Cytopathology of the central nervous system. Part I. Utility of crush smear cytology in intraoperative diagnosis of central nervous system lesions

OBJECTIVE: To evaluate the utility of rapid intraoperative crush smear cytologic diagnosis of central and peripheral nervous system lesions and to determine the accuracy and relevance of the accuracy of the intraoperative cytologic diagnosis when compared to the final paraffin section diagnosis. STUDY DESIGN: The crush (squash) smear technique was introduced at Sher-i-Kashmir Institute of Medical Sciences in May 2003. The 8 months of 2003 were used for standardization of the procedure. In 2004, 151 patients with open neurosurgical specimens or stereotactic biopsies were diagnosed intraoperatively by crush smears, and the diagnosis was compared with final diagnosis on paraffin sections of the same tissue samples. No supplementation of frozen sections was used. RESULTS: Of 151 cases, 144 were diagnosed accurately intraoperatively by crush smear cytology when compared with the respective paraffin section diagnoses. The diagnostic accuracy attained was 95.36%. Each case was diagnosed within 10 minutes after receipt of sample. Neurosurgical procedure (open or stereotaxy) did not affect diagnostic accuracy. CONCLUSION: In the expert hands of a pathologist with good exposure neurosurgical specimens, crush smear cytology is an accura and reliable procedure for the intraoperative diagnosis central nervous system tumors.     

Intraoperative cytology (squash smear) in neurosurgical practice – pitfalls in diagnosis experience based on 3057 samples from a single institution

OBJECTIVES: The smear technique is challenging for a neuropathologist where rapid and accurate diagnosis is to be given on small biopsies. The present study, a large retrospective analysis of squash smears in neurosurgical practice, was conducted to assess the usefulness, accuracy and the diagnostic pitfalls of smear diagnosis. METHODS: The authors analysed 3057 central nervous system (CNS) lesions sent for intraoperative cytology (IC) during the years 1988-2005. The stain used was 1% alcoholic toluidine blue. The smear diagnosis was compared with the histological diagnosis to evaluate the diagnostic accuracy. RESULTS: Diagnostic accuracy irrespective of lesion and site ranged from 83.0% to 86.0% per year (mean=85%). The highest rate of correlation among common brain tumours was noted in schwannoma (96.6%) and pituitary adenoma (92.2%), followed by meningiomas (88.9%), astrocytomas (88.4%), chordomas (86.4%) and neurocytomas (86.9%). Infections as a whole contributed 380 cases. The most common infection was tuberculosis. CONCLUSION: This is the largest series reported from India to the best of our knowledge. Squash smear technique is a very reliable and rapid method of intraoperative diagnosis. Knowledge of clinical and neuroimaging details helps the experienced neuropathologist to improve the diagnostic accuracy.     

Cytology of desmoplastic medulloblastoma in imprint smears: a report of 2 cases

BACKGROUND: Desmoplastic medulloblastoma is a rare subtype of medulloblastoma with astroglial differentiation. The cytomorphologic features in intraoperative imprint smears from 2 cases of desmoplastic medulloblastoma are described. CASE REPORTS: A 22-year-old man and 27-year-old woman with a cerebellar tumor underwent craniotomy and tumor resection. The imprint cytologic smears contained cellular zones and nodular hypocellular areas containing astroglial and oligodendrogliallike elements. The cytology was misinterpreted as glial tumors, while the final histologic diagnosis in both cases were desmoplastic medulloblastoma. CONCLUSION: Desmoplastic medulloblastoma shows distinctive cytology in intraoperative smears. However, the occurrence of this rare type in adults and the presence of astroglial elements in imprint smears may cause a cytologic misinterpretation as gliomas.     

