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Metastasis to the uterine corpus is uncommon and secondary colorectal tumours of the endometrium are rare. We describe a uterine tumour with components of both primary endometrial and metastatic colorectal carcinomata. In this case, a 72-year-old obese woman presented with a 2-week history of postmenopausal bleeding per vaginum and weight loss. She had an abdominoperineal resection 3 years previously for a Dukes stage B rectal carcinoma. A transvaginal ultrasonography showed a thickened endometrium. Histology immunophenotyping showed a CK7+, CK20+, CA125− and CEA+ colorectal metastasis (a profile consistent with her previous cancer) associated with a primary CK7+, CK20−, CA125+ and CEA− endometroid endometrial adenocarcinoma. We conclude this represents endometrial metastasis of colorectal carcinoma with coincident primary endometrial adenocarcinoma. We speculate as to whether the endometrial carcinoma arose de novo or was induced by the colorectal metastasis, or whether the primary endometrial tumour provided a fertile site for the colorectal metastasis.
Although metastasis to the uterine corpus is uncommon, when it occurs, it is generally to the myometrium rather than the endometrium. Endometrial involvement by metastasis is almost always in conjunction with myometrial metastasis.1 Endometrial metastasis has been described in association with cancers of the breast, colon1 2 and stomach,3 4 as well as in association with malignant melanoma5; in most cases there is disseminated metastatic disease.6 We describe an unusual occurrence of isolated endometrial metastasis of a colorectal tumour, closely associated with a primary endometrial cancer.
A 72-year-old woman presented with a 2-week history of continuous fresh bleeding per vaginum and a 2-month history of a 3 kg weight loss. She denied urinary symptoms or change in bowel habit and there was no history of pain. Systemic review was unremarkable.
She was menopausal at age 58 and was gravida 4. There was no evidence of previous pelvic inflammatory disease and there was no history of hormonal therapy.
She had undergone an abdominoperineal resection of a colorectal carcinoma 3 years previously which proved to be a T3 N0 MX, well to moderately differentiated Duke's stage B adenocarcinoma with no other adverse prognostic features. Her postoperative recovery was long and complicated by a severe methicillin-resistant Staphylococcus aureus wound infection, wound dehiscence and poor diabetic control. Postoperative radiological examination showed no evidence of metastatic disease and the multidisciplinary team (MDT) decision was that no further treatment was necessary. Up-to-date follow-up colonoscopy showed no evidence of recurrence.
Her co-morbidities included poorly controlled type 2 diabetes mellitus, ischaemic heart disease, hypertension, a body mass index of 48 and non-alcoholic steatohepatitis. She was previously a heavy smoker, her diet was poor and she had poor exercise tolerance. Her regular medications were lisinopril 10 mg twice daily, metformin 500 mg twice daily and rosiglitazone 2 mg twice daily. She had no relevant family history.
On examination she was alert and well. Her abdomen was soft and non-tender and no masses or organomegaly were felt. Bimanual examination revealed a moderate cystocoele and the uterus could not be felt.
Transvaginal ultrasonography showed a thickened endometrium at 39 mm, with a mixed echogenic pattern and there was a small collection in the pouch of Douglas, findings suggestive of endometrial carcinoma. Hysteroscopy showed a thickened, yellow endometrium with a partly necrotic and partly viable tumour. Colonoscopy was normal. CT of the thorax, abdomen and pelvis showed no evidence of lymphadenopathy or metastatic disease as demonstrated in figure 1. Skeletal surveys are not routinely performed in the initial work-up of suspected colorectal or endometrial cancer at our institution and therefore a bone scan was not carried out.
Curettings were taken and microscopical examination of these showed a polyp associated with two separate tumour fragments of distinct histological and immunohistochemical phenotypes, as illustrated in figures 2 and and3.3. The first fragment had a mixed glandular and pseudopapillary pattern with extracellular mucin production, positive for CK7, CK20 and CEA but negative for CA125, ER and vimentin, suggesting a colorectal aetiology. The second fragment showed some solid areas with a distinct micropapillary pattern, positive for CK7, CA125, vimentin and ER positive but CK20 and CEA negative, consistent with endometrial cancer.
Immunohistochemical profiling of her previous adenocarcinoma was then carried out as illustrated in figure 4. This proved her previous tumour to be positive for CK7, CK20 and CEA, but negative for CA 125, ER and vimentin, consistent with the metastatic (but not endometrial) phenotype.
