Effect of Lean method implementation in the histopathology section of an anatomical pathology laboratory.

BACKGROUND: In the USA, the lack of processes standardisation in histopathology laboratories leads to less than optimal quality, errors, inefficiency and increased costs. The effectiveness of large-scale quality improvement initiatives has been evaluated rarely. AIM: To measure the effect of implementation of a Lean quality improvement process on the efficiency and quality of a histopathology laboratory section. METHODS: A non-concurrent interventional cohort study from 1 January 2003 to 31 December 2006 was performed, and the Lean process was implemented on 1 January 2004. Also compared was the productivity of the Lean histopathology section to a sister histopathology section that did not implement Lean processes. Pre- and post-Lean specimen turnaround time and productivity ratios (work units/full time equivalents) were measured. For 200 Lean interventions, a 5-part Likert scale was used to assess the impact on error, success and complexity. RESULTS: In the Lean laboratory, the mean monthly productivity ratio increased from 3439 to 4074 work units/full time equivalents (p<0.001) as the mean daily histopathology section specimen turnaround time decreased from 9.7 to 9.0 h (p = 0.01). The Lean histopathology section had a higher productivity ratio compared with a sister histopathology section (1598 work units/full time equivalents, p<0.001) that did not implement Lean processes. The mean impact, success and complexity of interventions were 2.4, 2.7 and 2.5, respectively. The mean number of specific error causes affected by individual interventions was 2.6. CONCLUSION: It is concluded that Lean process implementation improved efficiency and quality in the histopathology section.

Interobserver variability associated with the MIB-1 labeling index: high levels suggest limited prognostic usefulness for patients with primary brain tumors.

BACKGROUND: The use of the MIB-1 labeling index (LI) as a potential prognostic marker for patients with primary brain tumors is controversial. Many studies advocating its prognostic usefulness have suggested discrete MIB-1 LI cut-off values, above which patients have significantly worse outcomes. However, interobserver variability associated previously with MIB-1 LI calculation has not been reported despite the fact that the degree of interobserver variability impacts the clinical usefulness of such cut-off values. METHODS: MIB-1 LIs were calculated independently using a standardized protocol by six pathologist observers for 50 astrocytic gliomas of varying grades. The level of interobserver agreement was determined by calculating kappa statistics for pairwise pathologist comparisons using MIB-1 LI cut-off values of 2.5%, 5.0%, 8.0%, 11.0%, and 15.0%. Spearman rank correlation coefficients were used to assess the pairwise associations between observer MIB-1 LIs. RESULTS: Although there was general agreement among pathologists regarding whether an MIB-1 LI for a given astroglial tumor was low, moderate, or high based on the analysis of correlation, a high level of interobserver variability was associated with the determination of specific MIB-1 LIs. The highest level of agreement occurred using a cut-off value of 5.0%, with pairwise kappa statistics for this value ranging from 0.52 to 0.80. CONCLUSIONS: The high level of interobserver variability suggests that proposed discrete MIB-1 LI prognostic cut-off values most likely are not useful clinically for predicting outcome for individual patients with primary brain tumors. Further prospective studies are needed investigating the prognostic usefulness of MIB-1 LI ranges that optimize interobserver agreement.

Microtubule-associated protein-2: a new sensitive and specific marker for pulmonary carcinoid tumor and small cell carcinoma.

Microtubule-associated proteins (MAPs) are a major component of cytoskeleton family proteins associated with microtubule assembly. MAP-2 has been shown to be specifically expressed in neuronally differentiated cells. Pulmonary neuroendocrine carcinomas such as carcinoid tumors and small cell carcinomas are derived from neuroendocrine cells. We hypothesize that neuroendocrine cells may also express MAP-2, and therefore, MAP-2 may be used as a marker for pulmonary carcinomas of neuroendocrine differentiation. To investigate the utility of using MAP-2 expression to separate pulmonary neuroendocrine from non-neuroendocrine tumors, we examined the expression of MAP-2 immunohistochemically in 100 cases of pulmonary carcinomas. The immunoperoxidase method with antigen retrieval was used to characterize the expression of MAP-2, chromogranin, synaptophysin, and neuron-specific enolase in 25 small cell carcinomas, 25 carcinoid tumors, 25 adenocarcinomas, and 25 squamous cell carcinomas. All tumors were lung primaries. All 25 cases of carcinoid tumors (100%) as well as 23 of 25 cases (92%) of small cell carcinomas were positive for MAP-2. Four of 25 cases (16%) of adenocarcinomas were positive for MAP-2 and synaptophysin. Among the 25 squamous carcinomas, 4 cases (16%) were positive for MAP-2, 2 cases (8%) were positive for synaptophysin, 11 cases (44%) were positive for neuron-specific enolase, and none was positive for chromogranin. In conclusion, MAP-2 is a new sensitive and specific marker for the pulmonary tumors of neuroendocrine differentiation. We recommend that MAP-2 be added to immunohistochemical panels to separate non-neuroendocrine from neuroendocrine lung tumors.

