Papillary Serous Carcinoma Of The Peritoneum Research Articles

Primary Serous Papillary Carcinoma of the Peritoneum: CT Findings

AIM: To describe the computed tomography (CT) findings of primary serous papillary carcinoma of the peritoneum. MATERIAL AND METHODS: The clinical data and imaging studies of 36 women aged 37–85 years with primary papillary serous carcinoma of the peritoneum were retrospectively evaluated. Twenty-seven patients presented with general abdominal complaints; all had elevated levels of CA-125. Thirty-two women were post-menopausal, four had had bilateral salpingo-oophorectomy. RESULTS: The most common findings on pre-operative abdominal CT, performed in 30 patients, were a variable amount of ascites (n=29), omental involvement (n=28), irregular parietal peritoneum thickening (n=22) and mural thickening of the sigmoid colon (n=10). Thoracic findings included enlarged cardiophrenic nodes (n=15) and pleural effusion (n=11). Six patients had unilateral or bilateral adnexal masses of soft tissue density, which proved to be surface serous papillary carcinoma. CONCLUSION: Diffuse peritoneal disease on CT in patients with normal-sized ovaries or following bilateral salpingo-oophorectomy, with elevated level of serum CA-125, but without an identifiable primary tumour, should suggest the diagnosis of primary serous papillary carcinoma of the peritoneum. Associated adnexal masses or focal bowel wall thickening may be seen, representing surface involvement by this tumour. Zissin, R. et al(2001). Clinical Radiology56, 740–745.

Primary papillary serous carcinoma of the peritoneum in a man

Primary papillary serous carcinoma of the peritoneum is a well-known entity in women. The tumour is derived from the extraovarian mesothelium and the pelvis and lower abdomen mesothelia. The treatment strategies are similar to ovarian serous papillary carcinoma. A case of primary serous papillary carcinoma of the peritoneum in a man is presented. The patient, 53 years old, died 2 months after diagnosis. The histologic and immunohistochemical studies of the tumour will be presented. These studies, made during lifetime and at autopsy of the patient, confirm a diagnosis of primary serous papillary carcinoma of the peritoneum. primary serous papillary carcinoma of the peritoneum can occur in men, and should be considered in the differential diagnosis in cases of abdominal carcinomatosis of unknown origin. Treatment options remain to be determined.

Distinct allelic loss patterns in papillary serous carcinoma of the peritoneum.

Tumor and normal tissues from 55 patients with papillary serous carcinoma of the peritoneum (PSCP) were analyzed. Polymerase chain reaction amplification of tandem repeat polymorphism was used to screen for loss of heterozygosity (LOH). We mapped 22 oligonucleotide primers to chromosomes 1p, 3p, 6q, 7q, 9p, 11p, 17p, 17q, and Xq. Germline BRCA1 mutation status of 43 patients was determined previously. High frequencies (> 30%) of LOH in PSCP were observed on 6q, 9p, 17p, 17q, and Xq. Compared with allelic loss of serous epithelial ovarian carcinoma (SEOC), the frequency of LOH was significantly lower in PSCP on 1p, 7q, 11p, 17p, and 17q. Of 43 cases screened for germline BRCA1 mutations, 9 cases were identified with mutations. The frequencies of LOH were not significantly different among the BRCA1-related and BRCA1-unrelated PSCP cases. The high LOH rate identified on 6q, 9p, 17p, 17q, and Xq in PSCP suggests that candidate tumor suppressor genes residing in these regions may be important for the development of the tumor. Compared with allelic loss of SEOC, PSCP exhibits a significantly lower frequency of LOH on chromosomes 1p36, 7q31.3, 11p15.1, 17p13.1, and 17q21. An increase in susceptibility to the acquisition of allelic loss in BRCA1-related PSCP cannot be identified.

