Nicholas J. Mulvany

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 Womens 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.

Differentiated Intraepithelial Neoplasia of the Vulva

Summary We present the clinical and pathological findings of 6 women with intraepithelial neoplasia of differentiated or simplex type (DVIN). The mean age was 68 years (range 55-82). One lesion was still in situ, whereas 5 were associated with squamous carcinoma, 4 of well-differentiated keratinizing type and 1 of poorly differentiated spindle-cell type. The invasive depth of the squamous carcinomas ranged from 0.6 to 8 mm and the surgical margins of all of the resection specimens were uninvolved by neoplastic cells. In contrast, DVIN involved the surgical margins in 5 specimens while the remaining specimen had normal surgical margins. In all 6 vulvar specimens, DVIN showed intense immunoreactivity for Ki-67 in the basal and parabasal cells while only 4 specimens showed reactivity for p53. In 5 surgical specimens with DVIN the number of CD1a cells was increased but little if any immunoreactivity could be found amongst the corresponding invasive neoplastic cells. Four squamous carcinomas also showed diffuse p53 reactivity. There was little difference in the pattern of Ki-67 expression between DVIN and squamous carcinoma. For a number of reasons, DVIN present diagnostic difficulty and considerable interobserver variation also exists. Our study suggests that Ki-67 and p16INK4A are useful for distinguishing DVIN and classical VIN 3, whereas p53 and CD1a are useful for distinguishing DVIN and invasive squamous carcinoma. Furthermore, p53 appears to have higher specificity than sensitivity for distinguishing DVIN from normal squamous epithelium.

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.

Combined large cell neuroendocrine and endometrioid carcinoma of the endometrium.

Summary We present the surgical and pathological findings and follow-up of 5 women diagnosed with combined endometrioid and high-grade neuroendocrine carcinoma of large cell type (LCNEC) arising in the endometrium. The mean age of the women was 75 years (range, 50-88 years). Of the 5 tumors, 4 formed polypoid endometrial masses associated with extensive lymphovascular involvement of the myometrium by neoplastic cells. A single endometrial tumor was formed by LCNEC alone, and 4 tumors were composite with varying proportions formed by endometrioid (4/5) and small cell neuroendocrine carcinoma (1/5). In all 5 LCNEC tumor components, an insular growth pattern was noted, whereas a diffuse (solid) pattern was found in 4 tumors, a trabecular in 2, and rosettes/pseudorosettes in another 2. In all 5 tumors, the LCNEC tumor components were labeled with neuron-specific enolase (NSE). Four tumors were reactive for chromogranin A, CAM 5.2, and p53. Three tumors were labeled for AE1/AE3, CD56 (NCAM), p16INK4A, and cytokeratin 7. Synaptophysin was reactive in 2 tumors, and CD117 was found in only a single tumor. Of the 3 endometrioid tumor components examined, all were reactive for NSE. Two tumors were reactive for p16INK4A and p53, 1 for CD56, but none for synaptophysin orchromogranin A. We conclude that LCNEC of the endometrium is a distinct clinicopathological entity with a poor prognosis irrespective of stage. The gross and histomorphological features are often suggestive, but confirmation requires immunoperoxidases, including NSE, synaptophysin, chromogranin A, p16INK4A, and p53. Combined endometrioid and high-grade LCNEC possess more characteristics of a type II than a type I endometrial carcinoma.

Management of uterine leiomyosarcoma in Australia.

Summary: 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 Womens 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 (CGOs) 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 CGOs, 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.

Isolated dissection of the coronary artery: A postmortem study of seven cases

Summary 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.

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 patients subsequent clinical course. This case exemplifies the diagnostic challenge of spindle cell lesions arising in breast tissue and the value of immunoperoxidase stains.

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.

Bacillary angiomatosis of the spleen

&NA; 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 immunocompromized 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.

The pathology of cervical neoplasia.

The World Health Organization classification has clarified the typing of cervical tumours. The category of early stromal invasion has been eliminated from the International Federation of Gynecology and Obstetrics staging scheme of cervical carcinoma. Stage lal is defined now as depth of invasion less than or equal to 3 mm; stage la2 is defined as depth of invasion between 3 and 5 mm in depth. The width should not exceed 7 mm. Small cell carcinoma has been better delineated. An increased incidence of human papillomavirus infection and cervical intraepithelial neoplasia has been observed in patients suffering from the effects of human immunodeficiency virus, in whom invasive cervical cancers run a more aggressive course. The better understanding of pseudomalignant lesions, that is, deep cervical glands, various metaplasias and inflammatory pseudo tumours, as well as some rare tumours, enables the surgical pathologist to make a more accurate diagnosis, resulting in better patient care.