Clinical impact of identifying Trichomonas vaginalis on cervicovaginal (Papanicolaou) smears.

The purpose of this study was to understand how clinicians manage asymptomatic women after Trichomonas has been reported on Papanicolaou (Pap) smears. Clinical information was obtained from questionnaires sent to healthcare providers whenever Trichomonas was identified during the study period. Trichomonas was identified in 173 (1.4%) of 12,547 Pap smears examined. Completed questionnaires were returned on 95 (55%) patients, and 92 patients were included in this study. Sixty-three (68%) patients were asymptomatic, 16 (18%) had symptoms characteristic of infection, and 13 (14%) had nonspecific symptoms. Twenty-six (28%) patients received treatment during the original clinic visits. After the Pap smear reported Trichomonas, 49 (81%) of the 66 patients were contacted and treated, 7 (12%) were contacted and scheduled for further evaluation, and no action was taken on the remaining 10 (17%) patients. There was a significant association between presenting with symptoms and receiving treatment at the time of the original visit (P < 0.001), but not with receiving subsequent treatment. Clinical suspicion of infection was also associated with receiving treatment at the time of the original visit only (P < 0.001). Clinical suspicion of infection correlated with symptoms and results of wet mount smears (P < 0.001). In conclusion, the Pap smear report of Trichomonas identification directly impacted the management of 61% of patients and served as confirmation for clinical management in another 28% who had received treatment at the time of original visit. Despite the fact that most patients were asymptomatic, the majority received treatment and/or evaluation after the Pap smear report was received.

Clinical significance of identifying candida on cervicovaginal (Pap) smears.

This study was undertaken to determine the clinical significance of detecting candida on Pap smear. Clinical information was obtained from a questionnaire sent to the health care provider whenever candida was identified during the study period. Candida was identified in 309 (3.0%) of the 10,370 Pap smears examined. Completed questionnaires were returned on 137 (44.3%) patients. All 137 smears were reviewed. Ninety-nine (72%) patients were asymptomatic, 29 (21%) had symptoms typical of candida infection, and nine (7%) had nonspecific symptoms. Forty-four (32%) patients had been treated for candida during the original clinic visit. After the Pap smear reported candida, 19 (20%) of the 93 nontreated patients were contacted and treated, while 10 (11%) were scheduled for further evaluation. No action was taken on the remaining 64 (69%) patients. There was a significant association between having initial symptoms and receiving immediate treatment (P < 0.001) and undergoing subsequent treatment or further evaluation after the Pap smear report (P < 0.001). Marked inflammation was statistically associated with symptoms (P = 0.014), but the form or number of candida organisms was not. In conclusion, the identification of Candida on Pap smear does not necessarily indicate a symptomatic infection, although the Pap smear results had a direct impact on the treatment of 21% of patients in this study and served as a confirmation for clinical treatment in another 32% who had received such treatment at the time of the original visit.

Atypical glandular cells of undetermined significance on cervical smears. A study with cytohistologic correlation.

OBJECTIVE: The incidence of endocervical adenocarcinoma has increased steadily over the past two decades. Since the Bethesda System was introduced, the diagnosis of atypical glandular cells of undetermined significance (AGUS) has also risen and now accounts for 0.46-1.83% of all cervical (Pap) smears. The purpose of this study was to evaluate the significance of a diagnosis of AGUS using cytohistologic correlation. STUDY DESIGN: A retrospective review of archival material from 1993 through 1996 identified 64 patients who had smears diagnosed as AGUS and had a subsequent surgical biopsy. The smears were reviewed and cytologic features analyzed and correlated with the histologic diagnosis. RESULTS: On biopsy, 3 (5%) of the 64 cases showed endocervical adenocarcinoma in situ (AIS) (1 case with invasive adenocarcinoma also), 14 (22%) had a benign glandular lesion (endocervical polyp, tubal metaplasia, microglandular hyperplasia, reactive changes), 35 (54%) had squamous intraepithelial lesion (SIL) (15 diagnosed on the original smear), and 12 (19%) had no abnormality. Among the cytologic criteria evaluated, feathering (P = .01), palisading (P < .001) and chromatin clearing (P = .002) were shown to have a significant association with the histopathologic diagnosis of AIS/adenocarcinoma. These features were also useful in distinguishing AIS/adenocarcinoma from SIL and benign glandular changes from AIS/adenocarcinoma but not benign/reactive glandular changes from SIL. CONCLUSION: A diagnosis of AGUS correlated with a clinically significant lesion in the majority of cases. Squamous dysplasia (SIL) was the most common lesion identified. The presence of feathering, nuclear palisading and chromatin clearing increased the likelihood of a histologic diagnosis of AIS/adenocarcinoma.

