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Publications in this journal

• Molecular testing in colorectal cancer: diagnosis of lynch syndrome and personalized cancer medicine.

  Authors: Chanjuan Shi, Kay Washington

  American journal of clinical pathology. 137(6):847-59.

  Currently, molecular testing in colorectal cancer (CRC) is aimed at detecting Lynch syndrome and predicting response to anti-epidermal growth factor receptor (EGFR) therapies. However, CRC is aCurrently, molecular testing in colorectal cancer (CRC) is aimed at detecting Lynch syndrome and predicting response to anti-epidermal growth factor receptor (EGFR) therapies. However, CRC is a complex disease, with at least 3 molecular pathways of carcinogenesis. The importance of the EGFR signaling pathway in colorectal carcinogenesis is underscored by the availability of anti-EGFR monoclonal antibodies for the treatment of some metastatic CRCs. Potentially, mutations in any of the genes in the EGFR signaling pathway may be associated with prognosis and may predict response to anti-EGFR or other targeted therapies. Although not currently the standard of care, molecular testing of CRCs is expanding to include mutational analysis of the genes in the EGFR pathway, in addition to more widely performed tests for identifying cancers with high microsatellite instability. Multiplex molecular prognostic panels for therapeutic decision making in stage II CRCs also represent expanding use of molecular testing for this common cancer.

• Assessment of bone marrow fibrosis and angiogenesis in monitoring patients with multiple myeloma.

  Authors: Emina Babarovic, Toni Valkovic, Sanja Stifter, Ivana Budisavljevic, Irena Seili-Bekafigo, Antica Duletic-Nacinovic, Ksenija Lucin, Nives Jonjic

  American journal of clinical pathology. 137(6):870-8.

  The aim of our study was to emphasize the importance of accurate and standardized techniques for detailed monitoring of the microenvironment in multiple myeloma (MM). Bone marrow fibrosis,The aim of our study was to emphasize the importance of accurate and standardized techniques for detailed monitoring of the microenvironment in multiple myeloma (MM). Bone marrow fibrosis, angiogenesis, and plasma cell infiltrates in bone marrow biopsy (BMB) samples at the time of diagnosis and on completion of therapy were analyzed for 42 patients with newly diagnosed MM. Computerized image analysis was used for all slides stained with anti-CD138 and anti-CD34. The patients with fibrosis in pretreatment BMB samples had significantly higher microvessel density (MVD) and plasma cell infiltrates. In posttreatment BMB samples, nonresponders had a significantly higher frequency and grade of fibrosis and higher values of MVD, total vascular area, and plasma cell percentage. The overall survival of nonresponders and patients with increased marrow fibrosis in posttreatment BMB samples was significantly shorter. The obtained results confirm that complex morphologic examination of the bone marrow microenvironment during the monitoring of MM can provide better prognostic significance.

• Extended use of serum free light chain as a biomarker in lymphoproliferative disorders: a comprehensive review.

  Authors: Khalil M Charafeddine, Mark N Jabbour, Raneem H Kadi, Rose T Daher

  American journal of clinical pathology. 137(6):890-7.

  Serum free light chain (sFLC) assays were shown to improve detection, management, and prognostication in plasma cell disorders. Recently, sFLC assays improved detection of M proteins when combinedSerum free light chain (sFLC) assays were shown to improve detection, management, and prognostication in plasma cell disorders. Recently, sFLC assays improved detection of M proteins when combined with standard methods of protein electrophoresis/immunofixation in patients with non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL). Incidence of abnormal sFLC ratio (sFLCr) varied from 0% to 36% and 29.7% to 59% in NHL and CLL, respectively. Increased sFLC levels or abnormal sFLCr predict shorter overall survival in early-stage CLL. Furthermore, abnormal sFLCr correlated with advanced disease stage and poorer outcome. In diffuse large B-cell lymphomas, increased sFLC was demonstrated as an independent, adverse prognostic factor for overall/event-free survival. Moreover, abnormal sFLCr can be a diagnostic tool in central nervous system lymphomas. Finally, the quantitative FLC assay has the potential to become a new, easily measured biomarker for predicting prognosis and enhanced detection in NHL/CLL. It may be used serially at follow-up evaluations to provide clues to relapse.

