Pulmonary alveolar proteinosis: a spectrum of cytologic, histochemical, and ultrastructural findings in bronchoalveolar lavage fluid.

Pulmonary alveolar proteinosis (PAP) is defined as abundant extracellular proteinaceous periodic acid-Schiff (PAS)-positive material which represents surfactant distending alveolar spaces. While this lesion is defined by histologic findings, there are characteristic radiologic features and cytologic findings in bronchoalveolar lavage (BAL) specimens that together may provide a confident diagnosis. The BAL specimens from all patients for which a diagnosis of PAP was made or suggested on either cytologic or biopsy specimens at University of North Carolina Hospitals from 1990-1999 were reviewed. There were 23 cytologic specimens from 11 patients. Patient ages ranged from 6 wk to 76 yr. All 23 specimens had slides prepared for Papanicolaou stain, 22 specimens (all patients) had Diff-Quik stains, 10 specimens (6 patients) had PAS stains, and 8 specimens (5 patients) had lipid stains. Nine patients had lung biopsies in addition to cytologic specimens. The clinical charts of all patients were reviewed. Twenty-one cytologic specimens were described as cloudy or milky, and 2 were bloody. By chart review and/or biopsy results, 8 patients were felt to have definite PAP. The initial lavage specimens from 6 of these patients showed classic cytologic findings of PAP, consisting of paucicellular specimens dominated by adundant extracellular granular to globular material which was basophilic on Diff-Quik stain, pale to focally eosinophilic on Pap stain, and PAS-positive, diastase-resistant. Five of these patients had biopsies; 3 showed PAP, and 2 were insufficient. Later BAL specimens after therapeutic lavage from these patients were often less characteristic, with scant extracellular material present. The other 2 patients with PAP clinically and by biopsy had atypical cytologic findings, with one showing numerous macrophages with scant PAS-positive material and abundant lipid mimicking lipid pneumonia, and one showing moderate eosinophils in addition to the extracellular proteinacous material. The remaining 3 patients were felt not to have PAP clinically or by biopsy (1 lymphocytic interstitial pneumonitis, 1 rheumatoid lung, and 1 hemosiderosis), and their BAL specimens predominantly contained macrophages with rare proteinaceous extracellular globules. Electron microscopy was performed in 5 patients (4 considered to have PAP, and 1 with lymphocytic interstitial pneumonitis) and in all cases showed whorled myelin figures characteristic of surfactant. The PAP cases and the non-PAP case had identical ultrastructural findings. We conclude that BAL specimens with classic cytologic features and supporting clinical and radiographic evidence may be diagnosed as PAP. Atypical specimens should be approached with caution, and may represent either PAP or other pulmonary diseases with secondary accumulation of surfactant. Cytology specimens taken subsequent to therapeutic lavage from PAP patients may also not be diagnostic.

A clinical study of hypoxia and metallothionein protein expression in squamous cell carcinomas.

The objective was to discover whether the oxygen-regulated protein, metallothionein, is expressed in the hypoxic cells of squamous cell carcinomas. Twenty patients with squamous cell carcinoma of the uterine cervix or head and neck were infused with a solution of the hypoxia marker, pimonidazole hydrochloride, at a dose of 0.5 g/m2. The following day, biopsies were collected, formalin fixed, paraffin embedded, and sectioned at 4 microm. Sections from each biopsy were immunostained for pimonidazole binding, metallothioneins I and II, involucrin, and proliferating cell nuclear antigen. A total of 84 biopsies were analyzed. Sixty-four of 84 biopsy sections contained hypoxia. Of the hypoxia-containing sections, 43 of 64 or 67% showed no microregional overlap between hypoxia and metallothionein; 7 of 64 showed overlap; and 14 of 64 showed a combination of overlap and no overlap. On a tumor-by-tumor basis, 5 of 7 head and neck and 7 of 13 cervix tumors showed no overlap between metallothionein and hypoxia at the microregional level. Ranges for the percentage of the area of hypoxia in head and neck (<0.9 to 17%) and cervix (<0.1 to 14%) tumors were similar. In the hypoxia-containing sections, immunostaining for involucrin, a molecular marker for differentiation, overlapped with that for hypoxia in 82% of the cases. The majority of hypoxic cells in squamous cell carcinomas do not express metallothionein protein, although metallothionein is induced by hypoxia in human tumor cells in vitro. Hypoxic cells in human tumors tend to be in regions immunostaining for involucrin, and it seems possible that differentiation of hypoxic cells in squamous cell carcinomas might affect metallothionein I and II expression.

