High pathologic misdiagnosis of cervical adenocarcinoma in situ.

OBJECTIVE: The objectives of this research were to evaluate cases of adenocarcinoma in situ (AIS) and early invasive adenocarcinoma (AC) of the uterine cervix in order to: (1) calculate the pathologic discordance between initial biopsies and final surgical excision specimens and (2) describe the clinical and pathologic factors associated with discordance. MATERIALS AND METHODS: The University of California, Irvine and Long Beach Memorial tumor registries were used to identify 105 women with AIS and early AC treated between 1990 and 2008. The primary endpoint measured was change in diagnosis when comparing pathology from the initial biopsy to specimens from a large loop excision of the transformation zone (LLETZ), cold knife cone (CKC), or hysterectomy. The variables studied were: age, endocervical curettage (ECC), co-existing cervical intraepithelial neoplasia (CIN), race, and insurance type, as surrogates for socioeconomic status. RESULTS: Initial biopsies were diagnosed as AIS and AC in 44% and 56% of patients, respectively. Of the patients with a biopsy diagnosis ofAIS, 29% had a final diagnosis of AC after excisional procedure, and this discordance was not associated with any of the factors studied. CONCLUSIONS: A concerning high rate of discordance between colposcopic-guided punch biopsy and final pathology reinforces the current guidelines to always perform an excisional biopsy following diagnosis of AIS on punch biopsy.

Adenocarcinoma and dysplasia in an ileal neobladder after ileocystoplasty for interstitial cystitis.

We report a 54-year-old woman with an adenocarcinoma of an ileal neobladder arising upon a background of ileal mucosal dysplasia. We believe that no case study or report has previously documented neobladder ileal mucosal dysplasia adjacent to an ileal neobladder adenocarcinoma. This observation supports the current hypothesis that ileal neobladders are dynamic environments for potential malignancy, and moreover, suggests a sequence of morphologic and molecular derangements similar to that seen in colorectal carcinoma. Those patients status post ileal neobladder are at risk for glandular dysplasia and malignancy and should be followed closely.

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.

Bilateral pheochromocytoma in pregnancy heralding multiple endocrine neoplasia syndrome IIA. A case report.

BACKGROUND: Multiple endocrine neoplasia syndrome type IIA (MEN IIA) has rarely been encountered in pregnancy. CASE: A 22-year-old, nulliparous woman developed bilateral pheochromocytomas during pregnancy. This finding aroused suspicion for MEN IIA, and close endocrinologic follow-up was arranged. Four years later, hyperparathyroidism developed, and the diagnosis was established. The patient underwent prophylactic total thyroidectomy with parathyroid exploration. CONCLUSION: This was the first case of MEN IIA in pregnancy in which the diagnosis was established prior to the development of medullary thyroid cancer, thereby allowing prophylactic thyroidectomy. The presence of bilateral neoplastic disease in young patients may be indicative of a hereditary predisposition to malignancy.

The evolution of Linitis plastica as a consequence of advanced gastric carcinoma in pregnancy.

A 40-year-old multigravid woman was examined on multiple occasions during pregnancy because of persistent gastrointestinal symptoms. A metastatic, unresectable gastric carcinoma that had evolved to linitis plastica was diagnosed at 26 weeks' gestation. The patient was delivered of a viable infant at 27 weeks' gestation, and she died of disease 1.5 months after the diagnosis was made.

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.

[Thalidomide once more in the spotlight]. / Thalidomide opnieuw in de belangstelling.

Thalidomide was withdrawn from the market in the early sixties because of major teratogenic effects such as reduction defects of the limbs. Since, however, it has been found to be an effective drug in erythema nodosum leprosum. In the United States it was decided in September 1997 to admit thalidomide to the market for this indication, and in South America it has been available for this indication all the time. Thalidomide is also efficacious in other major disorders (e.g. aphtae and ulcers in aids) or its efficacy is being investigated in clinical trials (e.g. autoimmune diseases, other complications in aids). The American Food and Drug Administration has imposed conditions for the use of thalidomide. Users have to sign an informed consent and to take adequate contraceptive measures. Physicians should inform the patients and monitor side effects. Pharmacists should record and control the use.

Metastasis of an intracranial germinoma through a ventriculoperitoneal shunt: recurrence as a yolk-sac tumor.

