Scanning electron microscopy, x-ray diffraction, and electron microprobe analysis of calcific deposits on intrauterine contraceptive devices.

Deposits found intrauterine contraceptive devices (IUDs) were studied by scanning electron microscopy, x-ray diffraction, and energy dispersive x-ray microanalysis. All seven devices, including five plastic and two copper IUDs, were coated with a crust containing cellular, acellular, and fibrillar material. The cellular material was composed of erythrocytes, leukocytes, cells of epithelial origin, sperm, and bacteria. Some of the bacteria were filamentous, with acute-angle branching. The fibrillar material appeared to be fibrin. Most of the acellular material was amorphous; calcite was identified by x-ray diffraction, and x-ray microanalysis showed only calcium. Some of the acellular material, particularly that on the IUD side of the crust, was organized in spherulitic crystals and was identified as calcium phosphate by x-ray microanalysis. The crust was joined to the IUD surface by a layer of fibrillar and amorphous material. It is suggested that the initial event in the formation of calcific deposits on IUD surfaces is the deposition of an amorphous and fibrillar layer. Various types of cells present in the endometrial environment adhere to this layer and then calcify. Thus, the deposition of calcific material on the IUDs is a calcification phenomenon, not unlike the formation of plaque on teeth. Hum Pathol 16:732-738, 1985.

Aggressive uterine sarcoma with rhabdoid features: diagnosis by peritoneal fluid cytology and absence of INI1 gene mutation.

We report a primary uterine sarcoma with classic histologic, immunohistochemical, and ultrastructural features of a malignant extrarenal rhabdoid tumor (MERT). It arose in a 71-year-old woman who presented with postmenopausal bleeding, ascites, and a right pelvic mass. Malignant cells with rhabdoid morphology were identified by cytologic examination of the peritoneal fluid. Exploratory laparotomy revealed a 10-cm right adnexal mass and disseminated peritoneal tumor. Pathologic study showed diffuse expansion of the endometrial stroma by rhabdoid-like cells with transmural infiltration of the myometrium and extensive involvement of uterine serosa and right ovary by tumor. Neoplastic cells were immunoreactive for vimentin, cytokeratin, and epithelial membrane antigen, and cytoplasmic whorls of intermediate filaments were observed by electron microscopy. Fluorescence in situ hybridization (FISH) studies with chromosome 22-specific probes showed no loss of the INI1 gene, and no coding sequence mutation was identified.

p53 mutations and clonality in vulvar carcinomas and squamous hyperplasias: evidence suggesting that squamous hyperplasias do not serve as direct precursors of human papillomavirus-negative vulvar carcinomas.

Previous studies of vulvar carcinomas have shown two distinct subsets with respect to several clinicopathologic features. In younger women, the tumors are frequently human papillomavirus (HPV) positive, are usually of basaloid or warty histology, and are associated with vulvar intraepithelial neoplasia. In older women, the tumors are usually HPV negative, are typical keratinizing squamous carcinomas, and are associated with squamous hyperplasia--a lesion that has been purported to serve as a precursor to HPV-negative invasive carcinoma. In squamous carcinomas of the cervix, p53 inactivation (through gene mutation or interaction with the HPV E6 oncoprotein) occurs in most cases. Comparatively few studies have assessed p53 mutation and HPV status in vulvar carcinomas, and none has used molecular markers to evaluate squamous hyperplasias as direct precursors of HPV-negative invasive cancers. Of 18 invasive squamous carcinomas analyzed, seven (39%) were found to be HPV positive. Four p53 gene mutations were identified--all in HPV-negative tumors. DNA was subsequently prepared from microdissected archival tissues from all four specimens showing p53 gene mutations. DNA was separately isolated from normal squamous epithelium, invasive squamous carcinoma, and associated squamous hyperplasia. In each specimen, the p53 mutation was confirmed in the invasive tumor and absent in both normal and hyperplastic epithelium. To further investigate squamous hyperplasia as a potential precursor of HPV-negative invasive carcinoma, the authors determined the clonality of hyperplastic lesions adjacent to invasive carcinomas with p53 mutation. Clonality analyses were performed using a polymerase chain reaction (PCR)-based assay for X chromosome inactivation. Although all three informative carcinomas tested were monoclonal, corresponding normal epithelia and hyperplastic lesions were polyclonal. These findings underscore the heterogeneity of vulvar cancers with respect to loss of wild type p53 function either by interaction with the HPV E6 oncoprotein or somatic mutation of p53, and suggest that squamous hyperplasias do not serve as direct precursors of HPV-negative squamous carcinomas.

