The extra-ovarian peritoneal serous papillary carcinoma is a rare, primary, multicentric peritoneal tumor that is histologicallyidentical to ovarian serous carcinoma of equivalent grade, but can spare or minimally involve the ovaries.
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AGE SEX GEOGRAPHY EPIDEMIOLOGIC ASSOCIATIONS
Fam Cancer. 2004;3(3-4):265-81. Abstract quote
Women from families with multiple cases of breast and ovarian cancer, specifically those who carry cancer-associated mutations of BRCA1 or BRCA2 are at increased life-time risk for peritoneal carcinoma, even after previous surgery to remove the ovaries, fallopian tubes and uterus.
Hereditary breast-ovarian cancer (HBOC) syndrome and the associated BRCA1 and BRCA2 mutations are particularly prevalent in women of Jewish lineage, and specific BRCA1 and BRCA2 germline mutations have been linked with peritoneal carcinoma and HBOC syndrome in Jewish populations, especially those of Ashkenazi descent.
This review presents the currently available data and looks forward toward further and better understanding of peritoneal carcinoma in women with inherited susceptibility. Over 90% of peritoneal cancer in patients from HBOC syndrome kindreds and associated with BRCA1 and BRCA2 mutations are serous carcinomas, which is equivalent with the proportion of ovarian cancers that are serous carcinomas in similar patients. The best indications are that while many peritoneal carcinomas in genetically susceptible women may arise directly from malignant transformation of the peritoneum, others might represent metastases from primary ovarian or fallopian tube carcinomas. Although the incidence of borderline ovarian tumors may not be increased in HBOC syndrome kindreds and those who carry cancer-associated BRCA1 and BRCA2 mutations, these individuals could be susceptible to malignant transformation of borderline lesions of the ovaries and peritoneum. Moreover, recent reports raise the question of possibly increased risk in Jewish carriers of germline BRCA1 mutations for uterine papillary serous carcinoma, which could be the source of metastasis to the peritoneum in some cases. The penetrance of cancer-associated BRCA1 mutations for ovarian cancer is estimated to be 11%-54%, and for BRCA2 mutations the penetrance for ovarian cancer is 11%-23%. So far, available screening methods appear to be insufficient for early detection of many ovarian cancers. Prophylactic oophorectomy has been found to reduce the risk for ovarian cancer in women from HBOC kindreds and those who carry cancer-associated BRCA1 and BRCA2 mutations, leaving a residual risk for peritoneal carcinomatosis of well less than 5%. Therefore, surgical removal of the ovaries, fallopian tubes and uterus, after child-bearing has been completed and by early in the fifth decade of life, are appropriate prophylactic procedures in women whose genetic susceptibility puts them at increased risk for cancers of mullerian tract origin, including ovarian and fallopian tube carcinomas and possibly serous carcinoma of the uterus.
Hysterectomy, as well as salpingo-oophorectomy, removes the gynecologic organs targeted for malignant transformation in genetically susceptible women and simplifies decisions regarding hormone replacement therapy and chemical prophylaxis and treatment of breast cancer.
Unless a transabdominal operative approach is otherwise indicated, laparoscopic-assisted transvaginal techniques are well suited for intra-abdominal exploration, cytology, biopsies and prophylactic salpingo-oophorectomy and hysterectomy in women with hereditary susceptibility to gynecologic cancer.
DISEASE ASSOCIATIONS CHARACTERIZATION ENDOMETRIAL CARCINOMA
Gynecol Oncol. 2002 Feb;84(2):245-51. Abstract quote
OBJECTIVE: Papillary serous carcinoma of the peritoneum (PSCP) coexisting with, or after, endometrial carcinoma (EC) is an extremely rare condition with no documented patient series. The aim of this investigation was to describe our experience in treating five patients diagnosed with PSCP synchronously with EC and two others who developed PSCP metachronously after EC.
