Ovarian Carcinoma



Ovarian Carcinoma


Akram M. Shaaban, MBBCh

































































































(T) Primary Tumor


Adapted from 7th edition AJCC Staging Forms.


TNM


FIGO


Definitions


TX


Primary tumor cannot be assessed


T0


No evidence of primary tumor


T1


I


Tumor limited to ovaries (1 or both)



T1a


IA


Tumor limited to 1 ovary; capsule intact, no tumor on ovarian surface; no malignant cells in ascites or peritoneal washing



T1b


IB


Tumor limited to both ovaries; capsules intact, no tumor on ovarian surface; no malignant cells in ascites or peritoneal washings



T1c


IC


Tumor limited to 1 or both ovaries with any of the following: Capsule ruptured, tumor on ovarian surface, malignant cells in ascites or peritoneal washings


T2


II


Tumor involves 1 or both ovaries with pelvic extension



T2a


IIA


Extension &/or implants on uterus &/or tube(s); no malignant cells in ascites or peritoneal washings



T2b


IIB


Extension to &/or implants on other pelvic tissues; no malignant cells in ascites or peritoneal washings



T2c


IIC


Pelvic extension &/or implants with malignant cells in ascites or peritoneal washings


T3


III


Tumor involves 1 or both ovaries with peritoneal metastasis outside the pelvis



T3a


IIIA


Microscopic peritoneal metastasis beyond pelvis (no macroscopic tumor)



T3b


IIIB


Macroscopic peritoneal metastasis beyond pelvis = 2 cm in greatest dimension



T3c


IIIC


Peritoneal metastasis beyond pelvis > 2 cm in greatest dimension &/or regional lymph node metastasis


(N) Regional Lymph Nodes


NX


Regional lymph nodes cannot be assessed


N0


No regional lymph node metastasis


N1


IIIC


Regional lymph node metastasis


(M) Distant Metastasis


M0


No distant metastasis


M1


IV


Distant metastasis (excludes peritoneal metastasis)




























































































AJCC Stages/Prognostic Groups


Adapted from 7th edition AJCC Staging Forms.


Stage


T


N


M


I


T1


N0


M0



IA


T1a


N0


M0



IB


T1b


N0


M0



IC


T1c


N0


M0


II


T2


N0


M0



IIA


T2a


N0


M0



IIB


T2b


N0


M0



IIC


T2c


N0


M0


III


T3


N0


M0



IIIA


T3a


N0


M0



IIIB


T3b


N0


M0



IIIC


T3c


N0


M0




Any T


N1


M0


IV


Any T


Any N


M1








Low-power magnification of H&E shows ovarian carcinoma that is limited to 1 ovary with intact capsule (T1a). Sheets of tumor cells image are seen with intact capsule image. (Original magnification 20x.)






High-power magnification shows sheets of serous carcinoma cells image and an intact capsule image overlying ovarian stroma. (Original magnification 100x.)






Low-power magnification shows ovarian tumor extending through the capsule to the ovarian surface (T1c). The H&E stain shows ovarian tumor image extending to the ovarian surface image. Note normal ovarian tissue on the right side of the photomicrograph. (Original magnification 20x.)






Higher magnification shows a close-up of the cords and nests of tumor cells image and ovarian plump spindle stromal cells image. (Original magnification 100x.)







Low-power magnification of H&E stain shows a cross section of a fallopian tube image with ovarian tumor nodule image implanted on the serosal aspect. The inset shows a high magnification view of the neoplastic malignant cells of the nodule.






Low-power magnification of H&E stain shows an implanted ovarian nodule to the serosal surface of the recto-sigmoid colon (T2b). The mucosal side of the rectosigmoid is highlighted image, as well as the tumor nodule image. (Original magnification 40x.)






H&E section shows peritoneal metastasis of ovarian papillary serous carcinoma outside the pelvis (T3). The nodule in the upper part of the slide image represents the metastatic tumor and is implanted in the fibro-fatty tissue image of the peritoneum (lower aspect of the slide). (Original magnification 20x.)






Low-power magnification of H&E stain shows a metastatic ovarian carcinoma to a regional lymph node (T3c). The lymph node capsule is highlighted image; tumor nest image. is present within the lymph node. (Original magnification 40x.)







T1a tumors are limited to 1 ovary with intact capsule, no tumor on the ovarian surface, and no malignant cells in ascites or peritoneal washings.






T1b tumors are limited to both ovaries with intact capsules, no tumor on the ovarian surface, and no malignant cells in ascites or peritoneal washings.






T1c tumors are limited to 1 or both ovaries with capsule rupture, tumor on the ovarian surface image, or malignant cells in ascites or peritoneal washings.






T2a tumors involve 1 or both ovaries with pelvic extension to the uterus or fallopian tube. No malignant cells are found in ascites or peritoneal washings.







