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Introduction: The number of geriatric patients will increase dramatically over the next 2 decades, and providers across all specialties will need skills in diagnosis and management of common geriatric disorders. Geriatric depression is common and associated with significant psychiatric and medical morbidity yet is frequently not taught in clinical clerkships. To provide foundational knowledge on geriatric depression, we designed a two-part, online, self-learning module set for health professions learners., Methods: Learning objectives and content were chosen based upon consensus from a national panel of internal medicine and psychiatry clinician-educators. The two-part module set covers recognition of depression and use of screening tools for diagnosis, suicide assessment, patient education, and initial management approaches. Articulate software was used to create two complementary 20-minute modules that incorporate teaching points, interactive quizzes, and video clips of a clinician interviewing a standardized patient and her husband during the course of an initial clinical evaluation., Results: The modules were piloted with 11 senior medical students. Mean number of correct answers on 10 knowledge-test questions improved from 8.1 on pretesting to 9.4 on posttesting. On a 5-point Likert scale (1 = strongly disagree, 5 = strongly agree ), participants affirmed that the modules were easy to navigate (4.91) and increased understanding of geriatric depression (4.82) and that the videos added to the learner's understanding of objectives (4.64)., Discussion: These modules can be used by learners in health professions schools to improve foundational knowledge in geriatric depression and prepare for advanced clinical work with older patients., Competing Interests: None to report.

Background: It is estimated that approximately 10% of pancreatic cancers have a familial component. Many inheritable genetic syndromes are associated with increased risk of pancreatic cancer, such as Peutz-Jeghers syndrome, hereditary breast-ovarian cancer and familial atypical multiple mole melanoma, but these conditions account for only a minority of familial pancreatic cancers. Previous studies have identified an increased prevalence of noninvasive precursor lesions, including pancreatic intraepithelial neoplasia, in the pancreata of patients with a strong family history of pancreatic cancer. A detailed investigation of the histopathology of invasive familial pancreatic cancer could provide insights into the mechanisms responsible for familial pancreatic cancer, as well as aid early detection and treatment strategies., Methods: We have conducted a blinded review of the pathology of 519 familial and 651 sporadic pancreatic cancers within the National Familial Pancreas Tumor Registry. Patients with familial pancreatic cancer were defined as individuals from families in which at least a pair of first-degree relatives have been diagnosed with pancreatic cancer., Results: Overall, there were no statistically significant differences in histologic subtypes between familial and sporadic pancreatic cancers (p > 0.05). In addition, among surgical resection specimens within the study cohort, no statistically significant differences in mean tumor size, location, perineural invasion, angiolymphatic invasion, lymph node metastasis and pathologic stage were identified (p > 0.05)., Conclusions: Similar to sporadic pancreatic cancer, familial pancreatic cancer is morphologically and prognostically a heterogeneous disease., (Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Although the majority of post-transplant lymphoproliferative disorder (PTLD) cases are associated with Epstein-Barr virus (EBV), 20-42% of cases are EBV negative (EBV-N). The antigenic stimulus that drives EBV-N PTLD is unknown, but is likely heterogeneous. A common feature of PTLD, regardless of EBV status, is an abnormal polytypic lymphoplasmacytic infiltrate. Immunglobulin-G4 (IgG4) syndrome is also characterized by a polytypic lymphoplasmacytic infiltrate with a predominance of IgG4-positive (IgG4-P) plasma cells., Methods: We investigated the possibility of an association between EBV-N PTLD and IgG4 syndrome. Of 33 evaluated PTLD cases, 9 (27%) were EBV-N. EBV-N PTLD cases showed longer transplantation-to-diagnosis times than EBV-positive cases., Results: A single patient had a preceding benign duodenal biopsy with focally prominent IgG4-P plasma cells; however, no clinical data supported IgG4 syndrome, precluding an association between IgG4 syndrome and subsequent EBV-N PTLD in this patient., Conclusion: As none of 29 evaluable cases of PTLD (including all 9 EBV-N cases) were associated with an increase in IgG4-P plasma cells, IgG4 syndrome does not appear to play a role in the etiology of EBV-N PTLD. The significance of these findings and the current understanding of the etiology of EBV-N PTLD are discussed., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To validate the 2010 American Joint Committee on Cancer (AJCC) and 2006 European Neuroendocrine Tumor Society (ENETS) tumor staging systems for pancreatic neuroendocrine tumors (PanNETs) using the largest, single-institution series of surgically resected patients in the literature., Background: The natural history and prognosis of PanNETs have been poorly defined because of the rarity and heterogeneity of these neoplasms. Currently, there are 2 main staging systems for PanNETs, which can complicate comparisons of reports in the literature and thereby hinder progress against this disease., Methods: Univariate and multivariate analyses were conducted on the prognostic factors of survival using 326 sporadic, nonfunctional, surgically resected PanNET patients who were cared for at our institution between 1984 and 2011. Current and proposed models were tested for survival prognostication validity as measured by discrimination (Harrel's c-index, HCI) and calibration., Results: Five-year overall-survival rates for AJCC stages I, II, and IV are 93% (88%-99%), 74% (65%-83%), and 56% (42%-73%), respectively, whereas ENETS stages I, II, III, and IV are 97% (92%-100%), 87% (80%-95%), 73% (63%-84%), and 56% (42%-73%), respectively. Each model has an HCI of 0.68, and they are no different in their ability to predict survival. We developed a simple prognostic tool just using grade, as measured by continuous Ki-67 labeling, sex, and binary age that has an HCI of 0.74., Conclusions: Both the AJCC and ENETS staging systems are valid and indistinguishable in their survival prognostication. A new, simpler prognostic tool can be used to predict survival and decrease interinstitutional mistakes and uncertainties regarding these neoplasms.

