Bibliography. Serous Tumors of the Ovary. Nomenclature

Transcription

1 Bibliography Serous Tumors of the Ovary Nomenclature 1. Allison KH, Swisher EM, Kerkering KM, et al. Defining an appropriate threshold for the diagnosis of serous borderline tumor of the ovary: when is a full staging procedure unnecessary? Int J Gynecol Pathol 1993; 12: Lee KR, Tavassoli FA, Prat J, et al. Surface epithelial-stromal tumours. In: Tavassoli FA, Devilee P, ed. WHO Classification of Tumours: Pathology & Genetics of Tumours of the Breast and Female Genital Organs Lyon: IARC Press, 2003: Longacre TA, McKenney JK, Tazelaar HD, et al. Ovarian serous tumors of low malignant potential (borderline tumors): outcome-based study of 276 patients with long-term ( 5-year) follow up. Am J Surg Pathol 2005; 29: Seidman JD, Soslow RA, Vang R, et al. Borderline ovarian tumors: diverse contemporary viewpoints on terminology and diagnostic criteria with illustrative images. Hum Pathol 2004; 35: Silverberg, SG, Bell DA, Kurman RJ, et al. Borderline ovarian tumors: key points and workshop summary. Hum Pathol 2004; 35: Extraovarian lesions in ovarian serous neoplasms of low malignant potential 1. Bell DA, Weinstock MA, Scully RE. Peritoneal implants of ovarian serous borderline tumors. Histologic features and prognosis. Cancer 1988; 62: Bell KA, Smith Sehdev AE, Kurman RJ. Refined diagnostic criteria for implants associated with ovarian atypical prolifeartive serous tumors (borderline) and micropapillary serous carcinoma. Am J Surg Pathol 2001;25:

2 3. Camatte S, Morice P, Atallah D, et al. Lymph node disorders and prognostic value of nodal involvement in patients treated for a borderline ovarian tumor: an analysis of a series of 42 lymphadenectomies. J Am Coll Surg 2002; 195: Djordjevic B, Clement-Kruzel S, Atkinson NE, et al. Nodal endosalpingiosis in ovarian serous tumors of low malignant potential with lymph node involvement: a case for a precursor lesion. Am J Surg Pathol 2010; 34(10): Djordjevic B, Malpica A. Lymph node involvement in ovarian serous tumors of low malignant potential: a clinicopathologic study of thrity-six cases. Am J Surg Pathol 2010; 34(1): McKenney JK, Balzer BL, Longacre TA. Lymph node involvement in ovarian serous tumors of low malignant potential (borderline tumors): pathology, prognosis, and proposed classification. Am J Surg Pathol 2006; 30(5): Silva EG, Gershenson DM, Malpica A, et al. The recurrence and the overall survival rates of ovarian serous borderline neoplasms with noninvasive implants is time dependent. Am J Surg Pathol 2006; 30(11): Seidman JD, Kurman RJ. Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic indicators. Hum Pathol 2000; 31(5): Binary system for grading ovarian carcinoma 1. Brustmann H. Epidermal growth factor receptor expression in serous ovarian carcinoma: an immunohistochemical study with Galectin-3 and Cyclin D1 and outcome. Int J Gynecol Pathol 2008; 27: Gershenson DM, Sun CC, Malpica A, et al. Clinical behavior of stage II-IV low-grade serous carcinoma of the ovary. Obstet Gynecol 2006; 108(2): Kobel M, Huntsman D, Gilks B. Critical molecular abnormalities in highgrade serous carcinoma of the ovary. Expert Rev Mol Med 2008; 10:e Malpica A, Deavers MT, Lu K, et al. Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol 2004; 28:

