VIN 3: a clinicopathologic review.

A retrospective review of the management of vulvar intraepithelial neoplasia 3 (VIN 3) over a 16-year period from 1981 to 1997 was conducted. Complete information was available for analysis on 101 patients. The mean age was 53.9 years (range 14-102 years). The mean duration of follow-up was 36 months (range 2-184 months). Fifty-eight percent of patients presented with pruritus. The disease was multifocal in 51% and unifocal in 49% of cases and the left labium majus was the most frequently affected site (27%). Co-existent or previous genital disease was identified in 39% of patients and 8% had a history of invasive gynecological cancer. Histologic evidence of human papillomavirus (HPV) infection was found in 31% of patients. Wide local excision was the most frequently used treatment modality (78%). Thirty-eight percent of patients required at least one further treatment for recurrent disease. Smoking, multifocality, HPV effect, and positive surgical margins were not found to be significant predictors of recurrence. There were three (3%) cases of progression to invasive squamous cell carcinoma of the vulva, one at 6, 7, and 7 years after initial treatment.

Isolated dissection of the coronary artery: a postmortem study of seven cases.

We present the clinical and postmortem findings in seven adults (four females and three males), who died with dissection of the coronary arteries. The median age was 56 years. Five of the coronary artery dissections (CADs) were spontaneous and two followed trauma: one a motor vehicle accident, the other occurred during angiography. Four cases died suddenly or within 30 minutes. Three had symptoms of at least 24 hours duration and, not unexpectedly, had histological evidence of myocardial infarction. Four dissections involved the left anterior descending coronary artery, two the right coronary artery and one a dominant circumflex artery. Histological examination of the dissected arteries in four cases demonstrated necrosis of the medial smooth muscle which was intimately related to intimal tears and/or an inflammatory reaction. From a review of the literature and this study of seven cases, we conclude that CAD is multifactorial in causation and has a wide spectrum of clinical presentations. Presently the role of coronary vasospasm and prior trauma appears underestimated, and in many cases of CAD the nature of the primary initiating event remains open to speculation.

Prognostic significance of fallopian tube cytology: a study of 99 endometrial malignancies.

The purpose of the study was to relate fallopian tube lavage-cytology (tubal washings) from patients treated for endometrial malignancies with other recognized prognostic factors and also with patient survival. In 99 patients the following prognostic variables were analyzed: patient age, peritoneal washing cytology (PW), endometrial tumor grade, depth of myometrial invasion, myometrial vascular involvement, cervical stromal infiltration and peritoneal metastases. The association between tubal washings and preoperative hysteroscopy was also examined. Of the 99 patients with endometrial malignancy, 18 experienced their first tumor recurrence or died from tumor during the follow-up period (median 53 months, range 5-137 months). The remaining 81 patients were disease-free on their last visit or died from unrelated causes. Detailed statistical analysis revealed a complex inter-relationship between the variables but no independent prognostic significance for tubal washings. Furthermore, the absence of any statistical association between hysteroscopy and survival suggests that preoperative hysteroscopy has no deleterious effect. Although the small number of patients in this study limits any definitive conclusion, the analyzed data suggest that tubal washing cytology plays no useful role in the current management of patients with endometrial malignancies.

Spindle cell lipoma of the breast.

Spindle cell lesions, which commonly arise in the soft tissues, may present in the breast and be difficult to distinguish from primary mammary spindle cell tumors. We present the case of a 28 year old woman with a 1.5 cm circumscribed spindle cell lipoma lying deep within the tissue of the right breast. Thin, uniform spindle cells were associated with collagen bundles, mature adipocytes and entrapped normal mammary ducts, lobules, vessels and nerves, appearances which simulated an aggressively infiltrating tumor. The spindle cells proved immunoreactive to CD34 and vimentin but non-reactive for cytokeratin, S100, desmin, smooth muscle actin and Factor VIII. Although surgical resection was incomplete, the patient is alive and without evidence of tumor recurrence 12 months postoperatively. In our case, a conservative approach to management was justified and supported by the patient's subsequent clinical course. This case exemplifies the diagnostic challenge of spindle cell lesions arising in breast tissue and the value of immunoperoxidase stains.

Cervical/vaginal endometriosis with atypia: A cytohistopathologic study.

