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new england journal
case records of the massachusetts general hospital
Founded by Richard C. Cabot Nancy Lee Harris, m.d., Editor Jo-Anne O. Shepard, m.d., Associate Editor Sally H. Ebeling, Assistant Editor
Stacey M. Ellender, Assistant Editor Christine C. Peters, Assistant Editor
Case 37-2004: A 52-Year-Old Woman with Postmenopausal Bleeding and a Cystic Ovarian Mass
Richard T. Penson, M.D., Dushyant Sahani, M.D., and Debra A. Bell, M.D.
presentation of case
A 52-year-old woman visited her gynecologist because of a single episode of painless postmenopausal bleeding. Her last menstrual period had been more than one year previously. A pelvic ultrasonogram showed the endometrial stripe to be thickened, at 8 mm, and revealed a complex cystic mass, 12 cm in diameter, with a mural nodule in the right adnexa (Fig. 1A). This finding was confirmed by computed tomographic (CT) scanning (Fig. 1B). An endometrial-biopsy specimen revealed that the endometrium was normal. The patient had no gastrointestinal or urinary symptoms. Her weight was stable, and she reported no symptoms other than shortness of breath attributed to obesity. She had had normal Papanicolaou smears on a regular basis and two normal pregnancies 27 and 29 years previously. She had hypertension, which was controlled with metoprolol tartrate, and hypercholesterolemia, which was managed by diet. She had smoked in the distant past and she drank alcohol in moderation. Her 27-year-old daughter had been treated with radioactive iodine for thyroid cancer. Her father had died of renal-cell carcinoma at 72 years of age. On physical examination, the patient’s weight was 108.9 kg and the temperature 37.11°C. The blood pressure was 148/84 mm Hg and the heart rate 103 beats per minute with a regular rhythm. The results of an examination of the head, eyes, ears, nose, and throat were normal. Examination of the chest and heart revealed no abnormalities. The breasts appeared normal, and there was no axillary or supraclavicular lymphadenopathy. The abdomen was not distended. There was suprapubic fullness on palpation at the pelvic inlet, but no discrete mass, organomegaly, or inguinal lymphadenopathy. There was no tenderness, fluid wave, or shifting dullness. The bowel sounds were normal. There was no edema or calf tenderness, and the distal pulses were normal. A pelvic examination revealed normal external genitalia with minimal atrophy and good support. The cervix appeared normal, with no mucosal lesion. The uterus was normal in size and contour, nontender, but was deviated posteriorly by a prominent smooth anterior mass. There was no nodularity in the cul-de-sac on rectovaginal examination. The pelvic sidewalls were smooth and unremarkable. A rectal examination disclosed small hemorrhoids.
n engl j med 351;24 www.nejm.org december 9, 2004
From the Cancer Center, Department of Medicine, Division of Hematology–Oncology (R.T.P.), and the Departments of Radiology (D.S.) and Pathology (D.A.B.), Massachusetts General Hospital; and the Departments of Medicine (R.T.P.), Radiology (D.S.), and Pathology (D.A.B.), Harvard Medical School. N Engl J Med 2004;351:2531-8.
Copyright © 2004 Massachusetts Medical Society.
Downloaded from www.nejm.org on March 29, 2005 . This article is being provided free of charge for use in Indonesia. Copyright © 2004 Massachusetts Medical Society. All rights reserved.
