Showing papers in "American Journal of Clinical Pathology in 2013"
TL;DR: This article summarizes new advances in the diagnosis of HLH and includes a review of clinical findings, updated understanding of the pathogenesis, and promising new testing methods.
Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a frequently fatal and likely underdiagnosed disease involving a final common pathway of hypercytokinemia, which can result in end-organ damage and death. Although an early diagnosis is crucial to decrease mortality, the definitive diagnosis is often challenging because of the lack of specificity of currently accepted diagnostic criteria and the absence of confirmatory gold standards. Because of the wide range of laboratory assays involved in the diagnosis of HLH, practicing pathologists from a broad spectrum of clinical specialties need to be aware of the disease so that they may appropriately flag results and convey them to their clinical counterparts. Our article summarizes these new advances in the diagnosis of HLH and includes a review of clinical findings, updated understanding of the pathogenesis, and promising new testing methods.
290 citations
TL;DR: Exon sequencing has identified a mutation in K27M of the histone H3.3 gene in pediatric diffuse high-grade astrocytomas, and analysis of codon 27 mutational status could be useful in the differential diagnosis of these neoplasms.
Abstract: Brain tumors are one of the most common childhood malignancies. Diffuse high-grade gliomas represent approximately 10% of pediatric brain tumors. Exon sequencing has identified a mutation in K27M of the histone H3.3 gene ( H3F3A K27M and G34R/V) in about 20% of pediatric glioblastomas, but it remains to be seen whether these mutations can be considered specific for pediatric diffuse high-grade astrocytomas or also occur in other pediatric brain tumors. We performed a pyrosequencing-based analysis for the identification of H3F3A codon 27 and codon 34 mutations in 338 pediatric brain tumors. The K27M mutation occurred in 35 of 129 glioblastomas (27.1%) and in 5 of 28 (17.9%) anaplastic astrocytomas. None of the other tumor entities showed H3F3A K27M mutation. Because H3F3A K27M mutations occur exclusively in pediatric diffuse high-grade astrocytomas, analysis of codon 27 mutational status could be useful in the differential diagnosis of these neoplasms.
109 citations
TL;DR: Many of the causes of new-onset pancytopenia in adults and children are provided, with emphasis on bone marrow findings and recommendations of additional testing and clinical evaluation when needed, with the overall aim of aiding the pathologist's role as a consultant to the patient's treating physician.
Abstract: New-onset pancytopenia can be caused by a wide variety of etiologies, leading to a diagnostic dilemma. These etiologies range from congenital bone marrow failure to marrow space-occupying lesions, infection, and peripheral destruction, to name a few. Bone marrow examination, in addition to a detailed clinical history, is often required for an accurate diagnosis. The purpose of this review is to provide a brief overview of many of the causes of new-onset pancytopenia in adults and children, with emphasis on bone marrow findings and recommendations of additional testing and clinical evaluation when needed, with the overall aim of aiding the pathologist’s role as a consultant to the patient’s treating physician. Pancytopenia is a common indication for bone marrow examination and can have numerous causes. Cytotoxic therapies, including myeloablative radiation therapy and chemotherapy, are common, but predictable, causes of pancytopenia in patients being treated systemically for neoplasia. New-onset pancytopenia outside this setting, in both children and adults, can prove to be a diagnostic dilemma, and causes include congenital and acquired bone marrow failure syndromes, marrow space-occupying lesions, peripheral destruction of hematopoietic cells, autoimmune disorders, infection, and ineffective marrow production. Often, the workup of new-onset pancytopenia is extensive and should include a detailed clinical, medication, recreational drug, and environmental exposure history. Although bone marrow examination often reveals an underlying condition causing pancytopenia, it is not always conclusive. Understanding the various disorders that may cause pancytopenia can aid in the recommendation of additional testing and clinical evaluation when the marrow studies are not specific for a single etiology. Here, we provide a systematic overview of many of the causes of new-onset pancytopenia.
105 citations
TL;DR: Reliable automated blood cell characterization and quantification remain challenging in pathologic samples, whereas slide reviews due to unnecessary flagging should be avoided.
Abstract: Reliable automated blood cell characterization and quantification remain challenging in pathologic samples, whereas slide reviews due to unnecessary flagging should be avoided. We compared 4 modern hematology analyzers—Abbott Sapphire, Siemens Advia 120, Sysmex XE-2100, and Beckman Coulter DxH 800—regarding complete blood cell count (CBC), leukocyte differential count, and flagging efficacy in a total of 202 samples from hematology patients and normal controls. Manual differential count was used as reference. The analyzers exhibited very good correlation for CBC parameters. Neutrophils and eosinophils also showed very good correlations, whereas lymphocytes and monocytes correlated fairly. The Advia 120 displayed notably lower measurements for both parameters, which is attributable to classification of some events as large unstained cells. Basophil counts were unreliable with all analyzers. Flagging for blasts and immature granulocytes showed moderate sensitivity and specificity. Operators must not rely on blast flagging alone to detect leukemic samples with any analyzer.
