Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.

Neuropathological hallmarks of antenatal mitochondrial diseases with a corpus callosum defect.

Corpus callosum defects are frequent congenital cerebral disorders caused by mutations in more than 300 genes. These include genes implicated in corpus callosum development or function, as well as genes essential for mitochondrial physiology. However, in utero corpus callosum anomalies rarely raise a suspicion of mitochondrial disease and are characterized by a very large clinical heterogeneity. Here, we report a detailed pathological and neuro-histopathological investigation of nine foetuses from four unrelated families with prenatal onset of corpus callosum anomalies, sometimes associated with other cerebral or extra-cerebral defects. Next generation sequencing allowed the identification of novel pathogenic variants in three different nuclear genes previously reported in mitochondrial diseases: TIMMDC1, encoding a Complex I assembly factor never involved before in corpus callosum defect; MRPS22, a protein of the small mitoribosomal subunit; and EARS2, the mitochondrial tRNA-glutamyl synthetase. The present report describes the antenatal histopathological findings in mitochondrial diseases and expands the genetic spectrum of antenatal corpus callosum anomalies establishing OXPHOS function as an important factor for corpus callosum biogenesis. We propose that, when observed, antenatal corpus callosum anomalies should raise suspicion of mitochondrial disease and prenatal genetic counselling should be considered.

Successful laparoscopic surgical removal of a caesarean scar pregnancy (CSP) using temporary uterine artery ligation.

STUDY OBJECTIVE: To demonstrate a laparoscopic technique to remove a scar pregnancy. DESIGN: Stepwise demonstration of the surgical technique. SETTING: Santa Croce and Carle Hospital, Cuneo. INTERVENTION: Patient B.B. is a woman referred to our center for a suspected cesarean scar pregnancy (CSP) at 9 weeks gestation. CSP occurs approximately in 6% of all ectopic pregnancies. The estimated incidence is reported to be 1:1800 to 1:2500 in cesarean deliveries. Depending on its location, CSP can be categorized as either type 1, if the growth is in the uterine cavity, or type 2, if it expands toward the bladder and the abdominal cavity. If inadequately managed, it can lead to severe complications; most of them are hemorrhagic and can threaten the woman's life. There are several therapeutic approaches: local excision seems to be the most effective choice in type 2 CSP. In expert hands, the laparoscopic approach is perhaps the best surgical choice as tissue dissection, electrosurgical hemostasis, and vascular control can be effectively managed with minimal invasive access. Because severe intraoperative bleeding can occur, retroperitoneal vascular control is mandatory in this surgery. In type 1 CSP curettage, aspiration or hysteroscopic approach can be considered if the CSP is of small dimensions. A hysteroscopic approach can also be helpful in type 2 CSP during the laparoscopic removal, as intrauterine guidance. A potassium chloride local injection can be considered in a preoperative stage in the presence of a fetal heart rate. The systemic administration of methotrexate is usually ineffective as single agent, but it can be useful if administered as adjuvant therapy. Uterine artery embolization can be useful in an emergency setting to manage severe bleeding, but it can lead to complications in subsequent pregnancies and, more rarely, to premature ovarian failure. Considering poor bleeding at presentation, feasible dimensions, and the woman's desire for future pregnancy, ultrasound-guided aspiration and curettage was attempted. Because endouterine removal was incomplete, methotrexate injection was proposed as adjuvant therapy, but the administration was postponed as the patient tested positive for coronavirus disease 2019. A month later, beta-human chorionic gonadotropin level dropped from over 16 000 to 271 mU/mL, so an ultrasound and biochemical follow-up was performed. A month later, despite a low beta-human chorionic gonadotropin value, an increase in dimensions was observed at ultrasound, so surgical laparoscopic removal was offered. In this video article, laparoscopic removal of scar pregnancy is discussed in the following surgical steps: (1) Temporary closure of uterine arteries at the origin, using removable clips. (2) Retroperitoneal dissection to safely manage the scar pregnancy. (3) Dissection of the myometrial-pregnancy interface. (4) Double layer suture on the anterior uterine wall. CONCLUSION: Laparoscopic surgical management is a very effective surgical approach to remove CSP. Knowledge of retroperitoneal dissection and vascular control is necessary to carry out this surgical intervention safely and effectively.