METHODS: In this retrospective study, we reviewed and analyzed the clinical and pathological data of seven patients diagnosed and managed over a 10-year period. The diagnosis of PSCP was mostly based on the inclusionary criteria of the Gynecologic Oncology Group . Disease stages were determined using the FIGO criteria for epithelial ovarian cancer (EOC) and endometrial carcinomas . The treatment for PSCP was similar to that for advanced EOC and immunohistochemical studies were performed using archival material for PSCP and EC in order to determine p53, Bcl-2, HER2, and estrogen and progesterone receptor (ER, PR) status. Germline mutation analyses were performed for the two most common mutations pertaining to BRCA1 and the one most common mutation pertaining to BRCA2 genes only.
RESULTS: Five patients with PSCP and synchronous EC initially underwent surgical treatment. The remaining two underwent surgery originally for EC and, thereafter, for metachronous PSCP. All seven patients had advanced stages (III or IV) of PSCP and stage I only EC. At the time of analysis, four patients were alive. p53, Bcl-2, ER, and PR were found to have been expressed in various rates in both or one of the neoplasms. However, no HER2 was found to have been expressed, either in PSCP or in EC. All germline mutation analyses were negative.
CONCLUSIONS: The results obtained in this study show that PSCP can occur either synchronously or metachronously with lower stage EC that is associated with advanced disease stages. We suggest that this clinical form of PSCP with synchronous or metachronous EC is a very aggressive and lethal clinical form and differs markedly from the vast majority of multiple gynecologic neoplasms of the upper genital canal diagnosed in the ovarian-endometrial group, of which EOC are mostly diagnosed as stage I diseases with high-rate cures.
PATHOGENESIS CHARACTERIZATION GENERAL
Mod Pathol. 1996 Mar;9(3):166-73. Abstract quote
The clonality of disseminated serous carcinoma involving the ovary, peritoneum, and, occasionally, the endometrium is controversial. Histopathologic examination alone cannot unequivocally distinguish between a monoclonal origin and a multicentric origin.
Two patients with peritoneal serous carcinoma with minimal ovarian involvement (one with endometrial serous carcinoma), nine patients with stage III bilateral ovarian carcinoma, and one patient with stage III bilateral carcinosarcoma were studied for clonality. One patient with ovarian carcinoma that recurred after chemotherapy was also studied. Previous analyses of single frozen tumor specimens from these patients had identified different p53 gene mutations in each patient.
To test the hypothesis that the disseminated cancers had a monoclonal origin, we assayed DNA from numerous foci from each patient to determine whether the known p53 mutation was present in each specimen. Identical mutations were detected in the tumor foci from each patient with peritoneal dissemination and minimal ovarian involvement, including one patient with an endometrial serous carcinoma as well. In all the patients with bilateral ovarian cancer, the genetic change in p53 was identical in both ovarian tumors. Genetic progression was observed in two patients, one of whom showed a loss of heterozygosity involving the p53 gene in a recurrent tumor. In the second patient, a p53 mutation not present in either ovarian tumor was detected in a metastatic tumor from the omentum.
These results strongly suggest that disseminated serous carcinomas, whether primary in the ovary, endometrium, or peritoneum, are of monoclonal rather than multicentric origin; that bilateral stage III ovarian cancers are typically of monoclonal origin; and that additional genetic events involving p53 might occur during progression of these tumors.
CHARACTERIZATION RADIOLOGIC LABORATORY MARKERS
- Papillary serous carcinoma of peritoneum: case study and review of the literature on the differential diagnosis of malignant peritoneal tumors.
Koutselini HA, Lazaris AC, Thomopoulou G, Papayannopoulou A, Kairi-Vasilatou E.
Department of Cytopathology, "Areteion" Hospital, The Athens National and Capodistrian University Medical School, Athens, Greece.
Adv Clin Path. 2001 Jul;5(3):99-104. Abstract quote
The distinction between malignant mesothelioma and other malignant neoplasms diffusely involving the peritoneum is important for proper patient treatment. The extra-ovarian peritoneal serous papillary carcinoma is a rare, primary, multicentric peritoneal tumor that is morphologically identical to ovarian serous carcinoma of equivalent grade, but can spare or minimally involve the ovaries.
