The Seven Words That Changed My Perspective on Patient Care.

"I'm already in so much pain, I was stuck in the car for hours, and now I have to see a student instead of my doctor?" She scoffs, crosses her arms, and looks away. Trying to understand why she is in so much pain I ask, "Are you happy with the care you're receiving?" She looks at me for the first time and I see her shoulders drop. The response that followed is one I will never forget, and is part of a larger lesson I learned involving the power of open-ended questions and their ability to foster understanding of patients in the context of their life stories. Here, I share patient stories and the 7 words that taught me the gift of genuine curiosity.

Unraveling the Mysteries of Perineural Invasion in Benign and Malignant Conditions.

Perineural invasion (PNI) is defined as the dissemination of neoplastic cells within the perineural space. PNI can be a strong indicator of malignancy and is linked to poor prognosis and adverse outcomes in various malignant neoplasms; nevertheless, it can also be seen in benign pathologic conditions. In this review article, we discuss various signaling pathways and neurotrophic factors implicated in the development and progression of PNI. We also describe the methodology, benefits, and limitations of different in vitro, ex vivo, and in vivo models of PNI. The spectrum of presentation for PNI can range from diffuse spread within large nerves ("named" nerves) all the way through localized spread into unnamed microscopic nerves. Therefore, the clinical significance of PNI is related to its extent rather than its mere presence or absence. In this article, we discuss the guidelines for the identification and quantification of PNI in different malignant neoplasms based on the College of American Pathologists (CAP) and World Health Organization (WHO) recommendations. We also describe benign pathologic conditions and neoplasms demonstrating PNI and potential mimics of PNI. Finally, we explore avenues for the future development of targeted therapy options via modulation of signaling pathways involved in PNI.

The Usefulness of Elastin Staining to Detect Vascular Invasion in Cancer.

Tumor prognosis hinges on accurate cancer staging, a pivotal process influenced by the identification of lymphovascular invasion (LVI), i.e., blood vessel and lymphatic vessel invasion. Protocols by the College of American Pathologists (CAP) and the World Health Organization (WHO) have been established to assess LVI in various tumor types, including, but not limited to, breast cancer, colorectal cancer (CRC), pancreatic exocrine tumors, and thyroid carcinomas. The CAP refers to blood vessel invasion as "angioinvasion" (vascular invasion) to differentiate it from lymphatic vessel invasion (lymphatic invasion). For clarity, the latter terms will be used throughout this review. The presence of lymphatic and/or vascular invasion has emerged as a pivotal prognostic factor; therefore, its accurate identification is crucial not only for staging but also for providing the patient with an honest understanding of his/her prognosis. Given the prognostic importance of the correct identification of LVI, specific staining techniques are employed to distinguish lymphatic vessel invasion from angioinvasion and to differentiate true LVI from artifact. These encompass hematoxylin and eosin (H&E) staining, elastic staining, Factor VIII staining, Ulex europaeus I agglutinin staining, CD31, CD34, D2-40, ERG, and D2-40 (podoplanin) immunohistochemical (IHC) stains among others. Based on a review of numerous publications regarding the efficacy of various methods for LVI detection, elastin staining demonstrated superior accuracy and prognostic value, allowing for more targeted treatment strategies. The clinical significance of accurately detecting LVI cannot be overstated, as it is strongly linked to higher cancer-related mortality and an increased risk of tumor recurrence. This review aims to examine the existing literature on the use of elastin stains in the detection of vascular invasion among different types of tumors and its prognostic value.

Splenic Rupture Secondary to Amyloidosis: A Case Report and Review of the Literature.

Amyloidosis is a term describing the extracellular deposit of fibrils composed of subunits of several different normal serum proteins in various tissues. Amyloid light chain (AL) amyloidosis contains fibrils that are composed of fragments of monoclonal light chains. Many different disorders and conditions can lead to spontaneous splenic rupture, including AL amyloidosis. We present a case of a 64-year-old woman with spontaneous splenic rupture and hemorrhage. A final diagnosis of systemic amyloidosis secondary to plasma cell myeloma was made with infiltrative cardiomyopathy and possible diastolic congestive heart failure exacerbation. We also provide a narrative review of all documented cases of splenic rupture associated with amyloidosis from the year 2000 until January 2023, along with the main clinical findings and management strategies.

Epithelial-to-Mesenchymal Transition-Related Markers in Prostate Cancer: From Bench to Bedside.

Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide, with 288,300 new cases and 34,700 deaths estimated in the United States in 2023. Treatment options for early-stage disease include external beam radiation therapy, brachytherapy, radical prostatectomy, active surveillance, or a combination of these. In advanced cases, androgen-deprivation therapy (ADT) is considered the first-line therapy; however, PCa in most patients eventually progresses to castration-resistant prostate cancer (CRPC) despite ADT. Nonetheless, the transition from androgen-dependent to androgen-independent tumors is not yet fully understood. The physiological processes of epithelial-to-non-epithelial ("mesenchymal") transition (EMT) and mesenchymal-to-epithelial transition (MET) are essential for normal embryonic development; however, they have also been linked to higher tumor grade, metastatic progression, and treatment resistance. Due to this association, EMT and MET have been identified as important targets for novel cancer therapies, including CRPC. Here, we discuss the transcriptional factors and signaling pathways involved in EMT, in addition to the diagnostic and prognostic biomarkers that have been identified in these processes. We also tackle the various studies that have been conducted from bench to bedside and the current landscape of EMT-targeted therapies.

Anti-Cancer Stem-Cell-Targeted Therapies in Prostate Cancer.

Prostate cancer (PCa) is the second-most commonly diagnosed cancer in men around the world. It is treated using a risk stratification approach in accordance with the National Comprehensive Cancer Network (NCCN) in the United States. The main treatment options for early PCa include external beam radiation therapy (EBRT), brachytherapy, radical prostatectomy, active surveillance, or a combination approach. In those with advanced disease, androgen deprivation therapy (ADT) is considered as a first-line therapy. However, the majority of cases eventually progress while receiving ADT, leading to castration-resistant prostate cancer (CRPC). The near inevitable progression to CRPC has spurred the recent development of many novel medical treatments using targeted therapies. In this review, we outline the current landscape of stem-cell-targeted therapies for PCa, summarize their mechanisms of action, and discuss avenues of future development.

Hemophagocytic Lymphohistiocytosis in the Setting of Therapy-Induced Acute Myeloid Leukemia: An Autopsy Report.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory disorder that occurs due to immunologic dysregulation. HLH can be primary (hereditary) or secondary to infections, autoimmune diseases, immune deficiencies, metabolic diseases, drugs, or malignancies. Lymphoid neoplasms mostly accompany malignancy-associated HLH. We present a case of a 12-year-old boy with a history of precursor B lymphoblastic leukemia (B-ALL), who subsequently developed chemotherapy-induced acute myeloid leukemia (t-AML). The patient was admitted for febrile neutropenia and initial laboratory tests revealed hemophagocytic lymphohistiocytosis (HLH). The hospital course was complicated by multiple infections and septic shock. The patient received several broad-spectrum antimicrobials, dexamethasone, as well as a pericardial drain to drain the hemorrhagic pericardial effusion. Despite intervention, the patient expired, and an autopsy was performed. We provide a synopsis of the main autopsy findings.