Role of biliary brush cytology in primary sclerosing cholangitis

OBJECTIVE: To assess the role of brush cytology in the routine evaluation of patients with primary sclerosing cholangitis (PSC). STUDY DESIGN: From January 1995 to June 2000, 64 brush cytology specimens were obtained from 21 patients who had at least one cytologic sample obtained during endoscopic retrograde cholangiography. All patients had a diagnosis of primary sclerosing cholangitis. Cases were classified as benign, atypical or malignant according to major cytologic criteria (nuclear contour and chromatin irregularities) and minor cytologic criteria (polarity, cellularity, nuclear enlargement, mitosis, increased nuclear/cytoplasmic ratio) used by us to diagnose biliary brush cytology. Follow-up was available in all cases. RESULTS: Diagnoses were benign (13), atypical (5) and malignant (3) on cytology. Follow-up of the 13 benign cases showed bile duct stones (2), gallbladder adenocarcinoma at cholecystectomy (1), ascending cholangitis (1) and clinically/cytologically by benign follow-up (9). Five of 13 benign cases had subsequent liver transplantation for liver failure, with explants showing changes of primary sclerosing cholangitis. Of the 3 malignant cases, 1 had carcinoma in situ on biopsy, with the explanted liver showing high grade dysplasia; the second patient had cholangiocarcinoma on explant; and the third had hepatocellular carcinoma on liver five needle aspiration. The 5 patients with atypical cytology were reclassified on review as reactive (3) and atypical not otherwise specified (2). Follow-up showed benign disease in 3 of 3 atypical cases reclassified as reactive; 2 of 2 reclassified as atypical not otherwise specified showed low grade dysplasia in the explant. CONCLUSION: The overall incidence of malignancy was low (3 of 21) in patients with PSC. Bile duct brushing is a sensitive method of detecting neoplasia in the setting of PSC when well-defined cytologic criteria are applied.     

The role of cytology in the diagnosis and follow-up of patients with cervical adenocarcinoma

A review was undertaken of the 121 patients with cervical adenocarcinoma, ranging in age from 10 to 91 years, who had cytology specimens examined in this laboratory. All but two had cervicovaginal smears. Fifty-eight patients had cervical smears taken prior to treatment; 91% of these contained malignant cells. The commonest histologic subtype was mucinous adenocarcinoma (61 patients; 52%), followed by endometrioid carcinoma (26 cases; 22%), adenosquamous carcinoma (16 cases; 14%) and clear-cell carcinoma (12 cases; 10%). The cytologic characteristics were evaluated and correlated with the histopathology. During the follow-up period after definitive treatment, 119 patients had gynecologic smears taken; 24% were positive, representing 64% of those cases with central recurrences. In two patients, the abnormal smear was the first indicator of recurrence. Nine patients had 11 nongynecologic specimens revealing metastatic disease. Notable in this study were the 18 asymptomatic women, of whom 15 also had either no visible cervical lesion or minimal changes associated with benign conditions; cytology was abnormal in all but two. Cytology was effective in detecting disease. Its usefulness continued during the follow-up period in identifying or confirming recurrent or metastatic disease.     

Comparative study of cytology and punch biopsy in cervical intraepithelial neoplasia during pregnancy. A preliminary report

To elucidate the accuracy of cytology in diagnosing cervical intraepithelial neoplasia (CIN) during pregnancy, cytologic screenings for uterine cervical cancer in pregnant women were reviewed for a five-year period. Of the 967 pregnant women screened, abnormal cytologic findings were recorded for 15 (1.6%). Only nine of these were subsequently examined by colposcopy and punch biopsy, which demonstrated CIN in all cases, for an incidence of documented CIN during pregnancy of 0.93%. Including two referral cases also examined by colposcopy and biopsy, cytology and histology agreed on the degree of CIN in four cases and disagreed by one degree in four cases, by two degrees in two cases and by three degrees (mild dysplasia versus carcinoma in situ) in one case. Review of the specimens from these cases did not readily explain the poor concordance between cytology and punch biopsy; some findings suggest that overestimation of the punch biopsy sample may be the explanation.     

