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Background: Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor., Objective: To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell)., Design: Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases., Results: All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin., Conclusion: In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.

Context: DNA flow cytometry of breast cancer is a proposed tumor marker of prognostic significance that is of controversial clinical utility because of lack of standardization and confirmatory studies., Objective: To evaluate the prognostic significance of the more informative technique of multiparametric 2-color DNA flow cytometry as recommended by the 1992 DNA Cytometry Consensus Conference., Design: Three hundred thirty-two breast carcinomas with 7 to 12 years of follow-up were prospectively analyzed as fresh tumors that were mechanically dissociated into whole cell suspensions. These suspensions were dual fluorescence-labeled with propidium iodide (DNA) and antibodies to cytokeratin (epithelium) and leukocyte common antigen (internal leukocyte control) for gated analysis of subpopulations. Multicycle software with histogram-dependent algorithms employing background, aggregate, and debris correction were used in DNA and cell-cycle quantitation. Data were analyzed according to the DNA Flow Cytometry Consensus Conference recommendations., Results: DNA ploidy and proliferation stratified into 3 categories were not predictive of overall or disease-free survival. Sixty-five percent of tumors were nondiploid, and 35.4% were diploid. Two hundred six tumors were able to be evaluated for synthesis-phase fraction (SPF) analysis, with 74 of 206 cases in the low range (<13.4%), 36.4% in the intermediate range (>13.5 to <25.4%), and 27.6% in the high SPF (>25.5%) category. Aneuploid tumors tended to have a higher SPF. Univariate survival analysis showed prognostic significance of the following: tumor size, stage, TNM components, vascular invasion, nuclear grade, and histologic grade. Only T classification, presence of positive axillary lymph nodes, and distant metastases were significant independent predictors of survival in multivariate Cox regression models. Age and hormone receptor status showed no prognostic significance. Synthesis-phase fraction was significantly correlated with tumor size, stage, T classification, nuclear and histologic grade, presence of estrogen or progesterone receptors, and axillary lymph node status. None of the histologic parameters showed any significant association with DNA aneuploidy, except for high nuclear and histologic grade and the absence of estrogen receptors., Conclusions: Despite the use of state-of-the-art processing and flow cytometry analytic techniques, DNA ploidy and proliferation measurements were not predictive of survival in any stage of breast cancer. However, select histopathologic parameters and TNM stage were significant predictors of survival in univariate and multivariate analyses. We conclude that DNA ploidy and proliferation measurements do not provide significant prognostic information for clinicians to integrate into therapeutic decision making for patients with breast cancer.

Objective: To develop breast cancer outcomes data relating pathologic tumor variables at diagnosis with clinical method of detection., Design: Anatomic pathologists assessed 30 consecutive breast cancers at each institution, resulting in an aggregate database of 4232 breast cancers., Setting: Hospital-based laboratories from the United States (98%), Canada, Australia, and Belgium., Participants: One hundred ninety-nine laboratories in the 1999 College of American Pathologists Q-Probes voluntary quality improvement program., Main Outcome Measures: Pathologic variables indicative of favorable outcomes included percentage of carcinomas detected at the in situ stage, tumors < or = 1 cm in diameter, and invasive cancers with lymph nodes negative for metastases., Results: All outcomes measures, including percent in situ carcinomas (26.9% vs 13.8%), tumor size < or = 1 cm (57.8% vs 36.5%), and lymph node-negative status (77.8% vs 64%), were more favorable when tumors were detected by screening mammography (P <.001) compared to all other detection methods., Conclusions: This study demonstrates an opportunity for pathologists to develop outcomes information of interest to health care organizations, providers, patients, and payers by integrating routine oncologic surgical pathology and clinical breast cancer detection data. Such readily obtained interim outcomes data trended and benchmarked over time can demonstrate the relative clinical efficacy of preventive breast care provided by health care systems long before mortality data are available.

Objective: To review tenets of basic quality assurance and identify opportunities for quality improvement in the laboratory assessment of prognostic factors., Design: College of American Pathologists Q-Probes data obtained from hundreds of American laboratories throughout the 1990s are used to illustrate laboratory performance and practice opportunities in the preanalytic, analytic, and postanalytic phases of the total testing process., Results: A wide range of performance deficiencies are documented, most in the preanalytic and postanalytic phases, and contributed by individuals outside and not under the control of the laboratory. In the analytic phase, the effectiveness of checklists on the content and completeness of reported diagnostic and prognostic data for breast and colon cancers is proven., Conclusions: In the preanalytic phase, marked enhancements in quality would result from improvements in (1) patient and specimen identification, (2) adherence to patient-sampling and specimen-handling requirements, and (3) communication to the laboratory of the pertinent clinical context of the individual test. Once basic analytic quality control and laboratory quality assurance issues are resolved, a focus on standardization and enhancement of preanalytic and postanalytic communications and satisfaction of clinical expectations becomes the source of improved laboratory performance.

Objective: To evaluate cellular composition of salivary gland adenomas using 3 monoclonal antibodies that recognize a smooth muscle phenotype confirmed to be sensitive for myoepithelial differentiation., Design: Immunohistochemical evaluation of 25 salivary gland basal cell and canalicular adenomas., Setting: Archival pathology material from the files of Henry Ford Hospital, Detroit, Mich, and the University of California at San Francisco., Results: All basal cell adenoma variants exhibit some degree of myoepithelial cell participation with periductal, epithelioid, and spindled (stromal-like) morphologic structures. Only the canalicular adenomas, even if mixed with trabecular and solid patterns, are devoid of staining with these 3 antibodies, suggesting an adenoma composed exclusively of ductal luminal cells., Conclusions: There is an overlapping histomorphologic and common cellular composition of the basal cell adenoma variants with other recognized adenomas, such as pleomorphic adenoma and myoepithelioma. Relative differentiation toward 3 cell phenotypes (ductal luminal, basal, and myoepithelial) and the character of extracellular matrix production in varying proportions by the neoplastic myoepithelial cells distinguishes the spectrum of salivary gland adenomas identified in current classification schemes.