Ras Gene Activation and Infrequent Mutation in Papillary Serous Carcinoma of the Peritoneum

Objective. The ras genes are a well-studied family of proto-oncogenes whose involvement in many cancers has been delineated. However, K-ras mutations have not previously been examined in papillary serous carcinoma of the peritoneum (PSCP), a tumor which resembles serous epithelial ovarian carcinoma (SEOC) both in histology and epidemiology. In this study we examine the role of the K-ras oncogene in PSCP compared to SEOC.Methods. Using single-strand conformational polymorphism analysis and cycle sequencing protocols, we evaluated our collection of 51 cases of PSCP for K-ras mutations and compared these findings with the experience in SEOC. We then examined 5 cases of PSCP for activation of ras proteins and MAP kinase to evaluate the potential involvement of the ras pathway in PSCP tumorigenesis.Results. We found only one K-ras mutation in our 51 cases (2%) of PSCP compared to three mutations in 46 cases (6.5%) of high-grade, late-stage SEOC. This was not significantly different (P > 0.10). In the single PSCP case with a K-ras mutation, the mutation was found in only one of five tumor sites tested. All four mutations involved a single nucleotide alteration in codon 12 (GGT to GTT, Gly to Val). To evaluate the ras pathway in PSCP, we used the known activated ras binding domain on Raf-1 to perform an assay to test for activated ras. We identified ras activation in 4 of 5 PSCP cases tested and, to confirm that the activation was functional, we tested and found similar activation of MAP kinase, a downstream mediator for K-ras expression.Conclusions. K-ras mutations occur at low rates in both PSCP and high-grade, late-stage SEOC, and therefore K-ras mutations are not involved in the development of these two diseases. Finding the mutation in only one of multiple tumor sites in the PSCP case supports growing evidence for a multifocal origin of PSCP. Our findings of ras activation in four of five cases of PSCP suggest that ras activation by mechanisms other than genetic mutation is important for PSCP tumorigenesis.

Identification of a novel 9 cM deletion unit on chromosome 6q23–24 in papillary serous carcinoma of the peritoneum

To define regions of deletion on chromosome 6q in papillary serous carcinoma of the peritoneum (PSCP), we analyzed 103 tumor tissues from 53 patients by using 11 polymorphic microsatellite markers spanning loci from 6q23 to 6q27. Allelic losses on 6q were observed in 42 of 53 (79.2%) cases. We identified 3 distinct regions with a high percentage (>40%) of loss of heterozygosity. The first region is located at 6q23-24 and defined by D6S311 (15 of 35 informative cases, 42.9%). Detailed deletion mapping of chromosome 6q23-24 in these tumor samples identified a novel 9 cM minimal deletion region flanked by D6S250 and ESR. The second one is located at 6q25.1-25.2 and defined by D6S448 (17 of 36 informative cases, 47.2%). A second minimal deletion region of 4 cM was flanked by D6S420 and D6S442. The third region is located at 6q27 and defined by D6S297 (9 of 19 informative cases, 47.4%). Comparing these results with our cases of advanced staged invasive serous epithelial ovarian carcinoma (SEOC), we observed that allelic losses at D6S311 (6q23) and D6S149 (6q27) were significantly higher for PSCP than for SEOC. The pattern of allelic loss at each tumor site within an individual patient was also studied. A total of 36 cases displayed allelic loss for at least 1 of multiple tumor sites, and 35 of these patients exhibited nonidentical patterns of allelic loss at various tumor sites of the same patient. Furthermore, an alternating pattern of allelic loss in the same patient was identified in 3 of 53 patients studied. These results show that allelic losses on 6q are very frequent in PSCP, and we show 2 discrete minimal deletion regions on 6q, suggesting the existence of at least 2 tumor suppressor genes within 6q that may be involved in the pathogenesis of PSCP. In addition, the finding of different patterns of allelic loss at different tumor sites within the same patient indicate a mutifocal origin in some PSCP cases. These results provide strong evidence to support our previous reports that PSCP is a multifocal disease entity.