Cytology of bladder papilloma

Eighty-four urinary cytology specimens from 51 patients known to have bladder papilloma were reviewed and compared with 30 specimens from patients without neoplastic urologic disease, 12 specimens from patients later found to have papillomas that were unsuspected at the time of examination and 6 specimens from patients with a history of papilloma but no present evidence of the disease. No specific findings were identified that could be used to make a cytologic diagnosis of papilloma. However, the specimens from patients with papilloma were likely to contain an increased number of exfoliated epithelial cells, including atypically shaped cells that were small and round or, less frequently, elongated; they were also likely to contain a small number of red blood cells. This combination of cytologic findings yielded a pattern that can be described as consistent with or suggestive of papilloma in the appropriate clinical setting. It is not diagnostic since the absence of this cytologic pattern does not rule out papilloma, and the same cytologic features can be found (less frequently) in patients with other urologic diseases.     

Esophageal cytology in patients receiving cytotoxic drug therapy

Our experience with the cytology of esophageal brush specimens from patients who did not have either gastric or esophageal cancer but who received a variety of chemotherapeutic agents is reported. Ten patients received chemotherapy alone, and nine received combined chemotherapy and radiation therapy. Of the ten patients, three showed evidence of moderate to severe epithelial atypia, which was not seen in the combined treatment group or the control group. The cytologic atypias in the three patients consisted of variation in nuclear size with crowding and overlapping, an increased nuclear-cytoplasmic ratio and multiple nucleoli, many of which varied in size and shape. There was also evidence of cell death and keratinization. Although these patients had not been irradiated, other striking changes were similar to those seen following radiation therapy. The cytologic changes reported here pose a serious diagnostic problem because they may be so severe as to mimic malignant transformation. Evidence of infection by herpes simplex alone or herpes simplex associated with Candida was seen in 32% of the treated patients and in 4% of the control group.     

Age at first coitus and choice of contraceptive method: preliminary report on a study of factors related to cervical neoplasia.

The incidence of cancer of the uterine cervix appears to be species-specific, thus confounding extrapolation of results from studies with experimental animals. In humans, the incidence varies more by social groups than does any other primary cancer. In a recent study, Puerto Ricans were found to have a 25 times higher risk of cervical cancer than Jews. Blacks had 4 times the risk of non-Jewish Caucasians. Age at 1st coitus (AFC) and number of coital partners have been related to increased risks. Upper socioeconomic level women have had contraceptive pills prescribed more often than others. Initial interviews and recordings of gynecologic results have been completed by the Institute for Survey Research for 25,000 American women attending large clinics and group health centers in 9 continental cities and 3 cities in Puerto Rico. Data concerning contraceptive, sexual, and reproductive history have been completed for almost 12,000. Years of education and current age have had a significant effect (p less than .001) on AFC. Gravida was also significantly related to AFC (p less than .001). The AFC of North American blacks was lower than others. Women who chose to use the pill were found to have a higher prevalence of cytologic dysplasia at the time of choice than other women. Data provide no evidence to suggest that the widespread use of oral contraceptives since the mid-1960s has been followed by increasing rates of carcinoma in situ. Other epidemiological research has failed to reveal retrospective associations between oral contraceptive use and abnormal cervical cytology. Present results are consistent with this pattern.     

