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Clinical Pathology Laboratories

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Yoshida H.,Clinical Pathology Laboratories
International Journal of Gynecological Pathology | Year: 2017

Endocervical adenocarcinomas usually demonstrate infiltrative and/or destructive invasion, and the depth and horizontal extent of the invasion are known to have prognostic utility. Here, we report the unusual case of a patient with endocervical adenocarcinoma showing intracystic papillary growth and discuss our methods for measuring and staging this lesion. A 45-yr-old Japanese woman (gravida, 0; para, 0) underwent a cone biopsy for squamous cell carcinoma in situ and atypical glandular cells. Macroscopically, an intracystic tumor (∼7.5 mm in diameter) was detected in the cervix. Microscopically, we observed both squamous cell carcinoma in situ and adenocarcinoma involving the squamo-columnar junction. Adenocarcinoma cells lining the nabothian cyst showed papillary proliferation and expansile stromal invasion without desmoplastic reaction. We evaluated this macroscopically and found that the visible papillary growth and expansile invasion deviated from the adenocarcinoma in situ; hence, we concluded that this lesion was an International Federation of Gynecology and Obstetrics stage IB1 adenocarcinoma. The patient underwent an abdominal radical hysterectomy, followed by bilateral salpingo-oophorectomy and pelvic lymph node dissection. No residual cervical cancer, other gynecologic malignancies, or lymph node metastases were observed. Further studies using cases with the same growth pattern are needed to determine whether our evaluation method is optimal for this type of lesion. ©2017International Society of Gynecological Pathologists


Makise N.,Clinical Pathology Laboratories
American Journal of Surgical Pathology | Year: 2017

Dedifferentiated liposarcoma (DDLPS) demonstrates a variety of growth patterns, and their histologic resemblance to other spindle cell mesenchymal tumors has been widely recognized. However, epithelioid morphology in DDLPS has only rarely been documented. Here, we report 6 cases of DDLPS with striking epithelioid/epithelial features. The patients were 5 men and 1 woman with a median age of 61 years. All tumors were located in the internal trunk. During follow-up of 1 to 41 months, local recurrence, distant metastases, and tumor-related death occurred in 4, 2, and 4 patients, respectively. Beside well-differentiated liposarcoma component and conventional high-grade spindle cell morphology, all tumors focally exhibited growth comprising small or large epithelioid cells in diffuse or sheet-like proliferation. Rhabdoid cells were present in 2 cases. All 5 tumors tested harbored MDM2 amplification. Cytokeratin and/or epithelial membrane antigen were at least focally positive in all 5 tumors tested. One case contained a small focus of novel heterologous epithelial differentiation with acinar structures, wherein cytokeratin, MOC31, and claudin-4 were diffusely expressed and H3K27me3 expression was lost. DDLPS with epithelioid/epithelial features may lead to misdiagnosis of carcinoma or mesothelioma, and their diagnosis should be based on correlation with clinicopathologic and molecular findings. The epithelioid morphology in DDLPS may suggest an aggressive behavior based on this small series. In addition, we document 2 cases of MDM2-amplified undifferentiated neoplasm with epithelioid features in the internal trunk that lacked association with well-differentiated liposarcoma histology and showed rapid clinical course. Whether these latter tumors belong to DDLPS with epithelioid features requires further study. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


OBJECTIVE:: The aim of the study was to evaluate whether carcinoma in situ (CIS) residue at the ductal stump affects the survival of patients undergoing resection for extrahepatic cholangiocarcinoma. BACKGROUND:: Positive ductal margin with CIS has been treated as a tumor-free margin from a prognostic viewpoint because several studies have reported that residual CIS foci at the ductal stump do not affect survival after resection. METHODS:: Patients who underwent resection for extrahepatic cholangiocarcinoma were retrospectively reviewed. The surgical margin status was histologically divided into negative (R0), positive with CIS (R1cis), and positive with invasive cancer (R1inv). The survival and incidence of local recurrence were compared among the groups. RESULTS:: Of 684 consecutive resected patients, 172 patients with early-stage (pTis-2N0M0) cholangiocarcinoma (perihilar, n = 144; distal, n = 28) were analyzed. The cumulative incidence of local recurrence in R1cis patients was higher than R0 patients (32.8% vs 4.4% at 5 years, P < 0.001) and lower than R1inv patients (50.0% at 2 years, P = 0.012). The disease-specific survival for R1cis patients was worse than for R0 patients (35.1% vs 78.7% at 5 years, P = 0.005) and better than for R1inv patients (40.0% at 2 years, P = 0.002). The uni- and multivariate analyses identified the surgical margin status as an independent prognostic factor (R1cis vs R0, relative risk 2.39, P = 0.026; R1inv vs R0, RR 10.28, P < 0.001). CONCLUSION:: R1cis increases the incidence of local recurrence and shortens postoperative survival in patients with early-stage cholangiocarcinoma, although this prognostic effect was less severe compared with R1inv. R1cis should be avoided as much as possible in surgery for early-stage cancer, although it may be allowed in advanced tumors. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Zhao X.,Clinical Pathology Laboratories | Johnson R.L.,Clinical Pathology Laboratories
Archives of Pathology and Laboratory Medicine | Year: 2011

