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.

Solitary luteinized follicle cyst of pregnancy. Report of a case with cytologic findings.

BACKGROUND: Giant luteinized follicle cyst is a recently recognized cause of ovarian enlargement during pregnancy and the puerperium. Only rare cases of this clinical condition have been reported in the literature, and the cytologic features have not been previously described. CASE: A 34-year-old, pregnant woman presented at 10 weeks' gestation with a large, right ovarian cyst. Clinical management was initially conservative, but four weeks later the patient presented with acute abdominal pain. At laparotomy, the ovarian cyst was aspirated and a cystectomy performed. On cytologic examination, the presence of a luteinized follicle cyst of pregnancy was suggested. Subsequent histologic examination confirmed the diagnosis. CONCLUSION: This case illustrates the clinicopathologic features of a luteinized follicle cyst of pregnancy with special emphasis on the cytologic characteristics. The cytologic features are sufficient to establish the diagnosis in conjunction with the ultrasonographic appearance.

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.

Hilus cell tumour of the ovary in a virilized, premenopausal woman. Case report and review of hyperandrogenism of ovarian origin.

A 35 year-old woman presented with virilization and was found to have elevated serum testosterone levels. Investigation revealed an 11 mm hilus cell tumour in the left ovary. After unilateral oophorectomy, serum testosterone levels rapidly returned to normal levels. The various ovarian tumours and conditions causing virilization are described and a clinical approach to the investigation of virilization is outlined.

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.

Microinvasive adenocarcinoma of the cervix: a cytohistopathologic study of 40 cases.

Cervical smears obtained from 40 women with a histologic diagnosis of microinvasive adenocarcinoma (MIA) were reexamined for features of invasion. In our study MIA was defined as stromal invasion by adenocarcinoma cells to 5 mm or less beyond a surface epithelium and without lymphovascular involvement. In 24 cervices, squamous carcinoma in situ was a coincidental histologic finding. All 40 smears contained atypical glandular cells (AGC) forming pseudosyncytial clusters, and 12 showed additional features suggestive of invasion; pleomorphic nuclei, coarse irregular chromatin, karyorrhectic nuclei, and cell detritus. The invasive features tended to occur together and were found more than twice as frequently in this group than in the remaining 28 smears. There was little difference between the two groups in the frequency of super-crowded cell clusters, acini, cell strips, isolated cells, nuclear hyperchromasia, macronucleoli, or normal cervical glandular cells. Fourteen smears from the 24 cervices with squamous carcinoma in situ contained cells from a high-grade squamous intraepithelial lesion. It is concluded that cervical cytologic examination has a sensitivity of 30% (12/40) for the identification of stromal microinvasion in adenocarcinoma in situ. Cell detritus, present in 5/12 smears, is considered highly specific for invasion but lacks sensitivity. Due to the more proximal location and ease of sampling, cytologic examination has a sensitivity of 58% (14/24) for histologically confirmed coexisting squamous lesions.

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.

Cytohistologic correlation in malignant peritoneal washings. Analysis of 75 malignant fluids.

OBJECTIVE: To determine the value of peritoneal washing (PW) cytology alone in upstaging carcinomas of the female genital tract (FGT). STUDY DESIGN: The histologic reports and slides of surgically resected FGT carcinomas related to 75 malignant PWs were reviewed. For inclusion in the study, no ascites was present. The cases consisted of 28 primary and 4 metastatic ovarian tumors, 9 peritoneal "serous implants" from second-look laparotomy, 3 metastatic peritoneal carcinomas, 1 primary peritoneal serous carcinoma, and 19 endometrial, 6 cervical and 5 tubal carcinomas. RESULTS: Cytologic examination alone was responsible for the upstaging of 0-75% of carcinomas, depending on tumor origin. Malignant cells were seen in 97% (73/75) of the cytologic smears and in 51% (28/75) of the cell blocks prepared from the PWs. CONCLUSION: The clinical value of PW cytology lies in the upstaging of 63% of borderline ovarian tumors, 50% of primary ovarian malignancies of nonserous type and 11% of endometrial adenocarcinomas. PW cytology is not recommended for primary carcinomas of the cervix, fallopian tube or peritoneum or for ovarian carcinoma of serous and metastatic types. Furthermore, PW cell blocks were less sensitive than cytocentrifuged smears and contributed only a single additional malignant PW.

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.

Pseudomyxoma peritonei: a cytohistopathologic study of nine cases.

Cytologic examination of seven peritoneal fluids from nine patients with pseudomyxoma peritonei revealed papillary clusters and isolated neoplastic cells. In all patients, one or both ovaries were replaced by proliferating (borderline) mucinous epithelial tumors of grade I-II intestinal type while three patients had synchronous appendiceal tumors of similar morphologic appearance. Four of the nine patients demonstrated positive correlation between the presence of neoplastic cells in the ovarian interstitial mucin (pseudomyxoma ovarii), the extraovarian peritoneum, and the free peritoneal fluid. Two patients demonstrated a negative correlation. The submission of an inadequate amount of ovarian or appendiceal tissue for histologic examination may account for the discordance in three patients. It is concluded that pseudomyxoma peritonei is a distinct clinicopathologic entity which can be subdivided into two types, acellular and cellular. This distinction, unlike the specific cytomorphologic features, may have prognostic significance.

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.