Decreased CD44 standard form expression correlates with prognostic variables in ovarian carcinomas.

Expression of CD44 standard form (CD44s) was evaluated by automated immunohistochemical analysis using the anti-CD44 A3D8 clone in 101 ovarian epithelial neoplasms including 82 primary tumors (64 carcinomas and 18 tumors of low malignant potential [LMP]), 9 lymph node metastases, 8 malignant ascites, and 2 peritoneal implants. Immunostaining was scored semiquantitatively. Tumors were graded according to the FIGO (International Federation of Gynecology and Obstetrics) classification system. Tumor stage and patient survival were determined from the patient records. While 9 of 18 LMP tumors expressed CD44s, only 15 of 64 carcinomas expressed it. In the carcinomas, univariate analysis revealed that decreased CD44s expression correlated with high tumor grade, advanced stage, and shortened survival. Loss of CD44s expression also was noted in the tumor cells in 8 of 9 lymph node metastases, 7 of 8 malignant ascites, and 1 of 2 implants. Multivariate analysis revealed that only tumor stage independently correlated with patient survival. Loss of CD44s expression determined by immunohistochemical analysis is more common in ovarian carcinomas than in LMP tumors; correlates with prognostic variables including tumor grade, stage, and survival; and may have an important role in the dissemination of ovarian cancer.

Ultrasound-guided fine-needle aspiration biopsy of the thyroid.

BACKGROUND: We reviewed the Massachusetts General Hospital experience with ultrasound-guided fine-needle aspiration biopsies (FNABs) of the thyroid to determine the indications, rate of unsatisfactory smears, correlation with excisional biopsy results, and verification of efficient use of personnel time. METHODS: All radiologically guided FNABs of the thyroid from January 1993 through June 1997 were reviewed. As a measure of efficient use of technologist time, a sample of times spent by the technologist during the procedure for 20 cases in 1993 and 1997 was compared with that of an equal number of random nonthyroid image guided FNABs. RESULTS: Two hundred-ninety FNABs were identified in 251 patients, representing 12% of all thyroid FNABs and 11% of all radiologically guided FNABs. Indications in the 251 patients included multiple nodules (78), solitary nodules (61), complex nodules (39), prior failed FNAB (39), thyroid bed abnormalities post-thyroidectomy (21), difficult access (7), and investigation of recurrent tumor in residual thyroid lobe (6). Available records indicated 118 lesions were palpable and 45 were nonpalpable; the physical examination characteristics of the remainder (88) were not stated. Diagnoses included 44 unsatisfactory cases (15%), 103 macrofollicular lesions, 20 microfollicular lesions, 26 mixed macro/microfollicular lesions, 5 oxyphilic lesions, 1 trabecular pattern, 15 nonspecific follicular cell pattern, 9 follicular cell atypia, 30 cysts, 11 thyroiditis, 23 malignant tumors, and 3 other (1 parathyroid, 2 lymph node). Eighty-nine FNABs from 76 patients had subsequent surgical biopsy. Excisional biopsies in 14 unsatisfactory FNABs were benign. In the remaining 75 FNABs from 67 patients, 18 malignancies on FNAB were correctly diagnosed, but 3 other papillary carcinomas were only qualified as atypical follicular cells on cytology. No false-positive cases occurred. Of 15 macrofollicular lesions on cytology, 10 were adenomas on excision, only 2 of which were microfollicular adenomas, and 4 were adenomatous nodules. An aspirate of a parathyroid adenoma was misinterpreted as a macrofollicular lesion of the thyroid. Three microfollicular lesions on FNAB proved to be nodular hyperplasia on excision, and the other 11 were adenomas, 5 of them microfollicular. Average technologist time was significantly longer for thyroid FNABs than nonthyroid FNABs in 1993, but in the 1997 sample no significant difference was identified. CONCLUSIONS: Radiologically guided FNAB of the thyroid is a clinically useful procedure with a high correlation between benign lesions not needing excision (macrofollicular), and lesions that need excision (microfollicular/oxyphilic cell or malignant). Technologist time needed for immediate evaluation tends to decrease with increasing operator experience. Cancer (Cancer Cytopathol)

Cytological features of malignant metastatic ameloblastoma: a case report and differential diagnosis.

