Clinical Case Summary

An 82-year-old woman with history of arterial hypertension and mastectomy 30 years ago for breast carcinoma was referred to gastroenterology department for new onset iron deficiency anemia (Hb of 9,7 g/dL). Bidirectional endoscopic studies were performed revealing in upper endoscopy an irregular, nodular, ulcerated, and friable lesion in gastric posterior antrum suggestive of gastric neoformation (Figure 1). Colonoscopy showed various ulcerated, irregular, nodular lesions in sigmoid colon at 20 cm and 30cm from anal margin. The most proximal one induced lumen stenosis and no possibility of further colonic exploration (Figure 2). Multiple biopsies were taken from all the lesions and referred for pathological examination, suspecting a synchronic gastrointestinal (colorectal and gastric) tumor. Histology revealed typical findings of serous ovarian carcinoma in all samples, confirmed by detailed immunohistochemistry (Figure 3). A computed tomography scan and a magnetic resonance were performed for loco-regional and distance staging revealing a bilateral ovarian mass of 71x60mm and 40x20mm infiltrating sigmoid colon, metastasic implant in stomach, liver metastasis and peritoneal carcinomatosis. (Figure 4).
Metastases in gastrointestinal system and synchronic lesions in stomach and colon are an unusual form of first presentation of primary ovarian cancer. Endoscopic findings can be superimposable on primary digestive neoplasia. This case illustrates a diagnostic challenge when detecting malignant lesions in endoscopic studies, bringing the importance of a wide differential diagnosis in iron deficiency anemia and lesions suggestive of malignancy, especially histological and immunohistochemical studies, to establish a definitive diagnosis and therefore apply best treatment regimen.

References

1. Lisio MA, Fu L, Goyeneche A, Gao ZH, Telleria C. High-Grade Serous Ovarian Cancer: Basic Sciences, Clinical and Therapeutic Standpoints. Int J Mol Sci. 2019 Feb 22;20(4):952.
2. Buza N. Immunohistochemistry in gynecologic carcinomas: Practical update with diagnostic and clinical considerations based on the 2020 WHO classification of tumors. Semin Diagn Pathol. 2022 Jan;39(1):58-77.
3. Orr B, Edwards RP. Diagnosis and Treatment of Ovarian Cancer. Hematol Oncol Clin North Am. 2018 Dec;32(6):943-964.
4. Szucs RA, Turner MA. Gastrointestinal tract involvement by gynecologic diseases. Radiographics. 1996 Nov;16(6):1251-70; quiz 1461-2.

Clinical Case Summary

An 80-year-old woman with a history of right ovarian cancer, treated with total hysterectomy and bilateral salpingo-oophorectomy followed by adjuvant radiotherapy in 1984, presented with tenesmus and rectal bleeding. She had long-standing radiation-induced enteritis. Colonoscopy revealed a 50mm ulcerated neoplasm in the distal rectum. Histopathological analysis confirmed a low-grade rectal adenocarcinoma with loss of nuclear expression of the mismatch repair proteins MSH2 and MSH6. Staging with thoracoabdominal CT and pelvic MRI showed a distal rectal adenocarcinoma invading the vagina and levator ani muscle (cT4), cN0, with a suspicious left inguinal lymph node (possible cM1). Given her prior exposure to pelvic radiotherapy and the presence of chronic radiation-induced injury, a multidisciplinary team, after discussion with the patient and her family, decided to initiate off-label neoadjuvant treatment with dostarlimab for six months, completing a total of eight cycles. Six weeks after completion of immunotherapy, flexible sigmoidoscopy demonstrated a clinical near-complete response (near-cCR) and pelvic MRI showed radiologic complete response (rCR), with no evidence of residual tumor or lymphadenopathy. A new flexible sigmoidoscopy is scheduled in four weeks. If cCR is confirmed, the patient will enter a Watch and Wait surveillance program. Traditionally, rectal cancer treatment has relied on a combination of chemoradiotherapy and surgery, resulting in pathologic complete response in up to 25% of patients, but frequently associated with complications and treatment-related toxicity. Recent studies have demonstrated promising results with immune checkpoint inhibitors, particularly dostarlimab as single agent, an antiprogrammed cell death protein 1 monoclonal antibody. In recent studies so far, this agent was remarkably effective in mismatch repair–deficient, locally advanced rectal cancer, showing high rates of cCR and prolonged overall survival.

