Mr JS, 23yo man Initially presented with haematochezia, abdominal pain and IBS-like Sx Family Hx of father with bowel cancer, age 40 Diagnosis of Lynch syndrome – Unclear how or when this diagnosis was made Otherwise well, ex-smoker (3 pack years) On colonoscopy investigating haematochezia, multiple polyps were found and excised

Malignant sigmoid polyp (sessile serrated adenoma) Subsequent staging investigations confirmed T1N0M0 disease

Synchronous tubular adenoma with low grade dysplasia

Treatment of the Colon Ca Diagnosed with Lynch syndrome – Unclear how or when this diagnosis was made Underwent total colectomy for definitive treatment of colon cancer and prophylaxis – No neoadjuvant or adjuvant therapy at this time Complications of this treatment: – Urinary symptoms, incl. pis-en-deux, trouble initiating and urinary retention – Short bowel syndrome

Follow up CT Chest at 1 year follow up showed: – 14mm LLL lesion – L) hilar and aortopulmonary lympadenopathy These areas were shown to be intensely avid on FDG-PET CT Abdo at this time showed (non-avid): – Small calcified opacities – Bulky L) adrenal, nil definite mass – 2x small mesorectal nodes

Biopsy EBUS and biopsy was undertaken Results: – Poorly differentiated adenocarcinoma – Signet ring morphology – TTF1 and CK7 +ve – CK20 and CDX2 –ve – This IHC is consistent with primary lung adenocarcinoma

Signet ring cells

Initial treatment of the Lung Ca Not resectable RT to the chest Complicated by severe radiation oesophagitis – Requiring 2/52 admission for IV fluid therapy Coupled with sensitising CTx regime – Cisplatin/Etoposide

Progress Repeat PET following radiochemotherapy – Hilar nodal disease shrunk, although remained avid – New avid areas L5 transverse process L) adrenal 2 nd line CTx with Carboplatin/Pemetrexed

Chemotherapy SEs He is troubled by fatigue and severe stabbing headaches Other SEs he has experienced include: – Nausea – Hiccoughs – Hot flushes – Sleep disturbance – Nosebleeds

Social Hx Lives at home with parents and older sister Has a girlfriend Works as a partner manager, previously full time – Now works from home when able Father has not been formally diagnosed with Lynch syndrome Others in the family are considering screening They are all extremely worried for him

Social Hx (cont.) Otherwise he is active, getting out of the house on days when he feels well enough ECOG 1, symptoms limiting him only sometimes Sees friends often, goes to parties, etc.

Lynch syndrome Hereditary cancer syndrome, mediated by mutation to one of several DNA mismatch repair genes – Examples include MLH1, MSH2, MSH6 and PMS2 Phenotypically expressed as increased risk of several types of cancer (~30-50% risk), including: – Bowel – Endometrial – Ovarian – Renal pelvis TCC No proven association with lung cancer

Screening for hereditary Ca syndrome Genetic screening based on probability of gene being found – Funded test if probability >10% Bowel cancer at a young age alone is not necessarily enough to score a test FHx feature typical of a hereditary syndrome: – Multiple cancers in the family – Young age at onset of cancer – Multiple cancers in the same individual In Lynch, tumour typing may involve tests for MMR and MSI, which detects additional cases

Bowel Ca screening Population Average risk individuals: FOBT funded at 50, 55, 60 and 65 years Recent budget included provisions for 2 yearly FOBT for those aged 50-74, to be phased in by 2020 Moderate risk individuals: 5 yearly colonoscopy from age 50 or 10 years before earliest diagnosis in the family High risk individuals: Consider referral to a family cancer clinic Lynch syndrome Colonoscopy every 1-2 years from 25 years, or 5 years from earliest diagnosis in the family - Cancer Council guidelines (2008) Screening for other cancers associated with Lynch may be indicated, i.e. haematuria/urine cytology

Cancer prophylaxis in Lynch Aspirin 600mg d (CAPP2 trial) – Highly significant decreased risk of cancer vs. potato starch – No significant difference in adverse events while on aspirin Surgical prophylaxis – Total colectomy – Hysterectomy + salpingoophrectomy