Interobserver and intraobserver variability in the cytologic diagnosis of normal and abnormal metaplastic squamous cells in pap smears.

OBJECTIVE: Interoberver variability has important implications for patient care, diagnostic error and medical litigation. In the management of any cervical epithelial abnormality, its biologic significance as well as diagnostic reproducibility is very important. Interobserver variability has not been measured adequately for metaplastic squamous lesions. We analyzed interobserver and intraobserver variability and diagnostic accuracy in the diagnosis of dysplastic metaplastic cells. STUDY DESIGN: Sixty Pap smears from patients with abnormalities of metaplastic squamous cells of varying severity were selected from the files of Lankenau Hospital, Wynnewood, Pennsylvania, U.S.A., diagnosed between 1990 and 1996. These were reviewed by four observers with different levels of cytology experience. Each of the observers blindly and independently reviewed all Pap smears. Tabulated results were analyzed to determine interobserver and intraobserver variability and diagnostic accuracy. RESULTS: Statistically significant interobserver reproducibility was found between both inexperienced observers as well as between observers 1 (experienced) and 3 (inexperienced) and between observers 2 (experienced) and 4 (inexperienced). The observed degree of agreement between both experienced observers (1 and 2) reflected random rating rather than reproducibility. There was no difference in interobserver reproducibility in low vs. high grade lesions. Intraobserver reproducibility had no significant correlation with experience of the observer. The sensitivity ranged from 0.69 to 0.97 (mean, 0.79), while the specificity ranged from 0.09 to 0.46 (mean, 0.30). Mean diagnostic accuracy was better in benign and low grade squamous intraepithelial lesions in comparison to high grade squamous intraepithelial lesions. CONCLUSION: There was good interobserver agreement in classifying squamous metaplastic lesions. The agreement did not correlate with grade of dysplasia or experience of the cytopathologists. These findings should be considered in making treatment, quality assurance and legal decisions. A larger study is indicated to study interobserver and intraobserver variability and define cytologic criteria for lesions of metaplastic squamous cells.

Cost-effectiveness studies on cervical cancer.

Cost-effectiveness analyses are an important source of information for the design and evaluation of policies to reduce cervical cancer. This paper describes the recommendations of a panel on cost-effectiveness studies convened as part of the International Consensus Conference on the Fight Against Cervical Cancer. Recommendations for cost-effectiveness studies include: (1) the use of reference case methods to support comparisons across studies, (2) the use of a consistent standard of evidence on the clinical effectiveness of different screening strategies, (3)further research into the costs and effectiveness of different screening and treatment strategies for cervical cancer, (4) further research into screening and treatment strategies in a wide range of countries, (5) easily accessible and detailed descriptions of the methods and supplementary analyses underlying published studies, (6) greater use of newly developed models of cervical cancer, and (7) greater revelation of potential conflict of interest by researchers.

National practice characteristics and utilization of pathologists' assistants.

