Homer O. Wiland

Clinical criteria underestimate complete pathological response in rectal cancer treated with neoadjuvant chemoradiotherapy.

BACKGROUND: Published criteria define specific mucosal features of clinical complete response for rectal cancer after neoadjuvant chemoradiotherapy. OBJECTIVE: The aim of this study was to determine the performance of these criteria to identify a pathological complete response. DESIGN: Histopathology reports were retrieved for consecutive rectal cancers treated with neoadjuvant therapy followed by proctectomy. The mucosal appearance of residual disease was compared with the final pathological stage. SETTING: This study was conducted at a single-institution, tertiary referral center. PATIENTS: The study included 238 patients. INTERVENTIONS: All patients underwent neoadjuvant chemoradiation followed by proctectomy between 1997 and 2007. MAIN OUTCOME MEASURES: Gross mucosal appearance was compared with the final pathological stage. RESULTS: Following neoadjuvant chemoradiation, 61 of 238 (25%) patients were downstaged to ypT0. Forty-five of these 61 patients (74%) had a residual mucosal abnormality that precluded assignment of a complete response. Of these, 40 had residual ulcers (up to 10 mm in depth) and 5 had exophytic lesions. The remaining 16 patients with pathological complete response fulfilled criteria for clinical complete response and had either no visible abnormality or a scar. Although mucosal complete clinical response was statistically associated with ypT0 status (p < 0.0001), 6 of 22 (27%) patients with mucosal complete clinical response still had residual disease. Smaller size of residual mucosal abnormality was also associated with ypT0 status (p = 0.002). LIMITATIONS: This is a retrospective study and preoperative clinical assessment of response is not recorded for comparison to resected specimens. CONCLUSIONS: The majority of patients attaining ypT0 status do not display mucosal features of complete response. When present, a mucosal complete response is statistically associated with ypT0 status, but is poorly sensitive. If rectal conservation after chemoradiation is to be pursued, alternative means of restaging are required to maximize the number who might benefit from this approach.

Morphologic and Molecular Characterization of Traditional Serrated Adenomas of the Distal Colon and Rectum

Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62% of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF-mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration.

Depth and lateral spread of microscopic residual rectal cancer after neoadjuvant chemoradiation: implications for treatment decisions.

The aim of this study was to determine the distribution of residual tumour within the bowel wall in relation to residual mucosal abnormalities (RMAs) and surrounding normal mucosa in patients with rectal cancer who underwent neoadjuvant chemoradiation followed by curative surgery.

Interobserver Variability and Feasibility of Polymerase Chain Reaction-Based Assay in Distinguishing Ischemic Colitis From Clostridium difficile Colitis in Endoscopic Mucosal Biopsies

Polymerase chain reaction (PCR)-based assays using stool samples are currently the most effective method of detecting Clostridium difficile. This study examines the feasibility of this assay using mucosal biopsy samples and evaluates the interobserver reproducibility in diagnosing and distinguishing ischemic colitis from C difficile colitis. Thirty-eight biopsy specimens were reviewed and classified by 3 observers into C difficile and ischemic colitis. The findings were correlated with clinical data. PCR was performed on 34 cases using BD GeneOhm C difficile assay. The histologic interobserver agreement was excellent (κ= 0.86) and the agreement between histologic and clinical diagnosis was good (κ = 0.84). All 19 ischemic colitis cases tested negative (100% specificity) and 3 of 15 cases of C difficile colitis tested positive (20% sensitivity). C difficile colitis can be reliably distinguished from ischemic colitis using histologic criteria. The C difficile PCR test on endoscopic biopsy specimens has excellent specificity but limited sensitivity.

Limited utilization of serologic testing in patients undergoing duodenal biopsy for celiac disease

BackgroundClinical algorithms for the workup of celiac disease often recommend the use of serologic assays for initial screening, followed by duodenal biopsy for histologic confirmation. However, the majority of duodenal biopsies submitted to pathology for “rule out celiac” are negative. The objective of this study was to determine the underlying causes for this low diagnostic yield.MethodsWe performed a retrospective review of pathology reports from 1432 consecutive duodenal biopsies submitted for pathologic assessment to “rule out celiac” and correlated biopsy results with results for concurrent serologic testing for celiac autoantibodies.ResultsThe majority of patients had no record of serologic testing prior to biopsy, and evidence of positive serology results was found in only 5% of patients. Most duodenal biopsies were submitted as part of a multi-site GI sampling strategy that included biopsies from other locations. In this context, serologic results correlated with the likelihood of significant duodenal and non-duodenal findings, and were also helpful in evaluating patients with indeterminate duodenal histology.ConclusionsThe presence of a positive screening test for celiac autoantibodies does not appear to be a major driver in the decision to submit duodenal biopsies for evaluation of celiac disease, which accounts for the low incidence of findings in these samples. In patients where celiac serology testing was performed, the results were a good predictor of the likelihood of findings on biopsy.