Genetic Alterations of the WT1 Gene in Papillary Serous Carcinoma of the Peritoneum

Objective. The Wilms' tumor (WT1) gene product is consistently detectable in both normal ovarian germinal epithelium and human mesothelium. Ovarian carcinomas frequently exhibit alterations in WT1 function. Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining (mesothelium) of the pelvis and abdomen. The purpose of this study was to determine if genetic alterations of the WT1 gene are associated with the development of PSCP.Methods. Normal and tumor tissue specimens were retrieved from patients with stage III and IV PSCP (n = 38) and serous epithelial ovarian carcinoma (n = 38). Immunohistochemistry was performed using the anti-WT1 (C-19) antibody. Loss of heterozygosity (LOH) was performed at the WT1 locus. Clinical data were obtained and correlated with molecular findings.Results. Loss of normal WT1 expression was detected in 18 (51%) of 35 PSCP specimens and 18 (53%) of 34 ovarian carcinoma specimens. Six (27%) of 22 PSCP specimens and 3 (13%) of 24 ovarian carcinoma specimens had LOH at the WT1 locus (P = 0.27). Normal WT1 gene expression was maintained in 86% of tumors exhibiting LOH. Genetic alterations of the WT1 gene were not predictive of survival, nor were they associated with other clinical or molecular factors.Conclusions. Genetic alterations of the WT1 gene are associated with the development of PSCP. The loss of normal WT1 gene expression is a common event in both PSCP and advanced ovarian carcinoma, likely resulting from down-regulation by other regulatory factors—not from inactivating gene mutation and subsequent allelic loss.

Primary Papillary Serous Carcinoma of the Peritoneum: A Case Report

Primary papillary serous carcinoma of the peritoneum is a rare primary tumor involving the peritoneum. Histologically, it is indistinguishable from serous ovarian papillary carcinoma, although it either spares the o-varies or only microscopically involves their surface. The characteristic features of this tumor are extensive peritoneal and omental masses or implants with psammomatous calcification, and ascites. In addition, it can occur focally in the pelvic peritoneum. We report the CT findings, with histopathologic correlation of primary papillary serous carcinoma of the peritoneum occurring in the upper mesorectum.

Experience with Platinum–Paclitaxel Chemotherapy in the Initial Management of Papillary Serous Carcinoma of the Peritoneum

Objective.The objective of this study was to assess the activity and toxicity of combination platinum–paclitaxel chemotherapy in the initial management of patients with papillary serous carcinoma of the peritoneum (PSCP).Methods.Patients initially treated at The Cleveland Clinic Foundation (CCF) for PSCP with platinum–paclitaxel combination chemotherapy regimens were identified and clinical information was abstracted by chart review. Toxicity data, progression-free survival, and overall survival were determined.Results.Thirty-eight patients (36 Stage IIIC and 2 Stage IV) were identified. All chemotherapy was administered as outpatient infusions. All patients received paclitaxel (135 or 175 mg/m2) and 12 received cisplatin and 26 carboplatin. Two hundred thirty-two cycles were administered, with only three (1.3%) episodes of grade 3 toxicity and no grade 4 toxicity. Ninety-two percent of patients experienced at least a 50% reduction in their CA-125 levels and 55% experienced a greater than 90% reduction. Median progression-free survival (Kaplan–Meier) was 15 months and median overall survival was 40 months. Survival for optimally debulked patients (median not yet reached with median follow-up of 24 months) was significantly better than for suboptimally debulked patients (median 32.8 months) (P= 0.012).Conclusion.Platinum–paclitaxel chemotherapy regimens have substantial utility in the initial management of PSCP patients. The toxicity profile is modest. Carboplatin or cisplatin in conjunction with paclitaxel is the current first-line recommended chemotherapy for PSCP.

