Syphilis in Hematopathology Practice: A Diagnostic Challenge.

CONTEXT.­: Syphilis, a reemerging disease caused by spirochete Treponema pallidum, is becoming more frequent in surgical pathology and hematopathology practices. Hematopathologists typically receive lymph node biopsies from patients with syphilis who have localized or diffuse lymphadenopathy. Occasionally, syphilis infection in the aerodigestive tract can show a prominent lymphoplasmacytic infiltrate and mimic lymphoma. Besides the varying and occasional atypical morphology, the fact that clinical suspicion tends to be low or absent when histologic evaluation is requested adds to the importance of making this diagnosis. OBJECTIVE.­: To summarize histologic features of syphilitic lymphadenitis and syphilis lesions in the aerodigestive tract, and to review differential diagnosis and potential diagnostic pitfalls. DATA SOURCES.­: Literature review via PubMed search. CONCLUSIONS.­: Characteristic histologic findings in syphilitic lymphadenitis include thickened capsule with plasma cell-rich inflammatory infiltrate, reactive follicular and paracortical hyperplasia with prominent lymphoplasmacytic infiltrate, and vasculitis. Lymph nodes, however, can show a number of other nonspecific histologic features, which frequently makes the diagnosis quite challenging. In the aerodigestive tract, syphilis is characterized by plasma cell-rich infiltrates. Immunohistochemistry for T pallidum is the preferred method for detecting spirochetes; however, this immunohistochemical stain shows cross-reactivity with other treponemal and commensal spirochetes. Differential diagnosis of syphilis in lymph nodes and the aerodigestive tract is broad and includes reactive, infectious, and neoplastic entities. Pathologists should be aware of the histologic features of syphilis and keep this challenging entity in the differential diagnosis.

High-grade B-cell lymphoma with concurrent MYC rearrangement and 11q aberrations: clinicopathologic, cytogenetic, and molecular characterization of 4 cases.

High-grade B-cell lymphoma with 11q aberrations (LBL-11q) resembles Burkitt lymphoma (BL), is negative for MYC rearrangement, and harbors chromosome 11q aberrations. Rare cases of high-grade B-cell lymphoma with concurrent MYC rearrangement and 11q aberrations (HGBCL-MYC-11q) have been described. In this study, we report the clinicopathologic, cytogenetic, and molecular findings in 4 such cases. Diagnoses were made on tissue or bone marrow biopsies. Karyotype, fluorescence in situ hybridization, genomic microarray analyses, and next-generation sequencing were performed. All patients were male (median age, 39 years). Three cases were diagnosed as BL, while one was diagnosed as diffuse large B-cell lymphoma. Karyotypes (available in 2 patients) were complex. In 1 patient, copy number analysis showed gains at 1q21.1-q44 and 13q31.3 and loss of 13q34, abnormalities typically seen in BL. All of our cases showed 2 or more mutations that are recurrent in BL, including ID3, TP53, DDX3X, CCND3, FBXO1, and MYC. Two cases showed a GNA13 mutation, commonly seen in LBL-11q. Cases of HGBCL-MYC-11q display overlapping morphologic and immunophenotypic, as well as cytogenetic and molecular features between BL and LBL-11q, with a mutational landscape enriched for mutations recurrent in BL. Concurrent MYC rearrangement with 11q abnormalities is important to recognize, especially as it has implications for their classification.

Strategies for Combatting Health Disparities in Prioritization Schema for Medically-Necessary Time-Sensitive Orthopaedic Surgeries.

A decrease in non-emergent procedure volume was observed during the COVID-19 pandemic to conserve protective equipment, increase hospital capacity, and limit nosocomial infection. Decreasing COVID-19 infection rates, paired with increasing hospital financial pressure and concerns for patient welfare, have prompted the development of guidelines for re-introduction of medically-necessary time-sensitive (MeNTS) procedures. Such protocols have received criticism for potentially perpetuating inequities disfavoring vulnerable populations. Limited access to testing supplies and protective equipment, coupled with higher incidence of medical comorbidities attributable to social determinants of health, disadvantages vulnerable populations in seemingly objective prioritization schema. Here, we detail both an analysis of current guidelines as well as strategies aimed at mitigating these disparities (including prioritizing essential infrastructure workers, implementing questionnaires, improving scheduling communication, tracking patients via ZIP codes and insurance status, facilitating post-operative rehabilitation, acknowledging physician bias, and favoring lottery selection over first-come, first-served). These guidelines and strategies can apply to future pandemics and even routine prioritization schema.

Classic Hodgkin Lymphoma - Old Disease, New Directions: An Update on Pathology, Molecular Features and Biological Prognostic Markers.

