Differential expression of MHC class I antigens on the placenta of the rat. A mechanism for the survival of the fetal allograft.

In some mating combinations in rats, there is a maternal antibody response to the maternal antigenic components of the placenta without any previous immunization of the mother. The highest response occurs in the WF (u) female mated to the DA (a) male, and it is against a unique MHC-encoded class I antigen, the Pa antigen, and not against the major allele-specific transplantation antigen of the DA strain, RT1.Aa. The development of mAbs to the Pa and Aa antigens allowed us to localize these antigens on the placenta and to explore the reason for the differential antibody response to them using immunohistochemical and biochemical techniques. Both antibodies reacted with the WF X DA placenta and stained the endovascular and interstitial trophoblast of the decidua, the basal trophoblast, Reichert's membrane, and the yolk sac epithelium, but they did not stain the labyrinthine trophoblast. Blocking studies showed that each antibody reacted with a separate molecule in the placenta. Anti-class II mAbs reactive with the a or u haplotype did not stain the WF X DA, DA X DA, or WF X WF placenta; hence, there are no class II antigens in the placenta. Electron microscopic studies of the semiallogeneic WF X DA placenta using the immunogold technique with both single- and double-labeling showed that only the Pa antigen was expressed on the surface of the basal trophoblast, but that both the Pa and Aa antigens were in the cytoplasm of these cells; neither antigen was found in the labyrinthine trophoblast. By contrast, the placenta from the syngeneic DA X DA mating expressed both the Pa and Aa antigens on the surface of the basal trophoblast as well as in the cytoplasm; neither antigen was found in the labyrinthine trophoblast. These observations were quantified morphometrically using electron photomicrographs of single-labeled tissues. Both the Pa and Aa antigens isolated from the plasma membrane of lymphocytes have heavy chains of 46 kD, but those antigens isolated from the plasma membrane of basal trophoblast cells have heavy chains of 43 kD. Based on densitometric measurements of autoradiographs, the Pa/Aa ratio in the basal trophoblast membrane is 23.5, whereas it is 0.46 in lymphocyte membranes. These studies show that there is differential regulation of the expression of class I antigens on basal trophoblast cells in semiallogeneic pregnancies, but not in syngeneic pregnancies, such that the major allele-specific transplantation antigen is scarcely expressed on the surface of the basal trophoblast.(ABSTRACT TRUNCATED AT 400 WORDS)

Lymphocytes infiltrating human ovarian tumors: synergy between tumor necrosis factor alpha and interleukin 2 in the generation of CD8+ effectors from tumor-infiltrating lymphocytes.

Tumor-infiltrating lymphocytes (TIL) were isolated by enzymatic digestion and gradient centrifugation from 18 human ovarian carcinomas. These cells were cultured in a complete medium supplemented with recombinant interleukin 2 (IL2) alone or recombinant IL2 plus recombinant tumor necrosis factor alpha (TNF-alpha), and their growth and antitumor cytotoxicity were determined. TIL cultured in the presence of IL2 plus TNF-alpha (1000 units/ml each) for 6 days showed significantly higher cytotoxicity against fresh autologous tumor targets than did TIL cultured with IL2 alone (e.g., mean lytic units/10(7) cells for 8 TIL preparations were 290 versus 74; P less than 0.05). No differences in [3H]thymidine uptake or natural killer cell activity were observed among these TIL cultures. In titration experiments, optimal synergistic concentrations of IL2 and TNF-alpha were determined as 10(2) and 10(3) units/ml, respectively. Using these concentrations for culturing the TIL, effector cells developed which preferentially lysed autologous tumor and displayed a CD8+ phenotype (up to 75% positive). However, the autologous tumor cytotoxicity mediated by these cultured TIL on day 6 was short lived. By day 12, it was replaced by non-major histocompatibility complex-restricted, lymphokine-activated killer cell-like activity mediated by CD3-CD56+ effector cells. Simultaneously, the production of gamma-interferon and interleukin 1 decreased in these cultures. In contrast to TNF-alpha, anti-CD3 antibody synergized with IL2 to increase 2-3-fold TIL proliferation but not their cytotoxic activity against autologous tumor cell targets. These data suggest that TNF-alpha and IL2 synergize early in culture to induce tumor-reactive CD8+ effectors, some of which may be specific for autologous ovarian tumor cells. However, the conditions needed to sustain the specific autologous tumor responses in long-term cultures of human TIL remain to be determined.

