Fertility sparing treatment for in situ and early invasive adenocarcinoma of the cervix.

OBJECTIVE: To explore the outcome and long-term follow-up of fertility sparing surgery for cervical adenocarcinoma in situ and early invasive adenocarcinoma. METHODS: Between 1985 and 1996, all women with adenocarcinoma in situ (AIS) and stage I adenocarcinoma were identified. Data were abstracted from clinical records and pathology reviewed. RESULTS: One hundred thirty three women with stage I adenocarcinoma of the cervix were treated. Twenty subjects met the criteria for International Federation of Gynecology and Obstetrics stage IA1 lesions. Fourteen subjects were treated with radical hysterectomy, whereas two were treated with simple hysterectomy. Because of the desire to preserve fertility, four women with adenocarcinoma were treated with cervical conization alone, and three women have gone on to deliver viable infants. Forty-two women with adenocarcinoma in situ were identified, of whom 20 were treated with fertility sparing surgery (conization). Five women treated with conization had positive margins recurring in two, and one developed an invasive adenocarcinoma 5 years after conization. None of the women with adenocarcinoma treated with cervical conization have developed recurrent disease after a median follow-up of 48 months. Cone margin status was predictive of residual disease at hysterectomy. CONCLUSION: Women with adenocarcinoma in situ and negative margins may be treated with conservative, fertility sparing surgery. Education is essential regarding the risks of residual/recurrent disease because subjects can develop lethal recurrent disease. The fertility sparing management of invasive stage IA1 adenocarcinoma of the uterine cervix may also be entertained among women who desire future fertility and have negative margins of resection.

Complete response of a stage IV uterine papillary serous carcinoma to neoadjuvant chemotherapy with Taxol and carboplatin.

Uterine papillary serous carcinoma (UPSC) is an aggressive histologic subtype of endometrial cancer. Currently, no effective chemotherapy regimens exist. We report a case of complete response of a stage IV UPSC to neoadjuvant chemotherapy with Taxol and carboplatin.

Placental site trophoblastic tumor: human placental lactogen and pregnancy-associated major basic protein as immunohistologic markers.

Placental site trophoblastic tumor (PSTT) consists of a neoplastic proliferation of intermediate or extravillous trophoblast (also known as X cells). Pregnancy-associated major basic protein (pMBP) is a marker for placental intermediate trophoblast. We compared the distribution of pMBP and human placental lactogen (hPL) in 24 PSTT and 3 exaggerated placental site (EPS) specimens using two distinct immunohistologic methods. Statistical analyses were used to compare staining intensities in metastatic and nonmetastatic lesions. By immunofluorescence, 77% of the PSTT specimens and 100% of the EPS specimens stained with antibodies to pMBP, and the pMBP was localized in intermediate trophoblast and surrounding extracellular areas. By immunohistochemistry, 78% of the PSTT specimens and 100% of the EPS specimens stained for pMBP with a pattern comparable with that of immunofluorescence. Likewise, by immunohistochemistry, hPL stained 96% of the PSTT specimens and 100% of the EPS specimens. Immunohistochemical staining intensities for pMBP and hPL correlated (r2 = +.24; P = .013), but hPL staining was mainly confined to intermediate trophoblast and was more intense. Anti-pMBP tended to stain metastatic PSTT weakly. Thus, pMBP is a useful marker for intermediate trophoblast tumors and could help distinguish these from other forms of trophoblastic disease.

Trophoblastic lesions of the placental site.

The trophoblast of the chorionic villi as well as the hydatidiform mole and choriocarcinoma have been recognized and studied for many years. However, the trophoblast comprising the implantation site, chorionic plate, chorion laeve, cell islands and septa have only in recent years received attention in the literature. These "extravillous" trophoblastic cells were originally referred to as "X" cells due to doubt regarding their derivation from either maternal or fetal tissue (70). Subsequent studies determined that they were trophoblastic in origin (42), but the term X-cell is still in use today by some researchers (30, 4). Due to continued uncertainty regarding their nature and origin, many other terms have been used including syncytial wandering cells (21), placental site trophoblast, placental site giant cells (42), extravillous trophoblast (25), extravillous cytotrophoblast, nonvillous trophoblast, and intermediate trophoblast (49). Light microscopic and immunohistochemical studies have led to elucidation of specific morphologic and biochemical features of the extravillous trophoblast (48-50) which is commonly designated as the "intermediate trophoblast". Lesions of the "intermediate" or extravillous trophoblast of the placental site include the exaggerated placental site, the placental site trophoblast tumor and the recently described placental site nodule. This article will review the clinical and pathologic features of these lesions, their differential diagnosis, treatment, and prognostic factors after discussion of the origin, nature and definition of the "intermediate" trophoblast.

