A Review of the Molecular Determinants of Therapeutic Response in Non-Small Cell Lung Cancer Brain Metastases.

Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide. Metastases in the brain are a common hallmark of advanced stages of the disease, contributing to a dismal prognosis. Lung cancer can be broadly classified as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). NSCLC represents the most predominant histology subtype of lung cancer, accounting for the majority of lung cancer cases. Recent advances in molecular genetics, coupled with innovations in small molecule drug discovery strategies, have facilitated both the molecular classification and precision targeting of NSCLC based on oncogenic driver mutations. Furthermore, these precision-based strategies have demonstrable efficacy across the blood-brain barrier, leading to positive outcomes in patients with brain metastases. This review provides an overview of the clinical features of lung cancer brain metastases, as well as the molecular mechanisms that drive NSCLC oncogenesis. We also explore how precision medicine-based strategies can be leveraged to improve NSCLC brain metastases.

An Insidious Case of Severe Acquired Factor VIII Inhibitor.

Acquired hemophilia occurs when neutralizing antibodies inhibit the activity of coagulation factors, commonly occurring with factor VIII. Most cases are idiopathic; however, autoimmune diseases, certain medications, and malignancies can predispose patients to the development of these inhibitors. Moreover, the initial presentation of the disease is more often catastrophic bleeding, with ecchymosis or mucosal bleeding being less common. This case report outlines an incidental finding of a severe factor VIII inhibitor (with 0% activity) with non-catastrophic bleeding at presentation in the setting of potential lymphoma. Subsequently, the patient was treated with recombinant factor VIIa and immunosuppression with steroids. The case sheds light on the benign presentation of a rapidly fatal disease, thus necessitating urgent and rapid identification. Given the insidious presentation, further research is required on the various factor inhibitors to reduce health costs and improve mortality.

Rare case of primary bone lymphoma of the femur.

Primary bone lymphoma is a rare type of lymphoma that arises from skeletal tissue. Most cases described are non-Hodgkin's lymphoma with diffuse large B-cell lymphoma being the most common subtype. While it is common for non-Hodgkin's lymphoma to have secondary skeletal system involvement, primary involvement of the skeleton is surprisingly rare. Primary bone lymphoma accounts for less than 5% of all primary bone malignancies, 4%-5% of extranodal lymphomas and less than 1% of all non-Hodgkin's lymphoma. We present an interesting case of a young adult male who was diagnosed with primary bone lymphoma of the femur. Interestingly, his initial X-ray imaging revealed no osseous abnormality and subsequent MRI revealed an infiltrating mass. The patient was treated with chemotherapy of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone resulting in complete remission.

Intraperitoneal anatomy with the aid of pathologic fluid and gas: An imaging pictorial review.

The peritoneum is a large serosal membrane enveloping the abdomen and pelvic organs and forming the peritoneal cavity. This complex relationship forms many named abdominopelvic spaces, which are frequently involved in infectious, inflammatory, neoplastic, and traumatic pathologies. The knowledge of this anatomy is essential to the radiologist to localize and describe the extent of the disease accurately. This manuscript provides a comprehensive pictorial review of the peritoneal anatomy to describe pathologic fluid and gas.

Non-Cutaneous Visceral Kaposi's Sarcoma Diagnosis Confounded by Mycobacterium Avium Complex Lymphadenitis.

Kaposi's sarcoma (KS) is an Acquired Immune Deficiency Syndrome (AIDS)-defining illness, with cutaneous KS being a more common presentation. Visceral involvement, particularly in the gastrointestinal (GI) tract, without cutaneous involvement, is rare. Consisting of generally non-specific symptoms, GI-KS can have potentially fatal outcomes, including hemorrhage or perforation, making prompt diagnosis and treatment imperative. Our case describes a 31-year-old male with AIDS who presented with a neck mass and purulent, bloody rectal drainage. The neck mass was biopsied and identified as caseated necrotic cervical lymphadenitis caused by Mycobacterium avium complex (MAC). The patient presented with rectal drainage, and additional abdominal necrotic lymph nodes were discovered on CT. A subsequent colonoscopy was completed, confirming the diagnosis of visceral KS. Delayed diagnosis of visceral KS can lead to an extensive, widespread disease requiring adjuvant and prolonged treatment. Prompt diagnosis can reduce morbidity and mortality. This case aims to shed light on a rare presentation of a common disease state with potentially fatal complications and emphasizes the importance of maintaining a broad differential diagnosis.

Guillain-Barre Syndrome, a Leptomeningeal Metastasis Mimic, in a Patient With Metastatic Breast Carcinoma.

