotic nuclei was always remarkably low in the transient compartments of the wall of the telencephalon. The moderate number of apoptotic cells suggests that cellular mechanisms other than apoptosis are involved in the dissolution of the ventricular zone. Neither proliferating nor apoptotic cells were seen in the cortical plate. The topography of cell proliferation and death in the developing cerebellum did not account for a mutual relationship between the two events. The prolonged duration of the cell-cycle in the human developing CNS may explain its increased vulnerability to various DNA-damaging conditions, which can lead to either destructive lesions or malformations., (Copyright 1999 Wiley-Liss, Inc.)

Evidence has recently been provided to support a role for genomic imprinting in the regulation of embryonic implantation and development and placental growth, as well as in the pathogenesis of proliferative trophoblastic diseases. The cyclin-dependent kinase inhibitor p57KIP2 has recently been recognized as a maternally imprinted gene. We investigated p57KIP2 expression in first-trimester normal placentas from interrupted pregnancy, spontaneous abortions, and different types of proliferative trophoblastic diseases using single- and double-marker immunohistochemical techniques. In normal placenta, nuclear p57KIP2 expression was observed at high frequency (up to 100%) in extravillous trophoblast, cytotrophoblast, and implantation-site interstitial trophoblast, but was absent in syncytiotrophoblast. p57KIP2 was also expressed in the stromal cells of maternal decidua, which was one of the few adult tissues retaining p57KIP2 expression (most other adult tissues investigated were negative). p57KIP2 expression was either absent or low in all cases of diploid/tetraploid complete moles (20 cases) and in three cases of gestational choriocarcinoma. On the other hand, all spontaneous abortions (12 cases) and triploid partial moles (19 cases) showed p57KIP2 levels comparable to those observed in normal placenta. These findings are in line with the hypothesis that deregulation of genomic imprinting, particularly the loss of cell-cycle inhibitors such as p57KIP2, is involved in the abnormal development of androgenetic trophoblastic proliferations. In addition, this simple immunohistochemical analysis could provide a useful diagnostic marker in difficult cases.

Evidence has been recently provided on the relevant role of genomic imprinting in the regulation of implantation, embryonic development, placental growth, and also in development of proliferative trophoblastic diseases and human carcinogenesis. Among the various imprinted genes the cyclin-dependent-kinase inhibitor p57KIP2 (maternally imprinted) is particularly interesting since it can function as a tumor suppressor gene. In this review we describe the different roles of genomic imprinting in human diseases, with particular emphasis on the role of p57KIP2 in molar pregnancy and in tumorigenesis.

A 34-year-old man and a 71-year-old woman underwent radical removal of mediastinally sited chondrosarcoma, presumably originating in the periosteum of the vertebral body. The man (with mesenchymal chondrosarcoma) died of remote metastasis 6 years postoperatively. The woman (poorly differentiated chondrosarcoma, grade 2-3) is still alive 2 years after the operation.

A 44-year-old male affected by mesenchymoma of the mediastinum was treated surgically. The neoplasm, localized in the postero-inferior mediastinum with prevalent development to the left, was found to consist of adipose, leiomuscular and myxoid tissue. The patient was asymptomatic. Complete removal of the neoplasm proved possible, and one year after surgery no signs of recurrence were present. Few cases of mediastinal mesenchymoma have been reported.

A case of brown-tumor of the vomer in a 21-year-old woman is described. The term giant cell lesions encompasses a variety of conditions. Three distinct entities are found in the facial area i.e. giant cell reparative granuloma, true giant cell tumor and brown-tumor. After having described the clinical, radiological and histopathological characteristics of the lesion, emphasis is placed on the importance of clinical, anamnestic, laboratory, radiological and histological findings in accurately differentiating the various types of giant cell lesions of the facial skeleton.

In this study the authors investigated the serum levels of the released soluble form of interleukin-2 receptor (sIL-2R) in patients with non-Hodgkin's lymphomas (NHLs). Data were evaluated in relationship to the morphologic and immunophenotypic heterogeneity of NHL at diagnosis and in progressive advanced diseases. Increased sIL-2R levels were found in most cases, when compared with levels observed in healthy controls. No obvious statistical correlation has been observed between sIL-2R values in different NHL subtypes as defined by current classifications. On the other hand, major significance was related to the extent of the disease. Very high values, comparable to those observed in hairy cell leukemia, were observed in a number of large cell NHLs complicating low-grade B-cell lymphoproliferations and in a single case of T-cell Kil+ NHL. The authors' findings suggest that the detection of sIL-2R in NHL may represent a good marker in improving risk assignment of single cases and/or for monitoring remissions and exacerbations during the treatment of cases with very high levels at diagnosis. Nevertheless, the observed overlap between groups on an individual case basis can render the clinical application of this marker problematic.