Immunohistochemical detection of a fatty acid synthase (OA-519) as a predictor of progression of prostate cancer.

Prostate cancer is the most common newly diagnosed non-skin cancer and the second leading cause of cancer death in men. It is a unique neoplasm because of the large discrepancy between its clinical incidence and the much higher incidence of latent cancer. Predicting the prognosis of prostate cancer, especially the cancers detected incidentally or by screening, remains a clinically important problem. Immunoreactivity for Onco-antigen 519 (OA-519), a recently described fatty acid synthase (FAS), has been associated with poor prognosis in breast cancers. The authors have previously shown that its detection in prostate cancer correlated with high-grade, large volume, and advanced stage tumors. This study examines the association between OA-519 immunoreactivity in primary prostate cancer and disease progression. The authors used immunohistochemistry with an affinity-purified anti-OA-519 antibody and examined primary prostate cancers (stages A1 to D1) from 99 men with a mean follow-up of 4 years (range = 2 to 9.3). Survival analysis was used to evaluate differences in progression-free survival. OA-519 immunoreactivity was seen in 56 (57%) of the 99 primary prostate cancers examined. OA-519-positive cancers were more likely to progress than the OA-519-negative cancers (P < .04). Univariate survival analysis showed that OA-519 (FAS), histological grade (Gleason score), and clinical stage were significant predictors of disease progression. Multivariate analyses of all cases showed that only histological grade was significant. However, multivariate analysis of the 85 cancers with Gleason scores 2-7 (ie, low to intermediate grade) showed OA-519 (FAS) immunoreactivity to be the only statistically significant predictor of cancer progression (P < .02). Expression of the fatty acid synthase OA-519 by prostate cancers is potentially a clinically useful predictor of disease progression. It appears to be independent of histological grade (Gleason score), at least in cancers with low to intermediate grades. Further studies are needed to evaluate the role of fatty acid synthase in malignancy and the potential therapeutic implications of enzyme blockers.

Immunohistochemical detection of p53 protein as a prognostic indicator in prostate cancer.

Mutation of the p53 gene is the most common genetic alteration in human cancers. The mutant p53 protein is more stable than the wild type and can be detected by immunohistology. The objective of the current study was to evaluate the immunohistological detection of p53 protein in prostate cancer and its utility as a prognostic indicator. We used a monoclonal anti-p53 antibody and immunostained primary prostate adenocarcinomas (stages A1 to D1) from 109 patients with a mean follow-up of 3.8 years (range, 1.3 to 9.3 years). Immunoreactivity for p53 was seen in 23 cancers (21%). There were 12 instances of progression (14%) among the p53-negative cancers versus seven (30%) among the p53-positive group. Survival analysis using three univariate statistical tests showed that p53 reactivity (P < .03), Gleason score (P < .01), and stage (P < .05) had significant effects on time to progression of prostate cancer. Multivariate analyses showed that Gleason score was significant with all three tests; p53 reactivity was significant with the Wilcoxon test but only approached significance by the log rank and Cox tests. When the analyses included only patients with Gleason scores 2 to 7 (N = 94), univariate analyses showed that p53 reactivity was strongly related to progression of prostate cancer (P < .007). Stage also was significant (P < 0.04), but Gleason score was not. Multivariate analyses showed only p53 reactivity to be significant (P < .007). In conclusion, mutation of the p53 gene may be involved in prostate cancer carcinogenesis. p53 reactivity marks an aggressive subset of prostate cancer and appears to be an independent prognostic indicator that is particularly valuable among the low to intermediate grade cancers.

Paranuclear blue inclusions: an aid in the cytopathologic diagnosis of primary and metastatic pulmonary small-cell carcinoma.