In situ hybridisation for cytokine gene transcripts in the solid tumour microenvironment.

To determine if mononuclear cells (MNC) infiltrating various types of human solid tumours express genes for cytokines, in situ hybridisation with 35S-labelled cDNA antisense probes for interleukin 2 (IL2), interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), interleukin 1-beta (IL1-beta), transforming growth factor beta (TGF-beta) and interleukin 2-receptors (IL2R) was performed. Fresh-frozen tissue samples of ovarian carcinomas (n = 13), breast carcinomas (n = 12), and squamous cell carcinomas of the head and neck (SCCHN, n = 7) were evaluated for the presence and localization in the tumour of MNC positive for cytokine genes. In ovarian tumours and those breast carcinomas producing little or no mucin, only rare positive MNC were observed. In contrast, breast carcinomas producing mucin and all SCCHN contained numerous MNC expressing gene transcripts for IL2, IFN-gamma, TNF-alpha, IL2R as well as TGF-beta. In tumour-involved lymph nodes of patients with SCCHN, MNC expressing genes for cytokines were found around tumour metastases but not in non-involved areas. These data suggest that tumours expressing immunogenic antigens (e.g. mucin) contain many activated MNC, while other tumours either fail to activate or suppress functions of infiltrating MNC. In SCCHN or tumour-draining lymph nodes, local down-regulation of antitumour responses might be mediated by TGF-beta produced by activated tumour-infiltrating MNC.

Electron microscopic localization of the Pa and RT1.Aa antigens on the placenta of the rat.

A major factor in the ability of the placenta to avoid allograft rejection is the differential expression of MHC class I antigens on its surface. Using monoclonal antibodies and the electron microscopic immunogold technique, we have demonstrated that only the pregnancy-associated (Pa) antigen, which carries a broadly shared antigenic determinant, is expressed on the placental surface in the rat, whereas the allele-specific classical transplantation antigens are not. Both types of antigens are, however, present in the cytoplasm of the basal trophoblast but completely absent from the labyrinthine trophoblast.

Tumor-simulating retrorectal heterotopia of bone marrow.

A retrorectal tumor-simulating mass of extramedullary hematopoiesis was discovered during work-up for uterine bleeding in a 40-year-old woman. It was excised in toto. The only hematologic abnormality at the time was iron deficiency, which was corrected. Six years later the patient is free of recurrence or any hematologic abnormality. It is suggested that this case represents heterotopic marrow arising either as a remnant of embryonic hematopoiesis or from activated primitive cells retaining the embryonic potentiality of hematopoiesis. The difficult diagnostic problems, pathogenesis and treatment are discussed, and the importance of recognizing the trilineage of hematopoiesis using Wright's-stained imprints of the mass is emphasized.

Detection of human papillomavirus in cervical swab samples by ViraPap and in cervical biopsy specimens by in situ hybridization.

Human papillomavirus (HPV) detection in cervical swab specimens by ViraPap and in cervical biopsies by the ViraType in situ hybridization assay was correlated with concurrent cytologic and histologic findings in 149 patients. Seven percent of patients with normal samples were positive for HPV DNA, compared with 29% and 69% of patients with low- and high-grade squamous intraepithelial lesions (SILs), respectively. The performance of both assays increased the rate of HPV detection in low-grade lesions but not in high-grade cases. ViraPap was more sensitive than the ViraType in situ hybridization assay in high-grade lesions. The present investigation suggests that HPV DNA detection may be useful in separating confirmed lesions from histologically questionable biopsies.

Repetitive idiopathic fetal hydrops.

Two cases of repetitive idiopathic fetal hydrops are reported, the second and third cases found in the literature. A normal pregnancy occurred in 1 of the patients following 2 successive pregnancies with fetal hydrops. Findings as well as diagnostic and therapeutic modalities are discussed.

