Search

PURPOSE: Kaposi’s sarcoma (KS) is the most common AIDS-related malignancy. Pulmonary involvement by KS (PKS) has carried a poor prognosis with median reported survival ranging from 3 to 10 months. We studied whether the introduction of highly active antiretroviral therapy (HAART; triple antiretroviral therapy including a protease inhibitor and two reverse transcriptase inhibitors) has been associated with improved survival for AIDS patients with PKS. PATIENTS AND METHODS: A retrospective study was performed of 37 consecutive patients with PKS and human immunodeficiency virus infection in the tumor registry at a large municipal hospital in New York City between 1994 to 1997. There were 16 patients from 1994 to 1995 (pre-HAART period) and 21 patients from 1996 to 1997 (post-HAART period). The primary end point was survival, which was defined as time from start of chemotherapy until death from any cause. RESULTS: Patients were analyzed by the date of diagnosis (pre- v post-HAART period) and whether or not they received HAART. Kaplan-Meier analysis showed significantly better survival in patients diagnosed in the post-HAART period (P = .0025). Additional Kaplan-Meier analysis indicated that patients on HAART had substantially better survival (P < .0001). Cox multivariate analyses showed that HAART therapy was associated with a reduced risk of death (hazard ratio = 0.09; 95% confidence interval, 0.03 to 0.69). CONCLUSION: In patients with AIDS-associated PKS and undergoing chemotherapy, administration of HAART was associated with increased survival.

The purpose of this study was to identify histopathological fallopian tube changes that might be related to the development of fallopian tube carcinoma (FTCA). Each of 14 unilateral cases of the latter was matched with 2 controls for age, hospital, and year of diagnosis. The uninvolved fallopian tube from patients with FTCA, all of which were of serous type, was compared to fallopian tubes from the same side in 28 matched controls. The features evaluated included plical bridging, trapped gland-like structures, inflammation, epithelial stratification, tufting, nuclear atypia, plical atrophy, luminal dilatation, and presence or absence of in situ carcinoma. The significant changes (p < 0.05) in the contralateral tubes of patients with FTCA were luminal dilatation (p = 0.0004), plical atrophy (p = 0.0015), and chronic inflammation (p = 0.0089). FTCA may therefore develop in tubes demonstrating histologic features of chronic healed salpingitis, findings that reflect bilateral tubal disease which apparently antedates the development of the FTCA. p53 stains were strongly positive in 9 of 14 FTCAs and in 5 of 6 foci of in situ carcinoma found in the tubes with unilateral FTCA. No p53 staining was found in any of the contralateral tubes. Serous FTCAs may be etiologically related to antecedent bilateral healed chronic salpingitis and arise from in situ carcinoma in a background of atrophy.

Abnormal uterine bleeding after Norplant administration is primarily responsible for the high discontinuation rate of this safe and effective long-acting implantable progestin-only contraceptive agent. Although tissue factor (TF) is the primary initiator of hemostasis, previous studies indicated that Norplant-associated bleeding persists despite relatively high TF levels in the stromal compartment. Recently, we determined that progestin-enhanced TF expression during decidualization of human endometrial stromal cells involves both the epidermal growth factor receptor and progesterone receptor (PR}. The current study evaluated TF levels in endometrial bleeding (BL) and nonbleeding (NBL) sites obtained by camera-guided hysteroscopy during Norplant contraception. After 1 yr of therapy, immunohistochemical TF levels were unexpectedly higher at BL than at NBL sites. Use of immunohistochemistry and Western blotting indicated that both sites displayed elevated epidermal growth factor receptor levels and that the ...

Prior studies indicate that tissue factor (TF), the primary cellular initiator of hemostasis, is persistently up-regulated in human endometrial stromal cells (HESCs) undergoing progestin-induced decidualization in vivo and in vitro. The mechanism underlying progestin enhancement of TF mRNA and protein levels in these cells involves transcriptional activation of the TF gene. Transient transfections of HESCs with the truncated TF promoters driving the luciferase reporter gene have demonstrated that the region spanning -111 to +14 bp retained differential progestin-enhancing effects. We now demonstrate that RU486 displays inhibitory effects on the progestin-induced TF promoter activity, confirming the involvement of the progesterone receptor. Since the TF minimal promoter (pTF 111 spanning -111 to +14 bp) contains three overlapping Sp1 and three Egr-1 sites, the present study determined whether Sp1 and/or Egr-1 were required for progestin-regulated TF expression. The results indicate that the three Sp1 sites are primarily responsible for both the constitutive and progestational activity of the pTF 111 promoter, whereas the Egr-1 sites have only a minor involvement in both activities. Overexpression of the Sp1 protein resulted in greater than a 6-fold induction in TF promoter activity. In contrast, no enhancement was observed when the Sp3 protein was overexpressed. The concomitant overexpression of Sp1 and Sp3 demonstrated that Sp3 completely blocked the induction of TF promoter activity by Sp1. Moreover, the addition of 10 nM mithramycin, a concentration that inhibits Sp1 binding to target DNA, blocked the progestational induction of TF mRNA expression. Immunohistochemical studies demonstrated increased Sp1 levels in perivascular stromal cells in secretory phase compared with proliferative phase endometria. In contrast, Sp3 expression was greatly decreased in stromal cells of secretory, compared with proliferative phase tissues. The levels of Egr-1 were low in both proliferative and secretory endometria. Immunocytochemistry of E2 vs. E2 + medroxyprogesterone acetate-treated HESCs demonstrated a dramatic reduction in Sp3 expression after progestin treatment, and Northern blots demonstrated progestational increases in Sp1 and reduction in Sp3 mRNA expression compared with controls. Taken together, our results demonstrate that progestin enhancement of TF gene expression in HESCs is mediated principally by Sp1. We propose that progestins regulate HESC TF gene expression in vivo by altering the ratio of Sp1 to Sp3 nuclear factors.

