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Intralaboratory timeliness of surgical pathology reports. Results of two College of American Pathologists Q-Probes studies of biopsies and complex specimens.

OBJECTIVE: To develop multi-institutional reference databases for intralaboratory timeliness of surgical pathology routine biopsies and complex specimens from the time of specimen accessioning to report completion, and to examine the influence of laboratory characteristics and practices on turnaround time (TAT). DESIGN: Participants in the Q-Probes quality improvement program of the College of American Pathologists took part in two separate studies, the first conducted in 1992 and 1993 and the second in 1993 and 1994. Each participant tracked the number of days from specimen accessioning to report completion for 30 routine biopsies and 30 complex specimens in each study. Based on this intralaboratory time interval, performance was compared with the College of American Pathologists' laboratory accreditation standard of 2 working days. PARTICIPANTS: Five hundred twenty-five surgical pathology laboratories responded to the study of routine biopsies, and 489 laboratories responded to the study of complex specimens. Participants were mainly located in the United States, but there were respondents from Canada, Australia, New Zealand, and Hong Kong as well. RESULTS: In the first study, evaluation of 15 725 biopsy cases showed that the cumulative aggregate percentage of routine biopsy cases processed from the time of specimen accessioning to report completion was 79% by 1 working day, 95% by 2 working days, and 98% by 3 working days. Individual participant's data revealed that all reports were completed by the second working day in 90% of the laboratories and by the third working day in 95% of laboratories. Factors that significantly contributed to increased report TAT included larger institutional size, a greater number of surgical pathologists, greater annual surgical pathology volume processed, technical processing resulting in delayed slide availability, pathology practices that integrated residency training, and reduced staffing levels of histotechnologists/technicians and transcriptionists. Shorter TATs were achieved in those institutions that had previously established a TAT goal for routine biopsy specimens. In the second study of 14 298 aggregate complex specimen cases, 68% required routine processing and 32% required special handling. Overall, 56% of all complex specimen reports were processed and completed in 1 working day, 81% in 2 working days, 91% in 3 working days, and 95% in 4 working days. On average, the percentage of cases processed and reports signed out in 2 working days or less was 80% for all complex specimen cases, 90% for routine cases, and 60% for special-handling cases. The mean of all participants' median TATs was 1.5 days (range 0-5 days) for complex specimens, 1.3 days (range 0-5 days) for cases requiring routine handling, and 2.6 days (range 0-13.5 days) for cases requiring special handling. Several factors were associated with increased report TAT: institutional occupied bedsize greater than 450, routine responsibility for gross dissection assigned to residents only, earliest availability of slides after 12 pm, resident involvement in sign-out, interposing a day between availability of slides and final slide sign-out for resident education purposes, and a greater number of surgical pathologists. CONCLUSIONS: We have documented that for the majority of routine cases, the College of American Pathologists Laboratory Accreditation Program's TAT standard of report completion time within 2 working days for the intralaboratory component of TAT is a reasonable goal. This standard was successfully met by participants in 95% of routine biopsy cases and 91% of routine complex specimens. Special-handling procedures for complex specimens contributed, on average, an additional delay of 1.3 days. To our knowledge these are the first systematic studies to describe timeliness from the time of specimen accessioning to report completion for surgical pathology specimens, and they may serve as reference databases for benchm

Biopsy↗

Error rates in Australian chemical pathology laboratories.

OBJECTIVE: To measure transcription and analytical errors made by Australian chemical pathology laboratories. DESIGN: Retrospective data collection covering the period 1 November 1993 to 1 April 1994. SETTING AND PARTICIPANTS: Fourteen pathology laboratories in five Australian States (seven in the public sector, and seven in the private sector). MAIN OUTCOME MEASURES: Error rates in transcribing information from request forms to computer record systems, and laboratory performance on chemical analysis. RESULTS: Pathology laboratories had a transcription-error rate of up to 39% and an error rate of up to 26% for analytical results. The worst-performing laboratory had errors (of patient identification or results of analysis) in 46% of requests. The three best-performing laboratories achieved 85% error-free reporting, with one achieving 95%. CONCLUSIONS: Error rates in Australian pathology laboratories vary widely, but may be as high as 46% for all specimens in some laboratories. The types of errors reported were under the control of the laboratory, and would affect the accuracy of reported pathology test results, with potential adverse outcomes for patient care and inefficient use of health-care resources. There is a need to establish broader quality assurance programs and performance requirements to reduce these types of error.

