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

MEDICAL HISTORY

Panic attacks

Varicose veins

Cholelithiasis

Distant ex-smoker (ages 18-27)

FAMILY HISTORY

Mother: ovarian ca (age 70+)

Maternal aunt: breast ca (age ~70)

Father: lung ca (smoker)

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

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

DIAGNOSIS

Adenocarcinoma of unknown primary

Possibly pancreatobiliary source

Distribution of disease not

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

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

TREATMENT COMPLICATIONSAcute:

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

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

CLASSIFYING CUP

Clinical manifestations i.e. isolated axillary lymphadenopathy in women vs. peritoneal disease

Pathological examination Cytology

Immunohistochemistry

Gene expression profiling

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

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

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