Immunohistochemical phenotype of ovarian granulosa cell tumors: absence of epithelial membrane antigen has diagnostic value.

Granulosa cell tumors (GCTs) represent 1.5% to 3% of primary and 6% to 10% of malignant ovarian neoplasms, and present little diagnostic difficulty in the typical case; however, other primary or metastatic tumors may mimic their various histologic patterns. For this reason, immunohistochemistry can be used to supplement routine histology to help determine a final tissue diagnosis. Previous reports on the utility of antibodies to intermediate filaments vary, as some investigators found keratin to be uniformly negative in GCTs while others reported immunoreactivity for keratin in 20% to 68% of cases. To determine the immunophenotype of granulosa cell tumors and to discover which antibodies are useful in differentiating GCTs from histologic look-alikes, we studied 52 GCTs, including 24 typical cases, 23 cases in which the diffuse pattern predominated, and five juvenile cases, with a panel of commercially available antibodies using an automated immunohistochemistry system. Immunoreactivity for granulosa cells in GCTs was as follows: 17 cases (32.7%) reacted with cytokeratin AE1/AE3, six cases (11.5%) reacted with cytokeratin MAK-6, three cases (5.8%) reacted with cytokeratin CAM 5.2, no case (0%) reacted with epithelial membrane antigen, 52 cases (100%) reacted with vimentin, no case (0%) reacted with desmin, 48 cases (92.3%) reacted with smooth muscle actin, and 26 cases (50%) reacted with S-100 protein. No attempt was made to quantify staining of background thecoma-like or fibroma-like elements in GCTs. Immunoreactivity was independent of the histologic subtype of GCT. Cytokeratin immunoreactivity showed a globoid pattern of staining and was consistent with the expression of 52.5-kD and 45-kD cytokeratins (8 and 18 of Moll's classification). For this reason, the presence of cytokeratin immunoreactivity by itself cannot be used to differentiate a primary or metastatic carcinoma from a GCT. The presence of smooth muscle actin and the absence of epithelial membrane antigen immunoreactivity are additional features that are characteristic of a GCT. S-100 protein immunoreactivity is a finding limited exclusively to GCTs among sex cord stromal tumors, and its presence may have some role in differentiating between Sertoli-stromal cell tumors and GCTs. Since epithelial membrane antigen immunoreactivity is present in many of the histologic look-alikes of GCTs, such as metastatic or primary carcinoma, the absence of staining in GCT has diagnostic value.

Experimental preeclampsia produced by chronic constriction of the lower aorta: validation with longitudinal blood pressure measurements in conscious rhesus monkeys.

OBJECTIVES: Our goals were (1) to determine whether hypertension, proteinuria, and glomerular endotheliosis can be produced by chronic reduction of lower aortic pressure in pregnant rhesus monkeys and (2) to study the time course of the development of hypertension by means of longitudinal arterial blood pressure measurements in conscious, unrestrained pregnant rhesus monkeys. STUDY DESIGN: Indwelling arterial catheters were placed at 103 +/- 4 days of gestation (term 160 days) for measurement of arterial pressure before and after reduction of lower aortic pressure. At 116 +/- 7 days lower aortic pressure was reduced by 24 +/- 11 mm Hg in 11 monkeys (experimental group) by a stricture on the aorta just below the renal arteries; six monkeys (controls) underwent a sham operation. Resting on the aorta just below the renal arteries; six monkeys (controls) underwent a sham operation. Resting pressures were measured three to five times per week by a tether-and-swivel system. RESULTS: Baseline arterial pressure averaged 81 +/- 6 mm Hg. In the experimental group four monkeys had adverse outcomes (one maternal death with severe hypertension, one abruptio placentae with stillbirth, and two spontaneous preterm deliveries with hypertension). There was one preterm delivery in the control group. Of the seven monkeys with aortic stricture who continued to term, four developed sustained hypertension (mean pressure 18 +/- 6 mm Hg above baseline), proteinuria, and moderate-to-severe glomerular endotheliosis. None of the controls had hypertension or proteinuria, but two had endotheliosis. CONCLUSION: These observations confirm that a syndrome resembling preeclampsia can be produced by a reduction of lower aortic pressure, and they demonstrate that the associated hypertension is not an artifact of anesthesia. This model may prove useful in studying the pathophysiologic mechanisms of preeclampsia.

Increased depth of trophoblast invasion after chronic constriction of the lower aorta in rhesus monkeys.