• Recommendations for appropriate activated partial thromboplastin time reagent selection and utilization.

  Authors: George A Fritsma, Francine R Dembitzer, Ankush Randhawa, Marisa B Marques, Elizabeth M Van Cott, Dorothy Adcock-Funk, Ellinor I Peerschke

  American journal of clinical pathology. 137(6):904-8.

  The activated partial thromboplastin time (aPTT) is widely used as a screening coagulation test and for monitoring unfractionated heparin therapy. Various commercial reagents are available, withThe activated partial thromboplastin time (aPTT) is widely used as a screening coagulation test and for monitoring unfractionated heparin therapy. Various commercial reagents are available, with different performance characteristics, particularly responsiveness to the lupus anticoagulant (LA). Because aPTT reagent selection significantly affects the interpretation of results, we reviewed College of American Pathologists proficiency testing data involving approximately 4,000 coagulation laboratories, and conducted a survey of coagulation laboratories (n = 93) using The Fritsma Factor hemostasis Web site to determine the basis for aPTT reagent selection. The data demonstrate that for routine aPTT testing, most laboratories use reagents with high/moderate responsiveness to LA. Significant misunderstanding was apparent regarding the use of appropriate aPTT reagent for routine testing and LA identification. We recommend aPTT reagents with low LA responsiveness to screen for coagulation factor deficiencies and heparin monitoring, and suggest continued education of laboratory professionals and reagent manufacturers about appropriate aPTT reagent use.

• A search for reliable molecular markers of prognosis in prostate cancer: a study of 240 cases.

  Authors: Alison Tradonsky, Tammy Rubin, Rodney Beck, Brian Ring, Robert Seitz, Sharon Mair

  American journal of clinical pathology. 137(6):918-30.

  Most prostate cancers are treated, although more than 80% remain clinically insignificant and fewer than 3% are fatal. This retrospective study of 240 radical prostatectomy cases with comprehensiveMost prostate cancers are treated, although more than 80% remain clinically insignificant and fewer than 3% are fatal. This retrospective study of 240 radical prostatectomy cases with comprehensive follow-up was a search for reliable markers of prostate cancer prognosis evaluable on biopsy specimens to enable minimization of unnecessary treatment, morbidity, and costs. Representative cancer and benign tissue from each prostatectomy specimen was made into tissue microarrays and stained with antibodies targeting 20 gene sequences. Traditional clinical and pathologic prognosticators and the 20 antibody stains were correlated with patient outcomes. By univariable analysis 4 of 20 antibodies (STMN1/stathmin 1, CYP4Z1/cytochrome p450-4z1, CDH1/E-cadherin, and Hey2), Gleason score, perineural invasion, and apical involvement were statistically significant outcome predictors for biopsy tissue. By multivariate analysis, Gleason score, Hey2, and CYP4Z1 were independently predictive. STMN1 and CDH1 were not independent of Gleason score but remain useful because marker interpretation is objective and Gleason scores often differ for biopsy and prostatectomy specimens.

• Differential Diagnostic Value of GPC3-CD34 Combined Staining in Small Liver Nodules With Diameter Less Than 3 cm.

  Authors: Fengmei Wang, Xiang Jing, Tao Wang, Ge Li, Tinghong Li, Qin Zhang, Yong Huang, Jun Li, Yijun Wang, Yingtang Gao, Tao Han, Zhi Du

  American journal of clinical pathology. 137(6):937-45.

