Results From a Randomized Phase II Trial of Sunitinib and Gemcitabine or Sunitinib in Advanced Renal Cell Carcinoma with Sarcomatoid Features: ECOG-ACRIN E1808.

Introduction: Sarcomatoid renal cancer (sRCC) patients have poor outcomes. EA1808 evaluated sunitinib and gemcitabine (SG) and sunitinib alone (S) in sRCC in a randomized cooperative group phase II trial (NCT01164228).

Patients And Methods: Pts were aggregated 1:1 to SG (45 pts) or S (40 pts) using a 2-stage design.

Adjuvant therapy in patients with sarcomatoid renal cell carcinoma: post hoc analysis from Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E2805.

Objectives: To study the effects of adjuvant therapy in patients with sarcomatoid renal cell carcinoma (sRCC) enrolled in the randomised phase III clinical trial E2805.

Patients And Methods: The original trial (E2805) was a randomised, double-blinded phase III clinical trial comparing outcomes in 1943 patients with RCC accrued between 2006 and 2010 and treated with up to 1 year of adjuvant placebo, sunitinib, or sorafenib. The present study analyses the cohort of patients with sRCC that participated in E2805.

Predicting Disease Recurrence, Early Progression, and Overall Survival Following Surgical Resection for High-risk Localized and Locally Advanced Renal Cell Carcinoma.

Background: Risk stratification for localized renal cell carcinoma (RCC) relies heavily on retrospective models, limiting their generalizability to contemporary cohorts.

Objective: To introduce a contemporary RCC prognostic model, developed using prospective, highly annotated data from a phase III adjuvant trial.

Design, Setting, And Participants: The model utilizes outcome data from the ECOG-ACRIN 2805 (ASSURE) RCC trial.

KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas.

Background: Metanephric adenoma (MA) is a rare benign renal neoplasm. On occasion, MA can be difficult to differentiate from renal malignancies such as papillary renal cell carcinoma in adults and Wilms̕ tumor in children. Despite recent advancements in tumor genomics, there is limited data available regarding the genetic alterations characteristic of MA.

Acute Hypersensitivity Pneumonitis Associated With a High Ki-67 Proliferative Index.

Hypersensitivity pneumonitis (HSP) is an interstitial lung disease caused by exposure to a large range of environmental antigens. Inhaling aerosolized particles leads to a heightened immune response. HSP comes in acute, subacute, or chronic forms, all with their own potential clinical and radiographic findings.

Predicting Renal Cancer Recurrence: Defining Limitations of Existing Prognostic Models With Prospective Trial-Based Validation.

Purpose: To validate currently used recurrence prediction models for renal cell carcinoma (RCC) by using prospective data from the ASSURE (ECOG-ACRIN E2805; Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma) adjuvant trial.

Patients And Methods: Eight RCC recurrence models (University of California at Los Angeles Integrated Staging System [UISS]; Stage, Size, Grade, and Necrosis [SSIGN]; Leibovich; Kattan; Memorial Sloan Kettering Cancer Center [MSKCC]; Yaycioglu; Karakiewicz; and Cindolo) were selected on the basis of their use in clinical practice and clinical trial designs. These models along with the TNM staging system were validated using 1,647 patients with resected localized high-grade or locally advanced disease (≥ pT1b grade 3 and 4/pTanyN1Mo) from the ASSURE cohort.

Targeting V-ATPase Isoform Restores Cisplatin Activity in Resistant Ovarian Cancer: Inhibition of Autophagy, Endosome Function, and ERK/MEK Pathway.

Ovarian cancer (OVCA) patients often develop tolerance to standard platinum therapy that accounts for extensive treatment failures. Cisplatin resistant OVCA cells (cis-R) display enhanced survival mechanisms to cope with therapeutic stress. In these cells, increased autophagy process assists in chemoresistance by boosting the nutrient pool under stress.

Hepatoid Carcinoma of the Ovary: Clinical, Histopathologic, and Immunophenotypic Features.

Hepatoid carcinoma of the ovary (HCO) is a rare malignant tumor of uncertain histogenesis that was first described by Ishikura and Scully in the late 1980s. Unlike hepatoid yolk sac tumor (HYST), one of its main differential diagnoses, HCO usually presents in perimenopausal and postmenopausal women without gonadal dysgenesis. Most cases show advanced local disease at initial presentation, with diffuse intraperitoneal dissemination.

Mixed Epithelial and Stromal Tumor of the Kidney with Extension into Inferior Vena Cava: Case Report and Discussion of Adult Biphasic Cystic Renal Lesions and the Significance of Vascular Involvement.

Mixed epithelial and stromal tumor (MEST) is a biphasic adult renal lesion composed of solid and cystic areas containing spindle cell stroma and epithelium that lines the tubules and cystic spaces. While most MEST lesions are benign, rare cases with malignant morphology and biology have been reported. We present a case of mixed epithelial and stromal tumor of the kidney (MEST) with extension into the inferior vena cava in a young adult male.

The role of next-generation sequencing in the differential diagnosis of composite neoplasms.

Composite neoplasms (CNs) are rare and diagnostically challenging lesions that require differentiating between mixed clonal tumors with divergent phenotypes (MT), collision of 2 independent tumors adjacent to each other (CT), and tumor-to-tumor metastasis (TTM). To that end, pathologists have traditionally used immunohistochemistry and limited molecular studies, such as Sanger sequencing. Herein we evaluate the potential application of NGS in the differential diagnosis of these rare neoplasms.

