Immunocytochemistry as an adjunct to diagnostic cytology.

Immunocytochemistry as a routine ancillary test remains a distant reality for most diagnostic laboratories. Notable barriers to the mass deployment of ICC include: the large variety of specimen preparations, the small specimen size, lack of validation and lack of control specimens. As clinicians constantly strive to answer questions relating to diagnosis, therapy and prognosis with minimally invasive sampling techniques, the cytopathology community must endeavour to adopt ancillary specimen testing by ICC as a core element of diagnostic cytology.

Intravascular lymphocytosis in acute appendicitis: potential mimicry of chronic lymphocytic leukaemia.

AIMS: Intravascular lymphocytosis (IVL) in appendectomy specimens is a fairly common phenomenon but has not been described and studied in detail. The aim was to describe the IVL phenomenon in appendiceal specimens removed for appendicitis that can mimic chronic lymphocytic leukaemia and to investigate factors that could contribute to the development of IVL. METHODS AND RESULTS: The clinicopathology of 100 appendectomy cases and the appendices from 20 right hemicolectomy cases were reviewed. The IVL phenomenon was more commonly seen in laparoscopic appendectomy specimens [Fisher's exact 0.011, odds ratio (OR) 3.14] and in patients <38 years old (Fisher's exact 0.012, OR 3.01). CONCLUSIONS: Surgical manipulation and the patient's innate immunity are contributary factors to the development of the IVL phenomenon. Pathologists should be aware of this histological artefact in order to prevent overdiagnosis of intravascular lymphoid neoplasia.

Microscopic colitis: a review for the surgical endoscopist.

Microscopic colitis (MC) is an inflammatory condition of the colon distinct from Crohn disease or ulcerative colitis that can cause chronic diarrhea as well as cramping and bloating. Although it was first described 30 years ago, awareness of this entity as a cause of diarrhea has only become more widespread recently. Up to 20% of adults with chronic diarrhea who have an endoscopically normal colonoscopy may have MC. Endoscopic and radiological examinations are usually normal, but histology reveals increased lymphocytes in the colonic mucosa, which typically cause watery nonbloody diarrhea. Treatment is initially supportive but can include corticosteroids and immunomodulatory therapy for resistant cases. Since surgeons perform a large number of colonoscopies and sigmoidoscopies to assess diarrhea, it is important to be aware of this disease and to look for it with mucosal biopsy in appropriate patients.

Microscopic colitis-defining incidence rates and risk factors: a population-based study.

BACKGROUND & AIMS: The burden and determinants of microscopic colitis (MC) in North America are inadequately defined. We determined the incidence rate of and risk factors for MC in a well-defined North American population. METHODS: A population-based cohort study was conducted between April 1, 2002, and March 31, 2004. All adults with a pathologic diagnosis of MC were identified and comprehensive chart review was undertaken to confirm the diagnosis and identify risk factors. Category-specific risks for developing MC were reported as rate ratios (RRs) with exact 95% confidence intervals (CIs). RESULTS: MC was identified in 164 individuals for an annual incidence rate of 10.0 per 100,000 person-years (lymphocytic colitis, 5.4; collagenous colitis, 4.6 per 100,000). Patients older than the age of 65 were more than 5 times more likely to develop MC (RR, 5.6; 95% CI, 4.0-7.7). Women were at higher risk of acquiring MC for both collagenous colitis (RR, 3.44; 95% CI, 2.07-5.97) and lymphocytic colitis (RR 6.29; 95% CI, 3.21-13.74). Elderly women with a history of malignancy were associated with a higher risk of MC (RR, 3.59; 95% CI, 1.68-7.01), as were patients with celiac disease (RR, 7.9; 95% CI, 4.0-14.2) and hypothyroidism (RR, 6.1; 95% CI, 3.5-10.0). CONCLUSIONS: This was a large population-based cohort study of MC and our incidence rates were consistent with previously reported population-based studies in North America and Europe. An increased incidence of MC was observed in several disease states with the novel finding of an increased risk of MC with malignancy.

