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CONTEXT.: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is characterized by neoplastic lymphocyte-predominant cells frequently rimmed by CD3+/CD57+/programmed death receptor-1 (PD-1)+ T cells. Because of the rarity of lymphocyte-predominant cells in most cases, flow cytometric studies on NLPHL often fail to show evidence of malignancy. OBJECTIVE.: To evaluate the diagnostic utility of PD-1 in detecting NLPHL by flow cytometry, in conjunction with the CD4:CD8 ratio and the percentage of T cells doubly positive for CD4 and CD8. DESIGN.: Flow cytometric data obtained from cases of NLPHL (n = 10), classic Hodgkin lymphoma (n = 20), B-cell non-Hodgkin lymphoma (n = 22), T-cell non-Hodgkin lymphoma (n = 5), benign lymphoid lesions (n = 20), angioimmunoblastic T-cell lymphomas (n = 6) and T-cell/histiocyte-rich large B-cell lymphomas (n = 2) were analyzed and compared. RESULTS.: Compared with the other groups, NLPHL showed significantly higher values in the following parameters: CD4:CD8 ratio, percentage of T cells doubly positive for CD4 and CD8, percentage of PD-1-positive T cells, and median fluorescence intensity of PD-1 expression in the doubly positive for CD4 and CD8 subset. Using a scoring system (0-4) based on arbitrary cutoffs for these 4 parameters, all 10 NLPHL cases scored 3 or higher, as compared with only 3 cases from the other groups, producing an overall sensitivity of 100% and a specificity of 96% (72 of 75). Two of the 3 outliers were non-Hodgkin lymphoma, and both showed definitive immunophenotypic abnormalities leading to the correct diagnosis. The remaining outlier was a case of T-cell/histiocyte-rich large B-cell lymphoma. CONCLUSIONS.: The inclusion of anti-PD-1 in flow cytometry is useful for detecting NLPHL in fresh tissue samples, most of which would have otherwise been labeled as nondiagnostic or reactive lymphoid processes.
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Enfermedad de Hodgkin , Linfoma de Células B Grandes Difuso , Linfocitos T CD8-positivos/metabolismo , Citometría de Flujo/métodos , Enfermedad de Hodgkin/metabolismo , Humanos , Linfoma de Células B Grandes Difuso/patología , Receptor de Muerte Celular Programada 1 , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/patologíaRESUMEN
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.
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Médula Ósea/patología , Linfoma de Células B/patología , Neoplasias de Células Plasmáticas/diagnóstico , Médula Ósea/inmunología , Citometría de Flujo/métodos , Humanos , Inmunohistoquímica/métodos , Inmunofenotipificación/métodos , Linfoma de Células B/inmunología , Sindecano-1/inmunología , Flujo de TrabajoRESUMEN
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.
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OBJECTIVES: To test whether academic centers (ACs) are more successful than nonacademic centers (NACs) in immunohistochemistry (IHC) external quality assessment challenges in the Canadian Immunohistochemistry Quality Control (CIQC) program. METHODS: Results of 9 CIQC challenges for breast cancer marker (BM) and various non-breast cancer marker (NBM) tests were examined. Success rates were compared between AC/NAC laboratories and those located in small or large cities. Performance was also correlated with annual IHC case volumes. RESULTS: There was no statistically significant difference in performance in any of the comparisons. However, overall performance on BM was significantly better (P < .0001, t test) than on NBM tests regardless of AC/NAC nature or city size. The mean failure rate on NBM was approximately twice that of BM tests. CONCLUSION: Our results suggest that recent emphasis on breast hormone IHC quality assurance has led to improved test quality.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Inmunohistoquímica/normas , Laboratorios/normas , Ensayos de Aptitud de Laboratorios/normas , Patología/normas , Centros Médicos Académicos , Canadá , Recolección de Datos , Femenino , Hospitales Rurales , Hospitales Urbanos , Humanos , Adhesión en Parafina , Garantía de la Calidad de Atención de Salud , Reproducibilidad de los Resultados , Análisis de Matrices Tisulares , Carga de TrabajoRESUMEN
p16 immunohistochemistry (IHC) is commonly used as a surrogate marker for human papillomavirus (HPV) detection in squamous cell carcinomas of the head and neck (SCCHN). However, the HPV status of tumors not staining strongly for p16 is difficult to interpret and may require the use of PCR, not available in all laboratories, as a final arbiter. We aim to determine if staining pattern in equivocal p16 staining and correlation to the percentage of positively stained tumor cells is predictive of HPV status. A retrospective review was performed on all SCCHN that underwent p16 IHC and PCR in our institution from 2007 to 2010. Descriptors of staining pattern in the original IHC report were retrieved. All available IHC slides were reviewed and reclassified using consensus staining pattern descriptors. Original and reclassified descriptors were compared to the final PCR HPV status for statistical significance using the χ(2) test. An estimate of the percentage of tumor cells that showed any form of staining was performed. Thirty-two SCCHN cases that underwent PCR HPV testing had equivocal p16 IHC results. Twenty-six cases available for review were reclassified into four staining patterns. Comparing age, sex, tumor site and diagnosis to HPV PCR status showed no statistically significant findings. However, comparing original descriptors to HPV status was statistically significant with isolated staining associated with negative HPV status (p = 0.0002). Analysis using reclassified descriptors showed strong association of membranous/cytoplasmic staining of isolated cells with negative HPV status and faint, diffuse nuclear and cytoplasmic staining with positive HPV status (p = 0.00006). HPV-negative cases with the former pattern had no more than 30 % positively-stained tumor cells and HPV-positive cases with the latter pattern had 50-90 % positively-stained cells. Our results suggest that pattern of staining in p16 IHC is associated with HPV status. For instance, a diffuse nuclear and cytoplasmic staining pattern, regardless of intensity, is associated with HPV positivity. The HPV-positive cases determined by staining pattern were also associated with a higher percentage of stained tumor cells.