Extraneural metastases of intracranial germinomas, although infrequent, are associated with a generally poor prognosis despite the high radiosensitivity of localized primary tumors. Ventriculoperitoneal shunts have been implicated in facilitating metastatic spread of primary intracranial germinomas. We present a case of a successfully irradiated suprasellar germinoma recurring after 13 months as an intra-abdominal yolk-sac tumor in a young man. The tumor was eradicated with a combination of systemic chemotherapy and local irradiation, with no residual viable tumor cells confirmed at final surgical extirpation. The role of cerebrospinal fluid (CSF) shunts in metastases, mixed germ-cell tumor histology, and tumor markers in recurrences as well as radiation doses and volumes for treating primary tumors are discussed. Systemic chemotherapy may be utilized as prophylaxis against shunt metastases when CSF drainage is necessary.

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.

Occipital encephalocele and MURCS association: case report and review of central nervous system anomalies in MURCS patients.

The combination of MURCS association (Müllerian duct and renal agenesis, upper limb and rib anomalies) and occipital encephalocele occurred in a stillborn girl of 41 weeks gestation. The malformations are compatible with a defect in the organization of the paraxial mesoderm that gives rise to occipital, cervical, and thoracic somites and adjoining intermediate mesoderm. These structures contribute to the occipital bone, cervical spine, upper limbs, and urogenital system. Brain imaging may be useful in assessing MURCS patients, if cranial malformations prove to be clinically important in these individuals.

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.

Myometrial expression of mRNA encoding epidermal growth factor receptor (EGFR) throughout the menstrual cycle.

PROBLEM: To investigate the quantitative changes in expression of EGFR mRNA in the myometrium throughout the menstrual cycle. METHOD: Myometrium was collected at hysterectomy from 27 women with a history of regular cycles. Total RNA (20 micrograms) was isolated and analyzed by Northern blot using a human EGF-R specific 32P-labeled cDNA probe. The hybridization signals were quantified by densitometry, standardized, and reported in densitometry signal units (DSU). Endometrial specimens from the same uteri were simultaneously evaluated for histologic dating of menstrual cycle day. EGFR gene expression in endometrium was previously reported. Statistical significance of the differences in myometrial gene expression between menstrual phases was evaluated by student's t test. RESULTS: EGFR mRNA was expressed in all myometrial tissues tested. Levels were higher in the late proliferative phase than in all other phases (P < .05). Women over 40 years old had lower proliferative phase expression than younger women. CONCLUSION: This data suggests that myometrial EGFR mRNA expression varies in association with the histologic phases of the normal menstrual cycle, and may be affected by aging, even when cycles occur at regular intervals.

Absence of a dose-response effect of leuprolide acetate on leiomyomata uteri size.

OBJECTIVE: To evaluate the effects of two different doses (3.75 mg versus 7.5 mg) of leuprolide acetate (LA, Lupron; Tap Pharmaceuticals, Deerfield, IL) on myoma size, blood loss during myomectomy, on magnetic resonance imaging (MRI) signal quality, and histopathologic changes in women requiring myomectomy. DESIGN: Prospective, nonrandomized, sequential study. SETTING: Urban center teaching hospital. PATIENTS: Twenty-eight women with uterine leiomyomata requiring myomectomy. INTERVENTIONS: Nine women were entered as controls (group 1), 10 women received 3.75 mg IM (group 2), and 9 women received 7.5 mg IM of LA (group 3) each for 3 months before myomectomy. RESULTS: The uterine size and hematocrit among the three groups of patients before treatment was not significantly different. A significant reduction of 34.5% and 34.6% in myomata size was seen in groups 2 and 3. The estimated average blood loss at myomectomy was 745 +/- 101 mL, 615 +/- 177 mL, and 722 +/- 192 mL in groups 1, 2, and 3, respectively. The postoperative hematocrit was not different among the three groups (29.8% +/- 0.9%, 30.4% +/- 1.6%, and 29.8% +/- 1.2%). There was no evidence of cytologic atypia, increased mitosis, or change in fibrosis in LA-treated women. There were no characteristic MRI or histologic changes seen after LA treatment as compared with controls. CONCLUSIONS: The results of this study have demonstrated that both doses of LA (3.75 and 7.5 mg) can induce a significant and similar degree of size reduction in myomas and that neither dose of LA aided in the reduction of blood loss at myomectomy and therefore should not be used routinely.