GALT/Dome Adenocarcinoma in a Patient With MLH1-Deficient Lynch Syndrome: Navigating a Clinical and Management Dilemma

ABSTRACT

A woman in her early 40s with MLH1-deficient Lynch syndrome was incidentally found to have a cecal gut-associated lymphoid tissue (GALT)/dome carcinoma during routine surveillance colonoscopy. This case highlights the co-occurrence of 2 rare entities: a germline MLH1 pathogenic variant and a GALT/dome carcinoma, now recognized within the lymphoglandular complex-like carcinoma spectrum, which carries potential for nodal metastasis. The intersection of mismatch repair deficiency and GALT/dome carcinoma raises a management dilemma: prophylactic colectomy vs endoscopic surveillance in the absence of high-risk histologic features. We review the literature to guide management in this rare scenario.

INTRODUCTION

Gut-associated lymphoid tissue (GALT)/dome carcinomas are exceptionally rare colorectal neoplasms, with only 26 cases reported in the English-language literature, and only a minority have occurred in the context of hereditary cancer predisposition syndromes such as Lynch syndrome or familial adenomatous polyposis (FAP).^1,2 Of prior cases, only 2 involved a confirmed hereditary colorectal cancer syndrome: 1 in Lynch syndrome³ and 1 in FAP⁴; the present case is therefore the third such example.¹ Conventional colorectal adenocarcinomas arise from mucosal epithelium through established oncogenic pathways and are defined by glandular proliferation within the lamina propria.⁵ Gut-associated lymphoid tissue (GALT)/dome carcinomas differ in 2 fundamental ways: They originate within submucosal lymphoid tissue rather than from surface epithelium, and their glandular elements are enveloped by dense lymphoid infiltrate without intervening lamina propria, a combination of features that renders them both biologically and morphologically distinct.^1,6 While historically regarded as indolent tumors carrying excellent prognosis, recent evidence under the designation lymphoglandular complex-like carcinoma (LGCC) challenges this assumption, demonstrating nodal metastasis in a meaningful subset of cases.⁷

CASE REPORT

A female patient in her early 40s with a confirmed MLH1 deleterious germline mutation was followed for Lynch syndrome (LS) surveillance. Her most recent colonoscopy, performed 18 months after her prior examination, identified a solitary 9 mm pedunculated cecal polyp (Paris classification 0-Ip; Figure 1), which was removed by en bloc snare polypectomy with histologically clear resection margins. No synchronous lesions were identified. Histopathologic examination of the polypectomy specimen confirmed GALT/dome carcinoma arising in an adenomatous polyp with tubulopapillary architecture (Figures 2 and 3). Adenomatous glands extend into dense submucosal lymphoid aggregates devoid of lamina propria, consistent with defining GALT/dome carcinoma morphology. Invasion was confined to the submucosa (pT1, Sm1). Tumor budding was Bd1. Lymphovascular invasion and perineural invasion were absent. Desmoplasia and single-cell infiltration were not identified. The patient fulfills Amsterdam II criteria for the clinical diagnosis of LS. Four years prior, she was diagnosed with stage Ia, grade I endometrioid endometrial carcinoma (EC) and subsequently underwent laparoscopic hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Her family history is significant for colorectal cancer (CRC) in her brother (age 28 years), her father (age 45 years, requiring total colectomy and gastrectomy), and her paternal grandfather (age 42 years). After discussion of hemicolectomy vs surveillance, the patient opted for 6-monthly endoscopic surveillance and remains on active follow-up.

Figure 1.

Endoscopic view of the solitary 9 mm pedunculated cecal polyp (Paris classification 0-Ip), identified incidentally during routine surveillance colonoscopy in a patient with MLH1-deficient Lynch syndrome. The polyp was resected en bloc by snare polypectomy, with histologically clear resection margins confirmed on pathologic assessment. Despite its benign endoscopic appearance, histopathology confirmed GALT/dome carcinoma arising in an adenomatous polyp with submucosal invasion. GALT, gut-associated lymphoid tissue.

Figure 2.

Hematoxylin and eosin-stained section at low magnification (scale bar: 600 μm). Black arrow: Adenomatous glands in tubulopapillary architecture with prominent adjacent lymphoid aggregates extending into the submucosa. These glands lack the surrounding lamina propria characteristic of conventional adenomas and are instead enveloped by dense lymphoid tissue, a defining histologic feature of GALT/dome carcinoma. Blue arrow: Dilated adenomatous glands extending into dense submucosal lymphoid aggregates devoid of adjacent lamina propria, confirming submucosal invasion confined within the GALT compartment (pT1). The absence of conventional lamina propria and the intimate association of glandular elements with lymphoid tissue are critical diagnostic features distinguishing this entity from conventional colorectal adenocarcinoma. High-risk histologic features (lymphovascular invasion, perineural invasion, desmoplastic stromal response, and single-cell infiltration) were absent in this specimen, consistent with a low-risk pathologic profile. GALT, gut-associated lymphoid tissue.

Figure 3.

Hematoxylin and eosin-stained section at higher magnification (scale bar: 50 μm). A well-formed germinal center is surrounded by a dense lymphoid cuff, within which dilated adenomatous glands are embedded. The intimate encasement of glandular elements by organized lymphoid tissue, without intervening lamina propria, supports the diagnosis of GALT/dome carcinoma. In this case, lymphovascular invasion, perineural invasion, desmoplasia, and single-cell infiltration were absent, consistent with the low-risk histopathologic profile. GALT, gut-associated lymphoid tissue.