Preoperative brush and impression cytology in ocular surface squamous neoplasms

OBJECTIVE: Preoperative cytologic diagnoses of ocular surface squamous neoplasms were evaluated and compared with histologic diagnoses. STUDY DESIGN: Impression cytology (Millipore filter paper) and brush cytology were applied to 32 patients who had conjunctival neoplasms. Papanicolaou-stained cytologic preparations and hematoxylin and eosin-stained histologic sections were examined by light microscopy. RESULTS: The brush technique was used on 27 patients; impression cytology was applied in 5 cases. Cytologic and histologic diagnoses were concordant in 26 cases. Squamous cell carcinoma or carcinoma in situ was diagnosed in 18 and dysplasia in 4 cases. Squamous metaplasia and normal-appearing conjunctival epithelial cells were diagnosed cytologically in four cases; of those histologic diagnoses, one was pterygium and three, conjunctival nevus. Four cases revealed discrepancies between the cytologic and histologic preparations. There was one false positive result, and one case was subconjunctival invasion of basal cell carcinoma of the eyelid. CONCLUSION: Impression and brush cytology are fast, cost-effective, reliable and noninvasive diagnostic tools for ocular surface squamous neoplasms. However, the brush technique has several advantages over impression cytology.     

Imprint cytologic features of intracytoplasmic lumina in ependymoma. A report of two cases

BACKGROUND: Intracytoplasmic lumina have been recently recognized as a characteristic histologic feature of ependymoma. However, the cytologic diagnostic usefulness has not been discussed. We encountered two imprint cytology cases of spinal cord ependymomas in which there were intracytoplasmic lumina in the tumor cells. CASES: Two women had spinal cord tumors on magnetic resonance imaging. Imprint cytology study was carried out on the resected tumors. The cytologic specimen of the first case, aged 52, showed tumor clusters consisting of elongated epithelioid cells, a few of which also had intracytoplasmic lumina. Histologically, tumor cells formed ependymal rosettes and pseudoperivascular rosettes. There were a few tumor cells with intracytoplasmic lumina. The cytologic specimen of the second patient, aged 37, had scattered and isolated tumor cells with intracytoplasmic lumina resembling signet-ring cells and paired tumor cells forming small, glandlike structures. Histologically, the tumor was composed mainly of signet-ring-like cells containing intracytoplasmic lumina. CONCLUSION: Intracytoplasmic lumina were observed in the imprint cytologic specimens of spinal cord ependymoma. The diagnosis of ependymomas can be made cytologically when intracytoplasmic lumina are found since no other primary neuroepithelial tumors of the central nervous system possess such a characteristic feature.     

Anal cytology in an HIV-positive population: a retrospective analysis

OBJECTIVE: To retrospectively evaluate cellularity and correlate the presence of columnar cells with specimen interpretation in conventionally prepared anal cytologic smears from an HIV-positive population. STUDY DESIGN: Two cytopathologists and 1 senior cytotechnologist, blinded to the original diagnosis, screened 114 samples from 110 patients collected between 1997 and 2002. One hundred nine males and 1 female were included, age ranging from 23 to 52 years. Discrepancies were reviewed for consensus. The interpretations, cellularity, and presence or absence of columnar cells were noted. The relationships between diagnosis and presence of columnar cells, visible anal lesions, concurrent HIV viral load and CD4+ T-cell counts were assessed. RESULTS: The cytologic findings were as follows: 7, unsatisfactory (6%); 29, negative (25%); 25, atypical squamous cells of undetermined significance (22%); and 53, dysplasia (47%) (42 anal intraepithelial lesion 1 [37%] and 11 anal intraepithelial lesion 2/3 [10%]). Nearly 50% of the smears, 51, showed the presence of columnar cells (45%); 37 of those specimens had some degree of dysplasia (74%). Of the 63 specimens with no columnar cells, 16 (25%) showed dysplasia. Columnar cells were absent from all unsatisfactory specimens. CONCLUSION: A highly significant association between the presence of columnar cells and anal intraepithelial lesion (p<0.001) and a significant association between the presence of columnar cells and atypical cytology when a visible lesion was absent (p=0.0019) were found. No significant relationship was found between the presence/degree of dysplasia and CD4+ T-cell counts or HIV viral load. Lack of clinical follow-up precluded evaluation of the false negative rates in this data set.     