BRCA1 gene mutations in women with papillary serous carcinoma of the peritoneum

Objective: To compare BRCA1 mutations in papillary serous carcinoma of the peritoneum and papillary serous ovarian carcinoma. Methods: Germline DNA from 17 consecutive patients with peritoneal carcinoma was screened for mutations in the BRCA1 gene using single-strand conformation polymorphism analysis. Shifted DNA bands were sequenced. Patients with germline BRCA1 mutations were screened for allelic loss in tumor DNA at the BRCA1 locus. Results: Two of the 17 patients (11%, 95% confidence interval 0.07, 0.37) exhibited the 185 delAG germline BRCA1 mutation described in the Ashkenazi Jewish population. The family history of one patient was notable for a mother and five aunts with breast or ovarian cancer. The other patient had a personal history of breast cancer. Both patients exhibited allelic loss of the normal BRCA1 allele in their tumor. A third patient was found to have a previously undescribed exon 11 single base pair substitution at nucleotide 1239 (CAG to CAC) resulting in a missense mutation (Gln to His). The patient had no family or personal history of breast or ovarian cancer, and her tumor did not exhibit loss of heterozygosity. Conclusion: Germline BRCA1 mutations occur in papillary serous carcinoma of the peritoneum with a frequency comparable to the BRCA1 mutation rate in ovarian cancer. Although the penetrance is unknown, peritoneal carcinoma should be considered a malignancy expressed in the familial breast ovarian cancer syndrome.

BRCA1 Gene Mutations in Women With Papillary Serous Carcinoma of the Peritoneum

BRCA1 Gene Mutations in Women With Papillary Serous Carcinoma of the Peritoneum

CT appearance of primary papillary serous carcinoma of the peritoneum.

Our objective was to describe the CT characteristics of primary papillary serous carcinoma of the peritoneum. The presence of peritoneal masses, extensive omental calcification, and the absence of an ovarian mass on CT--particularly in postmenopausal women--is highly suggestive of primary papillary serous carcinoma of the peritoneum and should alert the radiologist to the possibility of this diagnosis.

Molecular evidence for multifocal papillary serous carcinoma of the peritoneum in patients with germline BRCA1 mutations.

Papillary serous carcinoma of the peritoneum (PSCP) diffusely involves peritoneal surfaces, while it spares or only superficially involves the ovaries. PSCP is histologically indistinguishable from serous epithelial ovarian carcinoma, and it may develop years after oophorectomy. The molecular pathogenesis of PSCP remains unresolved, although preliminary data suggest a multifocal origin in some cases. Patients with germline BRCA1 mutations may develop PSCP in addition to breast and ovarian carcinomas. The purpose of this study was to utilize the androgen receptor (AR) gene locus to test the hypothesis that some cases of PSCP have a multifocal origin and to determine if patients with germline BRCA1 mutations develop multifocal PSCP. Specimens of normal and tumor tissues from 22 women with PSCP were obtained, and DNA was extracted. The AR gene locus was evaluated for patterns of loss of heterozygosity (LOH) and X-chromosome inactivation. The methylation-sensitive Hpa II restriction enzyme was used to differentiate the active and inactive X chromosomes. Germline BRCA1 mutation status of the patients was determined previously. Genetic analysis of tumor specimens indicated that five (23%) of 22 case subjects had patterns of selective LOH at the AR locus, consistent with multifocal, polyclonal disease origin. Two patients with selective LOH also had alternating X-chromosome inactivation patterns. Patients with germline BRCA1 mutations were more likely to have evidence of multifocal disease (two-sided Fisher's exact test, P = .01). Our results show that PSCP has a multifocal origin in at least some cases. Furthermore, patients with germline BRCA1 mutations are more likely to develop multifocal PSCP than are patients without BRCA1 mutations.