Fine needle aspiration cytology (FNAC) of adrenal masses

Between 1992 and 1998 at the Pathology Section, Cytopathology Unit of the Department of Oncological and Surgical Sciences of the University of Padova, we performed one hundred and twelve FNACs of adrenal masses under radiological guidance and seven intraoperative scrape smears; histological follow-up was available in 55 cases. Immediate on-site assessment of smears revealed a satisfactory adequacy rate (92%). With a simple diagnostic tree, we have been able to classify all smears except one as benign or malignant correctly, (accuracy 97.6%), differentiation of primary tumours from metastatic depositions remaining the most difficult task. In our experience FNAC is a safe and accurate tool in the diagnostic characterization of adrenal masses.     

Accuracy of cytologic diagnosis of central nervous system neoplasms in sterotactic biopsies

The cytohistologic correlation is reported for 112 of the 128 consecutive sterotactic aspiration biopsies performed on patients with clinical and neuroradiologic evidence of brain tumors investigated at the Neurosurgery Department, Karolinska Hospital, from 1976 to 1979. The cytodiagnostic accuracy of benign and malignant tumors was 87% when adequate cell material was obtained. In 17 benign tumors of the sellar region, the diagnostic rate was 88%; cytologic examination independent of histologic biopsy is feasible in this area. The cytodiagnostic accuracy for 95 malignant central nervous system (CNS) tumors was 87% after adjusting for the appreciable sampling error inherent in the use of a stereotactic procedure during the early phase of the study. Two histopathologically proven infectious lesions were reported cytologically as benign. The main microscopic problems were the recognition of highly differentiated astroglial neoplasms and the differential diagnosis between poorly differentiated brain neoplasms and metastases to the CNS. Cytodiagnostic accuracy of CNS tumors can be increased by technical improvements in the stereotactic device, diagnostic experience and immunochemical staining.     

Contribution of exfoliative cytology to the diagnosis of laryngeal lesions

OBJECTIVE: To estimate the diagnostic accuracy and reliability of exfoliative laryngeal cytology. STUDY DESIGN: Over three years (1996-1999) cytologic smears were obtained from clinically suspicious laryngeal lesions during laryngoscopy in a total of 31 selected patients (28 males and 3 females with an age range from 28-90 years). The cytologic diagnoses were analyzed and correlated with the histologic and final clinical diagnoses in 17 and 14 cases, respectively. Cytologic identification of the exact histologic type of the lesion was evaluated in 17 patients from whom both cytologic smears and biopsy material were obtained. RESULTS: The overall specificity was 100%, with no false positive diagnoses. The overall sensitivity was 93.3%, with one false negative cytologic diagnosis, in a case of non-Hodgkin's lymphoma. Cytohistologic correlation showed complete agreement between cytologic and histologic diagnoses in five of six benign lesions, in four cases of dysplasia and in six cases of squamous cell carcinoma. The overall diagnostic accuracy of cytology was 96.7% CONCLUSION: Exfoliative cytology by the smear technique is a reliable and accurate method in clinically suspected laryngeal lesions. Moreover, exfoliative cytology may be applied as the only alternative diagnostic method, especially in elderly patients with coexistent cardiorespiratory problems, when biopsy is not advisable or indicated.     

FNA of breast fibroadenoma: observer variability and review of cytomorphology with cytohistological correlation

OBJECTIVE: To determine the observer variability in reporting fibroadenoma of the breast by fine needle aspiration (FNA) and to review the cytomorphological features of the lesion with cytohistological correlation. METHODS: Retrospective analysis of FNA smears from 110 cases diagnosed as fibroadenoma of which surgical pathology follow-up was available in 33. Two pathologists were asked to categorize smears from 67 cases of breast lesions while blinded to the clinical finding as fibroadenoma, epithelial hyperplasia (usual and atypical) and malignant. All fibroadenoma (33) and cancer (15) cases were biopsy-proven. The same set of slides was re-circulated to one of the pathologists, and his first and second round results were compared. RESULTS: Pre-review cytohistological correlation was attained in 32 of 33 cases of fibroadenoma (97%). The overall agreement between the two observers was 87% [Kappa = 0.74, 95% confidence interval (CI) 0.72-0.76]. Cytohistological correlation was achieved in 26 of 33 (79%) cases. Intra-observer agreement was 91% (Kappa = 0.82, 95% CI 0.89-0.93) with cytohistological correlation in 29 of 33 (87%) cases. Causes of diagnostic errors included marked dissociation, pleomorphism, poorly cellular smears from hyalinized fibrodenoma, lacational changes and apocrine metaplasia with cystic changes. Multinucleated giant cells were frequently encountered in FNA smears from fibroadenoma (31.8%), but in none of the lumpectomy specimens. Their histiocytic nature was suggested by immunohistochemistry. CONCLUSION: FNA was a highly sensitive method for the diagnosis of fibroadenoma. Current cytological criteria were reliable and gave high inter- and intra-observer reproducibility.     

