Liquid-based cytologic specimen studies to screen for cervical dysplasia in rural El Salvador.

OBJECTIVE: To evaluate an alternative tool (ThinPrep; Cytye Corporation, Boxborough, Mass, USA) for cervical cancer screening in rural El Salvador. METHODS: Cervical samples were obtained from 471 women attending health fairs in rural El Salvador. The samples were read by American and Salvadoran pathologists after a 1-week training course in liquid-based cytologic studies in the United States. RESULTS: The system evaluated detected a significantly higher number of high-grade and above lesions than conventional cytologic studies (P=0.01). There were 0.4% and 1.7% of high-grade lesions and above detected with conventionally prepared slides in the United States and El Salvador, respectively, and 3.2% and 3.8% of such lesions detected with liquid-based samples in the United States and El Salvador. Intra-observer agreement among the pathologists reading the samples was substantial for the ThinPrep system, with a kappa value of 0.6. CONCLUSION: A short workshop is effective in training pathologists to use ThinPrep. In the studied population, liquid-based studies appear to offer significant advantages over conventional cytologic studies for detecting high-grade lesions.

Incidental coenurosis: larval cestode presenting as an axillary mass.

This article describes the occurrence of a coenurus, the encysted larval stage of a cestode of the genus Multiceps, within the axilla of a 40-year-old Nigerian woman. The patient had a history of intraductal carcinoma of the breast two years prior to the finding of an ipsilateral axillary mass. Pathologic evaluation of the biopsy specimen yielded the diagnosis of coenurosis. Only four other cases of human Multiceps infestation have been reported in the United States with fewer than 100 validated cases worldwide. Surgical removal of the larval parasite is the only known effective therapy.

Use of anion gap for the quality control of electrolyte analyzers.

A simple model for the simulation of patient Na, CO2, Cl, and anion gap was formulated from patient electrolyte data. Analytical error, either random or systematic, was incorporated into the simulation of the electrolyte data and allowed study of the response of anion gap to error. Power functions, plots of probability of error detection vs. size of analytical error, were constructed and indicated a low probability of error detection when single patient specimens with abnormal anion gaps were reanalyzed. These power functions showed that pooling of the anion gap data by averaging consecutive anion gaps resulted in a high probability for detecting systematic error. We recommend, as a useful quality control procedure, averaging at least eight consecutive anion gaps and testing for a significant difference between the average and the established mean gap.

Quality control of electrolyte analyzers. Evaluation of the anion gap average.

The authors have shown previously that averaging at least eight patient anion gaps provides a sensitive technic for the detection of systematic error in electrolyte analysis (Am J Clin Pathol 79:688-696, 1983). They conducted a retrospective and prospective evaluation of this technic on the ASTRA 4. One month of patient and control data were studied retrospectively and showed that 17/71 abnormally low patient anion gap averages were associated with violations in a multi-rule procedure, and 41/71 low averages were associated with violations in cusum, a more sensitive procedure. In the prospective study, a total of 36 runs of eight patient specimens with low anion gap averages (less than 7.5 mmol/L) were reanalyzed after appropriate recalibration and/or maintenance. Thirty-one of the 36 groups had significant changes in either Na (nine groups, delta Na = +1.5 mmol/L), Cl (14 groups; delta Cl = -1.8 mmol/L), or in both Na and Cl (eight groups; delta Na = +1.2 mmol/L; delta Cl = -0.9 mmol/L). Because the average error detected was small, the authors recommend that the average of anion gaps be used as an early indicator of drift. It must be used, however, in conjunction with standard quality control procedures such as the multi-rule approach.

Do proficiency test results correlate with the work performance of screeners who screen Papanicolaou smears?

We rescreened Papanicolaou smear slides from 40,245 women, which had been examined by 81 cytology screeners, scored the screeners' work performance, and compared these scores with the results of the screeners' performance on glass slide and computer-based proficiency tests. All diagnoses (i.e., from the proficiency tests, the original slides, and the rescreened slides) were classified in the 4 diagnostic categories specified in the Clinical Laboratory Improvement Amendments. The rescreening scores were standardized to account for different distributions of abnormalities in the proficiency tests and rescreened slides. We compared a standardized score with the proficiency test scores. Of the cases, 91% were categorized as normal, benign, or reactive changes when rescreened, and 98% of these agreed with the original diagnosis. Sixteen percent of low-grade and 15% of high-grade intraepithelial lesions were classified as normal. The rank correlation between the rescreening scores and both proficiency tests was 0.24 using a scoring scheme for cytotechnologists. The correlation between the rescreening and proficiency testing scores indicates that performance on a 10-slide test gives some indication of the true performance of screeners. The computer-based test shows promise as an alternative to the glass slide test but needs further development and validation.

