Carla Merisio

Uterine smooth muscle tumor of uncertain malignant potential: a three-case report

Based on the degree of cytologic atypia, mitotic activity, and other features, uterine smooth muscle tumors have historically been grouped into two classes: benign leiomyomas and malignant leiomyosarcomas. However, this separation holds true more in principle than in practice because the tumors biological potential may not always be determined with certainty, complicating diagnosis, and therapy. We report three cases of patients with uterine smooth muscle tumors of uncertain malignant potential. Surgery was radical in two and conservative in one. During the follow-up, one patient developed diffuse lung metastases. The two other patients have not shown any signs of relapse to date. Uterine smooth muscle tumors of uncertain malignant potential may have an unpredictable clinical course and may metastasize to seemingly low-grade neoplasms in distant sites even after several years and even in the absence of important negative prognostic predictors, such as coagulative tumor cell necrosis. At present, no final consensus has been reached on the choice of the best strategy for surgery and adjuvant therapy

Preoperative Transvaginal Ultrasonography and Intraoperative Gross Examination for Assessing Myometrial Invasion by Endometrial Cancer

Endometrial cancer is the most common gynecologic malignancy. The cornerstone of treatment remains surgery according to International Federation of Gynecology and Obstetrics staging. The aim of this study was to evaluate the concordance between myometrial infiltration detected by ultrasonography and gross examination with respect to definitive histologic examination and to select a population in which lymphadenectomy could be excluded. We also evaluated the concordance for the degree of tumor differentiation between diagnostic biopsy and final histologic results.

Role of human papillomavirus in the development of epithelial ovarian neoplasms in Italian women

Aim:  In this article, for the first time, we investigate the presence of human papillomavirus (HPV) DNA in ovarian epithelial neoplasms from a group of 71 Italian women. The follow ups of the patients with or without HPV DNA were also considered to evaluate whether HPV DNA in these tumors could be an indicator of prognosis.

Vulvar acantholytic squamous carcinoma: a case report with immunohistochemical and molecular study.

Acantholytic carcinoma is a subtype of squamous carcinoma, characterized by tubular and alveolar formations as a consequence of the acantholysis. We report a case of vulvar squamous acantholytic carcinoma (VSAC) in a 69-year-old woman, who was admitted to our institution for vulvar pruritus and the presence of a large, bilateral, exophytic, and ulcerated lesion, measuring 7×8 cm. The patient had never received vulvar or pelvic radiation therapy. Pathological examination with an immunohistochemical study showed features of VSAC and high p16INK4a protein expression. Molecular study by polymerase chain reaction amplification of DNA tumor revealed a weakly positive signal for human papillomavirus. In conclusion, our case, which is the first case of VSAC with polymerase chain reaction analysis and immunohistochemical expression of p16INK4a protein, suggested that this neoplasm could be related to human papillomavirus infection.

Randomised prospective study of abdominal wall closure in patients with gynaecological cancer.

Background:  Median laparotomy is the most common approach to the abdominopelvic cavity in patients with gynaecological tumours.

Human papilloma virus (HPV) status, p16INK4a, and p53 overexpression in epithelial malignant and borderline ovarian neoplasms.

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer.

Uterine tumors resembling ovarian sex cord tumors: a case report of conservative management in young women.

Abstract Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are distinguished into two separate groups: endometrial stromal tumors with sex cord-like elements (Group I), which have an unfavorable prognosis; and UTROSCT proper (group II), with more than 40% sex cord-like differentiation and less endometrial component, which are biologically less aggressive than the tumors of the other group. We report the case of a young woman with UTROSCT treated by minimally invasive hysteroscopic surgery. This is one of the few cases reported in the literature that have been managed conservatively.

Two cases of low-grade endometriod carcinoma associated with undifferentiated carcinoma of the uterus (dedifferentiated carcinoma): a molecular study.