which could be benign. and A it was palpable above the umbilicus on abdominal examination.nejm. gastrocolic omentectomy. the left ovary was not identified. rather than the planned laparoscopy. 1A). 2532 n engl j med 351. The uterus was normal. Metastases to the ovary are usually bilateral and solid. Penson: May we review the imaging studies? Dr. differential diagnosis B Figure 1.org december 9 . Enlarged lymph nodes that appeared to be hyperplastic rather than containing metastatic carcinoma were present in both obturator fossae.org on March 29. appendectomy. 2004 Downloaded from www.nejm. A total abdominal hysterectomy.24 www. 58 U per liter.6 U per milliliter. there was a right adnexal mass that originated from the right infundibulopelvic ligament. This article is being provided free of charge for use in Indonesia. hysterectomy. malignant. and the pelvis. by hysteroscopy to rule out an occult endometrial tumor and therapeutic endometrial ablation. It was adherent to the superior aspect of the uterus with no evidence of other surface involvement. The patient consented to undergo laparotomy. Because of the large size of the mass. 118 U per liter. The diameter of the mass was approximately 18 cm. followed. 38 U per liter. an exploratory laparotomy was performed. The left ovary and the remainder of the abdomen appeared normal. On exploration. the uterus was found moved posteriorly and to the left by a mass that was fixed to the uterine fundus on the right side. and a full staging procedure were performed. which was thought probably to be a low-grade cystadenocarcinoma. The contrast-enhanced CT scan (Panel B) confirms the finding of a unilocular cystic mass in the right ovary and shows the enhancement in the mural nodule (arrow). Endometriosis was considered unlikely because of the large size of the mass. its fixation to the uterus. Radiologic Studies. and she was discharged on the sixth hospital day. The level of CA-125 was 49. Therefore. The left ovary could not be identified. All rights reserved. unilocular cystic mass with a mural nodule was identified in the right adnexa. and the endometrial stripe measured approximately 10 mm. A pelvic ultrasonogram (Panel A) shows a large cystic mass in the right ovary with a mural nodule (arrow).The new england journal of medicine The hemoglobin level was 11. or borderline. Laboratory measurements of the levels of blood chemicals yielded the following results: alanine aminotransferase. A surgical procedure was planned to begin with laparoscopy. The results of other laboratory tests were within normal ranges. and oophorectomy. The patient’s postoperative recovery was uneventful. Dr. bilateral oophorectomy.6 percent. 1B). and the elevated level of CA-125. 2005 .8 g per deciliter and the hematocrit 33. or to other abdominal or pelvic organs. Again. to the lymphatics. aspartate aminotransferase. A large. and alkaline phosphatase. Dushyant Sahani: Imaging studies included transabdominal and transvaginal pelvic ultrasonography. . Richard T. lymph nodes were removed up to the bifurcation of the aorta. Multiple random biopsy specimens were obtained from the diaphragms. During an examination performed while the patient was under anesthesia. Copyright © 2004 Massachusetts Medical Society. The differential diagnosis includes a primary cystic ovarian neoplasm. Microscopic examination of an intraoperative frozen section disclosed a serous papillary cystic tumor. the pericolic gutters. The mass and uterus were removed en bloc. involving the right ovary (Fig. if these procedures were required. including examination and palpation of all peritoneal surfaces. There was no evidence of metastasis to the peritoneum. if the findings were benign. An abdominal pelvic CT scan was obtained. and again showed a large cystic mass with a posterior mural nodule (Fig.
grade 2 to 3 of 3. 2) revealed that the large unilocular cyst in the right ovary was lined by a single layer of ciliated cells that ranged in shape from cuboidal to columnar. and they are lined with polygonal cells with an elevated nuclear-to-cytoplasmic ratio. The attached fallopian tube was unremarkable. Protruding into this large cyst was a single polypoid mass measuring 1. .5 by 0. 2004 2533 Downloaded from www. Smoothly contoured papillae are lined with fine micropapillae. At higher magnification (Panel B). Two centimeters from this intracystic mass. branching papillae that progressively decrease in size (hierarchical branching).24 www.5 by 1. This article is being provided free of charge for use in Indonesia. The 1. Histopathological Features of the Tumor (Hematoxylin and Eosin). Panel E shows an area of serous carcinoma.7 cm and had a bosselated unremarkable surface.2 by 1.0 cm.case records of the massachusetts general hospital pathological discussion Dr.8 to 2.5 cm in thickness. 