Neoplastic or atypical glandular epithelial cells of uncertain significance were reported in the preoperative smears from 10 women with cervical or vaginal endometriosis. Subsequent conization and vaginal biopsy revealed endometriotic tissue with variable epithelial atypia, but no evidence of in situ or invasive carcinoma. Review of the smears revealed appearances similar to those seen in "high cervical sampling" or in smears from patients with tubal metaplasia. The presence of large cohesive cell sheets with retained cell polarity and well-defined cytoplasmic edges, of endometrial cell "whorls" and tubular structures, and of endometrial-like stromal cells coupled with the absence of three-dimensional cell clusters, peripheral cell-sheet crowding, "cell feathering," and pseudostratified cell strips are features helpful in the distinction between cervical/vaginal endometriosis and adenocarcinoma. Diagn. Cytopathol. 1999;21:188-193.

Management of uterine leiomyosarcoma in Australia.

Uterine leiomyosarcoma is an uncommon malignancy for which the management varies widely between individual gynaecologists and gynaecological oncology units. We have performed a retrospective review of patients treated at both the Royal Women's Hospital in Melbourne (1970-1997) and King George V Hospital in Sydney (1987-1993). In addition we have performed a survey of Certified Gynaecological Oncologists (CGO's) to assess the current management of uterine leiomyosarcomas in Australia. The results show varied management practices exist in Australia, many of which are not supported by evidence in the current literature. Oophorectomy in the premenopausal patient appears unnecessary unless the ovaries are macroscopically involved. The role of pelvic lymphadenectomy is debatable. This practice was recommended by many CGO's, yet these nodes are rarely positive unless obvious extrauterine disease is present. Adjuvant chemotherapy appears not to have a role at present unless in a trial setting. Adjuvant radiotherapy does appear to have a potential palliative role as it prevents locoregional relapse, although survival is not prolonged. Until suitable phase 3 trials are available, gynaecological oncology units should be meticulous in prospectively recording the clinical course of their patients and critically analyzing their current management strategies.

First reported case of endometrial carcinoma in association with HIV infection.

Endometrial adenocarcinoma is the most common gynecologic cancer in developed countries, although it has never before been documented in a female infected with human immunodeficiency virus (HIV). By contrast, cervical carcinoma is well described in association with HIV infection and in 1993 was added to the AIDS case definition. We present the unique case of a 38-year-old HIV-infected female with endometrial carcinoma, who became rapidly disseminated following her initial surgery. Although HIV is unlikely to have an etiologic role in endometrial carcinoma, it is conceivable that immunosuppression contributed to an accelerated course of her malignancy.

Fallopian tube cytology: a histocorrelative study of 150 washings.

The aim of the study was to assess the relationship between fallopian tube lavage cytology and recognized microscopic prognostic features in cancer of the uterine corpus. Tubal (TW) and peritoneal washing cytology (PW), endometrial tumor grade, and tumor involvement of the cervix, myometrium, myometrial vessels, and peritoneum were assessed in 150 patients. Endometrioid adenocarcinoma grade I was considered a low-grade tumor, while endometrioid carcinoma grades 2/3, serous/clear cell carcinoma, carcinosarcoma, and high-grade stromal sarcoma were considered high grade. The overall concordance rate for paired TWs and PWs was 72% (108/150). Forward stepwise logistic regression analysis of the 150 tumors revealed that only PWs and cervical involvement were independently predictive of TWs. No relationship was evident between TWs and depth of myometrial invasion, myometrial vascular involvement, or peritoneal metastases. It is concluded that retrograde transtubal spread by malignant endometrial cells occurs independently of myometrial histoprognostic features. TWs provide supporting evidence for diagnostically difficult PWs, and malignant TWs may be detected in the presence of minimally invasive serous/clear cell carcinoma and carcinosarcoma of the endometrium.

Desmoplastic melanoma of the vulva.

The clinical and pathological features of a nonulcerated desmoplastic melanoma in the vulva of a 52-year-old woman are presented. Pleomorphic neoplastic spindle cells, fibroblasts and collagen formed a poorly demarcated 18 mm dermal mass. No adjacent intraepidermal component was seen. Immunoreactivity was demonstrated for S100 protein, vimentin, neuron-specific enolase and actin, but not for HMB-45, CAM 5.2, cytokeratin, epithelial membrane antigen, desmin or CD34. Electron microscopic examination was noncontributory. Treatment included a left hemivulvectomy with ipsilateral groin node dissection followed by radiotherapy. The tumor recurred six weeks later and was unresectable. The patient is alive with symptoms nine months after presentation. This is the first case report of a vulvar desmoplastic melanoma without neural involvement or an intraepidermal component. The variable tumor cytomorphology, nonspecific immunohistochemical and ultrastructural features render a diagnosis more difficult than with other primary cutaneous melanomas.

