The "suspicious" gynecologic smear

"Suspicious" gynecologic smears from 842 patients over a seven-year period were analyzed for their causes and outcomes. The frequency of the cytologic diagnosis of "suspicious" ranged between 0.5% in 1979 and 1.44% in 1975 of all smears examined. Review of the smears showed that this classification was used to report a variety of conditions, including equivocal possible precancerous changes as well as the presence of severe inflammation, degenerative or atrophic changes, abnormal glandular cells and metaplasia. The cytologic follow-up, following anti-inflammatory or hormonal therapy, showed a conversion to negative findings in 65.1% of all cases, usually within 12 months. In 294 cases, histologic analysis became necessary, revealing precancerous changes or cancer in 147 patients (17.5% of the study group). Smears of postmenopausal women with suspicious glandular or endometrial cells received special analysis. Significant numbers of such cases had histologic findings positive for malignancy (20% of smears with glandular cells and 21.3% with endometrial cells), as did also smears showing post-irradiative changes (34.6%) or atrophic and degenerative changes (17.1%). Therefore, "suspicious" smears in these groups were considered to indicate an increased risk of malignancy. A regimen for the proper management of cases with "suspicious" smears has been established.     

Cytologic and DNA cytometric diagnosis and therapy monitoring of squamous cell carcinoma in situ and malignant melanoma of the cornea and conjunctiva

OBJECTIVE: To investigate the diagnostic accuracy of exfoliative cytology of the cornea and conjunctiva and DNA image cytometry for quality control and monitoring of therapy for malignant neoplasms. STUDY DESIGN: Conjunctival or corneal smears from six cases clinically suspicious for malignant melanomas and eight suspicious for carcinomas in situ were investigated. Smears from 18 cases clinically nonsuspicious for neoplastic diseases served as negative controls. Repeated smears were obtained during and after local mitomycin C (MMC) therapy. RESULTS: In none of 18 nonsuspicious cases, cytology revealed abnormal cells. DNA cytometry showed nonaneuploidy in all of these. All smears from patients with histologically proven malignant melanomas (MM) and squamous cell carcinomas in situ revealed abnormal cells. Image cytometry demonstrated DNA aneuploidy in 66.6% of patients with MM and 80% with carcinoma. Sensitivity of cytology thus was 100% for both MM and carcinoma; specificity also was 100%. DNA measurements after MMC therapy revealed euploid polyploidization of nonneoplastic squamous cells. DNA cytometry provided an objective identification of tumor cell regression. CONCLUSION: Cytologic examination of corneal and conjunctival smears is a noninvasive tool with high diagnostic accuracy for detection of epithelial neoplasms. DNA image cytometry can serve for quality control and for objective monitoring of the effect of local chemotherapy.     

Predictive value of DNA cytometry in CIN 1 and 2. Image analysis of 193 cases

OBJECTIVE: To investigate DNA image cytometry for predicting the prognosis of cervical intraepithelial neoplasia (CIN). STUDY DESIGN: Smears from 151 women affected by CIN 1 or 2 on cytology with minimal follow-up of three years were included. Sixty-seven showed progression, with histologically confirmed carcinoma in situ or invasive cancer. Eighty-four cases showed regression of the disease, which was cytologically, histologically and colposcopically confirmed. Papanicolaou-stained smears were destained, and the Feulgen reaction was performed with consecutive image DNA cytometry of suspicious cells using an image analysis system (Cires, Zeiss, Germany). The DNA index of the greatest stemline and the number of single aneuploid cells, using 9c exceeding events, were computed. RESULTS: In the group with progression, an aneuploid DNA stemline was found in 25 smears (26.9%). In 64 cases (66.7%) more than one aneuploid event was detected. The total number of aneuploid cases in this group was 76 (81%). In the group without progression, the number of aneuploid stemlines was 2 (2%). Single aneuploid cells could be found in five cases (5%). The overall number of aneuploid cases in that group was five. The sensitivity was 74.3%, positive predictive value 85.2% and negative predictive value 77%. CONCLUSION: Aneuploidy is a marker for prospective malignancy in cervical Papanicolaou smears. DNA image cytometry, as an additional method, can be used to predict outcome in patients with CIN 1 and 2 of the cervix. DNA cytometry is not a screening method but can add further information for a treatment decision in doubtful cases.     

Cytophotometric studies in suspicious cervical smears.