Vaginal adenosarcoma arising from endometriosis.

OBJECTIVE: Malignant transformation of endometriosis has been well documented. Endometrioid adenocarcinoma is the most common malignancy to occur in this setting, although other carcinomas and rarely stromal tumors can be seen. We present the first case in the literature of adenosarcoma, a rare mixed mullerian or mesodermal tumor, arising in extrauterine vaginal endometriosis. CASE: A 42-year-old woman underwent multiple medical therapies and surgeries for aggressive endometriosis. A pelvic exenteration was abandoned secondary to severe fibrosis, and low-dose radiotherapy was used to control bleeding from vaginal endometriosis. The pathologic diagnosis of recurrent endometriosis was confirmed multiple times over her 4-year course. Excision of a recurrent vaginal mass revealed adenosarcoma with heterologous elements. CONCLUSION: It is important to biopsy or excise recurrent endometriosis, as malignant transformation can occur, giving rise to epithelial, stromal, or mixed epithelial-mesenchymal tumors.

Changes in connexin 43 protein expression in human endometrial carcinoma.

The expression of connexin 43 was studied using immunohistochemical and Western blot analyses on cell lines of endometrial epithelial origin. Connexin proteins were examined because decreases in their expression and function have been correlated with carcinogenesis. The cell lines were chosen to represent increasing grades of endometrial cancer progression starting from FEEC (fetal endometrial epithelial cells; transformed with SV40 large T antigen) to HEC-1A (stage 1A endometrial carcinoma) to RL-95-2 (grade 2 endometrial carcinoma). Parallel studies using connexin 43 polyclonal antibodies for both Western blots and immunofluorescence showed that the levels of connexin 43 expression were normal endometrial stromal cells = FEEC > HEC-1A > RL-95-2. Consequently, we applied the immunofluorescence assay to analyze paraffin-embedded uterine sections from hysterectomy specimens of patients with normal endometrium and from patients diagnosed with grade 1, 2, and 3 endometrial cancer. Using five different cases from each category, we found an inverse correlation between connexin 43 expression and tumor grade. Our data indicate that connexin 43 expression may be useful as an adjunctive marker of progression for endometrial carcinoma.

Predictors of recurrent dysplasia after a cervical loop electrocautery excision procedure for CIN-3: a study of margin, endocervical gland, and quadrant involvement.

Loop electrocautery excision procedure (LEEP) increasingly is being used for the treatment of cervical intraepithelial neoplasia (CIN). Few published studies address the possible correlation between the histologic findings of the LEEP cone biopsy and the incidence of residual/recurrent dysplasia We identified 248 patients with CIN-3 treated by LEEP at the University of North Carolina from September 1991 through September 1996. Computerized files of these patients were then reviewed through August 1997 for pathology follow-up results. Two hundred patients had pathology follow-up and interpretable material. LEEP cone slides were reviewed to confirm CIN-3 and to assess involvement of margins, endocervical glands, and multiple quadrants. Cytologic and histologic follow-up data were categorized as negative or positive, with the latter including high-grade squamous intraepithelial lesions, low-grade squamous intraepithelial lesions, and atypical squamous cells of undetermined significance. Fifty-five patients (27.5%) had residual/recurrent dysplasia, including 36 high-grade squamous intraepithelial lesions (66%), 14 low-grade squamous intraepithelial lesions (25%), and 5 atypical squamous cells of undetermined significance (9%). Greater recurrence rates were noted for cases with high-grade dysplasia involving margins (39% positive vs. 15% negative; P = .0001), endocervical glands (33% positive vs. 14% negative; P = .0044), and multiple quadrants (33% multiple vs. 14% single; P = .0036). In cases with negative margins, greater recurrence rates were still observed with high-grade dysplasia involving endocervical glands (20% positive vs. 9% negative; P = .0808) and multiple quadrants (20% multiple vs. 8% single; P = .0495). Positive margins, positive glands, and multiple quadrant disease are all predictors of residual/recurrent dysplasia after LEEP. Surgical pathology reports for LEEP cone biopsy specimens should include information on the presence of high-grade dysplasia involving margins, endocervical glands, and multiple quadrants. Continued close follow-up is especially warranted for patients whose LEEP cone biopsy specimens contain any of these histologic predictors of residual/recurrent dysplasia.

