Primary pulmonary lymphangiectasia in infancy and childhood.

Primary pulmonary lymphangiectasia (PPL) is a rare disorder of unknown aetiology characterised by dilatation of the pulmonary lymphatics. PPL is widely reported to have a poor prognosis in the neonatal period and little is known about the clinical features of patients who survive the newborn period. The current authors report the outcome in nine patients diagnosed in infancy with PPL over a 15-yr period at a single university-based hospital clinic and followed for a median of 6 yrs. Although all of the patients initially experienced respiratory distress, respiratory symptoms improved in most patients after infancy and were notably better by the age of 6 yrs. Many patients had poor weight gain in the first years of life, which eventually improved. Radiological scans showed progressive resolution of neonatal infiltrates, but were characterised by hyperinflation and increased interstitial markings in older children. Most patients had evidence of bronchitis and grew pathogenic organisms from quantitative bronchoalveolar lavage culture. Pulmonary function tests showed predominantly obstructive disease that did not deteriorate over time. In conclusion, these results suggest that primary pulmonary lymphangiectasia does not have as dismal a prognosis as previously described and symptoms and clinical findings improve after the first year of life.

Comparison of clinical and pathological features in African-American and Caucasian patients with localized prostate cancer.

OBJECTIVE: To examine patient characteristics, prostate specific antigen (PSA) levels, and established preoperative and pathological prognostic factors to determine differences between Caucasian and African-American patients with localised prostate cancer, as it remains controversial whether African-American men present with more aggressive disease. PATIENTS AND METHODS: One hundred consecutive patients (aged 53-76 years) undergoing radical retropubic prostatectomy (RRP) at an equal-access tertiary-care centre were retrospectively reviewed. All patients had preoperative PSA levels, a physical examination (including clinical staging), and sextant biopsy. Insurance information was also collected. The same urological oncologist determined clinical staging and performed all the RRPs, and the same genitourinary pathologist determined the Gleason grade for biopsies and surgical specimens, pathological stage, percentage of tumour involvement, and specimen weight. African-American and Caucasian patients were compared for PSA, clinical stage, pathological stage, biopsy and pathological Gleason grade, organ confinement, margin status and specimen weight. Using preoperative and pathological data, both groups were also compared for over- and under-staging and -grading. The Wilcoxon rank test with P < 0.05 was used to determine statistically significant differences. RESULTS: African-American patients were more likely to be Medicaid or self-insured than Caucasian patients. Age, biopsy grade and clinical stage were not significantly different between the groups. African-American patients presented with a mean PSA level of 11.9 ng/mL and Caucasians with a mean of 8.5 ng/mL (P = 0.03). When clinical and biopsy data were compared with pathological data there were no differences between the groups in under/over-grading or under/over-staging. African-American patients had larger prostates per surgical specimen than their Caucasian counterparts (59.3 g vs 51.6 g, respectively; P = 0.04). CONCLUSIONS: In a referred, equal-access system, African-American patients presented with higher serum PSA levels and had larger prostates in the surgical specimen. However, African-American patients did not present at an earlier age or with higher Gleason grade or clinical stage, nor were pathological grade and stages higher. Other pathological features were no different. African-American patients were not under- or over-staged or under- or over-graded more than their Caucasian counterparts. This retrospective study does not suggest that African-American men present with more aggressive disease.

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.

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.

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.

Pulmonary clear cell carcinoid tumor: another entity in the differential diagnosis of pulmonary clear cell neoplasia.

A clear cell variant of primary pulmonary carcinoid tumor is described. The tumor arose in a 53-year-old woman who was incidentally found to have a solitary pulmonary nodule in the left upper lobe during routine chest roentgenography. Histologically, the tumor was composed of predominantly clear to lightly eosinophilic, polygonal cells with bland nuclei arranged in sheets and nests. Nuclear pleomorphism, necrosis, vascular invasion, and mitotic figures were not seen. The tumor cells were negative for oil-red-O and periodic acid-Schiff stains with and without diastase pretreatment on frozen and formalin-fixed sections, respectively. During immunohistochemical evaluation, the tumor cells were focally positive for cytokeratin and diffusely positive for neuron-specific enolase and chromogranin. Electron microscopy performed on paraffin block-retrieved tissue showed the presence of electron-dense, neurosecretory-type granules and variably sized vacuolated areas within the cytoplasm. the nature of which remained unclear. Intracytoplasmic glycogen or lipid were not identified. To our knowledge, this is the first report of pulmonary clear cell carcinoid tumor.

Downregulation of the beta4 integrin subunit in prostatic carcinoma and prostatic intraepithelial neoplasia.

