Multiple synchronous malignant neoplasms in an elderly lady with a history of early onset breast cancer

Synchronous tumours are two or more distinct tumours occurring at the same time in the same organ, opposite sides of paired organs, or different organs (1). Cases of three or more synchronous tumours are rare and have been reported in the breast, colon, genitourinary tract, female reproductive tract, gastrointestinal tract and skin (2-6). We report an unusual case of synchronous tumours of the breast, colon and ovary occurring in a female with history of early onset breast cancer.


Introduction
Synchronous tumours are two or more distinct tumours occurring at the same time in the same organ, opposite sides of paired organs, or different organs (1).Cases of three or more synchronous tumours are rare and have been reported in the breast, colon, genitourinary tract, female reproductive tract, gastrointestinal tract and skin (2)(3)(4)(5)(6).We report an unusual case of synchronous tumours of the breast, colon and ovary occurring in a female with history of early onset breast cancer.

Case History
A 71 year old woman who had been treated for carcinoma of the right breast at the age of 29 years, presented with altered bowel habits associated with loss of appetite and loss of weight of six months duration.She had no family history of malignancy but had a history of primary subfertility.
Examination revealed an irregular left breast lump measuring 3x2x2cm in the upper outer quadrant that was highly suspicious of malignancy on mammography.A large tumour in the rectosigmoid colon was seen on colonoscopy.It was confirmed to be an adenocarcinoma on biopsy.
A Trucut biopsy of the breast lump was performed followed by an anterior resection for the colonic tumour.During surgery for the colonic tumour, she was incidentally found to have a tumour arising from the right ovary and an oophorectomy was also performed.All three samples were received at our laboratory.The latent time interval of over forty years seen in this patient is unusual for a chemotherapy induced malignancy.There was no history of exposure to carcinogens.
We were unable to determine the cause of multiple synchronous tumours in our patient.
However, an inherited breast cancer syndrome such as BRCA1 and BRCA2 syndromes or Li Fraumeni syndrome is a possibility.BRCA1/2 syndromes are inherited in an autosomal dominant fashion, associated with a markedly increased risk of breast and ovarian tumours and have a high association with breast carcinoma occurring below 35 years.

Confirmation of diagnosis requires genetic
testing by sequencing of patient DNA samples in a clinically approved diagnostic laboratory.(7) The lack of a positive family history and high grade "medullary like" histopathological features in the tumour such as pushing margins, lymphoid infiltrate and a high mitotic count (9) are against the diagnosis of a BRCA1 associated cancer.However, if this patient was diagnosed with a BRCA1 associated syndrome by genetic testing, counseling could have been offered to other family members.In addition since tumours carrying BRCA1/2 are sensitive to PARP (poly ADP ribosome polymerase) inhibitors it also provides an opportunity for targeted therapy (10).
Li Fraumeni Syndrome is caused by germline mutations in TP53 gene and is associated with multiple primary neoplasms of which breast cancer is the most common.The breast cancer associated with this syndrome is ussually diagnosed at an early age <30 years.
The histology of breast carcinoma is similar to sporadic tumours but it is usually associated with amplification of HER2.Although guidelines are in place for testing and screening of carriers, the clinical benefit is currently limited (7).

Conclusion
Although rare, the possibility of an inherited cancer syndrome should be considered in patients presenting with breast cancer at a young age and in patients with multiple malignancies.
Sections from the breast biopsy revealed a tumour with a cribriform architecture comprising glandular spaces lined by luminal and myoepithelial cells.The constituent cells had bland, hyperchromatic, angulated nuclei and scanty cytoplasm.Small true lumina containing PAS positive material with pseudolumina containing Alcian blue positive mucin were present.The luminal cells were positive for CK7 and negative for CK20.The myoepithelial cells were highlighted by S100.The tumour was negative for oestrogen, progesterone and HER2 receptors.The breast tumour was diagnosed as an adenoid cystic carcinoma which was confirmed by a subsequent mastectomy.The lymphnodes did not contain metastases.