In this report, the cytological features and differential diagnosis of the metastasis from and subsequent local recurrence of an unusual case of malignant (metastatic) ameloblastoma are described, with histological confirmation. Characteristic cytological findings included fibrovascular central cores surrounded by palisading crowded basaloid or columnar cells or both and rosette-like structures of tumor cells with central fibrillary material. Keratin debris in the background and cystic cavities were prominent components of the metastatic ameloblastoma. The basaloid cells showed scant-to-absent cytoplasm, round-to-oval to tear-shaped nuclei, rare longitudinal nuclear grooves, single or multiple nucleoli, and smooth-to-clefted nuclear contours. No features to predict malignant behavior were identified (abundant mitotic activity, necrosis, nuclear pleomorphism). The cytological features of ameloblastoma appear to be characteristic enough to allow definitive diagnosis. However, since the cytology of this tumor is underreported in the literature, the unwary observer could easily misdiagnose it, especially at metastatic sites.

Routine addition of an automated biopsy device to fine-needle aspiration of the lung: a prospective assessment.

OBJECTIVE: The purpose of this study was to prospectively assess the usefulness of the routine addition of an automated biopsy device (ABD) to fine-needle aspiration (FNA) of the lung and to examine the complication rate of this procedure. SUBJECTS AND METHODS: Fifty biopsies were performed under CT guidance using a coaxial technique with a 19-gauge introducer needle and a 22-gauge aspirating needle followed by a 20-gauge ABD. An average of 3.5 FNA specimens and 2.5 core specimens were obtained. Cytology and histology specimens were interpreted separately by two experienced pathologists who were unaware of the other's interpretation. Final diagnoses were based on surgery, microbiology, definitive biopsy diagnosis, and clinical follow-up. All complications were recorded. RESULTS: Of 34 malignant lesions, we achieved a diagnostic accuracy of 94% for FNA and 59% for core biopsy (p < .01). Combined accuracy was 94%. Of 16 benign lesions, an accurate definitive diagnosis was made in 31% of cases using FNA and in 69% of cases using core biopsy (p = .08). Combined accuracy was 69%. In the subset of benign lesions that were not acute infections (n = 8), an accurate definitive benign diagnosis was made in 12% of cases using FNA and in 75% of cases using core biopsy (p < .05). No false-positive diagnoses of malignancy occurred. Complications included pneumothorax, nine (18%) of 50 cases; chest tube, one (2%) of 50 cases minor pulmonary hemorrhage, seven (14%) of 50 cases; and minor hemoptysis, two (4%) of 50 cases. CONCLUSION: The complication rates of FNA with the addition of an ABD are similar to those reported in the literature for FNA alone. The addition of an ABD significantly increases the diagnostic accuracy only for the subset of benign lesions that are not acute infections.

Fine needle aspiration biopsy of the thyroid gland in patients with prior Graves' disease treated with radioactive iodine. Morphologic findings and potential pitfalls.

OBJECTIVE: To evaluate the morphologic findings and their potential pitfalls in fine needle aspiration biopsies (FNAB) of thyroid glands obtained following radioactive iodine (RaI) (131I) treatment for Graves' disease. STUDY DESIGN: Study of thyroid FNAB specimens from six patients with prior Graves' disease treated with RaI who developed palpable nodules and had subsequent thyroid resections. RESULTS: The cytologic changes attributed to radiation were quite variable among the six cases and were so pronounced in one case that a false positive diagnosis of papillary carcinoma was made even though a history of RaI had been provided. The FNAB specimen from the second case, submitted without a history of RaI treatment, was diagnosed as suspicious for papillary carcinoma. The smears from patient 3 were signed out descriptively because the pertinent clinical history had not been provided. The FNAB specimens from the last three patients were correctly interpreted because of the history of RaI therapy provided. All six thyroid surgical specimens showed changes consistent with radiation injury, and none contained evidence of malignancy. CONCLUSION: The study's findings demonstrate that the atypia produced by RaI may be severe, leading to an erroneous diagnosis of malignancy. Provision of the appropriate clinical history of Graves' disease treated with RaI may prevent this pitfall.

Significance of endothelium in the fine-needle aspiration biopsy diagnosis of hepatocellular carcinoma.