Accurate diagnosis of small-cell carcinoma of the lung (SCLC) is clinically important because of the therapeutic implications. SCLC must be distinguished from non-small-cell carcinoma (NSCLC) and lymphoma. Paranuclear blue inclusions (PBIs) were recently described as a feature of metastatic SCLC on air-dried Wright-stained bone marrow aspirate smears. To determine the utility of PBIs in distinguishing SCLC from NSCLC and lymphoma, we evaluated air-dried Diff-Quik-stained smears from 103 fine-needle aspiration (FNA) specimens and 14 touch imprint specimens. PBIs were identified in 24 (89%) of 27 cases of SCLC, in 6 (9%) of 64 non-small-cell carcinomas (P < 0.00001), and in two (8%) of the 26 lymphoma cases (P < 0.00001). No PBIs were seen on any of the alcohol-fixed Papanicolaou or hematoxylin-eosin (H&E) stained smears examined. In conclusion, PBIs appear to be a feature of SCLC on air-dried cytologic material stained with Romanowsky type stains. In the presence of cytologic features of SCLC, the identification of PBIs provides a useful diagnostic feature for differentiating between SCLC and NSCLC carcinomas, and between SCLC and lymphomas in FNA specimens and touch imprints from surgical specimens.

Proliferating cell nuclear antigen immunoreactivity in cervical intraepithelial neoplasia and benign cervical epithelium.

In the normal ectocervix, mitoses are rare and are usually confined to the basal layers. In contrast, they occur more frequently in cervical intraepithelial neoplasia (CIN) and are seen at higher levels, suggesting that CIN may be associated with a progressive dysfunction in proliferative activity of cervical cells. The objective of this study was to use proliferating cell nuclear antigen (PCNA) immunohistochemistry to examine the proliferative activity of cervical epithelial cells in CIN lesions. Sixty-eight cervical biopsies were examined; 20 were totally benign, 14 had CIN I, 21 CIN II, and 13 CIN III. In benign epithelia, PCNA staining was usually confined to the basal layers, whereas in CIN the staining was seen at progressively higher levels of the epithelium. There was a statistically significant correlation between the CIN grade and the highest level of PCNA staining (PCNA grade, r = 0.746, P < 0.001). In addition, the PCNA grade showed significant correlation with the highest level at which mitoses were seen (mitosis grade, r = 0.706, P < 0.001), and a strong direct correlation between the mitosis and CIN grades was also observed (r = 0.955, P < 0.001). These data demonstrate that (1) PCNA immunoreactivity in neoplastic cervical epithelium is different from that seen in the normal cervix, suggesting that CIN is associated with a dysfunctional proliferation of cervical epithelium, (2) that there is a significant correlation between the PCNA grade and CIN grades, and (3) the "mitosis grades" have a strong correlation with the CIN grades.

Expression of oncogenic antigen 519 (OA-519) in prostate cancer is a potential prognostic indicator.

Predicting the prognosis of patients with prostate cancer is a clinically important problem. Previous studies have indicated that the expression of haptoglobin-related protein epitopes in samples of breast cancer in early stages was associated with earlier relapses and higher risk for tumor recurrence. Oncogenic antigen 519 (OA-519) is the new marker designation for molecules expressing haptoglobin-related protein epitopes. The objective of this immunohistochemical study was to examine OA-519 expression in prostate cancer samples and its relationship to the established prognostic indicators of tumor grade, tumor volume, and clinical stage. Forty-two consecutive tissue samples of prostate adenocarcinoma were examined using an affinity-purified anti-OA-519 antibody. Twenty specimens (48%) tested positive, whereas 22 (52%) tested negative. No staining was observed in normal or hyperplastic prostate tissue. Staining occurred in 6 of 9 (67%) grade III, 14 of 23 (61%) grade II, and in none of 10 (0%) grade I cases (I vs. II and/or III: Fisher exact test, P less than 0.006). Twenty-three of the 42 samples were transurethral resection specimens with cancer; 11 (48%) of these tested positive. The mean percentage of tissue chips with tumor, a measure of tumor volume, was significantly higher in the positive group (57%) than in the negative group (15%) (P = 0.004). The proportion of positively stained cases increased with advancing clinical stage, with 25% of Stage A cases expressing OA-519, and 46%, 67%, and 64% of Stages B, C, and D, respectively, expressing OA-519. OA-519 expression correlates with higher tumor grades, larger tumors, and possibly with advanced stage, and thus, it is potentially of prognostic value in prostate cancer.

Radiation-induced changes in the breast: a potential diagnostic pitfall on fine-needle aspiration.

The authors report a case of fine-needle aspiration (FNA) of a breast mass in a 36-year-old woman with previous history of lumpectomy and therapeutic radiation for breast carcinoma. The changes seen were interpreted as recurrent carcinoma, while subsequent biopsy showed only radiation changes. Radiation-induced changes in breast tissue are a potential diagnostic pitfall. The characteristic cytopathologic changes and their differential diagnosis are discussed.

Expression of haptoglobin-related protein in primary and metastatic breast cancers. A longitudinal study of 48 fatal tumors.