  The diagnostic value of combining glypican-3 (GPC3) and CD34 staining for small nodules in liver biopsy specimens has not been evaluated. In this study, 201 thin-core biopsy specimens were assessedThe diagnostic value of combining glypican-3 (GPC3) and CD34 staining for small nodules in liver biopsy specimens has not been evaluated. In this study, 201 thin-core biopsy specimens were assessed using GPC3 and CD34 immunochemical staining, including 33 cirrhotic regenerative nodules, 31 high-grade dysplastic nodules, 70 hepatocellular carcinomas (HCCs) with nodules 3 cm or smaller, and 67 HCCs with nodules larger than 3 cm. The results showed that the accuracy of GPC3 staining (90.3%) among liver nodules 3 cm or smaller was better than its use among all nodules (P = .045). Furthermore, the positive expression rate of costaining was significantly greater than that observed for GPC3 or CD34 single staining (P < .001 and P = .002, respectively). These data demonstrate that GPC3 staining is more accurate for the diagnosis of HCC on thin-core biopsy specimens in nodules 3 cm or smaller compared with its use in all nodules, while GPC3 and CD34 costaining has better diagnostic value than does single staining.

• The dynamics of death in prostate cancer.

  Authors: Robin T Vollmer

  American journal of clinical pathology. 137(6):957-62.

  The hazard function provides the instantaneous probability of death (or other key end point) at various times after diagnosis. Unlike the survival curve, the hazard function illustrates graphicallyThe hazard function provides the instantaneous probability of death (or other key end point) at various times after diagnosis. Unlike the survival curve, the hazard function illustrates graphically or through calculations when deaths are common or uncommon. In this study, hazard functions were derived for prostate cancer by using survival data on large numbers of patients with prostate cancer with data in the Surveillance, Epidemiology and End Results (SEER) database. The results demonstrate a form of prostate cancer that rapidly evolves to cause death within 5 years, and this form of tumor is only partly identified by routine prognostic variables such as serum prostate-specific antigen (PSA) level, histologic grade, and quantity of tumor. The results also validate the presence of a reservoir of nonfatal prostate cancers that have increased rapidly during the PSA era, and they demonstrate that the incidence of fatal prostate cancers has declined.

• LMX1A as a Prognostic Marker in Ovarian Mucinous Cystadenocarcinoma.

  Authors: Chih-Kung Lin, Tai-Kuang Chao, Hung-Cheng Lai, Herng-Sheng Lee

  American journal of clinical pathology. 137(6):971-7.

  This study aimed to evaluate the relationship of LMX1A and osteopontin (OPN) expression with clinicopathologic parameters for the 4 most common ovarian surface epithelial carcinomas. Both biomarkersThis study aimed to evaluate the relationship of LMX1A and osteopontin (OPN) expression with clinicopathologic parameters for the 4 most common ovarian surface epithelial carcinomas. Both biomarkers were investigated immunohistochemically using tissue microarrays of 249 specimens including 91 serous cystadenocarcinomas, 56 mucinous cystadenocarcinomas, 64 endometrioid adenocarcinomas, 26 clear cell carcinomas, and 12 normal ovarian tissues. All 4 carcinomas showed significant expression of LMX1A and OPN. In addition, higher immunostaining scores and percentage of cells stained for LMX1A in mucinous cystadenocarcinomas correlated with T stage, American Joint Committee on Cancer clinical stage, poorer tumor differentiation, and poorer survival rate. In serous cystadenocarcinoma, higher percentage of staining for OPN and higher intensity or immunostaining scores for LMX1A correlated with poorer tumor differentiation. Thus, the expression of LMX1A may be an independent prognostic risk factor in mucinous cystadenocarcinoma and a helpful marker in evaluating this tumor's aggressiveness.

• Media review.

  Authors: Timothy Hilbert

  American journal of clinical pathology. 137(6):1011.

• Brain-to-Brain Turnaround Loop.

  Authors: Linda M Sandhaus

  American journal of clinical pathology. 137(6):1012-3.

• Absolute neutrophil counts from automated hematology instruments are accurate and precise even at very low levels.

  Authors: Erik K Amundsen, Petter Urdal, Tor-Arne Hagve, Mette R Holthe, Carola E Henriksson

  American journal of clinical pathology. 137(6):862-9.