We reviewed fine-needle aspiration biopsies (FNAB) of hepatocellular carcinoma (HCC) (n = 35), benign hepatic processes (n = 35), cholangiocarcinoma (CC) (n = 6), and metastatic tumors (n = 100) to evaluate the significance of endothelium present either peripherally-wrapping around groups of cells, (peripheral endothelium (PE)), or transgressing sheets of cells (transgressing endothelium (TE)), in distinguishing these lesions. These patterns were assessed as absent, focal, or prominent. Thirty-three of 35 (94%) HCCs contained either focal or prominent PE or TE, compared to only 3 of 35 (9%) benign hepatocytic lesions. Only one benign lesion contained a prominent endothelial component (TE only). Two cases of HCC failed to contain endothelium, one fibrolamellar variant and one well-differentiated HCC. These differences were statistically significant (P < 10(-5), sensitivity 94%, specificity 91%, and positive predictive value [PPV] 92%). Neither pattern of endothelium was present in any CC or metastatic tumor. These differences were also statistically significant (P < 10(-5), sensitivity 94%, and specificity and PVP 100%). We conclude that the presence of endothelium, at least focally in either one or both distinctive patterns, is highly sensitive and specific for HCC and aides in distinguishing it from benign hepatocytic lesions, CC, and metastases.

Struma ovarii simulating ovarian tumors of other types. A report of 30 cases.

Thirty cases of struma ovarii with unusual microscopic features are described. They occurred in women 23 to 71 (average 49) years of age. Most of the patients had the usual symptoms and signs of an adnexal mass. Three patients had ascites and two had Meigs' syndrome. The tumors, all unilateral and confined to the ovary, ranged from 4 to 25 (average 12) cm in greatest dimension. They were typically predominantly solid and red-brown but cysts were present within foci of struma in several cases; an associated dermoid cyst was noted grossly in nine cases. Microscopic examination showed a prominent diffuse pattern in 21 cases, prominent microfollicles imparting in many cases a pseudotubular appearance in 20 cases, abundant eosinophilic cytoplasm in nine cases, and abundant clear cytoplasm in four cases. A contiguous dermoid cyst which had not been recognized on gross examination was documented in five cases. The typical paucity of thyroid follicles in cellular areas of these tumors often caused either a failure to consider a diagnosis of struma ovarii or led to serious consideration of other diagnoses. Clues to the correct diagnosis were the presence of rare typical thyroid follicles in foci that were predominantly diffuse or pseudotubular, the presence of larger areas of typical struma in 22 cases, and the association with a dermoid cyst in 14 cases. Immunohistochemical staining for thyroglobulin confirmed the nature of the tumor in all five cases in which it was performed. The diagnosis of struma should be entertained when one is examining an ovarian neoplasm with solid or pseudotubular patterns or a content of oxyphilic or clear cells. A careful search for thyroid follicles should be undertaken to establish the diagnosis and immunohistochemical staining for thyroglobulin performed to confirm it in problematic cases.

Cystic struma ovarii: a frequently unrecognized tumor. A report of 20 cases.

Twenty cases of cystic struma ovarii in women aged 23 to 83 (average, 46) years are described. The patients had the usual signs and symptoms of an adnexal mass. The tumors, all of which were unilateral and confined to the ovary, ranged from 2 to 19 (average, 13.5) cm in greatest dimension. Eighteen were multilocular, two unilocular. They were typically filled with clear to green-brown fluid. Microscopic examination showed cysts of various sizes separated by fibrous septa, which in many areas appeared nonspecific, but in all the cases contained at least small numbers of thyroid follicles. The cysts were typically lined by nonspecific-appearing, flat to cuboidal epithelial cells. The paucity of thyroid follicles in many areas and the nonspecific appearance of the epithelial cells lining the cysts often caused the diagnosis of struma ovarii to be overlooked. Clues to the correct diagnosis, in addition to the thyroid follicles in the septa, included the presence of larger areas of typical struma in a few cases and the association with a dermoid cyst in three cases. Immunohistochemical staining for thyroglobulin confirmed the nature of the tumor in all three cases in which it was performed. The diagnosis of cystic struma should be entertained when examining a multilocular or unilocular cystic ovarian neoplasm whose features are not obviously those of another tumor type, and a careful search for thyroid follicles should be undertaken to establish the diagnosis. In problematic cases, immunohistochemical staining for thyroglobulin may be required to establish the diagnosis.

Clinical utility of fine needle aspiration biopsy in the diagnosis of Wegener's granulomatosis. A report of two cases.

