A Woman with Refractory Hemolytic AnemiaA 71-year-old woman with breast cancer and systemic sclerosis was admitted because of refractory hemolytic anemia. A diagnostic test was performed.

OBJECTIVES Primary central nervous system anaplastic large cell lymphoma, anaplastic lymphoma kinase positive (primary CNS ALCL, ALK+) is a rare CNS lymphoma whose description is limited to case reports. These tumors have a variable clinical course, and prognosis is primarily determined by age. We present the largest case series to date of primary CNS ALCL, ALK+, with observational data. METHODS A retrospective search of multiple academic centers was performed to identify cases of primary CNS ALCL, ALK+. We also performed a review of published cases of primary CNS ALCL, ALK+. Clinical history, radiography, pathology, and genetic testing data were obtained to determine the prognostic implications in the context of clinical course. RESULTS We identified three cases of primary CNS ALCL, ALK+ from our databases. A literature review identified 30 published reports of 31 individual cases. Clinical features for the combined 34 cases included a median age of 18.5 years, with a male to female ratio of 4.7:1, and the most common symptom was headache. Genetic studies demonstrated an ALK rearrangement by fluorescence in situ hybridization, and a gene fusion assay confirmed an NPM1-ALK gene fusion in one case. CONCLUSIONS We present the largest case series to date of a rare primary CNS lymphoma with additional diagnostic and clinical information.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. It is a clinically and morphologically heterogeneous entity that has continued to resist complete subtyping. Molecular subtyping efforts emerged in earnest with the advent of gene expression profiling (GEP). This molecular subtyping approach has continued to evolve simultaneously with others including immunohistochemistry and more modern genomic approaches. Recently, the veritable explosion of genomic data availability and evolving computational methodologies have provided additional avenues, by which further understanding and subclassification of DBLCLs is possible. The goal of this review is to provide a historical overview of the major classification timepoints in the molecular subtyping of DLBCL, from gene expression profiling to present day understanding.

A Woman with PancytopeniaAn 80-year-old woman was admitted with pancytopenia. Five weeks earlier, nausea, vomiting, diarrhea, chills, and fever had developed. CT revealed bilateral pelvic masses; examination of a peripheral-blood smear revealed schistocytes, anisocytosis, and a low platelet count. A diagnostic test was performed, and management decisions were made.

A 51-year-old gentleman with no significant past medical history presented to a gastroenterologist for dyspepsia, chronic diarrhea, and 15-pound unintentional weight loss over 5 months. His physical examination was normal with no evidence of any abdominal masses or lymphadenopathy. A complete blood count showed: white blood count 2.79 (cid:1) 10 3 / μ L, hemoglobin 12.7 g/dL, hematocrit 36.9%, mean corpuscle volume 91.8 fL, and platelets 160 (cid:1) 10 3 / μ L. Anti-nuclear antibodies (ANA) testing was positive but further testing was negative for anti-Smith and anti-dsDNA antibodies. A colonos-copy was performed, and nodular mucosa was identified at the junction of the hepatic flexure (Image 1A), and this area was biopsied. Histologic sections show an extensive, destructive lymphocytic infiltrate involving the lamina propria, and colonic epithelium of all biopsy fragments (Image 1B,C). The lymphocytes are small to medium-sized with a round to slightly irregular nuclei, condensed chromatin, inconspicuous nucleoli, and scant cytoplasm. Immunochemical stains show that the lymphocytes are positive for CD3, CD56, CD7, and CD117 (weak) and negative for CD4, CD8, CD10, CD5, CD2, CD25, CD30, TdT, lysozyme, BetaF1, T-cell receptor (TCR)