The ability to establish a prognosis for patients with early breast cancer is an important clinical issue. Recent studies have shown that antibodies to haptoglobin-related protein (Hpr) may be useful in stratifying early patients with breast cancer according to their relative risks of recurrence. Nearly 30% of early breast cancers express proteins bearing Hpr epitopes. Hpr-positive breast cancers are more likely to recur after primary resection and are associated with shorter disease-free intervals. This immunohistochemical study examines temporal changes in Hpr expression during the course of disease in 48 patients with fatal breast carcinoma. Thirty-seven primary tumors (77%) were Hpr positive. Ten of the 11 initially negative tumors (91%) were Hpr positive at the time of recurrence. In contrast, only 10 of the 37 initially positive tumors (27%) were Hpr negative with relapse. Of 18 axillary nodes that were examined, 16 (89%) were Hpr positive; all four lymph nodal metastases in patients with initially negative primary tumors were Hpr positive. The authors conclude that the acquisition of Hpr expression parallels increased malignant potential and that Hpr expression, once acquired, tends to remain a permanent characteristic of any given mammary tumor.

The cytopathologic diagnosis of esophageal adenocarcinoma.

The diagnostic cytologic features were analyzed in 18 cases of histopathologically proven esophageal adenocarcinoma accessioned at the Johns Hopkins Hospital between 1975 and 1988 for which cytologic material was available. Primary esophageal adenocarcinoma was diagnosed in 15 of 18 cytologic specimens (83%); in 3 cases (17%), carcinoma was suspected, but the changes were nondiagnostic. The most consistent cytologic changes included both architectural features (loss of orientation and nuclear crowding) and criteria of malignancy (high nuclear/cytoplasmic ratios and prominent nucleoli). In the 15 diagnostic cases, the nucleoli were small in 8 and round in 11; in the majority of these cases, the nuclei contained one to three nucleoli. In addition, nuclear and cytoplasmic molding was seen in 9 of these 15 cases, hyperchromasia was present in 8, coarse chromatin clumps were seen in 5, and tissue fragments tended to be multilayered. Review of the three nondiagnostic cases showed that scant material was present in two; the third case had abundant material, but only nondiagnostic changes, suggesting a sampling error. Barrett mucosa was seen in 7 of the 18 cases. These cases show that esophageal adenocarcinoma can be reliably diagnosed on cytologic preparations, based on the consistent architectural features and the usual cellular criteria of malignancy.

Solid and papillary epithelial neoplasms of the pancreas.

Seven patients with solid and papillary epithelial neoplasms of the pancreas are reported. All were young women with a mean age of 22 years (range, 16 to 33 years old). Each patient had a large asymptomatic abdominal mass. The tumors ranged in size from 7 to 20 cm (average size, 13 cm) and were evenly distributed throughout the head, body, and tail of the pancreas. One patient had a metastatic tumor to her liver, which was unresectable. All other patients underwent resection, which included two distal pancreatectomies, two total pancreatectomies, one pancreaticoduodenectomy, and one local excision. Four of the seven patients had evidence of local invasions alone, and one had a liver metastasis and local invasion. All patients had the characteristic histologic pattern of a solid and papillary epithelial pancreatic neoplasm. All patients are alive with a mean follow-up of 10 years (range, 4 to 20 years). This is an unusual malignant neoplasm of the pancreas occurring predominantly in young women. Even though they are locally invasive, long-term survival is the rule. Surgical therapy should be aggressive, since liver metastasis may occur.

Immunohistochemical detection of chlamydial antigens in association with cystitis.

To investigate the etiologic role of Chlamydia trachomatis in cystitis, the authors used the immunoperoxidase technique with a monoclonal antibody against Chlamydia and examined paraffin sections from 36 cases of histologically proven cystitis. The average patients' age was 60 (range, 2-85) years. Biopsies were taken for follow-up of treated bladder carcinoma (19), hematuria (8), and other nonneoplastic conditions (9). Chlamydial antigens were detected by immunohistochemistry in 12 (33%) of these 36 cases. Staining for Chlamydia occurred in the upper layers of the transitional epithelium and involved long stretches of epithelium. Underlying inflammation was usually chronic but did not have specific distinguishing features. Eight of the Chlamydia-positive biopsies were taken for follow-up of treated carcinoma, two were for hematuria, one for neurogenic bladder, and one for evaluation of sterile pyuria. Eleven (92%) of these 12 positive cases had a history of recent urologic instrumentation, in contrast to only 11 (46%) of 24 negative cases (P less than 0.02). There was no significant difference in the age or sex distribution between the two groups. The authors conclude that Chlamydia trachomatis can ascend the urethra and infect the bladder urothelium. Urologic instrumentation enhances the ability of Chlamydia to reach the bladder. Chlamydia trachomatis may play an etiologic role in cystitis.