Sebaceous carcinoma of the breast in a patient with a pathogenic BRCA2 (886delGT) mutation - focus on histopathologic and immunohistochemical features.

Sebaceous carcinoma of the breast (SCB) is a rare variant of ductal carcinoma arising within the mammary gland and containing at least 50% of malignant cells with sebaceous differentiation. Only 11 cases that adjust to the criteria delineated in the WHO classification have been published in the English literature, to the best of our knowledge. Here, we present the first SCB arising in the context of a deleterious BRCA2 mutation, focusing on the histopathologic and immunohistochemical features of this exceedingly rare tumor.

Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805.

Increased vascularity is a hallmark of renal cell carcinoma (RCC). Microvessel density (MVD) is one measurement of tumor angiogenesis; however, its utility as a biomarker of outcome is unknown. ECOG-ACRIN 2805 (E2805) enrolled 1,943 resected high-risk RCC patients randomized to adjuvant sunitinib, sorafenib, or placebo.

A novel cytogenetic and molecular characterization of renal metanephric adenoma: Identification of partner genes involved in translocation t(9;15)(p24;q24).

Renal metanephric adenoma (MA) is a rare benign tumor frequently misclassified when microscopic features alone are applied. The correct classification of a renal tumor is critical for diagnostic, prognostic, and therapeutic purposes. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to MA development have been recognized.

Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial.

Background: Renal-cell carcinoma is highly vascular, and proliferates primarily through dysregulation of the vascular endothelial growth factor (VEGF) pathway. We tested sunitinib and sorafenib, two oral anti-angiogenic agents that are effective in advanced renal-cell carcinoma, in patients with resected local disease at high risk for recurrence.

Methods: In this double-blind, placebo-controlled, randomised, phase 3 trial, we enrolled patients at 226 study centres in the USA and Canada.

Papillary thyroid carcinoma with extensive squamous dedifferentiation metastatic to the lung: BRAF mutational analysis as a useful tool to rule out tumor to tumor metastasis.

Tumors containing elements of both papillary thyroid carcinoma (PTC) and squamous cell carcinoma (SCC) are rare but well documented. When they present initially as metastatic disease in an organ that can harbor a primary SCC, the possibility of a tumor to tumor metastasis (TTM) must be considered. The aim of this case study is to illustrate how BRAF mutational analysis can be used to help differentiate between these two diagnoses.

BEST: A Randomized Phase II Study of Vascular Endothelial Growth Factor, RAF Kinase, and Mammalian Target of Rapamycin Combination Targeted Therapy With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma--A Trial of the ECOG-ACRIN Cancer Research Group (E2804).

Purpose: On the basis of evidence that resistance to vascular endothelial growth factor (VEGF) receptor inhibition is caused by hypoxia-driven residual VEGF and other proangiogenic factors, combinations of agents from these classes were hypothesized to improve treatment outcomes relative to single-agent VEGF pathway blockade.

Patients And Methods: A total of 361 patients with metastatic clear cell renal cell carcinoma were randomly assigned equally to arm A (bevacizumab monotherapy 10 mg/kg intravenously [IV] every 2 weeks), B (bevacizumab 10 mg/kg IV every 2 weeks and temsirolimus 25 mg IV every week), C (bevacizumab 5 mg/kg IV every 2 weeks and sorafenib 200 mg orally twice daily on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26), or D (sorafenib 200 mg twice daily and temsirolimus 25 mg IV weekly). Progression-free survival was the primary end point.

Angiogenin interacts with the plasminogen activation system at the cell surface of breast cancer cells to regulate plasmin formation and cell migration.

Angiogenin (ANG), a 14-kDa pro-angiogenic secreted protein, has been shown to play a role in cell migration and tumor invasion, which involve proteolytic cleavage of plasminogen to generate plasmin. However, the mechanism by which ANG regulates plasmin formation and cell migration was not known. Our studies here detected elevated levels of secreted and cell surface-bound ANG in highly invasive metastatic breast cancer cells.

Small-intestine pneumocystis jiroveci pseudotumor as an acquired immunodeficiency syndrome-presenting illness: report of a case and review of the literature.

A Pneumocystis jiroveci infection-associated mass clinically mimicking a malignancy (ie, pseudotumor) is rare and usually occurs in the lung in association with Pneumocystis pneumonia. Pneumocystis jiroveci pseudotumors of the small intestine are extremely rare and represent an unusual form of disseminated P jiroveci infection. We present a case of small-intestine P jiroveci pseudotumor as an acquired immunodeficiency syndrome-presenting illness in a patient with coinfection with cytomegalovirus, no pulmonary symptoms, and no known risk factors for human immunodeficiency virus infection.

Erlotinib eradicates brain metastases from epidermal growth factor receptor mutant non-small cell lung cancer.

Erlotinib is active in patients with lung cancer; especially those who demonstrate a mutation in exons 18-21 in the epidermal growth factor receptor (EGFR) gene. Patients with lung cancer and brain metastases have poor prognosis as systemic chemotherapy is ineffective in treating the central nervous system (CNS) metastases due to its inability to cross the blood brain barrier. Herein, we report a case of a 61 year old female who presented with stage IV adenocarcinoma of the lung with bilateral cerebral and cerebellar CNS involvement.