Referral to a clinical genetics service or familial cancer centre opens in a new tab or window for assessment should be considered for all people meeting the categories below:
Pathogenic variant identified in the family |
UNTESTED adult blood relative of a person with an identified germline pathogenic variant in an endometrial cancer or uterine tumour predisposition gene (e.g. MLH1, MSH2, MSH6, FH, PMS2, POLE, POLD1, PTEN). |
Blood relative of a person with a clinical diagnosis of a familial cancer syndrome that predisposes to endometrial cancer or uterine tumours (e.g. Lynch syndrome, PTEN hamartoma syndrome, hereditary leiomyomatosis and renal cell carcinoma [HLRCC]) |
Tumour pathology |
Characteristics that warrant referral irrespective of other factors |
Endometrial cancer that is MMR-deficient (except where there is loss of expression of MLH1, and hypermethylation of the MLH1 promoter is present) |
Uterine leiomyoma with atypical histopathology and FH deficiency on immunohistochemistry |
Rare endometrial tumours e.g. uterine sarcoma, uterine papillary serous carcinoma
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An individual with endometrial cancer in whom tumour testing has identified a somatic BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, POLE, POLD1 or PTEN pathogenic variant with a variant allele frequency (VAF) greater than 30%*
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For those with a personal history of endometrial cancer |
Individual characteristics that warrant referral irrespective of other factors |
Endometrial cancer diagnosed under age 45 years |
Endometrial cancer AND one of the following:
- personal history of a second Lynch syndrome-associated cancer#
- one close relative** with colorectal or endometrial cancer diagnosed under age 50 years
- two or more close relatives** with a Lynch syndrome-associated cancer#
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Endometrial cancer and features of PTEN hamartoma/Cowden syndrome, including but not limited to:
- macrocephaly
- hamartomatous colorectal polyps
- multiple oral mucosal papillomas
- multiple cutaneous trichilemmoma
- thyroid cancer (non-medullary)
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Uterine leiomyoma and features of hereditary leiomyomatosis and renal cell carcinoma (HLRCC):
- renal cell carcinoma (RCC) with histopathology consistent with HLRCC*** and/or FH deficient on immunohistochemistry OR
- multiple cutaneous leiomyomas (at least one histopathologically confirmed) OR
- uterine leiomyoma with atypical FH-associated pathology and/or which is FH deficient on immunohistochemistry OR
An individual with two or more of the following:
- a single cutaneous leiomyoma (histopathologically confirmed)
- multiple symptomatic uterine leiomyomas
- RCC with HLRCC-associated pathology (expert pathology review may be required)***
- a first-degree relative with a clinical feature of HLRCC
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For those with a family history of cancer |
Characteristics sufficient to warrant referral irrespective of other factors |
Close relative** with endometrial cancer and one or more Lynch syndrome-associated cancer(s)#, regardless of the age the cancers were diagnosed |
Two or more close relatives** with endometrial or colorectal cancer, with at least one of the cancers diagnosed under age 50 years |
Three or more close relatives** with a Lynch syndrome-associated cancer#, regardless of the age the cancers were diagnosed |
Family history of endometrial cancer and/or features of PTEN hamartoma/Cowden syndrome (see above) |
Family history of hereditary leiomyomatosis and renal cell carcinoma (HLRCC)
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*VAF of 30% or greater for single nucleotide variants (SNVs) and 20% or greater for small insertions and deletions is the recommended threshold for suspecting a variant may be germline
** Close relative = 1st or 2nd degree
***HLRCC-associated RCCs are predominantly high-grade with a papillary growth pattern. However, HLRCC-associated RCCs have been described to show tubulopapillary, tubulocystic, tubular, solid and cystic areas and may overlap morphologically with collecting duct carcinomas. Multiple architectural patterns, including sarcomatoid and rhabdoid components, may be seen within the same tumour. Large nuclei with prominent orangiophilic or eosinophilic nucleolus surrounded by a clear halo are often observed.rr
# Lynch syndrome-associated cancer includes adenocarcinoma of the colorectum, endometrium, small intestine, stomach, ovary, or pancreas, urothelial carcinoma of the ureter or renal pelvis, cholangiocarcinoma, brain tumour, sebaceous gland tumour