References

Andrea Cercek et al, A Phase Two, Single-Arm, Open-Label Study With Dostarlimab Monotherapy in Participants With Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer (AZUR-1), Clinical Colorectal Cancer

A. Cercek, M. Lumish, J. Sinopoli, J. Weiss, J. Shia, M. Lamendola-Essel, I.H. El Dika, N. Segal, M. Shcherba, R. Sugarman, Z. Stadler, R. Yaeger, J.J. Smith, B. Rousseau, G. Argiles, M. Patel, A. Desai, L.B. Saltz, M. Widmar, K. Iyer, J. Zhang, N. Gianino, C. Crane, P.B. Romesser, E.P. Pappou, P. Paty, J. Garcia-Aguilar, M. Gonen, M. Gollub, M.R. Weiser, K.A. Schalper, L.A. Diaz Jr. PD-1 BLockade in Mismatch Repair-deficient, Locally Advanced Rectal Cancer

Introduction

CDH1 gene mutations are associated with gastric and breast cancer. The risk of colorectal cancer may be increased in the presence of this mutation, although evidence is scarce.

Aims & Methods

Aims: To assess the presence of high-risk colorectal polyps (polyp with ≥10mm or with high-grade dysplasia, ≥5 adenomas, any serrated polyp ≥10mm or with dysplasia) and colorectal cancer in patients on surveillance program with mutation in CDH1 gene.
Methods: Retrospective study in patients with CDH1 gene mutation followed in a family risk appointment in a tertiary care hospital.

Results

Data from 36 patients with a mean age of 44.22±14.77 years, 20 males, with a mean follow-up of 5.5 years. Twenty-seven patients had family history of gastric cancer and 9 of gastric and breast cancer; twelve patients had never undergone colonoscopy (age ≤ 40 years). Of the 24 patients who had already undergone at least one colonoscopy, 12 (50%) never removed polyps. Only 4 patients had high-risk polyps (age 30, 52, 59 and 77 years) and no patient presented with colorectal cancer during follow-up.

Conclusion

Although this is a small sample, our study revealed a low percentage of patients with hereditary diffuse gastric cancer with high-risk colorectal polyps (and only one patient with a high-risk polyp aged <50 years) and no patients with colorectal cancer, similar to a population without a CDH1 mutation. Further studies with larger sample sizes are needed to clarify the impact of CDH1 mutation on colorectal cancer.

Introduction

Lynch syndrome (LS) is the most frequent hereditary cancer syndrome, responsible for 3-5% of all colorectal cancer (CRC) cases. Patients with LS are at increased risk for metachronous CRC, influenced by the specific gene involved and the extent of prior surgical intervention¹. However, the impact of colonoscopy surveillance on metachronous CRC incidence in LS carriers has not been clearly defined.

Aims & Methods

To characterize LS carriers at risk of developing metachronous CRC based on the affected gene and the extent of prior surgery. To describe follow-up characteristics, particularly the rate of colonoscopy surveillance. To report the incidence of metachronous CRC according to surgical extent and gene mutation. To analyze potential risk factors associated with metachronous CRC development.
This retrospective multicenter study included 583 LS carriers diagnosed with CRC; 43 were excluded due to missing surgical or follow-up data, resulting in 540 patients analyzed. Patients were categorized by high-risk genes (MLH1, MSH2) or low-risk genes (MSH6, PMS2) and by surgical extent (extensive or partial colectomy). Colonoscopy surveillance was defined as at least one colonoscopy following the initial CRC diagnosis or between successive CRC events in cases of metachronous CRC. Survival analysis assessed the incidence of metachronous CRC.