Integrins are adhesion receptors thought to be important in the process of cancer cell invasion and metastasis. Unlike other integrins, which attach a cell to extracellular matrix molecules, the alpha6beta4 integrin participates in the formation of hemidesmosomes, attaching epithelial cells to the basement membrane. Investigations of the alpha6beta4 integrin in human prostatic carcinoma have yielded conflicting results and have been primarily qualitative rather than quantitative. Expression of the beta4 integrin subunit was determined using rat monoclonal antibody 439-9B and image analysis in regions of benign prostatic epithelium (BPE), high-grade prostatic intraepithelial neoplasia (PIN), and prostatic carcinoma (CaP) in 38 patients treated by radical prostatectomy for clinically localized CaP. The beta4 integrin subunit was significantly downregulated in CaP compared with BPE; PIN stained intermediate in intensity between BPE and CaP. Thirty-four of 35 patients showed downregulation of the beta4 integrin subunit, and all 15 patients with PIN had downregulation of beta4 in PIN as compared with BPE. Degree of downregulation of the beta4 integrin subunit did not add prognostic significance to the information present at initial biopsy (age, clinical stage, clinical grade, and serum prostate-specific antigen level). There was no correlation between intensity of staining of CaP, absolute change in staining, or percent loss of beta4 integrin subunit staining with age, pathological stage, or Gleason's score. Downregulation of the beta4 integrin in CaP and PIN compared with BPE may be correlated with neoplastic transformation of the prostate and loss of hemidesmosomes or basal epithelial cells.

Metastatic sublines of an SV40 large T antigen immortalized human prostate epithelial cell line.

BACKGROUND: The available human prostate cancer cell lines that are metastatic in athymic nude mice all have complex, highly aneuploid karyotypes. Other prostatic cells immortalized by transforming genes of SV40 or HPV and converted to tumorigenicity by additional genetic manipulation are not reported to be metastatic. METHODS: Tumorigenic sublines of human prostate epithelial cells previously immortalized by transfection with the SV40T antigen gene were obtained by sequential passage in male athymic nude mice. These sublines were evaluated histopathologically for tumorigenicity and metastasis in athymic nude mice after subcutaneous, intraperitoneal, and intraprostatic injection. Each subline was characterized by standard (GTG-banding) cytogenetic and FISH analysis, and RNase protection assays for androgen receptor expression. RESULTS: Two sublines produced metastases in lungs and the diaphragm of most mice after either intraprostatic or intraperitoneal injection. The M2205 subline formed large local tumors after intraprostatic injection. Cytogenetic aberrations present in the metastatic sublines, but not in the tumorigenic, nonmetastatic lines or the parental P69SV40T line, included dup(11)(q14q22), der(16) t (16;19) (q24;q13.1), which resulted in the loss of the short arm and proximal long arm of chromosome 19 (19q13.1-->19pter), and loss of the Y chromosome. None of the sublines expressed the androgen receptor. CONCLUSIONS: These cytogenetically defined, SV40T-immortalized human prostate epithelial cell lines, with distinct biological behaviors in vivo, provide additional tools for the genetic analysis of the emergence of metastatic capacity.

Malpractice in gynecologic cytology: a need for expert witness guidelines.

The malpractice claims activity in anatomic pathology has sharply increased in recent years. On a relative and absolute basis, a leading area of increase for claims is cervicovaginal (Pap smear) cytology. As never before, pathologists are faced with the threat of litigation and acting as defendants in medical-legal actions. Defending claims of malpractice in Pap smear litigation can be difficult. The expert witness for the plaintiff often performs a selective retrospective review of the Pap smear of the plaintiff, compared with the screening examination performed by the defendant. In addition, it is unclear whether atypical or dysplastic cells are within the standard of practice and should be discovered by the Pap smear screener. A proposal for a forum to develop guidelines for expert witness testimony in Pap smear cytology is discussed.

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.

Cathepsin D and epidermal growth factor receptor immunohistochemistry does not predict recurrence of prostate cancer in patients undergoing radical prostatectomy.

PURPOSE: We determined if immunohistochemical expression of the epidermal growth factor receptor and cathepsin D in the primary tumor was of prognostic value in clinically localized prostate cancer after radical prostatectomy. MATERIALS AND METHODS: Immunohistochemical staining for epidermal growth factor receptor and cathepsin D was performed on 105 radical prostatectomy specimens from 2 academic centers. The epidermal growth factor receptor and cathepsin D expressions were graded using H scoring by an experienced pathologist blinded to other patient data, and compared with age, grade, stage, race and initial serologic (prostate specific antigen) recurrence. Univariate and multivariate statistical testing was performed. RESULTS: Immunohistochemically detectable epidermal growth factor receptor and cathepsin D expression was not correlated to age, race, stage or Gleason grade. In univariate and multivariate testing epidermal growth factor receptor and cathepsin D were not prognostic markers for disease progression following radical prostatectomy. CONCLUSIONS: Immunohistochemical analysis of the biomarkers cathepsin D and epidermal growth factor receptor in radical prostatectomy specimens does not predict disease recurrence. Further biological marker study is needed in clinically localized prostate cancer.

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.

Nuclear shape analysis for the assessment of local invasion and metastases in clinically localized prostate carcinoma.