Australia↗

[From "great Germans" and "proud peaks"--textbooks of German medical history and pathology (1858 to 1945)].

Textbooks on German medical history are a valuable source when analyzing the discipline's view on the foundation of scientific medicine. This paper deals with descriptions of the history of pathology found in textbooks between 1858 and 1945: In particular, pathological anatomy and Rudolf Virchow's "cellular pathology" were the cornerstones of the foundation of modern medicine in the 19th century. The way textbooks deal with the history of pathology mirrors the development of German history of medicine: Since the turn of the century the latter felt devoted to an ahistoric teleological approach which did not change in the "Third Reich". This situation hampered a critical histoography which would show relations of the history of pathology to cultural, social and political history.

Education, Medical↗

Amended reports in surgical pathology and implications for diagnostic error detection and avoidance: a College of American Pathologists Q-probes study of 1,667,547 accessioned cases in 359 laboratories.

OBJECTIVES: To evaluate amended report rates relative to surveillance methods and to identify surveillance methods or other practice parameters that lower amended report rates. DESIGN: Participants in the 1996 Q-Probes quality improvement program of the College of American Pathologists were asked to prospectively document amended surgical pathology reports for a period of 5 months or until 50 amended reports were recorded. The methods of error detection were also recorded and laboratory and institutional policies surveyed. Four types of amended reports were investigated: those issued to correct patient identification errors, to revise originally issued final diagnoses, to revise preliminary written diagnoses, and to revise other reported diagnostic information that was significant with respect to patient management or prognosis. PARTICIPANTS: Three hundred fifty-nine laboratories, 96% from the United States. RESULTS: A total of 3147 amended reports in all four categories from a survey of 1,667,547 surgical pathology specimens accessioned during the study period were issued by the participants. The aggregate mean rate of amended reports was 1.9 per 1000 cases (median, 1.5 per 1000 cases). Of these, 19.2% were issued to correct patient identification errors, 38.7% to change the originally issued final diagnosis, 15.6% to change a preliminary written diagnosis, and 26.5% to change clinically significant information other than the diagnosis. Most frequently, a request from a clinician to review a case (20.5%) precipitated the error detection. Although not statistically significant, a higher amended report rate (1.6 per 1000) for all error types was associated with routine diagnostic slide review that was performed after completion of the surgical pathology report. This is compared to rates for institutions that had routine diagnostic slide review of cases prior to finalization of pathology reports (1.2 per 1000) and institutions that had no routine diagnostic slide review (1.4 per 100). Slide review of cases prior to completion of reports lowered the rate of amended reports issued for two types of amended reports: those in which the originally issued final diagnosis was changed and those in which information other than the diagnosis was changed for patient management or prognostic significance. Other laboratory practice variables examined were not found to be associated with the amended report rate. CONCLUSIONS: There is an association between lower amended report rates and diagnostic slide review of cases prior to completion of the pathology report. The level of case review and type of case mix that is necessary for optimal quality assurance needs further investigation.

Diagnostic Errors↗

Magnetic resonance imaging signatures of tissue pathology in frontotemporal dementia.