Objective.—To test the hypothesis that CD44 standard (CD44[s]) and its other variants, CD44v6 and CD44v7-8, might be useful markers of squamous differentiation in epithelial tumors. Design.—We studied expression of CD44(s), CD44v6, and CD44v7-8 using immunohistochemistry in human tumors that had squamous differentiation, glandular differentiation, or both arising in the colon, stomach, esophagus, lung, pancreas, gallbladder, or uterus/cervix, as well as in adjacent nonneoplastic tissues. Formalin-fixed, paraffin-embedded archival tissue specimens of 33 adenosquamous tumors were used. All were stained with monoclonal antibodies against a conserved portion of CD44(s) and its variants, CD44v6 and CD44v7-8, using the avidin-biotin peroxidase method. Results.—CD44(s) and its variants consistently and strongly stained areas of tumors with well-developed squamous differentiation. These markers also consistently and strongly stained normal squamous mucosa. Reactivity for CD44 and its variants was lacking in normal glandular type epithelium and in adenocarcinomas composed entirely of well-differentiated mucin-producing glands. Areas of well-differentiated carcinoma, both squamous and adenocarcinoma, were consistent with respect to both extent and intensity of staining. Staining in lymph nodes was similar to that in the primary tumors, with well-differentiated squamous foci being consistently positive, well-differentiated mucin-producing adenocarcinoma foci consistently negative, and poorly differentiated foci showing variable staining. Although staining was less intense with the variants, it followed the same staining pattern as found for CD44(s). No differences in the extent or intensity of staining were identified in the metastatic versus primary tumor foci, nor was any difference identified between superficial and deeply invasive areas of primary tumors. Conclusions.—Our study shows that CD44(s) and its variants are good markers of squamous epithelial differentiation in several types of normal epithelium and tumors, and that these markers can identify areas of well- to moderately differentiated elements in adenosquamous neoplasms. However, poorly differentiated tumors show an inconsistent staining pattern with CD44, such that it cannot be used as a reliable and practical marker of squamous differentiation in poorly differentiated neoplasms.

Summary This case, a rare example of low-grade endometrial stroma sarcoma with extensive smooth muscle differentiation which extended to the inferior vena cava and cardiac chambers closely resembling intravenous leiomyomatosis grossly and microscopically, illustrates the importance of extensive sectioning and the usefulness of immunohistochemistry. Although spindle cell components arranged in interlacing bundles consistent with smooth muscle differentiation were recognizable in the primary tumor (on retrospective review), extensive smooth muscle differentiation in the recurrent tumors masked prototypical morphologic features of stromal sarcoma and only small neoplastic stromal components were preserved in limited areas, leading to initial failure to distinguish the lesion from intravenous leiomyomatosis. The immunophenotyping disclosed two distinct cell populations in the tumor: i.e. vimentin-positive and smooth muscle marker negative stromal cells, and vimentin-negative spindle-shaped desmin-positive smooth muscle cells. Our observation suggests that the predominance of a smooth muscle component in such a tumor can be misleading and does not always warrant a diagnosis of intravenous leiomyomatosis, nor does it predict a benign clinical course. This case also provides an insight into the relationship of the endometrial stroma and myometrium, and their cell of origin and the histogenesis of endometrial stromal sarcoma.

The role of CYP1A1 genotype in lung cancer risk was assessed in African Americans through a case control study. The complete CYP1A1 genotype, including the frequency of all three polymorphisms (Msp1 [CYP1A1*2], exon 7 [CYP1A1*3] and African American specific [CYP1A1*4]) was determined by PCR on 307 controls and 105 cases of lung cancer among African Americans. We have confirmed our earlier observation of a significant increased risk (odds ratio = 2.8, 95% CI = 1.3-6.5) for lung adenocarcinoma among people with the *4 polymorphism, although we did not observe any association of this polymorphism with overall lung cancer risk. As previously reported, we found that lung adenocarcinoma patients with the *4 RFLP smoked significantly less than patients without this polymorphism, suggesting an important role in cancer risk of low exposure levels to cigarette smoke in subjects carrying susceptibility polymorphisms. There was no association with the other two polymorphisms and lung cancer in this population. When we examined lung cancer risk as a function of composite genotype, taking into account all three polymorphisms simultaneously in each subject, our preliminary data suggested an association of one rare genotype (homozygous Msp1, heterozygous exon 7 or *2/*2*3) with overall lung cancer risk (OR = 8.4, 95% CI = 1.6-43.2).

Apoptosis (i.e. programmed cell death) plays a key role in maintaining reproductive function in the ovary, mammary and prostate glands, uterus, and testis. The purpose of the present report was to determine, based on biochemical and morphological parameters, whether cells in human fetal membranes undergo apoptosis and express Fas (CD95), a cell surface receptor that mediates apoptosis. Using the terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling immunohistochemical technique, apoptotic nuclei were identified in amnion epithelial, chorionic trophoblast, and decidua parietalis cell layers of human fetal membranes at term. Electron microscopy of fetal membranes revealed ultrastructural characteristics in amnion epithelium and chorion trophoblast cell layers consistent with apoptosis, including condensation of chromatin along the periphery of the nucleus and nuclear shrinkage. The apoptotic index (percentage of terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling-positive nuclei of the total nuclei) ranged from 8–29% in amnion epithelial, chorionic trophoblast, and decidual cell layers from women at 23–30, 31–36, and 37–42 weeks gestation. The apoptotic index was statistically greater in the 37–42 week group than in the 23–30 week group in chorionic trophoblast (P < 0.05) and decidual cell (P < 0.01) layers. In contrast, the apoptotic index in the amnion epithelial cell layer was statistically greater (P < 0.05) in the 23–30 week group than in the 31–36 week group, suggesting that apoptosis may be independently regulated in amnion epithelial, chorionic trophoblast, and decidual cell types. Based on the importance of Fas in mediating apoptosis, we investigated whether Fas was expressed by human fetal membrane cells. Immunohistochemical staining of fetal membranes with anti-Fas antibody localized Fas in amnion epithelial, chorionic trophoblast, and decidua parietalis cell layers. A 266-bp band corresponding to the cytoplasmic domain of Fas was detected in samples of amnion, chorion, decidua, and placenta by RT-PCR. Northern blotting revealed a molecular weight of approximately 1.9 kilobases for Fas messenger ribonucleic acid in amniotic tissue. These data suggest that apoptosis and Fas signaling may play a role in remodeling of fetal membrane architecture across gestation.

A high incidence of irregular uterine bleeding is the primary patient complaint limiting the utility of long term, progestin-only contraceptive agents such as Norplant. The onset of hemorrhage requires both inadequate hemostasis and impaired vascular integrity. Thus, we first tested whether Norplant-associated endometrial bleeding was accompanied by altered expression of perivascular stromal cell tissue factor (TF), the primary initiator of hemostasis. Norplant effects on TF messenger ribonucleic acid (mRNA) and protein expression by endometrial stromal cells were assessed by in situ hybridization and immunohistochemical examination of endometrial biopsies obtained from normally cycling control women (n = 14) and from patients experiencing Norplant-induced abnormal uterine bleeding (n = 24). TF mRNA and protein expression was increased 150% in secretory vs. proliferative phase endometrial specimens. By contrast, endometrial TF mRNA and protein levels were reduced during 1-6 months of Norplant treatment by about 2-fold (P < 0.05 for protein) compared to the values for control secretory phase specimens. These changes were consistent with observations that patients on Norplant begin to bleed during this interval. Further reductions of TF mRNA and protein levels to 2- and 3-fold of those in secretory phase control specimens were observed in endometria obtained after 6-12 months of Norplant therapy (P < 0.05 and P < 0.01, respectively). A modest rebound in TF mRNA and protein expression was observed after 12 months of Norplant therapy, which occurred commensurate with reduced patient complaints of abnormal uterine bleeding. Pathologically enlarged venous sinusoids were ubiquitous in endometrial specimens obtained after Norplant therapy. The combination of fragile blood vessels and reduced TF expression may account for bleeding in patients receiving Norplant therapy.