104 citations
TL;DR: A systematic review and meta-analysis of studies on the influence of ROSE on FNA adequacy found that on average, ROSE improves the adequacy rate by 12%, but there was considerable variability across studies.
Abstract: Rapid onsite evaluation (ROSE) has the potential to improve the adequacy rates of fine-needle aspiration (FNA) cytology. Studies have obtained variable results on the influence of ROSE. We conducted a systematic review and meta-analysis of studies on the influence of ROSE on FNA adequacy. We synthesized evidence across all anatomic locations. We only included studies that contained a control arm and compared cohorts with ROSE against cohorts without ROSE at a single location. We screened 2,179 studies and identified 25 studies that met our inclusion criteria. On average, ROSE improves the adequacy rate by 12%, but there was considerable variability across studies. The adequacy rate with ROSE depends on the non-ROSE adequacy rate. Sixty-five percent of the variability in the adequacy rate with ROSE was found to occur because of differences in the adequacy rate without ROSE. Studies with high non-ROSE adequacy rates showed low improvement after ROSE was implemented. Studies must account for the effect of the non-ROSE adequacy rate to determine the effect of ROSE on FNA adequacy rates.
99 citations
TL;DR: In this article, the usefulness of deletion of p16 with fluorescence in situ hybridization (FISH) and p16 hypermethylation with polymerase chain reaction for the diagnosis and prognosis of malignant pleural mesothelioma (MPM) was studied.
Abstract: The distinction between sarcomatoid mesothelioma and fibrous pleuritis is difficult based on histology, especially when the amount of tumor tissue examined via biopsy is small and immunohistochemical examination is inconclusive. We studied the usefulness of deletion of p16 with fluorescence in situ hybridization (FISH) and p16 hypermethylation with polymerase chain reaction for the diagnosis and prognosis of malignant pleural mesothelioma (MPM). We analyzed 50 MPMs, including 22 sarcomatoid mesothelioma cases and 10 fibrous pleuritis cases. We set the cutoff value of homozygous deletion pattern as 14.4% based on FISH signaling patterns using samples of fibrous pleuritis. The percentage of homozygous deletion pattern was higher than 14.4% in 55.6% of the epithelioid mesotheliomas (10/18) and in all of the sarcomatoid mesotheliomas (22/22). Methylation of p16 was observed in 7 (20.6%) of 34 informative cases. p16 FISH analysis can be a reliable test for distinguishing between sarcomatoid mesothelioma and fibrous pleuritis and a prognostic factor for MPM.
98 citations
TL;DR: The results demonstrate that molecular technology can be successfully deployed in a nonspecialty, high-volume, multidisciplinary core laboratory and identify viruses that would not have been detected with DFA.
Abstract: The FilmArray respiratory virus panel detects 15 viral agents in respiratory specimens using polymerase chain reaction. We performed FilmArray respiratory viral testing in a core laboratory at a regional children’s hospital that provides service 24 hours a day 7 days a week. The average and median turnaround time were 1.6 and 1.4 hours, respectively, in contrast to 7 and 6.5 hours documented 1 year previously at an on-site reference laboratory using a direct fluorescence assay (DFA) that detected 8 viral agents. During the study period, rhinovirus was detected in 20% and coronavirus in 6% of samples using FilmArray; these viruses would not have been detected with DFA. We followed 97 patients with influenza A or influenza B who received care at the emergency department (ED). Overall, 79 patients (81%) were given oseltamivir in a timely manner defined as receiving the drug in the ED, a prescription in the ED, or a prescription within 3 hours of ED discharge. Our results demonstrate that molecular technology can be successfully deployed in a nonspecialty, high-volume, multidisciplinary core laboratory.
93 citations
TL;DR: The study suggests that RDD does not belong in the spectrum of IgG4-RD, and the number of FOXP3-positive regulatory T cells (Tregs) since they were reported to be increased in IgG 4-RD is found to be low.
Abstract: Objectives: To assess the association between Rosai-Dorfman disease (RDD) and IgG4-related disease (IgG4-RD).
Methods: We studied the number of IgG4-positive plasma cells and the IgG4/IgG ratio in 32 biopsy specimens (13 nodal, 19 extranodal) from 29 patients with RDD and compared the findings with those in IgG4-RD of the pancreas and reactive lymph nodes. We also assessed the number of FOXP3-positive regulatory T cells (Tregs) since they were reported to be increased in IgG4-RD.
Results: We found that RDD cases had much lower numbers of IgG4-positive plasma cells and lower IgG4/IgG ratios compared with IgG4-RD but were similar to reactive lymph nodes. Furthermore, RDD had lower numbers of FOXP3-positive Tregs than did IgG4-RD. There were no significant differences in the number of IgG4-positive plasma cells and the IgG4/IgG ratio between the nodal and extranodal RDD cases.
