Metastatic Colorectal Carcinoma Mimicking Ovarian Carcinoma
Metastatic Colorectal Carcinoma Mimicking Ovarian Carcinoma
Introduction: Ovarian metastases occur in 3 to 8% of women with primary colon cancer. In the setting of a pre-existing colorectal carcinoma this would constitute a hereditary non-polyposis colorectal cancer, Lynch 2 syndrome, accounting for 5 to 10% of colon cancer cases. We unveil a case of 'giant' ovarian tumors mimicking primary ovarian cancer; ostensibly the first reported in East Africa.
Case presentation: A 58-year-old African woman was diagnosed with colorectal adenocarcinoma in June 2009. She had a right hemicolectomy with the tumor staged as regional cancer, following histopathological examination. Chemotherapy was administered both adjuvantly and 1 year later for what was thought to be a recurrence of tumor. Despite this, her general condition deteriorated. Following re-evaluation and an exploratory laparotomy she was found to have bilateral 'giant' ovarian tumors, with peritoneal seedlings and subcutaneous metastases (colonic in origin). A bilateral salpingo-oophorectomy was done, accompanied by histopathological analysis with institution of chemotherapy for ovarian cancer. Following immunohistochemistry tests and microsatellite instability analysis it was found that the ovarian tumors were secondaries from the colon. She was also identified as a Lynch syndrome case or a case of sporadic microsatellite instability, although with no suggestive family cancer history. The treatment regimen was changed to suit metastatic disease.
Conclusions: The case presents a diagnostic and thus treatment conundrum. Two primary tumors (suspected Lynch syndrome) had been perceived yet there is actually only metastatic colorectal cancer. We also have a rare and unusual metastatic presentation: 'giant' bilateral ovarian tumors and subcutaneous nodules, concurrently. Further still, she is a case of probable Lynch syndrome, requiring genetic analysis for definitive classification and surveillance for hereditary non-polyposis colorectal cancer-associated cancers.
Important inferences are drawn. Firstly, 'giant' ovarian tumors diagnosed as primary ovarian cancer may actually be colonic secondaries. Secondly, immunohistochemistry and microsatellite instability analysis tests ought to be part of the diagnostic package in colon cancer management, particularly for identifying tumor origin and the Lynch syndrome (a condition which has had little attention in resource-limited countries). Thirdly, multidisciplinary team collaboration is emphasized in colorectal cancer management.
Colorectal cancer is among the top five leading forms of cancer among women in Uganda. In some resource-rich countries it is the second leading cause of cancer-related deaths. The majority of colorectal cancer cases are sporadic, occurring in individuals without any known familial predisposition. Approximately 20% of all cases occur with a related family history, but most of the predisposing genetic factors are not yet identified.
The ovaries are an uncommon secondary site for metastatic colorectal carcinoma; the liver and lungs being commoner. In general, the ovaries are the organ of the female reproductive system most commonly affected by metastases. Ovarian metastases occur in 3 to 8% of women with primary colon cancer, with their prevalence at the time of diagnosis being 1.1%. Following surgery, the metachronous prevalence remains 1.1%. Colorectal cancer accounts for 65% of the malignancies found to have ovarian metastases at the time of primary surgery. Metastatic gastrointestinal cancers frequently mimic an ovarian primary in both pre- and postmenopausal women, yet covert gastrointestinal tumors may present as advanced ovarian cancer. Subcutaneous or skin metastases account for only 5% of metastases.
The occurrence of a primary ovarian carcinoma, metachronously, with colorectal carcinoma is a well-known entity. It is a presentation of hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome), the commonest hereditary type of colon cancer, and constitutes 5 to 10% of colorectal cancer cases. There are two phenotypic types of Lynch syndrome: type 1 and 2. Lynch syndrome 1 presents with two separate colorectal cancers, whereas Lynch syndrome 2 manifests as colorectal cancer with another extra-colonic cancer. The extra-colonic cancers are: endometrial, gastric, urinary tract, biliary tract, pancreatic, small bowel, brain and skin. Rarely, ovarian cancer may manifest in Peutz–Jeghers syndrome. Ovarian cancer is the second most common extra-colonic site in women, its overall lifetime risk of development being 6.7%.
Lynch syndrome is inherited in an autosomal dominant pattern. Because of the absence of an overt polyposis phenotype, it can be the most challenging hereditary colorectal syndrome to recognize. Germline mutations in one of several deoxyribonucleic acid (DNA) mismatch repair (MMR) genes are responsible for this syndrome. The MMR genes in the presence of microsatellites, define the Lynch syndrome genotype. Recent studies have suggested a median age of diagnosis of associated colorectal cancers of 61.2 years and a lifetime colorectal cancer risk of 52.2% in women. Synchronous and metachronous tumors are frequently observed.
To establish a diagnosis of Lynch syndrome, every patient with colorectal cancer should undergo a detailed family history. A suggestive family history is delineated by the Amsterdam II criteria, and Bethesda guidelines to maximize sensitivity. Specific features that should raise suspicion are: multiple family members affected with colorectal cancer or associated extra-colonic tumors; young age at diagnosis of colon cancer; or multiple Lynch syndrome-associated cancers in a single individual. Currently, fulfillment of the Amsterdam II criteria is insufficient to establish a definitive diagnosis of Lynch syndrome, and molecular testing is required for this purpose. We are very limited in capacity to conduct these tests in Uganda.