Use of Remifentanil Associated with Lidocaine for Feticides in Late Terminations of Pregnancy: A Randomized Clinical Trial.

INTRODUCTION: In France, performance of a termination of pregnancy is legally possible without any gestational age limit. After 22 weeks of gestation, a feticide is ethically performed using usually sufentanil and lidocaine. The aim of this study was to compare the use of remifentanil, a fast-acting morphine-derivating product, instead of sufentanil. METHODS: This 2-center randomized, controlled, single-blinded phase-III treatment trial had 2 parallel arms: an experimental group using remifentanil with lidocaine versus a control group receiving sufentanil associated with lidocaine. This trial took place over a 40-month period. The primary outcome was time to fetal asystole after lidocaine injection. The secondary outcome measures were the procedure's success rate, the rate of serious maternal side effects, and the presence of cellular or tissue modifications. RESULTS: The study included 66 women, randomized into 2 groups of similar size and characteristics. Time to fetal asystole did not differ significantly between the groups, with a delay of 4 min (Q1-Q3, 2-11) in the sufentanil group and 4 min (Q1-Q3, 1-10) in the remifentanil group (p = 0.84). Similarly, the success rate of the procedure did not differ significantly. Fetal asystole was procured in <2 min and persisted >1 min for 16 (25.8%) women in our total population: 7 (22.5%) in the sufentanil group and 9 (29.0%) in the remifentanil group, p = 0.77. No severe maternal side effects were observed. Among the 49 fetopathological examinations performed, the few tissue and cell modifications observed did not cause any interpretation difficulties in either group. DISCUSSION/CONCLUSION: Use of remifentanil instead of sufentanil for feticide procedure did not improve time to fetal asystole. No harmful effect was observed for either maternal tolerance or interpretation of the histologic slides.

Mosaic complete tetrasomy 21 in a fetus with complete atrioventricular septal defect and minor morphological variations.

BACKGROUND: Tetrasomy 21 is a very rare aneuploidy which could clinically resemble a Down syndrome. It was most often described in its partial form than complete. We report the prenatal, pathological and genetic characteristics of a fetus with mosaic complete tetrasomy 21. This is the second well-documented description of a complete tetrasomy 21 in the literature. METHODS: Prenatal and fetal pathological examinations, cytogenetic and molecular analyses were performed to characterize fetal features with tetrasomy 21. RESULTS: Prenatal ultrasound examination revealed an isolated complete atrioventricular septal defect with normal karyotype on amniotic fluid. After termination of pregnancy, clinical examination of the fetus evoked trisomy 21 or Down syndrome. Chromosomal microarray analysis and FISH on lung tissue showed a mosaicism with four copies of chromosome 21 (tetrasomy 21). CONCLUSION: Our observation and the review of the literature reported the possibility of very weak mosaicism and disease-causing confined tissue-specific mosaicism in fetus or alive patients with chromosome 21 aneuploidy, mainly Down syndrome. In case of clinical diagnosis suggestive of Down syndrome, attention must be paid to the risk of false-negative test due to chromosomal mosaicism (very weak percentage, different tissue distribution). To overcome this risk, it is necessary to privilege the diagnostic techniques without culture step and to increase the number of cells and tissues analyzed, if possible. This study highlights the limits of microarray as the unique diagnostic approach in case of weak mosaic and French cytogenetics guidelines recommend to check anomalies seen in microarray by another technique on the same tissue.

Complex Suicide by Self-stabbing and Drowning: A Case Report and a Review of Literature.