We report such a tumor in a 65-year-old female who had abdominal swelling, ascites with positive cytology and a high grade of nuclear atypia in malignant cells as well as elevated serum CA125. Exploratory laparotomy findings of intrabdominal carcinomatosis were not accompanied by any evident primary site; so the diagnosis of a primary papillary serous neoplasia of the peritoneum was strongly considered. Since the amount of residual disease may be an important prognostic determining factor in primary papillary serous carcinoma of the peritoneum, the patient was debulked to no macroscopic disease and was then given platin-based chemotherapy.
The tumor's differential diagnosis from malignant mesothelioma was based, apart from morphologic criteria, on the tumor's immunoreactivity to MOC-31, Ber-EP4 and TAG-72, as well as on the lack of immunostaining for keratin 5/6 and calretinin. Differential diagnosis from ovarian cancer was possible only after the pathological examination of the surgically resected ovaries; the tumor showed minimal superficial invasion of the ovarian cortex.
HISTOLOGICAL TYPES CHARACTERIZATION CYTOLOGY
J Natl Cancer Inst. 1996 Jul 17;88(14):980-7. Abstract quote
BACKGROUND: Microscopic evaluation of cells washed from the peritoneal cavity during surgery for gynecologic tumors is used to detect subclinical intraperitoneal metastases from these tumors. The prognostic significance of this test, however, has been questioned.
PURPOSE: Stressing histologic correlation and pitfalls in interpretation, we previously reported that the sensitivity of intraoperative peritoneal washing cytology was lower than was suggested earlier. This study evaluates the clinical utility of this test in the long-term follow-up of our patients.
METHODS: Staging (International Federation of Gynecology and Obstetrics [FIGO], 1971) and follow-up information was available for 355 unselected patients with primary tumors who had peritoneal washings performed during initial surgery at University Hospital-Stony Brook, NY, during the period from 1980 through 1989. There were 135 patients with endometrial carcinomas, 112 with ovarian carcinomas, 92 with cervical carcinomas, and 16 with borderline (i.e., of low malignant potential) ovarian tumors. The median follow-up of the patients was 57 months (range, 0-154 months). Follow-up data were obtained from the Tumor Registry at University Hospital-Stony Brook. Survival differences were determined by Kaplan-Meier analysis and were evaluated by two-tailed logrank test.
RESULTS. Peritoneal washing cytology was positive at initial surgery for 120 (33.8%) of 355 patients, including 90 (80.4%) of 112 patients with ovarian carcinomas, five (31.2%) of 16 patients with borderline ovarian tumors, 17 (12.6%) of 135 patients with endometrial carcinomas, and eight (8.7%) of 92 patients with cervical cancers. For 203 patients with stage I tumors, the peritoneal cytology was positive in 29.4% of the patients with ovarian carcinomas, 18.2% with borderline ovarian tumors, 6.1% with endometrial carcinomas, and 5.2% with cervical carcinomas. By use of peritoneal histology as the standard, peritoneal cytology was highly specific (98.1%) but less sensitive (82.9%) in detecting intraperitoneal involvement. For patients with stage I tumors, 80.0% with ovarian carcinomas, 83.3% with endometrial carcinomas, and 100% with cervical carcinomas who showed positive cytology died of their cancer, compared with 25.0% with ovarian carcinomas, 13.0% with endometrial carcinomas, and 21.9% with cervical carcinomas who showed negative peritoneal cytology. Four (2.0%) patients with stage I tumors had positive peritoneal cytology but negative peritoneal histology. Of these patients, three (two with ovarian carcinoma and one with cervical carcinoma) died of their cancer, whereas one patient with a borderline ovarian tumor was free of disease at the last follow-up. Survival analysis indicated that peritoneal washing cytology stratified for stage provides better prognostic information for each primary cancer site studied than does stage alone. All patients with borderline ovarian tumors were alive at last follow-up, regardless of disease stage or peritoneal status.