Effect of exogenous gonadotropins on endometrial maturation in oocyte donors.

OBJECTIVE: To determine the effects of controlled ovarian hyperstimulation (COH) on endometrial maturation. DESIGN: Prospective, before and after evaluation of midluteal endometrial biopsies in oocyte donor's spontaneous and subsequent COH cycles. SETTING: Tertiary academic medical center assisted reproductive technologies clinic. PATIENT(S): Nineteen oocyte donors. INTERVENTION(S): Exogenous gonadotropins, endometrial biopsies. MAIN OUTCOME MEASURE(S): Endometrial histology and an immunohistochemical marker of uterine receptivity, the alphavbeta3 vitronectin. RESULT(S): Glandular and stromal dyssynchrony was more common after COH in 16 (80%) of 20 cycles than 6 (30%) of 20 spontaneous cycles (P <.05). Glandular lag was more frequent in COH cycles and unaffected by progesterone administration. The beta3 subunit of the alphavbeta3 vitronectin receptor was present in 9 (45%) of 20 spontaneous and 2 (10%) of 20 COH cycles (P <.05). CONCLUSION(S): Exogenous gonadotropin use in healthy reproductive age women did not result in endometrial evidence of a luteal phase defect. A greater incidence of glandular-stromal dyssynchrony resulted from the use of exogenous gonadotropins. The presence of alphavbeta3 was noted in most endometrial specimens demonstrating in phase glandular maturation. We conclude that endometrial dyssynchrony that results from delayed glandular development most likely represents a normal histologic variant.

Pimonidazole: a novel hypoxia marker for complementary study of tumor hypoxia and cell proliferation in cervical carcinoma.

BACKGROUND: Tumor hypoxia may be associated with treatment resistance, cell proliferation, and metastatic potential, which contribute to poor prognosis. Complementary techniques for detecting hypoxia, cell growth, and metastases are required to study these relationships. OBJECTIVES: The purpose of this study was to demonstrate the clinical feasibility of quantitative hypoxia detection with pimonidazole, a novel hypoxia marker, and to correlate hypoxia with S-phase markers of tumor proliferation. METHODS: Pimonidazole binds to thiol-containing proteins specifically in hypoxic cells. Ten patients with cervical carcinoma received 0.5 g/m2 pimonidazole intravenously followed by biopsy of the cervical carcinoma the next day. Hypoxic cells were recognized by immunohistochemical detection of pimonidazole using a mouse monoclonal antibody. Cell proliferation was detected with a commercially available monoclonal antibody for proliferating cell nuclear antigen (PCNA). Assessment of hypoxia and cell proliferation was made qualitatively with light microscopy and quantitatively using point counting and image analysis software methods. RESULTS: No clinical toxic effects were associated with pimonidazole administration. Immunostaining with pimonidazole antibody was observed in 9 of 10 tumors, suggesting that hypoxia is a common occurrence in cervical carcinoma. Quantitatively, tumors that had large numbers of hypoxic cells had the greatest percentage of S-phase cells, but some tumors with smaller amounts of hypoxia also had substantial numbers of S-phase cells. CONCLUSION: Pimonidazole can be used for qualitative and quantitative assessment of tumor hypoxia.

Hypoxia and vascular endothelial growth factor expression in human squamous cell carcinomas using pimonidazole as a hypoxia marker.

Hypoxia in human tumors is associated with poor prognosis, but the molecular mechanisms underlying this association are poorly understood. One possibility is that hypoxia is linked to malignant progression through vascular endothelial growth factor (VEGF) induction and the associated angiogenesis and metastasis. The present clinical study measures hypoxia and VEGF expression on a cell-by-cell basis in human squamous cell carcinomas to test the hypothesis that hypoxia and VEGF protein expression are coupled in human tumors. Eighteen patients with invasive squamous cell carcinoma of the uterine cervix and head and neck have been investigated by a quantitative image analysis of immunostained sections from their tumors. The hypoxia marker pimonidazole was used to measure tumor hypoxia, and a commercially available antibody was used to measure VEGF protein expression. A quantitative immunohistochemical comparison of hypoxia and VEGF protein expression revealed no correlation between the two factors.