Real‐time augmented reality for delineation of surgical margins during neurosurgery using autofluorescence lifetime contrast

Current clinical brain imaging techniques used for surgical planning of tumor resection lack intraoperative and real‐time feedback; hence surgeons ultimately rely on subjective evaluation to identify tumor areas and margins. We report a fluorescence lifetime imaging (FLIm) instrument (excitation: 355 nm; emission spectral bands: 390/40 nm, 470/28 nm, 542/50 nm and 629/53 nm) that integrates with surgical microscopes to provide real‐time intraoperative augmentation of the surgical field of view with fluorescent derived parameters encoding diagnostic information. We show the functionality and safety features of this instrument during neurosurgical procedures in patients undergoing craniotomy for the resection of brain tumors and/or tissue with radiation damage. We demonstrate in three case studies the ability of this instrument to resolve distinct tissue types and pathology including cortex, white matter, tumor and radiation‐induced necrosis. In particular, two patients with effects of radiation‐induced necrosis exhibited longer fluorescence lifetimes and increased optical redox ratio on the necrotic tissue with respect to non‐affected cortex, and an oligodendroglioma resected from a third patient reported shorter fluorescence lifetime and a decrease in optical redox ratio than the surrounding white matter. These results encourage the use of FLIm as a label‐free and non‐invasive intraoperative tool for neurosurgical guidance.     

Cytologic features of pheochromocytoma and retroperitoneal paraganglioma: a morphologic and immunohistochemical study of 13 cases

OBJECTIVE: To review the cytologic features and potential pitfalls of pheochromocytoma and retroperitoneal paraganglioma and to evaluate complications of the aspiration procedure and the diagnostic utility of immunocytochemistry. STUDY DESIGN: We reviewed 15 cytologic specimens from 12 patients with 13 tumors (1 bilateral case). Ten were adrenal (pheochromocytomas) and 3 extraadrenal paragangliomas. Eleven specimens were from fine needle aspiration (FNA) procedures that were performed in collaboration with radiologists using 23-25-gauge needles. In 3 patients the cytologic material was obtained during intraoperative diagnosis. Immunocytochemistry was performed on alcohol-fixed smears. RESULTS: Two aspirates were hypocellular, while the remainder were cellular. Cells were distributed singly or formed discohesive groups. When present, cytoplasm was abundant and ill defined. Most cells had an eccentric nucleus and plasmacytoid morphology. Nuclear pleomorphism, binucleation and multinucletaion, naked nuclei and intranuclear preudoinclusions were common findings. In 2 cases a lipid background was seen focally. Evident cytoplasmic immunoexpression of synaptophysin or chromogranin was detected in the 10 cases analyzed. One patient developed a hypertensive episode during the FNA procedure. It was controlled medically without complications. CONCLUSION: When adequate cytologic material is present, the recognition of pheochromocytoma and extraadrenal paraganglioma is possible. Together with morphology, immunocytochemical studies allow a specific preoperative diagnosis. Scarce material can be a source of diagnostic errors. FNA of pheochromocytomas is not necessarily contraindicated. When analytic data are not diagnostic, FNA may follow. Aspiration must be performed in an area equipped with the therapeutic tools necessary to control a pheochromocytoma crisis.     

