Profiling of Tumour-Infiltrating Lymphocytes and Tumour-Associated Macrophages in Ovarian Epithelial Cancer-Relation to Tumour Characteristics and Impact on Prognosis.

Early evidence suggests a strong impact of tumour-infiltrating lymphocytes (TILs) on both the prognosis and clinical behaviour of ovarian cancer. Proven associations, however, have not yet translated to successful immunotherapies and further work in the field is urgently needed. We aimed to analyse the tumour microenvironment of a well-characterised cohort of ovarian cancer samples. Tumour markers were selected owing to their comparative underrepresentation in the current literature. Paraffin-embedded, formalin-fixed tumour tissue blocks of 138 patients representative of the population and including early stage disease were identified, stained for CD3, CD20, CD68 and CD163 and analysed for both the stromal and intertumoral components. Data were statistically analysed in relation to clinical details, histological subtype, borderline vs. malignant status, survival and management received. Mean stromal CD3, total CD3 count, mean stromal CD20 and total CD20 count all correlated negatively with survival. Malignant ovarian tumours consistently demonstrated significantly higher infiltration of all analysed immune cells than borderline tumours. Assessment of the stromal compartment produced a considerably higher proportion of significant results when compared to the intra-tumoural infiltrates. Customary assessment of solely intra-tumoural cells in advanced stage disease patients undergoing primary debulking surgery should be challenged, with recommendations for future scoring systems provided.

Assessment of endometrial carcinoma on biopsy as a predictor of final surgical pathology: Are we doing it right? A completed audit cycle and recommendations.

Background: Typing and grading of endometrial carcinomas (ECs) on small biopsy specimens is crucial to determine the need for full surgical staging. Histological subtype and grade are key factors available for risk stratification before surgery. However, this can be diagnostically challenging on small biopsy specimens, especially when morphologic features are subtle or overlapping. Aims: The aims of this audit were to assess concordance of endometrial carcinomas on biopsy specimens with hysterectomy specimens and to determine if the immunohistochemistry (IHC) panel being used in our practice was adequately subtyping ECs. Settings and Design: The audit was approved by the Clinical Effectiveness Team of the Royal College of Pathologists (UK) as meeting all the criteria and standards set out by the College. Materials and Methods: Biopsies from 67 cases of EC were compared for histological subtype and grade of endometrioid carcinoma with resection specimens. A re-audit was carried out on 59 cases after implementation of changes recommended by the initial audit. Results: Two of 35 (6%) tumours defined as G1 on biopsy were upgraded (to G2) on final pathology, as was one of 7 (14%) G2 tumours (to G3). One of these cases had solid areas just amounting to more than 6% on resection. In the second case, a comment was made that assessment had been difficult as the specimen was suboptimally fixed, but nuclei appeared atypical. Of seven G2 biopsies, one case was upgraded to grade 3 on final pathology based on proportion of solid areas. Our data show lower rates of discordance as compared to previous studies and on re-audit, the concordance between endometrioid and nonendometrioid serous carcinoma improved with the addition of immunohistochemistry (IHC) for Phosphatase and tensin homolog (PTEN) to biopsies. Conclusions: PTEN IHC can complement other stains and aid in the distinction of grade 3 endometrioid carcinoma from serous carcinoma on endometrial biopsies.

Immunohistochemical profiling of the tumour microenvironment in borderline and malignant ovarian tumours in young women.

Ovarian cancer is a major cause of cancer-related deaths in women. Our previous study highlighted the interaction between cancer cells and the host immune response in solid cancers. The present study aimed to analyse the proportion, density and distribution of T and B lymphocytes within the tumour and surrounding stroma, and their prognostic significance in young women with borderline and malignant ovarian surface epithelial tumours. Full clinicopathological and outcome data were collected for 57 women aged <50 years diagnosed between January 2010 and December 2015. Representative tumour sections were stained for CD3 (T cells) and CD20 (B cells) and tumour-infiltrating lymphocytes (TILs) were scored following the TILs Working Group Recommendations and described as stromal, intra-tumoural, lymphoid aggregates and touching lymphocytes. Data were statistically analysed and the association with clinicopathological variables was assessed. The median age was 41 years and the most common histological type was serous carcinoma (n=21). The risk of malignancy index was a significant predictor of ovarian cancer diagnosis (P<0.05). A total of 15 out of 34 patients with cancer died. There was significantly greater stromal infiltration of CD3 and CD20 TILs (P=0.01 and P=0.03, respectively) and higher intratumoral CD20 expression in ovarian epithelial cancers compared with borderline tumours. The highest CD3 stroma count and density were observed in serous carcinoma, which also exhibited the highest numbers of CD3 and CD20 aggregates. There was no statistically significant difference between touching lymphocytes and tumour histological subtype. There was no significant association between TIL expression and patient survival. The count, distribution and density of T and B lymphocytes in ovarian tumours varied depending on tumour type and invasiveness. Their topographic distribution within the tumour and surrounding stroma did not impact prognosis in young women with ovarian cancer. TIL analysis in an older age group of women with ovarian tumours is ongoing to determine its potential prognostic significance.

Extrapulmonary uterine lymphangioleiomyomatosis (LAM) and dysfunctional uterine bleeding: the first presentation of LAM in a tuberous sclerosis complex patient.

Lymphangioleiomyomatosis (LAM) is a rare disease that typically affects women of childbearing age. It most commonly affects the lungs (P-LAM) but can occasionally occur in extra-pulmonary sites (E-LAM). There is a strong association between LAM and the tuberous sclerosis complex (TSC). We report a case of a 42-year-old female TSC sufferer who presented with dysfunctional uterine bleeding. She was not known to have LAM. An endometrial biopsy revealed a spindled-cell lesion suspicious of leiomyosarcoma, which correlated with cross-sectional imaging. She underwent a hysterectomy that showed a bizarre (symplastic) leiomyomatous endometrial polyp with background uterine LAM. We discuss the clinical and pathological implications of this unusual case of E-LAM and the importance of clinicopathological correlation in TSC sufferers. The association of uterine LAM with TSC is important and LAM should be considered as a differential of dysfunctional uterine bleeding and a benign mimic to uterine leiomyosarcoma in patients with TSC.

Orbital presentation of a nasal midline destructive lesion in a young boy.

Midline Destructive Lesions (MDL) are well known to cause nasal problems. There is a long differential diagnosis of such lesions. However, in the pediatric population, the 2 main diseases to be aware of are Non-Hodgkin's T-cell lymphoma and granulomatosis with polyangiitis (previously known as Wegener's granulomatosis). The authors present the report of a 15-year-old boy who presented with epiphora, chemosis, and limitation of left abduction. CT scan of his orbits suggested a destructive lesion of the ethmoid sinuses. His laboratory investigations revealed a positive ANCA. The patient underwent endoscopic sinus surgery, and this was characteristic for granulomatosis with polyangiitis. He was treated with systemic steroids and then maintained on cyclophosphamide, which controlled his disease activity. This case highlights the need for ophthalmologists to have a high index of suspicion for MDL and concomitant orbital disease.