OBJECTIVE: To obtain descriptive information regarding the practice characteristics and utilization of US pathologists' assistants. DESIGN: A self-administered, mailed, voluntary, anonymous questionnaire was distributed to a cross-sectional sample of 515 US pathologists' assistants registered as members of the American Association of Pathologists' Assistants. The questionnaire contained items relating to subject demographics, practice characteristics, specific task performance, and amount of time spent per day on the performance of specific tasks. Descriptive statistics were used to describe the data in terms of measures of central tendency and dispersion. RESULTS: The response rate was 66.8%. The majority of questionnaires sent and received were from East Coast regions. Of all respondents, 46.6% were women, 57.6% were less than 40 years old, and 60.0% had been practicing 10 years or less. Over half (54.0%) had a master's degree. Almost the entire sample reported working 30 or more hours per week, with 43.4% reporting working more than 40 hours per week. The majority reported earning annual salaries between $56 000 and $75 000. Although task analysis of responses revealed a wide range of responses, the majority of the sample reported spending most of their daily time performing surgical specimen gross examinations (median 300 min/d). Approximately half of respondents also reported spending up to 90 minutes per day on nonspecific tasks such as logging specimens and answering the phone. Most respondents reported spending more daily time on such nonspecific tasks than on autopsy prosection or research. CONCLUSIONS: To our knowledge, this national survey provides the first description of pathologists' assistants across the United States. These data provide a useful tool for tracking changes in the profession.

Clinical perception of disease probability associated with Bethesda System diagnoses.

The degree to which clinical perceptions of Papanicolaou smear sensitivity contribute to patient mismanagement is uncertain. A voluntary, anonymous questionnaire was mailed to 350 obstetricians/gynecologists (OGYNs) and 350 other primary care providers (PCPs) located in Pennsylvania or Ohio. The clinicians estimated the probability of no disease, dysplasia, and invasive carcinoma for 1 of 7 Bethesda System diagnoses. Differences in probability estimates between provider types and between the clinicians and medical literature data were measured. The response rate was 22.7%. Compared with published values, clinicians estimated similar disease probabilities for many diagnoses. However, for some diagnoses, the probability estimates differed considerably from published values (e.g., overestimation of dysplasia and invasive carcinoma for benign diagnoses and underestimation of dysplasia for some dysplasia diagnoses), and such errors could contribute to patient mismanagement. OGYNs generally were more accurate in probability estimates than PCPs. Methods to convey more accurately these diagnostic disease probabilities should be examined.

De novo establishment and cost-effectiveness of Papanicolaou cytology screening services in the Socialist Republic of Vietnam.

BACKGROUND: Cervical carcinoma is the leading cause of cancer-related death among women in the developing world. The absence of cervical screening in Vietnam and other developing countries is due in large part to the perceived expense of implementing Papanicolaou cytology screening services, although, to the authors' knowledge, the cost-effectiveness of establishing such services has never been studied in a developing country. METHODS: Using decision analytic methods, the authors assessed cost-effectiveness of Pap screening from a societal perspective in Vietnam, the world's 9th most populous developing country (estimated 1999 population, 79 million). Outcomes measured included life expectancy, cervical carcinoma incidence, cost per woman, and cost-effectiveness. RESULTS: Total costs to establish a nationwide 5-year interval Pap screening program in Vietnam will average less than $148,400 annually during the 10-year time period assumed necessary to develop the program and may be considerably lower if only high risk geographic areas are targeted. Maintenance costs will average less than $0.092 annually per woman in the target screening population. Assuming 70% program participation, cervical carcinoma incidence will decrease from 26 in 100,000 to 14.8 in 100,000, and cost-effectiveness will be $725 per discounted life-year. Several assumptions used in this analysis constitute biases against the effectiveness of Pap screening, which in reality may be significantly more cost-effective than reported here. CONCLUSIONS: Contrary to widespread belief, Pap screening in developing countries such as Vietnam is extraordinarily inexpensive and appears to be cost-effective. Because prospects are uncertain regarding useful alternatives to the Pap test, the evidence-based argument for establishing conventional Pap screening services in developing countries such as Vietnam is compelling. Population-based conventional Pap screening services have been established de novo in Vietnam and are now operational.

Fine-needle aspiration for the diagnosis of primary epithelial tumors of the lacrimal gland and ocular adnexa.