2005 .8 cm in diameter were present in the myometrium. 13 by 12 by 9 cm.nejm.8 to 1 cm in diameter. Microscopical examination (Fig. An examination of the right ovary revealed a cystic ovary.cm papillary excrescence.org on March 29.2 to 1. Copyright © 2004 Massachusetts Medical Society.nejm. Panel C shows a micropapillary area in the serous borderline tumor. highly atypical nuclei with prominent nucleoli. the omentum. All rights reserved.5-cm intramural cyst contained a papillary proliferation.3. n engl j med 351.8 by 3. There are irregular. The polypoid mass that extended into the cyst was composed of sheets of cells and closely apposed glands and cysts. the right fallopian tube and ovary. The uterine cavity contained an endometrial polyp measuring 3. The opened specimen revealed that ovarian tissue had been replaced by a unilocular cyst that contained cloudy yellow fluid.org december 9. Panel A shows a typical area in a serous borderline tumor. and dissections of both the right and left pelvic lymph nodes. the papillae are lined with mildly to moderately atypical columnar and cuboidal cells. and several grossly typical leiomyomas ranging from 0. The cells were cuboidal to polygonal and contained highly pleomorphic nuclei with prominent and irregular nucleoli. Debra A. Bell: The specimens received in the pathology department were the uterus with attached left fallopian tube and ovary. The left ovary measured 3.3 cm. the micropapillae are five times as long as they are wide. the cyst wall was thickened and contained a smaller 1. The presence of solid masses of cells with a marked degree of nuclear atypia was sufficient for a diagnosis of serous carcinoma.0 by 2. At higher magnification (Panel D). Detached clusters of similar cells are present. The cut sur- face of the ovary revealed several smooth-walled cysts measuring from 0. The wall of the cyst was predominantly smooth and ranged from 0. the cells have irregular pleomorphic. Sheets of cells and closely apposed glands are present. At higher magnification (Panel F).5-cm cyst filled with a 1. The omentum was unremarkable. with a smooth surface and an attached and unremarkable fallopian tube. A B C D E F Figure 2.
the papillae were broader and had smooth contours.2.2-10 The typical pattern is characterized by hierarchically branching. more commonly. as compared with those of the typical type. and peritoneal involvement in micropapillary-type tumors. These features are those of a serous borderline tumor.11 The presence of a moderately differentiated or a poorly differentiated carcinoma arising within a tumor that shows a spectrum of epithelial differentiation from benign through borderline raises the issue of the role of benign and borderline tumors as precursors of serous carcinoma of the ovary. or edematous stroma. clear-cell tumors resemble renal-cell carcinoma or hypersecretory endometrium or endometrium associated with pregnancy. The architectural pattern of a micropapillary tumor is that of smoothly contoured. second. transitionalcell tumors resemble urothelium. and some authors have suggested an association with an increased frequency of invasive peritoneal implants. they usually have irregular nests of highly pleomorphic and atypical cells infiltrating a desmoplastic. Tumors of the epithelium of the ovary are categorized by the World Health Organization according to epithelial type and degree of epithelial differentiation. Serous borderline tumors of the ovary. Serous carcinomas of the ovary are characterized by the confluence or close approximation of glands and cysts that are lined with cells that have a high degree of nuclear atypia. borderline.2-10 An increase in frequency of stromal invasion in ovarian tumors has been reported. These histologic features are those of a serous borderline tumor. This article is being provided free of charge for use in Indonesia.7.org on March 29. typical type. These papillae were lined with moderately atypical cuboidal and columnar cells. Thus. 2005 . These were lined by elongated micropapillae that emanated directly from the broad fibrous papillae. These tumors are also classified on the basis of their degree of differentiation as benign. most studies have shown an increased frequency of surface involvement. with a high nuclear-to-cytoplasmic ratio and moderate cytologic atypia. endometrioid tumors resemble endometrium. bilaterality. have two distinct histologic patterns that may be present either in isolation or. The micropapillae were five times as long as they were wide and did not contain fibrovascular cores. and they contain detached clusters of atypical epithelial cells. however. micropapillary type.nejm. The prognostic significance of the micropapillary pattern in a