Cervical PEComa: Challenges in diagnosis and prognosis of a rare neoplasm.

•Cervical PEComas are rare neoplasms which present a diagnostic challenge.•Large tumour size is an important clinical prognosticator in cervical PEComa.•All reported cases of cervical PEComa classified as benign by Folpe criteria behaved in benign fashion clinically.•Tumours ≤ 4 cm may be assessed with cone biopsy, and simple hysterectomy considered if no adverse pathologic features.•Molecular characterization and linkage with coordinated rare tumour registries may identify novel treatments.

Risk of recurrence and pregnancy outcomes in young women with breast cancer who do and do not undergo fertility preservation.

PURPOSE: To assess the impact of fertility preservation (FP) requiring ovarian stimulation on breast cancer outcomes and pregnancy after breast cancer. METHODS: Women aged ≤ 40 years diagnosed with stage I-III breast cancer between 2007 and 2018 and referred for FP consultation prior to systemic therapy were identified from a British Columbia fertility center database. The primary endpoint was invasive breast cancer-free survival (iBCFS) and secondary endpoints were overall survival (OS) and achievement of pregnancy. Survival and pregnancy endpoints were compared using Cox and logistic regression analyses, respectively, for patients who did and did not undergo FP. RESULTS: The study included 153 patients, with 71 (46%) in the FP group and 82 (54%) in the non-FP group. Patients who underwent FP were more likely to be ECOG 0 (99% vs. 88%, p = 0.011) and receive chemotherapy (93% vs. 67%, p < 0.001), but had similar ER positivity status to non-FP patients (70% vs. 79%, p = 0.21). Over a median follow-up of 4.1 years, there were no differences in iBCFS (HR 1.006, 95% CI 0.416-2.438, p = 0.988) or OS (HR 0.789, 95% CI 0.210-2.956, p = 0.725) between FP and non-FP groups. Patients who underwent FP had higher odds of conceiving at least once (OR 3.024, 95% CI 1.312-6.970, p = 0.008). CONCLUSION: At a median follow-up of 4.1 years, FP did not impact iBCFS or OS, supporting its safety in young women with breast cancer. In addition, patients who underwent FP were more likely to become pregnant after breast cancer, highlighting the value of pre-oncologic treatment FP in survivorship family planning.

Interleukin-10 inhibits lipopolysaccharide-induced tumor necrosis factor-α translation through a SHIP1-dependent pathway.

Production of the proinflammatory cytokine TNFα by activated macrophages is an important component of host defense. However, TNFα production must be tightly controlled to avoid pathological consequences. The anti-inflammatory cytokine IL-10 inhibits TNFα mRNA expression through activation of the STAT3 transcription factor pathway and subsequent expression of STAT3-dependent gene products. We hypothesized that IL-10 must also have more rapid mechanisms of action and show that IL-10 rapidly shifts existing TNFα mRNA from polyribosome-associated polysomes to monosomes. This translation suppression requires the presence of SHIP1 (SH2 domain-containing inositol 5'-phosphatase 1) and involves inhibition of Mnk1 (MAPK signal-integrating kinase 1). Furthermore, activating SHIP1 using a small-molecule agonist mimics the inhibitory effect of IL-10 on Mnk1 phosphorylation and TNFα translation. Our data support the existence of an alternative STAT3-independent pathway through SHIP1 for IL-10 to regulate TNFα translation during the anti-inflammatory response.