We report a fatal case of invasive fungal sinusitis caused by Cunninghamella echinulata in a febrile, neutropenic 15-year-old male with relapsing acute leukemia. The isolate was recovered from a nasal biopsy from the right middle meatus, and microscopic examination of the tissue revealed angioinvasion and necrosis. Human infection caused by this organism has not been well documented; however, this report alerts us to its life-threatening potential., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Ochroconis spp. are dematiaceous fungi and have recently become recognized as the cause of human disease. Infections due to members of this genus have primarily occurred in patients with impaired immunity following organ transplantation or chemotherapy for hematologic malignancies. There is no universally agreed upon therapy or duration of treatment, but amphotericin B and/or triazoles are typically employed. We present a case of Ochroconis gallopava infection in a patient with chronic granulomatous disease (CGD). The organism exhibited elevated minimal inhibitory concentrations against itraconazole (0.5 μg/ml) and voriconazole (2 μg/ml) in comparison with results from other studies reported in the literature. This case illustrates the complexities associated with antibiotic susceptibility testing, selection of appropriate drugs, and management in patients with Ochroconis infections. We also review the literature of human infections with Ochroconis to date, and discuss its microbiology to apprise both clinicians and laboratory personnel of this infrequently encountered but potentially aggressive pathogen.

Anal duct carcinoma (ADC) is a rare lesion composed of glands undermining non-neoplastic squamous epithelium. We describe the clinicopathologic characteristics and follow-up of 5 cases of ADC. Four definitive cases had tissue available for immunohistochemistry (IHC; CK7, CK20, prostate-specific antigen [PSA], estrogen/progesterone receptors [ER/PR], and p16) and in situ hybridization (ISH) for high-risk human papillomavirus (HR-HPV); a fifth case, with a history of ADC, had limited tissue for immunolabeling with only CK7, CK20, and p16. The mean patient age was 69.8 years. All 5 cases were CK7-positive and p16-negative. Four of 5 cases were CK20-negative. All cases with sufficient tissue (4/4) were negative for HR-HPV by ISH, PSA-negative (men), and ER/PR-negative (women). Four of 5 patients had previous malignancies, and in all 4 cases with sufficient tissue, metastasis was excluded with IHC. Of 5 patients, 3 developed metastases, whereas 2 had isolated local recurrences. ADCs are neoplasms with metastatic potential and can result in poor outcomes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Distinguishing between solid-pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine tumors (PanNETs) may pose a diagnostic dilemma. Both can demonstrate solid growth patterns, and both can be immunoreactive with neuroendocrine markers such as synaptophysin and CD56. One well-established feature of SPNs is the presence of hyaline globules, which in contrast has only rarely been reported in PanNETs. Clinicopathologic features of 361 cases originally classified as PanNETs were examined. Of these, 24 tumors (6.6%) had hyaline globules, raising the possibility of SPN. Immunohistochemistry for β-catenin was performed on these 24 neoplasms, and showed nuclear labeling in 6 cases. These 6 cases, which also demonstrated cytoplasmic CD10 staining, were reclassified as SPNs. The remaining 18 cases maintained their original diagnosis as PanNETs, and the hyaline globules in these cases were periodic acid-Schiff (PAS) positive, diastase resistant, and immunoreactive with α-1-antitrypsin. All 24 cases were histologically re-evaluated, and the pattern of invasion, presence of clear cells, and nuclear grooves were found to be helpful in distinguishing SPNs from PanNETs. We conclude that the presence of hyaline globules should raise SPNs in the differential diagnosis of a solid cellular neoplasm of the pancreas. However, this should not be used as the sole criterion in the diagnosis of SPNs, as hyaline globules may also be seen in 5% of PanNETs. Immunohistochemical and histologic features supporting the diagnosis of SPNs over PanNETs include CD10 and nuclear β-catenin labeling, an insidious pattern of invasion, clear cells, and nuclear grooves.