Collagenous sprue is a severe malabsorptive disorder, histologically characterized by small intestinal villous and crypt atrophy, and a subepithelial collagen deposit, thicker than 12 μm, that entraps lamina propria cellular elements. Collagenous sprue is a rare disease entity, with only about 60 sporadic cases reported worldwide since it was first described in 1947. Its exact etiology is still under investigation, and its relationship with classic celiac disease and other refractory, spruelike intestinal disorders remains controversial. Two larger-scale studies, in 2009, brought new insights into this elusive, yet emerging, topic. Here, we present a review of the literature on the possible etiology of collagenous sprue, its proposed links to classic celiac disease and to refractory sprue, and its clinical, biochemical, histologic, and molecular features. To our knowledge, all case reports on collagenous sprue in the medical literature to date are summarized.


Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology.Leukemia advance online publication, 12 April 2016; doi:10.1038/leu.2016.67. © 2016 Macmillan Publishers Limited


Apple F.S.,Clinical Pathology Laboratories | Apple F.S.,University of Minnesota | Ler R.,Hennepin County Medical Center | Murakami M.M.,Hennepin County Medical Center
Clinical Chemistry | Year: 2012

BACKGROUND: Between-assay comparability of 99th percentiles for cardiac troponin concentrations has not been assessed systematically in a single population for a large number of assays. METHODS: We determined 99th percentiles for 19 cardiac troponin assays in heparin plasma samples from a population of 272 and 252 presumably healthy males and females, respectively. The assays evaluated included 1 cardiac troponin T (cTnT) assay from Roche and 18 cTnI assays from Abbott, Alere, Beckman, bioMerieux, Instrumentation Laboratory, Ortho-Clinical Diagnostics, Singulex, Siemens, and Roche. Five of these assays were categorized as high-sensitivity, 9 as sensitive-contemporary, and 5 as point-of-care (POC) assays. RESULTS: For high-sensitivity cTnI (hs-cTnI) assays 99th percentiles varied from 23 to 58 ng/L. At least 80% of individuals had measurable hs-cTnI, whereas only 25% had measurable high-sensitivity cTnT. All highsensitivity cardic troponin assays had 99th percentiles that were 1.2-2.4-fold higher in males than females. For the 9 sensitive-contemporary cTnI assays, 99th percentiles varied from 12 to 392 ng/L, and only the Beckman assay gave measurable concentrations in a substantial portion of the population (35% vs ≤6% for the others). Seven of these 9 assays had 1.3-5.0-fold higher 99th percentiles for males than females. For 5 cTnI POC assays, 99th percentiles varied from < 10 to 40 ng/L. The Instrumentation Laboratory assay gave measurable results in 27.8% of study participants vs ≤6% for the others. Correlations were generally poor among assays. CONCLUSIONS: Among cardiac troponin assays 99th percentile concentrations appear to differ. Highsensitivity assays provide measurable cardiac troponin results in a substantially greater fraction of presumably healthy individuals. © 2012 American Association for Clinical Chemistry.


Hasebe T.,Clinical Pathology Laboratories
Expert Opinion on Therapeutic Targets | Year: 2013

Introduction: Existing pathological diagnostic protocols for breast cancer do not fully reflect the biological characteristics of tumor stromata. To improve the pathological diagnosis of breast cancer, a new pathological diagnostic method capable of assessing the degree of breast cancer malignancy based on the histological features of the tumor stroma is needed. Areas covered: The presence of a fibrotic focus (FF), which consists of fibroblasts or collagen fibers, and the presence of atypical tumor-stromal fibroblasts are significantly associated with nodal metastasis or distant-organ metastasis in patients with invasive ductal carcinoma (IDC) of the breast. FF is the only factor that is significantly associated with an increase in tumor angiogenesis. The importance of FF and atypical tumor-stromal fibroblasts clearly indicates that the malignant potential of IDC does not depend only on the biological characteristics of the tumor cell, but also on those of the tumor stroma. Expert opinion: The biological characteristics of fibroblasts forming an FF or atypical tumor-stromal fibroblasts probably differ from those of fibroblasts located outside an FF or ordinary tumor-stromal fibroblasts. Thus, similar to tumor cells, the heterogeneity of tumor-stromal fibroblasts probably influences the outcome of patients with IDC of the breast. © 2013 Informa UK, Ltd.


