Postinfantile Giant Cell Hepatitis in Native and Allograft Livers: A Multi-Institutional Clinicopathologic Study of 70 Cases.

Postinfantile giant cell hepatitis (PIGCH) is a rare hepatitis pattern in adults with variable etiologies and clinical outcomes. We conducted a multi-institutional retrospective study to define the clinicopathologic characteristics of patients with PIGCH. A total of 70 PIGCH cases were identified and reviewed for pathological features, including fibrosis, cholestasis, inflammation, steatosis, necrosis, and apoptosis, as well as the distribution of giant cells and the maximum number of giant cells per high-power field. Demographic and clinical data, including age, sex, laboratory results, etiologies, and follow-up results, were recorded. Among the 70 cases, 40% (28/70) were associated with autoimmune liver diseases, followed by 9 (13%) with unknown etiology, 8 (11%) with viral infection, 5 (7%) with medications, 5 with combined etiologies, and 4 (6%) with malignancies (mostly chronic lymphocytic leukemia). Notably, another 16% were de novo PIGCH in liver allografts, most of which occurred after a rejection event. During follow-up, 26 (37%) patients died of the disease and 44 (63%) were alive. Deceased patients were characterized by older age (mean age, 54.9 vs 45.5 years; P = .02), higher alkaline phosphatase level (mean value, 253.3U/L vs 166.3 U/L; P = .03), higher fibrosis stage (stage 3-4 vs stage 0-2, 57.7% vs 29.6%; P = .03), being more likely to have de novo PIGCH after transplantation (23.1% vs 11.4%; P = .04), and being less likely to have primary autoimmune liver disease etiology (26.9% vs 47.7%; P = .04). These results indicate that PIGCH is a rare pattern of liver injury associated with different etiologies and variable clinical outcomes. Autoimmune liver disease with PIGCH is associated with better survival, whereas de novo PIGCH in allografts is associated with poorer survival. Older age, higher alkaline phosphatase level, and advanced fibrosis are adverse prognostic factors.

Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

Appendiceal sessile serrated lesions are distinct from their right-sided colonic counterparts and may be precursors for appendiceal mucinous neoplasms.

Low-grade appendiceal mucinous neoplasms (LAMNs) can occur concurrently with appendiceal sessile serrated lesions (SSLs). To interrogate relatedness, we performed multigene and immunohistochemical characterizations of paired and unpaired SSLs and LAMNs. We evaluated 62 serrated lesions from 50 appendectomy specimens for hotspot mutations in BRAF, KRAS, and GNAS genes. Cases were subdivided into 3 groups: 20 unpaired SSLs, 18 unpaired LAMNs, and 12 with an SSL and concurrent LAMN. ß-catenin and Annexin A10 immunostaining were performed on the SSL and LAMN components in the 12 paired cases, and 14 colonic SSLs served as controls. There was no significant difference in KRAS hotspot mutation rates in appendiceal SSLs (17/26; 65.4%) and LAMNs (16/30; 53.3%) (p = 0.42). BRAF V600E was identified in a single case (1/50; 2.0%) of SSL and concurrent LAMN (p = 1.0). Mutations in GNAS were more common in LAMNs (6/30; 20.0%) than in SSLs (1/31; 3.2%) (p = 0.05). The molecular genotypes between paired SSLs and LAMNs were concordant in most cases (10/12; 83.3%). Annexin A10 immunostaining was significantly greater in colonic SSLs (14/14; 100%) than in appendiceal SSLs (1/12; 8.3%) (p < 0.0001). ß-catenin immunostaining was significantly increased in LAMNs (10/12; 83.3%) compared with their paired appendiceal SSLs (2/12; 16.7%) (p = 0.003). Overall, appendiceal SSLs are predominantly driven by KRAS mutations and are not characterized by Annexin A10 immunostaining. Our data suggest that at least a subset of LAMNs may arise from a precursor SSL in which GNAS mutations and/or upregulation of the WNT signaling pathway are likely key events modulating this progression.

Primary Follicular Dendritic Cell Sarcoma of Urinary Bladder.