Teaching cytopathology in the undergraduate medical school curriculum: the experience at the University of North Carolina.

A formal instructional unit in cytopathology in the 2nd-year medical school pathology course at the University of North Carolina is described. This unit was added to the traditional mechanisms and organ systems instruction in the pathology course to increase the exposure of students to modern diagnostic techniques and informed use of laboratory testing. The unit is presented at the end of the pathology course as a summation of organ systems pathology and an introduction to the clinical practice of one branch of pathology. Two lectures cover the general principles of cytopathology, specimen procurement and adequacy, cytologic findings of common lesions in three organ systems (female genital tract, lung, and breast), specialized techniques, clinical advantages and disadvantages of cytologic techniques, and accuracy. Clinical correlation and appropriateness of testing are stressed. An accompanying laboratory session includes examination of glass slides predominantly prepared from surgical specimens and discussion of clinical cases with experienced cytologists using Kodachrome illustrations of cytologic slides and subsequent histologic and clinical follow-up. Our experience to date suggests that this unit informs students about the role of cytology in modern medical practice and helps to bridge the gap between the basic science of pathology and clinical medicine.

Villoglandular adenocarcinoma of the cervix: cytologic presentation.

Villoglandular adenocarcinoma of the uterine cervix is a recently described neoplasm which occurs primarily in young women and has an excellent prognosis. In many instances, these lesions may be treated conservatively with cervical conization rather than hysterectomy, a therapeutic option of particular importance for young women who wish to preserve reproductive capability. This paper describes the cytologic findings on cervical smears from three women with villoglandular adenocarcinoma, two treated conservatively with cervical conization and one managed with hysterectomy. Characteristic cytologic features in these cases included the presence of long villous fronds and papillae lined by columnar cells with intact cytoplasmic borders and minimal to moderate cytologic atypia. Also noted were strips and three-dimensional ball-like clusters of cells with smooth, intact communal cytoplasmic rims. Apoptotic bodies and scattered mitoses were observed. Recognition of the above features warrants inclusion of this entity in the cytologic differential diagnosis, with conservative histologic follow-up prior to more radical therapeutic measures.

Desmoid tumor of the vulva associated with pregnancy.

Extra-abdominal desmoid tumor is a locally aggressive neoplasm that occurs most commonly in the pelvic or shoulder region in the third or fourth decade. We have identified one previously reported case of primary desmoid tumor of the vulva. Herein, we describe another case and, to our knowledge, the first reported case of vulvar desmoid tumor associated with pregnancy.

Recurrent alveolar proteinosis following double lung transplantation.

We present a case of recurrent alveolar proteinosis following double lung transplantation.

Proliferation and hypoxia in human squamous cell carcinoma of the cervix: first report of combined immunohistochemical assays.

PURPOSE: To characterize the distribution of hypoxia and proliferation in human squamous cell carcinoma of the cervix via an immunohistochemical approach prior to initiation of therapy. METHODS AND MATERIALS: Patients with primary squamous cell carcinoma of the cervix uteri received a single infusion of the 2-nitroimidazole, pimonidazole (0.5 g/m2 i.v.), and 24 h later punch biopsies of the primary tumor were taken. Tissue was formalin fixed, paraffin embedded, and sectioned for immunohistochemistry. Hypoxia was detected by monoclonal antibody binding to adducts of reductively activated pimonidazole in malignant cells. Staining for endogenous MIB-1 and PCNA was detected in tumor cells via commercially available monoclonal antibodies. Point counting was used to quantitate the fraction of tumor cells immunostained for MIB-1, PCNA, and hypoxia marker binding. RESULTS: Immunostaining for pimonidazole binding was distant from blood vessels. There was no staining in necrotic regions, and only minimal nonspecific staining, mostly in keratin. In general, cells immunostaining for MIB-1 and PCNA did not immunostain for pimonidazole binding. Cells immunostaining for MIB-1 and PCNA showed no obvious geographic predilection such as proximity to vasculature. Quantitative comparison showed an inverse relationship between hypoxia marker binding and proliferation. CONCLUSIONS: Immunohistochemical staining for pimonidazole binding is consistent with the presence of hypoxic cells in human tumors and may be useful for estimating tumor hypoxia prior to radiation therapy. Immunostaining for pimonidazole binding is an ideal complement to immunohistochemical assays for endogenous proliferation markers allowing for comparisons of tumor hypoxia with other physiological parameters. These parameters might be used to select patients for radiation protocols specifically designed to offset the negative impact of hypoxia and/or proliferation on therapy. The inverse relationship between pimonidazole binding and proliferation markers is a preliminary result requiring verification.