Abdominal wall implantation of an endocervical-like mucinous borderline tumor.

We present the case of a 21-year-old woman in whom development of a bulky abdominal wall metastasis in a laparotomy scar led to discovery of bilateral endocervical-like mucinous borderline tumors in normal-sized ovaries. Tumor implants were also present in the mesosalpinx and a pelvic lymph node. We hypothesize that the abdominal wall metastasis resulted from seeding at the time of a prior exploratory laparotomy for trauma, before the ovarian tumors were discovered. We present evidence to support our theory of mechanical implantation of borderline tumor and explore other mechanisms leading to extraovarian mucinous neoplastic involvement.

Leuprolide acetate treatment and myoma arterial size.

OBJECTIVE: To compare the size of arterial vessels in myomas from women treated with GnRH agonist (GnRH-a) or given placebo. METHODS: Our study group included 46 women about to undergo myomectomy or hysterectomy; 30 were treated with leuprolide acetate (3.75 or 7.5 mg) in three monthly doses, and 16 were given placebo. Arterial diameters of the intramyomatous vessels were measured using an ocular micrometer on hematoxylin and eosin-stained slides. RESULTS: Clinically and radiologically, the uterine volume of GnRH-a-treated patients decreased by an average of 30%, and the diameter of the largest myoma decreased by 27%. The average diameter of intramyomatous arteries was 24% smaller in GnRH-a subjects compared with those receiving placebo (136 +/- 42 versus 178 +/- 60 microns, P < .01). In addition, arteriosclerotic changes, including intimal and medial fibrosis, were seen more often in the GnRH-a-treated subjects (48 versus 25%, P < .05). CONCLUSION: Intramyomatous arteries were smaller and more often showed arteriosclerotic changes in leiomyomas removed from women treated with GnRH-a compared with those given placebo. The estrogen deprivation induced by GnRH-a may cause a relative vasoconstriction of myomatous vessels. Whether this decreased vessel size is the principal contributor to decreased myoma size will require further study.

Angiogenesis in uterine cervical squamous cell carcinoma.

This study tested the hypothesis that increased angiogenesis in squamous cell carcinoma of the cervix is an indicator of poor prognosis. We retrospectively studied 70 cases and related the microvessel count to stage and follow-up. We performed immunohistochemical staining for Factor VIII and counted the number of microvessels in a 400x field in the area of greatest density of vessels. The mean vessel count in stage I was 18.3 +/- 5.4 (26 cases), in stage II 18.0 +/- 6.8 (21 cases), in stage III 17.9 +/- 3.9 (18 cases), and in stage IV 22.2 +/- 13.6 (five cases). We found no correlation between the mean vessel count and stage (p < 0.85) or between mean vessel count and disease status on an average follow-up of 21 months (p < 0.65). With a power of approximately 70%, this study excludes the hypothesis that an increased density of microvessels is associated with a worsened prognosis in cervical squamous cell carcinoma.

The placental site nodule: an immunohistochemical study.

The placental site nodule and plaque (PSN-P) is a recently described, benign proliferation of intermediate trophoblast cells (ITs) in the endometrium or endocervix occurring after an intrauterine gestation. We performed an extensive immunohistochemical study of 11 cases of PSN-P. Cytokeratins (AE1/AE3 and MAK 6) were strongly positive in all cases stained. Epithelial membrane antigen (EMA) was positive in all cases, in 5% to 75% of lesional cells. Expression of human placental lactogen (hPL) was weak and focal, and a minority of cases were positive for human chorionic gonadotropin (hCG). More helpful in identifying the trophoblastic nature of the lesion was pregnancy-specific beta-1 glycoprotein (SP1), which was present in 100% of cases, and placental alkaline phosphatase (PLAP), present at least focally in 90% of cases stained. Vimentin was strongly positive in all cases stained. The presence of vimentin, SP1 and PLAP in PSN-P has not been documented previously. In our opinion cytokeratin, vimentin, and SP-1 are the most important monoclonal antibodies to aid in the differential diagnosis of PSN-P.