OBJECTIVE: Our purpose was to evaluate whether tamoxifen has estrogenic endometrial effects as defined by histologic study or alterations in steroid hormone receptor expression. STUDY DESIGN: Nineteen postmenopausal tamoxifen-treated breast cancer patients who also had endometrial sampling were identified from files in the Department of Obstetrics and Gynecology. To examine the subgroup of 15 polyps, age-matched, non–hormonally treated patients with polyps ( n = 8) or atrophic endometria ( n = 5) served as comparison groups. Proliferative ( n = 3) and secretory ( n = 5) endometria served as procedural controls. Immunohistochemical studies for steroid receptors (estrogen, progesterone) were performed. RESULTS: Glandular cell progesterone receptor was significantly increased and stromal cell estrogen receptor was significantly decreased in tamoxifen-treated versus atrophic endometria. Progesterone receptor staining was not significantly different in tamoxifen-treated versus control polyps, although staining was high in both groups. Stromal cell estrogen receptor staining was significantly reduced in tamoxifen-treated versus control polyps, although there were no histologic differences. Reduced stromal cell estrogen receptor and increased glandular cell progesterone receptor staining was found in all tamoxifen-treated endometria regardless of the diagnosis. CONCLUSION: The tamoxifen-associated changes in endometrial steroid receptors support an estrogenic effect that is independent of histologic diagnosis and duration of use. This may contribute to the pathogenesis of tamoxifen-associated polyps and carcinomas. (Am J Obstet Gynecol 1997;176:129-37.)

The CYPlA1 gene codes for aromatic hydrocarbon hydroxlase (AHH), a critical enzyme in the metabolism of carcinogenic polycyclic aromatic hydrocarbons. Polymorphisms in this gene have been implicated in aberrant gene function, and in increased risk of cancer from exposure to hydrocarbons such as those found in tobacco smoke. We have discovered a novel restriction polymorphism (“AA RFLP”) in this gene that is found only in people of African descent. African Americans suffer a disproportionate high incidence of lung and prostate cancer. This is not due to increased smoking, but may be related to either environmental or genetic factors. We have examined the possibility that the African American specific CYPlA1 RFLP may be associated with higher risk for tobacco related carcinogenesis. The incidence of the AA polymorphism in the healthy African-American population was 14.5%. In African-Americans with adenocarcinoma of the lung the incidence of the polymorphism was doubled. We observed no difference be...

Ovarian serous tumors of borderline malignancy frequently show morphologically benign and borderline areas within the same tumor. This study was undertaken to determine if these two morphologically disparate areas differ in their proliferative activity and p53 expression. Formalin-fixed, paraffin-embedded archival tissue from 17 ovarian serous borderline tumors with morphologically benign and borderline areas were immunostained with monoclonal antibodies against p53 and MIB1. The percentage of positive cells was determined by counting 100 consecutive cells for each stain in the most intensely stained areas in morphologically benign and borderline portions of these tumors. There was a significantly increased proliferation (MIB1 expression) in borderline areas compared with benign areas (37.05 +/- 15.3 versus 12.88 +/- 6.7, p = 0.0001). More than 30% of cells were positive for MIB1 in 13/17 borderline areas compared with none of the 17 benign areas (p < 0.0001). The expression of p53 was also higher in borderline areas compared with benign areas (7.12 +/- 8.8 versus 2.94 +/- 4.46, p = 0.0078). More than 10% of cells were p53 positive in 5/17 borderline areas compared with 1/17 benign areas (p = 0.08). However, there was no significant correlation between p53 expression and MIB1 expression in either the benign or borderline areas (p = 0.4 and 0.2, respectively). In summary, morphologically borderline areas show significantly higher p53 expression and proliferation compared with morphologically benign areas in ovarian serous borderline tumors. Alterations of p53 may play a pathogenetic role in some ovarian serous borderline tumors. The lack of correlation between p53 expression and MIB1 expression, however, suggests involvement of other factors, in addition to p53, in determining the proliferative rate of ovarian serous borderline tumors.

Studies using cervical carcinoma cell lines usually show mutated p53 in cases without detectable HPV, and wild-type p53 in cases with detectable HPV. These findings suggest that loss of p53 function, either by mutation or by binding to HPV E6, is required for cervical carcinogenesis. Because mutated p53 is usually detectable immunohistochemically, one would predict an inverse relationship between the presence of HPV and detectable p53. In this study we examined 88 formalin-fixed paraffin-embedded clinical specimens of cervix for the presence of HPV and p53 expression. All cases were studied for the presence of p53 using immunohistochemical methods. The antibody used was mouse monoclonal PAb1801 (Biogenex). The presence of HPV was detected by PCR. Twenty-six specimens showed foci of p53 expression (0/7 normal, 1/8 (13%) condylomas, 1/6 (17%) CIN I, 3/7 (43%) CIN II, 6/20 (30%) CIN III, 13/22 (59%) SCC, 2/5 (40%) adenosquamous carcinomas, and 0/13 adenocarcinomas). p53 expression was more frequent in SCC than with CIN (P = 0.026). HPV was present in 15 of 24 cases with detectable p53 and 22 of 48 cases without detectable p53. No correlation was seen between HPV status and detection of p53. With the exception of one case, p53 expression was seen in less than 10% of cells. p53 expression was not detected in any of the 13 adenocarcinomas examined (P = 0.0016 vs SCC). Our results show that alterations of p53 may play a role in the pathogenesis of cervical squamous carcinoma. However, p53 expression was neither sufficient nor required for cervical carcinogenesis, irrespective of HPV status.