CONCLUSIONS: Regardless of FIGO stage, positive peritoneal washing cytology predicted poor prognosis for women with epithelial tumors of the genital tract, except for patients with borderline ovarian tumors. Patients in whom peritoneal cytology was the only evidence of intraperitoneal spread were few, but the disease in such patients was associated with poor outcome. IMPLICATIONS: Strict adherence to specialized cytologic criteria in peritoneal washing cytology allows for results that are highly predictive of survival. This information may be useful in stratifying women in therapeutic trials for treatment of genital tract carcinomas.
CHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE ESTROGEN AND PROGESTERONE RECEPTORS
- Value of estrogen and progesterone receptor immunostaining in distinguishing between peritoneal mesotheliomas and serous carcinomas.
Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Hum Pathol. 2005 Nov;36(11):1163-7. Epub 2005 Sep 22. Abstract quote
The differential diagnosis between peritoneal mesotheliomas and serous carcinomas involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry.
To determine whether estrogen receptors (ER) or progesterone receptors (PR) may have any value as immunohistochemical markers for discriminating between these malignancies, 40 serous carcinomas of the ovary metastatic to the peritoneum, 7 primary peritoneal serous carcinomas, 30 epithelioid peritoneal malignant mesotheliomas, 5 well-differentiated papillary mesotheliomas, and 4 adenomatoid tumors were immunostained for ER and PR. Reactivity for ER was obtained in 35 (88%) of the metastatic serous carcinomas of the ovary and 6 (86%) of the primary peritoneal serous carcinomas, whereas positivity for PR was observed in 24 (60%) of the metastatic serous carcinomas and 4 (56%) of the primary peritoneal serous carcinomas.
None of the mesotheliomas or adenomatoid tumors expressed ER or PR. It is concluded that, because of its high sensitivity for serous carcinomas, ER immunostaining could be very useful in distinguishing between serous carcinomas and peritoneal mesotheliomas. Immunostaining for PR, however, has little practical utility.
Am J Surg Pathol. 2005 Aug;29(8):1074-8. Abstract quote
Although differential WT-1 expression between ovarian and uterine serous carcinoma has been discussed in the literature, there have been no studies of WT-1 expression in serous carcinomas in the peritoneum with or without concurrent serous carcinoma in an endometrial polyp.
This study addresses this issue and includes a small series of uterine and ovarian serous carcinomas for comparison. Nine peritoneal serous carcinomas with coexistent serous carcinoma in an endometrial polyp, 10 peritoneal serous carcinomas without serous carcinoma in an endometrial polyp, 9 uterine serous carcinomas, and 12 ovarian serous carcinomas were stained with antibody to WT-1. Ninety-two percent of ovarian serous carcinomas and 80% of peritoneal serous carcinomas without serous carcinoma involving an endometrial polyp expressed WT-1. In contrast, 12% of peritoneal serous carcinomas with serous carcinoma in an endometrial polyp expressed WT-1 with the serous carcinoma in the endometrial polyp staining concordantly.
For uterine serous carcinoma without an endometrial polyp, only 11% expressed WT-1. Peritoneal serous carcinomas without coexistent serous carcinoma in an endometrial polyp have a WT-1 expression pattern similar to ovarian serous carcinoma while peritoneal serous carcinomas with coexistent serous carcinoma in an endometrial polyp have a staining pattern similar to uterine serous carcinoma.
The difference in WT-1 expression among serous carcinomas suggests a difference in biology based on the site of origin. Additionally, the difference in WT-1 expression between peritoneal serous carcinomas with and without coexistent serous carcinoma in endometrial polyps suggests that peritoneal serous carcinoma may have different pathogenetic pathways.
Int J Gynecol Pathol. 2003 Oct;22(4):374-7. Abstract quote
Wilms tumor gene (WT-1) expression has been reported in many human cancers, including most ovarian and peritoneal serous carcinomas, but has not been studied in carcinomas of the fallopian tube.
In this study, the authors evaluated the immunohistochemical expression of WT-1 in serous carcinomas of the fallopian tube and compared their reactivity with that of ovarian, peritoneal, and endometrial serous carcinomas. All primary serous carcinomas of the fallopian tube (13 cases), ovaries (25 cases), and peritoneum (3 cases) were reactive with the WT-1 antibody, whereas all five primary endometrial serous carcinomas were nonreactive. WT-1 reactivity in an unknown primary serous carcinoma is therefore suggestive of an extrauterine site.
