Archives of pathology & laboratory medicine最新文献

Context.—: It is known that a subset of cases of classic Hodgkin lymphoma (CHL) with B-cell-rich nodules (lymphocyte-rich CHL) exhibits morphologic and immunophenotypic features that overlap with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), raising diagnostic difficulties that can be resolved in most cases by performing an adequate battery of immunohistochemical studies.

Objective.—: To fully characterize cases of T-cell-rich Hodgkin lymphoma where a specific diagnosis of NLPHL (ie, pattern D) or CHL could not be made even after complete immunophenotypic investigation.

Design.—: The clinical, immunomorphologic, and molecular (when applicable) presentation of 3 cases of T-cell-rich Hodgkin lymphoma was thoroughly investigated.

Results.—: These 3 cases harbored lymphocyte-predominant-like and Hodgkin and Reed-Sternberg-like cells that partially expressed B-cell and CHL markers and were negative for Tiftein-Barr virus-encoded small RNA, in a T-cell-rich background with residual follicular dendritic cell meshworks; 1 case had frequent and the other 2 cases scant/absent eosinophils and plasma cells. Two patients with advanced-stage (III or IV) disease presented with axillary and supraclavicular lymphadenopathy, respectively, and without B symptoms. These patients underwent NLPHL-like therapeutic management with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], vincristine sulfate [Oncovin], and prednisone) chemotherapy; both are in complete remission 7 years posttherapy. One patient presented with stage I disease involving an internal mammary lymph node without B-symptoms and was treated with surgical excision alone; this patient is also in complete remission 1 year later.

Conclusions.—: These cases illustrate overlapping features of T-cell-rich NLPHL and CHL with neoplastic cells expressing both B-cell program and CHL markers. This underrecognized overlap has not been fully illustrated in the literature, although it portrays a therapeutic challenge. These neoplasms may deserve in-depth investigation in the future that may bring up diagnostic or theragnostic implications.

Context.—: Pleural effusion cytology has been widely used in the investigation of pathologic fluid accumulation in pleural spaces. However, up to one-tenth of the cases were not given a definitive diagnosis. These cases have largely been neglected in the bulk of the literature.

Objective.—: To provide real-world data on indefinite diagnoses including "atypia of uncertain significance" (AUS) and "suspicious for malignancy" (SFM) in pleural effusion cytology and to investigate pathologists' practice patterns on using these diagnostic categories.

Design.—: We reported the diagnoses of 51 675 cases. Descriptive statistics and correlation coefficients were used to analyze the relationships between different diagnostic categories and pathologists' practice patterns and possible explanatory variables.

Results.—: The diagnoses AUS and SFM were reported in 4060 cases (7.86%) and 1554 cases (3.01%) in the cohort, respectively. The mean rates for these indefinite diagnoses varied up to 3-fold between pathologists. Correlations were found between AUS and SFM, as well as between indefinite diagnoses and negative for malignancy (NFM). No correlations were found between pathologists' years of experience or case volume and the rates of indefinite diagnosis or diagnostic certainty.

Conclusions.—: A real-world baseline for the rates of indefinite diagnoses in pleural effusion cytology is provided in this large retrospective study. Pathologists show significant variation in their use of indefinite diagnostic categories, and the tendency to use these ambiguous terms was not correlated with individuals' experience or case volume. How to untangle the intertwined relationship between the uncertainty of indefinite diagnoses and that of NFM requires future prospective studies.

Context.—: The prothrombin time (PT) and activated partial thromboplastin time (APTT) are screening tests used to detect congenital or acquired bleeding disorders. An unexpected PT and/or APTT prolongation is often evaluated using a mixing test with normal plasma. Failure to correct ("noncorrection") prolongation upon mixing is attributed to an inhibitor, whereas "correction" points to factor deficiency(ies).

Objective.—: To define an optimal method for determining correction or noncorrection of plasma mixing tests through an international, multisite study that used multiple PT and APTT reagents and well-characterized plasma samples.

Design.—: Each testing site was provided 22 abnormal and 25 normal donor plasma samples, and mixing studies were performed using local PT and APTT reagents. Mixing study results were evaluated using 11 different calculation methods to assess the optimal method based on the expected interpretation for factor deficiencies (correction) and noncorrection (inhibitor effect). Misprediction, which represents the failure of a mixing study interpretation method, was assessed.

Results.—: Percentage correction was the most suitable calculation method for interpreting PT mixing test results for nearly all reagents evaluated. Incubated PT mixing tests should not be performed. For APTT mixing tests, percentage correction should be performed, and if the result indicates a factor deficiency, this should be confirmed with the subtraction III calculation where the normal pooled plasma result (run concurrently) is subtracted from the mixing test result with correction indicated by a result of 0 or less. In general, other calculation methods evaluated that performed well in the identification of factor deficiency tended to have high misprediction rates for inhibitors and vice versa.

