Micropapillary adenocarcinoma of lung: Morphological criteria and diagnostic reproducibility among pulmonary pathologists.

Context: Invasive micropapillary adenocarcinoma (MPC) is an aggressive variant of lung adenocarcinoma, frequently manifesting with advanced stage lymph node metastasis and decreased survival.

Objective: Identification of this morphology is important, as it is strongly correlated with poor prognosis regardless of the amount of MPC component. To date, no study has investigated the morphological criteria used to objectively diagnose it.

Tissue Continues to Be the Issue: Role of Histopathology in the Context of Recent Updates in the Radiologic Classification of Interstitial Lung Diseases.

Context.—: High-resolution computed tomography (HRCT) imaging has an increasingly important role in clinical decision-making in patients with interstitial lung diseases. The recent Fleischner Society white paper on the diagnostic criteria for idiopathic pulmonary fibrosis highlights the advances in our understanding of HRCT imaging in interstitial lung diseases.

High Frequency of MYD88 L265P Mutation in Primary Ocular Adnexal Marginal Zone Lymphoma and Its Clinicopathologic Correlation: A Study From a Single Institution.

Context.—: The pathogenesis of primary ocular adnexal marginal zone lymphoma (POAMZL) remains unclear. The reported associations with Chlamydia psittaci infection and MYD88 mutations are highly variable.

Association of Tumor Mutational Burden With DNA Repair Mutations and Response to Anti-PD-1/PD-L1 Therapy in Non-Small-Cell Lung Cancer.

Purpose: To examine clinical predictors of tumor mutational burden (TMB), to explore the association between TMB and DNA repair mutations, and to analyze TMB as a biomarker for response to immune checkpoint blockade in non-small-cell lung cancer.

Patients And Methods: TMB scores were determined retrospectively for 72 consecutive patients at our institution with next-generation sequencing comprehensive genomic profiling testing by Foundation Medicine. TMB scores were correlated with a number of clinical variables and presence of DNA repair mutations.

TLR4-dependent fibroblast activation drives persistent organ fibrosis in skin and lung.

Persistent fibrosis in multiple organs is the hallmark of systemic sclerosis (SSc). Recent genetic and genomic studies implicate TLRs and their damage-associated molecular pattern (DAMP) endogenous ligands in fibrosis. To test the hypothesis that TLR4 and its coreceptor myeloid differentiation 2 (MD2) drive fibrosis persistence, we measured MD2/TLR4 signaling in tissues from patients with fibrotic SSc, and we examined the impact of MD2 targeting using a potentially novel small molecule.

Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma.

Purpose: Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL) after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy.

Observations: A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.

Interpathologist Diagnostic Agreement for Non-Small Cell Lung Carcinomas Using Current and Recent Classifications.

Context.—: Measurement of interpathologist diagnostic agreement (IPDA) should allow pathologists to improve current diagnostic criteria and disease classifications.

Objectives.

Challenges and future of biomarker tests in the era of precision oncology: Can we rely on immunohistochemistry (IHC) or fluorescence hybridization (FISH) to select the optimal patients for matched therapy?

Molecular techniques have improved our understanding of the pathogenesis of cancer development. These techniques have also fueled the rational development of targeted drugs for patient populations stratified by their genetic characteristics. These novel methods have changed the classic paradigm of diagnostic pathology; among them are IHC, FISH, polymerase chain reaction (PCR) and microarray technology.

Immunohistochemistry of Pulmonary Biomarkers: A Perspective From Members of the Pulmonary Pathology Society.

The use of immunohistochemistry for the determination of pulmonary carcinoma biomarkers is a well-established and powerful technique. Immunohistochemisty is readily available in pathology laboratories, is relatively easy to perform and assess, can provide clinically meaningful results very quickly, and is relatively inexpensive. Pulmonary predictive biomarkers provide results essential for timely and accurate therapeutic decision making; for patients with metastatic non-small cell lung cancer, predictive immunohistochemistry includes ALK and programmed death ligand-1 (PD-L1) (ROS1, EGFR in Europe) testing.