Results of fine-needle aspiration (FNA) of solid-tissue neoplasms arising in the periocular glands are infrequently reported in the literature. To our knowledge, no previous series relating to this topic exist. Neoplastic processes that arise in the semiconfined area of the orbit behave as space-occupying lesions. Such lesions can exert significant pressure on the globe, be responsible for altered vision, and result in proptosis. When noninvasive techniques fail to confirm or rule out the suspicion of a neoplastic lacrimal or adnexal lesion, FNA may be of use in establishing a diagnosis in an efficient, reliable, timely, cost-effective, and safe manner. During the 14-yr interval from 1986-1999, 77 orbital/ocular needle aspiration biopsies were conducted by staff ophthalmologists at Allegheny General Hospital (Pittsburgh, PA). Review of the diagnoses for these specimens revealed seven primary solid-tissue lesions of the lacrimal gland and other adnexal glands, all arising in adult patients (age range, 45-92 yr; mean age, 74 yr). Primary lacrimal and adnexal gland neoplasms were found to represent approximately 9% of orbital fine-needle aspirations (7/79). The 7 cases included 3 lacrimal gland lesions diagnosed as benign mixed tumors, 3 lesions diagnosed as adenoid cystic carcinoma of the lacrimal gland, and 1 tumor diagnosed as sebaceous carcinoma of the meibomian holocrine glands. Cytologic diagnoses were rendered using standard criteria for salivary gland-type tumors. Tissue confirmation was available from surgical follow-up in 4 of the 7 cases, with 100% correlation. Although primary neoplasms of the lacrimal gland and glands of the eyelids are rare, accurate diagnoses of such lesions may be established with minimally invasive aspiration techniques. Preoperative aspiration biopsy diagnoses provide a great advantage to ophthalmic surgeons who routinely operate in a conservative fashion in an area of the body requiring great attention to cosmesis. Our experience indicates that FNA is a reliable and effective tool in the diagnosis and management of primary lacrimal and ocular adnexal tumors.

Pathologists' assistants practice: a measurement of performance.

Despite their widespread utilization, little is known about the quality of pathologists' assistants' services. Pathologists' assistants' performance was compared with pathology residents' performance using the metrics of lymph node retrieval and tissue resubmission rates. Lymph node retrieval was calculated by retrospective review of surgical pathology reports from a sample of axillary dissection, mastectomy, and colorectal specimens. Tissue resubmission rates were calculated by retrospective review of a sample of general surgical pathology reports. Pathologists' assistants retrieved a significantly greater total number of lymph nodes compared with pathology residents; however, there was no difference in the total number of positive lymph nodes retrieved. Cases for which pathologists' assistants performed the gross examination had a significantly decreased resubmission rate compared with those performed by residents. In this setting, the gross examination performance of pathologists' assistants was equivalent to or superior to that of pathology residents. These results provide the first information available relating to pathologists' assistants' performance in surgical pathology.

Fine-needle aspiration for the diagnosis of orbital hematolymphoid lesions.

Ocular and periocular hematolymphoid diseases are a diverse group of lesions affecting various soft tissue structures within the orbital cavity. Lymphoid proliferations in particular are among the most commonly diagnosed entities in orbital pathology. When noninvasive techniques fail to confirm or rule out the suspicion of orbital neoplasia, fine-needle aspiration (FNA) may be of use in establishing a diagnosis in a reliable, timely, cost-effective and safe manner. From 1986 to 1999, 79 orbital/ocular needle aspiration biopsies were conducted by staff ophthalmologists at Allegheny General Hospital. Slides from these cases and corresponding reports were pulled from the cytology files and grouped into the two broad categories of hematolymphoid and other. Specimens came from patients ranging in age from 14 to 88 years (mean, 64 years) with eight patients having known histories of hematolymphoid disorders. Immunocytochemical (ICC) studies were performed in 33% of the cases (14/43). Review of the diagnoses for the 79 aspiration specimens revealed 30 cases diagnosed as lymphoma/atypical lymphocytic infiltrate, cases diagnosed as inflammation or abscess, three cases diagnosed as plasmacytoma, three cases called suboptimal with scant inflammatory cells, and one case of Langerhans' cell histiocytosis. Hematolymphoid diagnoses accounted for 54% (43/79) of all diagnoses. Histologic correlation was available in 33% (14/43) of the cases (nine cases diagnosed as cytologically atypical/malignant and five cases called cytologically benign/suboptimal) with 100% correlation. Hematolymphoid lesions of the orbit are readily diagnosed by FNA. Because many hematolymphoid malignancies are treated as systemic or multiorgan system diseases and because ocular lymphomas may also involve the central nervous system, nonsurgical attempts at diagnosis have the potential to spare the patient procedural morbidity which may be associated with open biopsy. Our experience indicates that the combination of FNA, judicious use of immunocytochemical studies, and correlation with pertinent clinical information and imaging studies allows for reliable and effective classification and diagnosis of orbital hematolymphoid lesions.