3 5. Malpica A, Deavers MT, Tornos C, et al. Inter-observer and intra-observer variability of a two-tier system for grading ovarian serous carcinoma. Am J Surg Pathol 2007; 31(8): O Neill CJ, Deavers MT, Malpica A, et al. An immunohistochemical comparison between low-grade and high-grade ovarian serous carcinomas: significantly higher expression of p53, MIB1, BCL2, HER- 2/neu, and C-kit in high-grade neoplasms. Am J Surg Pathol 2005; 29: Plaxe SC. Epidemiology of low-grade serous ovarian cancer. Am J Obstet Gynecol 2008; 198:459.e1-459.e9. 8. Shih L and Kurman RJ. Ovarian tumorigenesis. A proposed model based on morphological and molecular genetic analysis. Am J Surg Pathol 2004; 164: Wong KK, Tsang-Lee YT, Deavers MT, Mok S, Zu Z, Sun CC, Malpica A, Wolf JK, Lu KH, Gershenson DM. BRAF mutation is rare in advanced stage low-grade ovarian serous carcinomas. AM J Pathol. 177(4):1611-7, Mucin in Serous Tumors 1. Che M, Tornos C, Deavers MT, et al. Ovarian mixed-epithelial carcinomas with a microcystic pattern and signet-ring cells. Int J Gynecol Pathol 2001; 20: Mooney J, Silva E, Tornos C, et al. Unusual features of serous neoplasms of low malignant potential during pregnancy. Gynecol Oncol 1997;65: Mucinous neoplasms in the ovary 1. Chiesa AG, Deavers MT, Veras E, Silva EG, Gershenson D, Malpica A. Ovarian intestinal type mucinous borderline tumors: are we ready for a nomenclature change? Int J Gynecol Pathol 29(2):108-12,

4 2. Hart WR. Mucinous tumors of the ovary: a review. Int J Gynecol Pathol 2004; 24: Lee KR, Tavassoli FA, Prat J, et al. Surface epithelial-stromal tumours. In: Tavassoli FA, Devilee P, ed. WHO Classification of Tumours: Pathology & Genetics of Tumours of the Breast and Female Genital Organs Lyon: IARC Press, 2003: Lee KR, Young RH. The distinction between primary and metastatic mucinous carcinomas of the ovary. Gross and histologic findings in 50 cases. Am J Surg Pathol 2003; 27: Lewis MR, Deavers MT, Silva EG, et al. Ovarian involvement by metastatic colorectal adenocarcinoma. Still a diagnostic challenge. Am J Surg Pathol 2006; 30: McKenney JK, Soslow RA, Longacre TA. Ovarian mature teratomas with mucinous epithelial neoplasms: morphologic heterogeneity and and association with pseudomyxoma peritonei. Am J Surg Pathol 2008; 32: Meridan Z, Yemelyanova AV, Vang R, et al. Ovarian metastases of pancreaticobiliary tract adenocarcinomas: analysis of 35 cases, emphasis on the ability of metastases to simulate primary ovarian mucinous tumors. Am J Surg Pathol 2011; 35(2): Riopel MA, Ronnett BM, Kurman RJ. Evaluation of diagnostic criteria and behavior of avarian intestinal-type mucinous tumors. Atypical proliferative (borderline) tumors and intraepithelial, microinvasive, invasive, and metastatic carcinomas. Am J Surg Pathol 1999; 23: Ronnett BM, Kajdacsy-Balla A, Gilks CB, et al. Mucinous borderline ovarian tumors: points of general agreement and persistent controversies regarding nomenclature, diagnostic criteria, and behavior. Hum Pathol 2004; 35: Ronnett BM, Seidman JD. Mucinous tumors arising in ovarian mature cystic teratomas. Relationship to the clinical syndrome of pseudomyxoma peritonei. Am J Surg Pathol 2003; 27: Ronnett BM, Yemelyanova AV, Vang R, et al. Endocervical adenocarcinomas with ovarian metastases: analysis of 29 cases with emphasis on minimally invasive cervical tumors and the ability of the metastases to simulate primary ovarian neoplasms. Am J Surg Pathol 2008; 32:

