Lynch Syndrome
Definition:
Syndrome
of multi-system oncogenesis due to hereditary mutation of DNA repair mechanism.
Urology relation: upper tract urothelial carcinoma
Inheritance: autosomal dominant
Mutation: mismatch
repair enzyme, most common MSH2 and MLH1
Pathogenesis: creating significant microsataliltes instability.
Clinical
morphology:
- Hereditary non-papillary colorectal cancer (HNPCC)
- HNPCC-related (Lynch Spectrum) tumors:
a.
Endometrial
b.
Ovarian
c.
Urothelial (ureter, renal
pelvis and bladder)
d.
Stomach
e.
Small intestine
f.
Biliary tract
g.
Brain (glioblastoma)
h.
Skin
i.
Sebaceous gland adenoma
j.
keratocanthoma
Why
urologist needs to diagnose Lynch Syndrome?
- Relatives of Lynch patients are at higher risk for UUT-UC and Bladder cancer.
- Patients need surveillance for UUT-UC by URS and urine cytology.
- Counseling and screening of family.
- Indication for Evaluation for other HNPCC tumors
Epidemiology
of Lynch Spectrum UUT-UC:
- 98%
0f Lynch-spectrum UUT-UC show mismatch repair gene mutation.
- 46%
of cases show microsatalite instability.
- Majority
is related to MSH2 mutation
- 9%
of all UUT-UC showed Lynch related mutation (while only 1% of bladder cancer
do).
- 13%
of UUT-UC patients screened positive for Lynch syndrome.
- 5%
of UUT-UC is confirmed Lynch syndrome.
Diagnosis:
Amsterdam criteria (1998),
to diagnose suspicious families:
- ≥3 relatives with Lynch spectrum tumors, AND
- ≥1 of them is first degree relative of the other, AND
- ≥1 of them affected before 50 years old, AND
- 2 of them in successive generations, AND
- Familial adenomatous polyposis excluded, AND
- All tumors are diagnosed pathologically.
Bethesda criteria (2003)for
diagnosis of suspicious patient, one of:
- A patient with Lynch related tumor (mainly colorectal) < 50 years old.
- A patient with colorectal with high microsatalite instability morphology < 60 years old.
- A patient with colorectal cancer and synchronous or metachronus lynch spectrum tumor.
- Patient with colorectal cancer, with 1st degree relative diagnosed with Lynch spectrum tumors < 50 years old, or adenomas < 40 years old.
- Patient with colorectal cancer and have 2 relatives with Lynch spectrum tumors.
- Patient < 65 years old
- Personal history of Lynch spectrum tumor, OR
- First degree relative with Lynch spectrum Tumor < 50 years old, OR
- Two first degree relative with lynch spectrum tumor.
The symbol of urological knowledge, fore-front training and patient oriented care, Dr. Dushiant Sharma is the one who conscientiously deserves the accentuated name of the top Urologist in Panchkula . The trustworthiness of Dr. Sharma’s clinic, echoing many years of top-class service, is strong enough for everyone who has been a patient to be sure that a personalised treatment, corresponding to every individual’s peculiarities, will be provided for every patient.
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