Conclusions: Our study suggests that RDD does not belong in the spectrum of IgG4-RD.
85 citations
TL;DR: Factor II and VIII activity contributes to discordance between APTT and anti-Xa results and ETP measurements may provide an additional assessment of anticoagulation status.
Abstract: We examined the concordance of heparin levels measured by a chromogenic anti-Xa assay and the activated partial thromboplastin time (APTT) during unfractionated heparin therapy (UFH) and the biochemical basis for differences between these measures. We also investigated the endogenous thrombin potential (ETP) as a possible measure of anticoagulation. Paired measures of anti-Xa and APTT were performed on 569 samples from 149 patients on UFH. The anti-Xa values and the APTT were concordant in only 54% of measurements. One hundred twelve samples from 59 patients on UFH were assayed for APTT, anti-Xa, factor II, factor VIII, and ETP. Supratherapeutic APTT values but therapeutic anti-Xa results had decreased factor II activity. Subtherapeutic APTT but therapeutic anti-Xa values had high factor VIII activity. ETP correlated with anticoagulation status and UFH dose. In conclusion, factor II and VIII activity contributes to discordance between APTT and anti-Xa results. ETP measurements may provide an additional assessment of anticoagulation status.
77 citations
TL;DR: It is demonstrated that samples containing therapeutic levels of dabigatran may lead to underestimation of intrinsic factor activities with abnormal activated partial thromboplastin time (aPTT) mixing study results and a false-positive factor VIII Bethesda titer.
Abstract: Dabigatran etexilate is a new oral anticoagulant that functions as a direct thrombin inhibitor. An inhibitor of thrombin has the potential to interfere with essentially all clot-based coagulation assays and select chromogenic assays, whereas the drug would not be expected to interfere in antigen-based assays. The purpose of this study was to evaluate the effect of dabigatran on various specialized coagulation assays using normal plasma specimens with varying concentrations of dabigatran (the active form of dabigatran etexilate). We have demonstrated that samples containing therapeutic levels of dabigatran may lead to underestimation of intrinsic factor activities with abnormal activated partial thromboplastin time (aPTT) mixing study results and a false-positive factor VIII Bethesda titer; overestimation of protein C and protein S activity and activated protein C resistance ratio when determined using aPTT-based methods; and overestimation of results based on chromogenic anti-IIa assays but no effect on antigen assays and select chromogenic assays.
77 citations
TL;DR: It is demonstrated that a subset of RDD shows features of IgG4-related disease and indicate an overlap between certain aspects of the 2 diseases.
Abstract: In this study we investigated the distribution of IgG4+ plasma cells and regulatory T (T REG ) cells, a major regulator of IgG4 production, in nodal and extranodal Rosai-Dorfman disease (RDD). Twenty-six specimens (15 nodal, 11 extranodal) were examined, with reactive lymph nodes and site-matched extranodal specimens as controls. Overall, 84.6% (22/26) of the specimens showed various degrees of sclerosis (7 mild, 8 moderate, and 7 severe). Nineteen cases (73.1%) exhibited more than 10 IgG4+ cells/0.060 mm 2 (photographed area at ×40), and 8 cases (30.8%) showed more than 40% of IgG+ cells being IgG4+. Only 1 control case exhibited more than 10 IgG4+ cells/0.060 mm 2 (P < .05). The number of T REG cells was comparable between nodal RDD and controls, whereas extranodal RDD exhibited significantly higher numbers of T REG cells than controls. These findings demonstrate that a subset of RDD shows features of IgG4-related disease and indicate an overlap between certain aspects of the 2 diseases.
Boston Children's Hospital1, Harvard University2, University of Nebraska Medical Center3, Nationwide Children's Hospital4, National Institutes of Health5, Ohio State University6, University of Texas Southwestern Medical Center7, Fred Hutchinson Cancer Research Center8, Seattle Children's9, University of Oklahoma10
TL;DR: To address the role of fusionstatus in risk stratification, pathologists should include both a histologic diagnosis and an evaluation of fusion status for all new ARMS diagnoses.
Abstract: Objectives: To examine whether the frequency of fusion-negative alveolar rhabdomyosarcoma (ARMSn) increased coincident with changes in the definition of alveolar histology.
Methods: We re-reviewed alveolar rhabdomyosarcoma (ARMS) in the Children’s Oncology Group study D9803, comparing histopathology with fusion status.