Background: We have previously studied the immunoreactivity of 3 novel smooth muscle-specific proteins, alpha-smooth muscle actin, smooth muscle myosin heavy chains, and calponin, to assess myoepithelial differentiation in pleomorphic adenomas., Objective: To further expand our knowledge of myoepithelial differentiation in other benign and malignant salivary gland tumors., Design: Formalin-fixed paraffin sections of 135 salivary gland tumors with associated normal glands were stained with monoclonal antibodies using the avidin-biotin complex immunoperoxidase method and enzymatic and microwave heat-induced epitope retrieval., Results: In adenoid cystic carcinomas and epithelial-myoepithelial carcinomas, all 3 markers exclusively highlighted the myoepithelial cell components and the epithelial cells were entirely negative. No immunostaining was detected in canalicular adenomas, oncocytomas, Warthin tumors, acinic cell carcinomas, mucoepidermoid carcinomas, squamous cell carcinomas, and polymorphous low-grade adenocarcinomas. Salivary duct carcinomas and adenocarcinomas, not otherwise specified had a distinctive pattern of uniform periductal staining of reactive myofibroblastic cells, and in salivary duct carcinomas some ducts retained a peripheral immunoreactive myoepithelial cell layer., Conclusion: Immunoreactivity for these 3 smooth muscle-specific proteins confirms the known neoplastic myoepithelial component of adenoid cystic carcinomas and epithelial-myoepithelial carcinomas. The consistently positive staining pattern in adenoid cystic carcinomas may be diagnostically useful in discriminating histologically similar but consistently negative polymorphous low-grade adenocarcinomas. Periductal linear staining in adenocarcinoma, not otherwise specified and salivary duct carcinomas is distinctive and appears to represent a tight cuff of myofibroblasts associated with the infiltrating glands.

Objective: To determine the rate of diagnostic uncertainty in rendering diagnoses on prostate needle biopsies and to examine pathology practice variables that influence that rate., Design: Anatomic pathology departments participating in the College of American Pathologists Q-Probes laboratory quality improvement program retrospectively reviewed their last 50 consecutive prostate needle biopsy diagnoses. For each diagnosis, participants provided information concerning patients' prostate-specific antigen levels; number, locations, and laterality of biopsy specimens; number of tissue levels examined; performance of high-molecular-weight cytokeratin immunoperoxidase staining; and acquisition of consultations from general pathologists or experts in prostate pathology. Characteristics of pathology practices included yearly surgical and prostate needle biopsy caseloads, number of pathologists rendering biopsy diagnoses, use of standard descriptive checklists, access to patients' prostate-specific antigen and digital rectal examination results, percentages of prostate needle biopsies routinely submitted for internal consultations, and presence of departmental experts in prostate pathology., Setting and Participants: Three hundred thirty-two public and private institutions located in the United States (n = 318), Canada (n = 6), Australia (n = 5), United Kingdom (n = 2), and Guam (n = 1)., Main Outcome Measure: The rate of diagnostic uncertainty in prostate needle biopsy diagnoses., Results: Participants submitted diagnoses on a total of 15 753 prostate needle biopsy cases, of which 33.4% were adenocarcinoma; 55.5% were benign; 3.9% were carcinoma in situ, prostatic intraepithelial neoplasia, or both; and 7.1% were diagnostically uncertain. The median rate of diagnostic uncertainty was 6%, ranging from 0 at the 10th percentile to 14% at the 90th percentile of all participating laboratories. Performing high-molecular-weight cytokeratin immunoperoxidase staining resolved diagnostic uncertainty in 68% of cases in which it was performed, and obtaining intradepartmental and extradepartmental consultations resolved diagnostic uncertainty in 70% to 87% of cases for which they were obtained. Knowledge of patients' prostate-specific antigen results and examining multiple biopsy cores had marginal effects on the rate of uncertainty. Thoroughness of prostate gland sampling and examination of multiple tissue block levels were not associated with the aggregate rate of diagnostic uncertainty. We found no particular pathology departmental practices or institutional demographic characteristics associated with institutional rates of diagnostic uncertainty., Conclusions: Use of high-molecular-weight cytokeratin immunoperoxidase staining and obtaining intradepartmental and extradepartmental consultations may be effective in reducing diagnostic uncertainty in prostate biopsies.

Objectives: To examine the frequency and nature of problems caused by inadequate clinical data provided on surgical pathology requisition forms., Design: Participants in the 1996 Q-Probes voluntary quality improvement program of the College of American Pathologists were asked to document prospectively all surgical pathology cases with inadequate information. Inadequate clinical information was defined as the pathologist's need for additional clinical information before a diagnosis could be rendered, regardless of the amount of information already present on the requisition slip. Cases that had no clinical information on a requisition slip were not counted if the lack of history did not hinder diagnosis. The study concluded when 3 months had elapsed or 40 surgical pathology cases were documented. The following data were recorded for each case: anatomic site, type of procedure, nature of disease, method of obtaining additional information, importance of obtained information, and the length of delay in the final diagnosis., Participants: Three hundred forty-one laboratories, 322 of which were from the United States., Results: A total of 5594 cases (0.73%) required additional clinical information for diagnosis (10th through 90th percentile range, 3.01% to 0.08%). Institutions with greater average occupied bedsize, a greater number of cases accessioned per year, and a greater number of pathologists had a lower percentage of cases with inadequate clinical data (P <.05). Sixty-eight percent of these cases had no delay in completion of a case, 16.2% had a delay of 1 day or less, and 15.1% of cases were delayed more than 1 day. In 59.4% of cases, the additional clinical information obtained confirmed the initial diagnostic impression. In 25.1%, the information was not relevant to the pathologic diagnosis. In 6.1% there was a substantial change in the diagnosis or a revised report was issued, and in 2.2% no additional information could be obtained. Specific anatomic sites that correlated with a higher rate of changed diagnoses or revised reports in cases with inadequate information included the small bowel, the bronchus/lung, and the ovary. Resection specimens were also significantly associated with a higher rate of changed diagnoses or revised reports when additional information was obtained, as were malignant neoplasms and therapy-induced changes., Conclusions: This study establishes an aggregate rate of cases with inadequate clinical information for diagnosis (0.73%) and documents the extent of problems caused by inadequate clinical information. The criticality of appropriate clinical information provided to the pathologist is identified for specific anatomic sites and disease processes and is reflected in changed diagnoses or revised reports.

