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 adenomawith 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

• 2nd 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 screeningPopulationAverage 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