In two patients, pulmonary lesions of Wegener's granulomatosis (WG) were sampled by fine needle aspiration biopsy: one with the clinical diagnosis of primary pulmonary malignancy and the other with a clinical suspicion of WG. In the latter case the smears showed distinctive eosinophilic, collagen necrosis (pathergic necrosis), poorly formed granulomata composed of loose aggregates of elongated, often palisading epithelioid histiocytes, and multinucleate histiocytes. A cell block preparation in this case contained minute tissue fragments illustrating the distinctive, pathergic-type necrosis. In the former case, many of these features were present, but additionally there were several groups, atypical bronchial epithelial cells that, in light of the clinical impression, initially led to an incorrect diagnosis of bronchoalveolar carcinoma. Subsequent review of this case led to the diagnosis of WG. Antineutrophil cytoplasmic antibody (ANCA) serology was later obtained, confirming the diagnosis of WG in both cases. In our experience, the cytomorphologic findings of granular collagen necrosis, granulomata and multinucleate cells, although not specific, should alert the cytopathologist to consider the diagnosis of WG, especially when special stains for microorganisms are negative. A recommendation for ANCA serology testing early in the disease process, particularly in the limited forms of the disease, may lead to early recognition of WG, resulting in prompt institution of immunosuppressive therapy, greatly improving the patient's prognosis.

Oncocytic nodule. An unusual case of a submaxillary gland mass in an elderly patient.

A submaxillary gland mass in an elderly woman was diagnosed as an oncocytic nodule by cutting needle biopsy and was followed with serial fine needle aspiration (FNA) biopsy for seven years. All specimens showed pure populations of oncocytes. Oncocytic nodules of the salivary gland are unusual lesions that may represent hyperplastic proliferations or true neoplasms. Although oncocytic metaplasia is commonly identified in the salivary glands of elderly patients, oncocytes rarely form masses that are targets for needle biopsy. This case suggests that FNA biopsy may be a useful method of evaluating salivary gland lesions in elderly patients who are not candidates for surgery.

Lyme disease meningopolyneuritis simulating malignant lymphoma.

Lyme disease is a multisystem disorder resulting from infection by the tick-borne spirochete, Borrelia burgdorferi. Fever, chills, malaise and headaches; a characteristic rash; and subsequent polyarthritis typically herald the onset of this condition. Neurologic involvement may occur with skin and joint manifestations or present alone as meningitis, cranial neuritis, and radiculopathy known as Bannwarth's syndrome. We report the cerebrospinal fluid (CSF) cytomorphologic and immunocytochemical features of four patients who presented with isolated meningitis, cranial neuritis, and painful neuropathy without initial history of specific skin rash or previous tick bite. Initial CSF findings of significant numbers of markedly atypical plasmacytoid mononuclear cells suggested CSF non-Hodgkin's malignant lymphoma. Immunocytochemical studies on CSF specimens, however, revealed polyclonal surface immunoglobulin patterns consistent with an inflammatory reaction. Follow-up clinical history and/or peripheral blood serologic testing for antibody titers with B. burgdorferi antigen confirmed the diagnosis of Lyme disease in all four cases. We conclude that Lyme disease may present as atypical spinal fluid lymphoplasmacytic cellular infiltrates that simulate malignant lymphoma and that appropriate immunocytochemical studies and peripheral blood serologic testing be performed to establish this diagnosis and direct appropriate therapy.

Carcinoids, atypical carcinoids, and small-cell carcinomas of the lung: differential diagnosis of fine-needle aspiration biopsy specimens.

The acceptance of fine-needle aspiration biopsy in the diagnostic work-up of pulmonary masses has resulted in an increased number of neuroendocrine tumors of the lung first encountered as aspiration cytology specimens. The accurate cytologic identification of these neuroendocrine neoplasms is important in that they have relatively specific clinical and prognostic features in contrast to nonneuroendocrine neoplasms. We report on the cytologic features of 46 primary pulmonary neuroendocrine neoplasms initially encountered on fine-needle aspiration biopsies. The neoplasms are separated into three distinct cytologic groups, including the typical carcinoid (13 cases), the atypical carcinoid (3 cases), and small-cell carcinomas (30 cases). The clinical features of all cases--and histologic findings when they were available--are also considered. Finally, a detailed cytologic description of the three groups of neuroendocrine neoplasms is presented with emphasis on differential diagnosis including nonneuroendocrine pulmonary neoplasms.

Fine needle aspiration cytology of focal liver lesions. Results obtained with examination of both cytologic and histologic preparations.

