Concordance of "Case Level" Global, Highest, and Largest Volume Cancer Grade Group on Needle Biopsy Versus Grade Group on Radical Prostatectomy.

The practice of assigning "case level" biopsy Grade Group (GG) or Gleason Score is variable. To our knowledge, a comparison of the concordance of different biopsy "case level" GG with the prostatectomy GG has not been done in a post-2005 prostate cancer cohort. We evaluated the GG in 2527 patients who had biopsy and radical prostatectomy performed at our institution between 2005 and 2014. We compared the agreements, the upgrades, and the downgrades of 3 different "case level" biopsy GG, with the final GG: (1) Global GG (sum of most prevalent and highest Gleason grade in any biopsy part/site-specific specimen); (2) Highest GG (found in any biopsy part/site-specific specimen); and (3) Largest Volume Cancer GG (found in any biopsy part/site-specific specimen). The concordance between the biopsy and the final GG were evaluated using weighted kappa (κ) coefficient. The biopsy Global GG, Highest GG, and Largest Volume Cancer GG were the same as the final GG in 60.4%, 57.1%, and 54.3% cases, respectively (weighted κ values: 0.49, 0.48, and 0.44, respectively). When final GG contained tertiary 5, the overall GG agreement decreased: Global GG 41.5%, Highest GG 40.3%, and Largest Volume Cancer GG 37.1% (weighted κ: 0.22, 0.21, and 0.18, respectively). A subset analysis for cases in which the biopsy Global GG and Highest GG were different (n=180) showed an agreement of 62.4% (weighted κ: 0.37) and 18.8% (weighted κ: 0.16), respectively. In patients without a tertiary Gleason pattern on radical prostatectomy, the Global GG and the Highest GG were identical in 92.4% of biopsies. Assigning a biopsy "case level" Global GG versus using the Highest GG and the Largest Volume Cancer GG resulted in comparable and slightly improved agreement with the final GG in this cohort.

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.

Gastrointestinal Stromal Tumor Metastasis to the Orbit.

A 66-year-old woman was referred to the authors' service with a 1-week history of blurry vision in her left eye and retro-orbital ache. She had previously undergone a radical distal gastrectomy and omentectomy for gastrointestinal stromal tumor, epithelioid type, 7 years prior. Exophthalmometry confirmed 2 mm of left-sided proptosis. Computed tomography imaging revealed a solid-appearing mass straddling both the intra- and extraconal spaces and involving the superior rectus muscle. An excisional biopsy was performed. Histopathological examination revealed a relatively uniform epithelioid appearance with a high mitotic rate, and immunohistochemical analysis revealed positivity for both KIT (CD117) and CD34. To the best of the authors' knowledge, this is only the second histopathologically confirmed case of gastrointestinal stromal tumor metastasis to the orbit reported in the literature.

Malakoplakia associated with prostatic adenocarcinoma: Report of 4 cases and literature review.

Malakoplakia is an inflammatory process that has been rarely reported in the prostate. Malakoplakia in association with prostatic carcinoma is exceedingly rare with only 4 previously reported cases. We describe the clinical features and the associated pathology in 4 patients who demonstrated malakoplakia of the prostate in association with prostatic adenocarcinoma. Prostatic malakoplakia presenting in association with prostatic adenocarcinoma was identified in 4 patients through a search from the records of 3 institutional databases with large in-house and consult uropathology practices. In 2 of the patients the diagnostic needle biopsy contained only prostatic carcinoma; malakoplakia in association with prostatic carcinoma was documented on prostatectomy, performed 15 and 8weeks after the biopsy, respectively. Both patients experienced urinary infections during the interval between the biopsy and the prostatectomy. The third and fourth patient had a long-standing history of "prostatitis", and acute urinary tract infection with urinary retention, respectively. The needle biopsy in both patients showed concomitant malakoplakia and prostatic carcinoma. One of them also had malakoplakia on the initial biopsy containing only atypical glands and on the subsequent one demonstrating carcinoma. One patient was treated conservatively and one with prostatectomy. Although coexistent prostatic carcinoma and malakoplakia are exceedingly rare, malakoplakia can likely occur as an exceptionally rare complication of a prostate needle biopsy, particularly in individuals with long-term or acute urinary tract infections at the time of the biopsy.

Mixed epithelial-stromal tumor (MEST) of seminal vesicle: a proposal for unified nomenclature.