CA-549: immunohistochemistry and serum levels in breast carcinoma and other neoplasms.

CA-549 is a high molecular weight acidic glycoprotein found in the serum of breast cancer patients. Detection of CA-549 in serum using an immunoradiometric assay has [1] correlated with disease course in breast cancer patients and [2] aided in establishing the diagnosis of breast cancer in patients with metastatic disease. This study examines the expression of CA-549 using immunohistochemistry in normal breast, benign breast disease, breast carcinoma, and a variety of other carcinomas. In addition, in 29 patients both serum and tissue samples were available for correlation. CA-549 was constitutively expressed in normal breast tissue, but immunohistochemical positivity was restricted either to the luminal aspect or entire cell membrane. All patients with benign breast disease had normal levels of CA-549 despite immunohistochemical positivity. Nearly all (98 percent) of breast carcinomas showed reactivity for CA-549, with a majority (82 percent) of the cases showing cytoplasmic positivity. In patients with both serum and tissue studied, those with cytoplasmic staining of the breast carcinomas had mean serum level of 174 U per ml (range 1.9 to 785), compared to 37.3 U per ml (range 2.1 to 86.8) in those with only membrane or luminal staining of tumor (p = 0.0578). Immunoreactive CA-549 was found in many normal epithelia and in other types of carcinomas. CA-549 is [1] constitutively expressed on the cell membrane of normal breast epithelium, [2] commonly present in the cytoplasm of breast carcinomas, and [3] found often in a variety of carcinomas.

A new biomarker in monitoring breast cancer: CA 549.

Serum biomarkers are not very reliable in assessing outcome or predicting recurrence of breast cancer. Clinically, carcinoembryonic antigen (CEA) is widely used and is elevated in a majority of patients with metastatic breast cancer. However, it is falsely elevated in a wide range of nonmalignant conditions and correlates poorly with disease progression. We evaluated a newly described monoclonal antibody, CA 549, in an immunoradiometric assay which uses two monoclonal antibodies directed against tumor and milk fat globule membranes. CA 549 and CEA were studied in 682 patients, 331 of whom had breast diseases and 99 of whom were followed with multiple serum samples. Of 69 patients with benign breast diseases, 1.5% had elevated CA 549, 0% of 30 pregnant women had elevated CA 549, and 26% of patients with nonmalignant liver disease had CA 549 elevation. In metastatic cancer of prostate, ovary, endometrium, colon, and lung CA 549 was elevated in 12% to 50% of cases with levels less than 120 U/mL. In breast cancer, CA 549 was elevated in 11% of 88 patients who received adjuvant chemotherapy and had no evidence of metastasis; in 23% of 16 patients in complete remission after chemotherapy; in 63% of 52 patients in partial remission after therapy; and in 83% of 106 patients with progression of breast cancer compared with 63% with elevated CEA (P = .001). In diseases of the breast, CA 549 has a sensitivity In diseases of the breast, CA 549 has a sensitivity and specificity of 77% and 92% v 61% and 92% for CEA. Of 99 patients serially monitored with clinically documented breast cancer progression, regression, or stability of disease, CA 549 was statistically significantly superior to CEA in monitoring a greater than 25% change in those patients with metastatic progression (P = .03). CA 549 is a new serum marker that should be control tested in prospective clinical trials alone or in conjunction with other markers.

Immunohistochemical demonstration of Chlamydial antigens in association with prostatitis.

The occurrence of Chlamydia trachomatis in association with histologically proven prostatitis was investigated. We used the immunoperoxidase technique with a monoclonal antibody against Chlamydia and evaluated formalin-fixed, paraffin-embedded sections from 16 cases of histologically proven prostatitis. Chlamydial antigens were detected within the prostate glands in 5 (31%) of these 16 cases. In contrast, none of 19 cases of prostatic hyperplasia without significant inflammation used as a control group showed staining for Chlamydia in the prostatic glands (P less than 0.03). Chlamydial antigens were, however, detected in the urothelium of the prostatic urethra in one of these control cases. Staining for Chlamydia occurred focally in atrophic glands and was associated with a predominantly chronic nonspecific inflammation. No cytoplasmic inclusions or other specific morphologic features of chlamydial infection could be identified on routine hematoxylin-eosin- or Giemsa-stained tissue sections from these specimens. Our results demonstrate that Chlamydia can infect the prostatic glands, and that its presence is statistically associated with marked nonspecific inflammation. We suggest that C. trachomatis may have an etiologic role in nonbacterial prostatitis.

