Mrs PC, 63yo woman

1. Mrs PC, 63yo woman • Initially presented with chronic RIF pain • Found to have cholelithiasis, underwent a laparoscopic cholecystectomy • On the laparoscopy, nothing abnormal was noted in the abdomen • The pain persisted

2. Medical History • Panic attacks • Varicose veins • Cholelithiasis • Distant ex-smoker (ages 18-27)

3. Family History • Mother: ovarian ca (age 70+) • Maternal aunt: breast ca (age ~70) • Father: lung ca (smoker)

4. HOPC (cont.) • Went on to have transvaginal ultrasound, which showed a cystic lesion on the R) ovary • CT and PET scan showed: • Large avid pelvic mass • Avid serosal/peritoneal areas elsewhere • Small volume ascites in the pelvis which was mildly avid • Underwent laparotomy for radical debulking and biopsies

5. Pathology • Histology showed multicystic mucinous cells on samples of: • Serosal surface of the ovaries and fallopian tubes • R) and L) parametria • R) pelvic side wall • Staining: • Strong, diffuse CK7 and CDX2 positivity • Patchy CK20 positivity • ER negative • Felt by pathologist to be of pancreatobiliary origin

6. DIAGNOSIS • Adenocarcinoma of unknown primary • Possibly pancreatobiliary source • Distribution of disease not

7. Treatment • Following surgery, was given chemotherapy • FOLFOX + Avastin • Had an adverse drug reaction to oxyplatin x2 • Maintenance treatment  Xeloda • Achieved complete metabolic remission (on PET) for a period of 4-5 months

8. RECURRENCE • 6 weeks ago, PET showed: • Avid serosal/peritoneal deposits on sigmoid colon • Avid peritoneal fluid in the pelvis • Started on chemotherapy • CBDCA + Paclitaxel + Avastin

9. Treatment Complications Acute: • Oxyplatin hypersensitivity • Fatigue • Dry skin • Mucosal ulcers • Occasional nausea Permanent: • Incisional hernia • Peripheral neuropathy, stable • Manifest as paraesthesia and neuropathic pain in feet and fingers • Nil trouble with weakness, gait disturbance, unsteadiness, falls • Some trouble with getting out medications as a result

10. Carcinoma of unknown primary (CUP) • Heterogenous group of metastatic cancers where the primary site cannot be found • Small primaries may remain undetected • Primaries may have regressed • Primaries may be incidentally removed in treatment for other conditions • Accounts for 3% of cancer diagnoses • As they are heterogenous, they vary widely in prognosis and response to specific treatments

11. Classifying CUp • Clinical manifestations • i.e. isolated axillary lymphadenopathy in women vs. peritoneal disease • Pathological examination • Cytology • Immunohistochemistry • Gene expression profiling

12. Cytology • May differentiate tissue of origin but will not definitively determine primary site • SCC is likely to have come from respiratory tract, but may come from skin • Adenocarcinoma is particularly troublesome, as it may originate in many organs • Very poorly differentiated cancers may not be identifiable

13. Immunohistochemistry • Involves stains for specific proteins which may help to predict the primary site • CK7 and CK20 are commonly tested initially • Results of initial stains inform selection of further stains • The amount of tissue is often a limiting factor • IHC staining algorithms have been shown to predict the primary site correctly in approximately two thirds of cancers with KNOWN primary in blinded studies

14. Gene expression profiling • Tests gene expression of malignant cells using techniques such as rt-PCR and microarrays • Focuses on genes which help delineate organ of origin • Assays may test for up to 92 genes to delineate between up to 42 tumour types • GEP assays have been shown to predict the primary site correctly in approximately 85% of cancers with KNOWN primary in blinded studies (probably closer to 75% of CUP) • In CUP studies, shows ~78% concordance with IHC predictions • When IHC is more definitive (i.e. predicts single tumour type), GEP is more highly concordant than when IHC is ambiguous