Background: The histogenesis of alveolar soft part sarcoma remains elusive. Myogenic origin is favored, although conflicting data on immunohistochemical demonstration of muscle-associated markers exist. Myogenin and MyoD1, transcription factors of the myogenic determination family, have crucial roles in commitment and differentiation of mesenchymal progenitor cells to myogenic lineage and in maintenance of skeletal muscle phenotype. Their immunohistochemical detection is specific in characterization of rhabdomyosarcoma., Methods: Antibodies for myogenin, MyoD1, desmin, and muscle-specific actin were employed on a large series of cases (n = 19) of formalin-fixed, paraffin-embedded alveolar soft part sarcoma., Results: Minimal scattered nuclear staining was seen with myogenin. All cases had pronounced, nonspecific granular cytoplasmic immunostaining with MyoD1; nuclei were negative. All tumors were negative for desmin and muscle-specific actin. Ultrastructural study in 10 cases failed to reveal features of skeletal muscle differentiation., Conclusions: Cytoplasmic staining with MyoD1 in alveolar soft part sarcoma may correspond to cross-reactivity with an undetermined cytoplasmic antigen. The lack of immunostaining with myogenin, MyoD1, desmin, and muscle-specific actin provides evidence against a myogenic origin for alveolar soft part sarcoma.

Objectives: To document the level of involvement and communication with nonpathology clinical personnel regarding autopsies and to document the destination of autopsy reports., Design: The College of American Pathologists Q-Probes format was used to collect information on 15 consecutively performed autopsies per institution or for 6 months, whichever occurred first. The following information was recorded for each autopsy: decedent's age, hospital service, length of hospital stay, whether organs were donated, who was present at autopsy, methods of communicating preliminary and final autopsy results, special techniques used to arrive at a preliminary diagnosis, activities for which the autopsy was used, and destination of final report., Participants: Two hundred fifty-six laboratories collected information on 2755 autopsies., Results: The aggregate autopsy rate was 12.4% (median 8.5%). Nonpathology clinical personnel attended 35.8% of all autopsies. A clinical physician was more likely to attend an autopsy if the patient was from a surgical service. Three primary methods were used to communicate preliminary autopsy results, namely, written reports (82.5%), telephone calls (50.6%), and meetings (11.5%). The primary care physician was sent the autopsy report in 91.1% of cases. Approximately half of the autopsy cases were used in both pathology departmental and extradepartmental activities. Aggregate autopsy data were distributed in the majority of cases to various departmental chairpersons and institutional quality assurance committees., Conclusions: This study provides a comparative multiinstitutional database for the utilization of autopsy results by clinicians and clinical departments. Although autopsy rates are low, autopsy results are routinely being used for hospital quality assurance activities and for educational purposes.

Objective: To develop a multi-institutional reference database for quality improvement purposes using the autopsy to define clinical diagnostic discrepancies and resolve clinical questions., Design: Using the College of American Pathologists Q-Probes format, institutions prospectively assessed a maximum of 15 consecutive autopsies each, excluding forensic cases and stillborn infants, conducted over a 6-month period. They documented answers to clinical questions provided at autopsy and classified unexpected disease diagnoses according to a standardized system., Setting and Participants: Hospital-based autopsies performed at 248 institutions participating in the 1993 College of American Pathologists Q-Probes Quality Improvement Program., Main Outcome Measures: Percentages of clinical questions resolved by the autopsy and percentage of autopsies with unexpected findings of graded clinical impact., Results: In the aggregate database of 6427 questions from 2479 autopsies, overall 93.0% were answered by the autopsy. The 3 most common question categories were (1) identify pathology to account for clinical signs or symptoms (28.0%); (2) establish the cause of death (21.0%); and (3) confirm a clinical diagnosis (19.0%). At least one major unexpected disease finding that contributed to the patient's death was discovered in 39.7% of the total number of autopsies. There were no differences in the percentages of autopsies with these major unexpected findings when the data were stratified by institutional demographics or decedent characteristics., Conclusion: This multi-institutional study underscores the clinical relevance of postmortem examination in current medical practice by consistently providing answers to unresolved clinical questions and frequently revealing major unexpected findings that contributed to the patient's death. It is our strong belief that this postmortem-derived clinicopathologic information is a key indicator of effectiveness of care. Integration of this information into institutional quality improvement programs will improve system processes and clinician performance.

Objective: To survey the scope of current written institutional policies for types of surgical pathology specimens exempt from submission to the laboratory and those that may be examined by gross inspection only., Design and Setting: In the first quarter of 1997, a total of 413 voluntary participant institutions enrolled in the College of American Pathologists Q-Probes quality improvement program completed a checklist of 115 proffered specimens. Also included was a questionnaire defining demographic, practice, and reimbursement variables., Main Outcome Measures: The number and types of specimens exempt from submission and submitted for gross examination only based on written institutional policy rather than on unapproved actual practices., Results: Most institutions had a written policy for types of specimens deemed exempt from submission to pathology (87.1 %) and for types of specimens subject to gross examination only (76.6%). There was a wide range of numbers of specimen types with a median number of 17 (range, 2-40) in the exempt category and 29 (range, 6-57) in the category of gross examination only. Significantly higher absolute counts of specimens exempt from submission to pathology were reported by institutions with a greater surgical pathology volume in 1996 and by nonteaching institutions. No aspect of practice was associated with numbers of specimens for gross examination only., Conclusions: This Q-Probes study creates a multi-institutional reference database of current practices to assist pathologists and clinical staff in the development of written guidelines pertaining to surgical pathology specimen submission exceptions and gross-only examinations.