Electronic imaging in cytopathology.

Electronic imaging is becoming important for conveying instructional and diagnostic information. This article presents an overview of the acquisition and display of microscopic images for day-to-day cytologic and histologic practice. The devices, software, and methods for image capture and manipulation are described.

Significance of apparent intratympanic meningiomas.

Meningioma is the most common tumor of the central nervous system, but it has only been reported in 79 patients to involve the temporal bone. The 4 cases presented here show striking clinical similarity to a subgroup of 20 meningiomas reported to be entirely intratympanic; however, in each instance the extent, origin, and potential of the disease was not initially evident. Precise histopathologic diagnosis may be aided by electron microscopy. Current concepts of embryology lend credence to the possible role of arachnoid endothelial cells in the pathogenesis of intratympanic meningioma. An advanced intracranial meningioma may be overshadowed by the hearing loss, tinnitus, and otalgia calling attention to an intratympanic component. The clinician should remain suspicious of intracranial disease even after excision of an apparently well circumscribed intratemporal lesion. Progressive sensorineural hearing loss and persistent otalgia portend recurrent or intracranial disease. Follow-up for at least 10 years with judicious use of CT scans is suggested.

Analysis of false-negative diagnoses on endoscopic brush cytology of biliary and pancreatic duct strictures: the experience at 2 university hospitals.

CONTEXT: Endoscopic brush cytology is a valuable technique for the diagnosis of pancreatobiliary malignancy. Despite its widespread use, the sensitivity of this method has been reported as approximately 50%. The specificity is usually higher than 95%. Few reports have systematically analyzed the reasons for this relatively low sensitivity. OBJECTIVES: To determine the rate and reasons for false-negative diagnoses in endoscopic brushing cytology of biliary and pancreatic ducts based on the results of sensitivity, specificity, accuracy, and positive and negative predictive values. DESIGN: Retrospective analysis of laboratory data and slide review of false-negative cases. SETTING: Two tertiary care state university hospitals. PATIENTS: A total of 183 pancreatobiliary brushing specimens obtained from patients undergoing endoscopic retrograde cholangiopancreatography for biliary or pancreatic duct disease for a 4- to 5-year period. INTERVENTION: Endoscopic retrograde cholangiopancreatography brushings. MAIN OUTCOME MEASURES: Determination of sensitivity, specificity, accuracy, and positive and negative predictive values. Analysis of false-negative results. RESULTS: The sensitivity, specificity, accuracy, and positive and negative predictive values, overall, were 48%, 98%, 79%, 92%, and 76%, respectively. Sampling error was a major cause of false-negative diagnoses (67%), followed by interpretive (17%) and technical errors (17%). CONCLUSIONS: Improvements in sensitivity and diagnostic accuracy for cancer of the pancreatobiliary tract can be achieved by optimizing slide preparatory techniques. Also, enhancement of the cytologist's diagnostic skills enables the identification of the morphologic features of premalignant lesions. Repeat brushings are indicated for suspicious or negative results not consistent with the clinical or radiologic findings.

Thin-layer technology: tempered enthusiasm.

