Jerry W. Hussong

Cutaneous T-cell lymphoma (CTCL): Current practices in blood assessment and the utility of T-cell receptor (TCR)-Vβ chain restriction

BACKGROUND Accurate quantification of malignant cells in the peripheral blood of patients with cutaneous T-cell lymphoma is important for early detection, prognosis, and monitoring disease burden. OBJECTIVE We sought to determine the spectrum of current clinical practices; critically evaluate elements of current International Society for Cutaneous Lymphomas (ISCL) B1 and B2 staging criteria; and assess the potential role of T-cell receptor-Vβ analysis by flow cytometry. METHODS We assessed current clinical practices by survey, and performed a retrospective analysis of 161 patients evaluated at Yale (2011-2014) to compare the sensitivity, specificity, positive predictive value, and negative predictive value of parameters for ISCL B2 staging. RESULTS There was heterogeneity in clinical practices among institutions. ISCL B1 criteria did not capture 5 Yale cohort cases with immunophenotypic abnormalities that later progressed. T-cell receptor-Vβ testing was more specific than polymerase chain reaction and aided diagnosis in detecting clonality, but was of limited benefit in quantification of tumor burden. LIMITATIONS Because of limited follow-up involving a single center, further investigation will be necessary to conclude whether our proposed diagnostic algorithm is of general clinical benefit. CONCLUSION We propose further study of modified B1 criteria: CD4/CD8 ratio 5 or greater, %CD4(+) CD26(-) 20% or greater, or %CD4(+) CD7(-) 20% or greater, with evidence of clonality. T-cell receptor-Vβ testing should be considered in future diagnostic and staging algorithms.

Expression of Apoptosis-related Antigens, Fas, bcl-2, and p53, and Mib-1 Proliferation Index in the Hypoplastic Thymus of DiGeorge Syndrome

Apoptosis, along with cellular proliferation, plays a major role in normal developmental processes and tissue homeostasis. We hypothesized that altered apoptosis-related pathways and/or reduced cell proliferation might play a role in the thymic hypoplasia or aplasia in DiGeorge syndrome (DG). We used immunohistochemistry to evaluate the apoptosis-related antigens Fas (CD95), bcl-2, and p53, as well as Mib-1 proliferation index in the thymuses from six patients with DG. The results were compared with those from the thymuses from six patients with non-DG congenital heart disease. All DG patients (age 32 weeks GA to 4 months) had hypoplastic thymuses ranging from microscopic foci to 2.7 g in weight (expected for age, 4.7 ± 3.6 g to 10 ± 6 g). The thymic weights from the patients with non-DG congenital heart disease (age 37 weeks GA to 1 month) ranged from 3 to 5.6 g and were at the lower range of expected weight by age (expected for age, 8.4 ± 5.6 g to 12 ± 7 g). All thymuses showed histologic features of stress-induced involution. In both groups, a - 50% Mib-1 proliferation index was found in the cortical thymocytes, whereas <5% Mib-1 labeling was seen in the medullary thymocytes; Fas stained medullary epithelial cells (3+) and cortical epithelial cells (1+); bcl-2 stained medullary thymocytes (3+) and cortical thymocytes (1+); p53 stained less than 1% of nuclei in all sections. No significantly altered Mib-1 proliferation index or expression of Fas, bcl-2, and p53 was observed in the hypoplastic thymuses in DG, compared to these same measures in non-DG. These results suggest that thymic hypoplasia in DG may be mediated by mechanisms other than reduced cellular proliferation and/or altered Fas, bcl-2, and p53 apoptotic pathways.

Web-based oil immersion whole slide imaging increases efficiency and clinical team satisfaction in hematopathology tumor board

Background: Whole slide imaging (WSI) is widely used for education and research, but is increasingly being used to streamline clinical workflow. We present our experience with regard to satisfaction and time utilization using oil immersion WSI for presentation of blood/marrow aspirate smears, core biopsies, and tissue sections in hematology/oncology tumor board/treatment planning conferences (TPC). Methods: Lymph nodes and bone marrow core biopsies were scanned at ×20 magnification and blood/marrow smears at 83X under oil immersion and uploaded to an online library with areas of interest to be displayed annotated digitally via web browser. Pathologist time required to prepare slides for scanning was compared to that required to prepare for microscope projection (MP). Time required to present cases during TPC was also compared. A 10-point evaluation survey was used to assess clinician satisfaction with each presentation method. Results: There was no significant difference in hematopathologist preparation time between WSI and MP. However, presentation time was significantly less for WSI compared to MP as selection and annotation of slides was done prior to TPC with WSI, enabling more efficient use of TPC presentation time. Survey results showed a significant increase in satisfaction by clinical attendees with regard to image quality, efficiency of presentation of pertinent findings, aid in clinical decision-making, and overall satisfaction regarding pathology presentation. A majority of respondents also noted decreased motion sickness with WSI. Conclusions: Whole slide imaging, particularly with the ability to use oil scanning, provides higher quality images compared to MP and significantly increases clinician satisfaction. WSI streamlines preparation for TPC by permitting prior slide selection, resulting in greater efficiency during TPC presentation.

An Analysis of Clinical Consultation Activities in Clinical Pathology Who Requests Help and Why

OBJECTIVES To examine the distribution of callers who made consultation requests and to identify associations between caller categories and consultation topics. METHODS Review of prospectively collected database of consultations. RESULTS Direct care personnel made more consultation requests than non-direct care personnel. Consultation topics varied by caller type. Direct care personnel requested more consultations on test interpretation and few consultations on test selection than laboratory personnel. Differences in consultation requests by primary care physicians and specialists were significant. CONCLUSIONS At our laboratory, consultation requests primarily originate from primary care physicians. Consultation requests vary by caller type.