Gynecologic pathology as a hybrid subspecialty.

Gynecologic pathology is a discipline that encompasses the pathologic changes of the female genital tract and placenta. As a field, it may encompass 30-50% of the overall case load of surgical pathology. Five pathways of study that may lend to a career concentrated in gynecologic pathology are reviewed. Pathology training, with pathology board certification in anatomic or anatomic and clinical pathology, with fellowship training in gynecologic pathology, is the course of training taken by those in active concentrated practice in this field. The advantages and disadvantages of the various training options in gynecologic pathology are discussed. The advantages of additional training and experience in cytopathology as well as the advantages of clinical experience in gynecology and obstetrics are discussed.

Tissue section image analysis of breast neoplasms. Evidence of false aneuploidy.

Two methods have emerged for measuring the DNA content of paraffin-embedded tissue using image cytometry: (1) analysis of thin sections, and (2) analysis of nuclei extracted from thick sections. These methods were evaluated using 31 breast tumors for which paraffin-embedded material was available. Cases selected represented 11 diploid, 11 tetraploid, and 9 aneuploid tumors. Results generated using image cytometry methods were compared with those obtained using flow cytometry. For thin sections, the tissue correction feature of the CAS 200 Image Cytometer was used to estimate the DNA content of whole nuclei from measurements made on sectioned nuclei. DNA histograms were generated from tissue sections cut at the same microtome setting (5 microns) before and after software corrections of 4.5 microns, 5.0 microns, 5.5 microns, 6.0 microns. 6.5 microns, 7.0 microns, and 7.5 microns. A comparison of flow cytometry and thin-section image analysis in the absence of tissue correction showed 90% concordance for diploid, 27% concordance for tetraploid, and 77% concordance for aneuploid tumors. The ploidy estimated on thin sections by at least one of the correction values was discordant in 72% of diploid, 91% of tetraploid, and 78% of aneuploid tumors. For cell nuclei extracted from paraffin, excellent agreement was found between flow and image cytometry (r = 0.933). It was concluded that in most cases, cell nuclei extracted from paraffin are preferable to tissue sections for ploidy analysis of breast tumors using image cytometry.

Carcinoembryonic antigen and L-fucose in malignant and benign mammary disease.

A prospective study of 123 patients was undertaken to determine whether carcinoembryonic antigen (CEA) or L-fucose could be used as "tumor markers" to distinguish patients who had mammary cancer (41) from patients who had benign mammary disease (41) and patients who did not have mammary cancer (41). The predictive value of positive test results for both L-fucose and CEA was lower for patients who smoked than for those who did not. The sensitivities of CEA and L-fucose indicators are both below 55%. There were frequent false-positive and false-negative results. A substantial overlap in the levels of CEA and L-fucose was found for the patients who had mammary cancer and those who had benign mammary disease. CEA and L-fucose performed similarly in distinguishing cancer from benign disease. For patients who smoked, however, the predictive value of L-fucose was only 44%. The effect of smoking on L-fucose levels may account for discrepancies in L-fucose data reported in previous studies of mammary cancer. Neither CEA nor L-fucose were found to be of value in screening for mammary cancer.

Peritoneal osteosarcoma following irradiation therapy of ovarian cancer.

A peritoneal osteosarcoma occurring after irradiation therapy for cystadenocarcinoma of ovary is described. Only 6 cases of postradiation extraosseous osteosarcomas have been reported and none of them have arisen within the peritoneum. The clinical presentation and histopathology of this unusual tumor is presented with a review of the literature.

Recurrent squamous cell carcinoma of the cervix within pelvic-abdominal lymphocysts.

Two cases of recurrent squamous cell carcinoma of the cervix within pelvic-abdominal lymphocysts are presented. The majority of symptomatic lymphocysts after radical pelvic surgery present in the early postoperative period. When lymphocysts become clinically apparent many months after surgery, differentiating the usual benign cystic masses from those involving the recurrent tumor may be difficult. The diagnosis and management of the late-occurring lymphocysts are discussed. From the authors' experience and a review of the literature, it can be concluded that a lymphocyst occurring six months after surgery is unusual, and this should be highly suspect of harboring recurrent tumor. Adequate excision of the lymphocyst wall for histologic study is the most accurate method to rule out recurrent carcinoma.

Vulvar surgery for neurofibromatosis.