•Accurate lymph node staging for lung cancer resection specimens requires collaborative efforts by both the surgical team and the pathology team.•A focused pathology intervention resulted in a significant increase in the number of peribronchial lymph nodes identified in lung cancer resection specimens.•Overall tumor size and invasive tumor size correlated with likelihood of lymph node metastases.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. Cell-of-origin classification in DLBCL has identified activated B cell (ABC) and germinal center B cell (GCB) as two major subtypes. Patients with the ABC subtype show reduced overall survival with standard therapies. Development of a quantitative RT-PCR-based lymphoma cell-of-origin (LCOO) assay to determine ABC, GCB, and unclassifiable subtypes in formalin-fixed, paraffin-embedded tissue (FFPET) DLBCL samples is reported. The LCOO classifier was trained on two DLBCL cohorts with validation performed by using an analytical grade assay in an independent cohort of 60 FFPET DLBCL samples. In the validation cohort, LCOO classification was 88.1%, 84.7%, and 84.7% concordant with microarray, immunohistochemistry (Hans classification), and Lymphoma Subtyping Test, respectively. Importantly, LCOO and Lymphoma Subtyping Test assays commonly assigned subtypes in 17 (94.4%) of 18 ABC samples and 34 (89.5%) of 38 GCB DLBCL samples from this cohort. Progression-free survival and overall survival of ABC and GCB subtypes, as classified by all platforms, were not significantly different in the validation cohort. LCOO classification using publicly available microarray gene expression from two independent data sets (414 fresh frozen and 474 FFPET DLBCL biopsies) revealed a significantly worse outcome for the ABC subtype compared with that of the GCB subtype. Thus, a sensitive, reproducible, LCOO assay developed on an easy to standardize quantitative RT-PCR platform may be an important clinical tool for DLBCL cell-of-origin classification.

BACKGROUND Human chorionic gonadotropin (hCG) assays are used to detect pregnancy, and urine point-of-care tests are frequently used to triage patients. Under certain conditions, urine tests can fail to detect pregnancy, which can have serious consequences for patient management. OBJECTIVES To understand the prevalence of different factors contributing to false-negative urinary hCG testing results at our institution. METHODS Clinical data for patients with negative urine hCG results and subsequent positive or equivocal serum hCG results within a 1-year period were reviewed. RESULTS Out of 9447 negative urine hCG results, 11 potential missed diagnoses were identified, with early gestational age as the most common factor, followed by β-core hook effects. CONCLUSIONS Although false-negative urine hCG test results are rare, understanding the commonly encountered reasons for inaccurate testing results can help clinical centers develop strategies to minimize risk for patients.

Aim: The study aimed to determine the additional value of staging laparoscopy in patients with pancreatic cancer deemed potentially resectable based on computed tomography imaging. Methods: A systematic literature search was performed using MEDLINE and the Cochrane Register of Controlled Trials (January 1995 to June 2017). Primary outcome measures were the overall yield and sensitivity to detect non-resectable disease. Quality of studies was assessed with the Newcastle-Ottawa Scale. Results: From 156 records, 15 studies including 2,776 patients met the inclusion criteria. In 12 studies, reporting outcomes on 1,756 patients with resectable disease after standard imaging, 350 (20%, range 14-38%) cases of non-resectable cancer were detected with staging laparoscopy. In 3 studies on 242 patients with locally advanced disease after standard imaging, staging laparoscopy detected metastases in 86 patients (36%). The failure rate of staging laparoscopy to detect non-resectable disease was 5% (64 of 1,406). Conclusion: Staging laparoscopy reduces the non-therapeutic laparotomy rate, and in locally advanced or borderline resectable disease, staging laparoscopy could more accurately select patients for neoadjuvant protocols. (c) 2018 S. Karger AG, Basel

Aim: The study aimed to determine the additional value of staging laparoscopy in patients with pancreatic cancer deemed potentially resectable based on computed tomography imaging. Methods: A systematic literature search was performed using MEDLINE and the Cochrane Register of Controlled Trials (January 1995 to June 2017). Primary outcome measures were the overall yield and sensitivity to detect non-resectable disease. Quality of studies was assessed with the Newcastle-Ottawa Scale. Results: From 156 records, 15 studies including 2,776 patients met the inclusion criteria. In 12 studies, reporting outcomes on 1,756 patients with resectable disease after standard imaging, 350 (20%, range 14–38%) cases of non-resectable cancer were detected with staging laparoscopy. In 3 studies on 242 patients with locally advanced disease after standard imaging, staging laparoscopy detected metastases in 86 patients (36%). The failure rate of staging laparoscopy to detect non-resectable disease was 5% (64 of 1,406). Conclusion: Staging laparoscopy reduces the non-therapeutic laparotomy rate, and in locally advanced or borderline resectable disease, staging laparoscopy could more accurately select patients for neoadjuvant protocols.