BACKGROUND: The pathologic substrates of frontotemporal dementia (FTD) are difficult to predict in vivo. OBJECTIVE: To determine whether different pathologic substrates of FTD have distinct patterns of regional atrophy on magnetic resonance imaging (MRI). DESIGN: Retrospective case study. SETTING: The Institute of Neurology, University College London, and the Institute of Psychiatry, King's College London. Patients Twenty-one cases of FTD selected on pathologic grounds (9 with ubiquitin-positive [tau- and alpha-synuclein-negative] inclusions [FTD-U], 7 with Pick disease [PiD], and 5 with familial FTD with tau exon 10+16 mutations [tau exon 10+16]) and 20 healthy controls were studied. MAIN OUTCOME MEASURES: Patterns of gray matter atrophy in each group as assessed by voxel-based morphometry (VBM) and a blinded visual assessment of each MRI study. RESULTS: All pathologic substrates were associated with atrophy that involved the inferior and medial temporal and inferior frontal lobes. Additionally, specific VBM signatures were identified for each subgroup: FTD-U was associated with asymmetric (left > right) temporal lobe atrophy, PiD was associated with severe dorsolateral bifrontal atrophy, and tau exon 10+16 was associated with asymmetric (right > left) medial temporal lobe atrophy. The VBM findings were supported by blinded visual assessment. CONCLUSION: These findings suggest that MRI patterns of regional gray matter atrophy constitute signatures of tissue pathology in FTD.

Atrophy↗

Pathologic features of prognostic significance for adrenocortical carcinoma after curative resection.

OBJECTIVE: To identify the pathologic features of prognostic significance in patients with resectable adrenocortical carcinomas. DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Review of the Memorial Sloan-Kettering Cancer Center prospective adrenocortical carcinoma database from 1986 through 1996 identified 46 patients who underwent curative adrenalectomy for primary disease. All cases were reviewed by a single pathologist and each primary tumor was characterized by 16 separate pathologic parameters. MAIN OUTCOME MEASURE: Overall survival rates in the patient population. RESULTS: The 5-year overall survival rate for the entire cohort was 36% (median survival rate, 28 months). Of the pathologic factors analyzed, tumor size, number of mitotic figures, and the presence of intratumoral hemorrhage were independent prognostic factors. Patients presenting with primary tumors larger than 12 cm (n = 30) had a worse outcome compared with those with smaller tumors (n = 16) (5-year survival rate: 53% vs. 22%, P<.05). Mitotic count (> or =6 per 10 high-power fields) was a negative prognostic feature (n = 15) with a 5-year survival rate of 13% vs. 51% for 0 to 6 mitotic figures per 10 highpower fields (n = 31, P<.05). Intratumoral hemorrhage (n = 23) was also a negative prognostic factor compared with no evidence of intratumoral hemorrhage (n = 23) (5-year survival rate, 53% vs. 22%, P<.05). Overall survival rates were also calculated based on the number of pathologic risk factors. Patients with no risk factors had an 83% 5-year survival rate, which decreased to 42% with 1 factor, 33% with 2 factors, and 0% with all 3 risk factors. CONCLUSIONS: Tumor size, hemorrhage, and mitotic count correlate with survival rates for patients undergoing curative resection. Based on these pathologic factors, adrenocortical carcinomas may be divided into low- and high-risk groups.

Adrenal Gland Neoplasms↗

Ultrasound can estimate the pathologic size of infiltrating ductal carcinoma.

HYPOTHESIS: Ultrasound (US) of the breast will accurately measure breast tumor size when compared with size as determined by pathologic examination. DESIGN: Retrospective case series. SETTING: University hospital-based breast center. PATIENTS: Thirty-five women with a diagnosis of breast cancer who had US as a component of their evaluation. MAIN OUTCOME MEASURE: Tumor size as measured by US compared with size measured by pathologic examination. RESULTS: Size measured by US ranged from 0.45 to 3.81 cm. Size measured by pathologic examination ranged from 0.5 to 5 cm. The mean difference of size measured by US vs pathologic size was 0.4 cm (P = .01). When only tumors with invasive ductal histology are evaluated, the mean difference in size is 0.33 cm (P = .008). The range of difference was -1.6 cm to +0.42 cm. Seventeen percent of invasive ductal tumors were underestimated by more than 1 cm; none were underestimated by more than 2 cm. CONCLUSIONS: This study demonstrates that, although US tends to underestimate the pathologic tumor size, 83% of invasive ductal tumors fall within a 1-cm and 100% fall within a 2-cm extension of the US-measured tumor size. Therefore, it is possible to use US to monitor the extent of treatment size when developing very localized therapeutic tools.