Results: Our review of 255 original ARMS cases (compared with a control group of 38 embryonal rhabdomyosarcomas [ERMS] cases) revealed that many had an ARMS-like densely cellular pattern with cytologic features and myogenin expression more typical of ERMS. Following re-review, 84 (33%) cases of original ARMS were rediagnosed as ERMS. All reclassified ERMS, including dense ERMS, were fusion negative, whereas 82% of confirmed ARMS cases were fusion positive. Total ARMS diagnoses returned to historic rates of 25% to 30% of all rhabdomyosarcomas, and ARMSn decreased from 37% to 18% of ARMS cases. The outcome of reclassified ERMS was similar to confirmed ERMS.
Conclusions: To address the role of fusion status in risk stratification, pathologists should include both a histologic diagnosis and an evaluation of fusion status for all new ARMS diagnoses.
TL;DR: A significant proportion of HP or SSA/P precursor lesions accompanied by TSAs can be detected by endoscopy based on both their flat-elevated growth and type II pit patterns.
Abstract: Objectives: To investigate the clinicopathologic and endoscopic features of precursor lesions associated with traditional serrated adenomas (TSAs).
Methods: Mutation studies for BRAF, KRAS, PIK3CA, and EGFR and immunohistochemical staining for Ki-67 were performed on 107 TSAs from 104 patients.
Results: Nondysplastic hyperplastic polyp (HP) or sessile serrated adenoma/polyp (SSA/P) precursor lesions were found in 56 (52.3%) TSAs, among which 32 (57.1%) cases showed a flat-elevated lesion with a type II pit pattern during endoscopy. TSAs with an SSA/P precursor lesion were usually found in the proximal colon, while TSAs with an HP or with no precursor lesion were mainly located in the distal colon and rectum ( P < .001). TSAs with a precursor lesion showed a lower frequency of conventional epithelial dysplasia and KRAS mutation as well as a higher frequency of BRAF mutation compared with those with no precursor lesion ( P = .002, P < .001, and P < .001, respectively).
Conclusions: A significant proportion of HP or SSA/P precursor lesions accompanied by TSAs can be detected by endoscopy based on both their flat-elevated growth and type II pit patterns. The heterogeneity of TSAs in terms of clinicopathologic and molecular features correlated with the status or type of precursor lesions.
TL;DR: It is concluded that CL-4 is a highly specific and sensitive immunohistochemical marker for assisting in distinguishing epithelioid mesotheliomas from metastatic carcinomas to the serosal membranes.
Abstract: Claudin-4 (CL-4) is a tight junction-associated protein that is expressed in most epithelial cells but absent in mesothelial cells. The purpose of this study is to evaluate the utility of CL-4 immunostaining for assisting in the differential diagnosis of mesothelioma. Sixty mesotheliomas (40 epithelioid, 10 biphasic, and 10 sarcomatoid), 185 carcinomas of different origins that can potentially be confused with mesotheliomas, 37 soft-tissue sarcomas, and 5 melanomas were investigated for CL-4 expression. All 60 mesotheliomas were CL-4 negative. In contrast, 169 (91%) of 185 carcinomas expressed this marker. Five of 8 desmoplastic small round cell tumors and the epithelial component of all 5 biphasic synovial sarcomas were CL-4 positive, whereas none of the remaining soft-tissue sarcomas or melanomas expressed this marker. It is concluded that CL-4 is a highly specific and sensitive immunohistochemical marker for assisting in distinguishing epithelioid mesotheliomas from metastatic carcinomas to the serosal membranes.
TL;DR: The approach recommended for making a confident diagnosis of MF and its clinically significant variants is summarized; pitfalls in evaluating early MF, assessing nodal involvement, and diagnosing transformed MF are emphasized; the relationship between MF and primary cutaneous CD30+ T-cell lymphoproliferative disorders is discussed; and Sézary syndrome is discussed.
Abstract: Session 1 of the 2011 Workshop of the Society for Hematopathology and European Association for Haematopathology focused on mycosis fungoides (MF), the most common cutaneous lymphoma. The 62 cases in this case group demonstrated a wide spectrum of clinicopathologic features, including those seen in typical cases as well as those, by contrast, with atypical clinical history, morphology, immunophenotype, and/or genotype. Of the 62 cases, 27 (44%) were presented at the workshop and highlighted diagnostic challenges plus related issues. This report summarizes the approach recommended for making a confident diagnosis of MF and its clinically significant variants; emphasizes pitfalls in evaluating early MF, assessing nodal involvement, and diagnosing transformed MF; and discusses the relationship between MF and primary cutaneous CD30+ T-cell lymphoproliferative disorders. Last, Sezary syndrome is discussed, with concentration on those features distinct from MF.
TL;DR: The necessity to integrate histologic, immunophenotypical, genetic, and in particular, clinical data to arrive at the correct diagnosis, and subsequently provide adequate treatment, is emphasized.