Detection of anal dysplasia is enhanced by narrow band imaging and acetic acid.

Anal intraepithelial neoplasia precedes the development of anal squamous cell carcinoma. Detection of the lesion is essential to management. This paper describes a prospective study to detect and ablate anal squamous intraepithelial lesions (SILs) using white light narrow band imaging (NBI) and NBI with acetic acid (NBIA).

Defining the Gray Zone: Client Billing and Contractual Joint Ventures

Client billing is a practice in which the referring clinician pays the dermatopathology laboratory a fixed amount for both the technical and professional fees to prepare and interpret the biopsy, and then the clinician bills the Please provide affiliation details for all authors.patient or insurer. Although not inherently illegal or unethical, the practice becomes ethically suspect when a clinician takes advantage of client billing to secure personal profit, or fails to act in the patient’s best interest by not selecting the highest quality laboratory to interpret the patient’s biopsies. Contractual joint ventures are practice models which allow groups of clinicians to bill for work done by independently contracted (‘pod” model) or employed pathologists (“vertically integrated” model), practices that otherwise would not be permitted under Medicare reassignment rules. This chapter presents ethical arguments for and against these practices using illustrative case scenarios.

Hepatic angiosarcoma mimicking sinusoidal obstruction syndrome/venoocclusive disease: a pathologic-radiologic correlation

We present a case of a 63-year-old man with liver dysfunction and biopsy findings of venoocclusive disease (VOD) who, at autopsy, was discovered to have multifocal hepatic angiosarcoma. After double lung transplantation, he initially presented with signs of liver failure and portal hypertension resulting in recurrent high-volume ascites. Clinically, VOD was considered, and tacrolimus was discontinued, due to its known association with VOD. This, however, did not result in clinical improvement, and computed tomography eventually revealed the development of multiple low-attenuating hepatic lesions over the course of several months. Biopsies of the masses and background liver demonstrated changes most consistent with VOD, characterized by sinusoidal congestion affecting the centrilobular areas with associated hepatocyte atrophy and dropout. A reticulin stain highlighted deposition of reticulin fibers within the sinusoids and central veins. Scattered sinusoidal atypical cells were identified; however, a definitive diagnosis of malignancy was not possible. He eventually passed away because of complications of liver disease. At autopsy, there were multiple firm, red-brown masses identified throughout both hepatic lobes. Upon histologic review, the masses were shown to be angiosarcoma. Away from the tumor, the liver also demonstrated features of VOD. It is likely that the histologic appearance of VOD in the background liver probably represents secondary changes due to injury to the hepatic sinusoids by the primary malignancy. We conclude that it is necessary to consider the possibility of unsampled vascular malignancy when hepatic masses are identified on imaging and histology is consistent with VOD.

Anal Condyloma Acuminata and Anal Dysplasia

Anal condyloma acuminata and anal dysplasia are human papillomavirus-related intraepithelial lesions that are precursors of anal squamous cell cancer. Risk factors include immunosuppression for patients who have inflammatory bowel disease, cervical cancer, human immunodeficiency virus, a history of solid organ transplantation, as well as viral transmission by person-to-person contact. Assessment includes disease-specific history and physical examination, selected tests, and biopsy of suspicious lesions. Treatment includes antiviral agents, anticytotics, strong acid, or ablation using a variety of techniques. Vaccine prophylaxis against four types of human papillomavirus is available. This chapter discusses infection, diagnosis, and treatment of condyloma acuminata and anal dysplasia.

Ethical Adventures in 21st Century Dermatopathology

Several ethical challenges are either unique to or particularly significant for the practice of dermatopathology. These challenges include: conflicts of interest when clinicians read their own biopsy slides, the appropriate role for clinical recommendations within a pathology report, ethical behavior by expert witnesses in malpractice trials, and the role of managed care in controlling access to dermatopathology. Relevant ethical codes and a commitment to patients’ best interests can help guide physicians through these contemporary ethical challenges in dermatopathology.