5 12. Seidman JD, Kurman RJ, Ronnett BM. Primary and metastatic mucinous adenocarcinomas in the ovaries. Incidence in routine practice with a new approach to improve intraoperative diagnosis. Am J Surg Pathol 2003; 27: Seidman JD, Soslow RA, Vang R, et al. Borderline ovarian tumors: diverse contemporary viewpoints on terminology and diagnostic criteria with illustrative images. Hum Pathol 2004; 335: Vang R, Gown AM, Wu LSF, et al. Immunohistochemical expression of CDX2 in primary ovarian mucinous tumors and metastatic mucinous carcinomas involving the ovary: comparison with CK20 and correlation with coordinate expression of CK7. Mod Pathol 2006; 19:

6 Mucinous and Serous Tumors in the Ovary: The Most Frequently Asked Questions The International Society of Gynecological Pathologists Meeting USCAP 2011 Annual Meeting Anaís Malpica, M.D. Professor of Pathology and Gynecologic Oncology

7 The Most Frequently Asked Questions Ovarian Mucinous Tumors: Nomenclature issue Mucinous neoplasm of low malignant potential (LMP)/borderline mucinous tumor versus atypical proliferative mucinous tumor Sampling of mucinous tumors in the ovary Metastasis versus primary

8 Heterogeneous Tumors, with Areas with Columnar Cells with Nuclear Stratification, Oval Nuclei and Goblet Cells

9 Columnar Cells with Nuclear Stratification, Oval Nuclei and Goblet Cells

10 WHO (2003) Borderline Mucinous Tumor (Mucinous Tumor of Low Malignant Potential) In our opinion it is not advisable to use the term Atypical Proliferative Tumor Problems to obtain staging Some cases can contain carcinoma

11 Review of 33 FIGO stage 1 cases with at least 5 years of follow-up Two pts with recurrences at 12 and 14 months, respectively (first patient with tumor incompletely excised due to adhesion to the ileum and sigmoid; second patient treated with cystectomy only) After the completion of this study, we have encountered rare patients with tumors initially diagnosed as a mucinous tumors of low malignant potential, intestinal type, who developed pelvic carcinomatosis or lung metastasis within a few years after dx, 1-3 years (SAMPLING ARTIFACT ISSUE) In our opinion, the current nomenclature should be retained to ensure the follow-up of patients affected by this disease until an evidence based sampling protocol becomes available

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14 Primary Ovarian Mucinous Tumors How many sections do we submit for microscopic examination? Tumor < 10 cm 1 section per cm considering the largest dimension of the tumor Tumor 10 cm or tumors of any size with worrisome features (i.e., intraepithelial carcinoma, microinvasion) 2 sections per cm considering the largest dimension of the tumor

15 Mucinous Carcinoma Metastatic to the Ovary More frequent than primary ovarian mucinous carcinoma Primary Ovarian Invasive Mucinous Carcinoma is usually Unilateral FIGO stage I Expansile type IHC In situ hybridization for HPV Clinical correlation is of utmost importance to determine with certainty the origin of a subset of cases

16 Gross Features of Mucinous Carcinoma in the Ovary Metastasis Ovarian Primary Bilateral 10 cm With Tumor Outside the Ovary Unilateral > 10 cm Tumor Limited to the Ovary Seidman JD et al., 2003

17 Bilateral Ovarian Involvement

18 Multinodular Growth Pattern Separated by Normal Ovary

19 Tumor Invasion into Normal Structures of the Ovary

20 Prominent Desmoplastic Response

21 Ovarian Surface Involvement

22 Signet-Ring Cell Pattern

23 Numerous Pools of Mucin Dissecting the Stroma

24 Mucinous Carcinoma Metastatic to the Ovary with Areas Resembling a Mucinous Cystadenoma, note Numerous Mitoses

25 Mucinous Carcinoma Metastatic to the Ovary with Areas Resembling a Mucinous Cystadenoma, note Numerous Mitoses

26 Ovary, Papillary Tumor with Unusual Features (Intracellular Mucin, Cribriform Pattern and Marked Cytologic Atypia) Metastatic Carcinoma of Cervical Origin