Results

Among the 540 included carriers, 247 (45.7%) had MLH1 mutations, 181 (33.5%) MSH2, 80 (14.8%) MSH6, and 32 (5.9%) PMS2. Participants were grouped into four categories: high-risk/extensive colectomy (N=58), high-risk/partial colectomy (N=370), low-risk/extensive colectomy (N=9), and low-risk/partial colectomy (N=103). Age at first CRC diagnosis was significantly higher in high-risk groups compared to low-risk groups. No differences were found between groups regarding sex, tumor location, or tumor stage. Median follow-up duration was 8.6 years (IQR 4.5-14.6), with no significant differences among groups. During follow-up, 107 cases of metachronous CRC occurred. Survival analysis revealed significant differences in metachronous CRC incidence (Log-rank test: p=0.006), with 10-year incidence rates of 6.4% for high-risk/extensive colectomy, 17.9% for high-risk/partial colectomy, 0% for low-risk/extensive colectomy, and 4.8% for low-risk/partial colectomy groups. Risk factors significantly associated with metachronous CRC included high-risk gene mutations (HR 2.49, 95% CI 1.2-4.77) and initial CRC diagnosis before the year 2000 (HR 1.61, 95% CI 1.02-2.55). Colonoscopy surveillance was associated with a reduced risk of metacronous CRC (HR 0.06, 95% CI 0.04-0.09).

Table 3. Metachronous CRC risk factors

Conclusion

Individuals carrying pathogenic variants in MLH1 or MSH2 who undergo partial colectomy face a markedly increased risk of developing metachronous CRC. Nonetheless, the introduction of structured colonoscopic surveillance and optimized management strategies after the year 2000 has significantly mitigated this risk. These findings are essential for informing surgical decision-making in patients with LS and CRC, particularly when evaluating the most appropriate extent of colectomy.

References

Eikenboom EL, Moen S, Van Leerdam ME, Papageorgiou G, Doukas M, Tanis PJ, et al. Metachronous colorectal cancer risk according to Lynch syndrome pathogenic variant after extensive versus partial colectomy in the Netherlands: a retrospective cohort study. The Lancet Gastroenterology & Hepatology. 2023 Dec;8(12):1106–17.

Introduction

Aims & Methods

Aims: To assess for evidence of association between a symptomatic FIT ≥10μgHb/g and 1 year risk of other GI cancers and influence of age and anaemia on these associations.
Methods: A regional cohort study inclusive of all patients who underwent a symptomatic FIT between 2017-2023 in Nottingham. Heatmaps, stratifying by age group and blood results were constructed to display the cumulative 1-year cancer risks using Kaplan-Meier estimates.

Results

370 (0.54%) out of 68,538 patients were diagnosed with a non-colorectal GI cancer within 1-year of symptomatic FIT. 242/54,855 (0.44%) patients diagnosed with non-colorectal GI cancer had a FIT<10μgHb/g compared to 128/13,683 (0.94%) with a FIT≥10μgHb/g (p<0.0001). A FIT≥10μgHb/g was associated with increased risk of oesophagogastric (p<0.0001) and small bowel (p<0.0001) cancer compared to FIT<10μgHb/g, yet the absolute risks of each were low (<0.5%). There was no association between FIT result and subsequent hepatopancreatobiliary malignancy. When stratified by FIT result, age and blood results the highest risks were seen in patients with anaemia (Table 1). The cumulative risk of small bowel cancer with a FIT≥10μgHb/g in patients under 40 years with anaemia was 0.8% (95%CI: 0-2.35%). The cumulative risk of oesophagogastric cancer with FIT≥10μgHb/g and anaemia in the age group 71-85 was 0.85% (95%CI: 0.49-1.2%).

Conclusion