  Using 106 samples from patients with an absolute neutrophil count (ANC) less than 2.0 × 10(9)/L, two 5-part differential hematology instruments (Sysmex XE-2100, Sysmex, Kobe, Japan, and Advia 2120i,Using 106 samples from patients with an absolute neutrophil count (ANC) less than 2.0 × 10(9)/L, two 5-part differential hematology instruments (Sysmex XE-2100, Sysmex, Kobe, Japan, and Advia 2120i, Siemens Healthcare Diagnostics, Deerfield, IL), two 3-part differential hematology instruments (Sysmex K4500, Sysmex, and Advia 60, Siemens Healthcare Diagnostics), and an automated system for examination of microscopic slides (CellaVision DM96, CellaVision, Lund, Sweden) were compared with a flow cytometric (FCM) neutrophil count using monoclonal antibodies for cell classification. The precision and accuracy of the 5-part differential instrument ANC was very good at more than 0.1 × 10(9)/L, although a small systematic difference (10.3%) was found between the 2 instruments. The ANC of the 3-part differential instruments was less reliable, but the WBC count correlated very well with the WBC count from the 5-part differential instruments. Also, the neutrophil count from the CellaVision DM96 compared very well with FCM. When used in the correct laboratory setting, all of the evaluated instruments provide ANCs and WBCs with adequate accuracy and precision.

• Clinicopathologic analysis of peripheral T-cell lymphoma, follicular variant, and comparison with angioimmunoblastic T-cell lymphoma: bcl-6 expression might affect progression between these disorders.

  Authors: Hiroaki Miyoshi, Kensaku Sato, Daisuke Niino, Fumiko Arakawa, Yoshizo Kimura, Junichi Kiyasu, Masanori Takeuchi, Maki Yoshida, Yosuke Okada, Yukihiko Nakamura, Yasuo Sugita, Koichi Ohshima

  American journal of clinical pathology. 137(6):879-89.

  We examined clinicopathologic findings in 17 cases of peripheral T-cell lymphoma, follicular variant (f-PTCL), and compared these findings with angioimmunoblastic T-cell lymphoma (AITL) to determineWe examined clinicopathologic findings in 17 cases of peripheral T-cell lymphoma, follicular variant (f-PTCL), and compared these findings with angioimmunoblastic T-cell lymphoma (AITL) to determine whether they were identical to the spectrum of changes seen in AITL and how each of the findings in f-PTCL were related to the characteristics of AITL. Almost all f-PTCL cases showed pathologic characteristics of AITL and immunohistochemical positivities in lymphoma cells for CD4, CD10, Bcl-6, PD-1, and CXCL13. Except for pathologic characteristics, clinicopathologic findings in f-PTCL had few significant differences from AITL. The positive rate for Bcl-6 expression in neoplastic cells was significantly associated with the frequency of polymorphic infiltrates, vascular proliferation, B-immunoblasts, clear cells, Epstein-Barr virus-positive lymphocytes, hepatosplenomegaly, and skin rash. Our study confirmed the continuity between f-PTCL and AITL. Moreover, Bcl-6 expression in f-PTCL was statistically associated with the characteristics of AITL.

• Effect of carryover of clot activators on coagulation tests during phlebotomy.

  Authors: Yoko Fukugawa, Hiroaki Ohnishi, Takahiro Ishii, Ayako Tanouchi, Junko Sano, Haruko Miyawaki, Tomonori Kishino, Kouki Ohtsuka, Hideaki Yoshino, Takashi Watanabe

  American journal of clinical pathology. 137(6):900-3.

  We investigated the effect of clot activators carried over from the serum tube on major coagulation tests during phlebotomy. First, blood specimens from 30 normal subjects were mixed with smallWe investigated the effect of clot activators carried over from the serum tube on major coagulation tests during phlebotomy. First, blood specimens from 30 normal subjects were mixed with small amounts of fluid containing clot activators, and their effects on various coagulation tests were determined. Only the value of fibrin monomer complex displayed a remarkable change when thrombin-containing fluid was added to the blood specimens. Subsequently, 100 paired blood specimens (taken from 75 healthy volunteers and 25 patients taking warfarin) were collected in coagulation tubes before and after the serum tube using standard phlebotomy procedures. Various coagulation tests were performed to determine the effect of contamination of thrombin-containing blood on coagulation parameters. Differences between the 2 tubes were minimal but significant for some of the coagulation tests. Therefore, we conclude that the effect of clot activators in the serum tube on coagulation tests is minimal when standard phlebotomy procedures are used.