Usefulness of bile cytology in the diagnostic management of patients with biliary tract obstruction

Eighteen patients with evidence of biliary tract obstruction had a total of 29 satisfactory bile samples submitted for diagnostic cytology during a two-year period. These 29 specimens were reviewed in order to determine if bile cytology is useful in the diagnostic management of patients with obstructive biliary tract disease. Twenty-one of the bile specimens were from patients with malignant biliary stricture, and eight were from patients with benign biliary obstruction. Bile cytology was positive for carcinoma in eight samples from patients with malignant stricture and was inconclusive for malignancy in two. There were no false positives. The diagnostic specificity of bile cytology was 100%, the diagnostic sensitivity was 48%, and the diagnostic accuracy was 62%. When carefully collected and promptly processed, bile proved an excellent specimen for cytologic evaluation and was a valuable adjunct to other diagnostic procedures for the detection of carcinoma causing biliary tract obstruction.     

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.     

Early detection of precancerous lesions in dysplasias of the lung by rapid DNA image cytometry

Hematoxylin-and-eosin-stained cytologic smears of sputum from 28 patients with dysplastic and suspicious cell findings were subjected to DNA image cytometry after Feulgen restaining. The nuclear DNA contents were measured with a TV-based image-analysis system, the Leitz TAS plus, combined with an automatic microscope. Computation of DNA data was performed according to an algorithm for the diagnosis and grading of malignancy. Of the 19 cases that were proven to be malignant in the follow-up, either by histologic examination, sputum cytology, fine needle aspiration biopsy or autopsy, the algorithm identified 17 as malignant in a stage (dysplasia) in which cytology was not yet able to present a definite diagnosis of malignancy. Only two cases of bronchial carcinoma were not detected in the state of dysplasia by this procedure. The periods between the DNA diagnosis of malignancy in dysplasia and the morphologic evidence of cancer varied from three days up to six months. Of the 11 cases that had been classified as benign by the algorithm, 9 were confirmed as benign during the clinical follow-up. Rapid DNA image cytometry appears able to separate squamous dysplasias of the lung into precancerous and nonprecancerous lesions.     

"Repair cells" in equine uterine cytologic and histologic specimens

Cells resembling those known as "repair cells" in gynecologic cytology specimens from women were identified in uterine cytology specimens from infertile mares treated with antibiotics using indwelling uterine catheters. This prompted a study of the effect on the equine uterus of indwelling catheterization without antibiotic infusion, using light microscopic examination of cytologic and biopsy specimens and electron microscopic examination of biopsy specimens. Cytologic and biopsy specimens had features within normal limits at the start of the study. Following five days of indwelling catheterization, neutrophils were present in both cytologic and biopsy specimens. In cytologic specimens, numerous groups of "repair cells" were present; similar cells in biopsy specimens indicated this was a focal reaction. The large nuclei and prominent nucleoli of the "repair cells" suggested cellular proliferation or regeneration. However, this was contradicted by the ultrastructural sparsity of ribosomes, endoplasmic reticulum, Golgi apparatus and mitochondria. Inflammation and "repair cells" were not present in cytologic or biopsy specimens collected 40 days after the start of the study. Although these cells may be a component of a repair process, our results support the hypothesis that "repair cells" in human and equine gynecologic cytology specimens are injured, rather than regenerating, cells. The term dysphaneroplastic (Greek: "abnormal cytosol development") is proposed to describe these cells since the cytoplasm does not reflect the features of cellular activity suggested by the nuclear appearance.     

Cervicovaginal cytology in patients 16 years of age and younger

A four-year survey of cervicovaginal cytology in 1,664 patients 16 years of age and younger showed 13 cases of dysplasia (0.78%). All were mild or moderate in degree. No cases of severe dysplasia, carcinoma in situ or invasive carcinoma were detected. Small numbers of cases of herpesvirus infection and of condyloma were also detected. The occurrence rate of trichomoniasis, however, was twice that normally seen in an adult population. The cytologic diagnosis of a low but significant number of cases of cervical dysplasia indicates a population whose continued surveillance by cytologic or other means is warranted. In this young population the detection of other sources of morbidity, such as trichomoniasis, offers an opportunity for beneficial medical intervention.     