Breast↗

Effect of core-needle biopsy vs fine-needle aspiration on pathologic measurement of tumor size in breast cancer.

HYPOTHESIS: Core-needle biopsy (CNB) and fine-needle aspiration (FNA) play an important role in the initial diagnosis of breast cancer. However, CNB might alter the size of the tumor, which might subsequently change its pathologic stage and thus affect the decision about adjuvant chemotherapy. PATIENTS: Between January 2000 and May 2002, we studied 291 patients with invasive carcinoma lesion in a retrospective analysis. One hundred ninety-nine patients underwent ultrasonography-guided CNB. Ninety-two patients had FNA before surgical manipulation. MAIN OUTCOME MEASURES: The clinically measured tumor size using ultrasonography was compared with the pathologic tumor size in both the CNB and FNA groups. The difference in each group was determined and analyzed using a t test. The mean +/- SD preoperative ultrasonographically measured size in the CNB group was 2.09 +/- 1.06 cm and in the FNA group, 2.16 +/- 0.92 cm (no significant difference). The pathologic measurement of the lesion on surgical specimens revealed that the mean pathologic tumor size was 2.09 +/- 0.90 cm in the CNB group and 2.36 +/- 0.92 cm in the FNA group. The changes in size from preoperative measurements by ultrasonography to pathologic measurements on surgical specimens were greater in the CNB group (0.003 +/- 0.65 cm) than in the FNA group (0.20 +/- 0.39 cm; P = .001). CONCLUSIONS: Although the reduction in tumor size might be small with patients who undergo CNB, it must be considered when deciding adjuvant treatment, especially for tumor sizes on the "borderline" in establishing the indication for and the type of adjuvant treatment.

Biopsy, Fine-Needle↗

Eating pathology before and after bariatric surgery: a prospective study.

OBJECTIVE: The objectives of the study were (1) to determine the prevalence of eating pathology in patients before bariatric surgery and at follow-up; (2) to assess the relationship of presurgical eating pathology to various measures of psychopathology; and (3) to assess the relationship between presurgical eating pathology and outcome. METHOD: One hundred sixteen patients were evaluated prior to surgery and at follow-up an average of 5.5 years after surgery. RESULTS: Preoperative binge eating occurred in 52% of patients, 16% met criteria for binge eating disorder, and 10% had the night eating syndrome. All three forms of presurgical eating pathology were statistically associated with cognitive distortions. At follow-up, 33% of patients were vomiting at least weekly. There was no relationship between presurgical eating pathology and weight outcome or presence of vomiting at follow-up. DISCUSSION: Although postoperative vomiting usually does not represent purge behavior, it may represent failed attempts to binge.

Adult↗

Pathologic findings from the national surgical adjuvant breast project. Correlations with concordant and discordant estrogen and progesterone receptors.

Pathologic materials were available for review from 1597 women with Stage II (positive regional node metastases) invasive breast cancer in whom estrogen receptor (ER) and progesterone receptor (PR) assays of the primary tumor were performed. These women were enrolled in a clinical trial comparing the effect of postmastectomy adjuvant L-phenylalanine mustard (L-PAM) and 5-fluorouracil (5-FU) with and without tamoxifen (NSABP Protocol No. 9). Significant pathologic and clinical associations with receptor status were similar for both ER and PR except that the latter, unlike ER, was not related to patient age. Regression analyses revealed that the most significant pathologic features related to a concordant positive ERPR receptor status was low (well differentiated) nuclear and histologic grades, slight or absent tumor lymphoid infiltrate, slight or absent necrosis and moderate or marked elastica in decreasing order of importance. All of the factors enumerated are directly or indirectly related to tumor differentiation. Recognition of four or five conforming pathologic features allows for the prediction of either ER or PR status in 70% to 80% of instances respectively, and the presence of three features in 69%. This latter figure is similar to that of estimation of nuclear grade alone. Thirty percent of ERPR estimates were discordant i.e., either ER-PR+ or ER+PR-. Pathologic features associated with discordant assays were not similar to those found when the ERPR estimates were concordant. Life table analyses revealed patients with discordant receptors to exhibit disease-free survival intermediate to that of those with ER+PR+ and ER-PR- values. This information suggests that a discordant receptor status is more reflective of an aberration of ER metabolism than a methodologic error. Histograms correlating frequency of nuclear grades with levels of ER and PR were comparable and revealed patterns indicating the propriety of relating values less than 10 fm/mg as being receptor negative. The frequency of well-differentiated nuclei increased with ascending levels of ER and PR.