Prehysterectomy curettage.

The efficacy of prehysterectomy curettage in ruling out an endometrial cancer was evaluated in three ways. First, by an evaluation of the extent of routine prehysterectomy curettage; second, by the assessment of the clinicians' ability to recognize endometrial cancer on the basis of curettings; and third, by evaluating the presence of a gross endometrial lesion in those uteri removed without a preoperative diagnosis of an endometrial malignancy. It was concluded that the examination of the opened excised uterus was more valuable than prehysterectomy curettage for the operative diagnosis of an endometrial malignancy.

PIP: The efficacy of prehysterectomy curettage in screening for endometrial cancer was evaluated by 1) assessing the extent of prehysterectomy curettage in 50 postoperative uterine specimens, 2) a review of clinical records to assess recognition of cancer from curettage and 3) analysis of opened uteri removed without preoperative diagnosis for the presence of gross endometrial lesion. The routine prehysterectomy curettage was found to be incomplete in 60% of the cases. In evaluating the clinical recognition of curetted malignant material, a failure to suspect malignant tissue was found in 45% of the cases. In the open uterine specimens for which there was no preoperative diagnosis, gross lesions were found in 74.5%. It would appear, therefore, that gross examination of the excised uterus would be a more accurate way of gross screening for possible endometrial malignancy.

Diffuse vaginal adenosis associated with imperforate hymen.

A case of imperforate hymen associated with adenosis of the proximal surface of the obstructing membrane and of the vaginal wall is reported. The histogenesis of vaginal adenosis coexisting with congenital obstructive lesions is discussed, and the importance of careful follow-up of the patients with this type of anomaly is emphasized.

Vaginal evisceration: presentation and management in postmenopausal women.

BACKGROUND: Vaginal evisceration is a rare event, often associated with previous vaginal surgery in postmenopausal women. To date, 57 cases have been described in the world literature since 1901. STUDY DESIGN: We report three cases of vaginal evisceration and review risk factors and management described in the current literature. RESULTS: Of 60 reported cases of vaginal evisceration, 41 occurred in postmenopausal women. A common triad of previous vaginal surgery (73 percent), postmenopausal status (68 percent), and the presence of an enterocele (63 percent) was identified. Histopathologic evaluation of one case revealed a chronic vaginal-peritoneal fistula, and immunohistochemistry highlighted migration of squamous cells to multiple peritoneal serosal surfaces. This finding emphasizes the chronic nature of factors that predispose to the acute evisceration of abdominal contents. Most eviscerations were managed by primary repair of the vaginal disruption and the accompanying disorder of the pelvic floor, after assessing the viability of the prolapsed bowel and resecting any compromised segments. However, most surgeons agreed that delayed vaginal repair was preferable if the vaginal tissues appeared acutely inflamed or nonviable. CONCLUSIONS: Vaginal evisceration is primarily seen with obstetrical or postcoital trauma, but in postmenopausal women it is most often associated with a history of vaginal surgery and a pelvic support disorder. Hypoestrogenism, atrophy, and devascularization from previous surgery seem to play a significant role. Management is directed toward resecting any compromised bowel, repairing the vaginal defect, and correcting the contributing defect in the pelvic floor.

Malignant fibrous histiocytoma of the head and neck. A report of 12 cases.

The clinical and pathologic features of 12 cases of malignant fibrous histiocytoma of the head and neck were studied. These tumors occurred in seven men and five women ranging in age from 21 to 75 years (average, 55 years). The sinonasal tract was the most common site (four cases), followed by the parotid area (two cases), oral cavity (two cases), soft tissues of the neck (two cases), mandible (one case), and larynx (one case). Pathologically, 11 of the tumors were subclassified as storiform-pleomorphic and one as inflammatory. All were treated initially with surgery with or without postoperative irradiation. Five (42%) of the patients experienced local recurrences, three (25%) developed distant metastases (especially to the lungs), and five (42%) died of their disease, all of the latter occurring within two years of diagnosis. No patient developed bona fide cervical lymph node metastasis, although one did have a positive paraparotid node as a result of direct extension from an adjacent tumor.