Cytologic detection of esophageal squamous cell carcinoma and its precursor lesions using balloon samplers and liquid-based cytology in asymptomatic adults in Llinxian, China

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is associated with very high regional mortality rates in several countries. Our initial test of esophageal cytology screening devices found them not sensitive enough for an early detection program. The current study tested a newly designed "mechanical" balloon and a traditional Chinese inflatable balloon, followed by liquid-based cytology, to detect biopsy-proven squamous dysplasia and early cancer. STUDY DESIGN: Participants were randomized to a cytologic sampler, followed by endoscopy with iodine staining. For each patient, the cytologic diagnosis (test) was compared with the worst endoscopic biopsy diagnosis (truth). RESULTS: Seven hundred forty subjects completed both examinations. Approximately 30% showed atypical squamous cells of undetermined significance (ASCUS), and 10% showed squamous intraepithelial lesions. Seven hundred twenty-five subjects (98%) had satisfactory biopsies, and 32% had low grade dysplasia or worse disease. Defining > ASCUS, favor neoplastic, as a positive screening test, the sensitivities/specificities of the mechanical and inflatable balloons were 39%/85% and 46%/84%, respectively, for detecting any squamous dysplasia or cancer. CONCLUSION: These esophageal cell samplers performed equivalently, but the accuracy was still too low for a primary screening test. These results highlight the need to develop new cytologic criteria or molecular markers that can better detect early squamous esophageal disease [corrected]     

Clinical and Virologic Course of Herpes Simplex Genitalis

The clinical and virologic course of herpes simplex genitalis in women and men was examined in order to identify measurements useful in antiviral trials. Factors influencing the clinical course included initial disease versus recurrent disease, wet-skin versus dry-skin lesions, female versus male sex. Women with initial genital herpes had higher mean peak lesion virus titers than those with recurrent disease (10^4.5 pfu compared with 10^2.5 pfu) and excreted virus longer (13 to 15 days compared with 6 to 8 days). Men with recurrent lesions had higher mean peak virus titers than women (10^4.0 pfu compared with 10^2.5 pfu), but the duration of virus excretion was shorter (three to four days compared with six to eight days). There was pronounced variation in the clinical and virologic course of recurrent lesions among different patients and even within the same patient. These observations indicate several difficulties that must be considered in conducting careful antiviral trials in patients with herpes simplex genitalis.     

Cytomorphology of the variants of small-cell carcinoma of the lung

Cytologic classification of subtypes of small-cell carcinoma of the lung (SCCL) was retrospectively performed on respiratory material of 90 cases of lung carcinoma cytologically diagnosed as SCCL. Additionally, the cytologic material was reexamined for the presence of variants of SCCL in 68 cases of lung carcinoma whose types had not been conclusively defined by cytology. The type of lung cytology specimens reviewed were sputa, bronchial washings and brushings and fine needle aspirations. The study included review of pretreatment tumor histology, when present, and examination of the ultrastructure of the tumor in selected cases whose type had not been well defined by histology. Subtype recognition depended on the adequacy of the specimens rather than on the type of cytologic material examined. The cytologic subtyping was generally in agreement with the histologic subtyping of the tumor, except for cases in which SCCL was combined with other types of lung carcinoma, where certain discrepancies were noted.     