Keratin 19 (K-19) expression has been strongly correlated with dysplasia in oral epithelium. Expression of K-19 was evaluated by immunoperoxidase staining in formalin-fixed normal ectocervical tissue, normal endocervical tissue, cervical dysplasia, squamous metaplasia, atrophic epithelium, cervical condylomas, and invasive carcinoma to determine if a correlation of K-19 expression with dysplasia was present in the cervical epithelium. Uniform expression of K-19 was seen in endocervical epithelium and in the basal layer of normal ectocervical epithelium in all areas where these epithelia were present. Cervical dysplasia without associated condylomatous changes showed increased expression of K-19 in suprabasal epithelium, corresponding to the level of immature cells. Squamous metaplasia was characterized by scattered cells with increased staining (patch-quilt pattern). There was considerable overlap in the patterns of K-19 expression in dysplastic and metaplastic epithelium. Thus K-19 staining pattern could not be used as a distinctive marker for dysplasia in the cervical epithelium. Atrophic epithelium showed a characteristic uniform but low-level expression of K-19 in suprabasal areas. This pattern may be of diagnostic use in differentiating atrophic lesions from dysplasia. Condylomas showed focal loss of K-19 in the basal layer, suggesting induction of premature differentiation in the basal layer by human papillomavirus infection. Invasive carcinomas showed variable patterns. K-19 is a marker of immature cervical squamous epithelium, with generally distinctive but sometimes overlapping patterns of expression in various diagnostic categories.

A case of primary lymphoma of the ovary with extensive stromal luteinization is presented. Immunohistochemical markers that work satisfactorily in fixed tissues allowed a diagnosis of B cell lymphoma to be made on formalin-fixed tissue sections. Immunohistochemical analysis of frozen tissue and genotypic analysis confirmed the diagnosis of B cell lymphoma. By electron microscopy two populations of cells, including large atypical lymphoid cells and luteinized stromal cells, were identified. Presentation with amenorrhea and resumption of menstrual periods after removal of the tumor suggested the possibility of functional activity in the luteinized stromal cells. Stromal luteinization has not been previously described in primary ovarian lymphoma.

Eight patients with mucinous ovarian tumors and pseudomyxoma peritonei were matched by their original ovarian tumor histology with eight tumor controls without pseudomyxoma peritonei. In each group, four tumors were benign, three were low malignant potential, and one was malignant. Cases compared with controls more frequently showed cyst rupture (3 vs. 2), periovarian adhesions (5 vs. 4), mucinous lesions of the appendix (4 vs. 0), goblet cells (8 vs. 4), and tumor necrosis (3 vs. 1). All cases displayed pseudomyxoma ovarii, which contained mucinous epithelial cells. Only one control exhibited pseudomyxoma ovarii, but it did not contain epithelial cells. In all cases, the peritoneal mucin contained epithelial cells. Two cases were noteworthy, each of which displayed a change in histology (benign to low malignant potential and benign to malignant) 6 years after the original ovarian tumor operation. One of these cases was not associated with pseudomyxoma peritonei until the first recurrence of the benign ovarian tumor. These data suggest that pseudomyxoma ovarii, with epithelial cells, may presage the development of pseudomyxoma peritonei and/or malignant recurrence.

A case of myxoid leiomyosarcoma of the uterus arising in a leiomyoma is reported. Although the tumor showed very low mitotic activity ranging from zero to 2/10 HPF, the presence of infiltrative pattern of growth and a high MIB-1 index (60% of cells positive) established the diagnosis. Myxoid leiomyosarcoma may arise in leiomyoma.

The prognostic significance for residual or recurrent disease of cervical intraepithelial neoplasia Grade III in endocervical glands by cone biopsy was examined in 341 consecutive patients diagnosed from 1979 through 1983 and followed through 1988. Treatment by hysterectomy, within 8 weeks of cone biopsy, was done in 96 patients. The only variable that could predict residual disease at hysterectomy was positive margins (P = 0.059). However, both positive margins and positive glands were (independently of one another and after the effects of length of follow-up, hospital of admission, and age at time of first diagnosis were held constant) highly significant predictors of residual or recurrent disease in the 245 women who did not undergo a hysterectomy (P = 0.000 for each). The authors therefore conclude that information concerning gland involvement on cone biopsy specimens should influence patient management.

Both atrophic and dysplastic cervical squamous epithelia show lack of maturation, nuclear crowding, and increased nuclear/cytoplasmic ratio. Because of these similarities, distinguishing dysplasia from atrophy in cervical biopsies from elderly patients is often problematic. Because dysplasia shows increased proliferation and atrophy has decreased proliferation, the possible utility of MIB-1 in distinguishing dysplasia from atrophy was evaluated. One or more of the following criteria were present in all nine cases with dysplasia and in none of the 17 cases with atrophy: MIB-1 expression in > 20% of cells in the basal one-third of the epithelium, > 5% of cells in the middle one-third of the epithelium, and > 1% of cells in the upper one-third of the epithelium. MIB-1 immunostaining is useful in distinguishing dysplasia from atrophy.

This study examined factors affecting the survival of 28 consecutive patients with malignant mixed Mullerian tumors diagnosed at New York University Medical Center from 1971 through 1985. The cumulative 5-year survival for all patients was 38%. Patients with pedunculated tumors (18/25) had a significantly improved 5-year survival of 53% compared with patients having a tumor with a broad-based attachment (7/25), all of whom died within 1 year (p less than 0.01). Eleven patients whose tumors demonstrated vascular invasion had a worse prognosis compared with 14 patients without demonstrable vascular invasion (18% versus 53% 5-year survival; p less than 0.05). Interestingly, patients with pedunculated tumors persisted in having an improved survival even after correcting for vascular invasion, compared with patients having broad-based tumor attachment. Small tumor size (less than or equal to 7 cm) also proved to be a significant and independent prognostic indicator for improved survival. Advanced stage, heterologous sarcomatous elements, and deep myometrial invasion (greater than one-third invasion) tended to be associated with decreased survival, but not with statistical significance. Patient age and grade of the carcinoma element did not appear to affect survival.

Recent studies have indicated that the nuclear DNA content of certain malignant neoplasms can be used as an adjunct in predicting their biologic behavior. The DNA content of 99 ovarian carcinomas was determined by flow cytometric analysis of nuclei obtained from paraffin-embedded tissue. Of the 99 tumors, 51 were diploid and 48 showed one or more aneuploid peaks. The 5-year survival for patients with diploid tumors (50%) was significantly higher than for patients with aneuploid tumors (22%) (P less than 0.01). Other factors which significantly affected survival were clinical stage (P less than 0.001), tumor pattern grade (P less than 0.01), DNA index (P less than 0.01), the presence of ascites (P less than 0.001), peritoneal carcinomatosis (P less than 0.0001), and residual tumor at second-look laparotomy (P less than 0.05). Diameter of the primary ovarian tumor, diameter of the largest peritoneal implant before debulking, and the percent S-phase had no significant correlation with survival. Of 16 patients with aneuploid tumors who underwent second-look laparotomy, nine (56%) had residual tumor, compared to six of 22 of patients with diploid tumors (27%). Of seven patients with aneuploid tumors and a negative second-look laparotomy, four (57%) died from recurrent tumor. By comparison, of 16 patients with diploid tumors and a negative second-look laparotomy, only four (25%) died from recurrent tumor. The determination of DNA ploidy in ovarian carcinomas may be used as an adjunct in predicting tumor behavior, response to chemotherapy, and late recurrence of disease.

