Anisa Kanbour

Ultrastructure and observations on the histogenesis of mesotheliomas, "adenomatoid tumors", of the female genital tract.

The morphological characteristics of three mesotheliomas, the so‐called “ade‐nomatoid tumors” of the female genital organs, were studied by light and electron microscopy, in search of information on the histogenesis of these neoplasms. The histology and ultrastructure of normal peritoneal mesothelium of the urogenital region were also studied for comparative correlation. The observations made in this investigation strongly support the theory that these tumors are of mesothelial origin. It is then proposed that the term mesothelioma be encouraged to designate these benign neoplasms of the genital sphere.

A case‐matched molecular comparison of extraovarian versus primary ovarian adenocarcinoma

Extraovarian müllerian adenocarcinoma (EOM) resembles primary ovarian carcinoma (POC) both histologically and clinically, yet little is known regarding the molecular genetic characteristics of this entity. The objective of this study was to compare the expression of three molecular markers of tumor behavior in EOMs and POCs.

The spectrum of morphomolecular abnormalities of the E-cadherin/catenin complex in pleomorphic lobular carcinoma of the breast.

Pleomorphic lobular carcinoma of the breast is a high nuclear grade variant of lobular carcinoma. E-cadherin, a tumor-invasion suppressor gene, codes for a transmembrane protein that functions in intercellular adhesion. The E-cadherin protein internal domain binds with α, β, γ, and p120 catenins to anchor the E-cadherin complex to the actin cytoskeleton of the cell. The E-cadherin gene is routinely mutated in lobular neoplasia. This study examines the morphomolecular spectrum of the components of the E-cadherin-catenin complex in lobular neoplasia. Fifteen cases of pleomorphic lobular neoplasia, 8 cases of classic lobular neoplasia and 4 ductal carcinomas were studied. Normal breast epithelium and invasive ductal carcinomas all showed intense linear cell membrane immunostaining with antibodies to E-cadherin, α, β, γ, and P120 catenins. Membrane immunostaining of the catenin antibodies in lobular neoplasia was negative, except for rare cases that displayed beaded or dotlike patterns. Cytoplasmic immunostaining patterns for all lobular lesions included coarse paranuclear granules of β catenin or diffuse intense cytoplasmic staining for P120 catenin. These immunostaining patterns demonstrate that catenins α, β, γ, and p120 are routinely dislocated from the cell membrane into the cytoplasm in lobular neoplasia and that the disrupted catenin patterns parallel absence of membrane E-cadherin in all cases. The diffuse cytoplasmic immunostaining of p120 in lobular neoplasia may be useful diagnostically as a positive marker for lobular neoplasia.

Clinical significance of cytologic diagnosis of atypical squamous cells, cannot exclude high grade, in perimenopausal and postmenopausal women

We used cytohistologic correlation to determine the clinical significance of atypical squamous cells, cannot exclude high grade (ASC-H) in perimenopausal and postmenopausal women. A computer search identified 250 Papanicolaou smears from women older than 45 years with a diagnosis of ASC- H. Cases were considered perimenopausal (45 to < 55 years; 150 cases) and postmenopausal ((3)55 years; 100 cases). No follow-up data were available for 33 cases, which were excluded. The remaining 217 cases (perimenopausal, 127; postmenopausal, 90) had surgical or cytologic follow-up. Results of follow-up colposcopic biopsy were available for 176 (81.1%) and cytology for 41 (18.9%) women. Follow-up results were as follows: perimenopausal women, negative, 50 (39.4%); mild dysplasia (low-grade squamous intraepithelial lesion [LSIL]), 46 (36.2%); high-grade dysplasia (high-grade SIL [HSIL]); 28 (22.0%); and ASC of undetermined significance (ASC-US), 3 (2.4%); postmenopausal women, negative, 52 (58%); LSIL, 31 (34%); HSIL, 5 (6%); and ASC-US, 2 (2%). The diagnosis of ASC-H in postmenopausal women usually is associated with LSIL or a negative diagnosis on follow-up, suggesting a less aggressive surveillance and treatment regimen is needed for postmenopausal women with ASC-H.

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.

Risk Factors and Prognosis in Stage II Endometrial Cancer

Abstract Ninety-seven patients with Stage II endometrial cancer were analyzed by life table analysis for survival as a function of patient age, cell type, grade of tumor, depth of invasion, treatment, surgical stage, and extent of cervical involvement. The corrected 5-and 10-year survival was 65.9% and 57.9%, respectively. Cumulative 5-year survival of patients treated with radiation was 77.0%, with surgery 66.1%, and with combined therapy 58.5%. The extent of tumor, including depth of invasion, degree of cervical involvement, and presence of occult distant metastases, was most important in assessing prognosis. Of 36 patients without preoperative radiation, all those with superficial tumors lived at least 5 years, as compared with 57.9% of patients with deeply invasive tumors. These factors were less valuable in patients treated initially with radiation therapy where 30% of patients without residual tumor in the uterus died with recurrence within 5 years. The accuracy of endocervical curettage in determining cervical extension from an endometrial cancer and the patterns of recurrence were also analyzed. Less than half of patients with a normal-appearing cervix and positive endocervical curettage had tumor found in the nonirradiated hysterectomy specimen. There was poor correlation between the stage of disease and the extent of tumor found at operation. Agreement between the stage and operative findings was found in only half the patients treated initially with surgery.

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.

Squamous cell carcinoma in situ of the endometrium and fallopian tube as superficial extension of invasive cervical carcinoma

Five cases of squamous cell carcinoma of the cervix associated with widespread squamous cell carcinoma in situ of the endometrial surface are reported. In one case, carcinoma in situ was also found in one fallopian tube in continuity with the cervicoendometrial lesion. A survey of the literature reveals only 20 cases with similar surface endometrial involvement by cervical squamous cell carcinoma. Of these, the fallopian tubes were involved by an identical lesion in six cases only. Pyometra and cervical stenosis were reported in about 66% of the cases. This rare form of upward cervical cancer extension was present in five of 680 cases (0.7%) of squamous cell carcinoma of the cervix in the file of the Tumor Registry of Magee‐Womens Hospital.

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.

Carcinoma of the vagina following cervical cancer

Vaginal carcinomas at Magee‐Womens Hospital were reviewed for a 25‐year period: 51 were cases of invasive carcinoma and 23 were of carcinoma in situ. Invasive vaginal carcinoma accounted for 2.1% of all female genital tract neoplasms. Of the 23 cases of in situ carcinoma of the vagina, 16 (70%) were synchronous with or subsequent to cervical cancer; of the 51 with invasive vaginal carcinoma, 14 (27%) had concurrent or antecedent cervical cancer. This strikingly high frequent association of vaginal cancer with cervical neoplasia emphasized the multicentric occurrence of carcinoma in the lower female genital tract. The importance of lifelong periodic clinical and cytologic examinations of all patients with or without a history of previous cervical neoplasia is stressed for the detection of early vaginal lesions.