Metastatic mucinous carcinomas in the ovary are readily recognized when they show characteristic features, including bilateral involvement, only moderate tumor size, surface and superficial cortical involvement, nodular growth, and an infiltrative pattern. However, it is well established that some metastatic mucinous carcinomas can simulate primary ovarian mucinous tumors grossly and microscopically. Metastatic pancreaticobiliary tract adenocarcinomas present a particular diagnostic challenge due to their ability to exhibit borderline-like and cystadenomatous growth patterns, which can be misinterpreted as underlying primary ovarian precursor tumors and can be erroneously used to support interpretation of the carcinomatous components as arising from these purported precursors within the ovary. Thirty-five cases of metastatic pancreaticobiliary tract adenocarcinomas were analyzed. The mean patient age was 58 years (median, 59 y; range, 33 to 78 y). In 15 cases (43%), the pancreaticobiliary tract and ovarian tumors presented synchronously and in 2 cases (6%) the ovarian tumors presented earlier as the first manifestation of the disease. Ovarian tumors were bilateral in 31 cases (89%). Mean and median tumor sizes were 10.6 and 9.5 cm, respectively (range, 2.5 to 21.0 cm). Nodularity was present in 22 cases (63%) and surface involvement was identified in 14 cases (40%). An infiltrative growth pattern was present at least focally in 28 cases (80%), accompanied by borderline-like and/or cystadenomatous areas in 17 (49%) cases and as the exclusive pattern in 11 cases (31%). Conversely, borderline-like and cystadenomatous patterns were identified in 24 cases (69%) and as the exclusive patterns (either pure or combined with one another) in 7 cases (20%). Dpc4 expression was lost in 20 of 33 tumors analyzed (61%). Of 25 patients with follow-up, 23 patients had died of disease (mean/median time, 9/6 mo; range, 1 to 39) and 2 patients were alive with disease (at 1 and 25 mo). Frequent bilateral ovarian involvement, moderate tumor size, nodularity, and infiltrative patterns are useful features for identifying these ovarian tumors as metastatic. However, many tumors exhibit borderline-like and cystadenomatous patterns that, when dominant and combined with synchronous presentation, make recognition as metastases an ongoing challenge. Loss of Dpc4 expression provides the most useful immunohistochemical evidence for establishing the pancreaticobiliary tract as the most likely source of these metastatic mucinous carcinomas in the ovary.

Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus-negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background & Aims: Recurrent hepatitis C with ensuing fibrosis is the leading cause of liver allograft loss. We investigated whether histologic features in early posttransplant liver biopsies could predict the rate of fibrosis progression in this population., Methods: From 1999 to 2007 there were 476 liver transplants performed for hepatitis C at our center. We reviewed all available posttransplant biopsies for these patients; patients were categorized as rapid, intermediate, or slow fibrosers based on their METAVIR fibrosis score at 24 months. Stage F0 biopsies for rapid and slow fibrosers were analyzed histologically and immunohistochemically., Results: We identified 52 rapid fibrosers and 61 slow fibrosers in our cohort. There was a significant increase in the fibrosis progression rate in the group transplanted between 2003 and 2007 compared with between 1999 and 2002. The course of fibrosis progression was determined early in the posttransplant period and the rate was constant. Rapid fibrosers had more hepatocyte apoptosis than slow fibrosers (P = .001), but no difference in hepatitis activity on stage F0 biopsies. Rapid fibrosers also experienced more episodes of acute rejection after transplantation (P < .001). Cytokeratin 19 (CK19) and vimentin expression on F0 stage biopsies could distinguish rapid from slow fibrosers (CK19: area under the curve, 0.71; P = .0034; vimentin: P = .0219)., Conclusions: CK19, vimentin, and hepatocellular apoptosis are promising early markers of rapid fibrosis progression in patients transplanted for hepatitis C. The rate of fibrosis progression is established early in the posttransplant period; this initial rate dictates long-term outcome., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)