T2b tumors involve 1 or both ovaries with pelvic extension &/or implants to other pelvic organs. No malignant cells in ascites or peritoneal washings are found.






T2c tumors involve 1 or both ovaries with pelvic extension &/or implants, with malignant cells in ascites or peritoneal washings.






T3a tumors involve microscopic peritoneal metastases beyond the pelvis. This cannot be visualized by imaging; rather, it is found through peritoneal biopsy at staging laparotomy.






T3b tumors feature macroscopic peritoneal metastases beyond the pelvis that are less than or equal to 2 cm in greatest dimension.







T3c tumors involve macroscopic peritoneal metastases beyond the pelvis greater than 2 cm in greatest dimension.






The main ovarian lymphatics follow the ovarian veins to the paraaortic lymph nodes image. Lymphatic spread may also occur through the broad ligament to the pelvic lymph nodes image and along the round ligament to the inguinal lymph nodes image.

































image


METASTASES, ORGAN FREQUENCY


Liver


45-48%


Lung


34-39%


Pleura


25%


Adrenal gland


15-21%


Spleen


15-20%


Bone


11%


Kidney


7-10%


Skin and subcutaneous
tissue


5%


Brain


3-6%




OVERVIEW


General Comments



  • Primary peritoneal carcinoma (unusual tumor of similar histiogenic origin to primary ovarian carcinoma) included with ovarian carcinoma in 7th edition AJCC Staging Manual


Classification



  • Primary ovarian carcinomas are differentiated by cell origin



    • Epithelial ovarian tumors (EOT): 90% of ovarian carcinomas



      • Serous cystadenocarcinoma (60%)


      • Endometrioid carcinoma (10%)


      • Clear cell carcinoma (10%)


      • Carcinosarcoma (10%)


      • Mixed (5%)


      • Mucinous cystadenocarcinoma (3%)



        • Less common than initially thought


        • Many mucinous tumors of ovaries are actually metastatic from gastrointestinal primary


      • Undifferentiated carcinoma (1%)


      • Brenner tumor (< 1%)


    • Nonepithelial ovarian tumors: 10% of ovarian carcinomas



      • Germ cell tumors



        • Dysgerminoma


        • Embryonal carcinoma


        • Immature teratoma


        • Olyembryoma


        • Choriocarcinoma


        • Mixed tumors


      • Tumor of sex cord or stroma



        • Malignant granulosa cell tumor


  • Nonepithelial primary ovarian cancers may be staged using TNM classification system


PATHOLOGY


Routes of Spread



  • Understanding pattern of spread is crucial for adequate radiological and surgical staging


  • Local spread



    • Direct extension to surrounding pelvic structures



      • Commonly fallopian tubes, uterus, and contralateral adnexa


      • Less commonly rectum, bladder, and pelvic sidewall


    • Uterine involvement



      • Independent primary tumors of low histologic grade, usually of endometrioid type, with involvement limited to endometrium and ovary



        • Favorable prognosis; often no additional treatment


      • Tumors metastasizing from uterus to ovary or from ovary to uterus



        • Worse prognosis; adjuvant therapy is generally indicated


      • Distinction between primary vs. secondary involvement relies on histological examination


  • Peritoneal seeding



    • Most common mode of tumor spread


    • Malignant cells shedding from tumor surface into peritoneal cavity


    • Malignant cells are distributed by gravity into cul-de-sac or follow normal routes of peritoneal fluid circulation



      • Preferential flow and seeding along right paracolic gutter, liver capsule, and right hemidiaphragm


    • Peritoneal fluid normally drains through rich lymphatic capillary network of diaphragm to supradiaphragmatic lymph nodes



      • Occlusion of these lymphatics by tumor cells blocks absorption of peritoneal fluid


      • Contributes to accumulation of malignant ascites


    • Most common sites of peritoneal metastases



      • Cul-de-sac


      • Greater omentum


      • Paracolic gutters


      • Small and large bowel surface


      • Liver surface


      • Subphrenic spaces


    • Other potential sites of metastases



      • Porta hepatis


      • Fissure for ligamentum teres


      • Lesser sac


      • Gastrosplenic and gastrohepatic ligaments


      • Splenic hilum


    • Primary peritoneal carcinoma



      • Unusual tumor of similar histiogenic origin to primary ovarian carcinoma


      • Primary tumor of peritoneum that diffusely involves peritoneal surface but spares or only superficially involves ovaries


      • Generally diagnosed in state of peritoneal carcinomatosis


      • Poor prognosis


      • Biopsy important to differentiate primary peritoneal carcinoma from peritoneal carcinomatosis (due to other cancers, mesothelioma, lymphomatosis, or tuberculous peritonitis)