Testicular vasculitis: implications for systemic disease.

Nine cases of testicular vasculitis were identified from the surgical pathology and autopsy files of the Johns Hopkins Hospital. In three cases this was the initial manifestation of polyarteritis nodosa. Two of these men presented with recurrent testicular pain and fever, with orchiectomy samples showing focal infarcts and necrotizing vasculitis. The third man presented with epididymitis, with his biopsy specimen showing vasculitis. In two cases, men presented with systemic and testicular signs of polyarteritis nodosa, and the diagnosis was made on testicular biopsy and later studied at autopsy. In another case, the testicular lesions were seen with Goodpasture's syndrome; the patient was thoroughly studied at autopsy, and no evidence of polyarteritis nodosa was found. In the remaining three cases, testicular vasculitis was identified incidentally without diseases associated with vasculitis, one at orchiectomy for prostate adenocarcinoma and the other two at autopsy. Polyarteritis nodosa is the most common cause of necrotizing vasculitis of the testes, and pathologists should recognize the rare testicular presentation of this disease. However, testicular vasculitis also may be seen with other systemic diseases associated with vasculitis. Three of our cases were seen without systemic vasculitis, suggesting that testicular vasculitis may occur as an isolated finding without being a manifestation of systemic disease.

Nuclear grooves: a useful criterion in the cytopathologic diagnosis of papillary thyroid carcinoma.

A recent report emphasized the usefulness of the grooved nucleus as a diagnostic criterion of papillary thyroid carcinoma (PTC) in histopathologic material. The present study was undertaken to evaluate whether grooved nuclei can serve as an additional diagnostic criterion for PTC in cytologic material obtained by fine-needle aspiration (FNA). Slides from 124 consecutive thyroid FNAs were reviewed. Specimens included 11 PTCs, one follicular carcinoma, six follicular adenomas, eight follicular neoplasms not otherwise specified, 10 cases of chronic thyroiditis, and 88 colloid nodules/adenomatous goiters. Among the PTC cases, grooved nuclei were found in all 11 (100%), intranuclear inclusions in nine (82%), papillary fragments in seven (64%), and psammoma bodies in two (18%). Nuclear grooves were also observed in two of the 113 non-PTC cases (1.8%), both of which were colloid nodules, one with extensive Hurthle-cell change. The grooved nuclei were best identified on Papanicolaou-stained material. They were inconspicuous and difficult to identify in air-dried Diff-Quik-stained material. It appears that the recognition of grooved nuclei among tumor cells is a valuable diagnostic feature of PTC in cytologic material stained with polychromatic Papanicolaou stain.

Cytopathologic detection of Chlamydia trachomatis in vaginopancervical (Fast) smears.

The value of the Papanicolaou-stained vaginopancervical (Fast) smear in the detection of chlamydial infection has been disputed. We examined 116 satisfactory Fast smears from 203 women enrolled in the Johns Hopkins Fertility Control Clinic and compared tissue-culture results with cytopathologic detection using various published morphologic criteria. All Chlamydia culture-positive cases were reviewed, and certain cytologic features considered helpful in the detection of chlamydial infection in cervical smears obtained from this selected high-risk population were identified. The changes that had the highest correlation with tissue culture included fine vacuolation of metaplastic endocervical cells, giving their cytoplasm a rarefied "moth-eaten" appearance. Using these criteria, cytopathologic changes of chlamydial infection were observed in 24 of 28 cases of tissue-culture-positive cases and in 8 of 88 tissue-culture-negative cases. The sensitivity and specificity of the Fast-smear cytodiagnosis of Chlamydia infection utilizing these morphologic changes and compared with tissue culture were 86% and 91%, respectively. Other cytologic features, including inflammatory background and intracytoplasmic structures consistent with initial and intermediate chlamydial bodies within the metaplastic cells, were found to be useful although less specific and less sensitive. The implications of these diagnostic features, the conditions to be considered in their differential diagnosis, and the pitfalls of chlamydial cytodiagnosis and the chlamydia culture studies have been critically reviewed. Study design and the high unsatisfactory cervical smear rate are discussed.