Abstract: Primary cutaneous T-cell lymphomas (CTCL) excluding mycosis fungoides (MF) were discussed in 2 sessions of the 2011 Society for Hematopathology/ European Association of Haematopathology Workshop, Los Angeles, CA. Session 2 focused on primary cutaneous CD30+ T-cell lymphoproliferative disorders and their differential diagnosis, including systemic CD30+ T-cell lymphoma secondarily infiltrating the skin. Interesting features like special morphologic variants and atypical phenotypes were presented. In addition, the possibility of rare ALK+ primary cutaneous lymphomas was discussed. Session 3 examined other more uncommon non-MF CTCLs, including subcutaneous panniculitis-like T-cell lymphoma, extranodal NK/T-cell lymphoma, hydroa vacciniforme-like T-cell lymphoma, and rare subtypes of primary cutaneous peripheral T-cell lymphoma, not otherwise specified. In addition, systemic T-cell lymphomas involving the skin secondarily, such as angioimmunoblastic T-cell lymphoma, were included in this session. In this report, novel findings, areas of special interest, and diagnostic challenges emerging from the cases submitted to the workshop will be highlighted. The necessity to integrate histologic, immunophenotypical, genetic, and in particular, clinical data to arrive at the correct diagnosis, and subsequently provide adequate treatment, is emphasized.
TL;DR: The low diagnostic accuracy of histopatho-logic and cytopathologic examination of Aspergillus species (spp) indicates that several fungal organisms can morphologically mimic Asper gillus and can only be distinguished by fungal culture and DNA sequencing.
Abstract: To assess the diagnostic accuracy of histopatho-logic and cytopathologic examination (HCE) of Aspergillus species (spp), we performed an 11-year retrospective review to correlate surgical/cytology cases with a diagnosis of Aspergillus spp with their concurrent fungal culture results. Diagnostic accuracy was defined as the percentage of cases with culture-proven Aspergillus spp divided by the number of cases diagnosed as Aspergillus spp on HCE that had growth on fungal culture. Ninety surgical/cytology cases with concurrent fungal culture were reviewed, 58 of which grew a fungal organism. Of these 58 cases, 45 grew an Aspergillus spp, whereas 13 grew an organism other than Aspergillus spp, including both common (Scedosporium, Fusarium, and Paecilomyces spp) and uncommon mimickers (Trichosporon loubieri), resulting in a diagnostic accuracy of 78%. The low diagnostic accuracy indicates that several fungal organisms can morphologically mimic Aspergillus spp and can only be distinguished by fungal culture and DNA sequencing.
TL;DR: CK5, TTF1, and napsin A are sensitive markers for squamous cell carcinoma and adenocarcinoma of the lung.
Abstract: Objectives: To assess immunohistochemical (IHC) stains differentially expressed between different types of lung cancer. Methods: We evaluated 16 different IHC stains in 209 prospectively included, surgically treated primary lung cancers, including 121 adenocarcinomas, 65 squamous cell carcinomas, 15 large-cell carcinomas, 5 adenosquamous carcinomas, 2 sarcomatoid carcinomas, and 1 small-cell carcinoma, using the tissue microarray technique. Results: Cytokeratin 5 (CK5) and P63 were both positive in 10% or more of the cells in 97% of the squamous cell carcinomas, with the former being positive (<10% of the cells) in only 2 non-squamous cell carcinomas. Thyroid transcription factor 1 (TTF1) and napsin A were positive in 10% or more of the cells in 88% and 87% of the adenocarcinomas, respectively, with 94% of the adenocarcinomas being positive in at least 1 marker. Fifteen percent of the adenocarcinomas were positive for estrogen receptor. Conclusions: CK5, TTF1, and napsin A are sensitive markers for squamous cell carcinoma and adenocarcinoma of the lung. (Less)
TL;DR: The clinicopathologic characteristics of PD were closely associated with those of microsatellite instability, and the outcomes of MSI-PD tumors were better than those of MSS- PD tumors, but this finding did not reach statistical significance.
Abstract: Objectives: To evaluate the association of microsatellite instability (MSI) with clinicopathologic features and oncologic outcomes in patients with poorly differentiated colorectal cancer (PD).
Methods: Study patients were divided into well-differentiated colorectal cancer (WD) and PD, which were compared according to histologic differentiation and MSI status.
Results: Among 1,941 patients, PD was more frequent among microsatellite-unstable tumors (23.6%) than among microsatellite-stable (MSS) tumors (4.2%, P < .001). Patients with PD had worse 4-year overall survival rates than patients with WD (78.6% vs 88.2%, P = 0.010). Compared with MSS-PD tumors, MSI-PD tumors were characterized by right-colon predilection, larger size, and infrequent lymph node metastasis ( P < .001 to P = .007).
Conclusions: The clinicopathologic characteristics of PD were closely associated with those of MSI. The outcomes of MSI-PD tumors were better than those of MSS-PD tumors, but this finding did not reach statistical significance.