• Protein C assay performance: an analysis of north american specialized coagulation laboratory association proficiency testing results.

  Authors: Jason M Baron, Stephen M Johnson, Marlies R Ledford-Kraemer, Catherine P Hayward, Piet Meijer, Elizabeth M Van Cott

  American journal of clinical pathology. 137(6):909-15.

  To determine the performance and frequency of protein C reagents currently used by clinical laboratories, we analyzed North American Specialized Coagulation Laboratory Association (NASCOLA) protein CTo determine the performance and frequency of protein C reagents currently used by clinical laboratories, we analyzed North American Specialized Coagulation Laboratory Association (NASCOLA) protein C proficiency testing data from 6 surveys conducted in 2009 and 2010 (2009-1 to 2009-3 and 2010-1 to 2010-3). Interlaboratory coefficients of variation (CV) for commonly used reagents on a survey with normal protein C ranged from 8% to 12% for antigenic assays, from 4% to 7% for chromogenic activity assays, and from 7% to 22% for clot-based activity assays. CVs for commonly used reagents on specimens with abnormal protein C ranged from 15% to 24% for antigenic, 4% to 11% for chromogenic, and 10% to 17% for clot-based assays (averaged across 3 surveys). Some reagents were used by relatively few laboratories and therefore additional study may be needed for those reagents. For all commonly used reagents, biases were usually small and often not statistically significant. All assessed reagents were clinically accurate, and were considered acceptable options for a specialized coagulation laboratory.

• Foxp3 expression patterns in microscopic colitides: a clinicopathologic study of 69 patients.

  Authors: Shuting Bai, Gene P Siegal, Nirag C Jhala

  American journal of clinical pathology. 137(6):931-6.

  Microscopic colitides, including lymphocytic (LC) and collagenous colitis (CC), are well-described pathologic conditions. An altered immune response is implicated in the pathogenesis of bothMicroscopic colitides, including lymphocytic (LC) and collagenous colitis (CC), are well-described pathologic conditions. An altered immune response is implicated in the pathogenesis of both entities. CD8+ T lymphocytes (CTLs) secrete interleukin 2 which stimulates proliferation of regulatory T cells (Tregs), and Tregs, in turn, inhibit CTLs, inducing cytotoxic tissue damage. In Tregs, Foxp3 regulates T-cell-related immune responses. The distribution of Tregs and CTLs in microscopic colitides has remained underexplored. To characterize differences in the distribution pattern of Foxp3 in biopsy specimens from patients with LC and CC, 71 colonic biopsy specimens from 69 consecutive patients were categorized into 1 of 3 diagnoses: no significant histopathologic abnormality (NSHPA), LC, or CC. Further immunohistochemical evaluation of all biopsy specimens was conducted using a panel of markers including CD8 and Foxp3. Our study demonstrated that CTL distribution pattern differences exist among these 2 colitides and that differences in the immunologic recruitment of Foxp3+ Tregs in the colonic mucosa correlate with differences in the spectrum of morphologic changes seen in patients with either LC or CC.

• Tissue-Sparing Application of the Newly Proposed IASLC/ATS/ERS Classification of Adenocarcinoma of the Lung Shows Practical Diagnostic and Prognostic Impact.

  Authors: William Sterlacci, Spasenija Savic, Thomas Schmid, Wilhelm Oberaigner, Jutta Auberger, Michael Fiegl, Alexandar Tzankov

  American journal of clinical pathology. 137(6):946-56.

