July 2006 Two Women with Ovarian Cancer: Mystery Metastasis vs. Primary Tumor Jennifer Erdrich,, HMS III Gillian Lieberman, MD
Ovarian Cancer 5 th most common cause of female cancer death 5 year survival rate < 35% Mortality has only decreased slightly in 30 yrs Most diagnosis made at advanced disease 2
Ovarian Tumors Majority derive from epithelial cells Benign ovarian tumors more common in women ages 20-45 Malignant ovarian tumors more common in women ages 40-65 3
Ovarian Tumors Risk Factors Nulliparity Family History Heritable Mutations (BRCA1, BRCA2) Protective Factors Oral Contraceptives Tubal Ligation Presenting Symptoms Lower abdominal pain Abdominal enlargement GI complaints Dysuria Back pain Fatigue Cramping Vaginal Bleeding 4
Ovarian Neoplasm Classification OVARIAN TUMORS EPITHELIAL Serous Mucinous Endometroid GERM CELL Teratoma Yolk Sac Tumor Dysgerminoma Mixed SEX CORD Granulosa Cell 5% of ovarian tumors arise from metastases 5
Our Patient: Ms. X 36 year old woman Increasing pelvic mass for last 2 months Abdominal distension Early satiety 6
Ms. X: Ultrasound Findings Uterus: Normal size No masses Endometrial thickness 0.88 cm (within nl) Ovary: Ovarian enlargement Relationship to uterus unclear Uterus PACS, BIDMC 7
Ms. X: Ultrasound Findings Ovarian enlargement: 12.79cm Another view shows bilateral enlargement with left ovary measuring 7.89 cm => Patient diagnosed with ovarian cysts PACS, BIDMC 8
Ms. X: CT Findings The patient s s symptoms worsen over the course of 2 months. CT shows massive ascites. PACS, BIDMC 9
CT: Normal compared to Ms. X Normal Female Pelvis Ms. X PACS, BIDMC 10
Ms. X: CT Findings Bilateral ovarian masses variable attenuation, solid and cystic components PACS, BIDMC 11
Ms. X up to this point: Bilateral ovarian masses Worsening symptoms Her age makes these more likely to be benign: benign: 20-45 yrs malignant: 40-65 yrs However, the massive ascites on CT looks ominous Ddx is extensive at this point as these images cannot even determine benign vs. malignant status with any certainty Does the WHO Classification System help to further characterize Ms. X s X s condition? 12
Ovarian Neoplasms Epithelial Germ Cell Sex Cord Mets Frequency 65-70% 15-20% 5-10% 5% Percent of Tumors Age group affected Types 90% 3-5% 2-3% 5% 20+ 0-25 All ages Serous Mucinous Endometroid Teratoma Dysgerminoma Choriocarcinoma Granulosa Cell Sertoli-Leydig Fibroma Variable KRUKENBERG TUMOR 13
Another look at the CT for Ms. X This coronal CT shows gastric thickening It becomes apparent on a second look at the axial images also PACS, BIDMC 14
Another look at the CT for Ms. X PACS, BIDMC The original axial CT image that demonstrated ascites also shows gastric thickening on a second look. 15
Could this be a Krukenberg Tumor? Profile of patients with Krukenberg: Young, premenopausal women Abdominal pain that is vague early in the disease, but more severe as the disease progresses Abdominal swelling Menstrual regularity still maintained Ovarian tumors are large, bilateral and associated with ascites 16
The next step for Ms. X Endoscopy! A single biopsy has 70% sensitivity for diagnosing gastric cancer Seven biopsies increase the sensitivity to 98% Ms. X undergoes endoscopy, which shows an ulcerated, fungating,, infiltrative mass with recent bleeding in the body and cardia; duodenum determined to be normal 17
Ms. X: Endoscopy ulceration Ulceration best seen here ulceration PACS, BIDMC Normal rugal folds Dx: : gastric adenocarcinoma Duodenum looks normal smooth pink mucosa adenocarcinoma,, predominantly signet ring cell 18
Ms. X Imaging modalities used: US, CT, endoscopy Dx: : gastric adenocarcinoma with mets to ovaries (Krukenberg tumor) Other findings: elevated CEA and CA-125; anemia; met in cul-de de-sac Surgery: ovarian resection, gastric resection Currently: chemotherapy Signet Ring Cells: mucin filled cells with nuclear displacement. Characteristic of Krukenberg Tumor. Ruhul Quddus, MD: www.brown.edu/.../female/krunkenberg2.html 19
