We retrospectively tested the prognostic and diagnostic significance of CD271+ mesenchymal stromal cell (MSC) density in cytopenic patients who underwent bone marrow biopsy to evaluate for ...myelodysplastic syndromes (MDS).
CD271+ MSC density was quantitated by automated image analysis of tissue microarray cores in 125 cytopenic patients: 40 lower grade MDS (<5% marrow blasts), 24 higher grade MDS, and 61 benign.
CD271+ MSC density was increased in higher grade MDS compared with benign (P = .006) and lower grade MDS (P = .02). CD271+ MSC density was predictive of survival among patients with MDS independent of Revised International Prognostic Scoring System (IPSS-R), history of transfusion, therapy-related MDS, and fibrosis (hazard ratio, 3.4; P < .001). Among low or intermediate IPSS-R patients, median survival was significantly shorter in the high CD271+ MSC density group (47 vs 18 months, P < .02).
High CD271+ MSC density is characteristic of higher grade MDS and is associated with poor risk independent of known prognostic factors.
-Professionalism issues in residency training can be difficult to assess and manage. Generational or role-based differences may also exist between faculty and residents as to what constitutes ...unprofessional behavior and how to manage it.
-To examine and compare how faculty and residents would approach the same 5 case scenarios detailing various aspects of unprofessional behavior.
-Five case scenarios highlighting various unprofessional behaviors were presented in a workshop at an annual meeting of pathology department chairs, residency program directors, and undergraduate pathology medical educators (ie, pathologists involved in medical student pathology education). The same cases were presented to a cohort of pathology residents currently in training. A standard set of responses were offered to the participants, polling results were collected electronically, and results were compared.
-Faculty and residents were fairly consistent within their respective groups. In a subset of cases, faculty were more likely to favor working with the individual in the scenario, whereas resident respondents were more likely to favor either no response or a severe response. Generational or role-based differences were also potentially evident.
-Assessing expectations and differences around professionalism for both faculty and residents should be considered as part of any educational and management approach for professionalism. Although a level of generational differences appears to be evident in this study regarding the recognition and management of unprofessional behavior, there was also agreement in some cases. Further exploration into the discrepant responses between faculty and residents may prove useful in developing educational, assessment, and remediation resources.
We sought to address the significance of isolated follicles that exhibit atypical morphologic features that may be mistaken for lymphoma in a background of reactive lymphoid tissue. Seven cases that ...demonstrated centroblast-predominant isolated follicles and absent BCL2 staining in otherwise-normal lymph nodes were studied. Four of seven cases showed clonal B-cell proliferations amid a polyclonal B cell background; all cases lacked the IGH-BCL2 translocation and BCL2 protein expression. Although three patients had invasive breast carcinoma at other sites, none were associated with systemic lymphoma up to 44 months after diagnosis. The immunoarchitectural features of these highly unusual cases raise the question of whether a predominance of centroblasts and/or absence of BCL2 expression could represent a precursor lesion or atypical reactive phenomenon. Differentiating such cases from follicular lymphoma or another mimic is critical, lest patients with indolent proliferations be exposed to unnecessarily aggressive treatment.
Primary cutaneous CD30+ lymphoproliferative disorders (pc-CD30-LPD) are a group of clonal T cell lymphoproliferative disorders that despite very similar tumor histology follow different and ...characteristic clinical courses, suggesting a homeostatic role of the tumor microenvironment. Little is known about tumor microenvironment and there is almost no literature about PD-L1 expression in pc-CD30-LPD.
This retrospective study presents a fully clinicopathologically characterized series of pc-CD30-LPDs from an academic medical center in Brazil, including 8 lymphomatoid papulomatosis (LyP), 9 primary cutaneous anaplastic large cell lymphoma (pcALCL) and 4 borderline lesions. All the cases were scored for FOXP3+ regulatory T-cells (Treg) and CD8+ cytotoxic tumor infiltrating lymphocytes (TIL) densities, as well as PD-L1 expression in tumor cells and tissue associated macrophages. The CD8+/FOXP3+ ratio was also evaluated.
Among the 21 cases of pc-CD30-LPD, PD-L1 expression is frequent in both tumor cells and tissue associated macrophages in pc-CD30-LPD across categories, suggesting that the PD-L1 axis may be a common feature of pc-CD30-LPDs. While reactive T cell infiltrates vary widely from case to case, a common feature across pc-CD30-LPDs is higher density of CD8 than FOXP3 + T cells. The distribution of T cells within the lesions however differed between LyP and pcALCL: we found that LyP lesions tend to be permeated by CD8+ and FOXP3+ T cells, whereas pcALCL tend to be surrounded by a rim of CD8+ TIL and FOXP3+ Tregs with relatively lower density infiltrates in the center of the lesion.
LyP has a trend to have denser immune cells throughout the lesion, with higher FOXP3+ Treg and CD8+ TIL in the center than the edge comparing with pcALCL. PD-L1+ is frequent in tumor cells and tissue associated macrophages in pc-CD30-LPD. The differential distribution of CD8+ and FOXP3+ TILs in LyP as compared to pcALCL could provide a clue to the relapsing/remitting course of LyP as compared to the less frequent spontaneous regression of pcALCL.