noninvasive tumor is controversial. mucinous tumors resemble either endocervical or gastrointestinal mucinous epithelium. or malignant tumors (Table 1). Borderline tumors are defined as tumors that show a degree of epithelial proliferation that is intermediate between obviously benign tumors and malignant tumors. large. . Cell type Serous Endometrioid Clear cell Mucinous Transitional cell Squamous cell Mixed Undifferentiated Degree of differentiation Benign Borderline (low malignant potential) Carcinoma 2534 n engl j med 351. Microscopical examination of the left ovary revealed a small serous borderline tumor. admixed with the other histologic types.1 The morphologic features of particular interest in this case are. the presence of a moderately differentiated or a poorly differentiated carcinoma arising in a neoplasm that shows a spectrum of abnormalities that range from benign to typical borderline to micropapillary borderline tumors. All rights reserved. Benign serous tumors of the ovary are characterized by a single layer of cuboidal or columnar cells that often contain cilia. In other areas. fibrous papillae with irregular contours that end in detached clusters of atypical cells. which are also referred to as tumors of low malignant potential or atypical proliferative tumors. The cells lining the papillae and also present in the micropapillae were polygonal. Welldifferentiated serous carcinomas almost always Table 1. Copyright © 2004 Massachusetts Medical Society.24 www.nejm. fibrous papillae from which thin. Classification of Ovarian Epithelial Tumors. Detached clusters of similar atypical cells were present as well. 2004 Downloaded from www. the presence of both typical and micropapillary variants in the borderline areas of the tumor and. Both types generally show only moderate cytologic atypia. without stromal invasion.1 The classification according to epithelial type is based on the resemblance of the epithelium in the tumor to normal epithelium. These tumors are characterized by the presence of epithelial atypia and tufting.org december 9 . and squamouscell carcinomas resemble squamous epithelium (Table 1). first. typical type. serous tumors have epithelium that resembles the fallopiantube type of epithelium. fibrous. elongated micropapillae emanate.The new england journal of medicine In some areas. hierarchically branching fibrous papillae with irregular contours were present.
30 All other tumors.nejm.case records of the massachusetts general hospital arise within an existing serous neoplasm. it was determined that this patient had ovarian cancer. such as women with BRCA mutations or with strong family histories of breast cancer or ovarian cancer.15.org on March 29.12 This known feature and the results of genetic alterations suggest that well-differentiated serous carcinomas arise by way of an adenomato-carcinoma sequence (from a benign serous cystadenoma to a typical borderline tumor to a micropapillary borderline tumor to an invasive. The cancer was stage IA of IV. A series of randomized. are considered high-risk. the diagnosis was made at an early stage because of the coincidental development of endometrial polyps with postmenopausal bleeding. Stage IA or IB (unilateral or bilateral disease confined to the ovaries) with well-differentiated or possibly moderately differentiated tumor is defined as posing a low risk. Although the tumor was completely resected with negative margins.13-15 In contrast. 2004 2535 Downloaded from www. well-differentiated carcinoma). All rights reserved. This article is being provided free of charge for use in Indonesia. two studies comparing chemotherapy n engl j med 351.21 In high-risk populations.24 www. with subtle symptoms that commonly result in a delayed diagnosis. A study in this issue of the Journal found that additional surgical debulking offered no survival advantage for patients with stage III ovarian cancer receiving chemotherapy. controlled trial showed that the amount of disease left at the completion of surgery (with <1 cm considered optimal and ≥1 cm suboptimal) was one of the most important prognostic factors for ovarian cancer. In the case of this patient. no study had shown a survival advantage with any form of postoperative therapy for patients such as this woman.26 Docetaxel. screening with the use of tumor markers or ultrasonography is not recommended at this time. the question of adjuvant therapy had to be decided. high-grade serous carcinoma.28 the five-year overall survival rate stands at 43 percent.31. in accordance with the classification system of the International Federation of Gynecology and Obstetrics (in which stage I is confined to the ovaries and stage IV involves metastases to the liver or lung). Most randomized trials have compared two treatments without a control group receiving no chemotherapy.17 These data have led to the suggestion that poorly differentiated serous carcinomas arise without a preceding benign or premalignant lesion from ovarian surface epithelium or from serous epithelial inclusion cysts. Penson: After careful staging. 