We observed that the ratio of in situ to invasive carcinomas of the cervix is significantly greater for squamous than for glandular lesions. We wondered whether Pap smears were less effective for the identification of in situ glandular lesions. The purpose of this study was to determine if the location, extent of disease, and growth patterns of endocervical adenocarcinomas influence the ability to detect malignant cells by Pap smears. Medical records, doctor's office records, and all pathology materials (reports and slides) including Pap smears, biopsies, LEEP/cone biopsies, and hysterectomy specimens from 53 consecutive patients diagnosed with endocervical adenocarcinomas were examined at New York University Medical Center (a total of 654 pathology slides and 51 Pap smears were reviewed). Findings were correlated for each patient using gross descriptions and histopathology and stratified by location/extent of disease and growth pattern (exophytic or endophytic or both). Ten patients had in situ disease, seven (70%) of which involved the transformation zone (TZ); all seven of these were identified by Pap smears. In contrast, of the other three cases that did not involve the TZ but were confined to the endocervix, only one was identified by Pap smear. Forty-three patients had invasive disease. Twenty involved the TZ, and 23 involved the endocervix but spared the TZ. Of the 20 tumors involving the TZ, 11 (55%) were identified by Pap smears, whereas of the 23 sparing the TZ, 11 (47.8%) were diagnosed by Pap smear. Among the 23 patients with invasive disease that spared the TZ, 6 (26%) had a documented history of negative Pap smears at New York University within 3 years of diagnosis. Conversely only 1 of the 20 patients with TZ involvement had a history of negative Pap smears, and 3 patients in this group denied having had Pap smears for several years. Including all 53 patients, a significantly higher proportion were not detectable by Pap smear if the TZ was spared (54% versus 25%, p = 0.036). Of the 23 invasive cancers that spared the TZ, 6 (14%) had verified negative Pap smears. These lesions did not shed malignant cells onto Pap smears. Noteworthy was the finding that two of these six lesions extended from the endocervix upward, through the stroma, and into the endomyometrium of the lower uterine segment. Four extended downward into the exocervix through the stroma, sparing the surface mucosa; one reached the upper vagina. All six displayed an endophytic growth pattern.

Atypical polypoid adenomyoma (APA) is a rare entity that is believed to follow a benign course. We report a case of APA with coexistent endometrial adenocarcinoma. The example raises the possibility that APA may progress to endometrial adenocarcinoma in some cases.

Objective Immunohistochemical analysis of MIB1, p53, estrogen, and progesterone receptors can provide prognostic information in endometrial adenocarcinoma. Since predictors of recurrence for low-grade endometrial stromal sarcoma (LESS) are still unknown, a battery of immunostains was performed to find markers, which might be useful to predict prognosis. Methods Eleven patients with an average age of 43.8 years (range 27–76) were identified with stage I LESS. Immunostains, including MIB1, p53, ER, and PR, were evaluated by two pathologists, independently. Results All tumors were positive for ER and PR; 1/11 was positive for p53; MIB1 ranged from 0 to 20% positive tumor nuclei. Mitotic counts ranged from 0 to 7/10 hpf. Two patients developed recurrences. One had a pelvic recurrence 7 years after diagnosis. This tumor had a mitotic count of 1/10 hpf, MIB1 expression in 10% of nuclei, and focal p53 expression. A second patient developed pulmonary metastases 10.8 years after diagnosis; the tumor showed a mitotic count of 7/10 hpf and MIB1 expression in 20% of nuclei, but was negative for p53. There was a significant difference in MIB1 reactivity scores between patients who did or did not develop recurrence ( P = 0.0303). A marginally significant association was detected between MIB1 ( P = 0.0896) or p53 ( P = 0.0833) positivity and length of recurrence-free survival. Conclusion Although MIB1 and p53 appear to be useful prognostic markers, a larger study would be necessary to confirm their validity.

Context.—Non–acquired immunodeficiency syndrome (AIDS)-defining malignancies that occur in patients infected with human immunodeficiency virus (HIV) and the demographics and pathologic features associated with these malignancies have not been completely defined. Objective.—This study describes the age of onset of malignant disease in patients seropositive for HIV and in control patients presumed to be negative for HIV, but with the same primary site. We compare the demographics and histopathology for both groups. Design.—From 1993 to 1997, 57 cases involving HIV-positive patients with malignancies from 16 primary sites were recorded in the Cancer Registry files at Bellevue Hospital; 519 cases involving patients negative for HIV were recorded during this same period. We compared the age at diagnosis, sex, race, tumor histology, stage, and grade between these 2 groups. Results.—The average age of HIV-positive patients was 47.6 years, compared with 60.3 years in the control group (P < .001). When the 16 cancer sites were compared individually, HIV-positive patients were significantly younger at onset of lung (HIV-positive patients/control group) (19/245), skin (11/77), penile (3/5), laryngeal (3/18), tongue (5/16), and colorectal (2/38) carcinomas. Patients infected with HIV had a more frequent history of smoking (41/328; P = .04) and illicit drug use (30/49; P < .001). The HIV-positive patients also were found to have a lower clinical stage of disease, compared with controls, largely due to the higher prevalence of stage 0 tumors (13/46; P = .01). Conclusions.—The finding of younger age at diagnosis in HIV-positive compared to presumed HIV-negative patients may be related in part to earlier detection, as well as preexisting immunosuppression. The specific sites for which a significant difference in age between the HIV-positive and control cases was observed may be related to the mechanisms of immunosurveillance in parts of the body that have ready access to the outside environment. Knowledge of younger age of onset for these malignancies should prompt closer physical examination of these sites by clinicians.

Sex cord-stromal tumors represent uncommon group of ovarian tumors which are present with a wide range of endocrine manifestations due to estrogenic or androgenic hormone secretion. These are interesting neoplasms from a clinical, morphological, and embryologic perspective. The morphologic features in these tumors are diverse and are categorized as biphasic neoplasms, composed of both stromal and sex-cord elements derived from male and female anlage. Two distinct categories of ovarian and testicular homologous cell types are present in these tumors namely granulosa and Sertoli cells and theca, Leydig, and nonspecific stromal type cells (stromal elements). The sex cord-stromal tumor emphasizes the biphasic nature of these neoplasms represented by an epithelial-like component. Granulosa-stromal cell tumors are composed of neoplastic cells resembling granulosa cells, theca cells, or stromal fibroblasts in various combination.