Rapid On-Site Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspirations for the Diagnosis of Lung Cancer: A Perspective From Members of the Pulmonary Pathology Society.

Context: - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a very useful tool in the field of diagnostic respiratory cytology. Rapid on-site evaluation (ROSE) of EBUS-TBNA not only has the potential to improve diagnostic yield of the procedure but also to triage samples for predictive molecular testing to guide personalized treatments for lung cancer.

Objective: - To provide an overview of the current status of the literature regarding ROSE of EBUS-TBNA in the diagnosis of lung cancer.

Peritumoral cuffing by T-cell tumor-infiltrating lymphocytes distinguishes HPV-related oropharyngeal squamous cell carcinoma from oral cavity squamous cell carcinoma.

Background: It is unclear why human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has improved clinical behavior compared to HPV-negative HNSCC. We sought to better characterize the immune microenvironment of tongue cancers by examining the CD3 and CD8 TIL pattern in HPV-positive and HPV-negative tumors.

Methods: Histologic sections from 40 oral tongue and oropharyngeal cases were analyzed (n=21 HPV DNA-positive, n=19 HPV DNA-negative).

Hypersensitivity Pneumonitis A Perspective From Members of the Pulmonary Pathology Society.

Context: - Hypersensitivity pneumonitis (HP) is a lung disease that develops in susceptible individuals after inhalational exposure to an organic antigen or chemical compound. Pathogenesis is attributed to a combination of type III (immune complex-mediated) and type IV (delayed) hypersensitivity reactions to the inciting agent.

Objective: - To provide an overview of the current status of the medical literature regarding hypersensitivity pneumonitis.

Molecular and Immune Biomarkers in Acute Respiratory Distress Syndrome: A Perspective From Members of the Pulmonary Pathology Society.

Acute respiratory distress syndrome (ARDS) is a multifactorial syndrome with high morbidity and mortality rates, characterized by deficiency in gas exchange and lung mechanics that lead to hypoxemia, dyspnea, and respiratory failure. Histologically, ARDS is characterized by an acute, exudative phase, combining diffuse alveolar damage and noncardiogenic edema, followed by a later fibroproliferative phase. Despite an enhanced understanding of ARDS pathogenesis, the capacity to predict the development of ARDS and to risk-stratify patients with the disease remains limited.

A Small Case Series of Intravascular Large B-Cell Lymphoma with Unexpected Findings: Subset of Cases with Concomitant Extravascular Central Nervous System (CNS) Involvement Mimicking Primary CNS Lymphoma.

Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal lymphoma with growth mainly in the lumina of vessels. We studied a small series of IVLBCL and focused on its central nervous system (CNS) involvement.

Methods: Searching the medical records of Northwestern Memorial Hospital, we identified five cases of IVLBCL from January 2007 to January 2015.

Diagnosis of Acute Cellular Rejection and Antibody-Mediated Rejection on Lung Transplant Biopsies: A Perspective From Members of the Pulmonary Pathology Society.

Context: - The diagnosis and grading of acute cellular and antibody-mediated rejection (AMR) in lung allograft biopsies is important because rejection can lead to acute graft dysfunction and/or failure and may contribute to chronic graft failure. While acute cellular rejection is well defined histologically, no reproducible specific features of AMR are currently identified. Therefore, a combination of clinical features, serology, histopathology, and immunologic findings is suggested for the diagnosis of AMR.

Humoral Human Lung Allograft Rejection by Tissue-Restricted Non-HLA Antibodies.

A third of lung recipients have preexisting antibodies against nonhuman leukocyte self-antigens (nHAbs) present in the lung tissue. These nHAbs also form de novo in about 70% of patients within 3 years after transplantation. Both preexisting and de novo nHAbs can cause murine lung allograft dysfunction.