Ovarian mixed-epithelial carcinomas with a microcystic pattern and signet-ring cells.

Primary ovarian carcinomas with unusual histologic patterns can be difficult to differentiate from metastases. In this study, we reviewed 15 cases of mixed-epithelial carcinoma (12 serous, 1 serous and endometrioid, 1 endometrioid, 1 undifferentiated) with a predominant microcystic pattern and signet-ring cells. The patients' ages ranged from 31 to 78 (mean 58) years. The microcystic component in 11 patients had features of high-grade carcinoma and in 4 patients had features of low-grade carcinoma associated with areas of borderline tumor. The tumors in all 15 patients showed a predominant microcystic growth pattern composed of small cysts that were variable in size and shape. Signet-ring cells were also present in all cases (diffusely in nine cases, focally in six cases) within the neoplastic epithelial proliferation. Mucin was present in the lumina of some of the microcysts and in the cytoplasm of most of the signet-ring cells. A microcystic pattern and mucin-containing signet-ring cells can be seen as small foci or as a predominant component in primary epithelial nonmucinous ovarian carcinomas. It is important for pathologists to recognize these unusual findings in ovarian neoplasms, because they may produce a confusing apperance, even potentially suggesting a metastasis.

Low levels of cell cycle inhibitor p27kip1 combined with high levels of Ki-67 predict shortened disease-free survival in T1 and T2 invasive breast carcinomas.

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for better prognostic markers to identify those subsets of patients who would benefit from more aggressive therapy because their tumors show an increased risk of poor clinical behavior. p27kip1 is an important inhibitor of the cell cycle that acts by binding and inactivating cyclin-dependent kinases (CDKs). The aim of this study was to determine the prognostic value of loss of p27 protein in invasive breast cancer. We performed an immunohistochemical study of 147 patients with T1 and T2 invasive breast cancers and compared survival in the high p27 expressing group with that of the low p27 expressing group. On univariate analysis comparing tumor size, nodal status, Ki-67, c-erbB-2, p53 and estrogen receptor, low or absent p27kip1 is a strong predictor of reduced disease-free survival. Importantly, on multivariate analysis, the combined effect of low p27 with high Ki-67 is a stronger predictor of reduced disease-free survival than either marker alone. This simple, reliable and inexpensive assay, particularly when used in combination with Ki-67, improves the ability to predict disease recurrence and could become a useful adjunct of breast cancer evaluation to better identify high risk patients.

Mild ductal atypia after large-core needle biopsy of the breast: is surgical excision always necessary?

BACKGROUND: The aim of the current study was to identify a select group of patients with mild atypia who do not need surgical excision after large-core needle biopsy (LCNB) of the breast. METHODS: Nineteen (70%) of 27 patients with ductal atypia found on LCNB had subsequent surgical excision. These 19 patients were retrospectively assigned to 3 groups according to the severity of the atypia found, which was compared with the final pathologic specimen after surgical biopsy. RESULTS: Cancer was identified through surgical biopsy in 6 (32%) of 19 patients. The severity of atypia seen on the LCNB specimen strongly correlated with subsequent cancer identification (P<.01). Two (33%) of 6 patients in group 2 (true atypical ductal hyperplasia [ADH]) and 4 (80%) of 5 patients in group 3 (severe ADH, borderline ductal carcinoma in situ) had cancer after surgical biopsy. No cancer was found after surgical biopsy in 8 patients in group 1 (mild atypia, not meeting criteria for ADH). CONCLUSIONS: The results of this study suggest that surgical excision can be avoided after LCNB of the breast in patients with only mildly atypical lesions that do not meet criteria for ADH. Patients with true ADH should continue to have surgical excision.

Octreotide induced remission of a refractory small cell carcinoma of the endometrium.