The marked difference in WT-1 staining raises the possibility of genetic differences between serous carcinomas arising in the endometrium compared with those arising in the ovaries, fallopian tubes, and peritoneum.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES MESOTHELIOMA
- The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study.
1Department of Pathology, MD Anderson Cancer Center, The University of Texas, TX, USA.
Mod Pathol. 2006 Jan;19(1):34-48. Abstract quote
The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas.
The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas.
The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.
- Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum.
Attanoos RL, Webb R, Dojcinov SD, Gibbs AR.
Department of Histopathology, Llandough Hospital, Cardiff & Vale NHS Trust, Penarth, Vale of Glamoran, UK.
Histopathology. 2002 Mar;40(3):237-44. Abstract quote
AIMS: To evaluate the role of mesothelial markers (calretinin, thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal carcinoembryonic antigen, Leu-M1, CA-125 and Ber-EP4) in distinguishing diffuse peritoneal malignant mesothelioma from primary serous papillary adenocarcinoma of the ovary and peritoneum.
METHODS AND RESULTS: Paraffin-embedded formalin-fixed blocks from 32 diffuse peritoneal mesotheliomas of epithelial subtype (all females), 20 serous papillary ovarian carcinomas and three primary peritoneal serous papillary carcinomas were studied. Calretinin and Ber-EP4 appeared to be the best positive mesothelial and carcinoma marker, respectively. Nuclear calretinin expression was identified in 28 of 32 malignant mesotheliomas with no nuclear immunoreactivity in the cohorts of serous papillary ovarian and peritoneal carcinomas, thus yielding 88% sensitivity and 100% specificity. Ber-EP4 showed 95% sensitivity and 91% specificity for serous papillary ovarian carcinoma. Thrombomodulin, cytokeratin 5/6 and CD44H immunoreactivities were seen in 18 (56%), 17 (53%) and 15 (47%) of peritoneal mesotheliomas, respectively, and in six (30%), five (25%) and five (25%) of the ovarian tumours, respectively. None of the three primary peritoneal serous papillary carcinomas expressed calretinin, thrombomodulin, cytokeratin 5/6 or CD44H. Polyclonal and monoclonal CEA, and Leu-M1 were expressed by two (10%), one (5%) and seven (35%) serous papillary ovarian carcinomas, respectively. None of the serous papillary peritoneal carcinomas expressed polyclonal CEA, monoclonal CEA or Leu-M1. CA-125 was positive in 19 (95%) and two (67%) ovarian and peritoneal carcinomas, respectively, and in eight (25%) peritoneal mesotheliomas.
CONCLUSIONS: Calretinin and Ber-EP4 are useful discriminant markers in distinguishing peritoneal mesothelioma in women from serous papillary ovarian and peritoneal carcinoma. The other mesothelial markers (thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal CEA, and Leu-M1) yielded a too low sensitivity for practical use.
SEROUS CARCINOMA, OVARY
- Value of immunohistochemistry in distinguishing peritoneal mesothelioma from serous carcinoma of the ovary and peritoneum: a review and update.
From The University of Texas M. D. Anderson Cancer Center, Houston.
Adv Anat Pathol. 2006 Jan;13(1):16-25. Abstract quote
At present, a large number of immunohistochemical markers that can be used in the differential diagnosis between epithelioid peritoneal mesotheliomas and serous carcinomas are available. However, great differences of opinion exist regarding the individual value of some of these markers.
This article provides a critical review of all of the information that is currently available on those markers that have the greatest potential for assisting in distinguishing between peritoneal mesotheliomas and serous carcinomas. The conclusion of this review indicates that the positive serous carcinoma markers, by and large, have a higher degree of sensitivity and specificity in assisting in discriminating between these malignancies than the positive mesothelioma markers.
