Adenocarcinoma in situ of the uterine cervix: an experience with 100 cases.

OBJECTIVE: The aim of this study was to ascertain whether cold knife conization alone for cervical adenocarcinoma in situ is safe. METHODS: One hundred consecutive patients with a histologically proven adenocarcinoma in situ (AIS) of the cervix were studied from 1970 to 1992. RESULTS: Ninety-two women presented with abnormal smears, and of these 56% contained abnormal glandular cells. Sixty-seven (74%) of 90 women who underwent colposcopy had an abnormal examination, but a glandular abnormality was suspected in only 19 (28%). In all, 80 cold knife conizations were performed. In 7, no abnormality was found following punch biopsy. The margins were free of disease in 55 (75%). The most commonly involved margin in the remainder was the apical. Conization was followed by hysterectomy in 20 women: in 8 of these the cone margins were free and residual disease was found in 2 of the extirpated uteri: as these were extramural cases, inadequate sampling could not be excluded. Of the 12 women where hysterectomy followed conization with diseased margins, 9 had residual disease in the hysterectomy specimen. The definitive therapy was cold knife conization in 56 patients, hysterectomy in 38, and electrocoagulation diathermy in 6. Follow-up of the 53 patients treated by conization alone ranging from 1 to 16 years, with a mean of 8 years (3 have been lost to follow-up) revealed no recurrence of AIS or adenocarcinoma to date. CONCLUSION: It is concluded that cold knife conization is a safe therapeutic modality, provided that the cone biopsy has been adequately sampled and the margins are free.

Early invasive adenocarcinoma of the uterine cervix.

In an attempt to determine the natural history of early invasive adenocarcinoma of the cervix, defined as depth of invasion of 5 mm or less, an extensive review of the literature was undertaken, together with recent unpublished material of the author. Many of the cases had to be extracted from series dealing with microinvasive squamous cell carcinoma. The pons asinorum for the pathologist is the differentiation between adenocarcinoma in situ and early invasion. The criteria for microinvasion are: 1.) obvious invasion to 5 mm or less; 2.) usually complete obliteration of the normal endocervical crypts; 3.) extension beyond the normal glandular field; and 4.) a stromal response characteristic of invasive carcinoma. Not all of these criteria are present in every case. In all 436 cases were collected. Allowing for vagueness of reports, 126 patients were treated by radical hysterectomy, and none had parametrial involvement. No cases of adnexal tumors were found in the 155 patients in whom one or both ovaries were removed. Of the 219 patients with pelvic lymph node dissection, five (2%) had metastasis. There were 15 recurrences and six tumor-related deaths in the 436 patients. Only 21 patients had conization as the only treatment, and none has suffered a recurrence. It appears that early invasive adenocarcinoma behaves in the same way as its squamous counterpart. Cold knife conization is acceptable treatment only when the cone biopsy has been adequately sampled and the margins are free, especially when preservation of fertility is an issue. Loop excision procedures obscure depth of invasion and margins and are not acceptable either for diagnosis or therapy. Multicentricity does not appear to require cylindrical cones. If hysterectomy is contemplated, removal of the adnexa, per se, is unnecessary.

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.

A clinicopathologic study of glandular dysplasia of the cervix.

With the increasing incidence of cervical adenocarcinoma there is a growing interest in the detection and treatment of glandular precursors. A major obstacle to this research is that endocervical glandular dysplasia (EGD) is rare and infrequently reported. From a study of 30 patients it appears that EGD often occurs with concomitant squamous dysplasia and also benign and preinvasive glandular changes in the cervix and endometrium. If EGD is detected on cervical biopsy hysteroscopy, dilatation and curettage and cone biopsy should be performed.

Adenocarcinoma in situ of the uterine cervix progressing to invasive adenocarcinoma.

This report documents a case of adenocarcinoma in situ (AIS) of the cervix progressing to invasive adenocarcinoma. The patient, who was 32-years-old at the time of diagnosis of AIS, was followed with negative smears for 7 years after conization when a smear showed malignant glandular cells. A repeat conization demonstrated well differentiated papillary adenocarcinoma. The patient remains well 8 years after radical hysterectomy and lymph node dissection. The clinicopathological features of this case and a brief review of the literature are presented.

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.

Ceroid granulomas in the female genital system.

Three cases of ceroid granulomas of the female genital system are presented, involving the cervix in two and lesions in the ovaries and bowel serosa in the other. Ceroid granulomas are unusual and interesting lesions formed when suitable substrates accumulate within macrophages to such an extent that a relative lack of biological antioxidants results and auto-oxidation and conversion to ceroid is favoured. This may occur in the setting of haemorrhage and necrosis, whether from tumour necrosis or associated with endometriosis. Other sources of lipids and lipoproteins include bile, meconium and vernix caseosa.

Malignant mesonephric neoplasms of the uterine cervix. A report of eight cases, including four with a malignant spindle cell component.