Adenoma malignum of the cervix: a reappraisal.

We here report a case of adenoma malignum of the cervix in a 59 year old woman with a 6 month history of a clear watery vaginal discharge. The tumor was an incidental finding in a hysterectomy specimen. Histological examination revealed irregular neoplastic glands formed by mucinous columnar epithelial cells with minimal cytological atypia and a focal stromal reaction. The endothelium of several large veins within the cervical stroma was replaced by neoplastic cells. All seven preoperative Pap smears were normal. The ovaries were normal. The difficulties in making a histological diagnosis of adenoma malignum justifies its separation from the more common well differentiated cervical adenocarcinomas. Furthermore in view of the difference in prognosis, cytohistomorphology and the known association with ovarian tumors, we recommend that the term "adenoma malignum" be retained but restricted to the mucinous endocervical type of minimal deviation adenocarcinoma.

Granulosa cell tumors of unilocular cystic type.

We reviewed the clinical, pathological and immunohistochemical features of six unilocular cystic granulosa cell tumors (UCGs) of the ovary. The mean age of the patients was 46 years and the presenting features included abdominal distension, pain, urinary frequency, dyspareunia and amenorrhea. The tumors were unilateral, thin walled and consisted of a single large cavity with a smooth internal lining. The mean tumor-diameter was 10 cm and in all instances the UCGs were of adult histological type. The granulosa cells in six tumors demonstrated immunoreactivity for vimentin, five neoplasms showed reactivity for both alpha-inhibin and progesterone-receptor protein and four showed reactivity for smooth muscle actin. All tumors were nonimmunoreactive with antibodies to epithelial membrane antigen, beta-inhibin, estrogen-receptor protein, testosterone and s100 antigen. Only one of the three patients tested preoperatively had an elevated serum inhibin concentration and this returned to normal six weeks post-operatively. We conclude that UCGs are distinguished by the infrequency of diagnostic serum tumor markers and clinically evident endocrine activity. Correct diagnosis is dependent on histological examination and the finding of a monotonous population of cells, a trabecular growth pattern, nuclear grooves, low mitotic activity and an immunohistochemical profile compatible with granulosa cell tumors.

Non-primary cervical adenocarcinomas.

We reviewed 16 non-primary cervical adenocarcinomas collected during a six year period. Ten tumors originated in the endometrium, three in the ovary and one each in the bladder, colon and fallopian tube. Tumor spread was identified by combined lymphovascular involvement and stromal invasion in five of the 16 cervices, lymphovascular involvement alone in four cervices, stromal invasion alone in two cervices, lymphovascular involvement with stromal invasion and cervical implantation in two cervices and cervical implantation alone in three cervices. The three tumors with surface implantation alone were of endometrial origin, had minimal if any myometrial invasion, no extrauterine metastases and two had malignant peritoneal washings. Of the 13 tumors with cervical lymphovascular involvement and/or stromal metastases, 11 had ovarian, nodal and/or peritoneal metastases. We conclude that cervical implantation occurs exclusively with endometrial adenocarcinomas, that it follows previous cervical instrumentation and that the prognosis is dependent on the histoprognostic features of the primary endometrial tumor. In contrast, cervical lymphovascular involvement and/or stromal metastases usually reflects disseminated pelvic or abdominal malignancy with a poor prognosis. However histological examination may not afford separation of these two lesions if local cervical invasion is advanced, if spread has occurred by more than one mode or if insufficient clinical/surgical information is provided.

Aspiration cytology of ovarian cysts and cystic neoplasms. A study of 235 aspirates.

OBJECTIVE: To assess the diagnostic value of aspiration cytology in individual cystic lesions of the ovary. STUDY DESIGN: During a 42-month period, 235 cystic ovarian lesions were investigated by fine needle aspiration with cytologic examination (FNA). RESULTS: Almost 56% (131/235) of the aspirates were devoid of diagnostic cells. The 104 diagnostic aspirates comprised 49 follicular cysts, 4 endometriotic cysts, 45 neoplastic lesions and 6 paraovarian/paratubal cysts. Cyst fluid estradiol (E2) content > 20 nmol/L identified an additional 43 follicular cysts. Histologic examination of the ovarian lesions with acellular cyst fluid containing low E2 revealed 2 corpus luteum hematomas, 1 atretic follicular cyst, 7 endometriotic cysts and 27 serous/mucinous epithelial tumors. The remaining 51 lesions were composed of other entities. Although the specificity of FNA for most nonfollicular cystic ovarian lesions approaches 100%, the sensitivity ranged from 36% for endometriotic cysts to 83% for proliferating/malignant serous tumors. CONCLUSION: Prior to FNA of the ovary in an individual patient, consideration should be given to the likely diagnosis, the limitations of the technique and the high false negative rate for nonfollicular cystic lesions.