Yamamoto S.,National Defense Medical College | Tsuda H.,Clinical Pathology Laboratories | Takano M.,National Defense Medical College | Tamai S.,National Defense Medical College Hospital | Matsubara O.,National Defense Medical College
Modern Pathology | Year: 2012

ARID1A is a recently identified tumor suppressor gene that is mutated in 50% of ovarian clear-cell carcinomas. This mutation is associated with loss of ARID1A protein expression as assessed by immunohistochemistry. The present study aimed at determining the timing of the loss of ARID1A protein expression during the development of ovarian clear-cell carcinoma and assessing its relevance in correlation to PIK3CA gene mutations. A total of 42 clear-cell carcinoma cases with adjacent putative precursor lesions (endometriosis-associated carcinoma cases (n28) and (clear-cell) adenofibroma-associated carcinoma cases (n14)) were selected and subjected to immunohistochemical analysis for ARID1A protein expression and direct genomic DNA sequencing of exons 9 and 20 of the PIK3CA gene. ARID1A immunoreactivity was deficient in 17 (61%) of the 28 endometriosis-associated carcinomas and 6 (43%) of the 14 adenofibroma- associated carcinomas. Among the precursor lesions adjacent to the 23 ARID1A-deficient carcinomas, 86% of the non-atypical endometriosis (12 of 14) and 100% of the atypical endometriosis (14 of 14), benign (3 of 3), and borderline (6 of 6) clear-cell adenofibroma components were found to be ARID1A deficient. In contrast, in the 19 patients with ARID1A-intact carcinomas, all of the adjacent precursor lesions retained ARID1A expression regardless of their types and cytological atypia. Analysis of 22 solitary endometrioses and 10 endometrioses distant from ARID1A-deficient carcinomas showed that all of these lesions were diffusely immunoreactive for ARID1A. Among the 42 clear-cell carcinomas, somatic mutations of PIK3CA were detected in 17 (40%) tumors and majority (71%) of these were ARID1A-deficient carcinomas. These results suggest that loss of ARID1A protein expression occurs as a very early event in ovarian clear-cell carcinoma development, similar to the pattern of PIK3CA mutation recently reported by our group, and frequently coexists (not mutually exclusive) with PIK3CA mutations. © 2012 USCAP, Inc. All rights reserved.


Gilligan P.H.,Clinical Pathology Laboratories
Clinics in Laboratory Medicine | Year: 2014

Survival has improved in patients with cystic fibrosis (CF), in part because of aggressive antimicrobial management. Two multidrug-resistant environmental bacteria, the Burkholderia cepacia group and nontuberculous mycobacteria, have emerged. Improving genomic and proteomic technologies are allowing better identification of bacteria and fungi found in the CF lung and detection of viral agents that may be associated with pulmonary exacerbations. Anaerobic bacteria and Streptococcus angionsus group organisms may play a role in chronic CF lung infections. The diversity of organisms declines perhaps as a result of aggressive antimicrobial therapy, and an apex predator, Pseudomonas aeruginosa, may emerge in many patients with CF. © 2014 Elsevier Inc.


Setsu N.,Clinical Pathology Laboratories
American Journal of Surgical Pathology | Year: 2016

Myxoid liposarcomas (MLSs) are genetically defined by the presence of DDIT3 gene fusions and most commonly arise in the extremities of young adults. Whether MLSs develop primarily in the retroperitoneum is controversial, and a recent retrospective study found no molecularly confirmed examples. Because MLSs tend to metastasize to deep soft tissues, purported examples of primary retroperitoneal lesions might represent distant metastasis, most commonly from extremities. In addition, well-differentiated or dedifferentiated liposarcomas, which are characterized by MDM2 amplifications, may exhibit prominent myxoid changes and mimic MLSs. Here, we document 5 cases of MLSs that originated in the retroperitoneum that were identified through critical clinicopathologic reevaluation. These cases accounted for 2.3% of 214 primary retroperitoneal liposarcomas and 3.2% of 156 MLSs in our database. They occurred in 3 men and 2 women with a median age of 32 years. All tumors were localized to the retroperitoneum at presentation, and no patient developed extra-abdominal recurrences during the clinical course (median, 50 mo). All 5 cases exhibited at least focal classic histologic findings. All harbored DDIT3 gene rearrangements, and none harbored MDM2 amplifications according to fluorescence in situ hybridization. This study demonstrates that primary MLSs can occur in the retroperitoneum, albeit rarely, and can be accurately diagnosed through combined clinicopathologic and molecular analysis.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0/ Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

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