Objectives: To study the turnaround time (TAT) for rendering diagnoses on routine biopsy specimens, to examine pathology practice variables that influence TAT, and to assess the level of surgeons' satisfaction with biopsy TAT., Design: Over a 3-month period, voluntary participants in the College of American Pathologists Q-Probes laboratory quality improvement program prospectively collected TAT data on up to 20 biopsy specimens performed on elective surgical cases, completed questionnaires profiling their institution's practice characteristics, and had surgeons complete questionnaires indicating their satisfaction with biopsy report TAT., Setting and Participants: One hundred fifty-seven private and public small hospitals located in 43 American states (n = 153), Canada (n = 1), and Australia (n = 3)., Main Outcome Measures: The routine surgical biopsy report TATs for 2 testing intervals, each commencing when surgeons acquired the biopsy specimens. One interval concluded when pathologists signed off the biopsy diagnoses, and the other concluded when surgeons received the hard-copy reports., Results: Pathologists signed off 85.9% of 5384 biopsy diagnoses by the second working day, and surgeons received 88.3% of the hard-copy reports by the fourth working day. In 90% of hospitals participating in this study, pathologists signed off half their biopsy diagnoses between the second and third postcollection days, and 90% of surgeons received half their final hard-copy reports by the fourth postcollection day. Institutional practice variables associated with fewer sign-off and/or hard-copy receipt TATs exceeding the institutional 90th percentile performance benchmarks included yearly surgical caseloads greater than 2000 cases per full-time equivalent pathologist, provision of pathology support services on site, and accreditation of the hospital by the Joint Commission on Accreditation of Healthcare Organizations and of the laboratory by the College of American Pathologists. Most (96.4%) surgeons indicated that they were satisfied with hard-copy TATs and that they believed most (98.1%) of the hard-copy TATs had no effect on the lengths of their patients' hospital stays., Conclusions: Pathologists are capable of signing off most routine biopsy diagnoses within 2 working days and delivering the final hard-copy reports to surgeons within 4 working days (both intervals measured from the time that surgeons collect biopsy specimens). Most surgeons report they are satisfied with this level of performance.

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.

Objectives: To study the intraoperative turnaround time for performing a frozen section (FS) and to examine pathology practice variables that influence it., Design: Over a 4-month period in 1995, participants in the College of American Pathologists Q-Probes laboratory quality improvement program prospectively collected data on up to 30 FS procedures performed on elective inpatient surgical cases and completed questionnaires profiling their FS practice characteristics., Setting: Surgical pathology laboratories serving private and public hospitals., Participants: Seven hundred institutions located in North America (667), Australia (12), New Zealand (1), the United Kingdom (3), Hong Kong (1), Mexico (1), and Norway (1)., Main Outcome Measures: The 90% FS block completion time defined as the time interval, in minutes, within which the fastest 90% of all FS blocks were completed, measured from the time pathologists received FS specimens to the time they communicated FS results to the surgeon., Results: Participants submitted data on 32868 FS blocks. Ninety percent of FS procedures were completed within 20 minutes. Frozen section turnaround times exceeding 20 minutes, termed outlier turnaround times, were more likely to occur when more than one pathologist participated in the FS diagnosis, pathology residents and medical students participated in the FS procedure, the pathologist had to retrieve and review previous case material during the FS procedure, the pathologist simultaneously received additional specimens from other FS cases, the pathologist was unable to reach a final FS diagnosis, and when technical problems occurred during the FS procedure. Seventy percent of all participating hospitals completed 90% of their frozen sections within 20 minutes. The institutional 90% completion times were shorter for hospitals containing 300 or fewer occupied beds than for those containing more than 300 occupied beds., Conclusions: The data suggest that 90% of FS block turnaround times can be performed within 20 minutes, measured from the time that pathologists receive FS specimens to the time that pathologists return FS diagnoses to surgeons.

Objectives: To determine (1) the information that clinical physicians want in surgical pathology reports of biopsies performed for mammographic abnormalities, (2) how specimens are received and processed, and (3) what information is actually present in pathology reports., Design: The standard data collection and questionnaire format of the College of American Pathologists' Q-Probes quality improvement program was used. Laboratories (1) surveyed clinical physicians working in selected specialties involved in the care of patients with breast disease concerning what information they wanted in a surgical pathology report, (2) documented laboratory specimen handling for 20 consecutive breast biopsy tissues obtained to investigate mammographic abnormalities, and (3) documented the information content of surgical pathology reports of these cases., Participants: Four hundred thirty-four participating laboratories surveyed 1469 clinical physicians and collected information on 7300 cases regarding specimen processing and report content., Results: Clinical physicians were unanimous in the majority of items they desired for patient care. The information, however, differed depending on the diagnosis. In processing of tissues, 89% of specimens were received without fixative. In 83% of cases, radiographs were performed. Eighty-two percent of specimens were marked in some manner, but in only 45% of cases was a report of the radiographic abnormality given to the Pathology Department. The median number of blocks used to sample the lesion and the whole specimen was three and six blocks, respectively. The latter correlated with specimen size. Fifty-seven (13%) surgical pathology laboratories had radiography equipment. Radiographs of specimens and tissue blocks were made in 5% and 4% of cases, respectively. Correlation of a mammographic abnormality with a microscopic finding was documented in 62% of reports. In 92% of malignant cases the margin status was reported, and 77% of reports contained the lesion size. Eighty-three percent of reports with invasive carcinoma stated the tumor grade, and 76% stated the extent of intraductal carcinoma. The percentage of reports containing information items was significantly higher (P < .05) for institutions using checklists., Summary: This multi-institutional Q-Probes study describes the current clinical expectations and laboratory practices associated with mammographically directed biopsies. Disparities between pathology reporting and clinician desires, as well as radiology and laboratory specimen handling practices, have been identified and may help focus future quality improvement efforts.