In contrast to the common tumors of the prostate, seminal vesicle demonstrates low potential for neoplastic proliferation. Of the rare primary seminal vesicle tumors, adenocarcinoma is the most common, but there are also rare seminal vesicle neoplasms which demonstrate epithelial and stromal components. These neoplasms have been described in the literature under various names, including "epithelial-stromal tumor," "cystic epithelial-stromal tumor," "cystadenoma," "cystomyoma," "mesenchymoma," "Müllerian adenosarcoma-like tumor," "phyllodes tumor," and "cystosarcoma phyllodes." The spectrum of reported mixed epithelial-stromal tumors (MEST) of seminal vesicle encompasses low, intermediate and high-grade tumors, but the precise distinction and nomenclature for these tumors remain unsettled. We propose a common nomenclature for these tumors, based on the review of published cases and 2 index cases from our practice, which represent the low-grade category. The first patient was 46 years old and presented with seminal vesicle neoplasm detected on routine rectal examination. The neoplasm measured 4 cm in greatest dimension, and completely replaced the left seminal vesicle. The tumor was circumscribed and consisted of multiple cysts separated by spindle-cell stroma. The second patient was a 60-year-old man, who had an incidental seminal vesicle neoplasm, which was discovered when he underwent a radical prostatectomy for a prostatic adenocarcinoma, (Gleason score 3+4, stage 3a). Both neoplasms contained hypercellular stroma, which was composed of uniform spindle cells, arranged in fascicles and interspersed between the glands. Both tumors lacked worrisome morphology, such as infiltrative borders, cell atypia, increased mitotic activity, hemorrhage, and necrosis. The stromal cells were reactive for estrogen and progesterone receptors, and desmin. The cysts and dilated glands were lined by epithelial cells, which were positive for cytokeratin 7 and were negative for prostate-specific antigen and prostate-specific acid phosphatase. The first patient underwent prostatectomy and was alive and without evidence of disease recurrence or progression after 11 years of follow-up. Similarly, the second patient had no evidence of disease recurrence or progression after 8 months of follow-up. We propose that term seminal vesicle "mixed epithelial-stromal tumor" be used to designate the tumors of the seminal vesicle containing epithelial and stromal components, with a distinction of grade based on the histologic features and the biological behavior. Histologic features to be evaluated for grade separation include stromal atypia, mitotic activity, nuclear pleomorphism, and tumor necrosis. Designations "low-grade MEST," "intermediate-grade MEST (uncertain malignant potential)," and "high-grade MEST" of seminal vesicle can be applied to these tumors to better characterize and study them in the future.

Synchronous appendiceal and intramucosal gastric signet ring cell carcinomas in an individual with CDH1-associated hereditary diffuse gastric carcinoma: a case report of a novel association and review of the literature.

BACKGROUND: Hereditary diffuse gastric carcinoma is an autosomal dominant cancer syndrome associated with mutations of the E-cadherin gene (CDH1). E-cadherin is normally involved in cell-cell adhesion, so it not surprising that individuals with this syndrome are predisposed to develop malignancies with dyshesive morphologies at a young age, such as diffuse (signet ring cell) gastric carcinoma and lobular breast carcinoma. Herein we describe the first reported case of primary appendiceal signet ring cell carcinoma arising in a CDH1-associated hereditary diffuse gastric carcinoma kindred with synchronous primary diffuse gastric carcinoma. CASE PRESENTATION: A 51- year old woman, with known CDH1 mutation carrier status and a prior history of lobular breast carcinoma underwent prophylactic total gastrectomy which revealed multifocal intramucosal signet ring cell carcinoma. An appendectomy was performed at the same time due to a prior episode of presumed appendicitis, with pathologic examination significant for a primary signet ring cell carcinoma of the appendix. CONCLUSION: As appendiceal signet ring cell carcinoma is exceedingly rare, the occurrence of this neoplasm in this patient, with this particular morphology, provides credence for it being part of the hereditary diffuse gastric carcinoma spectrum of malignancies.

Intramuscular myxoid lipoma in the proximal forearm presenting as an olecranon mass with superficial radial nerve palsy: a case report.

BACKGROUND: Extremity lipomas may occur in any location, including the proximal forearm. We describe a case of a patient with an intramuscular lipoma presenting as an unusual posterior elbow mass. CASE PRESENTATION: We discuss the case of a 57-year-old Caucasian man who presented with a tender, posterior elbow mass initially diagnosed as chronic olecranon bursitis. A minor sensory disturbance in the distribution of the superficial radial nerve was initially thought to be unrelated, but was likely caused by mass effect from the lipoma. No pre-operative advanced imaging was obtained because the diagnosis was felt to have already been made. At the time of surgery, a fatty mass originating in the volar forearm muscles was found to have breached the dorsal forearm fascia and displaced the olecranon bursa. Tissue diagnosis was made by histopathology as a myxoid lipoma with no aggressive features. Post-operative recovery was uneventful. CONCLUSION: We present a case of an unusual elbow mass presenting with symptoms consistent with chronic olecranon bursitis, a relatively common condition. The only unexplained pre-operative finding was the non-specific finding of a transient superficial radial nerve deficit. We remind clinicians to be cautious when diagnosing soft tissue masses in the extremities when unexplained physical findings are present.