A Limited Plasma Cell Flow Cytometry Panel With Reflex CD138 Immunohistochemistry Is an Optimal Workflow Process for Evaluating Plasma Cell Neoplasms in Bone Marrow Specimens

OBJECTIVES To determine the optimal workflow combination of flow cytometry (FC) and immunohistochemistry tests for efficient and cost-effective evaluation of plasma cell (PC) neoplasms (PCNs) in bone marrow (BM) specimens. METHODS Various workflow combinations of immunohistochemistry and FC for 4,031 BM specimens worked up for PCNs were compared. Turnaround time (TAT), immunohistochemistry usage, technical charges, and addendum/amendment rates were compared between periods to determine the optimal workflow combination. RESULTS Five distinct workflow periods were identified, with varying combinations of full or limited FC panels for assessing PC clonality and CD138/κ/λ immunohistochemistry for PC quantification. Replacement of full FC with limited FC was associated with significant reductions in TAT and number of immunostains performed per case. Elimination of immunohistochemistry on cases determined to be polyclonal by FC also resulted in significant reductions in immunohistochemistry usage and significant cost savings. CONCLUSIONS Assessment of PC clonality using a limited FC panel followed by reflex CD138 immunohistochemistry on cases that are monoclonal by FC provides an optimal and cost-effective workflow for evaluating PCNs in BM samples.

Impact of Continuous Improvement of Laboratory Test Result Comments on Requests for Consultation: A Case Series.

OBJECTIVES Test interpretation is an important part of the brain-to-brain loop. Poor test comments can lead to calls for explanations and impair test interpretation and possibly patient care. There has been little study on quality improvement of test result comments. The objective of this study was to investigate the impact of improvements in test comments on requests for consultation by clinicians. METHODS We monitored the volume of requests for consultation regarding test results before and after a test comment was modified. RESULTS Modifications of test comments eliminated calls for three different tests. Reductions were statistically significant for all tests (P < .007). CONCLUSIONS Quality improvement activities targeted at test comments can improve service, reduce costs, and improve patient care.

Neoplastic plasma cell aberrant antigen expression patterns and their association with genetic abnormalities

Abstract Little is known about aberrant antigen expression patterns and their association with cytogenetic aberrations in multiple myeloma (MM). We examined the correlation between flow cytometry and florescence in situ hybridization (FISH) in 167 marrow specimens with MM. Gene expression profiling of CD56, CD117, CD52 and CD20 mRNA in plasma cells (PCs) from patients treated on Total Therapy 2 and Total Therapy 3 trials were also evaluated. Higher expression of CD56 and CD117 was associated with hyperdiploidy. High CD52 mRNA expression was associated with c-MAF and FGFR3 subgroups. Higher expression of CD56 mRNA, but lower Kit expression, were noted in association with FGFR3. In contrast, the c-MAF subgroup showed high Kit expression but lacked NCAM mRNA expression. CKS1B amplification showed positive correlation with CD52 (p = 0.0065) but negative correlation with CD20 (p = 0.0207). These findings indicate that phenotypic differences in MM are associated with distinct genetic subgroups, which potentially has important diagnostic and prognostic value.

Immunophenotypic and cytogenetic evolution patterns of the neoplastic plasma cells in multiple myeloma relapsed after stem cell transplant

Multiple myeloma (MM) is a neoplasm characterized by proliferation of clonal plasma cells (PCs) and a combination of clinical manifestations. Flow cytometry is an important method for diagnosing and monitoring of MM. Cytogenetic profiling of neoplastic PCs provides important prognostic information. Although stem cell transplantation (SCT) has significantly improved the overall survival of patients with MM, most SCT recipients relapse. We have studied the immunophenotypic and cytogenetic dissimilarities in the neoplastic PCs before SCT and after relapse in patients with initial complete remission, and investigated a possible influence of such dissimilarities on the patients’ survival. We retrospectively reviewed results of flow cytometric studies of bone marrow specimens from 46 patients with MM who underwent SCT, demonstrated a complete initial response, but subsequently relapsed. In nine of these patients, fluorescence in situ hybridization (FISH) studies were performed both pre-SCT and post-relapse. We have shown a significant flow cytometric and cytogenetic diversity of the neoplastic PCs in relapsed MM post-SCT. Such changes were detected in a considerable number of cases (47.8% and 44.4%, respectively). The most frequent cytogenetic changes indicate an emergence of possibly a more aggressive PC clone, known to be associated with worse prognosis and poorer outcome. Our study has demonstrated that the acquisition of immunophenotypic changes predicts worse overall survival.

Moriates C, Arora V, Shah N, eds. Understanding Value-Based Healthcare.

C Moriates, V Arora, N Shah, eds. Understanding Value-Based Healthcare . New York, NY: McGraw-Hill Education, 2015, 416 pp,

Evidence of increased angiogenesis in patients with acute myeloid leukemia

49.50. The health care system is under increasing pressure to provide value. Although quality is the most important part of this equation, greater attention is being placed on the cost component of the equation. Within pathology, most hospitals have begun utilization management programs that are designed to reduce waste and increase value. Pathologists and laboratorians, however, need to become more knowledgeable and proactive to help the health care system provide greater value in health care. Understanding Value-Based Healthcare was written for physicians and other health care providers. It is not about high-level policy or economics. Rather, it is about actions that those on the front lines of health care can take to improve value. Although the book is written for a wide audience, it covers many topics that are relevant to pathologists. The book contains 16 chapters that are divided into three sections. The first section, “Introduction to Value in Healthcare,” has six chapters that provide background material. The first chapter describes how health care has become increasingly complex, inefficient, and expensive. As a result, approximately one-third of health care dollars are wasted. Compared with other countries, the US system fails to deliver value. This chapter is …