Twenty-four predominantly papillary carcinomas of the endometrium, 10 serous and 14 endometrioid, were compared using a variety of immunohistochemical antibodies, including p53, estrogen and progesterone receptors, carcinoembryonic antigen, and E-cadherin. These were selected to attempt to find clues to explain the disparate behavior of these two tumor subtypes. We found that 6 of 8 (75%) serous carcinomas had a p53 reactivity score of 300, whereas 90% of endometrioid tumors had a p53 reactivity score of less than 20 (p = 0.0008). Combined estrogen and progesterone hormone reactivity was positive in 13 (100%) of endometrioid lesions compared with 4 of 8 (50%) of serous lesions (p = 0.0117). The significantly greater p53 expression and its significantly diminished hormone receptor expression indicate that papillary serous carcinomas belong to the type II group of endometrial carcinomas that occur in a background of atrophic endometrium, are high grade, present with high stage disease, and have a poor prognosis. In contrast, papillary endometrioid carcinomas, which belong to type I carcinomas, often arise in a background of estrogen-stimulated endometrial hyperplasia, are usually well-differentiated, and have a good prognosis. Early p53 mutations in papillary serous carcinoma as well as in endometrial intraepithelial serous carcinoma may partially explain their proclivity for early intra-abdominal dissemination. Carcinoembryonic antigen expression was similar in both groups and therefore is not useful to characterize possible differences in the cell of origin. The reactivity scores for E-cadherin were also similar in the two tumor subtypes, thus not supporting the hypothesis that decreased cell to cell adhesion molecules might contribute to early dissemination of serous lesions.

The diagnosis of benign, uncertain malignant potential, and malignant uterine smooth muscle tumors depends on mitotic counts, nuclear atypia, and other morphologic features. This study was undertaken to evaluate the utility of selected immunohistochemical markers in differentiating these tumors. Fifteen cases of cellular leiomyoma, 7 cases of smooth muscle tumor of uncertain malignant potential (STUMP), and 12 cases of leiomyosarcoma were immunostained for MIB-1 (Ki-67), p53, estrogen receptor and progesterone receptor (PR) using monoclonal antibodies and the avidin-biotin-peroxidase method. The percentage of cells stained was subjectively assessed to the nearest 5%. One percent was used for rare positive cells. MIB-1 expression of > or =15% was seen in 11 and expression of p53 in > or =15% cells was present in 5 of 12 leiomyosarcomas. MIB-1 and/or p53 expression of >15% was seen in all 12 leiomyosarcomas but in none of the 7 STUMP or 15 cellular leiomyomas. PR was absent in 10 of 12 leiomyosarcomas but present in 7 of 7 STUMP and 14 of 15 cellular leiomyomas. MIB-1 of 5% to 10% was seen in 6 of 7 STUMP but in only 1 of 15 cellular leiomyomas. MIB-1, p53, and PR are useful in differentiating leiomyosarcoma from STUMP and cellular leiomyoma. MIB-1 is useful in distinguishing STUMP from cellular leiomyomas.

The search for new prognostic indicators is especially important in the diagnosis and treatment of ovarian cancer because clinicopathologic criteria currently used to predict survival are largely inadequate. We examined 2 groups of patients with epithelial ovarian cancer, 1 group of long-term survivors (>5 years), and 1 group of short-term survivors ( KIP2 , cyclin D1, and cyclin E and their relationship with survival. Our findings show that p57 KIP2 is not associated with prognosis, in contrast to p27 KIP1 expression, which is previously shown to be positively associated with long-term survival in univariate analysis ( P = .001). Cyclin E expression, in contrast to cyclin D1 expression, is marginally associated with short-term survival in univariate analysis for a group of 53 women. Among the short-term survivors, 15 (65%) of 23 were positive for cyclin E expression, compared with only 11 (37%) of 30 long-term survivors ( P = 0.054). This association remained significant ( P = .04) in a logistic regression analysis adjusted simultaneously for performance status and extent of residual disease, the 2 strongest predictors of survival in our study. We also found a significant difference in the frequency of the cyclin E staining pattern between nonserous and serous ovarian tumor subtypes ( P = .0002). Immunostaining for levels of cyclin E and p27 KIP1 expression may have potential as prognostic markers in the management of ovarian cancer. HUM PATHOL 32:808-813. Copyright © 2001 by W.B. Saunders Company

Glutathione S:-transferase M1 (GSTM1) can detoxify many carcinogens, including polycyclic aromatic hydrocarbons such as those from cigarette smoke. Though a number of studies have been published about the association between GSTM1 polymorphism and lung cancer, this association has received limited attention in the African-American population. We conducted a case-control study to investigate the role of GSTM1 polymorphism in the development of lung cancer in African-Americans. Specimens of DNA from 117 lung cancer cases and 120 controls were assayed for detection of GSTM1 genotype by polymerase chain reaction (PCR). The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1 gene and other risk factors were estimated by logistic regression. Thirty-seven of the 117 cases (31. 6%) and 24 of the 120 controls (20.0%) had the GSTM1 null genotype; the OR was 2.10 (95% CI 1.07-4.11) after adjustment for age, gender and smoking. The association was higher for squamous cell carcinoma (OR 2.98, 95% CI 1.09-8.19) than for adenocarcinoma (OR 1.95, 95% CI 0.81-4.66). We observed a stronger association between GSTM1 null genotype and lung cancer among heavy smokers with > or =30 pack-years (OR 4.35, 95% CI 1.16-16.23). This association was also found in squamous cell carcinoma (OR 6.26, 95% CI 1.31-29.91). In the analysis combining GSTM1 polymorphism and smoking, smokers with the null genotype had high risk (OR 8.19, 95% CI 2.35-28.62) compared with non-smokers with the wild-type genotype, and the risk increased with smoking cigarette pack-years (P: = 0.0001 for trend). Our results suggest that GSTM1 polymorphism plays a role in the development of lung cancer and modifies the risk for smoking-related lung cancer in African-Americans.

In a retrospective study to determine the accuracy of frozen section diagnoses in ovarian neoplasms, the results of consecutive frozen section diagnoses of 311 ovarian neoplasms from two institutions, New York University Medical Center and State University of New York Medical Center at Brooklyn, from 1980 through 1989 were compared with the final diagnosis results following extensive sampling on permanent sections. The final diagnosis was assumed to be correct for purposes of this study. Ovarian neoplasms were correctly diagnosed on frozen section as either benign or malignant in 292 patients (accuracy of 93.8%). Frozen section diagnoses were incorrect in 11 patients (3.5%). Frozen section diagnosis was deferred in 8 instances (2.6%). The positive predictive value was 100%. The negative predictive value was 95.3%, specificity 100%, and sensitivity 86%. There were no false positives. Of the 11 false negative frozen section diagnoses, 9 (82%) were due to limited sampling for frozen section. We therefore suggest that careful examination with sampling of any suspicious lesions be carried out at the time of surgery for patients with benign frozen section diagnosis, since this may avoid a second staging laparotomy, if the final diagnosis is malignant.