TL;DR: Intermethod variability in 25(OH)D assays continues to limit progress toward the establishment of reference values for 25( OH)D in health and the efforts to gain a better understanding of the role of vitamin D insufficiency as a risk factor for disease.
Abstract: Objectives: To compare total 25-hydroxyvitamin D [25(OH) D] results measured by 3 direct immunoassays, including the previous version of the DiaSorin Liaison2 assay and the current versions of the Siemens Centaur2 and the Abbott Architect assays, with results measured in serum extracts by liquid chromatography/tandem mass spectrometry (LC/MS) and radioimmunoassay (RIA).
Methods: Our study sample consisted of 163 consecutive clinical specimens submitted to our laboratory for 25(OH)D testing.
Results: Regression and bias analyses of the data revealed that results measured by the 3 direct immunoassay methods had high degrees of random variability and bias relative to the results determined by LC/MS and RIA. The relative biases between results measured by the direct assays and the comparison methods exceeded a recommended criterion for the total allowable error of a 25(OH)D test in as many as 48% of our clinical specimens. Of the subjects in our study sample, 33, 37, 30, 45, and 71 were classified as vitamin D deficient based on results determined by LC/MS, RIA, Liaison2, Architect, and Centaur2, respectively.
Conclusions: Intermethod variability in 25(OH)D assays continues to limit our progress toward the establishment of reference values for 25(OH)D in health and our efforts to gain a better understanding of the role of vitamin D insufficiency as a risk factor for disease.
TL;DR: Although not entirely specific, MYD88 L265P is a useful adjunct for bone marrow diagnosis in separating LPL from other small B-cell lymphomas and plasma cell myeloma.
Abstract: Objectives: To examine the usefulness of the MYD88 L265P somatic mutation in identifying cases of lymphoplasmacytic lymphoma (LPL) from other lymphoplasmacytic neoplasms in bone marrow biopsy specimens.
Methods: We studied 64 bone marrow biopsy specimens with involvement by various small B-cell lymphomas or plasma cell myeloma.
Results: The MYD88 L265P somatic mutation was present in 13/13 cases of LPL, 1/13 cases of hairy cell leukemia, and absent in the other mature B-cell neoplasms tested. A test set of diagnostically challenging bone marrow cases with lymphoplasmacytoid morphology (B-cell lymphoma, not otherwise specified) was selected for additional review and reclassified, without knowledge of the MYD88 L265P status. Of those 16 cases, 7 were positive for MYD88 , including 4/4 cases that were reclassified as LPL during the review.
Conclusions: Although not entirely specific, MYD88 L265P is a useful adjunct for bone marrow diagnosis in separating LPL from other small B-cell lymphomas and plasma cell myeloma.
TL;DR: In this article, the authors report a patient with primary effusion lymphoma who was negative for human herpesvirus-8 (HHV-8), human immunodeficiency virus, Epstein-Barr virus, hepatitis C virus, and hepatitis B virus.
Abstract: OBJECTIVES: To report a patient with primary effusion lymphoma who was negative for human herpesvirus-8 (HHV-8), human immunodeficiency virus, Epstein-Barr virus, hepatitis C virus, and hepatitis B virus, as well as review 54 reported cases of HHV-8-unrelated primary effusion lymphoma (PEL)-like lymphoma in the literature to clarify the nature of this entity. METHODS: The patients' characteristics, clinical presentation, pathogenesis, morphologic-immunophenotypic features, clinical management, and prognosis were studied. RESULTS: HHV-8-negative PEL-like lymphomas often occur in immunocompetent and elderly patients, are sometimes associated with chronic inflammation-related fluid overload, are mostly large B-cell or large B-cell with plasmacytic differentiation type, and are associated with a better prognosis. CONCLUSIONS: In various aspects, HHV-8-unrelated PEL-like lymphoma is a different entity from HHV-8-related PEL. Immunophenotype, morphology, and c-myc/8q24 status should be included for differential diagnosis. A test for c-myc or 8q24 abnormalities should be recommended for subdividing HHV-8-unrelated PEL-like lymphoma, which may have benefits in patient management.
TL;DR: The size of the largest LA best reflects the specific characteristics of CLR, and the 1-mm rule is expected to improve assessment reproducibility.
Abstract: We aimed to determine semiquantitative evaluation criteria for Crohn-like lymphoid reaction (CLR). We reviewed 1,032 patients with colorectal cancer and evaluated CLR by counting all peritumoral lymphoid aggregates (LAs) and by measuring the maximum diameter of the largest LA. The maximum diameter of the largest LA, rather than the number, had a significant impact on survival. Active CLR determined by the 1-mm rule was significantly associated with MLH1/MSH2 immunohistochemical staining deficiency. The group with LAs 1 mm or larger had lower recurrence (P = .0008) and a higher survival rate (P < .0001) than that without LAs 1 mm or larger. These results were similarly observed in another cohort of 500 patients with colorectal cancer. The k values for CLR evaluation among 8 observers were 0.67 for the 1-mm rule and 0.50 for Graham’s criteria. The size of the largest LA best reflects the specific characteristics of CLR, and the 1-mm rule is expected to improve assessment reproducibility.