Intraoperative cytodiagnosis of metastatic brain tumors confused clinically with brain abscess. A report of three cases

BACKGROUND: Cystic lesions of the brain may have diverse etiologies, ranging from true cysts to malignant tumors with cystic degeneration. Preoperative determination of the exact nature of them as well as intraoperative diagnosis may be sometimes difficult or even impossible. Sensitivity and specificity of diagnosis will be improved by introducing new methods or combining traditional procedures. CASES: Three metastatic brain carcinomas with primary sites of breast, pancreas and prostate presented as cystic lesions and were confused clinically with abscess. Intraoperative frozen section was not revealing. Cytologic study of sediments of aspirated fluid uncovered malignant cells. CONCLUSION: When combined with frozen section, intraoperative cytologic studies in the form of crush preparation, fine needle aspiration or evaluation of aspirated fluid in cystic lesions (as in our cases) can improve diagnostic accuracy by detecting important diagnostic features that otherwise may be missed.     

Rapid diagnostic DNA cytometry with an automatic microscope and a TV image-analysis system

A TV-based image-analysis system (Leitz TAS plus) combined with a Leitz automatic microscope was used for rapid DNA cytometry for diagnostic purposes. Malignant or suspicious cells found by the cytopathologists in conventionally stained smears were automatically relocated and measured. A program for automatic detection and measurement of nuclear DNA content was developed. DNA data are processed by an algorithm for the diagnosis and grading of malignancy. This diagnostic procedure is performed in real time and yields highly reproducible results. With this equipment, diagnostic DNA cytometry may be introduced in the routine cytology laboratory. Our mode of application does not replace the cytopathologist, but assists him or her in cases of doubtful diagnosis and in the grading of malignant tumors.     

Comparison of cytohistologic techniques in diagnosis of gastroesophageal malignancy

OBJECTIVE: To evaluate the diagnostic performance of various endoscopic cytologic techniques, namely, brushing cytology, touch smear cytology and crush cytology, and comparison with concurrent biopsy results in diagnosis of gastroesophageal malignancy. STUDY DESIGN: This prospective study was conducted on 100 patients, with 78 clinically suspected cases of esophageal malignancy and 22 cases of gastric malignancy. RESULTS: The diagnostic accuracy of touch smear in esophageal malignancy was significantly higher (94.12%) than brushing and crush smears (89.71% each), and endoscopic biopsy had the diagnostic accuracy of 88.24%. The diagnostic accuracy of combined brushing and biopsy was 100%; it was 97.06% for touch smears combined with biopsy. In comparison, the diagnostic accuracy in gastric malignancy was 75% for brushing alone, which was significantly lower than touch smear (87.5%) and endoscopic biopsy (87.5%). The diagnostic yield for crush smear was 81.25%. A combination of touch smears and biopsy had a diagnostic yield of 100%; it was 93.75% for combined brushings and biopsy. CONCLUSION: A combination of cytohistologic techniques resulted in a statistically significant increase in the diagnostic yield of gastroesophageal malignancies and thus cytologic techniques may act as adjunct to biopsy histology to increase the diagnostic efficiency.     

Fine needle aspiration cytology of breast fibroadenoma. A cytohistologic correlation study of 405 cases.

