a 71-year - old woman presented with a swelling on her left upper eyelid in 2009
. she also had a small mass on her right upper eyelid that been present for the previous 3 years .
she had a history of breast cancer occurring in 1991 , which was treated successfully without recurrence for 18 years .
there was a significant family history of cancer ; two of her brothers had also been diagnosed with cancers . surgical excision and
skin biopsy identified a sebaceous carcinoma in her right eyelid and a morphea - like basal cell carcinoma of her left eyelid ( fig .
immunohistochemical analysis was done using anti - mutl homolog ( mlh ) 1 ( mouse monoclonal ; 1:50 ; bd pharmingen , san diego , ca , usa ) and anti - msh2 ( mouse monoclonal ; 1:40 ; calbiochem , san diego , ca , usa ) .
a mlh1 gene product was present in both tumors , but no msh2 genes were found in either tumor ( fig .
colon cancer tissue obtained from another patient was used as a positive control specimen , with the patient 's permission .
mts is a rare autosomal dominant genodermatosis with variable expressivity , and is regarded as a variant of lynch syndrome .
inherited colorectal cancer syndromes such as familial adenomatous polyposis , muty human homologue ( myh)-associated polyposis , and lynch syndrome / hereditary nonpolyposis colon cancer are less common but account for as much as 5% of colorectal cancer cases .
a diagnosis is made based on the presence of at least one sebaceous neoplasm associated with visceral malignancy , or alternatively , multiple keratoacanthomas with visceral malignancies and a family history of mts .
fifty - six percent of the skin lesions in mts develop after diagnosis of the first internal malignant disease , 6% appear concomitantly , and 22% occur as the first tumor of the syndrome .
. other types of cancer , such as breast cancer , are uncommon ( 4% ) .
the present case had a history of breast cancer , and it was possible that her eyelid neoplasms resulted from breast cancer metastasis .
however , this is unlikely because the patient 's breast cancer did not recur for a period of 18 years and 2 different types of neoplasms were found in the eyelids .
more importantly , immunohistochemical staining for hmsh2 and hmlh1 was consistent with a diagnosis of mts , in addition to clinical findings that met the clinical criteria for mts .
considering these results , it would be safe to speculate that the case belonged to a spectrum of mts conditions .
sebaceous gland tumors are much more common in asians than in caucasians , with a reported frequency of 10.2% to 32.7% of malignant tumors in eastern asians in comparison to 0% to 3.2% in the us and europe
. indeed , sebaceous gland tumors in caucasians are so rare that their presence is considered a marker for mts , and lead to a search for an occult malignancy .
the incidence of mts in the asian population is not clear , but it is likely to be underestimated . because sebaceous gland neoplasms of the eyelid are so common in asia , and most of them are successfully treated by local excision , their presence is not regarded as a specific event .
even if another visceral malignancy occurred in the same patient after a long interval , it would often be diagnosed as a coincidence of independent tumors .
in fact , the diagnosis would not have been easy without the help of immunohistochemical analysis for mlh1 and msh2 , which were used in the present case .
many mts patients demonstrate germ - line mutations in genes encoding dna mmr proteins such as mlh1 or msh2 and , less commonly , msh6 .
these proteins function to detect and repair errors in base pairing that occur during dna replication , especially in regions of dna characterized by repetitive mono- or dinucleotide repeats , termed microsatellites .
mmr protein mutations , when paired with a second somatic mutational hit of the remaining functional allele , leads to increased susceptibility to tumor formation .
immunohistochemistry assessing msh2 , mlh1 , and msh6 activity , and microsatellite instability ( msi ) analysis are currently the two main screening tests for mts .
mmr genes encode proteins that recognize and remove improper genomic insertions and deletions and nucleotide mismatches that arise during dna replication and recombination .
collectively , these genes maintain the integrity of the genome and prevent mutations from accumulating . in mts ,
individuals are born with one defective copy of an mmr gene and acquire a second somatic mutation in the other allele during their lifetimes .
the first mutations identified in mts involved the mmr genes msh2 and mlh1 , the same genes known to cause lynch syndrome .
recent advances in immunohistochemistry and msi analysis have made the diagnosis of mts much easier and more reliable .
msi analyses and reviews of family history should guide cancer surveillance options for patients and their extended families after immunohistochemistry .
patients with visceral malignant disease as part of mts tend to survive longer than those with visceral malignant diseases outside of the syndrome , and even metastatic disease can respond to aggressive surgical treatment
. the role of ophthalmologists is much larger than before because 22% of skin lesions in mts develop prior to the diagnosis of the first internal malignant disease .
generally , sebaceous skin tumors characteristic of mts can be regarded as premonitory physical characteristics for an underlying cancer predisposition . at present ,
screening studies for msh1 and mlh2 on eyelid tumors would give us important information about future treatment and follow - up programs for patients .
 we report a case of muir - torre syndrome ( mts ) with a very rare combination of cancers , involving bilateral eyelid cancers and breast cancer . 
 a 71-year - old female with a history of breast cancer from 18 years prior presented with bilateral eyelid tumors . 
 one of her siblings had lung cancer , and another had pancreatic cancer . 
 she underwent excisional biopsy of the eyelid tumors and histopathology revealed sebaceous carcinoma of the right eyelid and basal cell carcinoma of the left . 
 she was diagnosed with mts : a skin cancer associated with visceral malignancy . 
 immunohistochemical tests for muts homolog 2 showed a lack of expression in both eyelid carcinomas . 
Case Report
Discussion