This is the first report of remission obtained with octreotide in a woman diagnosed with recurrent small cell carcinoma of the endometrium with neuroendocrine features, refractory to a combination of etoposide, cisplatin, and radiation therapy. Stabilization of disease was obtained with a combination of tamoxifen and leuprolide depot. Regression of disease was then achieved by the addition of octreotide. The use of octreotide as an antitumor agent is reviewed.

Induction of epithelial neoplasms in the ovaries of guinea pigs by estrogenic stimulation.

OBJECTIVE: We have been searching for an animal model for ovarian epithelial neoplasms. Our previous study suggested that by giving intermediate doses of testosterone to guinea pigs it is possible to induce cystadenomas in the ovaries in 6 to 10 months. METHODS: In this study we investigated the effect of different estrogens including estradiol, diethylstilbestrol (DES), estrone, dienestrol, and hexestrol in 24 guinea pigs. Five guinea pigs received sterile water and were used as controls. RESULTS: Bilateral serous cysts were seen in the ovaries of five guinea pigs that received low (0.25 and 0.35 mg) and intermediate (0.5 and 0.7 mg) doses of estradiol for 2 to 9 months. Surface papillary neoplasms were seen in the ovaries of four guinea pigs that received DES at an intermediate dose (6 mg) and high doses (10 and 12 mg) for 3 to 12 months. The ovaries of the other guinea pigs were unremarkable. Estradiol was measured by radioimmunoassay in three guinea pigs. In the serum it ranged from 450 to 580 pg/ml, and in the ovarian cystadenomas it ranged from 1020 to 6575 pg/ml. CONCLUSIONS: (1) It is possible to induce ovarian neoplasms using estrogenic hormones. (2) The best results are obtained with intermediate doses of estradiol and DES. (3) These two hormones induce different lesions: estradiol is associated with cystic lesions and DES with surface papillary tumors. These observations, together with our previous finding that testosterone induces neoplasms with a predominantly glandular pattern, establish the guinea pig as an excellent animal to study ovarian neoplasms, confirm the significance of hormones in the development of ovarian epithelial tumors, and suggest that the different histologic appearance of ovarian epithelial neoplasms might be related to different hormonal effects.

Serous borderline tumors of the ovary with noninvasive peritoneal implants.

BACKGROUND: The authors conducted this study to update their experience with patients who have ovarian serous borderline tumors with noninvasive peritoneal implants, with the objectives of gaining additional insight into the biologic behavior of these tumors and understanding better the effects of postoperative treatment. METHODS: Seventy-three patients who had ovarian serous borderline tumors with noninvasive peritoneal implants were identified in a retrospective review. Major end points selected for analysis were surgicopathologic response, time to relapse, type of relapse, progression free survival, and overall survival. Univariate and multivariate regression analyses were also performed. RESULTS: The median follow-up time was 10.3 years. Of 20 patients with macroscopic residual disease at completion of initial surgery who subsequently underwent second-look surgery, 3 (15%) had a response to chemotherapy. Twenty-two of 73 patients (30%) either developed progressive disease or had a relapse. The median time from the date of diagnosis to relapse was 7.1 years. Tissue was available from 20 of the 22 patients who had a relapse; 14 (70%) had invasive low grade serous carcinomas, and 6 (30%) had recurrent borderline tumors. Age was the only factor studied that had a significant influence on survival (P = 0.03). In both univariate and multivariate proportional hazards models, age and residual disease were found to be of borderline significance in predicting cancer specific survival. CONCLUSIONS: Approximately 30% of patients who have ovarian serous borderline tumors with noninvasive peritoneal implants will develop progressive or recurrent tumors, most commonly serous carcinomas. The presence of macroscopic residual disease appears to be a predictor of disease free survival. In this study, however, the authors were unable to elucidate the role of postoperative therapy or determine criteria for selecting patients for such therapy.

Paclitaxel-induced apoptosis is associated with expression and activation of c-Mos gene product in human ovarian carcinoma SKOV3 cells.

