Colonic metastases 13 years after the primary ovarian cancer: a case study with a brief review of literature

Abstract

Metastatic ovarian malignancy is a known and dreaded complication of ovarian malignancy. Ovarian malignancies primarily disseminate through the peritoneal cavity and are only superficially invasive. They rarely metastasise through the haematogenous route, but that occurs in the presence of heavy peritoneal disease. The involvement of the colon in advanced ovarian malignancy is mostly through the peritoneal seedlings. It is very rare for an ovarian malignancy to invade through the serosa into the submucosa and mucosa of an adjacent colonic segment in the absence of active peritoneal disease. This occurring 13 years after the primary malignancy and after receiving a full course of chemotherapy is very interesting. There is always a possibility of a second primary cancer but in this case immunohistochemistry clearly clinched the diagnosis of an ovarian metastasis to the colon.

Background

Metastatic ovarian malignancy is a dreaded complication of ovarian cancer. Ovarian malignancies primarily disseminate through the peritoneal cavity and are only superficially invasive. Haematogenous dissemination occurs in the presence of heavy peritoneal disease. The secondary involvement of the colon is through the peritoneal seedlings. It is very rare for an ovarian malignancy to invade into the mucosa of a colonic segment in the absence of an active peritoneal disease. This occurring 13 years after the primary cancer is rarer still. There is always a possibility of a second primary cancer but immunohistochemistry (IHC) clinched the diagnosis of an ovarian metastasis to the colon.

Case presentation

A 33-year-old woman presented with bilateral ovarian cysts in December 2003. On ultrasound the right ovary showed a simple 91 mm cystic lesion while the left ovary showed a 102 mm solid cystic lesion. Her CA 125 was 5 U/mL. She underwent a bilateral oophorectomy in January 2004 in a small 20-bed private hospital in her city. The final histology showed a right ovarian serous cystadenoma and left ovarian serous cystadenocarcinoma. A contrast-enhanced CT scan showed residual left adnexal mass. She received four cycles of paclitaxel plus cisplatin-based chemotherapy followed by completion hysterectomy with omentectomy and pelvic lymphadenectomy. In June 2004 her carcinoma antigen (CA) 125 levels were 150 prompting a review of histopathology slides in a tertiary care cancer institute. It showed poorly differentiated papillary adenocarcinoma. She then received three further cycles of chemotherapy and was followed up. In July 2017, at the age of 47 years, she was found to have an irregular deposit in the left iliac fossa.

Investigations

In August 2017 a Positron Emission Technology (PET) scan revealed an irregular enhancing mass lesion 3.3 × 3.6 × 3 cm in the pelvis abutting the sigmoid colon with Standardised Uptake Values (SUV) Max 17.98 (figure 1). A colonoscopy revealed area of infiltration along with friable mucosa bleeding to touch and causing luminal narrowing in the sigmoid colon about 25 cm from the anal verge (figure 2). Biopsy revealed high-grade adenocarcinoma of the sigmoid colon. The final histopathology showed the metastatic deposit of serous papillary adenocarcinoma involving sigmoid colonic wall transmurally and ulcerating through the mucosa with no lymphovascular embolisation or perineural invasion (figure 3). The omentum, and six pericolonic and five pelvic lymph nodes were all free from malignancy. IHC was positive for Wilms Tumour 1 protein (WT1) (figure 4) and PAX8 (figure 5) and negative for CDX2 (figure 6) confirming its mullerian origin.

Figure 1.

Positron Emission Technology (PET) scan revealed an enhancing mass lesion 3.3 × 3.6 × 3 cm in the pelvis abutting the sigmoid colon (SUV Max 17.98).

Figure 2.

Area of infiltration with friable mucosa, causing luminal narrowing in the sigmoid colon.

Figure 3.

Serous papillary adenocarcinoma ulcerating through the mucosa.

Figure 4.

WTI stain positive on immunohistochemistry.

Figure 5.

PAX8 stain positive on immunohistochemistry.

Figure 6.

CDX2 stain negative on immunohistochemistry.