Transplantation of congenital primitive neuroectodermal tumor of fetus to the uterus of mother: application of biotin-labeled chromosome-specific probes.

We report a 38-year-old gravida 3, para 3, white female with an unremarkable history and normal amniocentesis, who delivered a male infant with a large pedunculated and ulcerated tumor by vaginal delivery. A portion of the tumor was sheared and expelled with the normal placenta at the time of delivery. The biopsy of the infant mass and the expelled tissue showed histologic features of a small round cell tumor with immunohistochemical features of a primitive neuroectodermal tumor (PNET). The infant eventually died at the age of 4 weeks as a result of extensive dissemination of tumor. The mother had postpartum bleeding, and fractional dilation and curettage procedures at 6 weeks and 4 months after delivery revealed tumor similar to that of the infant. The mother underwent radical hysterectomy and bilateral salpingo-oophorectomy, which revealed a neoplasm at the junction of the lower uterine segment and cervix. Fluorescent in situ hybridization (FISH) study of both the infant's tumor and the mother's uterine tumor showed positivity for the Y chromosome by using a classical alpha-satellite Y chromosome-specific probe. These findings support the hypothesis that the tumor was transferred from the fetus to the mother.

Massive ovarian edema: a nonneoplastic pelvic mass of young women.

Two cases of massive ovarian edema are reported in addition to the eight previous cases published in the English literature. The predominance of the right-sided involvement and the histopathological characteristics of this lesion support the hypothesis that the basic pathogenetic mechanism is an impairment of the venous and lymphatic drainage of the ovary, triggered by recurrent partial torsion of the mesovarium. This nonneoplastic lesion should be recognized as a distinct entity in ovarian disease and treated conservatively.

Anencephaly and heterotopic central nervous tissue in lungs.

Heterotopic nodules of moderately well-differentiated central nervous tissue were seen in the lung of a full-term anencephalic baby who survived a few hours after birth. The pathogenesis of this rare condition remains obscure. None of the three hypotheses previously offered to explain this condition can be accepted or rejected on the basis of the recorded evidence.

Fine-needle aspiration cytology of metastatic ovarian carcinoma to the breast.

Metastatic ovarian carcinoma to the breast is rare. It represents a diagnostic challenge to the cytologist. It usually signifies a progressive widespread metastatic ovarian tumor with a poor prognosis. This report evaluates the breast fine-needle aspiration (FNA) cytomorphologic features of six cases of metastatic ovarian carcinoma and compares them to those reported in the literature. The cytologic features included hypercellularity, abundant papillary fragments, and necrotic background. The tumor cells showed high nuclear/cytoplasmic ratio, anisonucleosis, prominent nucleoli, and psammoma bodies in cases of serous papillary carcinoma. In addition, the clear-cell carcinoma had prominent finely vacuolated and clear cytoplasm, multinucleated giant cells, and papillary fragments with hobnail nuclei. Recognition of these unusual patterns in a breast FNA cytology should raise the suspicion of a metastatic ovarian tumor. Direct comparison between the breast FNA cytology and the original primary ovarian tumor should confirm the diagnosis. The proper diagnosis of metastatic ovarian cancer to the breast will prevent unnecessary surgical treatment and ensure the appropriate therapy.

Breast care consultation center: role of the pathologist in a multidisciplinary center.

The Breast Care Consultation Center (BCCC) is a multidisciplinary center providing, in a single setting, a complete outpatient facility for women who have been diagnosed with or suspected of having breast cancer. A team of specialists are available to provide comprehensive, diagnostic (radiologist, surgeon, and pathologist), therapeutic (surgeon, radiotherapist, and medical oncologist), and support options. The pathologist, as a member of the diagnostic team, evaluates the material obtained or received at the BCCC. These include fine-needle aspirations (FNAs) obtained on-site as well as previously prepared cytohistological specimens. The pathologist renders the diagnosis following examination of the material and consultation with the multidisciplinary team. Thus, this approach is conducive for appropriate and accurate diagnosis where all data are available. In addition, the pathologist discusses the findings of each patient in the multidisciplinary conference. One thousand four hundred eighteen patients were evaluated at Magee-Womens Hospital BCCC from February 1992 through December 1994, during which time 366 FNAs were performed. The accuracy for positive diagnosis was 100%. Six negative cases had cancer on histology; these were due to sampling error (the lesion was missed). A multidisciplinary team is ideal for the evaluation of breast lesions that are suspicious for malignancy as it provides one-stop shopping and same-day diagnosis and therapeutic decisions.