The aim of this paper is to review morphologic, immunophenotypic, and molecular features of classic Hodgkin lymphoma, as well as different prognostic markers in this neoplasm. Classic Hodgkin lymphoma (CHL) accounts for 15-25% of all lymphomas in the Western world. The hallmark of this disease is the neoplastic Hodgkin/Reed-Sternberg (HRS) cell, which is favored to be derived from germinal center B-cells but has lost many of the B-cell markers. HRS cells are scattered within a dense inflammatory infiltrate, and through a network of cytokines and chemokines they shape their microenvironment, evade immune response, survive, and grow. In the last two decades multiple prognostic markers related to HRS cells, the microenvironment or both, have been evaluated in patients with CHL. They include clinical, immunohistochemical, cytogenetic, and molecular markers that can predict survival and identify high-risk patients who will likely relapse after therapy. More recently, circulating tumor DNA analysis by next-generation sequencing has opened new avenues for diagnosis and disease monitoring after therapy. The increased understanding of molecular mechanisms underlying CHL pathogenesis has led to successful implementation of novel therapies, such as anti-PD-1 antibodies, which are becoming a mainstay of treatment in relapsed/refractory patients. CONCLUSION: Currently, pathologic prognostic markers are not routinely assessed at initial diagnosis of CHL. However, as more therapies become available, it will be important to identify patients with high-risk disease who may benefit from more intense or targeted therapy upfront.

The Patient-Pathologist Consultation Program: A Mixed-Methods Study of Interest and Motivations in Cancer Patients.

CONTEXT.­: There is a wide disconnect between patients and the pathologists who make their diagnoses. Recent literature highlights successful programs in which patients meet with pathologists to review their pathology reports and see their tissue under a microscope. We do not know how many patients are interested in such a service, nor do we understand what drives interested patients to want to meet with their pathologist and what specific value it may provide. OBJECTIVE.­: To quantify patient interest in a patient-pathologist consultation program and qualitatively assess motivations for patient interest or disinterest. DESIGN.­: Subjects were recruited from an academic cancer center and a local community cancer support group to respond to a survey about their interest in a patient-pathologist consultation program. Both online forms and paper surveys were available. The online survey was promoted via social media. RESULTS.­: There was a high level of patient interest, with 75% of respondents indicating they were definitely interested in a patient-pathologist consultation program. Key themes of interest were enhanced understanding of the diagnosis and disease, an opportunity to demystify the diagnostic process, and the perception that additional knowledge would empower the patient. CONCLUSIONS.­: In a select group of cancer patients, there is a very high level of interest in a patient-pathologist consultation program. Pathologists, clinicians, and hospital leadership should work together to pilot these programs in diverse settings. Additional quantitative work to scale interventions for the interested population and qualitative work to design effective, patient-centered consultation programs and to assess value are needed.

How Should Decision Science Inform Scarce Blood Product Allocation?

Blood products are a scarce resource in our health care system. This article discusses a pediatric case involving large quantities of blood products transfused at the end of life. It argues that decision aids could help clinicians determine when to request ethics consultation or re-evaluation of blood product usage in a specific patient care situation and considers questions about scarce resource allocation, futility, and parental involvement in decision making.

New/Revised Entities in Gastrointestinal Lymphoproliferative Disorders.

The gastrointestinal tract is a common extranodal site of involvement by lymphomas. These may be diagnostically challenging because they can mimic a variety of benign conditions and may be difficult to subclassify when malignant. The classification of gastrointestinal lymphomas is an evolving area with some recent changes. Although some of these entities are rare, they are important to recognize because of the variable clinical presentations, comorbidities, and treatment implications. This article explores new and revised entities in gastrointestinal lymphoproliferative disorders.

Update on Gastrointestinal Lymphomas.

Herein we review the following selection of gastrointestinal lymphomas: monomorphic epitheliotropic intestinal T-cell lymphoma; indolent T-cell lymphoproliferative disorder of the gastrointestinal tract; intestinal T-cell lymphoma, not otherwise specified; duodenal-type follicular lymphoma; and Epstein-Barr virus-positive mucocutaneous ulcer. Definitions reflect the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Clinical, morphologic, and immunophenotypic characteristics of each entity are emphasized.

Doctor in the Family: Stories and Dilemmas Surrounding Illness in Relatives.

This symposium includes twelve personal narratives from physicians with family members or close personal friends with medical illnesses. This issue also includes three commentaries on these narratives by scholars in the fields of bioethics, sociology, and law. The aim of this issue is to explore the benefits and potential harms that may arise when physicians are involved in the care of relatives, a role often fraught with conflicting moral obligations.

Primary Cutaneous Acral CD8+ T-Cell Lymphoma.

Primary cutaneous acral CD8+ T-cell lymphoma is a new provisional entity in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. This is a challenging diagnosis because of its rarity, as well as its morphologic and immunophenotypic overlap with other CD8+ cytotoxic lymphoid proliferations. Appropriate classification of this entity is crucial because of its indolent clinical behavior compared with other CD8+ T-cell lymphomas. Knowledge of the clinical setting, sites of involvement, and morphologic features can aid in correct diagnosis. Here, we review the clinical and pathologic features of primary cutaneous acral CD8+ T-cell lymphoma with an emphasis on the differential diagnosis among other C8+ T-cell lymphomas.

