Complex Case Study of a 63-Year-Old Woman with Adenocarcinoma

Mrs. PC, a 63-year-old woman, initially presented with chronic right lower abdominal pain due to cholelithiasis. Despite laparoscopic cholecystectomy, the pain persisted. Further investigations revealed adenocarcinoma of unknown primary, possibly of pancreatobiliary origin. Treatment included chemotherapy with complications and recurrence, leading to ongoing management challenges.

• Case study
• Adenocarcinoma
• Cholelithiasis
• Chemotherapy
• Complications

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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