27 The Most Frequently Asked Questions Ovarian Serous Tumors: Nomenclature issue Benign vs. serous neoplasm of low malignant potential (borderline serous tumor) Serous neoplasm of low malignant potential (borderline serous tumor) vs. atypical proliferative serous tumor

28 The Most Frequently Asked Questions Ovarian Serous Tumors: Extraovarian findings in ovarian serous tumors of low malignant potential Endosalpingiosis Implants, non-invasive vs. invasive Serous carcinoma Lymph node involvement

29 The Most Frequently Asked Questions Ovarian Serous Tumors: The binary system for grading serous carcinoma Diagnostic criteria Is this system useful? Heterogeneity How to make the diagnosis of serous carcinoma? Ovarian serous tumors with extracellular or intracellular mucin

30 Serous LMP tumor Epithelial stratification with tufting and cell detachment Hierarchical branching

31 What percentage of the tumor has to have this pattern to use the term serous tumor of low malignant potential? Many authors consider 10% as the cut-off point However, in our practice we have encountered rare cases with less than 10% of this pattern that have recurred or had extraovarian disease

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35 Therefore, if the serous neoplasm of low malignant potential area represents less than 10% of the tumor, the diagnosis of serous neoplasm of low malignant potential is made and the word focal is added to the diagnosis i.e., Focal Serous Neoplasm of Low Malignant Potential in a Serous Cystadenoma (Cystadenofibroma)

36 WHO (2003) Borderline Serous Tumor (Serous Tumor of Low Malignant Potential) It is not advisable to use the term Atypical Proliferative Tumor Problems to obtain staging Some cases evolve to carcinoma

37 Extraovarian Findings in Ovarian Serous Tumors of Low Malignant Potential Endosalpingiosis

38 Endosalpingiosis in Ovarian Serous Tumors of Low Malignant Potential Peritoneal It can be seen in 50% to 71% of the cases Lymph node It can be seen in up to 33% of the cases (significantly higher than in the control group) Djordjevic B, et al, 2010 It is seen in 58% to 63% of the cases with lymph node involvement

39 Extraovarian Findings in Ovarian Serous Tumors of Low Malignant Potential Non-invasive vs. invasive implants Conventional approach Emergent approach Prognosis Treatment

40 Non-invasive implant, epithelial type

41 Non-invasive implant, desmoplastic type

42 Invasive implant

43 Invasive implant

44 Micropapillary Pattern Emergent Approach Invasive Implants Clusters of Cells Surrounded by Clefts Devoid of Lining Epithelium

45 Implants Non-invasive implants excellent prognosis in most studies Overall survival: 95.3% Invasive implants poor prognosis Overall survival: 66% Seidman and Kurman, 2000

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47 Extraovarian Findings in Ovarian Serous Tumors of Low Malignant Potential Low Grade Serous Carcinoma

48 Extraovarian Findings in Ovarian Serous Tumors of Low Malignant Potential Lymph Node Involvement Limited Experience Incidence 21% to 42% of the cases No significant difference in the survival of cases with or without lymph node involvement Upstaged 13% of the cases McKenney JK et al., 2006

49 supradiaphragmatic mesenteric/ omental, paraaortic pelvic

50 Ovarian Serous Tumor of Low Malignant Potential with Lymph Node Involvement 87% of the cases associated with peritoneal implants Nodular pattern (epithelial aggregate >1 mm) associated with a higher risk of recurrence (equivalent to invasive implant) McKenney JK et al., 2006

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52 Lymph node involvement (LNI) is associated with a higher incidence of implants LNI is not an independent predictor of disease free-survival or overall survival LNI can be the only site of extra-ovarian involvement (22% of the cases) Grossly unremarkable lymph nodes are not at a decreased risk of LNI (LN size in cases with LNI, 0.2 to 4.0 cm comparable to control group)