The risk of microscopic colitis in solid-organ transplantation patients: a population-based study.

BACKGROUND: Microscopic colitis (MC) has not been recognized as a complication of transplantation because patients are on immunosuppressant medications. The objective of this work was to describe the risk of developing MC after solid-organ transplantation. METHODS: This population-based cohort study identified all cases of MC diagnosed after kidney, kidney and pancreas, or liver transplantation using pathology and transplantation databases. The annual incidence and point prevalence of MC after transplantation was calculated. The incidence rate of MC among transplantation patients was compared with the general population and presented as a Standardized Incidence Ratio (SIR) with 95% confidence intervals. RESULTS: Seven cases (0.9%) of MC were diagnosed in kidney (n=2), kidney and pancreas (n=1), and liver (n=4) transplantation recipients. The point prevalence of MC was 8.8 per 1000 transplantation recipients. The annual incidence rate of MC in solid-organ transplantation patients was 5.0 cases per 1000 person-years. The SIR of developing MC after transplantation was 50.5 (95% confidence interval 13.6-131.8). The average age of diagnosis of MC was 49.4+/-5.3 years, average time of onset from transplantation was 67.4+/-27.0 months, and the average latency period was 30.1+/-9.0 months. Once diagnosed, all patients responded to MC-specific therapy. CONCLUSION: Physicians should have a low threshold to investigate for MC in solid-organ transplantation recipients who present with chronic diarrhea because this population is at an increased risk of developing MC.

Large cell neuroendocrine carcinoma arising in a sessile serrated adenoma: a novel observation.

A 68-year-old woman underwent polypectomy of 2 right-sided colonic polyps identified by screening colonoscopy. Histologic examination of both polyps showed features of sessile serrated adenoma. The larger polyp harbored an invasive tumor composed of large, high-grade cells arranged in nests and cords without tumoral mucin production. Immunohistochemistry demonstrated synaptophysin, cdx-2, cytokeratin 7, and cytokeratin 20 positivity. Both invasive carcinoma and sessile serrated adenoma showed a decreased expression level to focal negative expression of hMLH-1 by immunohistochemistry. Combined morphologic and immunohistochemical features favored large cell neuroendocrine carcinoma arising in a sessile serrated adenoma. Specific carcinoma subtypes and special histologic features (eg, tumor-infiltrating lymphocytes) have been previously reported in carcinomas arising from sessile serrated adenomas. Large cell neuroendocrine carcinoma has not yet been reported in association with sessile serrated adenomas, with this case suggesting a rare but potentially novel end point for the microsatellite instability pathway.

Advantages of voice reproduction and the development of a biomimetic self-regulating double-clack valve for a prosthesis of the larynx--a feasibility study.

The human larynx is a versatile organ. Main functions are phonation, protection and regulation of the air ways. Patients suffer severely from the diagnosis of a laryngeal carcinoma of the stages T3 and T4. In most cases this diagnosis will lead to a total laryngectomy, which is usually dissatisfying in the sense of postoperative rehabilitation. The postoperative consequences include the loss of the native voice, the loss of regular air ways via mouth and nose, sense of smell, and the inability to build up an abdominal pressure. In this paper we focus on the feasibility of a modular larynx prosthesis which enables the laryngectomee to talk with his native voice, to breathe via the regular air ways, and to build up abdominal pressure. In particular we will give insights for a postoperative solution - a modular prosthesis based on a biomimetic self-regulating double clack-valve and on a voice reconstruction module, a so called vocoder. The vocoder is a device to reproduce the natural human voice. Most important for the use is an additional device required to analyze, conserve and manage voice characteristics of the patient before surgery. The self-regulating double clack-valve is designed to build up an abdominal pressure e.g. to cough. Therefore, our valve-system is working in both directions - a two-way valve system. By bridging the gap of the regular air ways lost by laryngectomy, the sense of smell and taste are restored. In the following we will present details and characteristics of these two main components required for a modular prosthesis of the larynx in laryngectomees.

Diverticular disease of the vermiform appendix: a diagnostic clue to underlying appendiceal neoplasm.