From a practical point of view, a combination of MOC-31 (or Ber-EP4), estrogen receptors, and calretinin immunostaining should allow a clear distinction to be made between epithelioid peritoneal mesotheliomas and serous carcinomas in most cases.
- Role of immunohistochemistry in distinguishing epithelial peritoneal mesotheliomas from peritoneal and ovarian serous carcinomas.
The University of Texas M.D. Anderson Cancer Center, Houston 77056, USA.
Am J Surg Pathol. 1998 Oct;22(10):1203-14. Abstract quote
The histologic distinction between epithelial peritoneal mesothelioma and papillary serous carcinoma diffusely involving the peritoneum may be difficult. Although some investigators have indicated that immunohistochemistry can facilitate this differential diagnosis. only a few studies using a limited number of markers have been published.
In this study, the immunoreactivity of keratin 5/6, vimentin, epithelial membrane antigen, thrombomodulin, calretinin, MOC-31, Ber-EP4, carcinoembryonic antigen, TAG-72 (B72.3), CD15 (Leu-M1), placental alkaline phosphatase, CA19-9, CA-125, HBME-1, 44-3A6, and S-100 protein was investigated in 35 epithelial peritoneal mesotheliomas, and 45 papillary serous carcinomas [30 ovarian (10 primary and 20 metastatic to the peritoneum) and 15 papillary serous carcinomas of the peritoneum].
After analyzing the results, it is concluded that calretinin, thrombomodulin, and keratin 5/6 are the best positive markers for differentiating epithelial malignant mesotheliomas from papillary serous carcinomas diffusely involving the peritoneum.
The best diagnostic discriminators among the antibodies considered to be negative markers for mesothelioma are MOC-31, B72.3, Ber-EP4, CA19-9, and Leu-M1. Immunostaining for carcinoembryonic antigen, placental alkaline phosphatase, epithelial membrane antigen, vimentin, HBME-1, 44-3A6, CA-125, or S-100 have little or no diagnostic utility in establishing the differential diagnosis between these conditions.
The results of this study also confirm previous observations indicating that both papillary serous carcinomas of the peritoneum and serous carcinomas of the ovary have a similar phenotype and, therefore, immunohistochemical studies are not useful in separating these entities.
PROGNOSIS CHARACTERIZATION METASTASES
Am J Surg Pathol. 2004 Dec;28(12):1646-51. Abstract quote
Metastasis of ovarian or peritoneal serous carcinoma to the breast and/or axillary lymph nodes is a rare event. Nevertheless, its recognition and distinction from mammary carcinoma are of great clinical importance because the treatment and prognosis differ significantly.
Eighteen cases of ovarian or peritoneal serous carcinoma metastatic to the breast and/or axillary LNs from a 14-year period (1990-2003) were retrieved from our files. Clinical information was obtained from the patients' charts. The age of the patients ranged from 21 to 67 years (median, 55 years). The primary tumors included 14 ovarian serous carcinomas (11 high grade and 3 low grade; 2 of the low-grade tumors presented as serous tumors of low malignant potential and recurred as low-grade serous carcinoma) and 4 peritoneal serous carcinomas (3 high grade and 1 low grade). Of the ovarian neoplasms, 1 was stage I and 10 were stage III tumors; the breast and/or axillary lymph node metastases were discovered on average 30 months after presentation (range, 7-135 months). Three of the ovarian serous carcinomas were stage IV tumors; in 1 case, there were axillary lymph node metastases at initial presentation; and in 2 cases, breast and/or axillary lymph node metastases developed at 18 and 102 months. Two of the 4 patients with peritoneal serous carcinoma presented with stage IV disease, having synchronous breast and axillary lymph node metastases; the other 2 patients developed them at 11 and 16 months after presentation. Four patients had multiple breast lesions and 8 patients had a single metastasis. In 4 cases, the breast metastases were initially interpreted as infiltrating ductal carcinoma. The remaining 6 patients had axillary lymph node involvement only. The metastases in 17 of the cases had papillary features, with psammoma bodies present in 4.