Objective: To study pathology intraoperative consultation practices and the accuracy of diagnoses made by frozen section., Design: In 1994, participants in the College of American Pathologists Q-Probes laboratory quality improvement program each completed questionnaires and prospectively collected data on up to 20 frozen section procedures performed over a 5-month period., Setting: Surgical pathology laboratories serving private and public hospitals with 300 or fewer occupied beds., Participants: Two hundred thirty-two North American institutions and one New Zealand institution., Main Outcome Measures: The discordance and deferral rates of frozen section diagnoses and the reasons for frozen section discordance relative to corresponding diagnoses made on permanent (paraffin) sections. Calculation of frozen section discordance rates excluded diagnoses of subtypes or grade of malignancy, biopsies on specimens in which there was no gross lesion (eg, mammographic specimens), thyroid follicular lesions, tissue taken only to determine adequacy for other studies (eg, estrogen-binding proteins), and frozen sections performed to evaluate margins of specimens oriented en face., Results: Out of 18,532 frozen section diagnoses performed on 327,884 surgical cases, 859 (4.6%) diagnoses were deferred until permanent sections were available for review; 17,357 (98.2%) nondeferred diagnoses agreed with, and 316 (1.8%) disagreed with, those diagnoses rendered on permanent sections. The most common cause of discordance was underdiagnosis of neoplasia, usually due to block- or tissue-sampling errors., Conclusions: We recommend that laboratories routinely monitor frozen section discordance, cut additional sections deeper into the frozen block and/or sample additional tissue when the initial frozen section diagnosis is negative or nonproductive, reconcile all discordant frozen section diagnoses in the final report, and periodically assess the value of performing frozen section examinations.

Objective: To develop a multi-institutional reference database of extraneous tissue (contaminants) in surgical pathology., Design: In 1994, participants in the College of American Pathologists Q-Probes quality improvement program performed prospective and retrospective evaluations of extraneous tissue found in surgical pathology microscopic sections for a period of 4 weeks or until 1000 slides were reviewed in each participating laboratory., Participants: Two hundred seventy-five surgical pathology laboratories institutions, predominantly from North America., Main Outcome Measures: Extraneous tissue contamination rate for slides in prospective and retrospective reviews; staffing and practice procedures; location of extraneous tissue on slides; type of extraneous tissue (normal, abnormal, nonneoplastic, neoplasm, microorganisms, etc); class of extraneous tissue (slide or block contaminants); source of extraneous tissue (different or same case); origin of extraneous tissue (pathology laboratory, physician's office or operating room); and degree of diagnostic difficulty caused by extraneous tissue., Results: Three hundred twenty-one thousand seven hundred fifty-seven slides were reviewed in the prospective study and 57083 slides in the retrospective study. There was an overall extraneous tissue rate of 0.6% of slides (2074/321757) in the prospective study and 2.9% of slides (1653/57083) in the retrospective study. Of those slides with extraneous tissue, the extraneous tissue was located near diagnostic tissue sections in 59.5% of the slides reviewed prospectively and in 25.3% of slides reviewed retrospectively; deeper sections were performed to evaluate extraneous tissue in 12.2% of prospective cases and in 3.1% of retrospective cases. Of the laboratories, 98% had written guidelines for changing solution in tissue processors, and 64.9% had guidelines for maintaining water baths free of extraneous tissue. A total of 98.9% used lens paper, filter bags, or sponges for processing fragmented and small specimens. Written protocols for documentation of extraneous tissue in surgical pathology reports were established in 6.1% of laboratories, for removal of extraneous tissue from blocks in 5.7%, and for removal of extraneous tissue from microscopic slides in 4.7%. In 24% of laboratories no comment or record was kept to document extraneous tissue. Extraneous tissue consisted of neoplasm in 12.7% of the prospectively reviewed slides and in 6.0% of the retrospectively reviewed slides. For the prospective study, 59.4% of extraneous tissue was classified as slide contaminants, and 28.4% was found to be contaminants within the paraffin block; for the retrospective study, 72.9% was classified as slide contaminants and 15.9% as block contaminants. For the prospective study, 63.2% of extraneous tissue was presumed to be from a different case, and in the retrospective study, 48.5% was presumed to be from a different case. Over 90% of extraneous tissue was thought to originate from the pathology laboratory. The degree of diagnostic difficulty caused by extraneous tissue was judged to be severe in 0.4% of slides in the prospective study and 0.1% of slides in the retrospective study. In the prospective study, it could not be determined whether the tissue in the diagnostic sections was extraneous in 0.6% of slides, and in the retrospective study, it could not be determined whether tissue in the diagnostic sections was extraneous in 0.1%., Conclusions: This study has documented the frequency, type, origin, source, and diagnostic difficulty of extraneous tissue and presents benchmarks of extraneous tissue experienced in the general practice of surgical pathology.

Objective: To develop a multi-institutional reference database of autopsy practice and performance for quality improvement purposes., Design: In 1990, participants in the Q-Probes quality improvement program of the College of American Pathologists (CAP) each retrospectively evaluated the 25 most recently completed consecutive autopsy reports and determined the number of deaths and autopsies that occurred in their institutions during 1989., Setting: Hospital-based autopsies excluding forensic cases and stillborn infants., Participants: Four hundred ten institutions in the United States and eight institutions in Canada., Main Outcome Measures: Completeness of face sheet information contained in final autopsy reports, turnaround time for completion of final reports, and institutional autopsy rates., Results: In the aggregate database of 10003 autopsies, the following six data items (from a total of 21) were present in 95% to 100% of the final autopsy reports in at least 85% of the participating institutions: institution where autopsy was performed, patient's name, patient's sex, autopsy number, autopsy date, and prosecter's name. The turnaround times for the final autopsy reports were as follows: 30 days or less in 47.6% of the cases, 31 to 60 days in 28.8%, and more than 60 days in 23.7%. A higher median percentage of autopsy final reports were completed in 30 days or less in institutions with the following characteristics: nonteaching (P < .004), no pathology residency program (P < .002), and rural location (P < .027). A lower number of autopsies performed in 1989 was associated with a higher median percentage of final reports completed in 30 days or less (P < .007). The aggregate autopsy rate for all participating institutions was 12.4%, and the median rate was 8.3%. Median autopsy rates for teaching institutions and institutions with pathology residency training programs were 15% and 19%, respectively., Conclusions: This multi-institutional study identified a core group of face sheet data items that were consistently present on final autopsy reports. However, the majority of the face sheet data items examined were inconsistently recorded. Approximately 75% of final autopsy report turnaround times were within the standard established by the Joint Commission on Accreditation of Healthcare Organizations. Nearly two thirds of the institutions reported autopsy rates for 1989 of 0% to 10%.