Papanicolaou stained smears of various cervical lesions diagnosed as "suspicious" by routine cytology were reviewed with regard to different cell types leading to this diagnosis. The smears were then submitted to Feulgen hydrolysis and redyed by Acriflavin-SO2 for fluorescence-cytophotometry. In nine of 14 cases measured, the DNA content of all types of "suspicious" cells was increased with DNA modes at euploid levels of 2 n, 4 n and 8 n indicating that the "suspicious" cells in those cases are polyploid. However, in five cases aneuploid DNA-distribution patterns were found similar to those observed in carcinoma in situ or severe dysplasia. Since polyploidization may be considered as a cellular response to higher functional requirement (i.e. inflammation or regeneration) a "suspicious" cervical smear with a polyploid DNA-distribution pattern may reverse to normal cervical epithelium after normal conditions are restored. However, a "suspicious" smear with an aneuploid DNA-distribution pattern should be considered more seriously as being related to a precancerous lesion requiring immediate surgical treatment.     

Fine needle aspiration cytology diagnosis of cutaneous leishmaniasis in a 6-month-old child: a case report.

BACKGROUND: Skin biopsy and scrape smear examination are the two most commonly employed investigatory techniques in the diagnosis of cutaneous leishmaniasis. Although cases Leishmania lymphadenitis are reliably diagnosed with fine needle aspiration (FNA) cytology, it has not attained popularity in the diagnosis of cutaneous leishmaniasis, and only a few reports are available. CASE: A 6-month-old Kuwaiti child presented with a skin lesion on her left forearm of five months' duration. Both scrape smears and FNA were performed from the lesion. FNA cytology smears showed a rich population of inflammatory cells predominating in lymphocytes and histiocytes and epithelioid cell granulomas. The amastigote forms of Leishmania were noted on the smears. The scrape smears were nondiagnostic. CONCLUSION: FNA cytology can be reliably used in the diagnosis of cutaneous leishmaniasis, especially in dry lesions, where scrape smears are likely to be nondiagnostic.     

Cystic degeneration in phyllodes tumor. A source of error in cytologic interpretation

OBJECTIVE: To examine problems encountered in the cytologic interpretation of phyllodes tumor (PT) with cystic degeneration and solutions thereof. STUDY DESIGN: Cystic degeneration was found in seven PTs (five benign, one low grade and one high grade). Aspirates from these yielded fluid and were usually labelled fibrocystic change on the original cytology. Smears were retrospectively analyzed, with special attention to the background, presence and nature of the epithelial and stromal fragments, foam cells and naked nuclei in the background. RESULTS: PTs with cystic degeneration on cytology showed thick fluid in the background, foamy macrophages (100%), apocrine cells (28%) and epithelial fragments, which showed nuclear atypia in two cases. On reviewing the smears, five of seven PTs had stromal fragments, albeit in small numbers. Most important, even in the absence of stromal fragments, all cases showed 5-50% naked nuclei of the fibroblastic type dispersed within the fluid background. CONCLUSION: In cases of fluid aspirates from well-defined lumps, one must search for fibroblastlike naked nuclei or stromal fragments within the fluid to clinch the diagnosis of phyllodes tumor.     

Abrasive bronchial brushing cytology. A preliminary study of 200 specimens for the diagnosis of neoplastic and nonneoplastic bronchopulmonary lesions

Two hundred subjects with chronic respiratory symptoms with a suspicion of malignancy were selected for bronchial brushing cytology. Prior sputum examination had shown malignant squamous cells in two cases only. The cytologic appearances of the brushing smears were divided into five categories: 41 (20.5%) smears with positively malignant cells; 20 (10%) smears predominantly showing chronic inflammatory features; 31 (15.5%) smears with mainly acute inflammatory changes; 60 (30%) smears with normal cytologic features; and 48 (24%) smears unsatisfactory for cytologic interpretation. Thirteen patients with a positive cytology had a positive tissue biopsy for malignancy. Among the group with chronic inflammatory changes, acid-fast bacilli were identified in nine cases, and one smear showed frank tuberculous granuloma. In the unsatisfactory group, two cases showed malignant cells in the postbrushing sputum. There was one false-negative report for malignancy in the entire study. This study confirms the sensitivity and accuracy of bronchial brushing cytology in the diagnosis of various bronchopulmonary lesions, especially malignancy and pulmonary tuberculosis, in India.     

Fish health assessment: a preliminary report on the use of impression smears of skin mucus

Preliminary results from this study suggest that impression smears of the skin mucus of fish can be used to aid in the evaluation of the fish's health status. Nonstressed Lagodon rhomboides and Carassius auratus have numerous superficial epithelial cells, occasional lymphocytes and other mononuclear cells in their cutaneous mucus. Smears of these fish 24 h post-stress had more cellular debris, micro-organisms and erythrocytes when compared to those made pre-stress. Components in the mucus of fish which recovered gradually became normal. Smears of fish, which died, had increasing amounts of debris and micro-organisms. The use of this relatively nontraumatic technique may be a useful adjunct in monitoring fish health.     