2005 .20.29 This patient had early ovarian cancer. such as TP53 mutations.19 Although early-stage disease may be identified by strategies such as proteomics analysis and CA-125 algorithms. or the presence of cytologically positive peritoneal washings). the development of effective chemotherapy has been a priority. since the majority of patients do not have disease that can be resected completely. including high-grade carcinoma and stage IC disease (defined by surface involvement. is used more often in Europe than in the United States. and she had an anticipated probability of survival at five years of 70 to 90 percent. Until 2003.18. which is usually a serous borderline tumor or adenofibroma — often one with micropapillary architecture. Several recent studies have shown that cisplatin and paclitaxel have greater efficacy than cyclophosphamide and cisplatin. several studies have shown that even the smallest highgrade serous carcinomas rarely arise within preexisting serous neoplasms16 and that such tumors have features. the disease is more successfully prevented by prophylactic oophorectomy than by relying on screening.27 The five-year overall survival rate for women with ovarian cancer has increased incrementally from 37 percent in the 1970s to 39 percent in the 1980s. Ovarian cancer is typically considered advanced when there are intraabdominal transcoelomic metastases (stage III disease) (Table 1). . controlled trials has defined the standard of care for chemotherapy in advanced ovarian cancer. discussion of management Dr. confined to the ovary.23-25 The most recent randomized trial finally confirmed the adoption of carboplatin plus paclitaxel.32 In 2003. earlystage ovarian cancer. and a recent ran- domized. Surgical resection has been the mainstay of treatment for ovarian carcinoma. as the standard of care for advanced ovarian cancer.2. Copyright © 2004 Massachusetts Medical Society. Several studies have shown an advantage with platinum-based therapy. that are typical of advanced-stage. a less neurotoxic alternative to paclitaxel. with a poorly differentiated component. rupture of tumor. but without a significant survival benefit. In the most recent data from the 1990s. with an improved toxicity profile as compared with that of cisplatin and paclitaxel.nejm.22 However. defined as cancer confined to the ovaries. which appears to offer freedom from relapse for a longer duration than melphalan or intraperitoneal radioactive phosphorus (32P) therapy.org december 9.
and they often also favor six cycles of carboplatin and paclitaxel. as compared with 50 percent for patients for whom staging was limited. All rights reserved. Currently.org on March 29. and some experts believe that observation should be restricted to patients with well-differentiated tumors. early-stage disease can be managed with observation and that the benefit from chemotherapy is seen in treating more advanced disease. fatigue. This article is being provided free of charge for use in Indonesia. There is a developing consensus that.24 www.The new england journal of medicine and observation in early-stage ovarian cancer were reported.nejm. This study therefore suggests that in patients who have undergone comprehensive and complete staging at laparotomy. chemotherapy had no advantage. there is evidence that careful staging remains the most important predictor of outcome and should determine the therapy. many oncologists have taken this study as support for limited treatment for patients with early-stage ovarian cancer that has a relatively good prognosis. particularly when recurrent disease is so devastating. Although chemotherapy appeared to improve overall survival.34-36 Even though these results may be interpreted to suggest that every patient with invasive epithelial ovarian cancer should receive adjuvant chemotherapy. Robert E.38 Since there was more toxicity with six cycles of chemotherapy. in patients whose cancer was poorly staged. Clinically. and surveillance with the tumor marker CA-125. and a longer time to clinical confirmation of disease recurrence is a significant predictor of a better response to further treatment.33. Finally. clinicians often favor chemotherapy over a second surgery. Scully (Pathology): As a pathologist. alopecia. which this patient received. equivalent to an area under the concentration–time curve of 5. a recent study comparing three cycles of paclitaxel and carboplatin with six cycles found that the disease-free and overall