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Carcinoma de Células Escamosas/virología , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Neoplasias de Cabeza y Cuello/virología , Infecciones por Papillomavirus/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Reacción en Cadena de la Polimerasa , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
An unusual case of ovarian adenosarcoma arising from a smooth-walled serous cystadenoma is described. The ovary was replaced by a multiloculated, fluid-filled cyst without any solid or papillary areas. The malignant component was underdiagnosed during frozen section examination as benign cystadenoma because of the deceptively benign gross appearance of the tumor. On the permanent sections, a phyllodes-like pattern of stromal proliferation and periglandular condensation of atypical stromal cells with a mitotic count of 3 per 10 high-power fields was more apparent and led to the diagnosis of adenosarcoma. The malignant component could not be distinguished from the benign component using immunohistochemical analysis. To our knowledge, this is the first reported case of an adenosarcoma arising from a grossly benign cystadenoma and the third case in the literature of an adenosarcoma associated with a cystadeno(fibro)ma. This case also shows the challenges in differentiating adenosarcoma from a benign counterpart on both frozen and permanent sections.
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Adenosarcoma/patología , Cistoadenoma/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Ováricas/patología , Adenosarcoma/metabolismo , Cistoadenoma/metabolismo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neoplasias Primarias Múltiples/metabolismo , Neoplasias Ováricas/metabolismoRESUMEN
A 24-year-old man presented with a ten-day history of severe headache leading to collapse. CT studies showed filling defects involving the anterior, middle and posterior cerebral arteries and evidence of ischemia and infarction. Post-mortem examination revealed multiple cerebral infarcts secondary to an arteritic process composed of multi-nucleated giant cells, lymphocytes and histiocytes in both middle and anterior cerebral arteries and one posterior cerebral artery. Both carotid siphons and one renal artery segment were also involved. Extensive workup and stains for systemic and infectious causes were negative, leading to a diagnosis of atypical giant cell arteritis (GCA). Disseminated GCA involving extracranial arteries and the anterior, middle and posterior cerebral arteries leading to cerebral infarction has not been previously reported. We report this atypical case of disseminated GCA in a young patient with clinical features distinct from classic GCA (temporal arteritis) and discuss the differential diagnosis.
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Encéfalo/patología , Infarto Cerebral/patología , Arteritis de Células Gigantes/patología , Cefalea/patología , Encéfalo/diagnóstico por imagen , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/etiología , Resultado Fatal , Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/diagnóstico por imagen , Cefalea/diagnóstico por imagen , Cefalea/etiología , Humanos , Masculino , Radiografía , Adulto JovenRESUMEN
Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury in both native kidneys and renal allografts. Disruption of the actin cytoskeleton is a key event with multiple repercussions on cell adhesion and function during IRI. However, receptors involved in regulating cytoskeletal repair following injury have not been identified. In an in vivo model of renal IRI, we used multiprobe RNase protection assay to examine the expression of Eph receptor tyrosine kinases, key regulators of actin dynamics in embryonic development. We found that one receptor in particular, EphA2, was strongly upregulated in the kidney following IRI. Ephrins, the cell-bound ligands of Eph receptors, were also strongly expressed. In cultured renal tubular cells, diverse injurious stimuli mimicking IRI also resulted in upregulation of EphA2 protein expression. Upregulation of EphA2 was inhibited by the Src kinase inhibitor PP2. Conversely, overexpression of Src kinases strongly enhanced the expression of endogenous EphA2 as well as the activity of a human EphA2 promoter construct. Activation of the Erk pathway was necessary, but not sufficient for full induction of EphA2 upreglation by Src kinases. Stimulation of renal tubular epithelial cells with the EphA2 ligand ephrin-A1 caused tyrosine phosphorylation of endogenous EphA2, paxillin, and an unidentified approximately 65-kDa protein and resulted in increased cortical F-actin staining. In summary, under in vitro conditions mimicking IRI, EphA2 expression is strongly upregulated through a Src kinase-dependent pathway. Interactions between upregulated EphA2 and its ephrin ligands may provide critical cell contact-dependent, bidirectional cues for cytoskeletal repair in renal IRI.