Breast Neoplasms↗

Prognostic significance of clinical and pathologic features in diffuse large B-cell lymphoma.

BACKGROUND AND METHODS: The diffuse large cell non-Hodgkin lymphomas are a heterogeneous group of neoplasms that are potentially curable. To identify important predictors of clinical outcome, the authors evaluated the clinical and pathologic features of 114 patients with newly diagnosed diffuse large B-cell lymphoma who were uniformly staged and treated with curative intent. The authors were particularly interested in determining whether any pathologic features added to the ability of the clinical features to predict patient survival. RESULTS: Several clinical and pathologic features were found to be associated with survival by univariate analysis. However, multivariate analysis disclosed that only the stage of disease and the symptom status were significantly associated with survival. Low stage and lack of B symptoms were favorable indicators of overall survival and failure-free survival. CONCLUSIONS: The authors suggest that the evaluation of pathologic features in diffuse large B-cell lymphoma has little prognostic utility and recommend that the pathology evaluation be limited to features that are useful for diagnostic purposes.

Aged↗

Pathologic stage III endometrial carcinoma. Prognostic factors and patterns of recurrence.

BACKGROUND: This review was done to assess the outcomes and patterns of recurrence in a group of patients with Stage III endometrial carcinoma that might help guide adjuvant therapy. METHODS: A retrospective review was performed of 105 patients treated from 1970-1990 at three institutions. All patients underwent abdominal hysterectomy, with 60 having pathologic node assessment and 45 having cytologic examination of peritoneal washings. A single extrauterine site was involved in 75% of patients; 20% and 5% had two and three sites involved, respectively. All patients received postoperative external beam irradiation to the pelvis or pelvis and paraaortic regions for pathologically positive paraaortic nodes. Actuarial techniques were used to estimate the survival and recurrence rates. RESULTS: The 5-year disease-free survival rate for all patients was 64%. Univariate analysis revealed that the depth of myometrial penetration, the clear cell or papillary serous pathologic type, the histologic grade, and the number of extrauterine sites predicted disease-free survival. Cox regression revealed the grade and pathologic findings to be independent predictors of disease-free survival. The overall 5-year pelvic recurrence rate was 21%, with multivariate analysis revealing the grade to be the strongest prognostic factor. Pathologic findings and the number of involved extrauterine sites were the most important prognostic factors for abdominal recurrence and other sites of distant relapse. CONCLUSIONS: The subgroup of patients with low-grade endometrial tumors or superficial myometrial penetration has a low distant relapse rate. Local control remains the goal of therapy in these patients. Patients with high-grade tumors, deep myometrial penetration, clear cell or papillary serous histologic types, or two or more involved extrauterine sites are at high risk for distant recurrence that may include the abdomen. Investigative strategies delivering aggressive adjuvant therapy are appropriate.

Adenocarcinoma↗

Alpha-synuclein pathology does not predict extrapyramidal symptoms or dementia.

Intracytoplasmic aggregation of alpha-synuclein protein as Lewy bodies in the brainstem neurons is diagnostic for Parkinson's disease, whereas if this process also occurs in the cortical neurons, it is considered pathognomonic for dementia with Lewy bodies. However, the link between alpha-synuclein incorporation into inclusions, neuronal dysfunction, and clinical symptoms needs to be clarified. Another important issue of the pathogenetic puzzle is to understand where alpha-synuclein pathology begins and how it progresses in the brain. To study this, we collected all cases from autopsy material (N = 904) that had alpha-synuclein pathology in the dorsal motor nucleus of vagus, substantia nigra, and/or basal forebrain nuclei. In this way, our study has a unique design because the selection of material is entirely based on the presence of alpha-synuclein pathology regardless of clinical phenotype. Retrospective clinical assessment then showed that only 32 (30%) of 106 alpha-synuclein-positive cases were diagnosed with a neurodegenerative disorder. The distribution or load of alpha-synuclein pathology did not permit a dependable postmortem diagnosis of extrapyramidal symptoms or cognitive impairment. Some neurologically unimpaired cases had a reasonable burden of alpha-synuclein pathology in both brainstem and cortical areas, suggesting that alpha-synuclein-positive structures are not definite markers of neuronal dysfunction.