Sharp force injuries and drowning are methods exceptionally combined in complex suicides. We report a challenging case of complex suicide by self-stabbing and drowning that illustrates the difficulty in discriminating between homicide and suicide in such circumstances of death. The corpse of a young man was found submerged in a river, stabbed nine times with two wounds that had penetrated the thorax and had caused lung injuries and a hemopneumothorax. The postmortem and histological examinations were consistent with a death caused by drowning, but the manner of death still remained undetermined. Police investigation finally concluded to a suicide, although no suicide note had been left and the victim had no underlying diagnosed mental disorder. The parameters that may help distinguish suicide from homicide at the autopsy should be interpreted in light of a thorough forensic investigation to determine the exact manner of death in such a case.

Mosaic parental germline mutations causing recurrent forms of malformations of cortical development.

To unravel missing genetic causes underlying monogenic disorders with recurrence in sibling, we explored the hypothesis of parental germline mosaic mutations in familial forms of malformation of cortical development (MCD). Interestingly, four families with parental germline variants, out of 18, were identified by whole-exome sequencing (WES), including a variant in a new candidate gene, syntaxin 7. In view of this high frequency, revision of diagnostic strategies and reoccurrence risk should be considered not only for the recurrent forms, but also for the sporadic cases of MCD.

Defective placental adhesion in voluntary termination of second-trimester pregnancy and risk of recurrence in subsequent pregnancies.

OBJECTIVE: To evaluate the prevalence of defective placental adhesion (DPA) in voluntary termination of second-trimester pregnancy and the risk of DPA recurrence in subsequent pregnancies. METHODS: We retrospectively reviewed the records of all patients who underwent voluntary second-trimester pregnancy termination in the period between January 2000 and December 2009. In all cases, the fetus and the placenta were submitted to pathological examination accordingly to our clinical protocol. RESULTS: Four hundred twenty-seven cases of voluntary termination of second-trimester pregnancy were included in the study. Ten histologically confirmed cases of placenta accreta were observed (2.3%). Two patients with histological diagnosis of placenta accreta were lost at follow-up. Among the eight remaining patients, six had further pregnancies. Overall, nine pregnancies were recorded, and placenta accreta recurred in one patient. CONCLUSIONS: This study shows that DPA occurs in 2.3% of second-trimester voluntary termination of pregnancy; these patients should have an accurate ultrasound examination of the placenta in subsequent pregnancies.

Decidual vascular patterns in first-trimester abortions.

In many cases of early spontaneous abortion (ESA), no reasonable etiology can be documented. However, some of these cases show abnormal decidual vessels that could be overlooked when examined on hematoxylin and eosin (H&E) slides alone. Diagnostic accuracy could be improved by the use of a limited histochemical (HC) and immunohistochemical (IHC) panel. We reviewed 1,095 ESAs, selecting 176 cases with abnormal decidual vessels and subclassifying them into three groups on the basis of decidual vascular pattern. Various HC and IHC stainings were performed in order to assess their use in improving diagnostic sensitivity. Histological findings on H&E were recorded and compared to the results obtained with HC and IHC. A variable role in the improvement of morphologic details was demonstrated for all three tested HC stainings (periodic acid-Schiff, Masson's trichrome, Weigert's stain for fibrin) and for two of the IHC markers (smooth muscle actin, human placental lactogen). In many cases of ESA, only compatibility diagnoses can be formulated. However, using a limited panel of HC and IHC stainings, some significant findings can be more reliably reported, allowing the pathologist to acquire confidence in his routine diagnostic work.

Breast cancer with synchronous massive metastasis in the uterine cervix: a case report and review of the literature.