TL;DR: The XN increases the sensitivity of abnormal cell detection compared with the other counters, permitting a seven-part differential between predefined levels, decreasing the slide review from 20% to 9%.
Abstract: Objectives To compare two hematological analyzers—the DxH-800 (DxH; Beckman-Coulter, Miami, FL) and XN-2000 (XN; Sysmex, Kobe, Japan)—with the Cell-Dyn Sapphire (SAPH; Abbott, Santa Clara, CA)
Methods We analyzed 4,375 samples Slide reviews were made in the presence of blast, abnormal lymphocyte, and immature granulocyte (IG) flags or nucleated RBC (NRBC) count
Results The analyzers exhibited excellent correlations for CBC and neutrophils but displayed a limit correlation for lymphocytes The XN did not miss circulating blasts (05%–95% in microscopy) For NRBCs, the XN demonstrated a sensitivity of 90%; DxH, 74%; and SAPH, 29% Only the XN demonstrated a correlation with microscopy, permitting a WBC six-part differential until 15% of NRBCs The XN and DxH gave useful IG counts with a cutoff less than 5% and a WBC level more than 2,500/mm3 For abnormal lymphocytes detection, only XN demonstrated sensitivity of more than 95%, but its specificity of 54% requires adaptation
Conclusion The XN increases the sensitivity of abnormal cell detection compared with the other counters, permitting a seven-part differential between predefined levels, decreasing the slide review from 20% to 9%
TL;DR: Needle-core biopsy is an effective technique for the diagnosis of lymphoma and should be considered the first-line procedure for cases with suspicion for lymphoma.
Abstract: Objectives: To evaluate the role of needle-core biopsy in the pathologic diagnosis of lymphoma.
Methods: One hundred and five cases with clinical suspicion for lymphoma were studied by 3 hematopathologists mimicking daily diagnostic service. The diagnostic result sheets were analyzed for diagnostic accuracy and reproducibility. The histologic pattern recognition by the 3 hematopathologists was also analyzed.
Results: The overall diagnostic accuracy, based on the consensus diagnosis, was 85% to 87%. High reproducibility of diagnosis in lymphoma was observed among pathologists. The tissue size was associated with the percentage of definitive diagnosis. Histologic patterns were well recognized on core tissues.
Conclusions: Needle-core biopsy is an effective technique for the diagnosis of lymphoma and should be considered the first-line procedure for cases with suspicion for lymphoma.
TL;DR: The new PLT-F method demonstrated excellent results for reproducibility in samples with platelet counts less than 50 × 10(9)/L and could be helpful in making better decisions for platelet transfusions.
Abstract: Objectives: In thrombocytopenia, high accuracy and precision of low platelet count is essential for appropriate decisions. The recently introduced Sysmex XN2000 analyzer (Sysmex, Kobe, Japan) offers 3 methods for platelet counting: impedance (PLT-I), optical (PLT-O), and a new fluorescence method (PLT-F). The precision of the PLT-F method in blood samples with platelet counts less than 50 ×103/μL (50 × 109/L) was investigated and compared with the ICSH CD61-ImmunoPLT reference method. For comparison, PLT-I and PLT-O were determined on the Sysmex XN2000 and Sysmex XE2100 analyzer.
Methods: Blood samples with platelet counts less than 50 ×103/μL (50 × 109/L) (n = 37) were analyzed on the Sysmex XN2000 and XE2100 analyzers. The CD61-ImmunoPLT method was performed on a Beckman Coulter FC-500 flow cytometer (Miami, FL).
Results: At a platelet count of 20 ×103/μL (20 × 109/L), reproducibility for PLT-I, PLT-O, and PLT-F on the XN2000 demonstrated coefficients of variation of 9.3%, 8.5%, and 3.0%, respectively. Correlation between PLT-O on the XN2000 and XE2100 yielded an r value of more than 0.977. Linear regression analysis between the PLT-F and CD61-ImmunoPLT methods resulted in a PLT-F of 0.71*CD61 – 0.8 ( r = 0.988). Linear regression between PLT-F and PLT-O on the XN2000 resulted in a PLT-F of 1.05*PLT-O – 2 ( r = 0.975), and using the transfusion threshold of 20 × 109/L platelets resulted in a PLT-F of 0.90*PLT-O – 0.4 ( r = 0.956).
Conclusions: The new PLT-F method demonstrated excellent results for reproducibility in samples with platelet counts less than 50 × 109/L. PLT-F could be helpful in making better decisions for platelet transfusions.