Dedifferentiated carcinoma (DC) is an uterine neoplasm containing both low-grade endometrioid carcinoma (LGEC) and undifferentiated carcinoma (UC). DC is an aggressive tumour even when the UC component represents only 20% of the entire neoplasm. In this paper, two cases DCs at different stages of development, in 61- and 83-year-old women respectively were reported. In addition, in these uterine malignancies microsatellite instability (MSI) and loss of heterozygosity (LOH) were investigated in order to explain its aggressive behavior, in both components. Case #1 presented metastases at diagnosis, while case #2 was at a lower stage. LGEC component was invasive in case #1 and intramucous in case #2. In both cases, UC components were characterized by a high degree of instability, in accordance of its aggressive behaviour and its architectural heterogeneity. Further studies with more numerous cases are mandatory to confirm these data.

Clinicopathologic implications of the epidermal growth factor receptor, cyclooxygenase 2 expression, and human papillomavirus status in squamous cell carcinoma of the uterine cervix in the elderly.

Objectives: To find information on invasive squamous cervical carcinoma in the elderly, 110 invasive squamous cervical carcinomas obtained from 2 groups of patients (aged <60 and >60 years) were analyzed for human papillomavirus (HPV) status by polymerase chain reaction study, for immunohistochemical epidermal growth factor receptor (EGFR), cyclooxygenase 2 (Cox-2) expression, and clinicopathologic features. Methods: The HPV status and the expression of Cox-2 and EGFR in the younger and older women were compared and correlated with the grading, staging neoplasm, and lymph nodal status, using Fisher test and Spearman nonparametric correlation test. Overall survival curves were drawn using Kaplan-Meier estimates and were compared using log-rank tests in the whole series of 110 patients. Multinomial logistic regression was also used. Results and Conclusions: The number of neoplasms with higher staging was significantly greater than those in the younger women (P = 0.04). The mortality was higher in the older group than in the younger patients (P = 0.006). In the elderly, the presence of HPV DNA in 65% of cases, and in the absence of sexual activity, could be due to reactivation of latent HPV infection, which might be due to an impairment of host immunologic response. The overexpression of Cox-2 in a number of cases was significantly higher in the older group than in the younger group (P = 0.032, Fisher exact test), but this immunoreactivity is not related to the staging, grading, EGFR expression, or to the presence of HPV. The simultaneous expression of Cox-2 and EGFR had a poor prognostic significance, showing lower survival rates than cases without this immunoreactivity (P = 0.002), on univariate analysis. On multivariate analysis, Cox-2 and EGFR immunopositivity did not reveal any correlation between these markers and prognosis probably because the number of cases considered was not particularly high.

Immunohistochemical Detection of Hematopoietic Cell–specific Protein-Tyrosine Phosphatase (Tyrosine Phosphatase SHP-1) in a Series of Endometrioid and Serous Endometrial Carcinoma

In this study, we evaluated the expression of SHP-1 (PTPN6) in endometrioid (Ec) and serous (Sc) subtypes of endometrial carcinoma by immunohistochemical analysis. In total, 114 patients with Ec carcinoma and 48 patients with Sc carcinoma were enrolled in this study. The correlation between the type of histology, the grade of tumor, the stage of development, and immunoreactivity to SHP-1 was evaluated. Kaplan-Meier and multivariate survival analyses, using a Cox regression model, were performed to establish whether this marker has prognostic value in these malignancies, on the basis of follow-up and stratification of the patients according to their SHP-1 immunoreactivity. A significantly higher SHP-1 expression was observed in the Ec group compared with the Sc group (P=0.0005, Fisher exact test). In the Ec group, SHP-1 immunoreactivity was correlated with grading, demonstrating that more differentiated lesions expressed SHP-1 more frequently than less differentiated neoplasms (G1 vs. G2, P=0.0243, statistically significant value, Fisher exact test; G1 vs. G3, P=0.0088, extremely significant value, Fisher exact test). Instead, in the Sc group, SHP-1 expression was not correlated with grading, as Sc is now defined as a high-grade carcinoma. SHP-1 expression did not change with neoplastic progression in Ec and Sc groups. From both univariate and multivariate analysis in the Ec group, expression of SHP-1 remained a positive prognostic factor (P=0.004, log-rank test) [HR=0.32 (0.11 to 0.94), P=0.039]. In contrast, in the Sc group, no correlation between SHP-1 expression and survival was noted (P=0.77, log-rank test). In this study, we observed that the absence of SHP-1 in immunohistochemical analysis might serve as a marker of poor prognosis for a subset of high-grade endometrial cancer.