Cytomorphologic features of classic and variant lobular carcinoma: A comparative study.

There are several subtypes of lobular carcinoma (LC), and their cytomorphologic features differ from classic lobular carcinoma (CLC). The finer details of the differences between CLC and variant lobular carcinoma (VLC) have not been adequately studied. A comparative study of 54 cases of CLC and VLC was done in order to verify any statistically significant differences between them. All cases had histologic confirmation of the diagnosis. Six parameters, which included cellularity, signet-ring cells, intracytoplasmic lumina (ICL), anisonucleosis, cell size, and prominent nucleoli, were studied. The only statistically significant findings were cellularity and cell size when compared to CLC. The cellularity in VLC was higher and the cells in VLC were larger when compared to CLC. There are no definite diagnostic features to identify VLC; however, in a cellular specimen with plenty of large cells with other features of LC, one should have a high index of suspicion of VLC.

Psammoma bodies and detached ciliary tufts in a cervicovaginal smear associated with benign ovarian cystadenofibroma.

Psammoma bodies and detached ciliary tufts, or ciliocytophthoria, were present in a cervicovaginal smear from a 38-year-old woman with a benign cystadenofibroma of the left ovary. This case demonstrates that psammoma bodies in cervicovaginal smears may occur in association with nonmalignant conditions of the female genital tract and that detached ciliary tufts may originate from the ovarian epithelium.

Fine needle aspiration biopsy of breast carcinoma in pregnancy and lactation.

OBJECTIVE: To delineate the cytomorphologic features seen in cancer of the breast during pregnancy and lactation, to compare them to the cytomorphologic parameters in benign conditions and to determine the feasibility of differentiating features of malignant breast carcinoma from those of benign breast lesions during pregnancy. STUDY DESIGN: The study group consisted of pregnant or lactating women with breast carcinoma and with benign breast lesions who underwent fine needle aspiration (FNA) of the breast lesions. The findings of FNA were reviewed, analyzed, tabulated and correlated with the pathologic diagnosis of the breast biopsies. RESULTS: Eleven patients had malignant cytomorphologic changes, including increased cellularity, multilayering, enlarged and pleomorphic nuclei, single or multiple nucleoli, mitosis and numerous isolated tumor cells. Secretory changes were scanty. The background was foamy and necrotic. FNA of the benign lesions showed a biphasic cell pattern with cohesion; minimal nuclear pleomorphism; single, regular nucleoli; and naked nuclei in a granular background with foamy macrophages. Increased cellularity with nuclear atypia, single cells and a dirty background was seen in benign and malignant conditions. CONCLUSION: The main cytologic features that differentiate breast carcinoma from benign conditions during pregnancy and lactation are crowding and overlapping of nuclei, dyscohesion and enlarged, pleomorphic nuclei with irregular nuclear membranes, coarse nuclear chromatin and mitoses. Pregnancy-related hyperplastic changes with atypia can potentially result in a false positive diagnosis of carcinoma.

Tracheal aspiration cytology in neonates with respiratory distress: histopathologic correlation.

This report evaluates the use of tracheal aspiration cytology in the differential diagnosis of respiratory distress in neonates by correlating cytologic features with histopathologic findings in 72 infants who died and were autopsied at Magee-Womens Hospital. It is concluded that the common causes of respiratory distress in neonates, including hyaline membrane disease (conventional and yellow), pneumonia, aspiration syndrome, pulmonary hemorrhage and bronchopulmonary dysplasia, may be diagnosed in adequate smears by this easily accessible, noninvasive, safe and repetitive method.