Objective: To assess concordant, discordant, and deferred diagnosis rates from frozen sections; to determine reasons for discordance; to identify pathologic processes associated with discordant diagnoses; to determine false-positive or false-negative rates for neoplasms; and to identify anatomic sites associated with discordant frozen section diagnoses., Design: Q-Probes study of the College of American Pathologists., Participants: Four hundred sixty-one institutions participating in the Q-Probes program from November 1, 1990, through March 31, 1991., Main Outcome Measures: Concordant and discordant diagnosis rates., Results: The frozen section concordance rate for diagnoses from the aggregate group was 98.58% and the discordance rate was 1.42%, when uncorrected for deferred diagnoses. During the study period, participating institutions accessioned 1,693,331 surgical pathology cases; 90,538 of these cases were evaluated by frozen section consultation, resulting in the examination of 121,668 specimens and 148,506 frozen section blocks. The majority of the frozen section discordances occurred because of misinterpretation of the original frozen section (31.8%), presence of diagnostic tissue in permanent sections of the frozen block when the frozen section was negative (30.0%), and presence of diagnostic tissue in the portion of the specimen not sampled by the frozen section (31.4%). Of the discordant diagnoses, 67.8% had false-negative diagnoses for neoplasm. The pathology processes and anatomic sites represented in discordant diagnoses are also evaluated., Conclusions: High diagnostic accuracy of frozen section consultations was demonstrated. Frozen sections are used to evaluate a variety of pathologic processes and anatomic sites.

Objective: To develop a multi-institutional reference database of autopsy practices and performance for quality improvement purposes., Design: In 1992, participants in the Q-Probes quality improvement program of the College of American Pathologists each prospectively evaluated consecutive autopsies performed over a 6-month period, up to a maximum of 20 autopsies per institution., Setting: Hospital-based autopsies, excluding forensic cases and stillborn infants., Participants: Four hundred forty-nine North American institutions and three Australian laboratories., Main Outcome Measures: Completeness of information contained on autopsy permit forms, timeliness of autopsy performance between patients' deaths and autopsy prosections, and turnaround time of preliminary autopsy reports., Results: In the aggregate database of 5434 autopsy cases, 7 of 11 selected data items were consistently present on autopsy permit forms in 80% of the participating institutions. The median percentage of autopsies in which permission was given for an unrestricted (complete) autopsy was 71%. The following median time intervals were obtained: time of the patient's death to time the autopsy permission was received, 5 hours, 23 minutes; time the autopsy permission was received to time the prosection was started, 3 hours, 30 minutes; and time of the patient's death to time the prosection was started, 14 hours, 52 minutes. Differences were observed in some time intervals when the participating institutions were grouped by reported demographic characteristics. Preliminary reports were completed in 2 days or less in 80.9% of the autopsies., Conclusions: Through this multi-institutional study, we have documented a consistent core of autopsy permit form information requested and a wide range of time intervals elapsed between the patients' deaths and autopsy performance. We have also established that the majority of participating institutions meet the College of American Pathologists' laboratory accreditation standard of providing a documented preliminary report of the gross pathologic diagnoses submitted to the attending physicians and institutional record within 2 working days following autopsy completion.

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

Objective: To examine and suggest improvements for deficiencies occurring in the specimen identification and accessioning process in the surgical pathology laboratory., Design: Using the College of American Pathologists' and the Joint Commission for Accreditation of Healthcare Organizations' requirements as the standard, each laboratory was asked to prospectively document deficiencies in specimen identification and accessioning for 4 months, or until a maximum of 4000 cases or 400 deficiencies were accrued., Participants: Four hundred seventeen laboratories in the College of American Pathologists' voluntary quality improvement program, Q-Probes, participated in this study., Results: Identification and accessioning deficiencies were found in 60 042 (6%) out of a total 1 004 115 cases accessioned (median deficiency rate of 3.4%). Errors related to specimen identification accounted for 9.6% of these deficiencies, discrepant or missing information items were present in 77%, and 3.6% involved specimen handling. The most common deficiency was "no clinical history or diagnosis present on the requisition slip," which represented 40% of all deficiencies. Deficiencies were most often detected by the person assigned to accessioning duties or by histology personnel. In 66% of cases, no action was taken to remedy the deficiency, but this varied dramatically according to the specific type of deficiency. An action was taken to remedy deficiencies in 69% of cases involving specimen identification errors, in 58% of specimen handling errors, and in 27% of cases with discrepant or missing information. Peer group stratifiers were associated with a lower deficiency rate. Laboratories with lower numbers (<15 000) of accessioned cases and laboratories with a formal written plan for the detection of errors in accessioning and specimen identification reported lower rates of deficiencies. Factors that correlated with a higher rate of deficiencies included submitting the specimen container and requisition slip in a unique secondary container (P<.005) and labeling the specimen container with only a patient's name or unique patient identification number (as opposed to both identifiers)., Conclusions: The majority of deficiencies occurring in surgical pathology specimen identification and accessioning are related to missing or inaccurate clinical information. Deficiencies are detected in multiple locations, including areas not typically thought of as quality check points, such as transcription. A variable amount of effort occurs to rectify deficiencies; this effort is largely dependent on the type of deficiency involved. Finally, laboratories with a formal error detection plan had fewer deficiencies.

Objective: To evaluate the reasons (indications) for and immediate intraoperative surgical results (outcomes) associated with pathology intraoperative consultation., Design: In 1992 and 1993, surgeons collaborated with pathologists in 472 voluntarily participating institutions from the United States (462), Canada (7), Australia (2), and New Zealand (1) in a study jointly sponsored by the College of American Pathologists and the Centers for Disease Control and Prevention. Pathologists selected 20 consecutive intraoperative consultations and assembled a cover letter, a checklist questionnaire, and a copy of the corresponding surgical pathology report, all of which were sent to the surgeon(s) for retrospective evaluation., Participants: The study was distributed to participants in the College of American Pathologists voluntary Q-Probes quality improvement and Surgical Pathology Performance Improvement programs and to Canadian and Australian hospitals with more than 200 beds., Results: Evaluation of 9164 cases established the five most common indications for intraoperative consultation: (1) establish or confirm diagnosis to determine type or extent of operation (51%), (2) confirm adequacy of margins (16%), (3) confirm nature of tissue to direct sampling for immediate culture or other laboratory study (10%), (4) expedite obtaining diagnosis to inform family or patient (8%), and (5) confirm sufficient tissue submitted to secure diagnosis in permanent section (8%). The information provided by the intraoperative consultation resulted in changed surgical procedures that were either modified, terminated, or newly initiated in 47%, 30%, 6%, 9%, and 28% of cases, corresponding respectively to each of the above five common indications. Rarely cited reasons for intraoperative consultation were to expedite obtaining diagnosis for surgeon's knowledge (3%), to facilitate patient management, other professional communication or discharge planning prior to permanent section availability (3%), academic protocol (< 1%), and consultation not needed or no reason for request (< 1%)., Conclusions: This multi-institutional, interdisciplinary database confirms that pathology intraoperative consultations, regardless of the initial indications, influence immediate patient care decisions, resulting in changed surgical procedures in an average of 39% of all operative cases.