OBJECTIVE: Our purpose was to investigate whether a reduction in uteroplacental perfusion pressure would produce changes in trophoblast-uterine interactions at the cellular level. STUDY DESIGN: Strictures were placed around the abdominal aortas of rhesus monkeys at 116 +/- 7 days of pregnancy to reduce uteroplacental perfusion pressure. Placental bed biopsy specimens were obtained at cesarean section, and cytotrophoblasts were identified by means of an anticytokeratin antibody. RESULTS: In monkeys without aortic strictures, interstitial trophoblast invasion was restricted to the outer half of the endometrium. Endovascular trophoblast invasion involved the entire endometrial portion of uterine vessels and extended through the subjacent half of their myometrial segments. In seven of nine monkeys with aortic strictures the depth of interstitial trophoblast invasion was substantially increased and extended throughout the entire decidua and at least a portion of the myometrium. In contrast, the pattern of endovascular trophoblast invasion was identical to that observed in the placental beds of control animals. CONCLUSION: These results suggest that uteroplacental perfusion pressure or oxygen content may be important physiologic factors controlling the depth of interstitial cytotrophoblast invasion.

Comparison between colposcopic, cytologic, and histologic findings in women positive and negative for human papillomavirus DNA.

Little is known about the role of detection of human papillomavirus (HPV) DNA in exfoliated cells of the cervix in aiding the colposcopic diagnosis of cervical lesions. The purpose of our study was to compare the colposcopic findings of young women who were positive and negative for HPV DNA. Eighty-four women aged 13-22 years attending family planning clinics were examined colposcopically with the aide of acetic acid and Lugol's solution and without knowledge of HPV DNA status. Lesions identified were given scores based on the severity of observed colposcopic changes. Samples for cytology and HPV DNA testing, which included types 6, 11, 16, 18, 31, 33, and 35, were obtained at the time of the examination. Biopsies were performed on women with significant lesions identified on examination or with cytology suggestive of neoplasia. Students t-test and chi 2 analysis were performed to compare colposcopic variables and HPV DNA type. Of the 84 women examined, 17 were positive for HPV DNA; 9 had type 16/18. The average length of sexual activity was 2.7 years. Women with HPV 16/18 had a mean of 1.7 lesions visible at colposcopy compared to 0.7 lesions visible in those negative for HPV 16/18 (this included HPV DNA negative women and women positive for HPV types 6, 11, 31, 33, and 35) (p < 0.001). Women who were positive for HPV 16/18 also had higher lesional scores than the HPV 16/18-negative group (3.4 versus 1.0, respectively, p < 0.001). All four women who had dysplasia either on cytology or histology were positive for type 16/18.(ABSTRACT TRUNCATED AT 250 WORDS)

Diffuse adenomatoid tumor of the uterus with a serosal papillary cystic component.

A 39-year-old woman undergoing immunosuppressive therapy following kidney transplantation for systemic lupus erythematosus presented with a uterine adenomatoid tumor that diffusely infiltrated the entire myometrium and contained a serosal papillary cystic component that resembled a cystic mesothelioma. This is the first reported case of an adenomatoid tumor showing both of these features. Although adenomatoid tumors are considered benign, the patient may be at risk for recurrence of the papillary cystic component (which is known to recur in 50% of cases) if this tumor reflects an inability to limit neoplastic processes.

The prognostic significance of nuclear DNA content in malignant epithelial tumors of the ovary.

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.

High signal intensity lesions of the chest in MR imaging.

The majority of pathologic lesions in the lung and mediastinum have relatively long T1 and T2 relaxation times and consequently yield medium to low signal intensity on T1-weighted images. Pulmonary lesions with high signal intensity on T1-weighted images are unusual and raise a special group of diagnostic considerations. In the current study, a mass with a lesion/fat signal intensity ratio of greater than 0.7 on a T1-weighted sequence was considered high signal intensity. The nature of these masses was ganglioneuroma or ganglioneuroblastoma (n = 3), atrial lipoma (lipomatous atrophy of the interatrial septum) (n = 3), pheochromocytoma (n = 2), bronchogenic cyst (n = 2), lymphangioma (n = 1), teratoma (n = 1), and a variety of primary and metastatic tumors of the mediastinum and lung. A single pathologic structure of these lesions was not present, but rather several underlying tissue compositions were noted, including fat, subacute hemorrhage, myxoid material, and cellular composition with high cytoplasmic/nuclear ratio. Thus, high signal intensity lesions of the thorax on T1-weighted images should suggest a number of differential diagnoses.

Intravascular lipoleiomyomatosis: a report of two cases.