The c-Mos gene product is a component of the cytostatic factor and, as such, stabilizes the maturation-promoting factor causing cell-cycle blockade at metaphase II in unfertilized eggs. The potential role of c-Mos in regulating cell-cycle progression and cell death in somatic cells remains unknown. We studied whether paclitaxel-induced M-phase arrest and apoptosis are associated with c-Mos gene expression and activation in SKOV3 ovarian carcinoma cells. The first cellular effect observed with continuous exposure to 50 ng/ml paclitaxel (ID50) was mitotic arrest with an increase in the accumulation of cyclin B1 and stimulation of cdc2/cyclin B1 kinase in a time-dependent manner during a 36-h incubation. DNA fragmentation determined by agarose gel electrophoresis and quantitation of [3H]thymidine-prelabeled genomic DNA was a later event, first detected at 24 h and peaking at 48 h (later time points were not studied). Induction of the c-Mos gene expression and activation were determined by Western blot analysis, immunoprecipitation using a polyclonal anti-mos antibody, reverse transcription-PCR assay, and 32P-ATP incorporation into c-Mos protein or the substrate of glutathione S-transferase mitogen-activated protein kinase kinase, respectively. Both induction and activation were clearly detected after 24 h of exposure to paclitaxel concentrations of >50 ng/ml, coinciding with drug-induced apoptosis. Mitogen-activated protein kinase activation preceded c-Mos gene induction. Paclitaxel-induced c-Mos gene expression was completely abrogated by cycloheximide and actinomycin D. Mos gene expression was also induced in SKOV3 cells that were treated with vinblastine but not in those that were treated with camptothecin, etoposide, or cisplatin. We concluded that tubulin-disturbing agents induce c-Mos gene expression and activation in SKOV3 ovarian carcinoma cells and that such an effect occurs after mitotic blockade and coincides with drug-induced apoptosis.

Phosphorylation of Bcl-2 is a marker of M phase events and not a determinant of apoptosis.

Phosphorylation of Bcl-2 protein is a post-translational modification of unclear functional consequences. We studied the correlation between Bcl-2 phosphorylation, mitotic arrest, and apoptosis induced by the anti-tubulin agent paclitaxel. Continuous exposure of human cervical carcinoma HeLa cells to 50 ng/ml paclitaxel resulted in mitotic arrest with a symmetrical bell-shaped curve over time. The number of mitotic cells was highest at 24 h (82%), then declined as arrested cells progressed into apoptosis, and barely no mitotic cells were present at 48-60 h. The time curves of paclitaxel-induced cyclin B1 accumulation and stimulation of Cdc2/cyclin B1 kinase activity were identical and superimposable to that of M phase arrest. In contrast, apoptosis was first detected at 12 h and steadily increased thereafter until the termination of the experiments at 48-60 h, when about 80-96% of cells were apoptotic. Bcl-2 phosphorylation was closely associated in time with M phase arrest, accumulation of cyclin B1, and activation of Cdc2/cyclin B1 kinase, but not with apoptosis. At 24 h, when about 82% of the cells were in mitosis, almost all Bcl-2 protein was phosphorylated, whereas at 48 h, when 70-90% of the cells were apoptotic, all Bcl-2 protein was unphosphorylated. Similar results were obtained with SKOV3 cells, indicating that the association of paclitaxel-induced M phase arrest and Bcl-2 phosphorylation is not restricted to HeLa cells. We used short exposure to nocodazole and double thymidine to synchronize HeLa cells and investigate the association of Bcl-2 phosphorylation with mitosis. These studies demonstrated that Bcl-2 phosphorylation occurs in tight association with the number of mitotic cells in experimental conditions that do not lead to apoptosis. However, a continuous exposure to nocodazole resulted in a pattern of Bcl-2 phosphorylation, M phase arrest, and apoptosis similar to that observed with paclitaxel. The phosphatase inhibitor okadaic acid was found to inhibit the dephosphorylation of phosphorylated Bcl-2 and to delay the progression of nocodazole M phase-arrested cells into interphase. In contrast, the serine/threonine kinase inhibitor staurosporine, but not the tyrosine kinase inhibitor genistein, led to rapid dephosphorylation of phosphorylated Bcl-2 and accelerated the progression of nocodazole M phase-arrested cells into interphase. Immune complex kinase assays in cell-free systems demonstrated that Bcl-2 protein can be a substrate of Cdc2/cyclin B1 kinase isolated from paclitaxel-treated cells arrested in M phase. Taken together, these studies suggest that Bcl-2 phosphorylation is tightly associated with mitotic arrest and fail to demonstrate that it is a determinant of progression into apoptosis after mitotic arrest induced by anti-tubulin agents.