Objective: To survey transfusion medicine practices in 1990, to determine the distribution of defects in the transfusion process, to examine the relationship between defects and complications, and to recommend improvements in the transfusion process., Design: A mail survey that divided the transfusion process into 24 risk-prone steps and gathered defect rates on each step, along with incidence data for eight known complications of transfusions and other demographic information., Settings: Hospitals, independent laboratories, and blood centers that provide transfusion medicine services., Other Participants: Respondents were 1365 participants in the College of American Pathologists 1991 Blood Bank Quality Assurance Survey., Results: While processing 6.2 million units of blood and blood products, respondents reported detecting over 88,000 defects: 41% in the preanalytic phase of testing, 55% in the postanalytic phase, and only 4% in the analytic phase, the phase to which most monitoring efforts were devoted. A median of eight steps were actively monitored by survey participants overall, whereas 96 facilities sought defects in all 24 steps., Conclusions: Analysis of the data showed several monitoring steps provide similar information. Although monitoring of the transfusion process could not be linked with prevention of the complications studied, active surveillance does focus attention on defect-prone steps and allows testing of strategies to improve the transfusion process. We describe how defect detection systems may be improved.

Histologic review of 48 radical prostatectomy specimens containing both prostatic adenocarcinoma (PC) and high-grade prostatic intraepithelial neoplasia (PIN) resulted in 23 cases containing neoplastic cribriform gland (CGs) at the periphery or within PC fields. The histologic characteristics of CG PIN mimic those of CG PC in that a discernible basal cell layer defines CG PIN, while CG PC lacks a basal layer. To detect the presence of basal cells in CGs, step sections were immunostained with monoclonal antibody 34 beta E12 to high-molecular-weight cytokeratins (HMCK) found in basal cells, but not in PC cells. Optimal staining of formalin-fixed sections required pepsin predigestion followed by 14-hour monoclonal antibody incubation at 4 degrees C. Of 436 CG foci identified, 239 (55%) were outlined by a circumferential HMCK-positive layer (identifying PIN); 182 (42%) totally lacked this layer (identifying PC), with appropriate internal controls; and 15 (3%) stained indeterminately. In an attempt to distinguish CG PIN from PC by routine histologic examination alone, CGs with open, round spaces were classified as classic (156 foci); nonclassic CGs (265 foci) featured irregular oblong to slitlike spaces. Cribriform gland PIN defined by HMCK outlining was more often nonclassic (193 CG foci) in histologic pattern, and CG PC was usually "classic" (110 CG foci) (chi 2 = 75; P < .001). We conclude that (1) more than half (55%) of the CGs in the PC tumors studied contain a basal cell layer fulfilling the definition of PIN; (2) focal and isolated HMCK positivity is found amid PC, and thus the overall pattern of staining together with morphological features is critical to correctly exclude carcinoma; (3) grading of PC on the basis of the presence of CGs may lead to erroneous results if PIN foci are misinterpreted as PC; and (4) since CG PIN is usually found in intimate anatomic association with PC, HMCK staining to detect basal cells in isolated CGs encountered in biopsy specimens may be a useful diagnostic discriminant.

The microscopic features of prostatic intraepithelial neoplasia (PIN) are said to identify a precursor of prostatic adenocarcinoma (PC). We investigated this sequence of neoplastic progression by studying the relationship of PIN and PC by static ploidy analysis so that PIN and PC nuclei could be distinguished morphologically from each other and separately analyzed. From 51 archival cases of PC with coexistent high-grade PIN (PIN grades II and III) 50 control nuclei, 100 PIN nuclei, and 100 carcinoma nuclei per case were identified and digitized in corresponding Feulgen-stained slides. Control and PIN ploidy histograms fit a log-normal distribution, whereas malignant nuclei fit a rectangular distribution. When the histogram patterns were classified, the incidence of aneuploidy was 25% in PIN and 41% in PC. By case, the concordance of ploidy between PIN and PC was heterogeneous, yet the DNA ploidy of PIN and the corresponding PC was significantly associated. In four cases, PIN was DNA aneuploid while the associated PC was DNA diploid. These results support the hypothesis that high-grade PIN is a neoplastic precursor of prostatic adenocarcinoma and suggest that further karyotypic instability may result in invasive adenocarcinoma with different DNA content detectable by image analysis.

In 1991, the College of American Pathologist's Q-Probes Quality Improvement Program evaluated practices in 532 institutions for pathologic information provided in surgical pathology reports of 15,940 resected primary colorectal carcinomas. Participating institutions studied their last 30 completed cases and were from the United States (98%), Canada (1.5%), and Australia (0.4%). The influence of various institutional differences and other practice patterns were analyzed to determine factors associated with an increased institutional likelihood of providing information on pathology reports. The one practice significantly associated with increased likelihood of providing complete oncologic pathology information on eight of 11 gross and microscopic information items surveyed was the use of a standard report form or checklist. Other institutional differences bearing inconsistent associations included teaching institution status, presence of pathology residency, use of microscopic descriptions, institution bedsize category, and performance of DNA ploidy analysis. The development and adoption of a standardized report form or checklist for each case is a simple but effective means to assure report adequacy and consistent communication of oncologic pathology information. In conjunction with accompanying criteria for its accurate use, this process can be considered a practice guideline or practice parameter that can be extended to the surgical pathology examination of all resected malignant neoplasms.