The pathologist workforce in the United States is a topic of interest to the health-care community as a whole and to institutions responsible for the training of new pathologists in particular. ...Although a pathologist shortage has been projected, there has been a pervasive belief by medical students and their advisors that there are “no jobs in pathology.” In 2013 and again in 2017, the Program Directors Section of the Association of Pathology Chairs conducted surveys asking pathology residency directors to report the employment status of each of their residents graduating in the previous 5 years. The 2013 Program Directors Section survey indicated that 92% of those graduating in 2010 had obtained employment within 3 years, and 94% of residents graduating in 2008 obtained employment within 5 years. The 2017 survey indicated that 96% of those graduating in 2014 had obtained employment in 3 years, and 97% of residents graduating in 2012 obtained positions within 5 years. These findings are consistent with residents doing 1 or 2 years of fellowship before obtaining employment. Stratification of the data by regions of the country or by the size of the residency programs does not show large differences. The data also indicate a high percentage of employment for graduates of pathology residency programs and a stable job market over the years covered by the surveys.
Angiogenesis is known to play a major role in neoplasia, including hematolymphoid neoplasia. We assessed the relationships among angiogenesis and expression of vascular endothelial growth factor and ...its receptors in the context of clinically and biologically relevant subtypes of diffuse large B-cell lymphoma using immunohistochemical evaluation of tissue microarrays. We found that diffuse large B-cell lymphoma specimens showing higher local vascular endothelial growth factor expression showed correspondingly higher microvessel density, implying that lymphoma cells induce local tumor angiogenesis. In addition, local vascular endothelial growth factor expression was higher in those specimens showing higher expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. The germinal center-like and nongerminal center-like subtypes of diffuse large B-cell lymphoma were biologically and prognostically distinct. Interestingly, only in the more clinically aggressive nongerminal center-like subtype were microvessel densities significantly higher in specimens showing higher vascular endothelial growth factor expression; the same was true for the finding of higher vascular endothelial growth factor receptor-1 expression in conjunction with higher vascular endothelial growth factor expression. These differences may have important implications for the responsiveness of the two diffuse large B-cell lymphoma subtypes to anti-vascular endothelial growth factor and anti-angiogenic therapies.
Competency-based medical education has evolved over the past decades to include the Accreditation Council for Graduate Medical Education Accreditation System of resident evaluation based on the ...Milestones project. Entrustable professional activities represent another means to determine learner proficiency and evaluate educational outcomes in the workplace and training environment. The objective of this project was to develop entrustable professional activities for pathology graduate medical education encompassing primary anatomic and clinical pathology residency training. The Graduate Medical Education Committee of the College of American Pathologists met over the course of 2 years to identify and define entrustable professional activities for pathology graduate medical education. Nineteen entrustable professional activities were developed, including 7 for anatomic pathology, 4 for clinical pathology, and 8 that apply to both disciplines with 5 of these concerning laboratory management. The content defined for each entrustable professional activity includes the entrustable professional activity title, a description of the knowledge and skills required for competent performance, mapping to relevant Accreditation Council for Graduate Medical Education Milestone subcompetencies, and general assessment methods. Many critical activities that define the practice of pathology fit well within the entrustable professional activity model. The entrustable professional activities outlined by the Graduate Medical Education Committee are meant to provide an initial framework for the development of entrustable professional activity–related assessment and curricular tools for pathology residency training.
Summary Clinical management of cutaneous T-cell lymphoma (CTCL) and angioimmunoblastic T-cell lymphoma (AITL) differs markedly. Diagnostic distinction is critical. Herein, we describe a series of 4 ...patients with clinically, molecularly, and histopathologically annotated mycosis fungoides or Sézary syndrome whose nodal disease mimicked AITL. The patients otherwise exhibited classic clinical manifestations of mycosis fungoides/Sézary syndrome preceding the onset of lymphadenopathy by 1 to 5 years. Skin biopsies revealed epidermotropic infiltrates characteristic of CTCL. Lymph node biopsies revealed dense CD4+ T-cell infiltrates that coexpressed follicular helper T-cell markers and were accompanied by proliferations of high endothelial venules and arborizing CD21+ follicular dendritic cell networks. Two patients had T-cell receptor gene rearrangement studies performed on their skin, lymph node, and peripheral blood demonstrating identical polymerase chain reaction clones in all 3 tissues. A small secondary clonal B-cell population was present in 1 patient that mimicked the B-cell proliferations known to accompany AITL and persisted on successive nodal biopsies over several years. This latter phenomenon has not previously been described in CTCL. The potential for patients to be misdiagnosed with AITL for lack of consideration of advanced-stage CTCL with nodal involvement underscores the necessity of information sharing among the various pathologists and clinicians involved in the care of each patient.
We report a patient with severe multi-organ dysfunction of unknown origin who presented with bilateral orbital and chorioretinal manifestations that led to the diagnosis of Erdheim-Chester Disease ...(ECD).
ECD is a rare, histiocytic, proliferative disorder characterized by multi-systemic organ involvement that has historically lacked effective therapy. Our patient underwent genetic testing that was positive for the
V600E mutation; therefore, the patient was treated with vemurafenib.
This case demonstrates the rare orbital and intraocular manifestations of ECD and the unfortunate impact of a delayed diagnosis, the importance of early gene therapy testing for management decisions, and the utilization of targeted directed therapy to improve visual outcomes and quality of life.
PDF