OBJECTIVE: To evaluate the cytohistologic correlation of breast fibroadenoma (FA) in order to assess the value of cytology in the conservative management of this lesion. STUDY DESIGN: A retrospective analysis of all aspirates diagnosed as FA or fibroadenomatous lesion (n = 1,549) for which a histologic follow-up study was available (n = 362). Forty-three aspirates, including 14 nonrepresentative smears, from histologically proven FAs with a different cytologic report were also included in the study. RESULTS: Cytohistologic agreement was present in 287 of the 362 cytodiagnoses. Lack of correlation was observed in 75 cases. Most diagnostic errors accumulated in the older patient group. The sensitivity of the cytologic diagnosis of FA was 86.9% (90.8% excluding nonrepresentative cases), with a positive predictive value of 79.3%. In 43 cases a histologic diagnosis of FA was given after previous erroneous (n = 29) or nonrepresentative cytodiagnoses (n = 14). The specificity of the cytologic diagnosis of FA reached 93.8%, with a negative predictive value of 96.3% (97.5% excluding nonrepresentative cases). Regarding malignancy, five tumors were diagnosed as FA and were malignant. No false positive diagnoses of malignancy were given, but nine aspirates were included in the category "suspicious for carcinoma." CONCLUSION: FA of the breast remains a diagnostic challenge for the cytopathologist. A considerable amount of benign breast lesions can mimic FA on cytology, and such diagnostic categories as "fibroadenomatous lesion" or "consistent with FA" are associated with low diagnostic accuracy. While the cytologic requisites for entering a program of conservative management of FA are established, it seems that strict diagnostic criteria should be applied even at the expense of diminishing sensitivity.     

Use of cytomorphometry and cytology in the diagnosis of transitional-cell carcinoma of the upper urinary tract

Because of the rise in incidence of upper urinary tract tumors, there is a need for a simple and reliable method for diagnosing these tumors, especially in people in a "high-risk" group. This retrospective study showed the usefulness of cytology and cytomorphometry in making the diagnosis of transitional-cell carcinoma of the upper urinary tract. The study also emphasized that the methods of collection and processing are of the utmost importance: the cytologic evaluation of ureteral catheterized urine specimens gave 100% accuracy as compared with a 40% false-negative rate in the cytologic diagnosis of voided urine specimens. A higher accuracy of urinary cytology for the diagnosis of upper urinary tract lesions clearly requires selective catheterization of the ureter. Objective cytomorphologic grading of the urinary cytology specimens was shown to compare favorably with histologic grading. Cytomorphologic grading not only can offer important information in determining the prognosis and in planning treatment but can also assist in quality control of other diagnostic methods and can help to resolve apparent diagnostic discrepancies.     

Value of image-guided needle aspiration cytology in the assessment of pelvic and retroperitoneal masses. A study of 112 cases

OBJECTIVE: To evaluate the diagnostic value of the noninvasive method of image-guided needle aspiration cytology (NAC) in the assessment of radiologically detected pelvic and retroperitoneal space-occupying lesions (excluding the pancreas, kidney and adrenal). STUDY DESIGN: NAC was performed under computed tomographic or ultrasound guidance on 112 patients suspected of having a pelvic or retroperitoneal mass. Cytologic examination was performed on site after staining smears with the Papanicolaou method. In addition, air-dried smears, fixed smears, filter preparations from needle washings and cell blocks were studied. The NAC diagnosis was supported by examining cell blocks; further support was obtained with a tissue biopsy in some cases. Additionally, pertinent immunoperoxidase and/or histochemical studies were done. RESULTS: Eighteen cases were diagnosed as inflammatory lesions, 17 cases consisted of normal cellular elements, and 12 cases showed scanty material and were considered unsatisfactory/inadequate for a diagnosis. Five cases were suspicious for malignancy, and in 39 cases metastatic tumors were diagnosed from a previously known primary. Thirteen cases were diagnosed as lymphoma, and in 8 cases a diagnosis of soft tissue sarcoma was made. There were no false positive diagnoses of malignancy. Cell block preparations and immunohistochemistry were helpful with tumor typing, although lymphoma subtyping and soft tissue tumor typing generally required open biopsy. CONCLUSION: NAC, as the first-line investigation, is not only useful in the diagnosis of space-occupying lesions of the pelvic and retroperitoneal region but can also help in choosing appropriate management. The technique is most useful in diagnosing metastases but is also helpful in excluding malignancy in some cases and in suggesting diagnoses of lymphomas and soft tissue tumors.     