Biochemical Characterization of Primary Peritoneal Carcinoma Cell Adhesion, Migration, and Proteinase Activity

Primary papillary serous carcinoma of the peritoneum (PPC) is clinically and histologically similar to advanced stage epithelial ovarian carcinoma. PPC classically presents with widespread intraperitoneal dissemination, superficial invasion, and minimal ovarian involvement. Surgical cytoreduction and combination chemotherapy utilized for patients with epithelial ovarian carcinoma have produced varying results for patients with PPC. These differences in response may be secondary to the stage of disease or due to biological differences in metastatic behavior between these carcinomas. In this study, short-term primary cultures of PPC and epithelial ovarian carcinoma (OVCA) were compared to enable biochemical comparison with respect to components of the metastatic cascade including adhesion, migration, and proteinase activity. These data demonstrated similar properties in adhesive profiles of PPC and OVCA, with preferential adhesion to type I collagen and vitronectin. Matrix-degrading proteinases including matrix metalloproteinases (MMP)-2, MMP-9, and urinary-type plasminogen activator were produced by both cell types. PPC migration was stimulated by multiple extracellular matrix proteins, whereas OVCA cells demonstrated maximal migration on type I collagen coated surfaces. Together our data suggest biochemical similarities between PPC and OVCA with respect to individual components of the metastatic cascade.

Papillary serous carcinoma of the peritoneum in women. A clinicopathologic and immunohistochemical study.

Papillary serous carcinoma of the peritoneum (PSCP) is a primary peritoneal tumor in women that histologically resembles papillary serous carcinoma of the ovary (PSCO). Recognition of PSCP as an entity is controversial, as is the histogenesis, histopathologic differential diagnosis, and treatment. Ten cases of PSCP retrieved from the pathology files of 4 hospitals in Kyoto and Nara, Japan, were studied clinicopathologically and immunohistochemically. Patient ages at presentation ranged from 40 to 74 years (median, 56 years). All patients were Asian (Japanese). None of the patients had a history of asbestos exposure. Most of the patients had abdominal swelling, ascites with positive cytology, and elevated serum CA125. At surgery, omental tumors with dissemination to the abdominal and pelvic peritoneum were found in all patients. The histology was similar to that of Grade 2 to 3 PSCO. Immunohistochemical studies using a panel of monoclonal antibodies against carbohydrates showed that Lewis Y is a good marker, in addition to S-100, placental alkaline phosphatase, CA125, and CD15 for separating PSCP from malignant mesothelioma (MM). With cytoreductive surgery and cisplatin-based combination chemotherapy and in some cases adoptive immunotherapy and radiation, a median survival of 27 months and a 5-year survival rate of 27% were attained. One patient with Grade 3 tumor has survived for more than 6 years after surgery. (1) Papillary serous carcinoma of the peritoneum is a definite clinicopathologic entity; (2) immunohistochemistry is a useful tool for distinguishing PSCP from MM; (3) cytoreductive surgery and cisplatin-based combination chemotherapy with other adjunct therapies such as immunotherapy and radiation may improve patient survival in PSCP.

Allelic loss and microsatellite instability on chromosome 17 in papillary serous carcinoma of the peritoneum (PSCP)

Allelic loss and microsatellite instability on chromosome 17 in papillary serous carcinoma of the peritoneum (PSCP)

Effectiveness of paclitaxel in treating papillary serous carcinoma of the peritoneum in an adolescent

A 15-year-old girl with papillary serous carcinoma of the peritoneum was seen with abdominal distension, ascites, and elevated CA 125 tumor marker. After other therapy failed, she achieved complete and continuing remission with paclitaxel.

Peritoneal Papillary Serous Carcinoma in a Woman with a History of in Utero DES Exposure

Antenatal exposure to diethylstilbestrol (DES) has been implicated in the development of clear-cell adenocarcinoma of the vagina and cervix. In addition, there are a handful of case reports of germ cell tumors and other benign ovarian tumors in the offspring of women treated with DES during pregnancy. This the first report of a papillary serous carcinoma of the peritoneum following in utero exposure to DES. As the population of women with a history of in utero exposure to DES is reaching into the fourth decade, these patients need to be closely monitored for the development of gynecologic malignancies, especially epithelial and germ cell ovarian tumors. We also encourage the reporting of these tumors of the DES registry to document the exact incidence of these malignancies.