Are epithelial cells in fat or connective tissue a reliable indicator of tumor invasion in fine-needle aspiration of the breast?

The diagnosis of breast carcinoma tumor invasion by fine-needle aspiration (FNA) cytology continues to be controversial. To assess the reliability of predicting tumor invasion by FNA, we examined the cytologic smears of 183 FNAs of benign and malignant solid epithelial lesions of the breast for which histologic follow-up was available. The study group consisted of 94 invasive carcinomas, eight pure ductal carcinomas in situ (DCIS), and 81 benign lesions (fibroadenoma, fibrocystic changes, papilloma, adenosis). Epithelial cellularity, presence of epithelial cells in dispersed fat droplets and presence of epithelium within intact fragments of fibrofatty connective tissue were tabulated. Epithelial cellularity in dispersed fat was semiquantitatively scored. The cytologic diagnosis of the epithelial cells in all cases was recorded as benign, malignant, or indeterminant for malignancy. Findings showed that 95.5% of invasive carcinomas, 100% of DCIS, and 68.1% of benign lesions contained epithelial cells in dispersed fat; 80.8% of invasive carcinomas, 66.7% of DCIS, and 60.7% of benign lesions contained epithelial cells in intact fibrofatty connective tissue. Corrected score of epithelium within fat was 0.781 for invasive carcinoma, 0.727 for DCIS, and 0.562 for benign lesions. The difference in values for all parameters was not statistically significant between invasive carcinoma and DCIS, but reached significance between invasive carcinoma and benign lesions. Eighteen cases (7/94 invasive carcinomas, 5/8 DCIS, 6/81 benign lesions) contained atypical epithelial cells indeterminant for malignancy, all of which had epithelial cells present in dispersed fat when dispersed fat was present on the slides, indicating that this criterion was not helpful in discriminating between a benign and malignant diagnosis. We conclude that the presence of epithelial cells either admixed within dispersed fatty droplets or seemingly within fragments of fibrofatty connective tissue is not a reliable indicator of tumor invasion in FNA of the breast, and is frequently found in both benign and malignant breast lesions. The presence of epithelial cells in intact or dispersed fat is most likely a mechanical artifact of aspiration and/or smear preparation.

Quantitative DNA analysis of fresh solid tumors by flow and image cytometric methods: a comparison using the Roche Pathology Workstation Image Analyzer.

The clinical utility of DNA ploidy and cell cycle parameters as prognostic indicators has been demonstrated for selected malignant tumors. Previous quantitative DNA analysis studies have used various tumor sample preparation methods and analyzers. We undertook a pilot study to compare the results of DNA analysis of fresh solid tumors by flow cytometry with the new Roche Pathology Workstation Image Analyzer. Flow cytometric DNA analysis was done on cell suspensions of fine needle aspirates from fresh tumor specimens and analyzed for ploidy and cell cycle statistics with a Becton-Dickinson FACScan Analyzer, using a rectangular model. Small aliquots from these same aspirates were prepared as direct cytologic smears and Feulgen stained for DNA analysis with the Roche Image Analyzer. Additional smears were stained with Diff-Quik for morphologic correlation with DNA histograms. The study group consisted of 40 malignant neoplasms. There was a high correlation between the flow and image DNA indices (R = 0.93, slope = 1.0036, P < 0.001) but a weaker relationship between the flow and image estimated S-phase fractions (R = 0.57, slope = 0.5401, P < 0.01). DNA ploidy categorization for the two methods was concordant in 30 (75%) cases, discordant in seven (17.5%) cases, and equivocal in three (7.5%) cases. In our experience, quantitative DNA analysis of fresh tumor aspirates by flow and image cytometric methods yielded comparable and/or complementary results, with each method having certain advantages and disadvantages. Proposed reasons for false and true discordances and an approach for evaluation are discussed.