Diagnostic value of needle aspiration cytology in the assessment of palpable axillary lymph nodes. A study of 336 cases

OBJECTIVE: To evaluate the diagnostic value of needle aspiration cytology (NAC) in the assessment of palpable axillary lymph nodes and determine whether ancillary procedures can be useful in enhancing the diagnosis. STUDY DESIGN: The material was analyzed in 336 cases with enlarged axillary lymph nodes in which NAC were performed by the conventional method. In all cases cytologic examination was done on site after staining the smears with the Papanicolaou method. In addition, air-dried smears, fixed smears, filter preparations from needle washings and cell blocks were studied. The NAC diagnosis was supported by examining cell blocks, which showed the reliability of histologic architecture; further support was obtained with tissue biopsy and/or comparison with the primary tumor in some of the cases. RESULTS: Twelve cases were diagnosed as inflammatory lesions, and 64 were unsatisfactory due to scanty/acellular samples (despite 2-3 repeat samplings). However, in 6 of these, malignant tumors were later found on a biopsy done due to persistent and continued enlargement of an axillary lymph node or nodes. One hundred twenty-two cases were regarded as negative (normal cellular elements, n = 52; reactive elements, n = 70), and 4 cases were suspicious for malignancy. In 124 cases a variety of metastatic tumors were diagnosed (breast, n = 63; melanoma, n = 22; others, n = 39), and in 10 cases a diagnosis of lymphoma was made. CONCLUSION: NAC of palpable axillary lymph nodes as a first-line of investigation is a cost-effective procedure and is not only useful in the diagnosis of various lesions but can also help in deciding on management. Also, histologic architecture from cell blocks can be correlated with cytology, and such material can be used for histochemical and immunomarker studies.     

Critical role of fine needle aspiration cytology and immunocytochemistry in preoperative diagnosis of pediatric renal tumors

OBJECTIVE: To evaluate accuracy and role of immunocytochemistry (ICC) in cytologic diagnosis of pediatric renal tumors. STUDY DESIGN: Fine needle aspirates from 75 cases of pediatric renal tumors were studied. Radiologic-guided aspirations were performed, with 6-7 smears stained with Papanicolaou and Giemsa stains. Smears were screened without the knowledge of final histologic diagnosis. Subsequently, clinical details, final histology and diagnosis rendered by the original cytologist were noted to judge accuracy of diagnosis by a sensitized cytologist. Five neuroblastomas that entered close differentials for Wilms tumor were also evaluated. ICC studies were also performed after staining. RESULTS: Of 58 Wilms tumors, 5 were misdiagnosed; 3 renal rhabdoid tumors and 1 clear cell sarcoma were missed on cytology. Non-Hodgkin's lymphomas presenting as renal masses were accurately diagnosed on cytology, but primitive neuroectodermal tumors (n = 3) and renal cell carcinomas (n = 2) were not accurately diagnosed. Accuracy rate improved from 65% to 92% on review by a cytologist aware of cytologic features of pediatric renal tumors. CONCLUSION: A good accuracy rate of diagnosis of pediatric renal tumors can be achieved by priming pathologists to typical features of tumors. Immunocytochemistry plays a supportive role in cases with atypical morphology or unusual presentations.     

Fine needle aspiration cytology of eyelid tumors

Fine needle aspiration (FNA) biopsy was performed on 19 patients with eyelid masses. Six of the patients also had preauricular/submandibular nodal enlargements aspirated. Histopathologic study was performed in ten of the cases. FNA cytology made the diagnosis of an epithelial malignancy in 17 cases (10 sebaceous carcinomas, 4 poorly differentiated carcinomas, 2 squamous cell carcinomas and 1 malignant melanoma). The diagnostic accuracy of FNA cytology in evaluating eyelid masses was thus 89.4%; there were two false-negative cases. All nodal FNA smears revealed metastases of the respective primary tumors. This study indicated that FNA cytology is a simple and efficient method for making the diagnosis of malignancy in eyelid masses, especially in those patients who are not suitable candidates for surgery. Subsequent nodal metastases and tumor recurrence were detected without difficulty using FNA smears.     