Follicular dendritic cell sarcoma is a rare malignant mesenchymal neoplasm composed of follicular dendritic cells. A subset of cases can be found at extranodal sites. Only 2 follicular dendritic cell sarcomas were previously reported in the urinary bladder. We report a follicular dendritic cell sarcoma that involved the urinary bladder of an 81-year-old woman, who presented with painless gross hematuria. The neoplasm was composed of large epithelioid cells with atypical nuclei, admixed with inflammatory cells. On immunohistochemistry, the neoplastic cells were reactive only for CD21, CD35, and vimentin. The tumor was considered unresectable due to its large size and proximity to the iliac vessels and the patient was treated with bortezomib, cyclophosphamide, and dexamethasone. Although a full course of chemotherapy was not completed due to adverse side effects, the tumor was reduced in size. A subsequent involved-field radiotherapy was performed. Three years postdiagnosis and 2 years after the radiotherapy treatment, a recurrent tumor was identified on imaging in the left posterolateral bladder wall. However, at that time the patient was found to have a newly developed advanced colonic adenocarcinoma. Three and a half months later she developed a bowel perforation and died.

Malignant Colorectal Polyp Pathology: Are We Getting Sufficient Information to Make Decisions?

BACKGROUND: The College of American Pathologists has published guidelines for malignant colorectal polyp pathology reports that list histopathological features that are "core elements" and "optional." Lack of element reporting may result in inaccurate tumor risk stratification.This study aimed to perform a population-based assessment of pathology reporting for T1 colorectal cancers and determine the completeness of reporting for core and optional histopathological elements.This is a retrospective cohort study.This study reviews the pathology reports of endoscopically resected malignant colorectal polyps in Alberta, Canada between 2014 and 2016.Individuals aged 18 years or older with T1 colorectal polyps were selected.Histopathological elements were dichotomized into core and optional. Malignant polyps were classified as high risk or low risk for lymph node metastases and local intraluminal recurrence. Addendum reports were compared with first reports.After applying exclusion criteria, 431 polyps were analyzed. The mean age of patients was 65.5 years; 59.4% were male. Histological grade, deep margin, and lymphovascular invasion were reported in 82.4%, 86.8% and 75.6%; all 3 were reported in only 66.4%. Tumor budding (not in the 2016 guidelines) was reported in 14.4%. One hundred ninety polyps (44.1%) were high risk. Thirty-seven polyps (8.3%) had an addendum report. Following the addendum, 1 polyp was downgraded to low risk, and 9 polyps were upgraded to high risk.The main limitation of the study is its retrospective nature. The decision making surrounding treatment for T1 cancers is complex, and factors other than histopathological tumor features may have been part of treatment decisions.There is a high rate of incomplete reporting of core and optional elements for malignant colorectal polyp pathology reports in Alberta. Several variables used by colorectal surgeons for decision making, such as tumor budding and depth of submucosal invasion, are not considered core elements and are infrequently reported. A pathology review by a second pathologist often results in a change in risk stratification. See Video Abstract at http://links.lww.com/DCR/B98. PATOLOGÍA DEL PÓLIPO COLORRECTAL MALIGNO: ¿ESTAMOS OBTENIENDO INFORMACIÓN SUFICIENTE PARA TOMAR DECISIONES?: El Colegio de Patólogos Americanos publico pautas para informes de patología de pólipos colorrectales malignos que enumeran características histopatológicas como "elementos centrales" y "opcionales". La falta de información elemental puede resultar en una estratificación de riesgo tumoral imprecisa.Valoración basada en una población de los informes de patología para los cánceres colorrectales T1 y determinar la precisión de los informes en cuanto los elementos histopatológicos centrales y opcionales.Estudio de cohorte retrospectivo.Este estudio revisa los informes de patología de pólipos colorrectales malignos resecados endoscópicamente en Alberta, Canadá, entre 2014 y 2016.personas mayores de 18 años con pólipos colorrectales T1.Los elementos histopatológicos se dicotomizaron entre elementales y opcionales. Pólipos malignos se clasificaron como de alto riesgo o bajo riesgo de metástasis en los ganglios linfáticos y recurrencia intraluminal local. Los informes enmendados se compararon con los informes originales.Después de aplicar los criterios de exclusión, se analizaron 431 pólipos. La edad media fue 65.5 años, con 59.4% masculinos. El grado histológico, el margen profundo y la invasión linfovascular se informaron confirmaron en 82.4%, 86.8% y 75.6% respectivamente; las tres características se demostraron en solo 66.4%. Un patrón tumoral en ciernes se reporto en 14.4-una característica que no se usaba en las guías de 2016. Ciento noventa pólipos (44.1%) eran de alto riesgo. Treinta y siete pólipos (8.3%) requirieron de un informe enmendado. Aplicación de los nuevos criterios resulto en que 1 pólipo se redujo a bajo riesgo y 9 pólipos se actualizaron como a alto riesgo.La principal limitación del estudio es el diseño retrospectivo. La toma de decisiones en torno al tratamiento de los cánceres T1 es compleja y otros factores además de las características histopatológicas del tumor pueden haber sido parte de las decisiones terapéuticas.Hay una alta tasa de informes incompletos de elementos centrales y opcionales para informes de patología de pólipos colorrectales malignos en Alberta. Algunas variables utilizadas por los cirujanos colorrectales para la toma de decisiones, como el patrón tumoral en ciernes y la profundidad de la invasión submucosa, no se consideran elementos centrales y se informan con poca frecuencia. Una revisión de patología realizada por un segundo patólogo a menudo resulta en un cambio en la estratificación del riesgo. Consulte Video Resumen en http://links.lww.com/DCR/B98. (Traducción-Dr. Adrian E. Ortega).