Clinicopathologic analysis of mullerian adenosarcoma: the M.D. Anderson Cancer Center experience.

The records of 41 patients diagnosed with adenosarcoma of the female genital tract between 1982 and 1996 were reviewed. The median age at diagnosis is 51 years (range, 14-84). The most common symptom is vaginal bleeding (71%). Clinical signs at presentation include pelvic mass (37%), uterine polyps (29%), and enlarged uterus (22%). In 71% of patients, the tumor originates from the uterus. Other sites include ovary (15%), pelvis (12%), cervix (2%). A history of thyroid cancer, benign ovarian cyst, and polycystic ovarian disease is found more frequently than expected in this patient population, whereas no relationship to endometriosis is observed. Surgery is the mainstay of treatment, but platin-based chemotherapy given upfront in inoperable patient has definite efficacy. An overall response rate of 92.5% was observed after primary therapy (surgery with or without radiotherapy, and/or chemotherapy), with a median survival of 48 months (range, 1-174). Thirty-eight percent of patients had recurrent disease. The median time to recurrence is 12 months (range, 5-132). Although 60% of patients with recurrence achieved a complete remission after treatment, only 1 (8%) is alive without disease, and 3 (22%), with disease at the time of this analysis. In our series, histologic sarcomatous overgrowth is a predictor of poor prognosis (p<0.03), however myometrial invasion and stage of disease seem to be of less prognostic significance. Adenosarcoma is a tumor with a fair prognosis. Most tumor can be cured with surgery, but recurrence carries a bad prognosis.

Ovarian serous borderline tumors with invasive peritoneal implants.

BACKGROUND: The objective of the current study was to update the authors' experience with patients with ovarian serous borderline tumors with invasive peritoneal implants to gain additional insight into the biologic behavior of these tumors and a better understanding of the effect of postoperative treatment. METHODS: Thirty-nine patients with ovarian serous borderline tumors with invasive peritoneal implants were identified through a retrospective review. Major endpoints selected for analysis were surgicopathologic response, time to recurrence, type of recurrence, progression free survival, and overall survival. Univariate and multivariate regression analyses also were performed. RESULTS: Median follow-up time was 111 months. Four of 7 evaluable patients who had second-look surgery (57%) had a response to chemotherapy. Twelve of 39 patients (31%) either developed progressive disease or had a recurrence. The median time from date of diagnosis to recurrence was 24 months. In 10 of these 12 patients with a recurrence, tissue was available; 9 had invasive low grade serous carcinoma and 1 had a recurrent borderline tumor. Macroscopic residual disease was the only factor studied that had a significant effect on survival; patients with no macroscopic residual tumor had a significantly better survival than those with any macroscopic residual tumor (P < 0.01). In univariate regression analysis, macroscopic residual disease and the presence of frankly invasive implants were significant predictors of progression free survival. Platinum-based chemotherapy was associated with a significantly shorter progression-free survival. Only macroscopic residual tumor was a significant predictor of survival. CONCLUSIONS: Greater than 30% of patients with ovarian serous borderline tumors with invasive peritoneal implants will develop progressive or recurrent tumor, most commonly serous carcinoma. The presence of macroscopic residual disease appears to be the major predictor of recurrence and survival. However, in this study, the authors were unable to elucidate the role of postoperative therapy or the criteria for selection of patients for such therapy.