Hypoxia-inducible factor signaling provides protection in Clostridium difficile-induced intestinal injury.

BACKGROUND & AIMS: Clostridium difficile is the leading cause of nosocomial infectious diarrhea. Antibiotic resistance and increased virulence of strains have increased the number of C difficile-related deaths worldwide. The innate host response mechanisms to C difficile are not resolved; we propose that hypoxia-inducible factor (HIF-1) has an innate, protective role in C difficile colitis. We studied the impact of C difficile toxins on the regulation of HIF-1 and evaluated the role of HIF-1alpha in C difficile-mediated injury/inflammation. METHODS: We assessed HIF-1alpha mRNA and protein levels and DNA binding in human mucosal biopsy samples and Caco-2 cells following exposure to C difficile toxins. We used the mouse ileal loop model of C difficile toxin-induced intestinal injury. Mice with targeted deletion of HIF-1alpha in the intestinal epithelium were used to assess the effects of HIF-1alpha signaling in response to C difficile toxin. RESULTS: Mucosal biopsy specimens and Caco-2 cells exposed to C difficile toxin had a significant increase in HIF-1alpha transcription and protein levels. Toxin-induced DNA binding was also observed in Caco-2 cells. Toxin-induced HIF-1alpha accumulation was attenuated by nitric oxide synthase inhibitors. In vivo deletion of intestinal epithelial HIF-1alpha resulted in more severe, toxin-induced intestinal injury and inflammation. In contrast, stabilization of HIF-1alpha with dimethyloxallyl glycine attenuated toxin-induced injury and inflammation. This was associated with induction of HIF-1-regulated protective factors (such as vascular endothelial growth factor-alpha, CD73, and intestinal trefoil factor) and down-regulation of proinflammatory molecules such as tumor necrosis factor and Cxcl1. CONCLUSIONS: HIF-1alpha protects the intestinal mucosa from C difficile toxins. The innate protective actions of HIF-1alpha in response to C difficile toxins be developed as therapeutics for C difficile-associated disease.

Mitogen-activated protein kinase pathways contribute to hypercontractility and increased Ca2+ sensitization in murine experimental colitis.

Inflammatory bowel disease (IBD) is associated with intestinal smooth muscle dysfunction. Many smooth muscle contractile events are associated with alterations in Ca(2+)-sensitizing pathways. The aim of the present study was to assess the effect of colitis on Ca(2+) sensitization and the signaling pathways responsible for contractile dysfunction in murine experimental colitis. Colitis was induced in BALB/c mice by providing 5% dextran sulfate sodium (DSS) in drinking water for 7 days. Contractile responses of colonic circular smooth muscle strips to 118 mM K(+) and carbachol (CCh) were assessed. DSS induced a T(H)2 colitis [increased interleukin (IL)-4 and IL-6] with no changes in T(H)1 cytokines. Animals exposed to DSS had increased CCh-induced contraction (3.5-fold) and CCh-induced Ca(2+)-sensitization (2.2-fold) responses in intact and alpha-toxin permeabilized colonic smooth muscle, respectively. The contributions of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) to CCh-induced contractions were significantly increased during colitis. Ca(2+)-independent contraction induced by microcystin was potentiated (1.5-fold) in mice with colitis. ERK and p38MAPK (but not Rho-associated kinase) contributed to this potentiation. ERK1/2 and p38MAPK expression were increased in the muscularis propria of colonic tissue from both DSS-treated mice and patients with IBD (ulcerative colitis >> Crohn's disease). Murine T(H)2 colitis resulted in colonic smooth muscle hypercontractility with increased Ca(2+) sensitization. Both ERK and p38MAPK pathways contributed to this contractile dysfunction, and expression of these molecules was altered in patients with IBD.

Multiple lymphomatous diverticulosis and comorbid chronic lymphocytic leukemia: novel manifestations of ileocolic mantle cell lymphoma.