This case-control study was designed to identify factors associated with long-term survival. We examined two groups of patients with epithelial ovarian cancer, one group of long-term survivors (>5 years) and one group of short-term survivors (

Cervical condylomas associated with HPV types 6/11 rarely progress to dysplasia; this progression is more commonly seen in cervical condylomas with HPV types 16/18/31/33/35. This investigation was undertaken to determine if more frequent atypical mitotic figures (MFs) and higher proliferative activity are seen in high-risk condylomas. HPV types present in cervical condylomas were determined by in situ hybridization with biotinylated probes. The cases were also stained immunohistochemically for MIB1. The percentage staining of basal, parabasal, and suprabasal cells was determined by counting 100 cells in the most intensely stained areas. MFs and atypical MFs were counted per 10 high-power-fields (HPFs). Condylomas with HPV 6/11 showed higher MIB1 expression in the basal layer than condylomas with HPV 16/18 and 31/33/35 (p = 0.013). Atypical MFs were seen more frequently in condylomas with HPV types 16/18/31/33/35 (p = 0.02). Differences in mitotic activity and in MIB1 expression in parabasal and suprabasal layers did not reach statistical significance. The presence of atypical MFs may make a greater contribution than increased proliferative activity to progression to dysplasia in cervical condylomas.

We report two cases of leuprolide acetate-treated leiomyomas with striking vascular changes and histologic features of vasculitis and atherosclerosis. These changes may cause ischemic damage if they occur in other organs. We describe the histologic findings and discuss their clinical implications.

This study examined the histologic changes associated with administration of leuprolide acetate, a gonadotropin-releasing hormone agonist, in leiomyomata. Thirty-seven women treated with leuprolide acetate who subsequently underwent myomectomy or hysterectomy were matched by age (+/- 3 years), race, and uterine size (+/- 2 weeks) with untreated controls. Tissue samples of leiomyomata (four to 10 slides per patient) were examined "blinded" by two pathologists and evaluated for cellularity, edema, myxoid change, hyalinization, fibrosis, inflammation, infarction, and vascular changes (thrombosis, intimal fibrosis, thickening of the vessel wall with narrowing of the lumen, perivascular fibrosis). A matched case-control analysis was conducted for each morphologic characteristic. Cellularity, hyalinization, and fibrosis were graded as 1(+) versus 2(+); all other characteristics were graded as present or absent. The analysis showed that leuprolide acetate-treated leiomyomata had significantly increased hyalinization (p0.005) and decreased cellularity (p0.10) as compared with controls; there was also thickening of blood vessel walls with narrowing of the lumen (p0.01). A subgroup of leuprolide acetate-treated patients categorized as clinical responders (having30% reduction in tumor size) more frequently had thickening of vessel walls (p0.05) and vascular thrombosis (p0.10) than did nonresponders. Our data suggest that a leuprolide acetate-induced hypoestrogenic state may cause vasoconstriction, thickening of blood vessel walls, and thrombosis, leading to ischemia, hyalinization, and atrophy of the leiomyoma.

Endometrial polyps are a frequent cause of abnormal uterine bleeding, but their pathogenesis is poorly understood. This study was undertaken to investigate if endometrial polyps result from localized overexpression of estrogen receptors (ERs) or reduced expression of progesterone receptors (PRs). Fourteen cases of endometrial polyps, in which normal cycling endometrium was also present on the same slide, were immunostained for ERs and PRs. Percentages of positive cells in glands and stroma for each receptor were subjectively assessed to the nearest 5%. The intensity of staining was recorded on a scale from 1+ to 4+. The level and intensity of staining in polyps were compared with the staining in normal endometrium. Fewer stromal cells in polyps expressed ERs and PRs compared with cycling endometrium (% ER = 55.9 +/- 25.8 vs. 74.3 +/- 25.8, p = 0.03; % PR = 56.1 +/- 28.2 vs. 87.5 +/- 10.1, p = 0.002). Stroma in polyps also had significantly reduced intensity of staining for PRs, but not for ERs (intensity PR = 2.7 +/- 1.4 vs. 3.5 +/- 0.7, p = 0.015; intensity ER = 2.1 +/- 0.7 vs. 2.4 +/- 0.8, p = 0.45). There were no significant differences in expression of ERs and PRs in the endometrial glands in endometrial polyps compared with normal endometrium (% ER = 75.4 +/- 32.5 vs. 70.7 +/- 39.2. p = 0.25; % PR = 79.6 +/- 32.8 vs. 80.4 +/- 34.4, p = 0.8; intensity ER = 2.7 +/- 0.9 vs. 2.4 +/- 1, p = 0.15; intensity PR = 2.9 +/- 1.4 vs. 3.4 +/- 0.7, p = 0.15). We conclude that endometrial polyps may result from a decrease in ER and PR expression in stromal cells. Because of these receptor-negative stromal cells, endometrial polyps may be relatively insensitive to cyclic hormonal changes.

This study compares morphometric features of endometrial papillary carcinomas, serous and endometrioid types, in an effort identify characteristics that predict clinical outcome. Fifty-one consecutive patients with papillary carcinoma were identified at NYU Medical Center from January 1979 through December 1991 and were followed through 1994. Morphologic analysis was conducted by investigators (R.D. and K.M.) blinded as to original diagnosis, depth of invasion, stage and outcome. Of 25 variables analyzed, six were significantly associated with reduced survival, namely marked nuclear pleomorphism, multinucleated cells, hobnail cells, psammoma bodies, uneven papillary borders, and inflammation. Serous carcinomas showed a highly significant (p = 0.0001) association with reduced length of recurrence-free survival, with a median survival of 27 months (mean +/- SE, 38.9 +/- 7.0) versus 95 months (106.7 +/- 15.3) for patients with endometrioid types. Of six morphologic characteristics that correlated with reduced recurrence-free survival by univariate analyses, only one, nuclear pleomorphism, showed a significant association with an adverse outcome in a multivariate regression analysis (p = 0.0020), even after adjustment for the effect of tumor stage. Therefore, we believe that the presence of marked nuclear pleomorphism should serve as the major criterion for making a diagnosis of serous carcinoma. In tumors with moderate nuclear pleomorphism, a diagnosis of serous carcinoma is aided by the presence of multinucleated cells, uneven papillary borders, high nuclear/cytoplasmic ratio, apical location of the nucleus, and hobnail cells. These features were significantly associated with a diagnosis of serous carcinoma in our patients.