Urothelial metaplasia of the seminal vesicle and ejaculatory duct associated with crossed-fused renal ectopia and Hutch diverticulum of the bladder.

The presence of urothelial epithelial metaplasia in a seminal vesicle is an exceptionally rare finding. We describe a unique case of urothelial metaplasia of the seminal vesicle and ejaculatory duct, found in a radical prostatectomy specimen from a patient with complex urogenital anatomy. A 70-year-old patient with organ confined (pT2) prostatic adenocarcinoma (Gleason score 3+4 = 7) had a right-sided Hutch diverticulum and a left crossed-fused renal ectopia. Although the histogenesis of urothelial metaplasia in the seminal vesicle remains unclear, in the patient presented herein it likely developed as a consequence of the previously unrecognized malformation.

Impact of an Integrated Hip Fracture Inpatient Program on Length of Stay and Costs.

BACKGROUND: Hip fractures are associated with significant morbidity and mortality. Co-management models pairing orthopaedic surgeons with hospitalists or geriatricians may be effective at improving processes of care and outcomes such as length of stay (LOS) and cost. We set out to determine the effect of an integrated hip fracture co-management model on LOS, cost, and process measures. METHODS: We conducted a single-center pre-post study of 571 patients admitted to an academic medical center with hip fractures between January 2009 and December 2013. The group receiving an integrated medical-surgical co-management incorporating continuous improvement methodology was compared with a control population. Primary outcome was LOS. Secondary outcomes included cost per case, time to surgery, osteoporosis (OP) treatment, preoperative echocardiogram utilization, mortality, and readmission. RESULTS: LOS decreased from 18.2 (1.1) to 11.9 (1.5) days, a reduction of 6.3 days (P < 0.001). Mean cost decreased by $4953 (P < 0.001) per case. Mean time to surgery decreased from 45.8 (66.8) to 29.7 (17.9) hours (P < 0.001). Initiation of OP treatment increased from 55.8% to 96.4% (P < 0.001). Preoperative echocardiogram use decreased from 15.8% to 9.1% (P < 0.05). There was a nonsignificant difference in mortality rate (5.0% vs. 2.1%, P = 0.06). Readmission rate remained unchanged (4.6% vs. 6.0%, P = 0.56). CONCLUSIONS: An integrated medical-surgical co-management model incorporating continuous improvement methodology was associated with reduced LOS, costs, time to surgery, and increased initiation of appropriate OP treatment. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.