Delayed metastatic endometrial carcinoma mimicking primary colon adenocarcinoma: A surprise histopathological finding

A 62‐year‐old female presented to a private gastroenterologist with 1 week of right upper quadrant pain, with no alterations in bowel habit, per rectum bleeding or melaena. This was on a background of grade 3 stage 1B endometrioid adenocarcinoma, managed by laparoscopic total abdominal hysterectomy (TAH), bilateral salphingo‐oophorectomy (BSO), bilateral pelvic node dissection and omental biopsy, followed by adjuvant radiotherapy, 5 years prior. A colonoscopy done 6 months after TAH‐BSO for a positive fecal occult blood test showed diverticular disease and a colonic polyp, which was removed. She has a family history of lung cancer in her father and maternal aunt. There was no family history of CRC. On examination, she was systemically well and haemodynamically normal. Her gastrointestinal examination was normal, abdomen soft, non‐tender, and there were no palpable masses, organomegaly or lymphadenopathy. Digital rectal exam was also unremarkable. Serum cardioembryonic antigen (CEA) was 1.7 ug/L (normal) and her other bloods were unremarkable. CT of her abdomen identified an irregular circumferential caecal thickening (Figure  1 ), with no adenopathy or metastatic disease, and uncomplicated sigmoid and descending colon diverticulosis. Colonoscopy showed a 4 cm centrally ulcerated, fungating lesion in the caecum (Figure  2 ) and preliminary histology of the caecal biopsy identified adenocarcinoma. Initial CT (top—axial, bottom—coronal) demonstrating caecal thickening. A 4 cm ulcerated, fungating lesion revealed during colonoscopy. She was thought to have a primary colorectal adenocarcinoma based on these findings and underwent a robotic right hemicolectomy, with no anesthetic or surgical complications. Intraoperatively, she was found to have a locally advanced caecal tumor involving the peritoneal side walls, with no visible liver or peritoneal disease. Histologically, full thickness invasion of the bowel wall (from serosa to ulcerated mucosa) by the tumor was observed, with no nodal involvement of the 22 resected lymph nodes. On immunohistochemistry (IHC), the resected tumor was stained positive for cytokeratin 7 (CK7), paired‐box gene 8 (PAX8) and estrogen receptor (ER). It was weakly positive to CDX 2, and negative to cytokeratin 20 (CK20) and special AT‐rich sequence‐binding protein 2 (SATB2). Similar results were observed on IHC of the caecal biopsies taken during the colonoscopy (Figure  3 ). These findings were suggestive of a metastatic endometrioid carcinoma. She recovered well postoperatively and was promptly commenced on adjuvant chemotherapy. Tumor cells from the caecal biopsy staining positive (brown) for PAX8 on IHC.

Hui Yuan Foong: Validation; writing – original draft. Jian Blundell: Conceptualization; resources; writing – review and editing. Cameron Law: Conceptualization; project administration; writing – review and editing. Ross Warner: Supervision; writing – review and editing.

As this was a single patient case report HREC approval was not required for this institution, however all measures have been undertaken by the researchers to obtain appropriate written participant consent. Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

Colonic metastases are a rare occurrence. The most common pathways in which metastases reaches the colon are via the lymphatics or vascular system, direct extension (i.e., invasion of contiguous colon wall), or peritoneal seeding. 6 Primary cancers that metastasize to the colon typically arise from the lung, breast, ovaries, prostate, kidneys, skin, stomach, or hepatobiliary system. 4 Metastatic lesions to the colon from an endometrial primary are even more uncommon, thus easily being confused for a primary colorectal cancer. To our knowledge, only six similar cases have been described in the literature (Table  1 ). Summary of cases of metastatic endometrial cancer to colon. Abbreviations: BSO, bilateral salphingo‐oophorectomy; CK, cytokeratin; CRC, colorectal cancer; ER, estrogen receptor; FIGO, International Federation of Gynecology and Obstetrics; IHC, immunohistochemistry; PAX8, paired‐box gene 8; TAH, total abdominal hysterectomy; WT1, wilms tumor‐1. As in the case described above, Anstadt et al. 7 Wou et al. 8 and Hubers et al. 9 all present a case of stage 1 endometrial cancer metastasizing to the colo‐rectum status post‐surgical management and were all presumed to be primary CRCs based on imaging and scope findings, proven otherwise by IHC. This highlights the importance of IHC to aid in diagnosis, particularly in poorly differentiated carcinomas that appear morphologically similar. On IHC, CRCs are typically positive for CK20 and CDX2, and negative for CK7 and ER. 10 The converse is true for endometrial carcinomas 10 ; as observed in the case above. Koury et al. 11 described a case of a 67‐year‐old with stage 1 endometrial cancer recurring in the sigmoid colon 15 months after neoadjuvant radiotherapy, who initially presented with haematochezia. Jauregui et al. 12 reported a case of disease recurrence of stage 3b endometrial cancer to the sigmoid colon 1 month after TAH‐BSO, in an 89‐year‐old who presented with haematochezia. Finally, Molnar et al. 13 presented a case of a 71‐year‐old who presented with sub‐occlusive syndrome, weight loss and anemia, found to have recurrence of stage 3b serous endometrial cancer 2 years status post‐surgical management and adjuvant chemoradiotherapy. Intraoperatively, she was found to have multiple metastatic lesions in the colon (ascending, transverse and descending) and the gastric antrum (with invasion of the lower pole of spleen). A retrospective cohort study by Sohaib et al. 14 showed that the peritoneum was one of the most typical sites of recurrent endometrial cancer, accounting for 28% of relapses. Additionally, malignant transformation of colorectal endometriosis resulting in the development of endometrioid carcinoma is a rare but well‐known complication, typically proven by IHC. 15 Interestingly in the case presented, the colonic metastasis occurred in the absence of peritoneal disease and any endometriosis. Finally, considering the existence of reports of diagnostic errors in pelvic tumors of different origins, from organs anatomically close but completely incompatible in pathology, 16 , 17 it is essential to accurately diagnose the origin of tumors if there is the slightest doubt, before taking action.

This case report highlights a rare occurrence of delayed metastatic endometrial carcinoma to the colon which was identified following surgical resection. It underscores the significance of including the colon as a possible site of metastasis in endometrial cancer, albeit uncommon, and the invaluable utility of IHC in facilitating an accurate diagnosis and possibly subsequent management. In this case, preoperative evaluation through to management of caecal mass would not have changed, regardless of delayed IHC findings, as resection was still indicated and performed in a standard oncological manner.

Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for 10% of all cancers and 9.4% of all cancer‐related deaths in 2020. 1 By 2030, the number of new CRC diagnoses is expected to increase by 60%, to over 2.2 million new cases worldwide. The rising incidence of CRC is mainly attributed to the increasing prevalence of obesity, alcohol and meat consumption, sedentary lifestyle, and an aging population. 2 Patients with CRC may be asymptomatic at diagnosis or have gastrointestinal symptoms such as bleeding, pain, change in bowel habit or bloating. 3 A small subset of patients may even present with non‐GI symptoms. 1 Approximately 1% of all colon cancers are metastatic lesions from distal primaries. 4 Recurrent endometrial carcinoma typically metastasizes to the peritoneum or lungs, whilst it is atypical for them to spread to the liver, adrenals, brain, bones, and soft tissue. 5 In the current literature, endometrial cancer metastasis to the colon is a rare occurrence and is only described in a handful of cases. In this article, we describe an unusual case of endometrial cancer with a delayed metastasis to the colon.

The authors declare no relationships, including financial or professional, which may pose a competing interest.