Lymphomatoid Granulomatosis in a Patient with Chronic Lymphocytic Leukemia and Rapidly Progressing Peribronchovascular Pulmonary Infiltrates.

Lymphomatoid granulomatosis (LG) is an EBV-associated angiodestructive lymphoproliferative disease with multiorgan involvement that predominantly affects the lungs. We present a case of a 72-year-old man with a history of chronic lymphocytic leukemia who presented with upper respiratory symptoms and multiple erythematous skin papules. Chest CT showed ill-defined, irregular solid pulmonary nodules with peripheral ground-glass opacities in a peribronchovascular distribution. The differential for this pattern of lung disease is vast which includes but is not limited to infection, vasculitis, sarcoidosis, lymphoma, and Kaposi sarcoma. Subsequent PET/CT showed rapid progression of lung opacities and marked FDG uptake of pulmonary opacities and skin nodules, which raised the question of Richter syndrome. Wedge biopsy under video-assisted thoracoscopic surgery was performed. Pathology showed an extensive lymphoid infiltrate involving lymphatic and bronchovascular bundles and consisting of a mixture of large lymphocytes and inflammatory cells. Special stains showed that the large lymphocytes expressed B-cell markers and EBV virus. Overall, the findings were consistent with LG.

Bcl-2 maturation pattern in T-cells distinguishes thymic neoplasm/hyperplasia, T-lymphoblastic lymphoma, and reactive lymph nodes.

Anterior mediastinal biopsies consisting predominantly of small lymphocytes can be a diagnostic challenge, especially in small core biopsies. In these cases, immunophenotyping is often employed using flow cytometry, and/or immunohistochemistry. However, due the overlap in T-cell phenotype between thymic neoplasm/hyperplasia (THY), T-lymphoblastic lymphoma (T-LBL), and reactive lymph nodes (RLN), biopsies consisting predominantly of T-cells may still be difficult to differentiate. Previous studies have shown a specific CD3/bcl-2 staining pattern in thymic T cells of humans and mice using flow cytometry. However, the utility of this finding in distinguishing T-cells of THY, T-LBL, and RLN has not been carefully evaluated. Our findings show that the pattern of CD3/bcl-2 expression in thymic T-cells can be used to help diagnose anterior mediastinal biopsies, even when limited specimen is provided. © 2017 International Clinical Cytometry Society.

Quality Improvement in the Coagulation Laboratory: Reducing the Number of Insufficient Blood Draw Specimens for Coagulation Testing.

OBJECTIVES: To report the efforts of our laboratory to reduce quantity-not-sufficient (QNS) specimens via several methods and to directly measure the effect of expired collection tubes on the amount of blood that can be drawn. METHODS: We tracked the number of QNS venous-blood specimens per month received by our coagulation laboratory from March 2008 to December 2012. Interventions involved communications that informed nurses and phlebotomists how to avoid drawing QNS specimens and floor sweeps, in which laboratory staff searched for and removed expired vacuum-based blood-collection tubes (VBCTs) from inpatient hospital floors. Also, we assessed 11 healthy donors to determine the amount of blood that could be drawn into expired VBCTs. RESULTS: During the study period, the rate of QNS specimens dropped from a mean of 0.7% to 0.3%. In expired VBCTs collected from healthy donors, we observed a statistically significant difference in the amount of blood drawn into nonexpired vs expired VBCTs (P <.001). Also, there was a negative relationship between the number of months that the VBCT had been expired and the amount of blood that could be drawn into the VBCTs (P <.001). For every month that VBCTs were expired, the amount of blood drawn decreased by approximately 1.8 mm (0.1 mL), using linear regression analysis. CONCLUSION: Our evidence strongly suggests that expired VBCTs consistently and progressively yield QNS specimens. Methods to reduce blood draws from expired VBCTs may include communications promoting proper blood draw technique, floor sweeps to remove expired VBCTs, and improved inventory management.

External quality assurance of fibrinogen assays using normal plasma: results of the 2008 College of American Pathologists proficiency testing program in coagulation.