Leptomeningeal metastasis (LM) is an outcome associated with a terminal prognosis for a patient with metastatic cancer. Symptoms associated with this type of cancer progression can be subtle and nonspecific. Evaluation of LM occurs with a lumbar puncture (LP) and magnetic resonance imaging (MRI). Guillain-Barre Syndrome (GBS) can present with a similar presentation of neurological symptoms to LM. Additionally, both disease states may present with similar MRI findings. The LP can be an important diagnostic evaluation to differentiate LM and GBS. However, an LP may be unremarkable in both disease states. Therefore, a comprehensive assessment of the patient based on clinical history, physical examination, laboratory, and radiologic evaluation is essential for prompt diagnosis and treatment. We present a patient with metastatic breast cancer that presented with generalized weakness. Thorough evaluation allowed the diagnosis and treatment of GBS.

Acute Promyelocytic Leukemia Treatment Masking Hepatic Tuberculosis: A Management Dilemma.

Acute promyelocytic leukemia is a form of acute myeloid leukemia (AML) that is characterized by presence of a promyelocytic leukemia-retinoic acid receptor alpha fusion. In most patients, this fusion is detected on conventional karyotype as the t(15;17)(q24.1;q21.2) translocation, but some patients have cryptic translocations with a normal karyotype. Historically, AML is associated with a poor prognosis. Treatment with all-trans retinoic acid and arsenic trioxide assures long-term survival in the majority of patients. This treatment is generally well-tolerated but may cause hepatotoxicity. This is usually identified by transaminitis but resolves after temporary cessation of treatment. Our patient's hepatotoxicity did not resolve following all-trans retinoic acid and arsenic trioxide cessation which posed a diagnostic dilemma. This prompted exploration of other possible causes of hepatotoxicity. An eventual liver biopsy identified acid-fast bacilli, confirming a diagnosis of hepatic tuberculosis. A broad differential diagnosis is imperative when investigating abnormalities in liver function, especially in chemotherapy patients when treatment cessation may cause cancer progression.

Unusual Instance of Primary Diffuse Large B-cell Lymphoma of the Colon.

Diffuse large B-cell lymphoma (DLBCL) commonly affects the gastrointestinal (GI) tract, although primary DLBCL rarely occurs in the colon. Primary colorectal lymphoma is a surprisingly rare diagnosis, accounting for a minute percentage of GI lymphomas and colorectal malignancies. We present an interesting case of an immunocompromised young adult female who was diagnosed with DLBCL confined to a cecum polyp after she underwent a colonoscopy for a GI bleed. The lymphoma presented endoscopically as a semi-sessile polyp in the cecum that was successfully removed. The patient was treated with appropriate therapy of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

Hemophagocytic Lymphohistiocytosis and Clostridium difficile Infection: A Diagnostic Dilemma.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition that often goes underdiagnosed because of broad and non-specific symptomatology, usually consisting of fever, hepatosplenomegaly, and multiorgan failure. This disorder can be driven by genetic components (primary) or acquired (secondary) causes related to infectious, autoimmune, or malignant processes. HLH pathogenesis derives from overactive and dysregulated immune system responses. This disorder often goes misdiagnosed because of similar clinical and laboratory findings to septicemia. Cases of HLH most commonly coexist with Epstein-Barr virus (EBV). Clostridium difficile (C. difficile) infection causing HLH has also rarely been described in the literature. A firm knowledge of HLH association with clostridial infection is essential to recognize. A presumed diagnosis of HLH in a decompensating patient may prompt the initiation of appropriate treatment earlier and improve clinical outcomes. We discuss the diagnostic and management difficulties associated with these concurrent conditions.

Myoepithelioma-like hyalinizing epithelioid tumor of the foot with OGT-FOX03 fusion gene: Imaging findings, surgical implications, and pathological correlates.

Myoepithelioma-like hyalinizing epithelioid tumors are rare neoplasms that share morphological characteristics of myoepitheliomas but lack traditional immunophenotypic findings. Though little is known about these tumors at present, a handful of recent studies have confirmed that they harbor a novel fusion gene known as "OGT-FOXO." Though closely resembling myoeptheliomas, Myoepithelioma-like hyalinizing epithelioid tumors are considered a distinct tumor entity, and few studies have explored their clinical characteristics or their potential for malignancy. Furthermore, literature describing imaging findings of these tumors is virtually non-existent. Understanding the radiological and pathological differences between Myoepithelioma-like hyalinizing epithelioid tumors and myoepitheliomas is helpful in developing a comprehensive differential for soft tissue neoplasms of the foot. We describe a case of MHET of the foot and correlate MRI findings with pathology in addition to describing surgical technique and implications to care.

18 F-FDG PET/CT Findings of Leptomeningeal Metastasis in Nasopharyngeal Carcinoma.

ABSTRACT: Nasopharyngeal carcinoma (NC) is an epithelial tumor with distinctive prevalence in East and Southeast Asia. Most patients with NC only experience regional metastasis. In cases of distant metastasis, prognosis is grim. Leptomeningeal spread of the disease is a rare occurrence, which is sparsely described in the literature. We present a case of a 33-year-old man with a history of high-grade NC with leptomeningeal metastasis. Initial MRI lumbar spine demonstrated subtle findings consistent with leptomeningeal disease. These findings are easily discernible on 18 F-FDG PET/CT.