Primary vs. Metastatic Ovarian Tumor The Case of Ms. D 56 year old woman w 4 months abdominal pain, chronic constipation PMH: GERD, HTN Physical Exam: pelvic masses felt bilaterally, cervix described as wrinkled but not erythematous normal colonoscopy 2 years ago Her presentation is similar to Ms.X What does CT reveal? 20
Ms. D: CT Findings PACS, BIDMC CT shows bilaterally enlarged ovaries with cystic and solid components 21
Ms. D: CT Findings omental caking diffuse peritoneal studding Light gray, soft tissue densities throughout PACS, BIDMC CT shows omental caking, peritoneal studding, and free pelvic fluid 22
Ms. D: CT Findings Nonuniform enhancing renal parenchyma; absence of contrast in collecting system Dilatation of large bowel CT shows complications from the ovarian tumors: obstructive renal failure and large bowel dilatation PACS, BIDMC 23
Ms. D Exploratory surgery found studding of the small and large bowel, omentum,, and peritoneum. It was determined that Ms. D had a primary mucin producing tumor that had spread throughout her abdomen. 24
Ms. X and Ms. D These women illustrate two examples of ovarian tumors Ms. X: stomach ovary ovary (Met) Ms. D: ovary abdomen (Primary) Their presenting symptoms and radiographic findings are similar. The findings alone cannot establish whether the malignancies are primary or metastatic. 25
Ms. X and Ms. D Surgery and histology are critical in diagnosis, staging and developing a treatment plan. Both were advanced in their disease at diagnosis. Could their tumors be detected earlier? 26
Could screening have helped these women? Possible screening tests Pelvic Exam Serum markers: CEA, CA-125 Ultrasound CT 27
Could screening have helped these women? Possible screening tests Pelvic Exam Early stage tumors rarely found due to deep anatomic location of the ovary Serum markers: CEA, CA-125 Nonspecific these markers can be elevated in a number of conditions Ultrasound CT 28
Radiographic characteristics that help differentiate benign and malignant adnexal masses Benign Simple cyst, < 10 cm Malignant Solid, or solid and cystic Septations < 3mm Multiple septations > 3mm Unilateral Calcifcation (especially teeth) Bilateral Ascites Gravity dependent layering of cyst contents 29
Ultrasound as a Screening Tool US Findings Suggesting Malignancy Solid component, often nodular/papillary Septations (>2-3 3 mm) Doppler demonstrates flow in solid component Presence of ascites Enlarged peritoneal nodes US Screening Studies Sensitivity has ranged from 80-100% Specificity has ranged from 94-99% 99% US has performed poorly in detecting early stage ovarian cancer in high risk women 30
Could screening have helped these women? Possible screening tests Pelvic Exam Serum markers: CEA, CA-125 Ultrasound CT Most useful for evaluating metastatic disease (M Stage) Cannot rely on it for T or N Staging CT is used to monitor recurrence Screening Risks Unnecessary surgery as follow-up to positive tests 31
Summary Case examples of metastatic and primary ovarian tumors Pelvic and abdominal anatomy Radiographic imaging is essential in diagnosis. Menu of Tests for these patients: US, CT, endoscopy. Ultrasound CT Endoscopy PACS, BIDMC 32
Summary Ovarian tumor classification System organized by cell of origin: epithelial, germ cell, sex cord, metastasis EPITHELIAL Serous Mucinous Endometroid OVARIAN TUMORS GERM CELL Teratoma Yolk Sac Tumor Dysgerminoma Mixed SEX CORD Granulosa Cell Radiographic features can help differentiate benign vs. malignant: evaluation of cystic/solid components unilateral/bilateral septations,, number and thickness 33
Summary Ovarian cancer 5 th most common cause of female cancer death Low survival rate Screening Screening Modalities Imaging: Ultrasound, CT Other: Physical exam, biomarkers Screening Studies Current screening ineffective at detecting malignancies early Screening could pose risk of unnecessary procedures 34
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Acknowledgements Melissa Gerlach,, MD Alice Fisher, MD Gillian Lieberman, MD Pamela Lepkowski Larry Barbaras 36