Clinico-pathological conference:Gynae Oncology

Friday Dec 7th 2007

Alex Laios,

Orla Sheils,

John O’Leary

HISTORY

• 43 yr old, Irish lady, married, P0+0

• Consulted GP with a 3/12 Hx of:– Abdominal distention (increasing abdominal girth)– Intermittent abdominal pain, progressively worsening

(like tightness across the abdomen)– Loss of appetite– Weight loss associated with lower abdominal

discomfort of ~3/52 duration– 1 recent episode of SOB and dry cough– No change in urinary or bowel habits

Questions

• What are the possible causes of increasing abdominal girth?

• What is the possible cause of weight loss in this woman?

• Why does this woman have shortness of breath and dry cough?

Questions

• What is the next step in managing this patient?

• What investigations would be ordered in this case?

Ultrasound examination of the abdomen-pelvis [ordered by GP]

• Massive ascites • 9 cm large complex cystic mass probably arising

from the pelvis, with multiple septations• Left ovary could not be visualized• Left hydronephrosis

Pelvis US scan

Referral to gynae oncology service

Physical examination • Thin lady, previously healthy• No lymphadenopathy• Breast examination was normal• Lung fields clear on auscultation• Abdominal distention to 28 weeks size by a mass of poor

mobility arising from pelvis and upper abdominal fullness, suggesting omental disease

• Clinical ascites• Distended pouch of Douglas with thickening on recto-

vaginal examination

Medical and Gynaecologic History

Medical Hx:– HTN, Ulcerative colitis (previously on long term steroids but no

evidence of DEXA osteopenia)– Medications: Centyl, Lipitor– Allergies: Penicillin

Surgical Hx: Arthroscopy, cholecystectomy Family Hx: Bowel Ca (father), breast Ca (mother)Gynae Hx:

– Menarche at age 12y– Regular cycles, no dysmennorhea, LMP 2/52 ago– Last Cx smear 3 years ago– Never on OCP

Laboratory investigations

On admission• FBC profile: Hb:13, WCC:9.8, PLTS:560• Renal profile: urea:10.3, sodium:140, potassium:3.6,

creatinine:93 (marginally elevated)• Liver profile: Albumin: 25 , LDH:385• CA125: 534• CA19.9: 3.9

Questions

• What is your provisional diagnosis?

• Can you identify any risk factors from her medical history?

• What is your interpretation of her blood results?– Albumin– urea, creatinine– Hb, plts

Radiology investigations

• CXR: – Lung fields appear clear– No cardiomegaly – No pleural effusion

• CT TAP (chest abdomen pelvis) – 11 X 12.5cm complex pelvic mass arising from the left ovary– Massive ascites– Omental cake– No evidence of retroperitoneal lymphadenopathy– Left hydronephrosis– Splenic hilar and peritoneal nodes

• 3-D colour Doppler• FDG-PET

CT- pelvis and abdomen

Omental cake

MRI scan -pelvis

3-D colour Doppler FDG-PET

Laparotomy:Optimal debulking

Findings on laparotomy

TAH, BSO,Omentectomy, Appendicectomy• Gross disease above pelvic brim• 4 litres of ascites was removed• Left ovary replaced by solid-cystic tumour at least 13 cm,

densely adherent to the left pelvic sidewall/peritoneum/POD• Tumour deposits on splenic hilum, small deposits in

subdiaphragmatic and liver capsule (less than 0.5cm)• Omental deposits

Describe the gross pathology findings

Peritoneal fluid

What does this show?

Histology

What does this show?

Immunocytochemistry: p53

Pathological diagnosis

• Papillary serous cystadenocarcinoma of the left ovary– TNM stage pT3, N1, Mx– FIGO stage IIIC

HISTORY

• Uneventful recovery• Histology available at day 9• Referred to medical oncologists for adjuvant

chemotherapy• Discharged on day 13• Returned 6 weeks after surgery for initiation of

chemotherapy

HISTORY

• Received 6 cycles of Carboplatin and Taxol– Question: what do these agents exactly do?

Actions of drugs

Mechanism of action of taxol

Mechanism of action of carboplatin

HISTORY

• Chemotherapy completed 3 months later• Remained well and returned for combined

follow-up with Gynae-Oncologists and Medical Oncologists– Question: what is entailed in the medical follow-up?

Follow-up

• History

• Clinical examination

• CA-125

HISTORY

• Routine follow-up [3 months] for the first 2 years, then every 6 months for the next 2 years, then annually.

• 14 months after the original surgery she complains of:– Tiredness– Intermittent low abdominal pain– Vaginal bleeding

Questions

• Why does this patient have a vaginal bleeding?

• What is the cause of the intermittent abdominal pain?

HISTORY

• On clinical examination, two nodules are identified close to the vaginal vault

• Raising CA125• CT of thorax, abdomen and pelvis performed

– Two small soft tissue masses suspicious for disease recurrence seen at the vaginal vault

• Biopsy performed of vaginal lesions

Vaginal vault biopsy

What does this show?

Relapse

• Will the patient benefit from the same chemotherapy?

• Will she benefit from excision of the nodules?

Recurrence in ovarian cancer

• 70% of ovarian cancer patients present with advanced ovarian cancer [stage III/IV]

• 50%-70% of patients relapse

• Less than 20% long-term survivors

• Gene pathways for ovarian cancer recurrence have just been defined

“The true Killer”RECURRENCE

An integrative model for recurrence in ovarian cancer

Management algorithm for patients with ovarian cancer

Our opportunity for intervention

CLINICAL DISEASE

CLINICAL DISEASE

NORMAL OVARY

PRE- MALIGNANT

CHANGE

PRE- CLINICAL DISEASE

Family history

CHEMO- PREVENTION

PROPHYLACTIC OOPHORECTOMY

SCREENING

TREATMENT

Environment

Ovulation

Module network procedure

Pre- processing

Image trait selection

Disease traits

Gene expression data

Image traits

Expression data

Clustering

Gene partition

Functional modules

Annotation analysis

Graphic presentation

Independent Validation

Classification program learning

Post- processing

Genes

Life sciences

Information sciences

Life and Information sciences

Pathological data

Proteomic data

MRI3-D colour doppler CT FDG-PET