The results of 197 consecutive fine needle aspirations (FNA) of focal liver lesions performed on 176 patients were reviewed, and the 176 single most diagnostic aspirates were analyzed in detail. The majority of specimens were obtained using a 20-gauge or 22-gauge needle with ultrasound guidance. An attempt was made to obtain both a cytologic and a tissue specimen from each aspirate. The overall accuracy of the procedure was 85%; the accuracies of the tissue and cytologic specimens were 67% and 73%, respectively. The combined procedure detected 81% of the documented malignant tumors; the tissue specimen detected 62%. Eleven tumors were identified only in the tissue specimen and 23 were identified only in the cytologic specimen. There were no false-positive diagnoses. Six of nine hepatocellular carcinomas were detected. These results show that FNA cytology is a safe, accurate, relatively noninvasive technique whose diagnostic yield may be improved by examination of both a histologic tissue and a cytologic preparation.

Supplementary tissue-core histology from fine-needle transthoracic aspiration biopsy.

Biopsies of 150 consecutive suspected lung cancers were performed with fine needles having circumferentially beveled tips that produced cytology and tiny tissue cores suitable for histology. Visible tissue cores were aspirated in 92% (n = 138) and histologic diagnoses were obtained in 72% (n = 108). There were 118 (79%) proven malignant and 27 (18%) proven benign lesions. Sensitivity and specificity of cancer diagnoses were 97% and 100%, respectively. Biopsy histology was the only positive cancer specimen in two biopsies (1.7%). Biopsy cytology was the only positive cancer specimen in 20 cases (17.2%). Biopsy cytology and histology agreed with the proven cell type in 71.8% and 78.6% of cancers, respectively. As expected, when large-cell undifferentiated carcinoma was regarded as a nonspecific cell type consistent with either poorly differentiated adenocarcinoma or poorly differentiated epidermoid carcinoma, biopsy-cell-type accuracy increased greatly. Specific benign diagnoses were obtained in 44% of the 27 biopsies of proven benign lesions: cytology (four), core histology (five), and bacteriology (nine). Simple and complicated pneumothorax occurred in 10% and 4% of biopsies, respectively. It was concluded that biopsy with fine, circumferentially beveled needles can produce useful histology to supplement biopsy cytology.

Adenoma malignum of the cervix. Cytologic findings.

The cytologic findings in three patients with adenoma malignum of the cervix are described. Two of them had the Peutz-Jeghers syndrome. One complained of vaginal bleeding, another of a mucoid vaginal discharge, and in the third case the tumor was discovered on routine physical examination. Cytologic material from these cases showed endocervical cells exhibiting a spectrum of atypical changes. The cells were arranged in multilayered strips, monolayered sheets and three-dimensional clusters. Individual cells ranged from cuboidal to columnar; the columnar cells typically had abundant lacy or vacuolated cytoplasm. The nuclei were round to oval and vesicular, and some of them contained prominent nucleoli. Variable numbers of mitotic figures were present. In one case the presence of numerous atypical cells was only suggestive of the diagnosis of malignancy; in the other two cases, although the majority of cells were only atypical, small numbers of frankly malignant cells were present.

Dysplasia and cytologic findings in 4,589 young women enrolled in diethylstilbestrol-adenosis (DESAD) project.

This report presents the cytologic findings and the rates of dysplasia for 4,589 young women enrolled in the National Cooperative Diethylstilbestrol-Adenosis (DESAD) Project. Mucinous columnar cells and/or metaplastic squamous cells with or without mucinous droplets were encountered in 22% of vaginal scrape smears from all diethylstilbestrol (DES)-exposed participants identified by review of prenatal records and in 43% of women in whom vaginal epithelial changes (VEC) were observed by colposcopy or by iodine staining. The frequency of cellular findings in the vaginal scrape smears was closely related to the timing of the administration of the DES to the mother. With increasing age of the daughters, the overall frequencies of both the mucinous and metaplastic cells decreased; relative to each other, an increasing proportion was metaplastic squamous cells. These data suggest that, as the women grow older, vaginal adenosis regresses by the process of squamous metaplasia. Endometrial type cells were found in 2% of vaginal scrape smears. Their cyclical occurrence during the menstrual cycle and lack of correlation with the presence of VEC indicated an origin from the uterine corpus rather than the tuboendometrial type of adenosis. Squamous cell dysplasia of the vagina and cervix was detected by biopsy or scrape smear specimens in 1.8% of DES-exposed women in the record review group. The rate of unexposed women was twice as high. In general, the rates of dysplasia were higher in the cervix than vagina, and the more severe degrees of dysplasia were encountered only in those women who were referred to the DESAD Project or who themselves requested entry. Four patients who were referred or who themselves requested entry were found to have clear cell adenocarcinoma of the vagina. The vaginal smear provided the first clue to the presence of an abnormality in three of them.