Mucin histochemistry of ovarian borderline tumors of mucinous and mixed-epithelial types.

Mucin histochemistry was studied in 23 intestinal-type mucinous borderline tumors, 21 endocervical-like mucinous borderline tumors, and 24 mixed-epithelial borderline tumors. The latter two tumors, which are of müllerian type, had a mucin composition similar to that of normal endocervix, with abundant neutral and acidic mucins in approximately equal amounts and a slight predominance of sialomucins over sulfomucins. Intestinal-type mucinous borderline tumors showed several patterns that most closely resembled gastric mucosa with varying degrees and types of intestinal metaplasia. In conclusion, mucin histochemistry shows striking differences between these two types of müllerian borderline tumors compared with intestinal-type mucinous borderline tumors and confirm the subclassification of mucinous borderline tumors into intestinal and endocervical types.

Fine needle aspiration cytology of breast ductal carcinoma in situ.

To evaluate the role of fine needle aspiration cytology (FNAC) in identifying in situ breast carcinoma, we reviewed 19 FNACs of histologically confirmed pure or predominantly ductal carcinoma in situ (DCIS). The cytologic diagnosis was positive for malignancy in 53%, suspicious in 31% and nondiagnostic in 16%. An intraductal lesion was suggested prospectively in 21%. Retrospective review showed three distinctive cytologic criteria in cases with DCIS: (1) cohesive groups of atypical ductal cells associated with scattered, individual malignant cells or a necrotic background; (2) hyperplastic ductal cells with associated malignant cells or necrosis; and (3) true tissue fragments composed of cohesive epithelial cells with a cribriform pattern. One or more findings were present in 81% of the malignant or suspicious FNACs; 19% could not be distinguished cytologically from invasive carcinoma. We studied a control group of 30 invasive ductal carcinomas; one or more criteria were found in 35% of cases with no or a minor DCIS component but in 73% of those with an extensive DCIS component. We conclude that these three criteria deserve further study as an aid in suggesting DCIS on FNAC.

Mural nodules in common epithelial tumors of the ovary.

The occurrence of mural nodules in cystic common epithelial tumors of the ovary is well established, but differences in terminology and difficulties in histopathologic interpretation have hampered adequate understanding of their differential diagnoses and prognoses. Using immunohistochemistry and ultrastructural analyses supplementally, we studied two cases, one a serous cystadenocarcinoma with nodules of undifferentiated sarcoma, the other a mucinous cystadenocarcinoma with mural nodules of anaplastic carcinoma. Based on these cases and a review of 48 cases in the literature, we propose a standardized terminology. Mural nodules may be either reactive or neoplastic. Neoplastic mural nodules may be composed of benign elements, carcinoma, carcinoma with reactive elements, sarcoma, or an admixture of carcinoma and sarcoma; the latter category has some similarities to malignant mixed mesodermal tumors. The prognosis of patients with malignant mural nodules is poor, with 50% mortality. Strict morphologic criteria supplemented by immunohistochemistry aids in the sometimes difficult differential diagnosis among these types of mural nodules.

Immunohistochemical characterization of ovarian borderline tumors of intestinal and mullerian types.

A panel of monoclonal antibodies (MAbs) including MOv2, MOv8, anti-CA 19-9, and anti-carcinoembryonic antigen (CEA), and a polyclonal antibody against CEA, was applied to three types of ovarian borderline tumors. The tumors included 19 intestinal-type mucinous borderline tumors (IMBTs), 22 endocervical-like mucinous borderline tumors (EMBTs), and 23 mixed-epithelial borderline tumors (MEBTs); the latter two tumors are of mullerian type. Statistically significant differences in the percentage of positive IMBTs compared to the mullerian tumors were seen for anti-CEA and MOv8; strikingly different staining patterns were also seen. IMBTs were more often and more diffusely CEA-positive than were the mullerian tumors; within the mullerian tumors, only one type of cell, the indifferent eosinophilic cell, was consistently CEA positive. The MAbs MOv2, MOv8, and anti-CA 19-9 showed more extensive positivity in the mullerian tumors than in the IMBTs. This study highlights the differences in cell types between IMBTs and these two types of mullerian borderline tumors.

The androgen insensitivity syndrome (testicular feminization): a clinicopathologic study of 43 cases.