With the introduction of new technologies we often see a pattern of development. As a useful technology moves into the public sector there is often an episode of wild enthusiasm and uncritical acceptance, followed by a time of progressive disillusionment. However, with time and experience, a proper place for the method becomes established. Thin-layer technology is certainly an improvement and solves many of our preanalytical problems; however, it introduces some difficulties of its own. The rounding up of cells in liquid fixation makes cells of high-grade lesions smaller than they would be on a conventional preparation. The abnormal cells are often separated. For both of these reasons they may be overlooked. Furthermore, benign glandular cells can take on an ominous appearance. These differences in conventional and thin-layer morphology are proving to be a fruitful area for publication. Thin-layer technology cannot be all things to all situations, and this is especially true in body fluid and fine-needle cytomorphology. In our experience, while occasionally helpful, the thin-layer technique should not be the primary method for diagnosis in nongynecologic specimens. Time and effort would be better spent on trying to educate select clinicians on how to obtain better samples than to totally convert to thin-layer methodologies. Regarding FNA, the patient is best served when the pathologist is directly involved with the initial sample acquisition. Reimbursement is available for immediate sample interpretation, so funding should be available for staffing if an institution has the interest. For the record, we believe that liquid fixation and thin-layer methodology should not be the primary method for FNA, unless circumstances are absolutely prohibitive. An important problem with thin-layer technology lies with its added cost. Thin-layer interposes another series of steps into cytologic sample preparation. There is additional labor, additional time, another machine in the laboratory, and the significant cost of the reagents. In a situation where the price of a cytologic test is already close to margin, costs of the vial, filter, and preservative throw the test into unprofitability. Price structures have to be changed. Some institutions are waiting until there is more competition in the market and costs decrease. Alternatively, a lot of effort has been expended in trying to get government and other groups to accept the additional costs of the new test for gynecologic examinations, and many payers seem to be falling in line to accept the methodology, secondary to clinician and patient demand. Basic questions about ancillary technologies and gynecologic samples remain to be answered. Cytology is big business. Every year a significant segment of the population has a Pap smear performed. Hardly any other laboratory test can claim the volume of activity of the cervical smear. Any business that can hook into that market stands to prosper. Since the Pap smear has some well-publicized problems, the door is open for technology to nibble away at a few percentage points of false negativity. We are far from the first to ask if we can afford the incremental improvements of thin-layer and other ancillary technologies. There is a conundrum. Government, insurance companies, and our administrators are calling for us to hold back cost increases in medical care. Alternatively, these new technologies, patient demand for the perfect test, increased regulatory oversight, and legal challenges are increasing the cost of doing business. We do not know how to respond to the often-voiced fear that these ancillary technologies increase the cost of cytology services beyond some patients' ability to pay. In this confusion, we do know that we should use the best test to get the most accurate answer for our patients. In selected scenarios this may mean that we will have to accept the cost and follow thin-layer technology.

Diagnosis of fibromatosis colli by fine-needle aspiration.

Fibromatosis colli is a benign disorder presenting as a neck mass in neonates and older children. The differential diagnosis includes malignancies such as rhabdomyosarcoma. Neck masses in ten infants, discovered between the second and sixth week of age, were evaluated by fine-needle aspiration (FNA). The male to female ratio was 7:3. In 8 patients there was good obstetrical history. Six of the 8 patients had a difficult delivery, as indicated by breech presentation or the need for forceps. Diagnostic aspirations were performed between the second to ninth week of age. The major cytologic finding was benign spindle fibroblasts, usually arrayed in clusters. The cells possessed plump, ovoid nuclei. There were also multinucleated cells consistent with degenerating skeletal muscle fibers. Only one case demonstrated significant inflammation. FNA can provide a rapid and reliable diagnosis in fibromatosis colli. There is support for the idea that in this setting, the disorder is related to perinatal muscular trauma.

Fine-needle aspiration diagnosis of spindle-cell lipoma: a case report and review of the literature.

Spindle-cell lipoma (SCL) is an uncommon subcutaneous soft-tissue neoplasm that usually arises in the posterior neck and shoulder of older male patients. To our knowledge, there have been only two reports describing the cytologic findings of this benign tumor, only one of which was confirmed by subsequent histologic examination. We report on a SCL of the occipital scalp in a 62-yr-old man diagnosed by fine-needle aspiration. Air-dried and alcohol-fixed smears revealed scattered clusters of mildly pleomorphic spindled cells admixed with mature adipocytes, numerous mast cells, and small fragments of collagen. The diagnosis was confirmed by histologic sections and immunohistochemical studies for CD34 and bcl-2 oncoprotein. Cytomorphologic features of SCL and a review of the literature are presented.

Cytologic diagnosis of true thymic hyperplasia by combined radiologic imaging and aspiration cytology: a case report including flow cytometric analysis.

