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High grade endometrioid endometrial cancer (HGEEC) is a heterogeneous group of tumors with unclear prognostic features. The aim of the present study is to evaluate the independent risk factors for recurrence and mortality and to describe the recurrence patterns of HGEEC. Ninety-six consecutive cases of HGEEC treated with primary surgery in a single Tertiary Center were retrospectively reviewed. Clinicopathological and treatment details were recorded, and all patients were closely followed up. Disease-free, overall and cancer-specific survival rates were 83.8%, 77.8% and 83.6%, respectively. Cervical stromal involvement was independently related to recurrence (HR = 25.67; 95%CI 2.95–223.30; p = 0.003) and cancer-related death (HR = 15.39; 95%CI 1.29–183.43; p = 0.031) after adjusting for other pathological and treatment variables. Recurrence rate was 16%, with 60% of these cases having lung metastases and only one case with single vaginal vault recurrence. 81.81% of the recurrences presented with symptoms and not a single recurrence was diagnosed in routine follow-up clinical examination. In conclusion, the recurrence pattern may suggest that patient-initiated follow-up (PIFU) could be considered a potential alternative to clinical-based follow-up for HGEEC survivors, especially for patients without cervical involvement and after two years from treatment. Additional caution is needed in patients with cervical stromal involvement.

Purpose:Using RNA sequencing, we recently developed the 52-gene–based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier.Experimental Design:We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n = 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs.Results:We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition–high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; P = 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; P < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors.Conclusions:The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.

Table S2. The QuPath classification results for the immunohistochemistry of CAPS in SOC tissue microarrays.

Purpose: Using RNA sequencing, we recently developed the 52-gene–based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier. Experimental Design: We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n = 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs. Results: We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition–high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; P = 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; P < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors. Conclusions: The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.

A patient in her 60s was referred to be investigated for an incidental large uterus with a history of renal cell carcinoma and melanoma. Uterine biopsy revealed features of perivascular epithelioid cell tumours (PEComas) and she underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Final histology confirmed PEComa with malignant features. Genomic studies did not reveal any deleterious germline variants; however, in view of her history, she is now under a 6-month follow-up with gynaecology-oncology. PEComas are rare tumours associated with tuberous sclerosis and melanoma, sharing genetic abnormalities. Gynaecological PEComas usually present with no or non-specific symptoms. Preoperative investigations are often misleading. Final histology and immunohistochemistry have overlapping features with smooth muscle tumours. Although rare, PEComas need to be treated aggressively to minimise the potential risk of spread. There is currently little evidence about further adjuvant treatment and no clear follow-up protocol. However, the literature suggests that the prognosis is generally good.

Similar to tumor-initiating cells (TICs), minimal residual disease (MRD) is capable of reinitiating tumors and causing recurrence. However, the molecular characteristics of solid tumor MRD cells and drivers of their survival have remained elusive. Here we performed dense multiregion transcriptomics analysis of paired biopsies from 17 ovarian cancer patients before and after chemotherapy. We reveal that while MRD cells share important molecular signatures with TICs, they are also characterized by an adipocyte-like gene expression signature and a portion of them had undergone epithelial-mesenchymal transition (EMT). In a cell culture MRD model, MRD-mimic cells showed the same phenotype and were dependent on fatty acid oxidation (FAO) for survival and resistance to cytotoxic agents. These findings identify EMT and FAO as attractive targets to eradicate MRD in ovarian cancer and make a compelling case for the further testing of FAO inhibitors in treating MRD.

The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured when informed by the molecular signatures of the normal fallopian tube epithelium (FTE) cells, the cells of origin of SOC. Surveying the transcriptomes of ∼6,000 FTE cells, predominantly from non-ovarian cancer patients, identified 6 FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH. Importantly, NGH-based stratification of ∼1,700 tumors robustly correlated with survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC. Using single-cell RNA sequencing, Hu et al. identify six subtypes of fallopian tube epithelium (FTE) cells in normal human fallopian tube tissues. The FTE cellular subtypes reveal intra-tumoral heterogeneity in serous ovarian cancer (SOC) and define SOC subtypes that correlate with patient prognosis.

SummaryThe inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH can be accurately measured when informed by the molecular signatures of the normal cells of origin. We surveyed the transcriptomes of ∼ 4000 normal fallopian tube epithelial (FTE) cells, the cells of origin of serous ovarian cancer (SOC), and identified six FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH that was previously unrecognized. Importantly, NGH-based stratification of ∼1700 tumors robustly predicted survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC.HighlightsThe projection of FTE subtypes refines the molecular classification of serous OCComprehensive single-cell profiling of FTE cells identifies 6 molecular subtypesSubstantial non-genetic heterogeneity of HGSOC identified in 1700 tumorsA mesenchymal-high HGSOC subtype is robustly correlated with poor prognosis

Introduction Epithelioid hemangioma is a rare vascular tumor found in the penis. It is essential to avoid misdiagnosis with Peyronie's disease and penile cancer, as management differs significantly. Case presentation We present a case of epithelioid hemangioma of the penis in a 50-year-old Caucasian man. We also review the literature to evaluate the incidence of benign vascular anomalies of the penis and their management. Conclusions Epithelioid hemangioma of the penis should be considered in the differential diagnosis of patients presenting with painful penile lumps. A thorough histological and immunohistochemical examination is required to make the diagnosis. Optimal management is complete local excision and periodic physical examination for local recurrence.

We present a case of an 81-year-old man who was diagnosed with a necrotising (malignant) otitis externa (NOE). Initial biopsies from the external auditory canal showed scanty squamous epithelium but no evidence of malignancy. Despite an initial improvement on intravenous antibiotics and subsequent discharge from hospital, the patient returned with worsening otalgia. Following readmission to the hospital, intravenous antibiotics were restarted. Despite this, the patient developed a lower motor neurone palsy of cranial nerve VII on the ipsilateral side of the pain. He was taken to the theatre for an exploration of the left mastoid with further biopsies. Adenocarcinoma was diagnosed histologically and the patient was started on palliative radiotherapy. This case adds to the known literature on metastatic disease in the temporal bone and highlights the need to exclude malignancy in cases of NOE.

This summer's orgy of sporting events has been eagerly awaited by youngsters and adults alike. Unlike the masses, however, I care for neither England nor any other team in Euro 2004. Watching men running around in shorts has always seemed like a waste of time to me. And for the patriots out there: aren't there more relevant reasons to be proud of your country? People are quick to blame trashy soaps for the rise of the couch potato, whereas watching football is seen to be the virtue of a true man. However, at 90 minutes a go (plus 30 minutes of halftime and postmatch arguing), a football match is three time as long …