Fine needle aspiration cytology of suspected tuberculous lymphadenitis

Fine needle aspiration cytology of suspected tuberculous lymphadenitis The aims of this cross-sectional study were to describe the distributional patterns of tuberculous lymphadenitis and to assess the correlation between fine needle aspiration cytology (FNAC) and the Ziehl Neelsen staining technique in diagnosing tuberculous lymphadenitis. Romanowsky's method (Wright's stain) for cytological diagnosis and Ziehl Neelsen (hot method) for the identification of acid-fast bacilli were utilized. Out of one hundred and twenty-eight consecutive patients attending the cytological diagnostic service of the Department of Pathology within Jimma University, 89 (69.6%) of the patients were younger than 30 years of age. The male to female ratio was 1.3 : 1. The cervical region was the most common site and involved 95 cases (74.2%), followed by the axillary and inguinal lymph node regions (20.3% and 4.3%, respectively). The Wright's-stained cytology smears were grouped into three categories: epithelioid granulomas without necrosis, epithelioid granulomas with caseous necrosis and necrosis without epithelioid granulomas. The Ziehl Neelsen stains were undertaken on separate slides: 20.0% of the cases showing epithelioid granulomas without necrosis, 61.9% of those with epithelioid granulomas with necrosis/abscesses and 69.7% of those with necrosis without granulomas were found to be positive for acid-fast bacilli. The overall positivity for the ZiehlNeelsen stained cases was 59.4%. It can therefore be concluded that FNAC is a reliable diagnostic tool in helping to avert the more invasive surgical procedures undertaken in the diagnosis of tuberculous adenitis. The ZiehlNeelsen stain for identification of acid-fast bacilli should be incorporated as an adjunct to increase the diagnostic accuracy of tuberculous lymphadenitis.     

Interpreting microbiopsies in cervical smears. A cytohistologic approach

OBJECTIVE: To assess interobserver variation in the diagnosis of thick tissue specimens (microbiopsies) in cytology smears and histologic sections taken from them, to evaluate the applicability of MIB-1 in histologic sections from microbiopsies and to evaluate whether processing microbiopsies in inconclusive smears has additional diagnostic value. STUDY DESIGN: Cytologic smears were selected in which there were diagnostic disagreements between pathologists and cytologists and microbiopsies were present. Interobserver variation among three pathologists and three cytologists in the diagnosis of these microbiopsies was investigated. The smears were processed for histologic sections, and interobserver variation between pathologist diagnoses were analyzed. An additional histologic slide stained for MIB-1 was used for consensus diagnosis. The consensus diagnosis was compared with available follow-up and its sensitivity and specificity determined. The value of applying the microbiopsy technique in slides diagnosed as inadequate or atypical squamous cells of undetermined significance (ASCUS) was analysed. RESULTS: From a series of 62,334 cervical smears, 49 with microbiopsies were selected. It was possible to derive histologic slides from 38 cases. Interobserver variability in the diagnosis of microbiopsies and histologic sections from them was moderate--kappa = .44 (SE = .06) and kappa = .44 (SE = .09), respectively. In the consensus meeting for all cases, a conclusive diagnosis was reached. The Pearson correlation coefficient between the consensus diagnosis and MIB-1 staining was r = .62. The sensitivity of the consensus diagnosis for the follow-up diagnosis was 71% and the specificity 60%. Diagnosis on approximately 50% of slides diagnosed as inadequate or ASCUS could be made. CONCLUSION: The histotechnical workup of microbiopsies is not difficult; however, their diagnosis can be a problem. Adequate diagnostic criteria are not available. Aided by MIB-1 staining, histologic sections from microbiopsies can be diagnosed, and the diagnoses correlated with follow-up in most cases. Processing of microbiopsies in smears with an inconclusive cytologic diagnosis or a diagnosis of ASCUS allowed correct diagnosis in 50% of cases in this study.