Evaluation of cathepsin D and epidermal growth factor receptor in prostate carcinoma.

Differential reactivity for cathepsin D (cath-D) and epidermal growth factor receptor (EGFR) was compared in 102 archival cases of human primary prostatic carcinoma and nine prostate carcinoma metastases by immunohistochemical techniques using commercially available antibodies (Ciba-Corning, Triton Diagnostics Division, Alameda, CA). Western immunoblotting confirmed that the anti-cath-D and anti-EGFR antibodies recognized the appropriate-sized proteins in extracts of human prostatic carcinoma cell lines. For immunohistochemical analysis, the primary prostate carcinomas ranged from Gleason's combined scores of 2 to 9. High-grade prostatic intraepithelial neoplasia was coexistent in 79 of the cases. Immunohistochemical staining was scored by summing the intensity of staining (0 to 3+) weighted by the percentage of tumor staining at each intensity (H score, theoretical range 0 to 300). Heterogenous moderate to strong reactivity with anti-cath-D was detected in 96 of 102 cases of primary prostate carcinoma (94%), with a mean H score of 176.5. EGFR reactivity was much less common and less strong, with 41 of 102 primary prostate carcinomas staining (40%) at a mean H score intensity of 29.2. The immunohistochemical (H) scores of cath-D and EGFR reactivity both significantly correlated with the Gleason's combined score of the tumors. There was no significant correlation between the cath-D and EGFR scores. Ninety-nine percent of the examples of prostatic intraepithelial neoplasia were reactive with anti-cath-D, with no clear correlation between the intensity of staining of prostatic intraepithelial neoplasia and the adjacent carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Human alveolar macrophage-56 and carcinoembryonic antigen monoclonal antibodies in the differential diagnosis between primary ovarian and metastatic gastrointestinal carcinomas.

The immunohistochemical expression and localization of monoclonal antibodies to carcinoembryonic antigen (CEA) and human alveolar macrophage (HAM-56) were evaluated in primary ovarian and metastatic gastrointestinal (GI) carcinomas. Immunohistochemistry was performed using an avidin-biotin-peroxidase complex method with capillary gap technology on formalin-fixed, paraffin-embedded tissues from 41 primary ovarian epithelial neoplasms, 17 metastatic gastrointestinal malignancies, and 10 tumors of uncertain primary origin. Overall, immunostaining for HAM-56 was positive in 35 (85%) ovarian epithelial neoplasms compared with only two (12%) gastrointestinal cancers. Carcinoembryonic antigen was positive in 16 (39%) ovarian versus 13 (76%) GI tumors. Of the primary ovarian neoplasms, 22 were positive for HAM-56 only, 13 were positive for both HAM-56 and CEA, three were positive for CEA only (all mucinous neoplasms), and three were negative for both. Of the primary GI neoplasms, 12 were positive for CEA only (including all eight colon cancers), one was positive for both HAM-56 and CEA, one was positive for HAM-56 only, and three were negative for both. Of the 10 neoplasms of unknown origin at initial presentation, six were positive for HAM-56 only, three were positive for CEA only, none was positive for both HAM-56 and CEA, and one was negative for both. Only three of these 10 neoplasms remained of indeterminate origin after pathological review and clinical follow-up. When positive, CEA was usually strong and generalized in GI cancers but weak and focal in ovarian neoplasms. The HAM-56 positivity in ovarian neoplasms was typically focal and largely limited to areas with glandular or papillary differentiation with apical linear accentuation. We conclude that an immunohistochemical panel using both HAM-56 (Enzo Diagnostics, Syosset, NY) and CEA monoclonal antibodies is helpful in differentiating primary ovarian neoplasms from metastatic gastrointestinal malignancies, and in evaluating metastatic adenocarcinoma of unknown primary site.

Primary adenocarcinoma of the gallbladder presenting as primary gynecologic malignancy: a report of two cases.