Aged↗

Development of multiorgan pathology in the wpk rat model of polycystic kidney disease.

Rodent models of polycystic kidney disease (PKD) have provided valuable insight into the cellular changes associated with cystogenesis in humans. The present study characterizes the morphology of renal and extrarenal pathology of autosomal recessive PKD induced by the wpk gene in Wistar rats. In wpk(-/-) rats, proximal tubule and collecting duct cysts develop in utero and eventually consume the kidney. Increased apoptosis, mitosis, and extracellular tenascin deposition parallel cyst development. Extrarenal pathology occurs in the immune system (thymic and splenic hypoplasia) and central nervous system (CNS; hypoplasia to agenesis of the corpus callosum with severe hydrocephalus). Severity of hydrocephalus varied inversely with size of the corpus callosum. In wpk(-/-) rats, the corpus callosum exhibits relatively few axons that cross the midline. This CNS pathology is similar to that described in three human renal cystic syndromes: orofaciodigital, genitopatellar, and cerebrorenal-digital syndromes. Collecting duct and ventricular ependymal cilia appear morphologically normal. To determine if rodent background strain and the presence of modifier genes affect severity of the disease, we crossed the Wistar-wpk rat with Brown Norway (BN) and Long Evan (LE) rats and found the degree of renal and cerebral pathology was diminished as evidenced by lower kidney weight as a percent of body weight and serum urea nitrogen concentration in cystic rats on LE or BN strains as well as less prominent cranial enlargement. Crosses with BN rats allowed us to localize the wpk gene on chromosome 5 very close to the D5Rat73 marker. The wpk gene lies within a chromosomal region known to harbor a PKD modifier locus. In summary, the types of renal and cerebral pathology seen in the Wistar wpk rat are a unique combination seen only in this rodent model.

Agenesis of Corpus Callosum↗

Interobserver variability in the pathological assessment of malignant colorectal polyps.

BACKGROUND: Treatment of patients with malignant large bowel polyps is highly dependent on pathological evaluation. The aim of this study was to evaluate interobserver variability in the pathological assessment of endoscopically removed polyps. METHODS: The records of 88 patients with colorectal cancer who underwent endoscopic removal of malignant polyps were reviewed. Study investigators reviewed the initial pathology report; three experienced gastrointestinal pathologists reviewed all slides in a blinded fashion. Interobserver variability of pathological assessment of malignant polyps was analysed by kappa statistics. RESULTS: Seventy-six (86 per cent) of the 88 patients had malignant polyps and 12 (14 per cent) had carcinoma in situ. Agreement between experienced pathologists was substantial with regard to T stage (kappa = 0.725), resection margin status (kappa = 0.668) and Haggitt's classification (kappa = 0.682), but comparison of initial and experienced pathologists' assessment demonstrated only moderate agreement in these areas (kappa = 0.516, kappa = 0.555 and kappa = 0.578 respectively). Agreement between even experienced pathologists was poor with respect to histological grade of differentiated adenocarcinomas (kappa = 0.163) and angiolymphatic vessel invasion (kappa = - 0.017). CONCLUSION: Pathological assessment of malignant polyps varies between observers. Specialist pathologists appear to have a higher degree of consensus among themselves than with generalist pathologists with respect to T stage. The high interobserver variability with regard to histological grade of differentiated tumours is clinically irrelevant. However, variability in the assessment of angiolymphatic vessel invasion limits the value of this measurement for clinical decision making.

Adult↗

A graph analysis of the relationship between population density and social pathology.