The comedo subtype of intraductal carcinoma. Cytologic characteristics.

Smears from 10 intraductal carcinomas of the comedo type without microinfiltration were compared with smears from 10 similar tumors with suspected or proven microinfiltration and smears from 10 invasive comedo carcinomas. Microinvasive tumors could not be separated from purely intraductal cases unless tumor cell infiltration in mammary fat was seen in the smear. The tumor cells in most of the intraductal cases were shed in cohesive groups and clusters, lying in necrotic cellular debris and with few or no scattered, single, dissociated tumor cells. Smears from invasive comedo carcinomas invariably showed tumor cell clusters and scattered, single, dissociated tumor cells, often with atypia in excess of what was seen in the intraductal cases. Also, in most cases the invasive tumors did not show a background of necrotic cellular debris.     

Cutaneous relapse in Hodgkin's disease: a case report

BACKGROUND: Skin involvement in Hodgkin's disease is rare, can be seen in advanced stages of the disease and indicates a poor prognosis. CASE: A young male presented with multiple nodular lesions on the chest wall and matted cervical lymph nodes. Aspiration smears from skin lesions showed atypical mononuclear cells with a prominent nucleolus, many lymphocytes and plasma cells. Smears from the lymph nodes showed classical Reed-Sternberg cells in a polymorphous background. The cytologic diagnosis of Hodgkin's lymphoma was entertained and later confirmed on skin biopsy. Past history revealed that the patient had been diagnosed with Hodgkin's disease and treated for it 2 years earlier, but had been lost to follow-up during treatment. CONCLUSION: Cutaneous Hodgkin's disease should always be considered in smears from skin lesions showing atypical mononuclear cells in a polymorphous background, even in the absence of a definitive clinical diagnosis at the time of presentation.     

Cytology of nipple discharge in florid gynecomastia

OBJECTIVE: To determine the cytomorphologic spectrum of nipple discharge in florid gynecomastia. STUDY DESIGN: During a 22-year period (July 1979-June 2001), nipple discharge from nine males with breast lesions were examined. Smears from four of these cases with histologically documented gynecomastia were reviewed along with the tissue sections. RESULTS: In the three patients with florid gynecomastia the smears were cellular, with numerous benign ductal cells and papillary fragments along with foam cells and inflammatory cells. Epithelial atypia was mild in two cases and moderate in one. One of the three cases had an associated breast lump that showed features of florid gynecomastia on fine needle aspiration cytology. The biopsy from this case showed cystic hyperplasia of the breast similar to that in women with an intraductal papilloma. One case of simple gynecomastia on histology showed two fragments of benign ductal cells with occasional apocrine and foam cells. CONCLUSION: Nipple discharge in florid gynecomastia may pose problems in identification as the cellularity and atypia may lead to a misdiagnosis of carcinoma.     

Cytologic and ultrastructural findings of a peculiar alteration in cervical cells from patients with human papillomavirus infections

Inclusion bodies were previously found in Papanicolaou smears of patients infected by the human papillomavirus (HPV). To ascertain their origin, 12 biopsies from patients with colposcopic evidence of papillomatous lesions were studied by cytology and electron microscopy. In several instances, koilocytotic atypias and electron-dense masses included within epithelial cells were observed. Some of these epithelial cells appeared to be surrounded by other cells in a sort of concentric arrangement. The electron-dense masses were composed of intermediate filaments, vacuoles and electron-dense material. They seemed to be dyskeratotic cells. They can be compared with apoptotic bodies and may be related to a disturbance of the involucrin expression caused by the HPV infection.     

Cytological diagnosis of endometritis in the mare: investigations of sampling techniques and relation to bacteriological results

Aim of this study was to compare uterine smears made using the Knudsen catheter, the cytology brush and a uterine culture swab with regard to diagnostic usefulness and the occurrence of neutrophils. Additionally correlation between culture results and the occurrence of neutrophils in uterine smears was investigated. Samples were collected from 340 mares, 81.5% of which were in estrus. Smears made using the cytology brush yielded more endometrial cells per high-power field than those made using the other two instruments (p<0.0001), and a larger proportion had PMNs compared with smears made using the uterine swab (p<0.0001). For smears made with the cytology brush, cultures of β-hemolytic streptococci were more often (p=0.002) accompanied by PMNs than cultures of bacteria other than β-hemolytic streptococci, and there was a positive correlation (r(s)=0.2 p=0.01) between the number of PMNs in smears and the number of colonies of β-hemolytic streptococci. The cytology brush was superior to the other methods because it generated a larger proportion of diagnostic useful smears and the occurrence of PMNs in smears was significantly correlated with the occurrence of cultures of β-hemolytic streptococci.     