Von Recklinghausen's neurofibromatosis is an unusual disorder with a wide variety of manifestations. The initial findings may at times involve the female genitalia. When the vulva is affected, the obstetrician-gynecologist has an opportunity for the establishment of an accurate diagnosis as well as for cosmetic correction. Two cases are presented which illustrate these concepts.

Borderline microinvasive carcinoma of the cervix.

This study identifies borderline microinvasive carcinoma of the cervix as a subgroup of microinvasive carcinoma. We define borderline microinvasive carcinoma of the cervix as the infiltration of neoplastic squamous epithelial cells into the stroma where the depth of infiltration is 1 mm or less from the basement membrane of the epithelial surface immediately adjacent to the site of infiltration without capillary-like or lymphatic-like space involvement. In a 20-year review of cervical neoplasia in our institution, 29 cases of borderline microinvasion were identified. None of these 29 patients had recurrent carcinoma. Of our in situ carcinomas, 4.8% were found to be borderline lesions on review. Of our cases initially interpreted as microinvasion, 27.1% were, in fact, borderline lesions. There are better data to establish the criteria for borderline microinvasive carcinoma than there are to establish the absolute depths of invasion that would be unequivocally acceptable as "microinvasion." Borderline microinvasive carcinoma of the cervix is a lesion which is not metastatic and can be treated by nonradical methods.

Endometrial involvement by cervical intraepithelial neoplasia.

Two cases of cervical intraepithelial neoplasia (CIN) with superficial extension to the endometrium are presented, and the English literature is reviewed. The concept of the radial growth phase of CIN is presented and discussed. The radial growth phase may precede the vertical or invasive phase of neoplastic growth. The possibility of endometrial involvement in CIN points to the potential hazard of not evaluating the endocervix and endometrium before treatment of cervical CIN.

Vulvar intraepithelial neoplasia and skin appendage involvement.

Vulvar intraepithelial neoplasia may extend into the pilosebaceous units of the hairy and non-hairy skin of the vulva, and inadequate removal may cause treatment failure. We measured with a calibrated microscope the thickness of vulvar intraepithelial neoplasia and the depth to which it extended into the underlying pilosebaceous units of the vulvar skin. The mean thickness of vulvar intraepithelial neoplasia in 329 histologic sections from 62 cases was 0.38 mm; 99.5% of all vulvar intraepithelial neoplasia measured less than 0.77 and 0.69 mm in the hairy and non-hairy skin, respectively. Sebaceous-gland and hair-follicle involvement by vulvar intraepithelial neoplasia was 21 and 32%, respectively. The mean depth of sebaceous-gland involvement was 0.77 mm in the hairy skin and 0.50 mm in its non-hairy counterpart; 99.5% of all vulvar intraepithelial neoplasias extended less than 2.03 and 1.07 mm in the hairy and non-hairy skin, respectively. The mean depth of hair-follicle involvement was 1.04 mm; 99.5% of all hair follicles were involved less than 2.55 mm. Our findings suggest that removal of vulvar intraepithelial neoplasia to a depth of 1.0 and 2.0 mm in the non-hairy and hairy skin, respectively, is appropriate for successful treatment.

Multicentric nature of vulvar carcinoma in situ.

A detailed histologic and DNA-microspectrophotometric study is presented of 31 lesions selected from 12 of 65 patients with vulvar carcinoma in situ whom the authors have seen. In 6 patients the lesions were multicentric and in 6 they were confluent. The purpose of the study was to determine whether or not there was a measurable biologic difference between these 2 distinctly different clinical lesions that would justify separating them into different categories. A hypothesis as to the clonal evolution of multicentric and confluent vulvar carcinoma is presented based on the authors' findings.

Amniotic fluid lecithin/sphingomyelin ratio changes related to centrifugal force.

Lecithin/sphingomyelin ratio (L/S ratio) in amniotic fluid has gained wide clinical acceptance as an index of fetal lung maturity. We determined L/S ratios of amniotic fluids centrifuged at various "g-forces." Our studies demonstrate that the L/S ratio value is highly dependent on the g-force used to prepare the fluid. We recommend standardization of the g-force, time, and temperature used in preparation of the amniotic fluid for L/S ratio determination.

Paget's disease of the vulva and carcinoma of the breast.

Vulvar Paget's disease is an intraepithelial change which is locally recurrent and has minimal if any propensity to invasion. Its major significance lies in the frequency with which concomitant carcinomas are discovered in association with the vulvar skin lesion. Adenocarcinoma of the vulvar apocrine glands is the most commonly associated tumor. Another apocrine adenocarcinoma, carcinoma of the breast, either antecedent or concomitant, is the second most frequently associated tumor, having been noted in 14 cases of vulvar Paget's disease. A case report illustrating this association is presented, and the importance of preoperative breast screening procedures in all patients with vulvar Paget's disease is demonstrated.