From the histology and immunohistochemical profiling we concluded that this patient had two distinct tumours, the first being a high grade serous endometrial carcinoma and the second, based on comparative histology with her previous adenocarcinoma and their identical immunohistochemical profiles, a coincident colorectal carcinoma metastasis without radiological evidence of local, or general, tumour dissemination.
Her histological diagnosis was discussed with the gynaecological MDT and subsequently with the colorectal MDT and the joint consensus was that metastasis from the previous primary gave her a poor prognosis from a colorectal cancer point of view, although a potentially curable stage I endometrial cancer. It was also apparent, however, that since her initial surgery her diabetic control had worsened, her weight had increased and her exercise tolerance had deteriorated and thus these factors combined with a likely surgically difficult, fibrotic abdomen made resection a very unfavourable option; chemotherapy or radiotherapy remained possible options but with limited potential for remission.
Due to her previously difficult postoperative recovery, our patient did not want to undergo another difficult operation and was also reluctant to undergo the ordeal of primary chemotherapy, leaving us with radiotherapy as her remaining option. Further investigation at this point therefore would not alter her management and thus no further imaging or biopsies were sought.
In the end our patient opted for a palliative course of external beam radiotherapy which was delivered in 10 daily sessions, each consisting of 10 meV fractions at anterior, left lateral, posterior and right lateral positions to a combined total of 30 Gy.
After this course of radiotherapy our patient remained stable for some 6 months, however she then rapidly declined and did not want any further intervention. Her final CT imaging showed para-aortic nodal disease, but again no dissemination and further investigation at this point would have been futile. After she died the coroner felt that a postmortem examination was not indicated and the family did not want a hospital autopsy.
Postmenopausal per vaginum bleeding must be considered cancer until proven otherwise and therefore must be investigated urgently. There are around 4500 new cases of primary endometrial cancer each year in the UK, but per vaginum bleeding secondary to a metastatic cause is rare.6 Other than in disseminated disease or familial colorectal cancer syndromes, breast cancers are the only tumours known to commonly metastasise to the endometrium.7 In our patient there was good immunohistochemical evidence that this was a rare example of an isolated endometrial metastasis of colorectal origin.8 This may represent concurrent metastasis of a colorectal carcinoma to a de novo endometrial tumour or it is possible that the endometrial primary had provided a fertile site for metastasis. This idea has been suggested before in sites of cancer,9 10 chronic inflammation, high cell turnover11 or local immunosupression by tumours,10 12 although there are no reports of this in the female genital tract, making this case unusual. It is also possible that the colorectal metastasis may have induced an endometrial carcinoma.
Immunohistochemical panels, where available, are now standard practice worldwide in the diagnosis of endometrial cancer, thus we have accordingly used the recognised markers in this case.8 13 However, there is growing evidence as regards multiclonal or heterogenous tumours, whereby antigen expression is mixed. It should be emphasised that there are emerging data which suggest there may be distinct antigenic subtypes of endometrial carcinoma14 15; at this time, however, the evidence is limited and its clinical relevance is unclear. We feel therefore, given this and the distinct (exclusive) immunohistochemical profiles demonstrated, that multiclonality is not likely to be a significant factor in this case.
Alternative conclusions should also be further considered. As mentioned, uterine metastases are most commonly found in disseminated metastatic disease, but no clinical or radiological evidence of this was ever demonstrated. The possibility of sample contamination was considered, however auditing showed no other colorectal pathology was processed that day in the dissection room or laboratory. The blocks and slides were also checked to exclude clerical error.
Finally, there was no evidence of intercurrent breast cancer and, although endometrial metastases are seen in familial colorectal cancer syndromes, a lack of family history made this very unlikely. It should be noted that the nosology of this group of diseases is evolving and Lynch syndrome is becoming recognised as a distinct entity where the occurrence of synchronous hereditary non-polyposis colorectal cancer-type tumours is recognised by diagnostic criteria alone16; this may therefore raise the need for genetic screening of this woman's family.
In conclusion, we describe an unusual case of metastasis of a primary colorectal adenocarcinoma to the endometrium with simultaneous primary serous endometrial adenocarcinoma. Such a case poses significant implications for surgical and oncological management, which should be determined on an individual basis.
Competing interests None.
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