Two cases of intravascular leiomyomatosis (IVL) with histologic features of a lipoleiomyoma (LPL) are reported. Both tumors arose from preexisting uterine leiomyomata. One tumor was found incidentally in a uterus removed for leiomyomata. The other tumor extended up the inferior vena cava into the right side of the heart and presented as a cardiac mass. Although LPL is considered to be a benign lesion, IVL recurs in approximately 10% of reported cases, and must be distinguished from low-grade endometrial stromal sarcoma and leiomyosarcoma with vascular invasion. The combination of features in these cases lends support to the theory that IVL may arise by intravascular extension of a preexisting leiomyoma.

Endometrioid and clear cell carcinoma of the ovary. Factors affecting survival.

Eighty-five patients, 52 with endometrioid carcinoma (EC), nine with mixed endometrioid and clear cell carcinoma (MC), and 24 with clear cell carcinoma (CC), were studied to determine if prognosis was affected by (a) mixed tumor histology, (b) grade of the endometrioid component in ECs, and MCs, (c) presence of benign or malignant squamous differentiation in ECs, (d) solid versus tubular histology in CCs, (e) endometriosis in the same ovary as the tumor or elsewhere in the pelvis, (f) tumor stage, (g) patient age, or (h) presence of a coexisting carcinoma of the endometrium. The 5 year survivals for the ECs, MCs, and CCs were 52%, 22%, and 69%, respectively, for all stages. The 5 year survivals for Stage I ECs and CCs were 82% and 93%, respectively. None of these differences were statistically significant. Higher stages of disease for all three tumor types and higher grades of the endometrioid component of the ECs and the MCs were associated with significantly decreased survival. Patients with CCs had a significantly increased incidence of pelvic endometriosis (67%) versus patients with ECs (17%) or MCs (22%) (p less than 0.001). Survival was not significantly affected by benign or malignant squamous differentiation in ECs, tubular differentiation in CCs, patient age, the presence of endometriosis, or a coexisting carcinoma of the endometrium.

Radiation-induced uterine changes: MR imaging.

To assess the capability of magnetic resonance (MR) imaging to demonstrate postirradiation changes in the uterus, MR studies of 23 patients who had undergone radiation therapy were retrospectively examined and compared with those of 30 patients who had not undergone radiation therapy. MR findings were correlated with posthysterectomy histologic findings. In premenopausal women, radiation therapy induced (a) a decrease in uterine size demonstrable as early as 3 months after therapy ended; (b) a decrease in signal intensity of the myometrium on T2-predominant MR images, reflecting a significant decrease in T2 relaxation time, demonstrable as early as 1 month after therapy; (c) a decrease in thickness and signal intensity of the endometrium demonstrable on T2-predominant images 6 months after therapy; and (d) loss of uterine zonal anatomy as early as 3 months after therapy. In postmenopausal women, irradiation did not significantly alter the MR imaging appearance of the uterus. These postirradiation MR changes in both the premenopausal and postmenopausal uteri appeared similar to the changes ordinarily seen on MR images of the nonirradiated postmenopausal uterus.

Pregnancy post-Stevens-Johnson syndrome: case report and review of the literature.

A pregnancy complicated by vaginal stenosis six years after diagnosis of Stevens-Johnson syndrome is described. The pathologic changes in the vagina have not previously been reported. The basic pathology of severe mucosal erythema multiforme was present, as well as ectasia of the superficial capillaries and small venules. The effect of the vaginal scars on the mode of delivery is discussed.

Immunocytochemical localization of chorionic gonadotropin, placental lactogen, and placental alkaline phosphatase in the diagnosis of complete and partial hydatidiform moles.

Complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs) represent different clinicopathologic entities with characteristic morphologic and cytogenetic findings. In the absence of cytogenetic data, the histologic distinction between these lesions and abortuses showing hydropic swelling (AHS) may be difficult. An immunocytochemical study analyzing the distribution of human chorionic gonadotropin (hCG), human placental lactogen (hPL), and placental alkaline phosphatase (PlAP) in CHMs, PHMs, and AHS was undertaken to determine whether the expression of these trophoblastic proteins might assist in the differential diagnosis. A total of 24 CHMs, 22 PHMs, and 13 AHS were selected on the basis of established morphologic criteria. Thirty-four specimens of abortuses without hydropic swelling and normal placentas, ranging from 6 to 24 weeks gestational age, were similarly analyzed. The immunocytochemical localization of the three trophoblastic proteins, predominantly in syncytiotrophoblast (ST), was scored using a semiquantitative scoring system. In CHMs hCG is widely distributed and PlAP is patchily distributed in ST regardless of the gestational age, whereas hPL tends to increase with increasing gestational age. In contrast, in PHMs hPL is more widely distributed in ST compared with CHMs regardless of gestational age, while PlAP increases with increasing gestational age; in PHMs the distribution of hCG is markedly less than in CHMs except early in the first trimester when the staining patterns are similar. The different patterns of distribution of hCG, hPL, and PlAP may reflect differences in the pathobiology of trophoblast in CHMs and PHMs and appear to be useful in the differential diagnosis of these conditions.