  The histologic subtype of non-small cell lung cancer (NSCLC) determines treatment strategies and the need for genetic analyses. Since most NSCLC are diagnosed on small biopsy or cytologic specimens,The histologic subtype of non-small cell lung cancer (NSCLC) determines treatment strategies and the need for genetic analyses. Since most NSCLC are diagnosed on small biopsy or cytologic specimens, an accurate but tissue-sparing approach is necessary. To date, consensus for a general diagnostic algorithm is lacking. To test the diagnostic and clinical relevance of the recently published multidisciplinary guidelines by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society, we examined 371 surgically resected NSCLCs brought into tissue microarray format. The antibody panel thyroid transcription factor-1 (TTF-1), p63, cytokeratin (CK)5/6, and CK7 is diagnostic for most cases (>94%). Faint/focal staining for CK7 is negligible for classificatory purposes. Grading adenocarcinomas according to histologic architecture is prognostically significant (median overall survival for well/moderate differentiation, 72.5 months; for poor differentiation, 38.5 months; P = .019). Double stains combining the aforementioned nuclear and membranous markers are highly diagnostic for NSCLC, conserving tumor tissue for subsequent analyses.

• Solitary fibrous tumor: is there a molecular relationship with cellular angiofibroma, spindle cell lipoma, and mammary-type myofibroblastoma?

  Authors: Karen J Fritchie, Paula Carver, Yang Sun, Galina Batiouchko, Steven D Billings, Brian P Rubin, Raymond R Tubbs, John R Goldblum

  American journal of clinical pathology. 137(6):963-70.

  Solitary fibrous tumor (SFT) is a mesenchymal tumor characterized by ovoid cells, branching blood vessels, stromal hyalinization, and CD34 immunoreactivity. Studies have shown loss of 13q in a groupSolitary fibrous tumor (SFT) is a mesenchymal tumor characterized by ovoid cells, branching blood vessels, stromal hyalinization, and CD34 immunoreactivity. Studies have shown loss of 13q in a group of morphologically similar entities, including cellular angiofibroma, mammary-type myofibroblastoma, and spindle cell lipoma. The histologic and immunophenotypic overlap between SFT and the latter group of tumors suggests that these tumors may be genetically linked. We tested a group of 40 SFTs to assess for loss of RB1 (13q14) by fluorescence in situ hybridization (FISH). All 38 SFTs with evaluable signals failed to show loss of RB1 (13q14) by FISH. All cases of cellular angiofibroma (1/1), spindle cell lipoma (6/6), and mammary-type myofibroblastoma (4/4), which were used as a control group, showed monoallelic or biallelic loss of RB1. The absence of RB1 loss in SFTs suggests that they are not related to cellular angiofibroma, mammary-type myofibroblastoma, or spindle cell lipoma.

• Ectopic Expression of TIM-3 in Lung Cancers: A Potential Independent Prognostic Factor for Patients With NSCLC.

  Authors: Xuewei Zhuang, Xiaoning Zhang, Xiyan Xia, Cuijuan Zhang, Xiaohong Liang, Lifen Gao, Xin Zhang, Chunhong Ma

  American journal of clinical pathology. 137(6):978-85.

  T-cell immunoglobulin- and mucin domain-3-containing molecule 3 (TIM-3) is a membrane protein expressed in various kinds of immune cells and plays a pivotal role in immune regulation. Recently, TIM-3T-cell immunoglobulin- and mucin domain-3-containing molecule 3 (TIM-3) is a membrane protein expressed in various kinds of immune cells and plays a pivotal role in immune regulation. Recently, TIM-3 was reported to be expressed aberrantly in melanoma cells, contributing to the low adhesion ability of tumor cells and promoting the survival of melanoma cells. We investigated TIM-3 expression in non-small cell lung cancers (NSCLCs), and further analyzed whether the aberrant expression of TIM-3 is related to the prognosis for patients with lung cancer. Tumor tissue samples from 30 patients with NSCLC were involved. Results of immunohistochemical analysis showed that TIM-3 stained positive on tumor cells in 86.7% (26/30) patients with primary NSCLC. The TIM-3 expression in NSCLC tumor cells was correlated with histologic type and pathologic T classification of the disease (P < .05). More importantly, patients with TIM-3-positive tumor cells had a significantly shorter survival time than those with TIM-3-negative tumors. Multivariate analysis demonstrated the significant role of TIM-3 expression in tumor cells as an independent prognostic factor for patients with NSCLC (relative risk, 4.481; 95% confidence interval, 1.790-11.22; P = .0005). Our results suggest that the ectopic expression of TIM-3 in tumor cells may be a potential, independent prognostic factor for patients with NSCLC.

