Small Cell Lung Cancer: State of the Art of the Molecular and Genetic Landscape and Novel Perspective.

Small cell lung cancer (SCLC) is a highly proliferative lung cancer that is not amenable to surgery in most cases due to the high metastatic potential. Precision medicine has not yet improved patients' survival due to the lack of actionable mutations. Intra- and intertumoral heterogeneity allow the neoplasms to adapt to various microenvironments and treatments. Further studying this heterogeneous cancer might yield the discovery of actionable mutations. First-line SCLC treatment has added immunotherapy to its armamentarium. There has been renewed interest in SCLC, and numerous clinical trials are underway with novel therapeutic approaches. Understanding the molecular and genetic landscape of this heterogeneous and lethal disease will pave the way for novel drug development.

Primary angiosarcoma of the breast: Case report of a rare vascular tumor.

This is a case report of a woman in her sixth decade of life diagnosed with primary angiosarcoma of the breast using mammography and ultrasound, confirmed with imaging-guided biopsy, and finally treated with surgery and radiation. Imaging studies obtained and discussed include mammography, ultrasonography, and MRI. Further discussion on the presenting symptoms, useful imaging modalities, and treatment options takes place. It is important to consider primary angiosarcoma of the breast, though rare, in any woman presenting with a palpable breast mass and, if feasible, an MRI will be most helpful in the diagnosis of this rare tumor.

Isolated presentation of congenital microphthalmia on fetal MRI.

A fetal growth scan was performed on a 34-year-old Caucasian woman, G4P3, with a history of gestational diabetes diagnosed at 32 weeks gestation. The examination revealed an absence of normal left globe with an echogenic mass in its expected location with a rim of surrounding hypoechoic fluid. The right orbit and globe were normal, and no other structural anomalies were identified. Prior to this examination, the patient had a normal anatomic survey and fetal echocardiogram at 20 weeks, however due to fetal positioning there was limited visualization of the orbits on initial scan. Fetal MRI was performed at 36 weeks gestation and confirmed near-complete absence of the left globe with asymmetrically smaller size of the left orbit. Normal right orbit and globe were present, and no additional fetal structural abnormalities were observed. Figure 1 congenital microphthalmia was diagnosed based on the imaging findings, preparing the family and alerting the medical team of appropriate care needed postnatally.

RET fusions in solid tumors.

The RET proto-oncogene has been well-studied. RET is involved in many different physiological and developmental functions. When altered, RET mutations influence disease in a variety of organ systems from Hirschsprung's disease and multiple endocrine neoplasia 2 (MEN2) to papillary thyroid carcinoma (PTC) and non-small cell lung cancer (NSCLC). Changes in RET expression have been discovered in 30-70% of invasive breast cancers and 50-60% of pancreatic ductal adenocarcinomas in addition to colorectal adenocarcinoma, melanoma, small cell lung cancer, neuroblastoma, and small intestine neuroendocrine tumors. RET mutations have been associated with tumor proliferation, invasion, and migration. RET fusions or rearrangements are somatic juxtapositions of 5' sequences from other genes with 3' RET sequences encoding tyrosine kinase. RET rearrangements occur in approximately 2.5-73% of sporadic PTC and 1-3% of NSCLC patients. The most common RET fusions are CDCC6-RET and NCOA4-RET in PTC and KIF5B-RET in NSCLC. Tyrosine kinase inhibitors are drugs that target kinases such as RET in RET-driven (RET-mutation or RET-fusion-positive) disease. Multikinase inhibitors (MKI) target various kinases and other receptors. Several MKIs are FDA-approved for cancer therapy (sunitinib, sorafenib, vandetanib, cabozantinib, regorafenib, ponatinib, lenvatinib, alectinib) and non-oncologic disease (nintedanib). Selective RET inhibitor drugs LOXO-292 (selpercatinib) and BLU-667 (pralsetinib) are also undergoing phase I/II and I clinical trials, respectively, with preliminary results demonstrating partial response and low incidence of serious adverse events. RET fusions provide a viable therapeutic target for oncologic treatment, and further study is warranted into the prevalence and pathogenesis of RET fusions as well as development of current and new tyrosine kinase inhibitors.