BACKGROUND: Carcinoma metastatic to the uterus from extragenital sites is rare. Such metastatic disease is typically diagnosed at autopsy or in patients with known primary malignancies. This report discusses two cases of primary carcinoma of the gallbladder presenting as abnormalities in gynecologic screening procedures. CASES: A 71-year-old woman presented with postmenopausal bleeding. Uterine curettage revealed poorly differentiated adenocarcinoma of presumed endometrial origin. Intraoperative frozen-section analysis of the uterus showed carcinoma involving the lymphatics, but no primary tumor. Further exploration revealed primary adenocarcinoma of the gallbladder, with widespread metastases. The second case was a 67-year-old asymptomatic woman. Routine cervical cytology showed adenocarcinoma, but tissue studies were negative. She developed jaundice 1 month later. Computed tomography of the upper abdomen revealed a mass in the gallbladder fossa, and needle biopsy of the lesion showed adenocarcinoma. CONCLUSIONS: Metastatic carcinoma of non-genital tract origin may present as primary gynecologic malignancy. The physician should be aware of the implications of both the common and unusual interpretations of screening and diagnostic procedures. When the clinicopathologic presentation is atypical, a thorough knowledge of the differential diagnoses of abnormal test results allows appropriate and expeditious patient management.

Pelvic granulomata mimicking endometriosis following the administration of oil-based contrast media for hysterosalpingography.

BACKGROUND: Hysterosalpingography is used commonly in the evaluation of infertility and in the diagnosis of anomalies of the uterus and fallopian tubes. There is continued debate over the safety and diagnostic or therapeutic efficacy of water-soluble versus oil-based contrast media. CASE: A 29-year-old woman with secondary infertility underwent hysterosalpingography with both water-soluble and oil-based contrast. The fallopian tubes appeared normal. Six months later, a plain abdominal radiograph obtained at the occasion of a minor motor vehicle accident revealed evidence of retained loculated pelvic contrast material. Subsequent laparoscopy identified adhesions and cul-de-sac implants strongly suspicious for endometriosis. Biopsy and pathologic study documented lipogranuloma. CONCLUSION: Oil-based contrast media instilled into the pelvis at hysterosalpingography can persist for prolonged periods and create granulomatous lesions mimicking endometriosis. In view of the controversy whether oil-based contrast materials are superior to water-soluble media, the routine use of oil-based contrast media should be considered carefully.

Subclassification of benign breast disease by fine needle aspiration cytology. Comparison of cytologic and histologic findings in 265 palpable breast masses.

The cytologic and histologic features of 265 benign breast masses were analyzed in order to examine the ability of fine needle aspiration cytology to accurately subclassify benign breast lesions. Two hundred two of the masses were pure histologic examples of benign breast lesions (72 nonproliferative fibrocystic change, 27 proliferative fibrocystic change, 65 fibroadenoma, 12 abscess, 8 fat necrosis, 7 papilloma, 7 duct ectasia, 2 tubular adenoma, 1 sclerosing adenosis, 1 microglandular adenosis), and 63 masses were mixed lesions. Part I of the study consisted of retrospective comparison of the original cytologic diagnoses with the histologic diagnoses. A nonspecific descriptive diagnosis had been rendered in 135 of 265 (51%) cases, and these descriptive diagnoses corresponded to fibrocystic change in the majority of cases (70%). A specific benign cytologic diagnosis had been made in 130 of 265 (49%) cases, and overall the specific diagnosis was correct in 80% of cases. Part II of the study consisted of the semiquantitative scoring of the cytologic findings of the 202 pure examples of benign breast masses and statistical analysis of differences in the expression of cytologic features between the different types of lesions. Overall cellularity, amount of bipolar stripped nuclei, amount and architectural arrangement of epithelium, epithelial atypia/pleomorphism/nuclear overlapping and amount of apocrine metaplasia, foam cells and stroma were the cytologic parameters that were statistically significant (P < .05) in distinguishing between the cases of fibroadenoma, abscess, papilloma, fat necrosis, duct ectasia and fibrocystic change as a group. No cytologic parameter reached statistical significance in distinguishing between proliferative and nonproliferative fibrocystic change. We conclude that the majority of benign breast lesions yield characteristic cytologic findings that allow their subclassification when sufficiently sampled by fine needle aspiration. The distinction between proliferative and nonproliferative fibrocystic change is less reliable, and cytologic differences observed within this spectrum did not reach statistical significance.