• ATHENA Trial CIN 2+ Cervical Biopsy Misclassifications Raise Questions.

  Authors: Robert Marshall Austin

  American journal of clinical pathology. 137(6):1012.

• Immunophenotypic Stability of CD200 Expression in Plasma Cell Myeloma.

  Authors: Horatiu Olteanu, Alexandra M Harrington, Steven H Kroft

  American journal of clinical pathology. 137(6):1013-4.

• IgG4-Related Systemic Sclerosing Disease of the Ocular Adnexa: A Potential Mimic of Ocular Lymphoma.

  Authors: Jason R Karamchandani, Sheren F Younes, Roger A Warnke, Yasodha Natkunam

  American journal of clinical pathology. 137(5):699-711.

  IgG4-related sclerosing disease has been described in the orbit and ocular adnexa. Of 164 biopsies of the ocular region for suspected lymphoma, we identified 6 cases of IgG4 disease, 4 of which wereIgG4-related sclerosing disease has been described in the orbit and ocular adnexa. Of 164 biopsies of the ocular region for suspected lymphoma, we identified 6 cases of IgG4 disease, 4 of which were previously unrecognized. All 6 cases demonstrated increased plasma cells in a background of sclerosis and increased absolute numbers of IgG4-expressing cells. Our results confirm the difficulty in diagnosing IgG4-related sclerosing disease in the ocular region. Based on the findings, we suggest that specimens from biopsies of the eye and ocular adnexa for which a definitive diagnosis of lymphoma is not established undergo further workup for IgG and IgG4, particularly if increased plasma cells and sclerosis are present. When IgG4-expressing plasma cells account for greater than 50% of IgG-expressing plasma cells, a diagnosis of IgG4 disease should be considered. Timely recognition would benefit patients by allowing appropriate management with corticosteroid therapy and avoiding more aggressive or unnecessary therapeutic options.

• CDX2 Expression in Columnar Cell Variant of Papillary Thyroid Carcinoma.

  Authors: Miriam L Enriquez, Zubair W Baloch, Kathleen T Montone, Paul J Zhang, Virginia A Livolsi

  American journal of clinical pathology. 137(5):722-6.

  The columnar cell variant of papillary thyroid carcinoma (CCV-PTC) is a rare subtype of PTC that exhibits morphologic features often described as reminiscent of secretory endometrium or colonicThe columnar cell variant of papillary thyroid carcinoma (CCV-PTC) is a rare subtype of PTC that exhibits morphologic features often described as reminiscent of secretory endometrium or colonic adenomas/adenocarcinomas. CDX2, a nuclear transcription factor, is important for intestinal development. It is normally expressed in intestinal epithelium and is also detected in adenoma and adenocarcinomas of the gastrointestinal tract; however, it has also been reported in tumors of other sites with intestinal-type morphologic features. We evaluated CDX2 expression in CCV-PTC and in a thyroid tissue microarray composed of various benign and malignant thyroid lesions. CDX2 expression was identified in 6 (55%) of 11 cases of CCV-PTC, but not in any other benign and malignant thyroid lesions. We conclude that CDX2 is selectively expressed in CCV-PTC and can be used in distinguishing it from other variants of PTC with overlapping morphologic features.

• Helicobacter pylori: To Stain or Not to Stain?

  Authors: S Brooks Smith, Anthony N Snow, Randall L Perry, Shadi A Qasem

  American journal of clinical pathology. 137(5):733-8.