Fine needle aspiration cytology of focal nodular hyperplasia of the liver

In five cases, the fine needle aspiration (FNA) cytologic study of ultrasonically detected solitary liver tumors yielded a diagnosis of focal nodular hyperplasia. Cytomorphologically, the lesions were characterized by the presence of both abundant normal hepatocytes and numerous epithelial cells in ductal formations, clusters or tightly packed groups in the FNA samples. In two of the five cases, the cytologic diagnosis was confirmed by subsequent histologic studies; in the remaining three cases, the clinical data were consistent with focal nodular hyperplasia of the liver. All five patients were women, four of whom had used oral contraceptives for long periods of time (5 to 15 years), which has previously been linked to the development of focal nodular hyperplasia of the liver. Based on the findings in this study, FNA cytology should be adequate for making the differential diagnosis of focal nodular hyperplasia versus liver-cell adenoma when solitary liver tumors are detected in such cases; it can yield a morphologic diagnosis and facilitate the decision as to whether surgical intervention is required.     

Fine needle aspiration biopsy versus sputum and bronchial material in the diagnosis of lung cancer. A comparative study of 168 patients

A group of 168 consecutive lung cancer patients in whom a definitive diagnosis of primary lung cancer was established either in a conventional cytologic specimen of sputum or bronchial material or in a specimen obtained by fine needle aspiration (FNA) biopsy was reviewed to compare the relative accuracies between the modalities of sputum and bronchial material on one hand versus FNA cytology on the other in the diagnosis of lung cancer. The patients included in the study were selected from a total of 1,093 patients who had been diagnosed and treated for lung cancer at Duke University Medical Center over the five-year period of January 1, 1980, through December 31, 1984. In 325 (29.8%) of the 1,093 patients, a definitive cancer diagnosis was established from histopathologic study alone, without any cytologic diagnoses. In 420 patients (38.4%), both histologic and cytologic material had been interpreted as being conclusively diagnostic for lung cancer. In 348 patients (31.8%), a cytologic diagnosis of lung cancer was made without a histologic confirmation. Thus, in a total of 768 (70.3%) of the 1,093 cases, a definitive cytologic diagnosis of cancer had been made. Of these 768 patients, 168 had been evaluated by both conventional respiratory cytologic methods (examination of sputum and bronchial material) and with FNA biopsy cytology. In 9 patients (5.4%), only conventional respiratory cytologic specimens were conclusively diagnostic for cancer. In 122 patients (72.6%), only the FNA biopsy specimen was diagnostic. In 37 patients (22.0%), both conventional respiratory specimens and FNA specimens yielded a definitive lung cancer diagnosis. The FNA specimen was the only positive cytologic specimen in 90.2% of large cell undifferentiated carcinomas, 79.5% of adenocarcinomas, 66.7% of small cell undifferentiated carcinomas and 58.2% of squamous cell carcinomas. In 26.5% of the patients, a diagnosis of cancer could have been established on conventional cytologic specimens, without the necessity of proceeding to percutaneous FNA biopsy. From this study, it is concluded that the techniques of conventional respiratory cytology and FNA biopsy cytology are complementary in the diagnosis of lung cancer. While the percentage of lung cancers diagnosed by FNA biopsy cytology alone is much greater than that obtained by conventional respiratory cytology alone, more than one-fourth of these cancers could be detected by the less invasive techniques of sputum collection and bronchoscopy.     

Cytologic changes in small hepatocellular carcinomas after radiofrequency ablation

OBJECTIVE: To illustrate the cytologic changes in hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). STUDY DESIGN: The study included 20 patients with 23 HCC who had undergone RFA under ultrasound guidance. Baseline cytomorphology of HCC was evaluated by fine needle aspiration (FNA) in all cases. Triphasic helical computed tomography (CT) and FNA cytology were done to evaluate the efficacy of the treatment within two weeks after RFA. The cytologic specimens were stained with Riu's method (Romanowsky stain). RESULTS: A range of cytologic findings after RFA was found, including granular and amorphous debris with artefactual aggregation, degenerated cells or necrotic material, and dyshesive, degenerated cells in a necrotic background. The cytologic patterns included necrotic cells and debris in 14 tumors and fine, granular necrosis in 9. Helical CT showed no enhancement in any of the tumors after RFA. CONCLUSION: The cell patterns indicated complete necrosis in HCC after RFA.