TL;DR: The analytical performance and the clinical utility of a thyrotropin receptor (TSHR)-stimulating immunoglobulin (TSI) bioassay were compared with those of a TSHR-binding inhibitory immunoglobeulin (TBII) assay, and the dilution analysis provided similar predictive values of both assays in GD.
Abstract: The analytical performance and the clinical utility of a thyrotropin receptor (TSHR)-stimulating immunoglobulin (TSI) bioassay were compared with those of a TSHR-binding inhibitory immunoglobulin (TBII) assay. Limits of detection (LoD) and quantitation (LoQ), assay cutoff, and the half-maximal effective concentration (EC(50)) were measured. Dilution analysis was performed in sera of hyperthyroid patients with Graves disease (GD) during antithyroid treatment (ATD). Titer was defined as the first dilution step at which measurement of TSI or TBII fell below the assay cutoff. The LoD, LoQ, cutoff, and EC(50) of the bioassay were 251-, 298-, 814-, and 827-fold lower than for the TBII assay. There were 22%, 42%, 23%, and 14% more positive samples in the TSI bioassay at dilutions of 1:3, 1:9, 1:27, and 1:81 (P < .0001), respectively. Responders to ATD demonstrated marked differences in titers compared with nonresponders. The bioassay detected lower levels of TSHR autoantibodies, and the dilution analysis provided similar predictive values of both assays in GD.
TL;DR: In 2008, the University of Michigan Health System (UMHS) created a Laboratory Test Utilization Program that included the establishment of a Laboratory Formulary Committee under the imprimatur of the Faculty Group Practice, the Office of Clinical Affairs, the Department of Pathology, and UMHS hospital administration as mentioned in this paper.
Abstract: In 2008, the University of Michigan Health System (UMHS) created a Laboratory Test Utilization Program that included the establishment of a Laboratory Formulary Committee under the imprimatur of the Faculty Group Practice, the Office of Clinical Affairs, the Department of Pathology, and UMHS hospital administration. A critical component of the program is UM-CareLink, an order entry system for inpatients and inpatient-like venues. UM-CareLink allows very basic decision support comment prompts. Through the application of peer-reviewed medical evidence, input by medical content experts, excellent cooperation by medical staff, and close oversight by Pathology of the Sendout Laboratory, this program has led to a robust process of test utilization oversight, excellent communication with clinical services, and significant UMHS activity-adjusted reductions in laboratory expense.
TL;DR: This article reviews features observed in cutaneous lymphoid hyperplasia, cutaneous drug reactions, lupus-associated panniculitis, pityriasis lichenoides, hypereosinophilic syndrome, histiocytic necrotizing lymphadenitis, traumatic ulcerative granuloma with stromal eOSinophils, and pigmented purpuric dermatosis.
Abstract: The Society for Hematopathology and European Association for Haematopathology workshop, from October 27 to 29, 2011, in Los Angeles, CA, exhibited many exemplary skin biopsy specimens with interesting inflammatory changes mimicking features of cutaneous lymphoma. This article reviews features observed in cutaneous lymphoid hyperplasia, cutaneous drug reactions, lupus-associated panniculitis, pityriasis lichenoides, hypereosinophilic syndrome, histiocytic necrotizing lymphadenitis, traumatic ulcerative granuloma with stromal eosinophils, and pigmented purpuric dermatosis, as well as a brief review of the pertinent literature and discussion of submitted conference cases. For the pathologist, it is important to be aware of diagnostic pitfalls as well as the limitations of ancillary testing (eg, clonality studies). Finally, correlation with total clinical information, good communication with clinical colleagues, close clinical follow-up with rebiopsy, and prudent use of laboratory studies are vital and will likely offer the best path toward a correct diagnosis.
TL;DR: It is important to remember that many other B-cell lymphomas/ plasma cell neoplasms can primarily, or more often secondarily, involve the skin, including cases also known as EBV-positive mucocutaneous ulcer.
Abstract: The diagnosis and classification of the cutaneous B-cell lymphomas can be quite a challenge, with a definitive diagnosis sometimes being elusive, even when an extensive workup has been performed. Distinction of benign from neoplastic disorders can be difficult, with some hyperplasias mimicking lymphomas and vice versa. There are only a limited number of skin-specific B-cell lymphomas, including primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type. Cutaneous marginal zone lymphomas have distinctive features but are classified with the other mucosa-associated lymphoid tissue lymphomas. It is important, however, to also remember that many other B-cell lymphomas/ plasma cell neoplasms can primarily, or more often secondarily, involve the skin. Some may mimic one of the skin-specific lymphomas but have very different clinical implications. Iatrogenic and senescent immunodeficiency-associated lymphoproliferative disorders that are often Epstein-Barr virus (EBV) positive can also primarily involve the skin, including cases also known as EBV-positive mucocutaneous ulcer.