CONTEXT: Proper diagnosis and therapy of fibrinogen deficiency requires high-quality fibrinogen assays. OBJECTIVE: To assess the interlaboratory bias, precision, and grading of fibrinogen assays used by laboratories participating in the United States College of American Pathologists proficiency testing program in coagulation. DESIGN: Two identical vials of normal plasma were sent to more than 3500 laboratories. Participants measured fibrinogen levels using local methods. RESULTS: Fifty different fibrinogen methods were evaluated. All-method bias was 8.3% (range of method-specific biases, 0.0%-27.0%) and all-method coefficient of variation was 7.7% (range of method-specific coefficients of variation, 0.7%-25.8%). After controlling for reagent/instrument type, mean fibrinogen levels were 11.6% higher for prothrombin time-based reagents compared to Clauss (P < .001), and coefficient of variation was 46% lower for mechanical endpoint instruments compared to photo-optical. Most testing events (97.4%) could be reliably graded as pass or fail using a target range of ±20% from the method mean (total pass rate, 98.8%). Total fail rate was 3.0-fold lower for mechanical instruments compared to photo-optical (0.5% versus 1.5%, P  =  .001). Nonetheless many photo-optical methods had very high precision and very low fail rates. CONCLUSIONS: Fibrinogen assays showed highly variable methodology and performance characteristics. Bias, precision, and grading were affected by the type of reagent or instrument used.

External quality assurance of antithrombin, protein C, and protein s assays: results of the College of American Pathologists proficiency testing program in thrombophilia.

CONTEXT: Hereditary and acquired deficiencies of antithrombin (AT), protein C (PC), and protein S (PS) are risk factors for venous thromboembolism. Proper diagnosis requires high-quality assays for these proteins. OBJECTIVE: To determine the accuracy and interlaboratory precision of AT, PC, and PS assays used by laboratories participating in the United States College of American Pathologists proficiency testing program in thrombophilia and to grade the performance of laboratories. DESIGN: Standardized normal plasma with assigned analyte values was sent in 2 separate challenges to participating laboratories. Participants measured AT, PC, and PS levels using local methods. RESULTS: When compared with the assigned values for the international standard, the order of assay accuracy from highest to lowest was AT activity, PC antigen, AT antigen, total PS antigen, PC activity, PS activity, and free PS antigen (range of assay bias, 2.6%-8.8%). The order of assay precision from highest to lowest was PC activity, AT activity, AT antigen, total PS antigen, PS activity, free PS antigen, and PC antigen (range of assay coefficient of variation, 6.1%-20.0%). Most testing events (87.8%) could be graded as pass or fail using a target range of ±3 standard deviations from the method-specific mean. The pass rate was 98.2% for all AT, PC, and PS testing events combined. CONCLUSIONS: Accuracy and precision were higher for AT assays and lower for PC and PS assays. It was feasible to grade individual laboratory performance.

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Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma.

The classification of primary cutaneous large B-cell lymphoma (PCLBCL) is based on standard morphology, immunohistochemistry, and clinical presentation. There are two major subtypes in the current WHO-EORTC classification: follicle center lymphoma and diffuse large B-cell lymphoma, leg-type (DLBCL-LT). The goals of this study were to examine a series of DLBCLs to determine (1) whether the immunohistochemical paradigm of germinal center B-cell and non-germinal center B-cell types of systemic DLBCL could be applied to PCLBCL; (2) whether application of the newly described germinal center B-cell marker, human germinal center-associated lymphoma (HGAL) also discriminates between these types as a further support for germinal center B-cell origin for primary cutaneous center lymphoma; and (3) whether any of these biologic markers were of prognostic significance. To this end, 32 cases of diffuse PCLBCL (22 primary cutaneous follicular center lymphomas and 10 DLBCL-LT) were classified based on the WHO-EORTC criteria and studied for expression of CD20, BCL2, BCL6, CD10, MUM-1, and HGAL by immunohistochemistry. Results were correlated with clinical features. HGAL and BCL6 expression and germinal center B-cell phenotype were associated with primary cutaneous follicular center lymphoma. The combination of HGAL and BCL6 positivity had the highest sensitivity (88%) and specificity (100%) for predicting subtype compared to either marker alone. Both HGAL and BCL6 were associated with the germinal center B-cell phenotype. The correlation of HGAL expression with the germinal center B-cell phenotype demonstrates the role of this marker in the classification of cutaneous large B-cell lymphomas. BCL6 expression was the only immunohistochemical marker associated with overall survival. Characterizing PCLBCLs with markers of B-cell maturation stage is a useful framework for studying, classifying, and clinically stratifying these lymphomas.