Accumulation of cyclin B1, activation of cyclin B1-dependent kinase and induction of programmed cell death in human epidermoid carcinoma KB cells treated with taxol.

Cyclin B1 plays a critical role in regulating cell-cycle progression from G2 through M phase (including exit from M phase). In this study, we investigated the relationship between taxol-induced M-phase arrest, disruption of the cyclin B1-regulation pathway and apoptosis in KB cells. Continuous exposure of KB cells to 0.5 microg/ml taxol caused mitotic arrest and >90% cell death at 48 hr. Mitotic blockade peaked at 24 hr, with 68% of cells in mitosis at that time compared with 3% at baseline, and decreased thereafter. Apoptosis assessed by morphological changes and DNA ladder fragmentation was a later event, peaking at 48 hr (later time points were not studied). Taxol also caused an increase in cyclin B1 accumulation, as assessed by Western blot analysis, and stimulated cyclin B1-dependent kinase. Cyclin B1 accumulation and kinase stimulation peaked at 12 and 24 hr, respectively, at which times they were 5-fold and 90-fold higher than in control untreated cells. These effects decreased thereafter. All taxol-induced cellular effects were abrogated by the protein and RNA synthesis inhibitors cycloheximide and actinomycin D. In contrast, the endonuclease inhibitors aurintricarboxilic acid and zinc markedly inhibited taxol-induced DNA ladder fragmentation without altering taxol-induced cell-cycle arrest, cyclin B1 accumulation, activation of cyclin B1 kinase activity and cytotoxicity. We conclude that taxol-induced stimulation of cyclin B1-dependent kinase activity parallels mitotic arrest, is more pronounced than mitotic arrest and precedes the induction of programmed cell death.

Tumor recurrence in stage I ovarian serous neoplasms of low malignant potential.

Eleven patients treated at the University of Texas M. D. Anderson Cancer Center for recurrent disease after resection of a stage I ovarian serous neoplasm of low malignant potential (SNLMP) are reported. At the time of diagnosis, the age of the patients ranged from 26 to 43 years (mean 33). Seven patients had stage IB tumors and 4 had stage IA tumors. All patients were treated with a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The size of the ovarian tumors ranged from 4 to 15 cm in maximum dimension. Stromal microinvasion was seen in 2 cases, and foci of endosalpingiosis were seen in the peritoneum in 8 cases. Nine patients were treated with radiotherapy and 2 with chemotherapy. The time to recurrent disease ranged from 7 to 39 years (mean 16). Eight tumors recurred in the pelvis or abdomen, 2 in the neck with subsequent abdominal involvement, and 1 in the pleura without abdominal or pelvic involvement. In 10 cases, the recurrent tumors were serous carcinoma, and in 1 case it was a SNLMP. Recurrences were treated with chemotherapy in 10 cases and with hormones in 1 case. Seven patients died of progressive serous carcinoma 2 to 5 years after the recurrence. One patient died of leukemia with recurrent ovarian tumor 10 years after the recurrence was detected. Two patients are alive with progressive disease 1 and 7 years after the recurrence, and 1 patient whose disease recurred as a SNLMP is alive with no evidence of disease 9 years after the recurrence. These 11 patients were compared with 16 patients who had stage I ovarian SNLMPs that did not recur after a minimum follow-up of 15 years. There was no difference in the age of the patients, gravidity, size of the tumors, or several microscopic parameters, including degree of epithelial proliferation, number of mitoses, and nuclear atypia. Microinvasion was found in one case. The only significant difference between the two groups was the low frequency of endosalpingiosis in the cases that had no disease recurrences (12.5% versus 72.7%). In summary, we found no clinical or pathologic features that can unequivocally predict the recurrence of stage I ovarian SNLMPs. Because of the long interval to recurrence, the fact that the recurrent tumors in 10 of 11 patients were serous carcinomas, and the result of the X-chromosome inactivation in one case, the recurrent tumors could represent independent primaries or a slow progression of one clone present in the SNLMPs.

MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines.

A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (approximately 10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (approximately 23%). Novel alterations identified in this gene include a missense variant in a melanoma sample and a splicing variant and a nonsense mutation in pediatric glioblastomas. Of 76 tumor cell lines prescreened for probable LOH, microsequence alterations of MMAC1 were detected in 12 (approximately 16%) of the lines, including those derived from astrocytoma, leukemia, and melanoma tumors, as well as bladder, breast, lung, prostate, submaxillary gland, and testis carcinomas. In addition, in this set of tumor cell lines, we detected 11 (approximately 14%) homozygous deletions that eliminated coding portions of MMAC1, a class of abnormality not detected by our methods in primary tumors. These data support the occurrence of inactivating MMAC1 alterations in multiple human cancer types. In addition, we report the discovery of a putative pseudogene of MMAC1 localized on chromosome 9.

Malignant peripheral nerve sheath tumor of the pleura with epithelial and rhabdomyoblastic differentiation: report of a case clinically simulating mesothelioma.

A primary malignant peripheral nerve sheath tumor (MPNST) of the pleura that clinically mimicked a malignant mesothelioma in a 57-year-old man is described. Histologically, the tumor had features similar to those described in cases of the so-called epithelioid MPNST. A unique finding in this case was the demonstration of keratin expression in the epithelioid component of the tumor, as well as the presence of rhabdomyoblasts. This is the first example of an MPNST with heterologous elements arising in the pleura. Immunohistochemical and ultrastructural studies were important in differentiating this tumor from other malignancies with sarcomatoid and epithelioid features involving the pleura.

The induction of benign epithelial neoplasms of the ovaries of guinea pigs by testosterone stimulation: a potential animal model.

We studied the effects of different hormones on the epithelial cells of the ovaries of 11 guinea pigs. Three received testosterone, two received estrone, three megestrol, and three chorionic gonadotropin. Three control guinea pigs received sterile water. Benign epithelial cysts larger than 1.5 mm were found in six guinea pigs, three who received testosterone, one who received megestrol, and two who received chorionic gonadotropin. In one of the three guinea pigs who received testosterone, 2.5-cm bilateral cysts were grossly identified. Papillary excrescences were found on the ovarian surface in four guinea pigs, three who received testosterone and one who received megestrol. The proliferating epithelial cells also formed benign glands in the ovarian stroma in two guinea pigs who received testosterone, the most exuberant epithelial proliferations, including large bilateral cystadenomas, papillary excrescence that formed a small papillary neoplasm, and glands in the ovarian stroma that formed adenomatous areas, were seen in the guinea pig who received an intermediate dose of testosterone for the longest time. By radioimmunoassay, the serum level of testosterone was 22 ng/dL in one of the controls and 10,000, 12,000, and 15,000 ng/dL in the three guinea pigs who received testosterone. In the guinea pig with the most exuberant epithelial proliferation, the level of testosterone in the uterus was similar to that in the serum (13,860 ng/mg), but in the wall of the ovarian epithelial cyst, it was three times higher than it was in the serum (44,000 ng/mg). Our study shows that testosterone stimulates the growth of epithelial cells in the ovaries of guinea pigs, resulting in benign cysts, small adenomas in the ovarian parenchyma, and papillomas on the ovarian surface. The study also shows that guinea pigs can be used as an animal model for epithelial tumors of the human ovary.

A phase II and pharmacokinetic study of enloplatin in patients with platinum refractory advanced ovarian carcinoma.