Primary, papillary serous carcinoma of the peritoneum; a report of experiences

A total of fourteen patients with primary papillary serous carcinoma of the peritoneum (PPSCP) were treated at the Department of Obstetrics and Gynaecology of the University of Graz between 1980 and 1991. The presence of tumours from other sites, particularly the pancreas and the ovary, had been excluded. Due to extensive spreading of the disease mainly in the upper abdomen, only seven of the 14 patients underwent exploratory laparotomy. The median overall survival time was 10 months (range, 1-28 months). These results are due to the extent of spreading of the disease at diagnosis, and also to the fact, that optimal cytoreductive surgery was possible only in four of the 14 patients. The four patients with optimal cytoreduction showed a better survival than those, who underwent less radical surgery. These results seem to indicate, that, as in primary ovarian cancer, the amount of residual disease may be an important prognostic determining factor in PPSCP.

Clinical Pharmacology, Metabolism, and Tissue Distribution of 90Y-Labeled Monoclonal Antibody B72.3 After Intraperitoneal Administration

B72.3 is a murine monoclonal antibody that recognizes a high-molecular-weight tumor-associated glycoprotein (TAG-72). Nine patients with TAG-72-positive ovarian carcinoma or papillary serous carcinoma of the peritoneum received an intraperitoneal infusion of 2, 4, or 10 mg B72.3 labeled with 0.5-1.2 (mean, 0.8) mCi 90Y. All patients had laparotomy, with multiple tissue and tumor samples removed 3-7 days later. The concentration of the total 90Y label in peritoneal fluid cleared with an extrapolated half-life of 68.6 +/- 4.5 hours. A low-molecular-weight 90Y-labeled species of metabolite was identified by high-performance liquid chromatography. The concentration of this low-molecular-weight species initially increased in the peritoneal fluid, with a half-life of 0.9 hour, and was rapidly cleared from the peritoneal cavity, with a half-life of 23.1 hours. Both the 90Y-labeled metabolite and the 90Y-labeled B72.3 were absorbed into the plasma, with half-lives of 16 +/- 2.2 hours and 25 +/- 5 hours, respectively. The clearance half-lives for these agents in plasma were 25 +/- 3 hours for the metabolite and 42 +/- 17 hours for B72.3. Approximately 8%-11% of the total injected 90Y label appeared in urine over 72 hours. Most of the label (about 70%) was present as the 90Y-labeled metabolite, but about 30% of the 90Y label in urine appeared identical to the authentic 90Y-labeled B72.3 standard when assayed by chromatography. Tissue distribution studies showed that normal tumor tissue and omentum contained the highest content of 90Y (about 0.017% of the injected dose per gram), followed in descending order by liver, normal lymph nodes, peritoneum, bone, and fascia. The lowest concentrations of 90Y were found in rectus abdominis muscle, bone marrow, and fat. There was substantial heterogeneity in the uptake of the 90Y label into tumor sites among patients and among different sites within the same patient. No correlation could be demonstrated between the TAG-72 content and the amount of 90Y label found in tumor sites. Preliminary radiation dosimetry estimates suggest that the tumor sites received about 82.8 cGy for each millicurie of 90Y administered. Thus, if an adequate total radiation dose can be achieved, 90Y-labeled B72.3 should be therapeutically useful for treating diffuse intraperitoneal disease.

RARE GYNECOLOGIC MALIGNANCIES

Fallopian tumor carcinoma and papillary serous carcinoma of the peritoneum are rare tumors that usually mimic advanced ovarian cancer. The current treatment for these tumors is similar to that for ovarian cancer with approximately an 80% response rate, but only a 20% 5-year survival. Uterine sarcomas are probably the most lethal of the gynecologic malignancies, with frequent recurrence and death despite apparent early diagnosis and aggressive therapy. Gestational trophoblastic tumors, on the other hand, are usually curable, even when widely metastatic disease is present. The clinical features, staging, and current treatment of each of these tumors is reviewed.