- Inflammatory myofibroblastic tumor in the female genital tract can mimic other more common benign and malignant tumors like leiomyoma, leiomyosarcoma, and endometrial stromal sarcoma. Familiarity with clinical and histologic features and use of ALK immunostaining can be critical for correct diagnosis.

Early detection of premalignant and malignant glandular lesions of the uterine cervix and their distinction from benign mimics is crucial but sometimes difficult. In this study, we investigated utility of expression of p16, CEA, Ki67, p53 and ER/PR in evaluating the benign, premalignant, and malignant glandular lesions of the uterine cervix. A total of 35 cervical cone or LEEP cases were collected including 14 adenocarcinoma in situ (AIS), 7 endocervical glandular dysplasia (EGD), and 14 benign mimics (BM). A histological score for each case according to the criteria proposed by Silverberg group was assigned independently by 4 pathologists. Formalin-fixed, paraffin-embedded sections were immunostained with p16, CEA, p53, Ki67, and ER/PR. Immunoreactivity was scored based on intensity (0 = none, 1 = mild, 2 = moderate, 3 = marked) and percentage of cells staining (0 = <1%,1 = 2-10%, 2 = 11-40%, 3 = >40%). A comparison of histological scores and immunoscores in 3 diagnostic categories was analysed. The histological scores assigned independently by 4 pathologists were all equal or above 6 for AIS, between 3 and 5 for EGD, and equal or below 3 for BM. There was increased expression of p16 and CEA in EGD compared with BM (P < 0.05), with further increase in expression of these markers in AIS compared with EGD (P < 0.05). Ki67 expression was significantly increased in AIS compared to EGD (P < 0.05) as well as compared to BM (P < 0.05). Ki67 expression was only slightly increased in EGD as compared to BM. There was a loss of ER/PR in cervical AIS, but not in EGD. Our results indicate that the Silverberg scoring system is a useful tool in differential diagnosis of cervical glandular lesions for increased diagnostic accuracy and interobserver agreement. Most cervical glandular lesions can be differentiated by using a combination of histological scores with a panel of immunomarkers.

Objectives To review the significance of MDM2 and cyclin D1 expression and loss of p16 expression in malignant and borderline Brenner tumors (BTs) of the ovary. Methods We describe 2 new cases of ovarian BT, 1 malignant and 1 borderline. We studied MDM2, p16, and cyclin D1 expression by immunohistochemistry in the benign, borderline, and malignant components of these 2 cases and in 5 additional cases of benign BT. We also reviewed and summarized the literature on the clinical, immunohistochemical and molecular characteristics of borderline and malignant BTs (BdBTs and MBTs). Results Nuclear expression of MDM2 was seen only in the MBT. Loss of p16 expression was seen in both BdBT and MBT. Cyclin D1 expression was in proportion to the degree of malignancy. Amplification of MDM2, loss of CDKN2A (p16-encoding gene), and amplification of CCND1 (cyclin D1–encoding gene) were confirmed by commercial next-generation sequencing in the case of MBT. Conclusions We are the first to report immunohistochemical expression of MDM2 in an MBT. Amplification of MDM2 and loss of p16 expression may have a role in malignant transformation of BT.

Aims Clear cell carcinoma of ovary (CCC) is considered a high‐grade malignancy by default and the role of histological grading for assessing clinical outcome is not established. We aimed to evaluate histopathological features associated with clinical outcome in CCC patients. Methods and results Seventy‐six cases of CCC with available clinical follow‐up information were studied. Histopathological features, including tumour size, architectural patterns, nuclear atypia, mitotic activity, intratumoral and peritumoral inflammation, presence of endometriosis, peritumoral and intratumoral budding, were evaluated. Multivariate analysis was performed with logistic regression and Kaplan–Meier survival curves with the log‐rank test were used for survival analysis. Forty cases (53%) presented at stage I. Complete response to treatment was achieved in 65%, while 35% of patients had tumour recurrence or progression of disease despite treatment. At last follow‐up, 13% had died of disease, 20% were alive with disease and 67% had no evidence of disease. Higher stage (P = 0.0016) and presence of intratumoral budding (P = 0.0454) were independently associated with recurrence/disease progression. Advanced stage (P = 0.0011), presence of lymph node involvement (P = 0.0003), intratumoral budding (P = 0.0023) and peritumoral budding (P = 0.0334) were significantly associated with shorter survival. Intratumoral budding was significantly associated with recurrent/progressive disease (P = 0.0195) and also shorter survival (P = 0.0277) within the cohort of low‐stage (I/II) patients as well. Conclusion We have shown that besides the classic prognostic factors of stage and lymph node status, the presence of tumour budding is associated with poorer outcome in patients with CCC. Specifically, evaluation of intratumoral budding may help to more clearly predict prognosis in patients with early‐stage disease.