Turner's syndrome with endometrial adenocarcinoma and stilbestrol therapy.

PIP: A 26-year-old white nulliparous woman, karyotype 45X-O, had consulted her physician at age 17 with primary amenorrhea, short stature, and sexual infantilism; she had been diagnosed as having Turner's syndrome. Diethylstilbestrol (DES), 1 mg/day for 28 consecutive days every 35 days, had been prescribed and taken. After 9 years, she developed endometrial adenocarcinoma. The DES was discontinued and progesterone was prescribed in an attempt to reverse the neoplastic process. When, after 4 months, the tumor was not responsive to progesterone, a hysterectomy was performed. Adenocarcinoma of the endometrium in patients with Turner's syndrome has been recorded in 4 patients previously, all of whom had received DES orally; this case is unusual because of the young age of the patient and the unresponsiveness of the tumor to progesterone therapy. The use of DES in patients with Turner's syndrome should be challenged; cyclic estrogen with cyclic progesterone supplementation is recommended instead.^ieng

Clinical delineation of trisomy 9 syndrome.

A rare but typical case of trisomy 9 mosaicism is reported. The infant showed the characteristic phenotype of this syndrome: low-set malformed ears, micrognathia, broad nose with bulbous tip, abnormal brain, congenital heart disease, abnormal hands and feet, cryptorchidism, micropenis, and early death. This infant, however, did not have dislocation of joints or microcephaly; the head was larger than normal and had almost a cloverleaf shape.

Techniques and results of aspiration cytology for diagnosis of benign and malignant diseases of the breast.

The use of fine needle aspiration to obtain cellular material for pathologic examination was introduced in 1930 but fell out of favor for several years. In today's medical environment, fine needle aspiration is proving to be more efficacious and cost effective than conventional breast biopsy. The authors detail the technique, its complications, the reliability of the results and ways to improve it, and the suitability of the material for hormone receptor assays, detection of tumor-related problems, and ultrastructural study as well as for standard cytologic diagnosis.

How complete is influenza immunization coverage? A study in 75 nursing and residential homes for elderly people.

BACKGROUND: Elderly people in residential accommodation are particularly susceptible to outbreaks of influenza. Up to 70% of residents can become ill and many will develop complications or die. Immunization can prevent such outbreaks and is cost-effective. AIM: A study was undertaken to measure influenza immunization coverage in residential accommodation for elderly people and to identify factors that might influence uptake. METHOD: In March 1992, a questionnaire survey was conducted of all 113 registered nursing and residential homes for elderly people, in South Glamorgan. It asked about the demographic characteristics of people resident on 1 October 1991, their influenza immunization history and the homes' arrangements for administering immunizations. RESULTS: Questionnaires were returned by respondents from 75 homes (66%). Mean influenza vaccine uptake was 67%. Uptake was higher in nursing homes (mean of 82% in eight nursing homes) than in homes registered as both nursing and residential homes (mean of 76% in six homes) or in residential homes (mean of 65% in 61 homes). Nearly all of those immunized (94%) had been immunized by the end of November 1991. Residents who were reported to have underlying disease that increased their risk of complications if they contracted influenza were no more likely to have been immunized than those without risk factors. Immunization coverage varied considerably both between homes and between general practices. Most general practices in South Glamorgan had several elderly people in residential accommodation on their list, but only nine out of 64 practices had immunized all the elderly residents on their list and 12 practices had immunized fewer than half. Routine recording of immunization status in nursing and residential homes was variable, often as a consequence of poor communication between the primary health care team and staff at the home. Even where recorded, retrieval of the data was sometimes a problem. CONCLUSION: Influenza immunization coverage could be improved if general practices held a case register of all at-risk patients including elderly residents, and if nursing and residential homes were encouraged to keep better immunization records. These measures would facilitate year-on-year monitoring of influenza immunization coverage and the targeting of homes with low immunization coverage.

Normal histology and nomenclature of the vulva, and malignant neoplasms, including VIN.

In this article, vulvar anatomy and histology are reviewed, and nonneoplastic and neoplastic epithelial disorders are presented. Included are lichen sclerosus, squamous cell hyperplasia, vulvar intraepithelial neoplasia, vulvar Paget's disease, and squamous cell carcinoma. Current terminology, tumor measurements, and staging for vulvar carcinoma are reviewed.