  We performed a retrospective study to investigate the usefulness of immunohistochemical stains for the diagnosis of Helicobacter pylori (HP). We reviewed 200 consecutive gastric biopsy specimens, asWe performed a retrospective study to investigate the usefulness of immunohistochemical stains for the diagnosis of Helicobacter pylori (HP). We reviewed 200 consecutive gastric biopsy specimens, as well as immunohistochemical stains for HP. Of the biopsy specimens, 32 were positive for HP by immunohistochemical staining; of those, HP was seen on H&E stains in 29 cases (91%). The number of high-power fields required to detect HP on H&E-stained slides ranged from 1 to 25 (mean, 5.75). Combined significant (2+ or 3+) acute and chronic inflammation had a specificity of 98% and a negative predictive value of 97%. Our results show that, in our institution, HP can be seen relatively easily with H&E staining in the majority of cases; however, a small number of cases with significant inflammation can be missed if stains are not used.

• Metaplastic and medullary mammary carcinomas do not express mammaglobin.

  Authors: Carolina Reyes, Carmen Gomez-Fernández, Mehrdad Nadji

  American journal of clinical pathology. 137(5):747-52.

  Mammaglobin A (MG-A) is purportedly useful for detecting metastatic carcinomas suspected to be of breast origin and has been advocated as a useful marker of micrometastasis in sentinel lymph nodesMammaglobin A (MG-A) is purportedly useful for detecting metastatic carcinomas suspected to be of breast origin and has been advocated as a useful marker of micrometastasis in sentinel lymph nodes and minimal residual tumor in bone marrow. Little is known about its expression frequency in histologic subtypes of breast cancer. Excisional biopsy specimens from 1,079 untreated invasive mammary carcinomas were evaluated for immunohistochemical expression of MG-A. In addition to estrogen (ER) and progesterone receptors (PR) and HER2, staining for p63 and HLA-DR was used to further characterize histologic subtypes. Of the carcinomas, 36 were classified as metaplastic (based on morphologic features, ER-/PR-/HER2-, p63+), 38 as medullary (ER-/PR-/HER2-, HLA-DR+), and 1,005 as ductal, no special type (NST). All metaplastic and medullary carcinomas were negative for MG-A. Of 1,005 ductal carcinomas, NST, 492 (49.0%) were MG-A+, 62.0% with a reaction in fewer than 25% of the cells. MG-A immunohistochemical studies failed to detect all medullary and metaplastic cancers and more than 50% of ductal carcinomas, NST. In two thirds of MG-A+ ductal carcinomas, the reaction was only focal and usually in a minority of cells. These findings suggest that MG-A has limited value in identifying the mammary origin of carcinomas, particularly in small biopsy specimens used to detect metastasis or minimal residual disease.

• Renal cell carcinoma associated with transcription factor e3 expression and xp11.2 translocation: incidence, characteristics, and prognosis.

  Authors: Tobias Klatte, Berthold Streubel, Friedrich Wrba, Mesut Remzi, Barbara Krammer, Michela de Martino, Matthias Waldert, Michael Marberger, Martin Susani, Andrea Haitel

  American journal of clinical pathology. 137(5):761-8.

  We studied the characteristics and prognosis of renal cell carcinoma (RCC) associated with Xp11.2 translocation and transcription factor E3 (TFE3) expression and determined the need for geneticWe studied the characteristics and prognosis of renal cell carcinoma (RCC) associated with Xp11.2 translocation and transcription factor E3 (TFE3) expression and determined the need for genetic analysis in routine diagnostics. Of 848 consecutive cases, 75 showed microscopic features suggestive of Xp11.2 translocation RCC or occurred in patients 40 years or younger. Of these cases, 17 (23%) showed strong nuclear TFE3 immunostaining, which was associated with more advanced tumors and inverse prognosis in univariate (P = .032) but not multivariate (P = .404) analysis. With fluorescence in situ hybridization and polymerase chain reaction, only 2 cases showed alterations of the X chromosome and the ASPL-TFE3 gene fusion, respectively. In our laboratory, the predictive value of TFE3 expression for the Xp11.2 translocation was 12%. Strong nuclear TFE3 expression is associated with metastatic spread and a poor prognosis. In our laboratory, TFE3 is not diagnostic for Xp11.2 translocation RCC. Diagnosis of Xp11.2 translocation RCC may be made only genetically.

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