Beyond Dose: Using Pretherapy Biomarkers to Improve Dose Prediction of Outcomes for Radioimmunotherapy of Non-Hodgkin Lymphoma.

INTRODUCTION: Non-Hodgkin Lymphoma patients respond differently to therapy according to inherent biological variations. Pretherapy biomarkers may improve dose-response prediction. MATERIALS AND METHODS: Hybrid single-photon emission computed tomography (SPECT)/computed tomography (CT) three-dimensional imaging at multiple time points plus follow-up positron emission tomography (PET)/CT or CT at 2 and 6 months post therapy were used to fit tumor response to combined biological effect and cell clearance models from which three biological effect response parameters (radiosensitivity, cold effect sensitivity, and proliferation potential) were determined per patient. A correlation of biological effect parameters and pretherapy biomarker data (ki67, p53, and phospho-histone H3) allowed a dose-based equivalent biological effect (EBE) to be calculated for each patient. RESULTS: Significant correlations were found between biological effect parameters and pretherapy biomarkers. Optimum correlations were found by splitting the patient data according to p53 status. Response correlation of progression free survival (PFS) and EBE were significantly improved compared with PFS and absorbed dose alone. CONCLUSIONS: It is possible and desirable to use pretherapy biomarkers to enhance the predictive potential of dose calculations for patient-specific treatment planning.

The use of an online comment system in clinical ethics consultation.

BACKGROUND: Although a mechanism for resolving ethical issues in patient care is required for accreditation of American hospitals, there are no formal qualifications for providing clinical ethics consultation (CEC), and there remains great variability in the composition of ethics committees and consult services. Consequently, the quality of CEC also varies depending on the qualifications of those performing CEC services and the format of CEC utilized at an institution. Our institution implemented an online CEC comment system to build upon existing practices to promote consistency and broad consensus in CEC services and enable quality assurance. METHODS: This qualitative study explored the use of an online comment system in ethics consultation and its impact on consensus building and quality assurance. All adult ethics consultations recorded between January 2011 and May 2015 (n = 159) were analyzed for themes using both open and directed coding methods. RESULTS: We found that comments broadly reflected three categories: expressions of approval/agreement (87% of consults), comments about the case (89%), and comments about the written record (72%). More than one-third of consults included responses to other comments (37%). The most common types of "comments about the case" included requests for additional information (36%), recommendations for additional services (21%), and references to formal policies/standards (28%). Comments often spanned multiple categories and themes. Comments about the written record emphasized accessibility, clarity, and specificity in ethics consultation communication. CONCLUSIONS: We find the online system allows for broad committee participation in consultations and helps improve the quality of CEC provided by allowing for substantive discussion and consensus building. Further, we find the use of an online comment system and subsequent records can serve as an educational tool for students, trainees, and ethics committee members.

Genomic analysis of adult B-ALL identifies potential markers of shorter survival.

B lymphoblastic leukemia (B-ALL) in adults has a higher risk of relapse and lower long-term survival than pediatric B-ALL, but data regarding genetic prognostic biomarkers are much more limited for adult patients. We identified 70 adult B-ALL patients from three institutions and performed genome-wide analysis via single nucleotide polymorphism (SNP) arrays on DNA isolated from their initial diagnostic sample and, when available, relapse bone marrow specimens to identify recurring copy number alterations (CNA). As B-cell developmental genes play a crucial role in this leukemia, we assessed such for recurrent deletions in diagnostic and relapse samples. We confirmed previous findings that the most prevalent deletions of these genes occur in CDKN2A, IKZF1, and PAX5, with several others at lower frequencies. Of the 16 samples having paired diagnostic and relapse samples, 5 showed new deletions in these recurrent B-cell related genes and 8 showed abolishment. Deletion of EBF1 heralded a significant negative prognostic impact on relapse free survival in univariate and multivariate analyses. The combination of both a CDKN2A/B deletion and an IKZF1 alteration (26% of cases) also showed a trend toward predicting worse overall survival compared to having only one or neither of these deletions. These findings add to the understanding of genomic influences on this comparably understudied disease cohort that upon further validation may help identify patients who would benefit from upfront treatment intensification.

Doctor Knows Best? Tubal Ligation in Young, Childless Women.

When a gynecologist asks a twenty-one-year-old patient about her use of contraception, he is surprised that she would like to have a tubal ligation. The patient says that she would "never want to bring a child into this screwed up world." She has discussed tubal ligation with her boyfriend of one year, and he has told her that he accepts her decision. She asks her doctor if she can schedule the procedure as soon as possible. Her gynecologist mentions that he is concerned that she is very young and may eventually change her mind about having children. She insists that she has thought about it carefully and is certain that she wants the procedure. Her doctor feels very uncomfortable about this request. He consults the hospital ethics committee. Should he do as the patient asks or suggest that she wait at least six months and reconsider?