survival estimates at five years in the two treatment groups were not significantly different. It is not our practice to conduct surveillance with CT scans. this benefit was not statistically significant and in the optimally staged group. Copyright © 2004 Massachusetts Medical Society. or by a single expert in the field of gynecologic pathology. Dr.35 A further metaanalysis of data from four studies suggested that even patients with well-differentiated stage IA tumors may gain a possible advantage with chemotherapy. with clinical examination. Although we know little about patients’ preferences with respect to this trade-off. . A separate multivariate analysis has identified the degree of differentiation as the most powerful prognostic indicator of the likelihood of diseasefree survival.32. since there is no proven survival advantage to treating patients with asymptomatic recurrence of ovarian cancer. the number of events (recurrences and deaths) in this group of patients with a good prognosis limits statistical power to show the significance of an apparently better outcome with six cycles of chemotherapy. this issue remains controversial.37 However. the stage was optimally determined at surgery in only 34 percent of patients. if present but not detected. Therefore.org december 9 . many patients are treated with the lowest reasonable dose of carboplatin. I have difficulty accepting the results of the two studies published in 2003 that showed a survival advantage associated with chemotherapy among patients with early-stage cancer because there was no central review of the pathological features of the epithelial tumors by an expert committee. We recommended follow-up every three months in the first year. above a certain threshold. 2004 Downloaded from www. For patients who do not wish to receive chemotherapy. 2005 . recommendations for this patient Although this patient had undergone optimal staging and had stage IA disease. or even a review by the local pathologist as the 2536 n engl j med 351. 15 months after completion of chemotherapy. there is no advantage to increasing the dose intensity of platinum. These patients had an estimated eight-year survival rate of approximately 80 percent.39 The patient had considerable hematologic toxic effects. However. the most common quandary for patients with apparently early-stage ovarian cancer in whom staging has been inadequate is the choice between repeated surgery with a staging laparotomy and adjuvant chemotherapy. the presence of poorly differentiated serous carcinoma prompted a recommendation for adjuvant chemotherapy with carboplatin and paclitaxel.35 In a study in which formal staging was required as part of the eligibility criteria.nejm. with a similar degree of benefit in every subgroup — although the results of subgroup analyses did not reach statistical significance.34 A meta-analysis published at the same time suggested a marked improvement in survival with adjuvant chemotherapy. so chemotherapy was discontinued after five cycles. the patient’s tumor remains in complete remission. and peripheral neuropathy. pelvic examination. staging is mandatory.
van Lent M. Dr. 5. Semin Oncol 1999.case records of the massachusetts general hospital cases were analyzed. Gorstein F. and micropapillary borderline areas. Slomovitz BM. 26. Scully RE. and lymph nodes: no evidence of cancer. J Natl Cancer Inst 2003. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer.334:1-6. Am J Surg Pathol 2001. Barakat R. Int J Biol Markers 1998. 20:202.351:2489-97. Shih IM.20:1331-45. Miller DM. 2. Randomised trial of paclitaxel in combination with platinum chemotherapy versus platinum-based chemotherapy in the treatment of relapsed ovarian cancer (ICON4/OVAR 2. Am J Pathol 2002. et n engl j med 351. Int J Gynecol Pathol 2003. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. Kurman RJ.25:419-32. Alkushi A. Seidman JD.13:216-20.org december 9. Ozols RF. atypical proliferative) tumors of the ovary: a consensus approach.26:Suppl 18:3440. Walton LA. Cancer 2002. N Engl J Med 2004. Hoskins WJ. including 18 with a micropapillary pattern and 20 with microinvasion. small. Lancet 2002. Prog Proc Am Soc Clin Oncol 2001. Brady MF. et al. Singer G. 3. arising as a polypoid intracystic mass in a serous tumor containing benign. Advanced ovarian cancer. 16. et al.160:1223-8.92:699-708. Am J Surg Pathol 1996. Bundy BN. Gretz HF III. 8. Ovarian serous borderline tumors with micropapillary and cribriform patterns: a study of 40 cases and comparison with 44 cases without these patterns. This article is being provided free of charge for use in Indonesia. Petricoin EF. Gershenson DM. 21. All rights reserved. Cancer 1994. Noninvasive and invasive micropapillary (low-grade) serous carcinoma of the ovary: a clinicopathologic analysis of 135 cases. Am J Surg Pathol 2003. Sobin LH. Prog Proc Am Soc Clin Oncol 2003. Refined diagnostic criteria for implants associated with ovarian atypical proliferative serous tumors (borderline) and micropapillary serous carcinomas. Bell DA.2:109-18. 