The cost-effectiveness of immunohistochemistry.

OBJECTIVE: To evaluate the cost-effectiveness of immunohistochemistry. DESIGN: Using a theoretical decision analytic model, the cost-effectiveness of immunohistochemistry was evaluated in different scenarios depicting the beneficial use of immunohistochemistry. Data regarding the effectiveness of immunohistochemistry were obtained from the medical literature and costs were obtained from Allegheny General Hospital. SETTINGS: The scenarios depicted both private practice and university patients from which anatomic pathology specimens were obtained. Immunohistochemistry was subsequently performed on these specimens. MAIN OUTCOME MEASURES: Cost, life expectancy, diagnostic certainty, ability to predict prognosis, and cost-effectiveness were evaluated. RESULTS: In all scenarios, immunohistochemistry was cost-effective at very low efficacies. Assuming a per-antibody cost of $50 and use of a 5-antibody panel, immunohistochemistry was cost-effective if it resulted in a 1-year gain of population life expectancy in 1 or more of every 200 cases in which it was applied. Alternatively, if the gain in diagnostic certainty by using immunohistochemistry was 10% and the value placed on a percentage gain in diagnostic certainty was $1000, immunohistochemistry was cost-effective if it produced this increase in certainty in 1 of every 40 tests. If a life-year was valued at $50 000, immunohistochemistry was cost-effective if it resulted in a change in patient prognosis of 0.5 years in 1 of every 100 tests. CONCLUSIONS: Using theoretical modeling, immunohistochemistry is extremely cost-effective. These data have implications in an era of managed care when providers attempt to trim laboratory services. Additional studies are needed to evaluate the actual practice efficacy of immunohistochemistry.

Quality assurance and risk reduction guidelines.

Cervical cancer continues to be a major cause of death in women worldwide. The major problem facing most women is the unavailability of screening Pap tests in poor and underdeveloped countries. While rates of cancer deaths have decreased 60-80% in developed countries since the Pap test became available, the accuracy of Paps was challenged recently. In order to instill public confidence and promote optimal patient care, measures to improve the quality of the entire screening process should be undertaken. Continuous quality improvement processes are more appropriate than traditional quality assurance monitors. Although no standards can be defined that are applicable to all laboratory settings and nations, this document provides current views on universal quality procedures and risk reduction. Procedure/policy manuals, workload assessment, hierarchic/peer review, discrepancy analysis, rescreening studies and cytohistologic correlation are examples of universally applicable quality tools. The variability in practices in different parts of the world is also discussed.

Cytologic features useful for distinguishing small cell from non-small cell carcinoma in bronchial brush and wash specimens.

One blinded observer (C.D.S.) retrospectively reviewed 76 previously diagnosed and biopsy-confirmed malignant bronchial brush and wash specimens, 46 non-small cell and 30 small cell carcinomas, obtained from 55 patients. Each case was scored for the presence or absence of 36 standard criteria (architectural, cytoplasmic, and nuclear). Logistic regression analysis was used to determine which criteria were most useful for separating small cell from non-small cell lesions. Although no single criterion displayed 100% sensitivity and specificity for small cell cancer, univariate statistical analysis indicated that 3 individual criteria (nuclear molding, finely granular or "salt and pepper" chromatin, and scant delicate cytoplasm) were more than 90% sensitive and specific in cases of small cell carcinoma. The presence of nuclear molding alone provided the best fit for the logistic regression model. When nuclear molding was present, the odds of a small cell diagnosis increased more than 300-fold. Nuclear molding, finely granular or salt and pepper chromatin, and scant, delicate cytoplasm are the 3 most sensitive and specific cytomorphologic features traditionally used to separate small cell from non-small cell carcinoma. Nuclear molding alone represents the most significant cytomorphologic feature for distinguishing between these malignant lesions.

Cytology of angiosarcoma. Findings in fourteen fine-needle aspiration biopsy specimens and one pleural fluid specimen.