Conclusions.—: No single method of mixing test result calculation was consistently successful in accurately distinguishing factor deficiencies from inhibitors, with between-reagent and between-site variability also identified.

Context.—: Detecting copy number variations (CNVs) at certain loci can aid in the diagnosis of histologically ambiguous melanocytic neoplasms. Droplet digital polymerase chain reaction (ddPCR) is a rapid, automated, and inexpensive method for CNV detection in other cancers, but not yet melanoma.

Objective.—: To evaluate the performance of a 4-gene ddPCR panel that simultaneously tests for ras responsive binding element protein 1 (RREB1) gain; cyclin-dependent kinase inhibitor 2A (CDKN2A) loss; MYC proto-oncogene, bHLH transcription factor (MYC) gain; and MYB proto-oncogene, transcription factor (MYB) loss in melanocytic neoplasms.

Design.—: One hundred sixty-four formalin-fixed, paraffin-embedded skin samples were used to develop the assay, of which 65 were used to evaluate its performance. Chromosomal microarray analysis (CMA) data were used as the gold standard.

Results.—: ddPCR demonstrated high concordance with CMA in detecting RREB1 gain (sensitivity, 86.7%; specificity, 88.9%), CDKN2A loss (sensitivity, 80%; specificity, 100%), MYC gain (sensitivity, 70%; specificity, 100%), and MYB loss (sensitivity, 71.4%; specificity, 100%). When one CNV was required to designate the test as positive, the 4-gene ddPCR panel distinguished nevi from melanomas with a sensitivity of 78.4% and a specificity of 71.4%. For reference, CMA had a sensitivity of 86.2% and a specificity of 78.6%. Our data also revealed interesting relationships with histology, namely (1) a positive correlation between RREB1 ddPCR copy number and degree of tumor progression; (2) a statistically significant correlation between MYC gain and nodular growth; and (3) a statistically significant correlation between MYB loss and a sheetlike pattern of growth.

Conclusions.—: With further validation, ddPCR may aid both in our understanding of melanomagenesis and in the diagnosis of challenging melanocytic neoplasms.

Context.—: Cytologic-histologic correlation (CHC) is a Clinical Laboratory Improvement Amendments-mandated requirement for gynecologic cytology, but no similar requirement exists for nongynecologic cytology. This study presents the findings from a College of American Pathologists survey of nongynecologic cytology practice patterns.

Objective.—: To survey the current CHC practices for nongynecologic cytology.

Design.—: Data were analyzed from a survey developed by the committee and distributed to participants in the Nongynecologic Cytopathology Education Program mailing.

Results.—: Adoption of CHC for nongynecologic cytology cases is worldwide, with 88.5% of institutions performing CHC on these specimens, a substantial increase from previous years. Performance of CHC varied by institution type, with clinic or regional/local independent laboratories and national/corporate laboratories performing CHC significantly less frequently than hospitals, university hospitals/academic medical centers, and Veterans Administration/Department of Defense hospital institutions. Most CHC was performed concurrently in real time, when the corresponding surgical specimen was reviewed. Selection for real-time concurrent CHC was by the interpreting pathologist, the pathologist diagnosing the surgical biopsy sample or cytopathology case, or both. Sampling was by far the most common reason for discordance. A 2-step difference was the most frequent threshold for discordance between cytology and surgical specimens, but this criterion varied among institutions, with no majority definition. The positive predictive value of a positive cytology finding was calculated rarely in North American institutions but was calculated more frequently in international institutions.

Conclusions.—: CHC practices for nongynecologic cytopathology mirror those found for CHC of gynecologic cytopathology.

Context.—: ALK and ROS1 rearrangements are essential biomarkers to be tested in advanced lung adenocarcinomas. While D5F3 Ventana assay is a companion diagnostic for anaplastic lymphoma kinase-targeted therapy, immunohistochemistry is only a screening tool for detecting ROS1 rearrangement. Confirmation by cytogenetic or molecular techniques is necessary.

Objective.—: To evaluate the utility of ALK and ROS1 fluorescence in situ hybridization as a complement to immunohistochemistry in routine predictive biomarker testing algorithms.

Design.—: The study was ambispective, spanning 4.5 years during which lung adenocarcinoma samples were subjected to EGFR mutation testing by real-time polymerase chain reaction and ALK/ROS1 rearrangement testing by immunohistochemistry (Ventana D5F3 assay for anaplastic lymphoma kinase protein; manual assay with D4D6 clone for Ros proto-oncogene 1 protein). Fluorescence in situ hybridization was performed in all anaplastic lymphoma kinase equivocal and Ros proto-oncogene 1 immunopositive cases.