Acquired diverticula of the vermiform appendix are rare and arise as a result of different pathogenetic mechanisms. One of the etiologies includes proximally located, often unsuspected small neoplasms. Although the association of appendiceal diverticulosis and neoplasia is known, it remains underemphasized in the teaching and practice of surgical pathology. To investigate the frequency of appendiceal neoplasms with acquired diverticulosis, we conducted a retrospective analysis of all appendectomy specimens received in our institution for a 55-month period (January 2002-July 2006). A total of 1361 appendectomy specimens were identified. Diverticulosis was diagnosed in 23 (1.7%) of all cases. Eleven (48%) appendectomy specimens with diverticulosis also harbored an appendiceal neoplasm. The association of appendiceal neoplasms with diverticulosis was statistically significant (P < .0001, 2-sided Fisher exact test). Neoplastic processes included 5 well-differentiated neuroendocrine tumors (carcinoids), 3 mucinous adenomas, 1 tubular adenoma, and 2 adenocarcinomas. In one case, routine representative sections sampled only a small focus of carcinoma, which originally went undiagnosed. We stress the need for meticulous gross assessment with histologic examination of the entire appendectomy specimen in cases of appendiceal diverticulosis. Thorough examination is required to rule out an underlying neoplasm as a cause of diverticulosis. As acquired diverticula represent a rare finding, examination of the entire appendix in this setting does not create a significant impact on the workload within the pathologic laboratory.

Role of chemical tests and scene investigation in determination of range of fire.

Forensic pathologists have historically found several characteristics of the entrance wound invaluable in determining range of fire in gunshot fatalities. Among these characteristics are the pattern and constituents of any deposited material such as soot and/or gun powder residues. We describe a case in which the application of previously described characteristics, in the absence of laboratory testing and examination of the crime scene, would have led to an erroneous conclusion with potentially grave consequences. We suggest that all attempts be made to use available laboratory tests and to perform detailed examination of crime scenes in determining the circumstances surrounding fatal gunshot injuries.

Sessile serrated polyp mimicry in patients with solitary rectal ulcer syndrome: is there evidence of preneoplastic change?

CONTEXT: Solitary rectal ulcer syndrome (SRUS) is associated with erythema and ulceration of the rectal wall. Serrated lesions of the colon are divided into conventional hyperplastic polyps and a new set of lesions that are variably called sessile serrated polyps (SSPs) and sessile serrated adenomas. The SSPs are epithelial proliferative lesions that appear to act as a unique pathway to colorectal carcinogenesis. No association between SRUS and SSPs has been previously reported. OBJECTIVE: To assess a possible association between SRUS and morphologic features that mimic SSPs. DESIGN: Twenty-six patients with SRUS, who presented to our institution between January 1, 1999, and November 14, 2004, were retrospectively reviewed for SSP-type morphologic features by 3 pathologists. Ki-67 and hMLH1 immunohistochemical stains were used. Control tissues included 10 conventional left-sided hyperplastic polyps, 10 right-sided large SSPs, 7 adenocarcinomas with known loss of hMLH1 gene expression, and 4 normal human tonsil tissues. RESULTS: Ten (38%) of 26 SRUS specimens demonstrated histologic features consistent with SSPs. These features included exaggerated serration within the lower crypt compartments, crypt branching, hypermucinous appearance of epithelium, and horizontal extension of crypt bases along the muscularis mucosa. All 10 cases of SRUS had positive basal Ki-67 staining in 10% to 20% of cells. Two (20%) of the 10 cases demonstrated focal superficial loss of hMLH1 mismatch repair gene expression within areas of serrated morphologic features. One hyperplastic polyp superimposed on SRUS showed a reduced number of surface epithelial cells that express hMLH1 protein. CONCLUSIONS: Up to 38% of patients with SRUS have histologic changes that mimic SSPs. More importantly, 20% of these serrated lesions were found to have focal loss of hMLH1 gene expression, indicating a potential of preneoplastic change. This phenomenon may reflect an increased propensity for neoplastic progression in response to repeated trauma and repair process in certain cases of SRUS.