PIP: This report presents the cytologic findings and the rates of dysplasia for 4,589 young women enrolled in the National Cooperative (DESAD) Diethylstilbestrol-Adenosis Project. Mucinous columnar cells and/or metaplastic squamous cells with or without mucinous droplets were encountered in 22% of vaginal scrape smears from all (DES) diethylstilbestrol-exposed participants identified by review of prenatal records and in 43% of women in whom (VEC) vaginal epithelial changes were observed by colposcopy or by iodine staining. The frequency of cellular findings in the vaginal scrape smears was closely related to the timing of the administration of the DES to the mother. With increasing age of the daughters, the overall frequencies of both the mucinous and metaplastic cells decreased; relative to each other, an increasing proportion was metaplastic squamous cells. These data suggest that, as the women grow older, vaginal adenosis regresses by the process of squamous metaplasia. Endometrial type cells were found in 2% of vaginal scrape smears. Their cyclical occurrence during the menstrual cycle and lack of correlation with the presence of VEC indicated an origin from the uterine corpus rather than the tuboendometrial type of adenosis. Squamous cell dysplasia of the vagina and cervix was detected by biopsy or scrape smear specimens in 1.8% of DES-exposed women in the record review group. The rate in unexposed women was twice as high. In general, the rates of dysplasia were higher in the cervix than vagina, and the more severe degrees of dysplasia were encountered only in those women who were referred to the DESAD Project or who themselves requested entry. 4 patients who were referred or who themselves requested entry were found to have clear cell adenocarcinoma of the vagina. The vaginal smear provided the 1st clue to the presence of an abnormality in 3 of them.

Diagnosis of cryptococcal meningitis by cytologic methods: an old technique revisited.

In six patients with cryptococcal meningitis, diagnosis was made by routine cytologic examination of cerebrospinal fluid (CSF). A seventh patient had a false-positive cryptococcal antigen titer, and no organism was seen on SCF examination. The patient had herpes simplex encephalitis on brain biopsy. Cytologic examination is recommended whenever cryptococcal meningitis is suspected.

A study of variability in cytologic diagnoses based on pulmonary aspiration specimens.

Reproducibility of cytologic diagnoses of malignancy and accuracy and variability of diagnoses of malignant cell types were assessed in a study of pulmonary aspirates from 100 patients. Original cytologic diagnoses were positive for 60 of the 80 patients who had malignancy (true-positive rate 75%). No false-positive diagnosis was made. Original cytologic diagnoses were negative for 15 of the remaining 20 patients (true-negative rate 75%). In "blindly" reviewing the slides, the pathologist who had made the original diagnoses (Observer A) and another pathologist (Observer B) confirmed the 60 original positive diagnoses. Observer A added four cases, Observer B 11 cases to the positive category. Cell types of original positive cytologic diagnoses and those of subsequent histologic diagnoses agreed for 23 of 33 malignancies (70%). Although two observers increased the proportion of positive cytologic diagnoses, the percentages of agreement with respect to histologic malignant cell types remained similar. For cytologic specimens, intraobserver agreement as to malignant cell types was 83% (50 of 60); interobserver agreement was 80% (48 of 60).

Cytologic diagnosis of giant cell tumor of bone metastatic to lung. A case report.

An unusual case of giant cell tumor of bone metastasized to the right lung and was diagnosed by percutaneous transthoracic needle aspiration biopsy.

Squamous cell dysplasia and carcinoma in situ of the cervix and vagina after prenatal exposure to diethylstilbestrol.

Squamous cell abnormalities of the vagina and cervix were evaluated in 1424 women exposed to diethylstilbestrol (DES) in utero. The prevalence of dysplasia was 2.1% and the incidence 0.85/100 person-years of followup. The dysplastic epithelial changes were almost always mild in women with no prior history of dysplasia and was slightly more frequent in the cervix than the vagina. Severe dysplasia and carcinoma in situ (CIS) were encountered only in those subjects specifically referred because of those abnormalities. The most common problem in the diagnosis of these squamous cell changes was the misinterpretation of mature and immature metaplastic cells for dysplastic squamous cells. Discordance between biopsy and cytology was common-place in the detection and followup of dysplasia, especially when it was mild. There were no instances in the study where cytology and biopsy samples from the vagina were both abnormal concurrently. Colposcopically directed biopsies did not increase the frequency of confirmation of cytologic findings. These data suggest that both cytology and biopsy of abnormal segments of the vagina and cervix remain an integral part of the examination of the DES-exposed female during long-term follow-up studies.