True thymic hyperplasia (TH) is an age-dependent increase in size and weight of the thymus gland, which by definition maintains a normal histologic architecture. TH can mimic other important diseases, including lymphofollicular hyperplasia, thymoma, lymphoma, and germ-cell tumors. Traditionally, separating these entities has required a formal surgical biopsy. Given that many of these conditions occur in children, this can be a traumatic experience for both the patient and family members. Fine-needle aspiration biopsy has the distinct advantage of being able to obtain diagnostic material without requiring general anesthesia. We are aware of only one previously reported case of an enlarged thymus being subjected to aspiration cytology. We therefore present a case of thymic hyperplasia in a 5-mo-old child diagnosed by combined radiologic and cytologic parameters, including flow cytometric analysis.

Leiomyosarcoma metastatic to the orbit: diagnosis of fine-needle aspiration.

A 47-yr-old man with history of metastatic low-grade rectal leiomyosarcoma presented with progressive protrusion of his left eye due to an enlarging orbital mass. The differential diagnosis included tumor metastasis or orbital infection due to an unknown infectious agent. Diagnostic fine-needle aspiration (FNA) of the orbit was performed on an urgent basis to institute proper therapy and to save the patient's eyesight. Cytomorphologic examination of the material demonstrated a spindle-cell neoplasm consistent with metastatic leiomyosarcoma. It is a rare event for leiomyosarcoma to occur in the orbit. On our review of the literature, the cytology of primary orbital leiomyosarcoma on FNA has only been reported once. To our knowledge, this is the first report of the FNA cytomorphology of metastatic leiomyosarcoma to the orbit.

Pulmonary parenchymal splenosis.

We describe the cytologic findings of a case of pulmonary parenchymal splenosis, a rare condition that follows lacerating trauma to the spleen, and may masquerade as a metastatic neoplasm. Approximately 24 cases of thoracic splenosis have so far been reported, the vast majority presenting as pleural-based nodules, and the cytological features of only two cases, both belonging to the latter group, have been described. We believe our case report to be the first to describe the cytological features of an intrapulmonary splenosis, and its features differ from the prior cases by having a mixed inflammatory cell infiltrate, with a predominance of lymphocytes, plus pulmonary macrophages and occasional endothelial cells. This condition has variable cytological features, but the correct diagnosis can be made in the presence of appropriate history and radiographic findings. Confirmation may require biopsy or radionucleide imaging.

Exfoliative cytology of primary poorly differentiated (small-cell) neuroendocrine carcinoma of the uterine cervix in ThinPrep material: a case report.

Poorly differentiated neuroendocrine (small-cell) carcinoma of cervical origin is a rare neoplasm that frequently metastasizes. Although the cytologic features have been described for conventional cervical smears, we know of no reports of its appearance in ThinPrep (TP) material. Therefore, we present a TP case of primary, small-cell carcinoma arising in a 46-yr-old female, confirmed by histologic and immunohistochemical analysis. Similar to conventional smears, the neoplastic cells occurred either individually or in small clusters. The cells were relatively monomorphic, with stippled chromatin and minimal amounts of cytoplasm. Unlike conventional smears, nuclear molding was not prominent (although overlap was observed), and nuclear smearing was not identified. The features are compared to TP cases of squamous-cell carcinoma, small-cell type, and endometrioid adenocarcinoma, which are close mimics of small-cell carcinoma. We conclude that correct diagnosis of small-cell carcinoma in TP is difficult, requiring a high degree of suspicion and immunohistochemical confirmation.

Immunocytochemistry controls using cell culture.

A continuing problem in cytology laboratories is the lack of adequate control material for immunocytochemical testing. Usual control procedures involve testing paraffin-embedded control materials along with the patient specimens. These control materials are fundamentally unlike cytologic preparations. We have developed a method to make control preparations for immunocytochemical analysis using cultured anaplastic cells with known antigenic features from commercial sources. Cell lines included melanoma, rhabdomyosarcoma, T-cell leukemia, and squamous-cell carcinoma. Modified Saccomano and acetone fixation coupled with the cytospin technique enabled good-quality preparations. Cell lines were tested with antibodies for HMB-45, actin, leukocyte common antigen (LCA) and cytokeratin, which avidin-biotin immunoperoxidase and diaminobenzidine (DAB) as chromogens. Our final preparations were easily interpretable with excellent morphologic preservation of cellular detail. Cultured cells provide a superior method for preparing almost unlimited numbers of control slides for immunocytochemistry for laboratories with access to a tissue culture facility.