Forty-three patients with the androgen insensitivity syndrome (AIS), ages 14 to 83 (average 27) years, were studied. Forty patients had complete AIS and three patients had incomplete AIS. Microscopic examination of the testes revealed immature tubules, which contained rare spermatogonia in 28% of the cases. Prominent Leydig cells and a spindle-cell stroma resembling ovarian stroma were found in a majority of cases. The organization of the testicular parenchyma could be classified into one of four patterns: diffuse tubulostromal, lobular tubulostromal, mixed tubulostromal, or stromal-predominant. Hamartomas were present in 63% and Sertoli cell adenomas in 23% of the cases. Malignant tumors developed in 9% of the patients and comprised two seminomas, one intratubular germ cell neoplasm with early stromal invasion, and a malignant sex cord tumor. At least one fallopian tube was present in 35% of the cases.

Long-term effects of prepubertal testicular vessel ligation on testicular function in the rat.

To determine the effects of unilateral testicular vein and artery ligation in the immature rat on the function and final location of the testis at adulthood, 10-day-old male rats underwent either a sham operation or unilateral ligation of these vessels of the still undescended testis. Testicular location, blood flow, size and histology as well as ventral prostate weights were measured 50 days later at adulthood. At age 60 days, it was determined that all testes were descended into the scrotum, and there were no differences in testis and ventral prostate weights, intratesticular sperm counts and mean seminiferous tubular area between the control and sham operated animals. However, there was an 18% reduction in testicular blood flow (ml. per 100 gm. per minute +/- standard error of mean) in the operated animals when compared to the sham (20.43 +/- 1.10 versus 16.69 +/- 0.74, p less than 0.02). These data indicate that although there is a slight but significant reduction in testicular blood flow at adulthood when the testicular artery and vein are ligated early in life, this diminution is not sufficient to alter the ultimate location, testicular weight and spermatogenic function of the testis. This would suggest that after ligation of the main testicular vessels to the immature testis, the collateral blood supply is able to compensate with time to allow normal growth and development of the testis. These experimental observations provide additional support for the 2-staged approach to the high undescended testis whereby the testicular vessels are initially ligated and a subsequent procedure is performed to place the undescended testis into the scrotum.

Testicular seminoma: clinical and pathological features that may predict para-aortic lymph node metastases.

Patients with clinical stage I testicular seminoma usually receive elective para-aortic lymph node radiation after orchiectomy, which is effective in controlling subclinical microscopic disease. However, the majority of patients with clinical stage I seminoma do not harbor occult metastases and, therefore, do not require elective nodal treatment. Vascular space invasion by the primary testis tumor recently has been shown to be an important predictor of metastases in nonseminomatous tumors but no such information exists to date in pure seminoma. Therefore, patients with clinical stage I testicular seminoma were compared to clinical stage II to IV cancer patients with respect to the presence of several features of the primary tumor. Vascular space invasion was identified significantly less frequently in stage I cancer patients (17%, 5 of 29) than in those with stage II or greater disease (39%, 11 of 28, p equals 0.03, 1-tailed t test). Microscopic invasion of the tunica and rete testis, and necrosis also were identified slightly more frequently in the higher stage cancer patients. Of the 12 patients with a maximum tumor dimension of more than 6 cm. 9 (75%) were in the stage II or higher group. Patient age, symptom duration and presenting complaint were similar in the 2 groups. Many higher stage cancer patients did not exhibit aggressive histological characteristics and, therefore, the absence of these features cannot be used to select patients for surveillance. On the other hand, patients with clinical stage I tumors that exhibit vascular space invasion may have an increased rate of occult para-aortic lymph node metastases. Therefore, the presence of vascular space invasion may be a useful criterion for exclusion of patients from surveillance protocols. Confirmatory data are needed before a final recommendation can be made.

Carcinosarcomas and mixed Müllerian tumors of the fallopian tube.