Immunoperoxidase studies for GCDFP-15 and WT-1 were performed in 4 cases; all 4 were positive for WT-1 and negative for GCDFP-15. Follow-up was available for 17 patients, with 7 patients known to be dead from disease (survival range, 2-31 months) after the development of metastatic disease to the breast or axillary lymph nodes. Ten patients were alive with disease at their last follow-up, which ranged from 1 to 30 months after the breast or axillary LN metastasis developed. Metastases to the breast or axillary lymph nodes from ovarian and/or peritoneal serous carcinomas are uncommon. Most of the patients in whom metastatic disease develops have a known history of advanced stage ovarian or peritoneal carcinoma.
Breast and/or axillary LN involvement at initial presentation can occur but is rare. Differentiation between metastatic and primary tumors of the breast is of great importance because treatment and prognosis differ significantly. Clinical history, the presence of papillary architecture, and WT-1 expression are useful in establishing the correct diagnosis.
TREATMENT CHARACTERIZATION GENERAL
- Grade 1 peritoneal serous carcinomas: a report of 14 cases and comparison with 7 peritoneal serous psammocarcinomas and 19 peritoneal serous borderline tumors.
Weir MM, Bell DA, Young RH.
James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, and the Department of Pathology, Harvard Medical School, Boston 02114, USA.
Am J Surg Pathol. 1998 Jul;22(7):849-62. Abstract quote
Low-grade peritoneal serous carcinomas have been the subject of limited study, and their distinction from peritoneal serous psammocarcinomas and serous borderline tumors is not always easy.
The clinicopathologic features of 14 low-grade serous carcinomas, 7 psammocarcinomas, and 19 serous borderline tumors of peritoneal origin were compared. Average ages were 58 years (low-grade serous carcinomas), 48 years (borderline tumors), and 40 years (psammocarcinomas). Typical clinical presentations were abdominal pain, abdominal mass, or both, with the tumors incidental in 37% (borderline tumors), 43% (psammocarcinomas), and 36% (low-grade serous carcinoma). Operative and gross findings varied from nodules to adhesions to a dominant mass. Treatment was surgical debulking in most cases, with biopsy alone for eight borderline tumors. Seven patients with low-grade serous carcinoma were alive when last seen, but follow-up duration is short (average, 1.2 years): five were without disease, one had recurrent disease and one persistent disease. One patient with serous carcinoma died of disease at 3.5 years, and two patients died of other causes. Three patients with psammocarcinoma were alive without disease (average 3.3 years). Fourteen patients with borderline tumors were alive (average 3 years): 10 were without disease, 2 had persistent disease, and serous carcinoma developed in 2. The low-grade serous carcinomas resembled the invasive implants of ovarian serous borderline tumors. lacked high-grade nuclear atypia, showed tissue, lymphovascular space invasion, or both and had appreciable solid epithelial proliferation. Some serous carcinomas showed abundant psammomatous calcification suggesting psammocarcinoma but had too much epithelial proliferation for that diagnosis. The psammocarcinomas showed at least 75% psammoma bodies, no more than moderate cytological atypia, tissue or lymphovascular space invasion, or both, and rare epithelial proliferation less than 15 cells across. Adequate sampling was necessary to identify invasion, with highest yields of invasive foci in omental samples; individual foci in some cases of carcinoma resembled borderline tumor.
The serous borderline tumors resembled the noninvasive implants of ovarian serous borderline tumors, lacked invasion, and did not show nuclear atypia of the degree seen in grade 2 or grade 3 serous carcinoma. Low-grade serous carcinoma, psammocarcinoma, and serous borderline tumors of peritoneal origin share some clinicopathologic features and may be underrecognized at surgery and gross examination. Because of overlapping microscopic patterns, adequate sampling is mandatory to identify small foci of invasion that exclude a borderline tumor and identify significant cellularity that excludes a psammocarcinoma.
Conservative therapy is merited for younger women with borderline tumors. Maximum debulking is recommended for bulky symptomatic borderline tumors, low-grade serous carcinoma, and psammocarcinoma. Although short-term outcomes for the carcinomas appear favorable, follow-up is too limited to determine long-term outcomes.
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