We report the cytologic features of 15 cases of angiosarcoma from various sites and include 14 fine-needle aspiration (FNA) biopsy specimens and 1 pleural fluid specimen. Six were initial diagnoses with histologic confirmation; an additional case in the liver was an initial diagnosis without tissue confirmation. One case represented lymph node metastasis from a primary prostatic epithelioid angiosarcoma. In 10 cases, immunohistochemical staining for factor VIII-related antigen, CD34, CD31, or Ulex europaeus agglutinin I was performed on the cytology or histology specimen. The aspirates varied in cellularity, and the degree of nuclear atypia ranged from relatively bland in a case of low-grade angiosarcoma of the prostate to highly pleomorphic in a lymph node metastasis from a facial cutaneous angiosarcoma. Vasoformative features such as intracellular RBCs, well-formed vessels, attempts at microacinar/lumen formation, and intracytoplasmic lumens were variably present. The background was bloody in all specimens, with necrosis in rare cases. This cytologic series emphasizes that the cytologic features are heterogeneous but that the diagnosis can be suggested by fine-needle aspiration (FNA) when vasoformative features are present. The diagnosis can be made conclusively by FNA with immunocytochemical confirmation of endothelial differentiation.

Effect of clinical history on diagnostic accuracy in the cytologic interpretation of bronchial brush specimens.

There has been little study of the effect of clinical history on pathologic diagnostic accuracy. Five pathologists retrospectively examined 97 bronchial brush specimens with and without clinical historic information. Forty-nine patients had a biopsy-proven malignant lesion, and 48 had a benign lesion. Diagnostic accuracy with and without history for each pathologist was determined with likelihood ratios and receiver operating characteristic curves. The overall diagnostic accuracy with and without history was 0.84 and 0.76, respectively. The average negative predictive value of a benign diagnosis decreased from 89.2% (with history) to 74.0% (without history). Overall, the cytopathologists were more reluctant to make a definitive malignant diagnosis without history compared with history. The average positive predictive value of a malignant diagnosis with and without history was almost identical. The absence of history leads to lower diagnostic accuracy in the cytologic interpretation of bronchial brush specimens partly because pathologists underdiagnose malignant lesions.

Small-cell variant of synovial sarcoma: fine-needle aspiration with ancillary features and potential diagnostic pitfalls.

We report a small-cell variant of synovial sarcoma examined by fine-needle aspiration (FNA) biopsy. The patient is a 23-yr-old female who had a synovial sarcoma involving the left infratemporal region, diagnosed at 7 yr of age, followed by a metastatic lesion involving the lung and chest wall 16 yr later. The chest wall metastases was sampled by FNA biopsy. The aspirate consisted of numerous, small, round cells with very high nuclear-to-cytoplasmic ratios. The cytomorphologic features could potentially be confused with other pediatric small round cell tumors. Ancillary studies demonstrated positive staining of the neoplastic cells for cytokeratin, epithelial membrane antigen (EMA), and CD99. The differential diagnosis of other small round cell tumors that may be mistaken for the small-cell variant of synovial sarcoma are presented. We believe that this is the first FNA report detailing the cytologic and ancillary features of the small-cell variant of synovial sarcoma.

Can glandular lesions be diagnosed in pap smear cytology?

Many reports have been published on the accuracy of the cervical vaginal smear for squamous lesions, and the literature contains fewer reports on the accuracy of the cervical vaginal smear for glandular lesions. The sensitivity of glandular lesion diagnosis depends on the subtype of lesion. The diagnostic sensitivity is highest for invasive endocervical adenocarcinoma and lowest for endometrial adenocarcinoma. The ability of some of the Bethesda system categories for glandular lesions to describe what they purport to describe is questionable. The Bethesda system categories of adenocarcinoma accurately classify adenocarcinomas. The Bethesda System category of atypical glandular cells of undetermined significance (AGUS) is a misnomer. Although many cases of adenocarcinoma in-situ are placed in this category, follow-up of patients with AGUS show that the majority of patients with clinically significant lesions have squamous dysplasias. Other categories of AGUS, such as AGUS favor endometrial origin, are more appropriately named and encompass endometrial lesions which are either neoplastic or non-neoplastic.