BACKGROUND: Nuclear shape analysis of histologic sections from radical prostatectomy specimens has retrospectively predicted outcome in patients with clinically localized prostate carcinoma. If outcome could be predicted preoperatively by nuclear shape analysis, patients might be selected better for definitive surgical therapy. Morphometric analysis of preoperative biopsies, however, has not correlated positively with values obtained from analysis of prostatectomy specimens. METHODS: The nuclear shapes of histologic specimens of 20 organ-confined carcinomas, 10 periprostatic fat-invasive carcinomas, 10 seminal vesicle-invasive carcinomas, and 12 lymph node-metastatic carcinomas from 52 patients who had undergone radical prostatectomy for clinically localized disease were evaluated. RESULTS: Nuclei from areas of extraprostatic invasion or regional lymph node metastases were less round than those from the corresponding intraprostatic portion of the tumor (nuclear roundness factor (mean +/- SD) PPF, 51.2 +/- 3.1 vs. 31.2 +/- 3.2; SV, 52.4 +/- 4.1 vs. 31.6 +/- 2.5; and LN, 57.3 +/- 3.1 vs. 36.4 +/- 1.8; paired Student's t tests, P < 0.001). Cells sampled from the periphery of organ-confined tumors had a greater nuclear roundness factor (49.1 +/- 1.5) than did those sampled from the center (34.5 +/- 2.0; P < 0.001) or randomly throughout the tumor (37.8 +/- 1.6; P < 0.001). Nuclear roundness factors for all extraprostatic tumor foci and for peripheral tumor cells in organ-confined disease were similar (analysis of variance, P > 0.05). The intraprostatic portions of randomly sampled primary tumors had similar nuclear roundness factors, regardless of pathologic stage (P > 0.05). Among organ-confined carcinomas, nuclear shape was unrelated to tumor volume. CONCLUSIONS: Pathologic stage in clinically localized prostate carcinoma cannot be determined by the nuclear shape profiles of intraprostatic tumor cells. Thus, patients with a poor prognosis or high pathologic stage can be recognized only when samples for morphometric analysis include high proportions of nuclei from the extra-prostatic carcinoma and nuclei from the periphery of organ-confined carcinoma that may not be sampled routinely by prostate biopsy.

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)

Nuclear morphometry in automatic biopsy and radical prostatectomy specimens of prostatic carcinoma. A comparison.

Nuclear shape analysis performed upon prostatectomy specimens of prostatic carcinoma distinguished individual patients with good and poor prognoses. In order to be useful for prognosis assessment preoperatively, nuclear morphometry must be measured on needle biopsy specimens. We compared nuclear morphometry on automatic biopsy and radical prostatectomy specimens in 20 patients with prostatic carcinoma. Nuclear size was smaller (paired Student t test, P < .0001) in biopsy specimens (perimeter 17.0 +/- SD 4.9 microns, area 29.9 +/- 6.6 microns2) than in prostatectomy specimens (perimeter 24.6 +/- 4.4 microns, area 48.2 +/- 8.7 microns2). Nuclear shape was more abnormal in automatic biopsy specimens (nuclear roundness factor 82.0 +/- 18.8, ellipticity 90.5 +/- 27.7) than in surgical specimens (nuclear roundness factor 43.5 +/- 8.8, ellipticity 54.0 +/- 14.7) (P < .0001). Study of specimens obtained by automatic biopsy preoperatively and automatic biopsy of the prostatectomy specimens at various steps of processing revealed that nuclear swelling and rounding occurred after 2-24 hours of formalin fixation. Automatic prostate biopsies may more accurately reflect true nuclear morphometry and should be studied for preoperative prognosis prediction in patients with clinically localized prostatic carcinoma.

Tumorigenicity of SV40 T antigen immortalized human prostate epithelial cells: association with decreased epidermal growth factor receptor (EGFR) expression.

Our primary objectives were to: 1) develop a system for the study of prostatic tumor evolution; and 2) examine the role of the epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) pathway in prostate tumor progression. Adult human prostate epithelial cells previously immortalized by transfection with the SV40 T antigen gene (P69SV40T) produced tumors in only 2/18 mice with a 6 month latency period. Reinjection of cells recovered from these tumors after 1 or 2 cycles of growth in nude mice produced tumors in 2/4 and 2/3 mice with markedly decreased latent intervals of 12, 25, 25 and 25 days each. The chromosomal complement of each tumor was human, consistently pseudodiploid, and retained the Y chromosome. In both anchorage-independent and adherent cell growth assays, EGF stimulated proliferation by approximately 2-fold in both the parental P69SV40T line and the tumor sublines. The tumor sublines expressed less EGFR protein than the parental line, as assessed by Western immunoblotting and flow cytometric analysis. Immunoprecipitation revealed increased production of the 18 and 25 kDa TGF-alpha precursors parallel to decreases in detectable EGFR. The growth of both the parental P69SV40T line and the tumor sublines was inhibited by a neutralizing antibody to TGF-alpha under serum-free defined conditions. Inclusion of the TGF-alpha neutralizing antibody consistently inhibited the proliferation of the tumor sublines more than P69SV40T in both proliferation and [3H]thymidine incorporation assays. This finding suggests that the increased tumorigenicity and decreased latent interval observed among the human prostate tumor cells is partially due to activation of the TGF-alpha/EGFR autocrine network.

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.

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.