Mantle cell lymphoma (MCL) has tropism for the gastrointestinal tract (GIT) identifiable as multiple polyps and mass lesions throughout the GIT. We describe 2 novel manifestations of MCL. A 60-year-old woman with known chronic lymphocytic leukemia (CLL) had an exophytic mass of the appendiceal orifice. Multiple polypoid masses of the distal ileum were identified in the right hemicolectomy specimen (multiple lymphomatous polyposis). Ancillary studies confirmed the coexistence of the 2 independent lymphoproliferative disorders. A 69-year-old man had recurrent urinary tract infections and pneumatouria caused by a colovesicular fistula complicating diverticulosis coli. Segmental resections of the sigmoid and ileocecum confirmed diverticulosis of the left and right colon. Histology identified infiltrates of MCL confined to the penetrating aspects of colonic diverticula. MCL has not been documented to coexist with CLL. An invaginating morphology of lymphoma, multiple lymphomatous diverticulosis is also a novel presentation. These 2 scenarios expand MCL's known manifestations within the GIT.

A definitive diagnosis of primary Hodgkin lymphoma on endoscopic biopsy material utilizing in-depth immunohistochemical analysis.

The esophagus and stomach can be primary sites for Hodgkin lymphoma (HL). The pathognomonic feature of HL is the Reed-Sternberg cell. Because these cells can be rare in HL tumours, biopsies obtained via endoscopy are usually inadequate for establishing a definitive diagnosis. A case of a gastroesophageal junction primary HL is presented that was diagnosed on endoscopic biopsy material with the assistance of the immunohistochemical stains PAX5 and MUM1 which verified the presence of Reed-Sternberg cells. The patient was effectively treated for HL and avoided traditional laparotomy or thoracotomy procedures to obtain the diagnosis. This advanced immunohistochemical approach should be the standard in the diagnosis of primary gastrointestinal HL. An endoscopy-based approach should obviate more invasive, open biopsy procedures for establishing HL diagnosis.

Enterocolic lymphocytic phlebitis: statistical analysis of histology features in viable and ischemic bowel.

Enterocolic lymphocytic phlebitis is a rare cause of segmental ischemic enterocolitis. This artery-sparing transmural vasculitis is classically a circumferential phlebitis with perivenular lymphocyte cuffing and thrombi in the absence of systemic manifestations. Myointimal hyperplasia may represent a chronic phase of enterocolic lymphocytic phlebitis. Subclinical or early stage enterocolic lymphocytic phlebitis is not well delineated. We analyzed 600 submucosal and subserosal veins from both ischemic and intact bowel segments to discern if vascular morphology varied between sites. Crescentic and circumferential lymphocytic phlebitis is more common in viable bowel than in the ischemic segment. A nonsignificant trend was found for increased crescentic morphology between intact bowel remote from the ischemic focus compared with that adjacent to the ischemic focus. Hallmarks of ischemic bowel are necrotizing phlebitis and thrombi formation. Thrombophlebitis morphology is distinctly different in viable and ischemic bowel, changing from the classic lymphocytic to necrotizing lesions respectively.

Intravascular synovial sarcoma of the external iliac vein and reconstruction with the superficial femoral vein.

Intravascular synovial sarcoma is a rare neoplasm that arises in large veins of the junctional zone between the proximal leg and lower trunk in adult women. Herein we report the first case of an intravascular synovial sarcoma of the external iliac vein. It was successfully treated with neoadjuvant radiotherapy, radical excisional surgery, and combined arterial and venous reconstruction. Intravascular synovial sarcoma should be considered in the differential diagnosis of any adult woman with deep venous thrombosis and a mass of the femoral or iliac venous system.

Acute hepatic failure and multi-system organ failure secondary to replacement of the liver with metastatic melanoma.

BACKGROUND: Metastatic malignant melanoma to the liver resulting in fulminant hepatic failure is a rare occurrence. CASE PRESENTATION: A 46 year old man presented to hospital with massive hepatomegaly, elevated liver enzymes and increased lactate three weeks following resection of a malignant melanoma from his shoulder (Clark level 5). Initially stable, he decompensated 24 to 48 hours subsequent to presentation with respiratory failure requiring mechanical ventilation, distributive shock requiring high dose vasopressor infusion, coagulopathy refractory to plasma infusion, progressive rise in liver enzymes and severe metabolic abnormalities including hyperkalemia, acidosis, hyperphosphatemia, hyperuricemia and hypocalcemia. Refractory to aggressive physiologic support he received palliation. Autopsy revealed >80% liver infiltration by metastatic malignant melanoma. CONCLUSION: We report a case of fulminant hepatic failure secondary to metastatic malignant melanoma infiltration of the liver.