OBJECTIVE:A subset of endometrial cancer is characterized by deficiencies in the mismatch repair (MMR) pathway. MMR testing is a well-established tool to screen for Lynch syndrome, but has also become a companion diagnostic test for immunotherapy. We compared the MMR status of primary and paired metastatic endometrial cancer to determine whether MMR deficiency can occur specifically in advanced endometrial cancer compared to primary tumor.METHODS:Matched primary uterine and metastatic endometrioid adenocarcinoma from 2009 to 2018 at our institution were identified. PMS2 and MSH6 protein expression in metastatic and matched primary tumor was assessed using clinically validated immunohistochemistry methods for Lynch syndrome screening. MLH1 promoter hypermethylation and microsatellite instability (MSI) were performed in discordant cases.RESULTS:29 patients were identified with paired primary endometrial endometrioid adenocarcinoma and metastasis or recurrence after the original hysterectomy. Fourteen of 29 cases (48.2%, 14/29) were found to be MMR deficient at the metastatic or recurrent site. Two patients (6.9%, 2/29) showed discordant MMR status with PMS2 protein loss at the metastatic sites and intact expression in the primary uterine tumors. Both discordant cases exhibited abnormal subclonal loss at primary site and MLH1 promoter hypermethylation. High levels of microsatellite instability (MSI-H) was confirmed in one discordant metastatic site.CONCLUSION:Advanced endometrial cancer can rarely (~7%) show somatic loss of MMR protein expression in recurrent or metastatic sites compared to matched paired primary tumor. MMR testing of recurrent or metastasis should be considered for guiding immunotherapy if primary uterine tumor exhibits abnormal subclonal MMR loss.

The case of a 16-year-old African-American girl with systemic lupus erythematosus, who developed diffuse alveolar hemorrhage with fatal consequences, is described. Diffuse alveolar hemorrhage is a rare but serious complication of systemic lupus. It occurs in three distinct but overlapping phenotypes, acute capillaritis, bland pulmonary hemorrhage, and diffuse alveolar damage, each of which is associated with a different group of underlying conditions. Diffuse alveolar hemorrhage is a medical emergency: choice of treatment depends on early diagnosis and determination of the underlying etiology. Acute infection, superimposed on diffuse alveolar hemorrhage in the setting of immune compromise, is often a terminal event, as in this case.

Ovarian cancer is the fifth most common cancer in women worldwide and has the highest mortality amongst gynecological cancers. miRNAs are a class of non-coding RNAs, approximately 22 nt long, that negatively regulate gene expression and have roles in cell growth, differentiation, metabolism, apoptosis and tumorigenesis. Dysregulated miRNA-223 expression has been implicated in a wide range of cancer subtypes. SMARCD1 is an integral protein component of the SWI/SNF complex, which remodels chromatin, and which has important roles in transcriptional control, DNA replication, recombination and repair. In this study, we examined whether the expression levels of miR-223 and SMARCD1 are altered in ovarian serous neoplasia and whether miR-223 functionally regulates the gene and protein expression of SMARCD1 in vivo, as has been predicted by in silico methods. Benign, atypical proliferative serous tumors (borderline) and malignant serous tumors (n = 144) were laser-capture microdissected, and relative expression levels of miR-223 and SMARCD1 were quantified by RT-PCR. Ovarian cancer cell line OC316 was reverse transfected with a miR-223 mimic, and relative expression levels of miR-223 and SMARCD1 were quantified by reverse-transcription polymerase chain reaction; protein expression of SMARCD1 was evaluated by Western blot. miR-223 expression was up-regulated in high-grade ovarian serous carcinoma samples (median RQ = 4.8881, P = .0045), whilst SMARCD1 was down-regulated (median RQ = 0.5107, P = .0492). In OC316 cells transfected with a miR-223 mimic, SMARCD1 gene expression was down-regulated 3-fold (P = .001), and SMARCD1 protein expression was down-regulated 2-fold (P = .002). These results suggest a regulatory role for miR-223 in ovarian serous neoplasia, linking it with SMARCD1.