Detection of T-regulatory cells has a potential role in the diagnosis of classical Hodgkin lymphoma.

Previous studies have demonstrated an increase in T-regulatory cells in the involved lymph nodes and peripheral blood of patients with Hodgkin lymphoma. Our study examined whether the detection of T-regulatory cells by flow cytometry could distinguish classical Hodgkin lymphoma (CHL) from benign cases and B-cell non-Hodgkin lymphomas (B-NHL). We measured CD4, CD25, and CD152 in 14 CHLs, 2 nodular lymphocyte-predominant Hodgkin lymphomas, 31 B-NHLs, and 54 benign cases. All T-regulatory cell parameters, including percent lymphocytes CD4+/CD152+ and CD4+/CD25+/CD152+, and mean and median CD152 expression in CD4+/CD25+ lymphocytes, were higher in CHL than in B-NHL and benign. Mean CD152 in CD4+/CD25+ lymphocytes distinguished CHL from benign with 79% sensitivity and 100% specificity, and from B-NHL with 71% sensitivity and 90% specificity. Overall, our results show that T-regulatory cells are increased in CHL and their detection may be a useful tool in differentiating CHL from other entities.

Case report: mantle cell lymphoma, prolymphocytoid variant, with leukostasis syndrome.

A 76-year-old man presented with leukostasis syndrome, including oculodynia, blurred vision, and visual field defects, due to mantle cell lymphoma, prolymphocytoid variant, with marked leukocytosis, 1227 x 10(9)/l. He had splenomegaly but no lymphadenopathy or hepatomegaly. The tumor cells were CD5+, CD19+, CD20+, FMC-7+, and kappa light chain restricted. Immunohistochemistry showed expression of p53 and of cyclin D1. Fluorescent in situ hybridization demonstrated t(11;14) with translocation between CYCLIN D1 and the immunoglobulin heavy-chain genes. The patient received leukapheresis and aggressive chemotherapy, but the leukocyte count remained above 100 x 10(9)/l. The patient's condition rapidly deteriorated with lymphomatous infiltration of his lungs and soft tissues, and he expired 6 months after diagnosis. While it is known that mantle cell lymphoma may have a leukemic phase, the degree of leukocytosis in this case exceeds that previously reported in the literature and resulted in a clinical syndrome of leukostasis.

Typical histologic features of Tunga penetrans in skin biopsies.

CONTEXT: Tunga penetrans is a flea that burrows into human skin, causing the disease tungiasis. Although the parasite is not endemic in the United States, patients may present with this disease upon returning from tropical locales. Histologic sections contain a variety of flea parts that may present a diagnostic dilemma for pathologists unfamiliar with this disease. OBJECTIVE: To determine the typical histologic features of T penetrans in biopsies from patients with tungiasis. METHODS: We reviewed biopsy specimens from 7 patients with tungiasis and sought 8 distinct structures: the exoskeleton, hypodermal layer, respiratory tract (tracheae), digestive tract, striated muscle, head, posterior end, and developing eggs. RESULTS: The exoskeleton, hypodermal layer, tracheae, digestive tract, and developing eggs were present in all biopsy specimens reviewed. Striated muscle, the posterior end, and head, however, were present in 57%, 43%, and 0% of the biopsies, respectively. In addition, we noted a unique, pale-staining layer in the exoskeleton at the posterior end of the organism that, to the best of our knowledge, has not previously been described and that may be of diagnostic value. CONCLUSIONS: Despite the absence of 3 key morphologic features in many (posterior end and striated muscle) or all (head) of our biopsies, the exoskeleton with a hypodermal layer, tracheae, and developing eggs were uniformly present, and together these features are sufficient for a diagnosis of tungiasis.