Radiologically guided percutaneous fine-needle aspiration biopsy of pelvic and retroperitoneal masses: a retrospective study of 68 cases.

Fine-needle aspiration (FNA) of the pelvis and retroperitoneum (excluding the pancreas, kidney, and adrenal masses) has not achieved its full potential as a diagnostic modality. We reviewed 68 percutaneous, radiologically guided FNAs from these locations to assess the clinical utility and complication rate of this procedure. Satisfactory material was obtained in 66 cases (97.1%), of which 37 were deemed positive (55%), 3 suspicious (4%), 4 atypical (6%), and 22 negative (32%) for malignancy; two cases (3%) were unsatisfactory. Compared to biopsy (36 patients) and clinical information, the sensitivity and specificity of FNA for malignancy were 90.2% and 100%, respectively, yielding a positive predictive value of 100% and a negative predictive value of 86.6%. The four false-negative cases (5.9%) were due to sampling error. One patient had a minor complication (hematoma) from the procedure. We conclude that FNA is the procedure of choice for detecting most malignancies in these two locations.

Multidisciplinary approach to deep-seated lesions requiring radiologically-guided fine-needle aspiration.

Fine-needle aspiration (FNA) is a diagnostic modality that continues to improve in accuracy as training and experience accumulate. With increasing operator expertise and improved localization techniques, greater numbers of patients are able to benefit from FNAs performed on sites that are otherwise difficult or dangerous to reach by conventional surgery. We present a retrospective review of a 2-yr experience with radiologically-guided deep-seated FNA. In 115 cases involving transthoracic and transabdominal sites, we achieved the following overall figures: 91.9% sensitivity, 100% specificity, 93.9% diagnostic accuracy, 100% positive predictive value, and 80.6% negative predictive value. Our results are compared to those in other series. When properly applied, FNA of deep-seated lesions through image guidance is equivalent to tissue diagnosis obtained by laparotomy or surgical procedures. The benefits of FNA with or without core biopsy vs. scalpel biopsy are readily apparent when one considers the morbidity, cost, turnaround time, and trauma to the patient.

Utility of additional slides from residual Preservcyt material in difficult ThinPrep gynecologic specimens: a prospective study of 58 cases.

ThinPrep purportedly increases the sensitivity of cervicovaginal cytology for detecting abnormal squamous and glandular cells. The value of additional slides from residual Preservcyt material to characterize difficult lesions is unknown. Fifty-eight cases were studied to determine the utility of additional slides for diagnosis and to assess cellular uniformity. In 32 (55%), repeat slides helped make a definitive diagnosis, including 18 atypical squamous cells of uncertain significance (ASCUS) reclassified as low-grade squamous intraepithelial lesion (LGSIL) (13), high-grade squamous intraepithelial lesion (HGSIL) (4), or endometrial adenocarcinoma (1); 5 LGSIL reclassified as HGSIL; 3 atypical glandular cells of uncertain significance (AGUS) reclassified as LGSIL (1) or HGSIL (2); 2 LGSIL?HGSIL classified as LGSIL; and 4 cases confirmed as LGSIL (2) or HGSIL (2). Results were compared to follow-up clinical information, including subsequent cervicovaginal samples and biopsies. The number of abnormal cells was similar between slides in most cases. We conclude that, while ThinPreps prepared from the same vial have similar numbers of abnormal cells, additional slides can be helpful for diagnosis in select cases.

Myoepithelioma presenting as a midline cystic tongue lesion: cytology, histology, ancillary studies, and differential diagnosis.

Salivary gland myoepithelioma (ME) is a neoplasm derived from myoepithelial cells that lacks the ductal and broad mesenchymal differentiation seen in the vast majority of mixed tumors. This report describes the cytologic findings of a cystic ME presenting in the midline of the dorsal tongue, a site where no salivary glands are generally present. The tumor was well circumscribed and composed of sheets of monotonous epithelioid cells without ductal cells. The cells were positive for S-100 protein and ultrastructurally had features of myoepithelial cells. The fine needle aspiration (FNA) biopsy findings, differential diagnosis, histology, immunohistochemistry, and electron microscopic features of this interesting and uncommon neoplasm are presented. To the best of our knowledge, there have been no cytologic reports of ME of the tongue.