This article deals with systematic variables--population density and pathological effects--at the level of a community or organizational system. Existing studies of the relationship between population density and social pathology (e.g., mortality, mental illness) in humans have failed to determine a strictly causal relationship between density and pathology in a linear model. They have not established a direct link between density and pathology in a simple two-variable, linear causal approach. Eliminating other variables by statistical control has obscured the conditions of a complex phenomenon. By incorporating socioeconomic variables into a general system model, this paper suggests that the total configuration of social organization, adaptation, previous group experience, and environment determine the effects of population density. Using a method of graph analysis, a model is presented of the relationship between population density and social pathology which has a high degree of isomorphism with the empirical situation.

Adrenocorticotropic Hormone↗

2-Fluoro-2-deoxy-D-glucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma.

BACKGROUND: The current study was performed to assess the value of 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in predicting the pathologic response and survival of patients with esophageal carcinoma treated with preoperative chemoradiation (CRT) and tumor resection. Preliminary reports suggest that FDG-PET may be predictive of the response of esophageal carcinoma patients to preoperative CRT. METHODS: Eighty-three patients with resectable esophageal carcinoma who underwent preoperative CRT and FDG-PET and tumor resection were evaluated for pathologic response to CRT, percent residual tumor, and survival. RESULTS: The majority of patients in the current study were men (74 of 83 patients; 89%). Most tumors were adenocarcinomas (73 of 83 tumors; 88%) and clinical (EUS)T3/4 (69 tumors; 83%) or N1 (46 tumors; 55%). FDG-PET after preoperative CRT identified pathologic responders but failed to rule out microscopic residual tumor in 13 of 73 cases (18%). Pathologic response was found to correlate with the post-CRT FDG-PET standardized uptake value (SUV) (P = 0.03) and a post-CRT FDG-PET SUV of or 4 was found to be the only preoperative factor to correlate with decreased survival (2-year survival rate of 33% vs. 60%; P = 0.01). On univariate Cox regression analysis, only post-CRT FDG-PET was found to be correlated with post-CRT survival (P = 0.04). CONCLUSIONS: Post-CRT FDG-PET was found to be predictive of pathologic response and survival in patients with esophageal carcinoma who undergo preoperative CRT. Esophagectomy should still be considered even if the post-CRT FDG-PET scan is normal because microscopic residual disease cannot be ruled out.

Adenocarcinoma↗

Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is a common malignancy in hereditary nonpolyposis colorectal carcinoma (HNPCC). Like colon carcinoma, endometrial carcinoma is diagnosed at an earlier age in women with HNPCC. In contrast to colon carcinoma, the pathologic features of endometrial carcinoma in HNPCC have not been studied in detail. It was the purpose of this study to pathologically characterize a series of HNPCC associated endometrial carcinomas. METHODS: Fifty women with HNPCC and endometrial carcinoma were analyzed from four different hereditary cancer registries. H&E stained slides and pathology reports were reviewed for clinically important pathologic features of endometrial carcinoma. These results were compared with those for two different groups of sporadic endometrial carcinoma--women younger than age 50 years (n = 42) and women of all ages with tumors demonstrating microsatellite instability (MSI-high) secondary to methylation of MLH1 (n = 26). RESULTS: Nearly one-fourth of HNPCC patients in this study had endometrial tumors with pathologic features that would require adjuvant therapy after hysterectomy. There was a trend toward the HNPCC patients having more nonendometrioid tumors; all of these patients were carriers of MSH2 mutations. Such nonendometrioid tumors were extremely rare in the MLH1 methylated group. A subset of MLH1 methylated sporadic tumors demonstrated a unique, 'undifferentiated' histology that was not observed in HNPCC or the young group. CONCLUSION: Data suggest a genotype-phenotype relation in which microsatellite instability resulting from MLH1 methylation is almost exclusively associated with classical or 'undifferentiated' endometrioid tumors, whereas microsatellite instability secondary to MSH2 mutation can result in a more variable histologic spectrum of endometrial carcinoma.

Adaptor Proteins, Signal Transducing↗