Choroidal cells in ovarian cyst fluid: a case report.

BACKGROUND: The ovary is conspicuous for the wide diversity of histologic tumor types that it contains. Unusual or rare tumors may present diagnostic difficulty on cytologic examination. CASE: A 36-year-old woman presented with an 80-mm cystic lesion in the left ovary. Fine needle aspiration provided 30 ml of transparent, light yellow fluid. On cytologic examination, numerous clusters and rosettes of benign cells, resembling choroid plexus cells, were seen. Surgical resection confirmed the presence of an ependymal cyst adjacent to a mature cystic teratoma (dermoid cyst). CONCLUSION: We report this unique case in order to alert cytologists unfamiliar with cerebrospinal fluid cytopathology to the rare entity of ovarian ependymal cysts.

Diffuse leiomyomatosis of the uterus.

The clinical and pathological features of four cases of the rare entity diffuse leiomyomatosis of the uterus are described. The patients, who ranged in age from 28 to 35 years, presented with a six month to ten year history of abnormal uterine bleeding, dysmenorrhoea and an enlarged uterus. Hysterectomy in each case revealed a symmetrically enlarged uterus containing numerous small ill-defined leiomyomatous nodules. On microscopic examination the nodules were composed of compact fascicles and interweaving bundles of plump uniform benign smooth muscle cells. The nodules blended with each other and merged imperceptibly with the surrounding less cellular normal myometrium. The four patients are alive and well without further treatment. The follow-up period ranged from six months to twelve years.

Arias-Stella reaction associated with cervical pregnancy. Report of a case with a cytologic presentation.

We report the case of an Arias-Stella reaction of the cervix presenting in the cervical smear from a 35-year-old woman who complained of heavy menstrual periods. The smear was originally reported as inconclusive. Colposcopy revealed an abnormal transformation zone extending out of range. Cervical conization was performed. Histologic examination revealed an ectopic cervical pregnancy associated with a cervical Arias-Stella reaction. The cytologic manifestations of the Arias-Stella reaction continue to cause diagnostic confusion with benign lesions and adenocarcinoma. We believe this to be the first reported case of a cervical Arias-Stella reaction associated with a cervical pregnancy; it should alert cytologists to the diagnostic implications.

Intravenous leiomyomatosis of the uterus: a clinicopathologic study of 22 cases.

Twenty-two cases of intravenous leiomyomatosis (IVL) of the uterus were examined at the Royal Women's Hospital, Melbourne, within a 22-year period. The mean age of the patients was 46 years (range, 23-66). Nine patients presented with a pelvic mass, nine with abnormal uterine bleeding, and one with prolapse of the uterus. In three cases, the presenting features were unknown. Surgical exploration confirmed the presence of a uterine mass (mean size, 7.8 cm) which in seven cases extended into the broad ligament. In only 11 cases was involvement of the myometrial vessels obvious on gross examination. However, no extension into the iliac veins or inferior vena cava was found. In seven cases, the tumor involved to a minimal degree the immediately adjacent or contiguous myometrial veins, and the diagnosis of IVL was made incidentally on microscropic examination. Of the 16 patients with follow-up (mean, 7.5 years) all are now disease free. Five years after the diagnosis of IVL, one patient (case 10) had a pulmonary smooth-muscle tumor resected. All 22 patients were treated by surgery alone, and to date none have died from disease. Our findings support the benign biologic behavior of IVL even in the presence of metastases.

Bacillary angiomatosis of the spleen.

Bacillary angiomatosis is a recently described vasoproliferative lesion associated with infection by a newly characterized rickettsial organism, Rochalimaea henselae. Most previous reports have described skin lesions in immunocompromised patients infected with human immunodeficiency virus. This is the first case report detailing the features of bacillary angiomatosis of the spleen occurring in a patient undergoing cytotoxic chemotherapy for disseminated ovarian carcinoma.