In 1990, the College of American Pathologists Q-Probes Quality Assurance Program studied performance in fine-needle aspiration (FNA) of pulmonary lesions derived by retrospective analyses of cases accessioned throughout 1989 by 436 institutions in North America. The aggregate database consisted of 13,094 lung FNA cases with 11,922 (91%) judged as satisfactory for cytologic evaluation. Of these satisfactory aspirates, 5264 (40%) had corresponding histologic tissue biopsy preparations and FNA diagnoses available for further evaluation and formed the basis for determining diagnostic accuracy. There was no significant difference in overall performance results derived from the data provided by all participants compared with the median of those reporting a greater number of correlated FNA cases. In the diagnosis of lung cancer by FNA, the following performance results were derived using the aggregate database: 89% sensitivity of FNA procedure, 99% sensitivity of FNA diagnosis, 96% specificity, 99% positive predictive value, 70% negative predictive value, 91% efficiency, 0.8% false-positive FNA interpretation, and 8% false-negative rate. The aggregate value and median performance values of sensitivity and specificity derived from this Q-Probe study, which reflects the general practices of mostly non-university hospitals in North America, compare very favorably with study results of similar design in the literature reflecting practices from academic centers. This appears to validate published rates from academic centers as reproducible in the general practice of pathology and validates the use of these values derived from an aggregate database as a benchmark to measure performance improvement in lung FNA.

In 1989, the College of American Pathologists Q-Probes Quality Assurance Program studied intraoperative frozen-section consultations performed in 297 institutions with mean bed size of 316 (range, 0 to 1351 beds) in North America during 5 consecutive months. The aggregate database was composed of 933,751 surgical cases (mean, 3144 per institution); 52,464 frozen-section cases (mean, 177); and 79,647 individual frozen sections performed (mean, 268). The rate of frozen sections per all surgical case accessions was 5.6% (cases with frozen section) and 7.3% (individual frozen sections performed), with an average of 1.5 frozen sections per case. Frozen-section rate increased proportional to bed size, from less than 5% in institutions with bed size below 150 to 15% in institutions with bed size above 600. Of all frozen sections performed, 4.2% were deferred. Deferrals to paraffin sections in pathologists' opinions were 92.6% appropriate, 1.2% inappropriate, and 6.2% not stated. When frozen-section diagnoses were compared with permanent section diagnoses, there was a 98.3% diagnostic concordance, adjusted for deferred diagnoses, but including the performance of frozen sections on mammographically directed biopsy specimens with no gross abnormalities in 80% of institutions. This practice accounted for 11.8% of the discordant frozen-section diagnoses. The reasons for diagnostic discordances were gross tissue sampling (44.8%); misinterpretation (40%); sectioning (12.7%); inadequate history (5.6%); staining (1.5%); labeling (0.5%); and other (3%). Assessment of diagnostic discordance on patient outcomes by the reviewing pathologist showed that patient management was unaffected in 74%, minimally affected in 20%, and greatly affected in 2.5%.

In 1989, the College of American Pathologists, Northfield, Ill, instituted a voluntary quality assurance program, called "Q-Probes," that utilized nationwide interinstitutional peer comparison. One of the anatomic pathology modules retrospectively assessed performance in fine-needle aspiration cytology (FNAC) of the breast from cytohistologic correlations that were made in 294 institutions by 988 pathologists on their own cases that were accessioned during a 6-month period. Of the 13,066 cases of FNAC, 10,751 (82%) were satisfactory for evaluation. Of these satisfactory aspirates, 3471 cases (33%) had histologic correlation, which formed the basis for determining diagnostic accuracy. Of breast aspirates, 2254 (17%) were unsatisfactory for evaluation, with the mean frequency of unsatisfactory aspirates obtained by nonpathologists (18%), ie, more than twice that of unsatisfactory aspirates obtained by pathologists (7.2%). In the diagnosis of breast cancer by FNAC, the following performance results were derived with the use of the aggregate data: 82% sensitivity of the FNAC procedure, 97% sensitivity of diagnosis, 97% specificity, 95% positive predictive value, 86% negative predictive value, and 90% efficiency. No significant difference in performance was detected when institutions were stratified by six peer group characteristics. We made the following conclusions: (1) the aggregate and median breast FNAC performance values obtained from this interinstitutional comparison of data from routine procedures performed in diverse settings in North America compared very favorably with performance from single institutions published in studies of similar design in the literature, and (2) these data may provide a reference point for participant institutions to measure future quality improvement in fine-needle aspiration of breast.

We compared the diagnoses from intraoperative frozen-section consultation with the final diagnosis using permanent tissue sections from 34 hospitals throughout North America. Participating pathologists who provided data from their practices volunteered for a pilot study of Q-Probes, a modular quality assurance program of the College of American Pathologists, Skokie, III. During 4 weeks, 186 pathologists evaluated 1952 frozen-section cases and deferred diagnoses to the final permanent sections in 77 cases (3.9%). Concordance between frozen-section and the final histologic diagnoses was 96.5%; whereas the mean and median concordance rates for participating institutions were 96.8% and 97.4%, respectively. Of 67 discordant diagnoses, 29 occurred from sampling of nonrepresentative tissue specimens, and 29 from diagnostic misinterpretations. The pathologists indicated that the diagnostic discordance had little or no effect on patient care in 94% of cases. We conclude that the North American pathologists studied interpret frozen sections with exceedingly high accuracy, approximating that reported from teaching hospitals.

DNA analysis is currently being applied to many solid tumors to determine DNA content and synthesis phase fraction. We compared DNA content measured by flow cytometry with multiple histologic parameters in 155 squamous cell carcinomas of the upper aerodigestive tract. Abnormal DNA content (aneuploidy) was identified in 107 (69%) of the neoplasms. Abnormal DNA content or aneuploidy correlated with above-median synthesis phase fraction and increased frequency of mitotic figures. Other histologic features predicting aggressive tumor behavior also correlated with abnormal DNA content and included small cords or single cell pattern of tumor invasion, high nuclear grade, and decreased stromal or desmoplastic response to the invading squamous cell carcinoma.