53 Lymph Node Involvement by Serous Neoplasm of Low Malignant Potential What does it look like? Individual cells Clusters of cells Papillae and small papillae Papillae and micropapillae Glandular proliferation Intraglandular proliferation Djordjevic B,and Malpica A, 2010

54 Focal Desmoplastic Reaction Djordjevic B, Malpica A, 2010

55 What is the Correct Term to Designate this Lymph Node Serous Lesion Associated with an Ovarian Serous Neoplasm of Low Malignant Potential? Low Grade Serous Carcinoma Djordjevic B,and Malpica A, 2010

56 Grading of Ovarian Serous Carcinoma The two-tier grading system is based: Primarily on the assessment of cytologic atypia Secondary feature, the mitotic rate User friendly Reproducible Meaningful segregation of cases

57 Low grade serous carcinoma: tumor with uniform cells with mild to moderate cytologic atypia and usually a low mitotic index ( 12 mitoses per 10 HPFs)

58 High grade serous carcinoma: tumor with pleomorphic cells with marked nuclear atypia ( 3:1 variation in size and shape), and a high mitotic index (>12 mitoses per 10 HPFs)

59 Ovarian High vs. Low Grade Serous Carcinoma-Differences Incidence High grade serous carcinoma is more common than low grades serous carcinoma Ovarian Tumorigenesis Model Prototypic type I: High grade serous carcinoma P53 mutation Prototypic type II: Low grade serous carcinoma KRAS and BRAF mutation KRAS mutation (MDACC experience)

60 Ovarian High vs. Low Grade Serous Carcinoma-Differences Immunohistochemistry High grade: higher expression of p53, Bcl-2, c-kit,p16, and EGFR Low grade: higher expression of ER, PR, and ECAD Genetic Risk BRCA1/2 germline mutations have been found in high grade serous carcinoma

61 Ovarian High vs. Low Grade Serous Carcinoma-Differences Behavior Low grade serous carcinoma appears to be less responsive to conventional chemotherapy than high grade serous carcinoma Patients with low grade serous carcinoma have a longer overall survival than patients with high grade serous carcinoma Patients with low grade serous carcinoma are younger and have a better survival than patients with high grade serous carcinoma

62 Low vs. High Grade Serous Carcinoma, Tumor Heterogeneity Uniform Cells

63 Low vs. High Grade Serous Carcinoma, Tumor Heterogeneity Nuclear Pleomorphism

64 Diagnostic Criteria for Ovarian Serous Carcinoma A serous tumor with low grade cytology Invasion is required = Low Grade Serous Carcinoma Invasion is identified by Size, measuring more than 3.0 mm or The presence of unequivocal desmoplasia A serous tumor with definitive high grade cytology Invasion is not required = High Grade Serous Carcinoma Note: Attention has to be paid to the cytologic features not to mistake a clear cell carcinoma for a serous neoplasm of low malignant potential

65 Serous Tumor of Low Malignant Potential, Hierarchical Branching, Epithelial Tufting and Cell Detachment

66 Papillae infiltrating the stroma

67 Tangentially cut cystic space, note the lining epithelium Spaces in areas of invasion lack lining epithelium

68 > 3mm, single dimension

69 Desmoplasia

70 Desmoplasia

71 A Serous Tumor with a Low Malignant Potential Pattern

72 High Grade Cytology

73 Clear Cell Carcinoma

74 Clear Cells, Nuclear Atypia, and Hyalinized Stroma

75 Focal Low Grade Serous Carcinoma in a Background of Serous LMP Note gelatinous papillae

76 Abundant Extracellular Mucin in a Serous Neoplasm of LMP This is a common finding in tumors detected during pregnancy

77 Serous Carcinoma with a Microcystic Pattern

78 Serous Carcinoma with a Microcystic Pattern - Mucicarmine +

79 Signet-ring Cells in Serous Carcinoma

80 Signet-ring Cells in Serous Carcinoma, WT-1 (+)

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