Eight mesonephric adenocarcinomas of the uterine cervix, four of which had a malignant spindle-cell component, occurred in women aged 34 to 71 (median 43, mean 54.5) years, bringing to 14 the number of cervical mesonephric carcinomas in the literature. The tumors with a malignant spindle-cell component ("malignant mesonephric mixed tumors") are, with one possible exception, the first reported examples at this site. The patients, almost all of whom presented with vaginal bleeding, underwent hysterectomy; five also had a pelvic lymph node dissection. The tumors were all stage IB, although microscopic lymph node metastases were found in two cases. Gross examination revealed an invasive cervical mass in each case. On microscopic examination, seven tumors were adjacent to mesonephric hyperplasia, which in five cases was florid and focally atypical; in the remaining case, occasional non-neoplastic mesonephric tubules were found only within the tumor. The adenocarcinomas typically exhibited a variety of patterns, including a ductal pattern resembling endometrioid adenocarcinoma, a small tubular pattern, a retiform pattern, a solid pattern, and a sex-cord-like pattern. These disparate patterns frequently caused diagnostic difficulty. The spindle-cell component generally resembled endometrial stromal sarcoma or a nonspecific spindle-cell sarcoma; one tumor also contained multiple foci of osteosarcoma and another, a single chondroid focus. Immunohistochemical staining for a variety of antigens failed to reveal a distinctive profile, although all the carcinomas were immunoreactive for vimentin. Follow-up in six cases revealed three patients to be alive without evidence of recurrence at postoperative intervals of 2 to 3 years. Recurrent tumor developed in a fourth patient 1 year after hysterectomy; she was treated with chemotherapy and was alive and free of disease at 2 years. Another patient had intra-abdominal recurrences (including liver metastases) at 9 and 11 years and was alive with tumor at 13 years. Death at 8.5 months in a final patient was probably due to an independent stage IIc ovarian clear-cell carcinoma. These and prior observations in the literature suggest that malignant mesonephric tumors of the cervix may be more indolent than their müllerian counterparts, from which they should be distinguished. Mesonephric carcinomas in this site should also be distinguished from florid mesonephric hyperplasia, with which they are usually associated.

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.

Alpha-fetoprotein-producing adenocarcinoma of the sigmoid colon with possible hepatoid differentiation.

A patient with adenocarcinoma of the sigmoid colon producing alpha-fetoprotein (AFP) is described. Hepatoid differentiation is suggested by the morphological appearance and production of hepatic-type AFP. The possible histogenesis of such a tumor is discussed.

Primary vulvar sarcomas.

Vulvar sarcomas are uncommon, comprising only approximately 2% of all vulvar malignancies. Consequently, most reported series contain only a few cases. We add to the literature 10 cases of various primary sarcomas of the vulva, including previously unreported cases of angiosarcoma and a neoplasm resembling Ewing's sarcoma. The only histologic feature helpful in determining prognosis was tumor necrosis.

Micro-invasive squamous cell carcinoma of the cervix: a clinico-pathologic study of 200 cases with long-term follow-up.

The clinico-pathologic details of 200 patients with micro-invasive squamous-cell carcinoma of the cervix have been analyzed. All tumors invaded 5 mm or less below the basement membrane. One hundred and nine were categorized as FIGO stage 1a1 (early stromal invasion) and 91 as FIGO stage 1a2 (micro-carcinoma). The horizontal spread (length) of 12 micro-carcinomas exceeded 7 mm. Twenty-three had stromal invasion 3 mm or more, and 22 had capillary-like space involvement. Fifty-eight patients underwent pelvic lymphadenectomy in addition to hysterectomy and none had positive nodes. Univariate and multivariate analyses of possible prognostic factors including depth, horizontal spread, width, area, volume, grade, growth pattern, capillary-like space involvement, and stromal reaction failed to show any to be significantly associated with recurrence. The median duration of follow-up is now 8 years (0-22 years). Despite complete resection, seven (3.5%) patients developed recurrence of in situ or invasive carcinoma (three after early stromal invasion and four after micro-carcinoma), all of which were located at the vaginal vault. There were two deaths, one due to pulmonary squamous-cell carcinomatosis 21 years after early stromal invasion, the connection being tenuous, and the other due to local recurrence. There have been no recurrences to date in 23 patients treated by conization alone. The uniformly good prognosis of patients in this study is attributed to meticulous sampling of operative specimens resulting in accurate diagnosis and appropriate treatment, which may be conization alone provided the margins are free, there is no capillary-like space involvement, and the depth of penetration is less than 3 mm.

Extragenital adenosarcoma arising in the pouch of Douglas.

We describe a rare case of extrauterine adenosarcoma, the first arising in the Pouch of Douglas, in a 49-year-old premenopausal woman with an elevated CA 125. The tumor consisted of benign glandular and malignant stromal elements. There was no associated endometriosis. Previously reported cases of extragenital adenosarcomas are reviewed.

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.

A case of malignant strumal carcinoid.

A malignant strumal carcinoid with widespread metastases resembling a well-differentiated thyroid follicular carcinoma is described. Strumal carcinoid is a rare ovarian tumor which usually behaves in a benign manner. Only one malignant case has been reported in the literature and in that case the carcinoid element metastasized. The clinical, histological, and immunohistochemical findings of the current case together with the relationship between strumal carcinoids and struma ovarii are discussed.