This was a study of enloplatin in 18 evaluable patients with platinum refractory ovarian cancer. They received an i.v. infusion of enloplatin over 1.5 h without prehydration every 21 days. One patient had a partial response (6%; 95% CI 0-26%) lasting 2.8 months. The median survival was 9.4 months (95%; CI 5.1-19.7%). Neutropenia was the dose-limiting toxicity. Nephrotoxicity was manageable. Enloplatin is the major form of the free drug in plasma. However, 13.5 h after initiation of treatment, 85% of the drug in plasma is protein bound. Elimination of the drug is mainly renal. Enloplatin pharmacokinetics is similar to that of carboplatin. Thus, the plasma pharmacokinetics of enloplatin is dictated by the cyclobutanedicarboxylato (CBDCA) ligand and not the novel amino ligand.

Ovarian serous neoplasms of low malignant potential associated with focal areas of serous carcinoma.

This is a study of 12 cases of Stage III ovarian serous neoplasms of low malignant potential associated with focal areas (< 50%) of serous carcinoma. The purpose of this study was to assess the prognosis of serous tumors that had areas of serous carcinoma but were predominantly of low malignant potential. Eleven serous carcinomas were low grade, and one was high grade. All of the patients underwent surgical resection of the neoplasm and then chemotherapy. Eight patients died of disease after a follow-up of 17 to 94 months (mean, 52 mo). Three patients had no evidence of disease at 60, 69, and 75 months. One patient is alive with progressive disease at 58 months. Serous neoplasms of low malignant potential associated with focal areas (< 50%) of serous carcinoma are aggressive neoplasms that have a prognosis similar to that of serous carcinoma.

Unusual features of serous neoplasms of low malignant potential during pregnancy.

Ten serous neoplasms of low malignant potential (LMP) resected during pregnancy were found in the files of the University of Texas M. D. Anderson Cancer Center (UTMDACC). Microscopically, all tumors had marked epithelial proliferation with abundant eosinophilic cells, and eight had intraluminal mucin. Multiple areas of microinvasion were found in eight cases. Additional unusual features were found in three cases. One patient presented with a serous LMP tumor in a supraclavicular lymph node. After resection of an ovarian serous LMP tumor, she was treated with chemotherapy and is without evidence of disease after 21 years. One patient had tumor resected at 24 weeks of gestation and at 2 months postpartum. Marked regression of the epithelial proliferation, the number of eosinophilic cells, and the amount of mucin was seen in the second specimen. Another patient had multiple peritoneal nodules at cesarean section, one of which was biopsied and diagnosed as a primary serous LMP of the peritoneum with multiple areas of microinvasion. Two months later a diagnostic laparoscopy was performed and no residual disease was found. All patients are alive with no evidence of disease. In summary, serous LMP tumors during pregnancy have microscopic and clinical features suggesting aggressive behavior; however, these features appear to regress at the termination of the pregnancy.

Remission of a chemotherapy resistant tumor of low malignant potential with tamoxifen.

Low Malignant Potential (LMP) tumor of the ovary represents 15% of all ovarian tumors. The prognosis is excellent even in patients with extensive tumor involvement. However 20% of the patients die of disease in a 20 year period. Management of patients after surgery is not defined. Chemotherapy has shown response rates of 20% but no improvement in survival. Toxicity has been reported. We present a case of chemotherapy resistant LMP tumor with serologic response to tamoxifen, no evidence of disease and an excellent quality of life. Hormonal therapy may be considered in the treatment of LMP tumors.

Remission with carboplatin of paclitaxel resistant primary peritoneal papillary serous carcinoma: case report.

Primary peritoneal papillary serous adenocarcinoma is histologically identical to ovarian papillary serous adenocarcinoma. This diagnosis is made if the ovaries are of normal size with either no tumor or only minimal surface involvement. We describe a patient with a primary peritoneal papillary serous adenocarcinoma which was resistant to initial therapy with paclitaxel, but subsequently achieved a partial response with carboplatin-based chemotherapy. Accordingly, carboplatin therapy should be considered in paclitaxel resistant primary peritoneal papillary serous carcinoma.