30. 14. Hum Pathol (in press). Silverberg S. Tortolero-Luna G. Ellenson LH. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. Silva EG. Micropapillary serous carcinoma of the ovary: a distinctive low-grade carcinoma related to serous borderline tumors. if not most.22:37-41. Serous borderline (low malignant potential. et al. Truskinovsky A. et al. Micropapillary and cribriform patterns in ovarian serous tumors of low malignant potential: a study of 99 advanced stage cases. 10.359: 572-7. Young RH. abstract. Kohn E. Chang HW. Bell DA. Int J Gynecol Pathol 2003.org on March 29. Curr Treat Options Oncol 2001. Cohen Y. 4. 20.24 www. Rose PG. Shih IM. Gilks CB. Kurman RJ. Advanced-stage serous borderline tumors of the ovary: a clinicopathological study of 49 cases. van der Burg MEL. 1999. et al. typical borderline. Kurman RJ. et al. Dr. Histological Dr. 22.73:1859-64. 7. Subclassification of serous borderline tumors of the ovary into benign and malignant types: a clinicopathologic study of 65 advanced stage cases. Copyright © 2004 Massachusetts Medical Society. 2004 2537 Downloaded from www. Ledermann J. New York: Springer-Verlag.22:446. abstract. Incidence patterns of invasive and borderline ovarian tumors among white women and black women in the United States: results from the SEER Program. Hum Pathol (in press).21:3194-200.2). et al.95:2380-9. Bertelsen K. but also in the grading of tumors and differentiation of cell types. 11. Am J Surg Pathol 2002. 17. Sehdev PS. anatomical diagnosis Right ovary: papillary serous cystadenocarcinoma.nejm.80:277. Lanvin D. Sherman ME. Smith Sehdev AE. of the published randomized studies. Smith Sehdev AE. Mink PJ. Uterus. 19. Singer G. Caputo TA. Yue JJ. Chemotherapy for ovarian cancer. Am J Surg Pathol 1999. 27. Randomized intergroup trial of cisplatinpaclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. Genetic analysis of ovarian carcinoma histogenesis. 25.26:1111-28. 2nd ed. . 13. Sherman ME.26:1129-41. Kurman RJ. Hitt BA. Lu KH. 18.23:397-409. I think this is a defect of many. Devesa SS. Kurman RJ. Ehlen TG. eds. De Nictolis M. Umudum H. not only in terms of separating borderline tumors from carcinomas. Scully RE. et al. Young RC. Am J Surg Pathol 2002. et al.332:629-34. Am J Surg Pathol 2002. Eichhorn JH. Serous borderline tumors of the ovary: a long-term follow-up study of 137 cases. Malpica A. Ardekani AM. and they will require comprehensive staging to ensure a good chance of cure. Nerenstone S. Ozols RF. N Engl J Med 1995. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. 23. Deavers MT. Jacobs IJ. Kurman RJ. and this should include making sure the tumors are correctly classified and graded. et al. Left ovary: serous borderline tumor. 12. 24. N Engl J Med 1996.27:725-36. Penson: I agree that for clinical studies the patient groups should be as homogeneous as possible. Buyse M. 28.20:1319-30. J Natl Cancer Inst 2000. Piccart MJ. Vasey P. Bell DA. Greer BE. Gynecol Oncol 2001. 29. A comparative analysis of 57 serous borderline tumors with and without a noninva- sive micropapillary component. 2005 . Pothuri B. J Clin Oncol 2003. Brady MF. Singer G.nejm. Leitao M. et al. 1978-1998. Mutational analysis of K-ras segregates ovarian serous carcinomas into two types: invasive MPSC (low-grade tumor) and conventional serous carcinoma (high-grade tumor). Diverse tumorigenic pathways in ovarian serous carcinoma. omentum. Burks RT. McGuire WP. Prat J. Copeland L. abstract. Preliminary results of the SCOTROC trial: a phase III comparison of paclitaxel-carboplatin (PC) and docetaxelcarboplatin (DC) as first-line chemotherapy for stage IC-IV epithelial ovarian cancer (EOC). Use of proteomic patterns in serum to identify ovarian cancer. The role of CA 125 in screening for ovarian cancer. Oldt R III. James K. typical type. van der Burg ME.26:592-600. Am J Surg Pathol 1996.22:29-36. Cho SK. Bell KA. 6. Ellenberg SS. typing of ovarian tumours. Penson: I think that only patients with welldifferentiated tumors can avoid chemotherapy. Rosenthal AN. Bell: Which patients with early ovarian cancer should be referred for staging and which should not? references 1. grade 2 to 3 of 3. Early de novo ovarian carcinoma: a study of fourteen cases. The epithelial tumors of the ovary are a category of tumors in which there is very poor interobserver and intraobserver reproducibility. 9. Borderline tumors of the ovary: a consensus approach. Secondary surgical cytoreduction for advanced ovarian carcinoma. Scully RE. 15.95:484-6.