    • Pseudomyxoma peritonei



      • Growing body of immunohistochemical and molecular genetic studies suggest that majority are actually secondary to appendiceal tumors in both men and women


      • Those that are ovarian in origin probably originated from mucinous tumors arising in teratomas


  • Lymphatic spread



    • 3 primary pathways for lymphatic drainage



      • Main lymphatics follow ovarian veins → paraaortic and aortocaval lymph nodes at level of renal veins


      • Through broad ligament → pelvic lymph nodes, including external iliac, hypogastric, and obturator nodes


      • Along round ligament → inguinal lymph nodes


  • Hematogenous spread



    • Least common mode of spread


    • Usually not present at initial diagnosis, can be found at restaging



      • In up to 50% of patients at autopsy


General Features



  • Genetics




    • Lifetime risk of ovarian cancer: 15-30% in women carrying genes responsible for most hereditary ovarian cancers (BRCA1, BRCA2)


    • Hereditary nonpolyposis colon cancer (Lynch syndrome) has also been associated with endometrial and ovarian cancers


  • Etiology



    • No known causative factor in development of ovarian carcinoma


    • Factors known to increase risk of developing ovarian cancer include



      • Family history is strongest known risk factor



        • ˜ 10% of cases are thought to have hereditary basis


        • Women who have had breast cancer or who have family history of breast or ovarian cancer are at increased risk


      • Nulliparity, early menarche, and late menopause


      • Estrogen use alone as postmenopausal hormone therapy


      • Obesity may be associated with increased risk


    • Pregnancy and long-term use of oral contraceptives reduce risk of developing ovarian cancer


  • Epidemiology & cancer incidence



    • Approximately 3% of all cancers among women


    • 2nd most common gynecological malignancy after endometrial carcinoma



      • Estimated 21,550 new cases in USA in 2009


    • Leading cause of death from gynecological cancers and 9th leading cause of cancer death in women



      • Estimated 14,600 deaths in USA in 2009


Gross Pathology & Surgical Features



  • General features



    • 2/3 of cases involve both ovaries


    • Range from microscopic to about 20 cm in diameter


    • Typically multilocular and cystic, with intracystic, soft, friable papillae



      • Cysts contain serous, turbid, or bloody fluid


    • External surfaces may be smooth or bosselated and may display grossly exophytic papillary tumor on surface (at least T1c)


    • Solid areas and intracystic nodules are more common in carcinomas than in cystadenomas


    • Hemorrhage and necrosis are often present


  • Endometrioid carcinoma arising in endometrioma



    • Gross findings of endometriotic cyst containing chocolate-colored fluid


    • 1 or more solid mural nodules reflecting foci of malignant transformation


Microscopic Pathology



  • Major histologic types



    • Serous cystadenocarcinoma



      • Most common type of ovarian cancer



        • Accounts for > 50% of malignant ovarian neoplasms


      • Complex papillary and solid patterns with marked nuclear atypia, qualify as high-grade carcinomas


      • Characteristic pattern is lace-like or labyrinthine pattern



        • May be focal but often diffuse


        • Characterized by extensive bridging and coalescence of papillae resulting in solid sheets of tumor cells with interspersed slit-like spaces


      • Serous carcinomas that display extensive solid areas usually are composed of uniform sheets of cells with high-grade nuclear atypia



        • Usually there are focal areas with papillary architecture that permit diagnosis of serous carcinoma as opposed to undifferentiated carcinoma


      • Psammoma bodies are present in 25% of cases


    • Endometrioid carcinoma



      • Well-differentiated endometrioid adenocarcinoma accounts for most cases


      • Confluent or cribriform proliferation of glands lined by tall stratified columnar epithelium with sharp luminal margins


      • Villoglandular growth pattern also occurs


      • Squamous differentiation is present in 50% of cases


    • Mucinous adenocarcinoma



      • Stromal invasion measuring > 5 mm


      • Stromal invasion in primary ovarian mucinous neoplasms is characterized by 3 different patterns



        • Confluent glandular growth with crowded glands without intervening stroma


        • Clusters of single cells with abundant eosinophilic cytoplasm surrounded by clear spaces


        • Glands of varying sizes infiltrating stroma in haphazard pattern


      • Cytoplasm is scant and eosinophilic with irregular borders and occasional mucin droplets


    • Brenner tumor



      • Rounded nests of transitional or squamous cells like epithelium and glandular structures of cylindrical cells within abundant fibrous nonepithelial tissue


      • Microscopically resembles urothelial transitional cell carcinoma


    • Clear cell adenocarcinoma



      • Ovarian epithelial tumor in which most cells have clear cytoplasm


      • High association with pelvic endometriosis


IMAGING FINDINGS


Detection



  • Primary goal of radiologic assessment is differentiation of malignant from benign tumors