The role of human papillomaviruses in the pathogenesis and histologic classification of precancerous lesions of the cervix.

It is clear that the relation between HPV infection and cervical neoplasia is more complex than initially realized. Preliminary molecular virologic data suggest preferential distributions of low- and high-risk HPV types in CIN that tend to correlate with the morphologic appearance. Thus, mild and moderate dysplasias (CIN I and II) contain a diverse distribution of HPV types, including a minority that have a high risk of malignant potential. HPV, therefore, appears to play a major role as a promoter. Neoplastic transformation is probably determined by specific HPV types but, in addition, requires initiation by some other carcinogenic stimulus, e.g., HSV II, cigarette smoking. Despite numerous studies, performed during the past 30 years, the long-term behavior of dysplasia remains uncertain. The natural history of HPV-associated lesions is unknown. Until this information is available, it is recommended that the conventional dysplasia--CIS or CIN nomenclature be used. The presence of associated viral changes can be considered and added to the diagnosis, e.g., "moderate dysplasia (CIN II) with evidence of papillomavirus infection." Treatment should be the same for all intraepithelial lesions, regardless of the presence of morphologic evidence of HPV. In the future, it may be necessary to modify the classification of precancerous lesions of the cervix if it is shown that a specific HPV type induces a characteristic morphologic alteration or that the HPV type, in and of itself, has greater prognostic significance. Until then, confusion will be minimized and management optimized if the conventional dysplasia--CIS or CIN nomenclature is employed.

Female adnexal tumor of probable Wolffian origin with multiple recurrences over 16 years.

The case history of a woman with a "female adnexal tumor of probable Wolffian origin" is described in which the neoplasm recurred three times during a 16-year interval and responded with prolonged remission after repeated surgical excision and radiotherapy. Ultrastructural data are given to support the Wolffian nature of the tumor. Although the tumor was considered in the past to be a benign neoplasm, the current report, as well as six others in which the tumor recurred or metastasized, indicates that the female adnexal tumor of probable Wolffian origin should be classified within the International Classification of Disease-Oncology and the Systematized Nomenclature of Medicine nomenclatures as "of low malignant potential."

Carcinoma of the anal canal.

J.W. is a 68-year-old white female who noted an "anal growth" 1 year prior to admission. She also complained of bleeding from her rectum when she was constipated. She attributed these symptoms to hemorrhoids. She noted increasing pain and more bleeding 1 month prior to admission. Locally applied hemorrhoid remedies gave her no relief. She was then admitted to a hospital where a biopsy of the anal mass was performed, and then referred to Rush-Presbyterian-St. Luke's Medical Center. On physical examination the patient was noted to be obese. There was no inguinal lymphadenopathy. There were no abdominal masses or hepatosplenomegaly. Rectal examination revealed a 3 X 4 cm mass protruding from the anus. Examination and protoscopy done under anesthesia revealed this mass to be approximately 4 X 5 cm and arising from the proximal anal canal. The mass was freely moveable and bled spontaneously when manipulated. Pelvic examination revealed a normal uterus and adnexa with no obvious tumor involvement of the vagina. Proctoscopic examination revealed no tumor proximal to the lesion described. Further evaluation included a liver-spleen scan that was negative for metastatic disease and intravenous pyelogram that showed no lesions. A barium enema revealed only diverticula. A gallium scan showed marked uptake at the area of the anal tumor but no other lesions. The chest x-ray was within normal limits. A CT scan of the abdomen and pelvis revealed no masses or lymphadenopathy. The CEA was 1.3 ng/ml. The patient underwent concomitant radiation therapy and chemotherapy. Over a 4-week period the patient received 5000 rads to the anal region. In addition, during the first week of radiation therapy and the fourth week of radiation therapy, the patient received 5-fluorouracil, 800 mg/m2 by continuous infusion for 5 days. In addition, the patient received mitomycin C, 15 mg/m2 on the first day of the first week of chemotherapy and the first day of the last week of chemotherapy. During the treatment period, the patient had mild diarrhea, perineal desquamation, and mild ulceration at the site of the anal tumor. During the third week of treatment, the patient had a white blood cell count nadir of 2800 and a platelet count of 86,000 per cubic millimeter. Her symptoms were managed with local emolients and antidiarrheal medications.(ABSTRACT TRUNCATED AT 400 WORDS)