35. Ann Oncol 1995. Bolis G. of the pertinent x-ray films. for use with a standard 35-mm projector. Guthrie D. J Natl Cancer Inst 2003. 35-millimeter slides for the case records Any reader of the Journal who uses the Case Records of the Massachusetts General Hospital as a medical teaching exercise or reference material is eligible to receive 35-mm slides. The slides are 2 in. Nieberg RM. by 2 in. Copyright © 2004 Massachusetts Medical Society. N Engl J Med 1990. All rights reserved. Colombo N. 2004 Downloaded from www.95:10512. Copyright © 2004 Massachusetts Medical Society. et al. et al.11:281-8.17:741-3. Vergote I. 357:176-82. gross specimens. The cost of the subscription is $450 per year. De Brabanter J. Parmar M. Vergote I. Adjuvant therapy in stage I and stage II epithelial ovarian cancer: results of two prospective randomized trials. J Clin Oncol 1999. 36. Massachusetts General Hospital. 33. Vergote I. et al. Hogberg T.322:1021-7. et al. Chiari S. 39.18:357. et al. Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma. Trimbos JB. Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument. Lage J. with identifying legends. abstract. 2538 n engl j med 351. These slides. abstract. 34. Young R.org december 9 . Randomized clinical trial of adjuvant treatment of women with early (Figo-I-IIA high risk) ovarian cancer — GOG #95. Each year approximately 250 slides from 40 cases are sent to each subscriber. Adjuvant treatment for early epithelial ovarian cancer: results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P). Fyles A. A randomized phase III trial of three versus six cycles of carboplatin and paclitaxel as adjuvant treatment in early stage ovarian epithelial carcinoma: a Gynecologic Oncology Group study. electrocardiograms.nejm. Young RC. et al. International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. Boston. Brady MF. Back to the future: multiagent chemotherapy in ovarian cancer revisited. 2005 . Impact of adjuvant chemotherapy and surgical staging in early-stage ovarian carcinoma: European Organisation for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian Neoplasm trial. 38.6:887-93.case records of the massachusetts general hospital al. Application forms for the current subscription year. Gynecol Oncol 2003.95:113-25. Rose G.88:156. et al. Colombo N.24 www. may be obtained from Lantern Slides Service. 37.nejm. 32. et al. are mailed from the Department of Pathology to correspond to the week of publication and may be retained by the subscriber. Cannistra SA. which illustrate the current cases in the Journal. MA 02114 (telephone 617-726-2974). Bolis G. 31. Slides from individual cases may be obtained at a cost of $35 per case. and photomicrographs of each case. Trope C.. J Natl Cancer Inst 2003.org on March 29. Kaern J. International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. Lancet 2001. Department of Pathology. Prog Proc Am Soc Clin Oncol 1999. Trimbos JB. . Pecorelli S. Ann Oncol 2000. which began in January. J Natl Cancer Inst 2003.95: 125-32. This article is being provided free of charge for use in Indonesia.
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