Abstract and Introduction
Abstract
Introduction: Ovarian metastases occur in 3 to 8% of women with primary colon cancer. In the setting of a pre-existing colorectal carcinoma this would constitute a hereditary non-polyposis colorectal cancer, Lynch 2 syndrome, accounting for 5 to 10% of colon cancer cases. We unveil a case of 'giant' ovarian tumors mimicking primary ovarian cancer; ostensibly the first reported in East Africa.
Case presentation: A 58-year-old African woman was diagnosed with colorectal adenocarcinoma in June 2009. She had a right hemicolectomy with the tumor staged as regional cancer, following histopathological examination. Chemotherapy was administered both adjuvantly and 1 year later for what was thought to be a recurrence of tumor. Despite this, her general condition deteriorated. Following re-evaluation and an exploratory laparotomy she was found to have bilateral 'giant' ovarian tumors, with peritoneal seedlings and subcutaneous metastases (colonic in origin). A bilateral salpingo-oophorectomy was done, accompanied by histopathological analysis with institution of chemotherapy for ovarian cancer. Following immunohistochemistry tests and microsatellite instability analysis it was found that the ovarian tumors were secondaries from the colon. She was also identified as a Lynch syndrome case or a case of sporadic microsatellite instability, although with no suggestive family cancer history. The treatment regimen was changed to suit metastatic disease.
Conclusions: The case presents a diagnostic and thus treatment conundrum. Two primary tumors (suspected Lynch syndrome) had been perceived yet there is actually only metastatic colorectal cancer. We also have a rare and unusual metastatic presentation: 'giant' bilateral ovarian tumors and subcutaneous nodules, concurrently. Further still, she is a case of probable Lynch syndrome, requiring genetic analysis for definitive classification and surveillance for hereditary non-polyposis colorectal cancer-associated cancers.
Important inferences are drawn. Firstly, 'giant' ovarian tumors diagnosed as primary ovarian cancer may actually be colonic secondaries. Secondly, immunohistochemistry and microsatellite instability analysis tests ought to be part of the diagnostic package in colon cancer management, particularly for identifying tumor origin and the Lynch syndrome (a condition which has had little attention in resource-limited countries). Thirdly, multidisciplinary team collaboration is emphasized in colorectal cancer management.
Introduction
Colorectal cancer is among the top five leading forms of cancer among women in Uganda. In some resource-rich countries it is the second leading cause of cancer-related deaths. The majority of colorectal cancer cases are sporadic, occurring in individuals without any known familial predisposition. Approximately 20% of all cases occur with a related family history, but most of the predisposing genetic factors are not yet identified.
The ovaries are an uncommon secondary site for metastatic colorectal carcinoma; the liver and lungs being commoner. In general, the ovaries are the organ of the female reproductive system most commonly affected by metastases. Ovarian metastases occur in 3 to 8% of women with primary colon cancer, with their prevalence at the time of diagnosis being 1.1%. Following surgery, the metachronous prevalence remains 1.1%. Colorectal cancer accounts for 65% of the malignancies found to have ovarian metastases at the time of primary surgery. Metastatic gastrointestinal cancers frequently mimic an ovarian primary in both pre- and postmenopausal women, yet covert gastrointestinal tumors may present as advanced ovarian cancer. Subcutaneous or skin metastases account for only 5% of metastases.
The occurrence of a primary ovarian carcinoma, metachronously, with colorectal carcinoma is a well-known entity. It is a presentation of hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome), the commonest hereditary type of colon cancer, and constitutes 5 to 10% of colorectal cancer cases. There are two phenotypic types of Lynch syndrome: type 1 and 2. Lynch syndrome 1 presents with two separate colorectal cancers, whereas Lynch syndrome 2 manifests as colorectal cancer with another extra-colonic cancer. The extra-colonic cancers are: endometrial, gastric, urinary tract, biliary tract, pancreatic, small bowel, brain and skin. Rarely, ovarian cancer may manifest in Peutz–Jeghers syndrome. Ovarian cancer is the second most common extra-colonic site in women, its overall lifetime risk of development being 6.7%.
Lynch syndrome is inherited in an autosomal dominant pattern. Because of the absence of an overt polyposis phenotype, it can be the most challenging hereditary colorectal syndrome to recognize. Germline mutations in one of several deoxyribonucleic acid (DNA) mismatch repair (MMR) genes are responsible for this syndrome. The MMR genes in the presence of microsatellites, define the Lynch syndrome genotype. Recent studies have suggested a median age of diagnosis of associated colorectal cancers of 61.2 years and a lifetime colorectal cancer risk of 52.2% in women. Synchronous and metachronous tumors are frequently observed.
To establish a diagnosis of Lynch syndrome, every patient with colorectal cancer should undergo a detailed family history. A suggestive family history is delineated by the Amsterdam II criteria, and Bethesda guidelines to maximize sensitivity. Specific features that should raise suspicion are: multiple family members affected with colorectal cancer or associated extra-colonic tumors; young age at diagnosis of colon cancer; or multiple Lynch syndrome-associated cancers in a single individual. Currently, fulfillment of the Amsterdam II criteria is insufficient to establish a definitive diagnosis of Lynch syndrome, and molecular testing is required for this purpose. We are very limited in capacity to conduct these tests in Uganda.