INTRODUCTION: Metastatic breast cancer is rare in the female genital tract, and when present it more commonly tends to involve ovary or endometrium; uterine cervix is only occasionally involved. This condition poses differential diagnostic problems in the settings of clinical and pathological investigations. CASE PRESENTATION: An asymptomatic 78-year-old woman came to our attention in the context of routine gynecological surveillance; clinical examination disclosed enlarged uterine body and cervix. Our patient then underwent computed tomography and magnetic resonance imaging that outlined the possibility of cervical cancer with parametrial involvement. Moreover, a suspect mass was found on the mammogram in the left breast. Breast surgical excision was performed, which revealed invasive breast carcinoma, while synchronous cervical biopsy discovered distant metastasis in the uterine cervix. On histological examination, both lesions showed non-cohesive architectural pattern consistent with lobular morphology; anyway, to rule out primary poorly differentiated cervical cancer, appropriate immunohistochemical panel was performed, which confirmed the mammary derivation of the tumor. Due to disseminate disease, the patient underwent multisystemic medical treatment including radiotherapy, chemotherapy and hormone therapy, and she is still alive at 30-month follow-up. DISCUSSION: Genital tract metastases in patients with known breast carcinoma can present with abnormal vaginal bleeding, but they often are asymptomatic. Therefore, only strict gynecological surveillance of these patients can permit early detection of these secondary lesions. Aggressive treatment of isolated cervical metastasis should be performed when feasible; otherwise, systemic chemotherapy with taxane could be sufficient in increasing survival. It should be emphasized that, in most cases, only accurate immunohistochemical investigation, particularly if performed on the primary lesion as well, can solve differential diagnostic problems and allow the clinician to establish appropriate treatment.

Squamous cell carcinoma of the breast: a case report.

INTRODUCTION: Pure primary squamous cell carcinoma of the breast is uncommon and it's debated the correct management of this disease. CASE PRESENTATION: A 54-years-old woman presented with signs and symptoms of mastitis of left breast. A palpable well circumscribed and firm mass, measuring about 40 mm, was present in the left lower lateral quadrant. She underwent antibiotic therapy without benefit. She performed an ultrasound and mammographic scan of the left breast. Fine needle aspiration cytology revealed an infiltrative poorly differentiated squamous cell carcinoma. Total body CT scan and bone scan excluded distant metastasis. Subsequently wide local excision of the left breast with ipsilateral axillary lymph nodes dissection was performed. The pathological examination revealed an infiltrative poorly differentiated squamous cell carcinoma of the breast. Adjuvant chemotherapy cisplatin and 5-fluorouracil based was administered. Patient refused locoregional radiotherapy. Twenty-eight months after surgery the patient was disease free. CONCLUSIONS: Pure primary squamous cell carcinoma of the breast is a rare and aggressive disease often treatment-refractory. An optimal systemic treatment is needed to improve patient's outcome.

Solitary nodule of the penis as unique manifestation of Rosai-Dorfman disease.

We report the case of a 53-year-old man with a solitary nodule located on the inner surface of the prepuce. The lesion was removed and the final diagnosis was Rosai-Dorfman disease (RDD/sinus histiocytosis with massive lymphadenopathy). This report, being the first case of RDD presenting as a single nodule of the penis, broadens the spectrum of the cutaneous expression of RDD.

Small bowel metastasis from primary neuroendocrine small cell lung carcinoma.

Small bowel metastases from a primary lung carcinoma are rare. We report a case of a 76-year-old male with a primary neuroendocrine small cell carcinoma of the lung, treated by chemotherapy, who developed fever and bowel symptoms (subocclusion and pain). On CT examination, he was found to have a tumour in the small bowel. The patient then underwent abdominal surgery. At operation we found small bowel occlusion by neoplasia and we therefore resected 15 cm of ileum with a side-to-side anastomosis. Early recognition of this rare condition is important due to the fact that complicated intestinal metastases from lung carcinoma can lead to high mortality rates and poor short-term outcomes. With advances in chemotherapy and palliative care, patients with metastatic lung carcinoma can sometimes survive more than a year with a reasonable quality of life.