  • CA-125 is glycoprotein that is assessed by monoclonal antibody OC-125



    • ↑ CA-125 serum level ≥ 30 U/mL indicates presence of malignancy


    • False-positive results



      • In women with conditions affecting peritoneal surface, such as endometriosis


    • False-negative results



      • In women with early-stage invasive disease and borderline ovarian tumors


  • General imaging findings suggestive of malignancy



    • Most predictive imaging findings for malignancy are



      • Solid mass, especially when necrosis is present


      • Presence of nonfat nodular components in cystic lesion


    • Other findings suggestive of malignancy




      • Irregular, thick wall or septa (> 3 mm)


      • Vascularity in solid mass or papillary projections



        • Doppler demonstration of blood flow


        • Enhancement on CT and MR


    • Ancillary findings that are strong indicators of malignancy



      • Ascites


      • Peritoneal metastases


      • Lymphadenopathy


      • Pelvic organ or sidewall invasion


  • Special tumor features may be present and can suggest specific type



    • Calcification in cystic or partially cystic tumor



      • Serous epithelial tumor


    • Associated endometrial hyperplasia or carcinoma



      • Endometrioid epithelial tumor (20-30% of patients)


    • Variable density (echogenicity) within loculi of multilocular tumor



      • Mucinous epithelial tumor


    • Pseudomyxoma peritonei virtually never occurs in association with primary ovarian mucinous tumors


  • Ultrasound



    • Low cost and wide availability


    • Modality of choice to evaluate suspected or palpable adnexal mass



      • Adnexal masses are found on US in about 10% of premenopausal women


      • US seems to be similar with CT and MR in differentiation of malignant from benign ovarian tumors



        • Pattern recognition on US correctly classified 93% of lesions as benign or malignant (in experienced hands)


    • Transvaginal ultrasound (TVU) and transabdominal ultrasound (TAU) should be used together



      • TVU allows best evaluation of pelvic masses but limited field of view


      • TAU is better for large mass or if ovaries are displaced by enlarged leiomyomatous uterus


    • Ovarian volumes



      • Premenopausal women: Up to 20 cm3


      • Postmenopausal women: Up to 8-10 cm3


      • Ovarian volumes progressively decrease with age and years since menopause


      • Enlarged ovary for age, or ovary > 2x volume of other ovary, may be early indication of ovarian neoplasm


    • Spectral Doppler findings suggestive of malignancy



      • Low-resistance waveforms due to tumor neovascularity and arteriovenous shunting


      • Resistance index < 0.4 and pulsatility index < 1


      • Considerable overlap with benign physiological lesions


      • More suspicious in postmenopausal women, in whom benign lesions are less frequent


      • Color Doppler flow imaging alone is significantly inferior to combined US techniques, morphologic assessment alone, and contrast-enhanced US in diagnosis of ovarian cancer


    • Hemorrhagic cysts may appear similar to neoplasm



      • Repeat scanning 4-6 weeks following initial detection of indeterminate ovarian mass


    • Mixed results reported for use of US ± CA-125 in screening for ovarian cancer



      • Routine US screening of asymptomatic women → ↑ false-positive results → unnecessary laparoscopy or laparotomy


      • Positive predictive value for invasive cancer is 3.7% for abnormal CA-125, 1% for abnormal TVU, and 23.5% if both tests are abnormal


  • CT



    • Increased number of incidental ovarian lesions discovered due to widespread use of CT


    • Recent advances in CT technology and availability of multidetector CT (MDCT) allow better detection and improved characterization of adnexal masses


    • MDCT: Sensitivity (90%), specificity (89%), positive predictive value (78%), negative predictive value (95%), and overall accuracy in diagnosing malignancy (89%)


  • MR



    • Used mainly as problem-solving tool in setting of sonographically indeterminate or complex adnexal mass


    • Can provide tissue characterization based on signal properties



      • MR is superior to US and CT in differentiation of benign from malignant masses


    • Adequate evaluation of adnexal masses on MR imaging requires



      • T1WI and T2WI to delineate pelvic anatomy and tumor


      • Fat-saturated T1WI to distinguish between fat and hemorrhage


      • Gadolinium-enhanced T1WI to improve detection of solid components


    • Dynamic contrast-enhanced MR imaging has been used to analyze perfusion of solid components contained in ovarian tumors



      • Can differentiate among benign, borderline, and malignant tumors


      • Different parameters have been used



        • Include enhancement amplitude (EA), time of half rising (Tmax), and maximal slope (MS)


      • Invasive tumors tend to show early intense and persistent enhancement


  • FDG PET/CT

Sep 18, 2016 | Posted by in OBSTETRICS & GYNAECOLOGY IMAGING | Comments Off on Ovarian Carcinoma
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