Retroperitoneal anatomy with the aid of pathologic fluid: An imaging pictorial review.

The retroperitoneum, a complex anatomical space within the abdominopelvic region, encompasses various vital abdominal organs. It is compartmentalized by fascial planes and contains potential spaces critical in multiple disease processes, including inflammatory effusions, hematomas, and neoplastic conditions. A comprehensive understanding of the retroperitoneum and its potential spaces is essential for radiologists in identifying and accurately describing the extent of abdominopelvic disease. This pictorial review aims to describe the anatomy of the retroperitoneum while discussing commonly encountered pathologies within this region. Through a collection of illustrative images, this review will provide radiologists with valuable insights into the retroperitoneum, facilitating their diagnostic proficiency to aid in appropriate patient clinical management.

Managing life-threatening 5-fluorouracil cardiotoxicity.

5-Fluorouracil (5-FU), a known cardiotoxin, is the backbone for the treatment of colorectal cancer. It is associated with arrhythmias, myocardial infarction and sudden cardiac death. Most commonly, it is associated with coronary vasospasm secondary to direct toxic effects on vascular endothelium.A woman with metastatic colon cancer, originally treated with a 5-FU infusion as part of the FOLFIRI (Folinic acid, 5-Fluorouracil, Irinotecan) regimen, was unable to tolerate the chemotherapy due to chest pain. She was transitioned from infusional 5-FU to inferior 1-hour bolus 5-FU, in an attempt to minimise cardiotoxicity, but had disease progression. A multidisciplinary decision was made to again trial 5-FU infusion and pretreat with diltiazem. She tolerated chemotherapy without adverse events. A multidisciplinary discussion is recommended for co-management of reversible 5-FU-associated cardiotoxicity. After coronary artery disease (CAD) risk stratification and treatment, empiric treatment with calcium channel blockers and/or nitrates may allow patients with suspected coronary vasospasm, from 5-FU, to continue this vital chemotherapy.

Refractory Thrombotic Thrombocytopenic Purpura to Therapeutic Plasma Exchange.

Thrombotic thrombocytopenic purpura (TTP) is a rare, potentially fatal hematologic disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and varying signs of visceral ischemia secondary to microvascular thrombosis. TTP is caused by a severe deficiency of ADAMTS13, a protease enzyme responsible for cleaving von Willebrand-factor (vWF) multimers. First-line therapy with plasmapheresis has increased survival rates immensely; however, there are few reported cases that are refractory to standardized treatment. We describe two cases of refractory TTP successfully managed with the addition of caplacizumab, an anti-von Willebrand factor immunoglobulin fragment that inhibits the interaction of vWF multimers with platelets.

COVID-19: A Rare Cause of Hemolytic Uremic Syndrome.

Hemolytic uremic syndrome (HUS) is a multisystemic condition characterized by a triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. HUS can be classified as atypical or typical, depending upon its association with the Shiga toxin-producing Escherichia coli (STEC). Approximately 90-95% of cases are classified as typical, while only 5-10% of cases are atypical. The pathogenesis of atypical HUS (aHUS) occurs when the complement cascade is activated and causes membrane attack complex (MAC) deposition in the renal tubular epithelium. Various infectious triggers have been associated with aHUS. A new and compelling correlation to this rare and potentially deadly diagnosis of aHUS is COVID-19 infection or vaccination. We present a case of COVID-19-induced exacerbation of a patient with a known history of aHUS. In addition, we performed a literature review of previously reported COVID-19-induced aHUS cases and identified the potential pathogenesis of the disease state.

Uterine Sarcoma Presenting as Hypercapnic Respiratory Failure.

Thyroid cancer is a type of malignancy that is considered to have a low morbidity and an indolent disease course in most patients. Though some of its pathologic variants such as anaplastic carcinoma may present with advanced disease staging, it is important to consider the possibility of metastasis to thyroid which may present like a thyroid primary. Solid organ carcinomas form the bulk of the uncommon metastasis to the thyroid, though sarcomas from various organs also rarely exhibit this activity. Literature demonstrating sound diagnostic criteria for these occurrences is sparse. We present a case of uterine sarcoma with distant metastasis to the thyroid gland that initially presented as hypercapnic respiratory failure. Only an inpatient episode of uterine bleeding prompted our team to explore the potential of a metastatic process. Our diagnosis was made utilizing a multidisciplinary approach that we feel is important for clinicians dealing with metastatic disease to the thyroid. In addition to sound physical exam, and use of appropriate imaging modality, we feel it is essential to utilize a detailed cytohistologic specimen evaluation, immunohistochemistry, and genetic sequencing to effectively work up such patients. Although our patient did not survive her hospital stay, we hope this paper brings greater awareness of this malignancy and acts as a benchmark for diagnosing such an unusual remote primary.