Treatment

She underwent an anterior resection with end-to-end colonic anastomosis in October 2017 at our centre. There was a mass lesion of about 3.5 × 3.5 × 3 cm in the sigmoid colon involving all the layers. There was dense fibrosis in the pelvis due to previous surgeries, but there were no peritoneal deposits, ascites, lymphadenopathy, and no involvement of bowel or liver and pericolonic adipose tissue. She was given adjuvant chemotherapy and has received three cycles of doxorubicin and platinum-based chemotherapy to date.

Outcome and follow-up

There has been a regular follow-up every 3 months initially and then every 6 months. The patient is healthy without any metastasis.

Discussion

In most of the population-based cancer registries in India, ovarian cancer is the third leading site of cancer among women, after cervical and breast cancers.¹ The age-adjusted incidence rates of ovarian cancer vary between 4.6 and 8.9 per 100 000 population in different parts of the country.¹ As per the Surveillance, Epidemiology and End Results program (SEER) guidelines, April 2017, 5-year survival for ovarian cancer is 46.5%.

Patients with ovarian malignancies usually present with advanced disease with spread to the pelvic peritoneum and local spread to the surrounding organs. The current standard of care is extensive debulking or cytoreduction followed by adjuvant taxol and platinum-based chemotherapy.² Debulking is possible because the ovarian tumours stay within the peritoneal cavity and only invade the mesothelium-lined surfaces. Even large tumour deposits in the omentum and the pelvic peritoneum are known to be superficially invasive, never invading through to the mucosa. Free tumour cells are carried by the peritoneal fluid and get attached to other peritoneal surfaces, where their fast and uncontrolled growth causes ascites and subsequent bowel obstruction. At this point they might spread through a haematogenous route.

Metastases to the colon and rectum are very rare and the most common organ of origin in a large autopsy series was revealed to be breast, lung and colon.^{3 4} Colonic metastases from the ovary are known to occur by direct spread, from peritoneal seedlings and haematogenous spread. Colonic metastases 13 years after an ovarian malignancy are very rare. Shibahara et al have described a case which presented 20 years after the primary ovarian malignancy while Nakamura Y have described a case that presented 22 years after the primary malignancy.^{5 6} Zighelboim et al have reported a case with only colonic mucosal involvement and no serosal involvement within 6 months of the initial diagnosis where the patient was not given adjuvant treatment.⁷ Ji-Hyeon Park et al have reported a similar case with an isolated sigmoid colon lesion 3 years following surgery and adjuvant chemotherapy.⁸ Slimani et al have also reported a case where an isolated rectal tumour with micrometastasis to the lung was diagnosed 9 years after the primary surgery.⁹

Reed et al¹⁰ have found colorectal mucosal involvement in 36% of ovarian malignancies during their autopsy findings of 77 patients while Rose et al¹¹ have documented colonic wall involvement in 50%–60% of 428 cases. In our case there was neither residual peritoneal disease nor systemic disease. Bowel serosa was involved but there was no adjacent adipose tissue involvement. Thirteen years after adequate surgery and chemotherapy, this finding was quite rare and a possibility of a second primary malignancy was there. IHC of the specimen revealed that the tumour was WT1-positive and PAX8-positive and CDX2-negative. Seventy-one per cent of serous adenocarcinomas of the ovary studied by Nakatsuka et al¹² show positive nuclear staining with WT1 while Nonaka et al found an 86.9% WT1 positivity.¹³ Ninety-nine per cent of high-grade ovarian serous carcinomas studied by Laury et al¹⁴ and 96% of cases by Nonaka et al¹³ had nuclear PAX8 positivity. All this conclusively points to a mullerian origin of the colonic malignancy.

Learning points.

• Ovarian malignancies usually present in the late stage of disease and the overall 5-year survival is less than 50%.

• Even though colorectal metastases from the ovary suggest a poor prognosis of the disease, the fact that the disease has recurred after 13 years indicates that aggressive treatment can give the patient a reasonable disease-free survival.