Diagnostic value of nucleolar organizer regions (AgNORs) in brush biopsies of suspicious lesions of the oral cavity.

OBJECTIVE: The aim of this retrospective study was to report on the diagnostic accuracy of AgNOR-analysis as an adjunctive diagnostic tool of conventional oral exfoliative cytology taken from suspicious lesions in our clinic. STUDY DESIGN: Cytological diagnoses obtained from brush biopsies of macroscopically suspicious lesions of the oral mucosa from 75 patients (final diagnoses: 53 histologically proven squamous cell carcinomas, 11 leukoplakias and other inflammatory oral lesions) and from 11 patients with normal mucosa as a negative control group were compared with histological and/or clinical follow-ups. Five smears were doubtful and seven suspicious for tumor cells in the cytologic report. Number of AgNOR's were counted in 100 squamous epithelial cell-nuclei per slide after silver-restaining. RESULTS: Sensitivity of our cytological diagnosis alone on oral smears for the detection of squamous carcinomas was 92.5%, specificity 100%, positive predictive value was 100% and negative 84.6%. The best cut-off value of the mean number of AgNOR dots per nucleus distinguishing benign from malignant cells was 4.8. The percentage of nuclei with more than three AgNORs had a cut-off level of 70%. Applying these methods to twelve doubtful or suspicious cytological diagnoses we were able to correctly establish the diagnosis of malignancy in ten cases of histologically proven cancers and to reveal benignity in two histologically proven cases. Thus we achieved a positive and negative predictive value of 100% each. CONCLUSIONS: Smears from brushings of visible oral lesions, if clinically considered as suspicious for cancer, are an easily practicable, non-invasive, painless, safe and accurate screening method for detection of oral cancerous lesions. We conclude that AgNOR-analysis may be a useful adjunct to other methods in routine cytological diagnosis of oral cancer that can help to solve cytologically suspicious or doubtful cases.     

Esophageal tuberculosis. Endoscopic cytology as a diagnostic tool

OBJECTIVE: To study the utility of endoscopic cytology in the diagnosis of esophageal tuberculosis in clinically unsuspected cases. STUDY DESIGN: During a period of four years, endoscopic cytology of esophageal lesions was performed on 228 patients. In eight (3.5%) the cytologic diagnosis of esophageal tuberculosis was suggested on smears. Upon endoscopic examination, the sites of involvement were mid esophagus (five cases), upper esophagus (two cases) and lower esophagus (one case). Linear ulcer was seen in six cases; growth and narrowing of the lumen were seen in one case each. Endoscopic brush smears in seven cases and fine needle aspiration cytology smear in one case were collected. Air-dried smears stained by Giemsa stain were reviewed for detailed cytologic assessment. RESULTS: Smears showed well-defined granulomas with necrosis in five cases and granulomas without necrosis in three. Cytologic evidence of concurrent poorly differentiated squamous cell carcinoma was observed in one case. Tubercle bacilli were demonstrated in five cases. Endoscopic biopsy showed granulomas in three cases and tubercle bacilli in one case. In six cases there was no clinical or radiologic evidence of tuberculosis at other sites, thereby suggesting the possibility of primary esophageal tuberculosis. The remaining two cases had a past history of tuberculosis; one presented with cervical lymphadenopathy and one mediastinal lymphadenopathy. All patients received antitubercular treatment, and the patient with concurrent malignancy also received radiotherapy. All but one of the patients who succumbed to aspiration pneumonia responded to treatment. CONCLUSION: Endoscopic cytology is a useful modality in the diagnosis of esophageal tuberculosis in clinically unsuspected cases.     