Results.—: Of 1874 samples included, EGFR mutations were detected in 27% (481 of 1796). Anaplastic lymphoma kinase immunohistochemistry was positive in 10% (174 of 1719) and equivocal in 3% (58 of 1719) of samples tested. ALK fluorescence in situ hybridization showed 81% (77 of 95) concordance with immunohistochemistry. Ros proto-oncogene 1 immunopositivity was noted in 13% (190 of 1425) of cases, with hybridization-confirmed rearrangements in 19.3% (26 of 135) of samples, all of which showed diffuse, strong- to moderate-intensity, cytoplasmic staining in tumor cells. Ros proto-oncogene 1 protein overexpression without rearrangement was significantly common in EGFR-mutant and ALK-rearranged adenocarcinomas.

Conclusions.—: Immunostaining is a robust method for ALK-rearrangement testing, with fluorescence in situ hybridization adding value in the rare equivocal stained case. ROS1-rearrangement testing is more cost-effective if immunohistochemistry is followed by fluorescence in situ hybridization after excluding EGFR-mutant and ALK-rearranged adenocarcinomas.

Context.—: The American Society of Clinical Oncology/College of American Pathologists 2018 update of the human epidermal growth factor receptor 2 (HER2) testing guideline includes a fluorescence in situ hybridization (FISH) group with a HER2 to chromosome 17 centromere (CEP17) ratio less than 2.0 and HER2 copy number 6.0 or greater (group 3), which requires integrated review of HER2 immunohistochemistry (IHC).

Objective.—: To assess the clinicopathologic features of group 3 patients and determine features associated with HER2-positive status after workup.

Design.—: Cases submitted for HER2 FISH between January 2019 and June 2022 were identified, and relevant clinicopathologic information was obtained.

Results.—: One hundred forty-two HER2 FISH cases (1.6%) were group 3. In 52 cases (36.6%) IHC was negative (0/1+), in 3 (2.8%) IHC was positive (3+), and in 86 (60.6%) IHC was 2+. Annotated IHC 2+ slides were recounted by a second reviewer in targeted areas, where 16 of 86 (18.6%) had a HER2:CEP17 ratio less than 2.0 and a HER2 copy number of 4.0 or greater to less than 6.0 (HER2 negative). After combined IHC/FISH review, 74 of 142 (52.1%) were classified as HER2 positive. HER2 copy number/cell was higher in HER2-positive compared with HER2-negative cases after the workup. The extent and intensity of staining in IHC 2+ cases did not correlate with the level of gene amplification. Twenty percent of HER2-positive patients achieved pathologic complete response.

Conclusions.—: About half of group 3 cases were classified as HER2 positive after additional workup. Pathologic complete response rates in HER2-positive cases were lower than expected for group 1 (HER2:CEP17 ratio ≥2.0; HER2 copy number ≥4.0) patients. IHC-targeted FISH recounts may be redundant and may potentially lead to classification of some patients as HER2 negative, resulting in withholding of targeted therapy.

Context.—: Spontaneous (nontraumatic) subdural hematomas have been reported yet have not been well studied.

Objective.—: To identify the neuropathologic features of acute spontaneous SDHs (ASSDHs) and their associated medical conditions.

Design.—: A retrospective study of 235 autopsy cases of SDH was conducted. Review of demographics, underlying medical conditions, and coagulation profile as well as gross and histopathologic examination of the brain and other organs were performed.

Results.—: Among the 32 cases of ASSDH, 5 cases (15.6%) had severe hemorrhage and 4 (12.5%) demonstrated brain herniation. Twenty-two cases (68.8%) had concurrent but nonconnecting subarachnoid hemorrhage or intraparenchymal hemorrhage. The most common underlying medical condition was thrombocytopenia (n = 21; 65.6%), followed by immunosuppression (n = 15; 46.9), bloodstream infections or sepsis (n = 12; 37.5%), hypertension (n = 13; 40.6%), and coronary artery disease (n = 12; 37.5%). Many patients with thrombocytopenia or immunosuppression had underlying malignancies, with leukemia being the most common type (n = 11; 34.4%). The use of circulatory devices or hemodialysis was noted in a significant portion of ASSDH cases. In terms of coagulation factors, most of our ASSDH patients had normal prothrombin time and activated partial thromboplastin time, but abnormal platelet count and D-dimer levels.

Conclusions.—: ASSDHs can be severe and are often associated with subarachnoid hemorrhage and/or intraparenchymal hemorrhage. The causes of ASSDH are limited to certain underlying medical conditions that ultimately lead to bleeding tendency. Autopsies are helpful in determining the etiology. Given their association with abnormal platelet count, correcting platelet deficiencies is a potential preventive measure for ASSDHs.