EP227 - Small Bowel Cancer in Lynch Syndrome: Diagnostic Pathway and the Role of Immunotherapy

Sunday, May 10, 2026

9:38 AM - 9:43 AM ET

ePoster Presenter(s)

Sara Keshavjee, MD (she/her/hers)

Colorectal Surgery Research Fellow
Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering Cancer Center
New York, NY, United States

Disclosure information not submitted.

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Author(s)

AL

Alicia Latham, MD, MS

Assistant Attending
Memorial Sloan Kettering Cancer Center
New York, New York, United States

Disclosure information not submitted.
Georgios Karagkounis, MD

Assistant Attending
Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering
New York, NY, United States

All disclosed relationships have been reviewed and managed prior to the start of this activity. Any relevant relationships will be listed below. This individual has no financial relationships to disclose
Emmanouil Pappou, MD, PhD

Assistant Attending
Memorial Sloan Kettering Cancer Center
New York, New York, United States

Disclosure information not submitted.
IW

Iris H. Wei, MD

Assistant Attending
Memorial Sloan Kettering Cancer Center
New York, New York, United States

Disclosure information not submitted.
TN

Thendral Nagarajan, n/a

Clinical Research Coordinator
Memorial Sloan Kettering Cancer Center
Hillsborough, New Jersey, United States

Disclosure information not submitted.
Maria Widmar, MD, MPH (she/her/hers)

Assistant Attending
Memorial Sloan Kettering Cancer Center
Weill Cornell Medical Center
New York, New York, United States

All disclosed relationships have been reviewed and managed prior to the start of this activity. Any relevant relationships will be listed below. This individual has no relevant financial relationships.
Martin R. Weiser, MD

Vice Chair for Faculty Affairs
Memorial Sloan Kettering Cancer Center
Cornell Medical College
New York, New York, United States

Disclosure information not submitted.
Philip B. B. Paty, MD

Attending Surgeon
Memorial Sloan Kettering Cancer Center
New York, New York, United States

Disclosure information not submitted.
Julio Garcia Aguilar

All disclosed relationships have been reviewed and managed prior to the start of this activity. Any relevant relationships will be listed below. This individual has no relevant financial relationships.
ZS

Zsofia Stadler, MD

Attending Physician
MSKCC
New York, New York, United States

Disclosure information not submitted.

Senior Author(s)

MA

Mohammad Ali Abbass, MD MPH

Assistant Attending
Memorial Sloan Kettering Cancer Center
New York, New York, United States

Disclosure information not submitted.

Purpose/Background: Small bowel adenocarcinoma (SBA), although rare, has a higher incidence in those with genetic cancer predispositions, such as lynch syndrome (LS). In the absence of proven screening strategies, we sought to characterize the diagnostic pathways and subsequent treatment strategies among LS patients with SBA at our institution.

Methods/Interventions: We conducted a retrospective analysis of patients with LS presenting to Memorial Sloan Kettering with SBA between 1997 and 2023. Clinical, pathologic and radiographic data were extracted from the medical record. Response to neoadjuvant immunotherapy was assessed radiographically and histologically. Categorical variables were compared using Fisher's exact test. Statistical significance was set at p < 0.05.

Results/Outcomes: Twenty-five patients with Lynch syndrome presented with 28 individual tumors, and 96% (23/24 with available staining) were mismatch repair deficient (dMMR). There were 13 patients with MSH2 mutations (52%), six with MLH1 (24%), four with PMS2 (16%), one with MSH6 (4%) and one with a concurrent MSH2 and EPCAM deletion (4%). Median age at presentation was 62 (SD=12.4), with most patients presenting as a first (n=7, 28%) or second (n=6, 24%) lifetime cancer diagnosis. None of these individuals had a family history of SBA or were enrolled in routine small bowel cancer screening programs. Anemia was the most common presenting symptom (n=11, 44%), while others presented due to obstruction (n=6, 24%), incidental CT or PET scan findings (n=5, 20%), or unintentional weight loss (n=2, 8%). Notably in anemic patients, traditional upper endoscopy and colonoscopy work-up was negative. For anemic patients, abnormality pointing to SBA was only identified after abdominal CT (n=4, 36%), CT enterography (n=3, 27%) or video capsule endoscopy (n=2, 18%). Median time to tissue diagnosis among those presenting with anemia was 10 months (range 1-30, SD 9.1 months). When comparing patients presenting with obstruction verses anemia undergoing upfront resection, Fisher's exact test showed no association with pathologic T4 disease (p=0.85).

In the neoadjuvant setting, five patients received PD-1 inhibitors, with four of five patients (80%) experiencing complete response (two on post-operative pathology and two radiographic, who never underwent surgery). Two of the complete responders presented with stage IV disease. Three of the four complete responders had MSH2 mutations, while the other had an MSH6 mutation. The one patient with residual disease at resection had an MLH1 mutation. All other patients underwent upfront resection.

Conclusion/Discussion: This series highlights the need to thoroughly investigate anemia in patients with confirmed or suspected LS, utilizing imaging modalities if traditional endoscopy and colonoscopy are negative. In LS patients with advanced SBA, immunotherapy may be of particular benefit, potentially leading to a non-operative approach.

Figure 1. Presentation and Treatment Pathways of Small Bowel Adenocarcinoma in Lynch Syndrome Patients

All patients receiving immunotherapy were treated with PD-1 inhibitors. Diagram created using yEd Graph Editor (yWorks, www.yworks.com). CT = computed tomography, CTE = CT enterography, VCE = video capsule endoscopy, EGD = esophagogastroduodenoscopy, immuno. = immunotherapy.

* one patient presented with two masses concurrently, for a total of 27 presentations to care.

**one case was noted on PET scan after negative CT, VCE, and CTE, another patient was diagnosed by trans-vaginal biopsy due to SBA invading post-hysterectomy vaginal cuff.