The expression of cytokeratin, epithelial membrane antigen, Leu-M1, B72.3, carcinoembryonic antigen, human placental lactogen, proliferating cell nuclear antigen, p53, and ovarian carcinoma-associated antigen OC-125 was evaluated in inclusion cysts in contralateral ovaries of patients with unilateral ovarian carcinoma. The findings were compared with the findings in inclusion cysts in ovaries of patients without ovarian carcinoma. Although there was more frequent expression of tumour markers B72.3 and CEA in patients with ovarian carcinoma, these differences did not reach statistical significance.

This study quantitates morphologic changes seen in partial moles and hydropic abortuses in an attempt to find a correlation with DNA content. Thirty-two products of conception were studied. Fifteen were diagnosed as definitive partial moles (DPM), and 17 had changes suggestive of a partial mole (SPM). We determined DNA ploidy by flow cytometry and quantitatively analyzed the following microscopic features: villous edema and sclerosis, central cistern formation, villous blood vessels, trophoblastic proliferation, and trophoblastic inclusions. No single pathologic feature significantly correlated with DNA content, even though triploid cases showed more inclusions than diploid cases (8.3 versus 7.2 on the average per ten x 100 fields). An overall diagnosis of DPM did correlate with ploidy; 12 of 18 triploid cases (67%) compared with only three of 13 diploid cases (23%) had been previously diagnosed as DPM (p < 0.05). Flow cytometric DNA ploidy estimates DNA content and cannot determine chromosomal origin. It is possible that detailed cytogenetic studies of moles compared with abortuses may show a significant correlation of the proportion of paternal chromosomes, morphologic changes, and the risk of persistent gestational trophoblastic disease.

Expression of Proliferating cell nuclear antigen (PCNA) was evaluated in formalin-fixed, paraffin-embedded normal and abnormal cervical squamous epithelia using immunoperoxidase stains and PC10 monoclonal antibody to PCNA. PCNA was exclusively expressed in the parabasal and basal layers of normal ectocervix and a similar pattern was seen in nine of the 11 cases with squamous metaplasia. Examples of cervical dysplasia showed expression in higher layers of cervical epithelium, corresponding to the degree of dysplasia. Increased staining was seen in condylomas and markedly reduced staining with atrophy. The percentage of basal cells that stained increased progressively from atrophic to normal, to condylomatous, to dysplastic epithelia. Proliferative activity can be satisfactorily assessed in formalin-fixed cervical epithelia using PC10 PCNA antibody. This assessment can be of potential diagnostic use in difficult cases.

Contralateral ovaries from patients with unilateral ovarian carcinoma were examined and compared to ovaries from age-matched control patients without ovarian carcinoma. The number of inclusion cysts were increased in ovaries from patients with ovarian carcinoma compared to the controls (p < 0.01). In addition, inclusions from cases with ovarian carcinoma showed serous differentiation more frequently than the controls (p < 0.01; odds ratio = 10.0; 95% confidence interval = 1.2-78.1). An age-related increase in the number of inclusion cysts was seen in the study group but not in the control group. These findings support a role of surface inclusion cysts in the genesis of ovarian carcinoma.

Nuclear enlargement of the superficial cervical epithelial cells in the absence of koilocytosis is frequently observed. The purpose of this study was to investigate whether this change represents human papillomavirus (HPV) infection. We reviewed 257 cervical biopsies with the diagnosis of "suggestive of condyloma," mild or moderate dysplasia, or both. Of the 257 consecutive biopsies, 23 fulfilled the two criteria: the superficial cells had a nuclear diameter of at least twice that of the basal nuclei, and complete absence of koilocytosis was seen. Parallel sections from each paraffin block were hybridized with biotinylated probes for HPV 6/11, 16/18, and 31/35/51 under high-stringency conditions. The cases that were negative at high-stringency conditions were then hybridized under low-stringency conditions with a mixture of the three HPV probes. Twelve of the 23 cases (52.17%) were positive for HPV, including one positive for HPV 16/18 in one area and for HPV 31/35/51 in another area, four positive for HPV 31/35/51, two positive for HPV 16/18, two positive for HPV 6/11, and three positive for HPV probe mixture at low-stringency conditions. The positive in situ hybridization was located predominantly in the enlarged nuclei in the superficial layers. In conclusion, HPV infection can be expressed as nuclear enlargement in the superficial layers of the cervical epithelium in the absence of koilocytosis.

We describe a low-grade endometrial stromal sarcoma coexistent with leiomyoma and adenomyosis treated with leuprolide acetate. We describe its histologic characteristics and clinical significance.

The uterus serves the function of providing the developing fetus with a relatively safe and nutritive environment in which to mature. It shows considerable variation in gross and microscopic appearance from neonate to adulthood to senescence.

Patterns of epidermal growth factor receptor (EGFR) and keratin B-2 (KB2) mRNA localization were studied in samples of normal cervical squamous epithelium and in samples of cervical intraepithelial neoplasia (CIN). 35S-Labeled EGFR and KB2 DNA probes were used for in situ hybridization on formalin-fixed tissue sections. Normal cervical squamous epithelium showed predominantly basal and parabasal expression of EGFR mRNA and suprabasal and midepithelial localization of KB2 mRNA. CIN lesions with moderate to severe dysplasia were generally characterized by continued expression of EGFR mRNA and decreased KB2 mRNA in midepithelial locations. Ratios of KB2 mRNA levels at the basal layer to KB2 mRNA levels at the midepithelial location were increased in moderate and severe dysplasia (CIN II and III) compared with normal epithelium (P less than .01). Ratios of EGFR mRNA levels at the midepithelial level to those of EGFR mRNA at the basal layer were increased in moderate to severe dysplasia compared with normal epithelium. These findings indicate a possible in vivo role of EGFR gene expression in normal and neoplastic proliferation and in prevention of differentiation of the cervical epithelium.

This study examined the morphology and immunocytochemical staining patterns of distribution of beta-human chorionic gonadotropin (beta-HCG), human placental lactogen (HPL), placental alkaline phosphatase (PLAP), and pregnancy-specific beta-1 glycoprotein (SP1) in 13 third-trimester placentas associated with hydrops fetalis and six normal control placentas matched for gestational age (+/- 2 weeks). Seven placentas were hydropic (540-1,080 g) and demonstrated histologic immaturity with large edematous chorionic villi showing few blood vessels, most of which contained immature hematopoietic elements. These placentas showed consistently increased staining for beta-HCG and decreased staining for PLAP when compared with control placentas, a pattern reminiscent of less mature placentas. HPL and SP1 staining were similar to those of controls. Six placentas were either sclerotic (four) or histologically unremarkable (two), and these did not differ in their immunocytochemical staining properties from control placentas. We conclude that third-trimester hydropic placentas, in addition to showing histologic immaturity, exhibit an immunocytochemical staining pattern associated with first-trimester placentas.