Four cases of carcinosarcoma and mixed müllerian tumors of the fallopian tube are presented. Each patient presented with abnormal bleeding and a pelvic mass. All underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, staging, and cytoreduction. Disease was limited to the pelvis in two patients, analogous to FIGO stage IIB ovarian carcinoma; the other two patients had upper abdominal disease, analogous to FIGO stage III. The primary tumors were intraluminal and papillary. There were equal amounts of carcinoma and sarcoma in three tumors; in one, sarcoma constituted only a small intraluminal focus. The sarcoma was predominantly homologous, with foci of heterologous elements present in three tumors. Adjuvant therapy consisted of pelvic radiation in two patients. One patient died of inanition within one year of diagnosis. The other patient, who had the small focus of sarcoma within a stage IIB carcinoma, had an 11-year disease-free interval before retroperitoneal recurrence of carcinoma. Two patients received chemotherapy. A stage IIB patient, after pelvic radiation, received Cytoxan and Adriamycin; she is clinically free of disease after 6 years. A stage III patient lived over 3 years after treatment with multiple agents; she responded to Cytoxan and cis-platinum before suffering a systemic relapse and death.

The testicular "tumor" of the adrenogenital syndrome. A report of six cases and review of the literature on testicular masses in patients with adrenocortical disorders.

The clinical and pathological features of 40 cases in which testicular masses developed in patients with the adrenogenital syndrome are reviewed; this study was based on six personally observed cases and 34 other cases in the literature. The adrenal disorder was of the salt-losing form in two-thirds of the cases and the non-salt-losing form in the other third. Although the clinical diagnosis of the adrenogenital syndrome had been established prior to the discovery of the testicular lesion in most of the patients, in 18% of them the diagnosis was not made until or after the development of a testicular mass. Two-thirds of the masses were palpable (up to 10 cm); these cases were usually discovered in early adult life (average, 22.5 years). The remaining one-third were small (under 2 cm) and were usually found in children either at autopsy or on testicular biopsy. Eighty-three percent of the masses were bilateral. Eighty-six percent of the small lesions were located in the hilus. The larger lesions involved the testicular parenchyma in all but one case. They formed well-demarcated but unencapsulated brown-green masses, typically separated into lobules by prominent bands of fibrous tissue. Microscopical examination revealed sheets, nests, and (rarely) cords of cells with abundant eosinophilic cytoplasm separated by bands of fibrous tissue. Lipochrome pigment was identified in the cytoplasm in many cases, but crystals of Reinke were uniformly absent. The major pathological differential diagnosis is Leydig cell tumor; the associated clinical and laboratory features--including the high frequency of bilaterality and a decrease in the size of the tumor with corticosteroid therapy--are diagnostic of a testicular "tumor" of the adrenogenital syndrome. Although a variety of origins have been suggested for these lesions, in our opinion an origin from hilar pluripotential cells, which proliferate as a result of the elevated level of adrenocorticotropic hormone, is most likely.

Ovarian mixed-epithelial papillary cystadenomas of borderline malignancy of mullerian type. A clinicopathologic analysis.

Borderline tumors with papillae that are architecturally similar to those of serous tumors but with a lining of more than one mullerian cell type have not been well characterized in in the literature. We have studied 36 such tumors. The patients averaged 35 years of age. Twenty-two percent of the tumors were bilateral; all were confined to the ovaries as confirmed at operation. Fifty-three percent were associated with endometriosis. Follow-up information was available on 34 patients for a mean interval of 4.8 years. A tumor developed in the contralateral ovary in one patient 2 years after unilateral salpingo-oophorectomy. Three patients had pelvic recurrences between 7 months and 3 years, but all of them were successfully treated and none have died. These tumors differ clinically and pathologically from intestinal-type mucinous borderline tumors, but they have many similarities with mullerian mucinous borderline tumors and, to a lesser extent, with serous borderline tumors.

Ovarian mullerian mucinous papillary cystadenomas of borderline malignancy. A clinicopathologic analysis.

Ovarian mucinous cystadenomas of borderline malignancy that contain foci of intestinal differentiation are well recognized. Borderline tumors lined by mucinous epithelium of endocervical type and characterized by papillae architecturally similar to those of serous borderline tumors, however, have not been described in the literature. We have studied 30 tumors of this type. The patients averaged 34 years of age. Forty percent of the tumors were synchronously bilateral and 30% were associated with endometriosis. Four tumors were complicated by peritoneal implants, one by both peritoneal implants and lymph node metastasis and one by lymph node metastasis alone. No patient had pseudomyxoma peritonei. Follow-up information was available on all the patients for a mean interval of 3.7 years. In two cases tumors developed in the conserved contralateral ovary; no deaths occurred. These tumors have important clinical and pathologic differences from mucinous borderline tumors with intestinal differentiation, but have many similarities to mixed-epithelial borderline tumors of Mullerian type.