Mastopathic fibroadenoma of the breast: a pitfall of aspiration cytology

OBJECTIVE: To assess the correlation between cytological diagnoses and histological subtypes of fibroadenoma (FA) and to clarify the cytological features of a specific group of FA displaying variable features similar to fibrocystic disease (mastopathic type, MFA), and to evaluate the significance of this subtype in cytological diagnosis. METHODS: A review of 141 cases of histologically proven FA was performed. We re-classified them into four subtypes according to Kinoshita's criteria [Jpn J Breast Cancer6 (1991) 377] and further selected 92 cases for which both fine needle aspiration (FNA) smears and histological specimens were available. Among them, 18 cases of MFA and their cytological smears were selected for the present study. RESULTS: There was significant correlation between MFA and cytological diagnosis of 'indeterminate' or 'suspicious for malignancy' (P < 0.01). Although no false-positive diagnosis was experienced in our series, 56% of the MFAs (10/18) had cytological diagnoses of indeterminate or were included in the category 'suspicious for malignancy'. Smears from MFA revealed high cellularity (9/18 smears had more than 10 epithelial clusters each composed of more than 50 cells), presence of cellular discohesiveness (13/18, 72.2%), but only mild nuclear atypia (5/18, 27.8%). Anisonucleosis was present in fewer than half the cases and no apparent condensed chromatin was identified. CONCLUSION: We highlight the significance of subclassification of MFA in aspiration cytology of breast. MFA had a significantly higher chance of falling into the 'suspicious for malignancy' or 'indeterminate' diagnostic category in aspiration cytology. It might be a diagnostic challenge for cytopathologist to identify this subtype of FA in FNA smears.     

Sialadenitis with crystalloid formation. Fine needle aspiration cytodiagnosis of 15 cases

OBJECTIVE: To assess the utility of fine needle aspiration cytology in the diagnosis of sialadenitis with crystalloid formation. STUDY DESIGN: In 15 cases, salivary gland masses were aspirated using a disposable, 20-mL syringe and 25-gauge needles, maintaining negative pressure. Smears routinely were air dried and stained by Diff-Quik (Dade Behring AG, Düdingen, Germany). Occasionally smears were fixed in alcohol and stained by the Papanicolaou method. RESULTS: The smears showed large numbers of non-birefringent crystalloids of varying sizes and shapes. The crystalloids stained deep blue with Diff-Quik and bright orange with Papanicolaou stain. Multinucleated histiocytes, neutrophilic leukocytes and benign salivary gland parenchyma were found, also. CONCLUSION: Fine needle aspiration cytology provides an accurate diagnosis of sialadenitis with crystalloids and is useful for avoiding unnecessary surgery.     

Previous cytology in patients with invasive carcinoma of the cervix

The cytologic history of 346 patients presenting with invasive carcinoma of the cervix was reviewed. A total of 74 patients (21%) reported that cervical cytology had been performed in the five years prior to presentation; confirmation of the cytologic history was obtained in 65 cases. Smears were available for review in 34 cases; of 28 smears originally reported as negative, 20 were found to be abnormal on review. The possible reasons for the failure of cytologic detection in these patients are discussed.     

Cervical dyskeratotic cells as predictors of condylomatous changes on biopsy

Human papillomavirus (HPV) infections cause the koilocytotic and dyskeratotic cell changes seen in cervical smears. Although the koilocyte is pathognomonic, the role of the isolated dyskeratocyte in predicting the presence of HPV infection is not yet defined. One hundred patients, ranging in age from 7 to 71 years (mean: 26 years), with a cytologic diagnosis of dyskeratotic cells and a simultaneous, colposcopically directed cervical biopsy, were studied to determine the tissue correlates of such cells. On biopsy, 61 had condylomatous changes; 14 of the 61 had an associated cervical intraepithelial neoplasia (CIN). Of the 39% without condylomatous changes, 12 had an unremarkable biopsy, 19 had squamous metaplasia, 5 had hyperkeratosis and 3 had CIN. Condyloma plus CIN was diagnosed at least two months previously in 14 of these 39 patients; 6 had CIN alone. The results show that dyskeratocytes in cervical smears are predictive of a simultaneous HPV infection in 61% of the cases and of an infection at some time in 75% of the cases. Since only 14% of the patients had a condyloma plus CIN and 3% had CIN alone, patients with a smear diagnosis of dyskeratotic cells may need a more careful follow-up. Other histologic correlates of the dyskeratocyte included squamous metaplasia and hyperkeratosis.     

Cellular Differences Between True Negative and False Negative Papanicolaou Smears

A matched case-control study of 123 false negative Papanicolaou smears and 488 true negative Papanicolaou smears was undertaken to determine the association between the types of cells present on the smear and the correctness of the cytology report. the false negative slides were significantly more likely to include endocervical columnar cells than the true negative slides (odds ratio 1.90, 95% confidence interval (CI) 1.21–3.01). No statistically significant difference in metaplastic cell status was evident (odds ratio 1.48, 95% CI 0.95–2.30). When considered together, metaplastic and/or columnar cells were significantly more likely to be present in false negative smears than in true negative smears (odds ratio 1.87, 95% CI 1.13–3.08). the implications of these findings for improving the accuracy of cervical cytology for the detection of precancerous lesions are discussed.