DISCUSSION

The total number of reported GALT/dome carcinoma cases remains uncertain due to inconsistent diagnostic terminology; GALT carcinoma, dome carcinoma, and GALT/dome carcinoma likely represent the same entity described under different names, complicating systematic case ascertainment. Our review identified 26 prior cases (Table 1). These tumors are characterized by submucosal localization, a prominent surrounding lymphoid infiltrate, and dilated glands lined by columnar epithelium.^6,8 They may present as polypoid, sessile, or plaque-like lesions and are typically identified incidentally during colonoscopy.⁸ Associated conditions include ulcerative colitis, Lynch syndrome, and FAP.^1,2 A 2018 study by Hayashi et al⁹ found GALT carcinomas lack GP2 expression, suggesting they are rare differentiated adenocarcinomas arising within GALT rather than M-cell derivatives.

Table 1.

Consolidated cases of gut-associated lymphoid tissue/dome carcinoma reported in the English literature

Case	Author/Year	Age	Sex	Symptoms	Bowel-associated condition	Location	Size (mm)	TNM	MMR/MSI status
1	Rubio/1984	57	M	NA	UC	Left colon	NA	NA	NA
2	De Petris/1999	44	M	Abdominal pain, weight loss	Lynch syndrome	Ascending	9	pT1N0	None
3	Jass/2000	56	M	No symptoms	FAP	Ascending	30	pT1N0	Stable (PCR)
4	Clouston/2000	63	F	None	None	Sigmoid	None	pT1N0	None
5	Clouston/2000	56	M	None	None	Sigmoid	14	pT1N0	None
6	Rubio/2002	53	F	Diarrhea	UC	Ascending	None	pT1N0	None
7	Stewart/2008	70	M	No symptoms	UC	Ascending	5	pT1N0	Stable (IHC)
8	Stewart/2008	63	F	Diverticulitis	None	Transverse	17	pT1N0	Stable (IHC)
9	Asmussen/2008	76	F	Bowel bleeding	None	Sigmoid	20	pT1N0	Stable (IHC)
10	Asmussen/2008	86	F	Bowel bleeding	None	Rectum	24	pT2N0	Stable (IHC)
11	Rubio/2010	53	F	No symptoms	Family history of CRC	Ascending	8	pT1N0	Unstable (IHC): MLH1
12	Coyne/2011	76	M	No symptoms	Family history of CRC	Cecum	23	pT1N0	Stable (IHC)
13	Puppa/2012	56	M	Constipation	None	Right flexure	8	pT1N0	Stable (IHC)
14	Yamada/2012	77	M	Abdominal discomfort	None	Transverse	30	pT3N0	Stable (IHC)
15	Rubio/2013	68	F	No symptoms	None	Transverse	None	pT1N0	None
16	Yamada/2013	76	F	No symptoms	None	Rectum	10	pT1N0	Stable (IHC)
17	Zhou/2015	47	M	Bowel bleeding	CRC	Descending	8	pT1N0	Stable (IHC)
18	Kannuna/2015	57	F	Abdominal pain	None	Cecum	30	pT1N0	Stable (IHC)
19	Hickey/2016a	78	M	None	History of tubular adenomas	Right colon	NA	NA	NA
20	Wataru/2017	80	M	Rectal bleeding	None	Sigmoid	None	pT1N0	MLH1, MSH2
21	Hayashi/2018	70	F	None	Previously resected adenocarcinoma	Sigmoid	13	pT1N0	None
22	Hayashi/2018	72	M	Blood in stools	Gastric cancer post gastrectomy	Rectum	4	pT1N0	None
23	Hayashi/2018	58	M	Blood in stools	None	Rectum	NA	pT1N0	None
24	Noh/2022	58	M	No symptoms	None	Rectum	16	pT1N0	Stable (IHC)
25	Kanesada/2025	90	F	Constipation	None	Sigmoid	13	pT2N0	Unstable (IHC): MLH1, PMS2
26	Fallas/2025	68	F	No symptoms	None	Sigmoid	22	pT1N0	Stable (IHC)
Present case	This report	Early 40s	F	None	Lynch syndrome; prior endometrial carcinoma	Cecum	9	N/A	N/A

Table adapted from Kanesada et al ¹⁰ and Rubio et al,¹ with additional cases and modifications by the authors. MMR/MSI status refers to the confirmed germline MLH1 pathogenic variant. Tumor-specific MMR IHC of the polypectomy specimen could not be performed.

CRC, colorectal carcinoma; FAP, familial adenomatous polyposis; IHC, immunohistochemistry; MMR, mismatch repair; MSI, microsatellite instability; NA, not available; PCR, polymerase chain reaction; UC, ulcerative colitis.

^aConference abstract (ACG Annual Scientific Meeting, Las Vegas, 2016); not peer-reviewed.

The landmark 2024 study by Yilmaz et al⁷ substantially revised the natural history of these tumors. This series of 20 cases, which proposed the unifying LGCC designation, identified nodal metastasis in 4 of 11 patients with available lymphadenectomy data (36%), lymphovascular invasion in 1 of 20 cases, invasion beyond the submucosa in 2 of 20 cases, and desmoplasia in 10 of 20 cases (Table 2). The 36% nodal metastasis rate reflects only patients who underwent formal lymphadenectomy and should not be extrapolated uncritically to all GALT/dome cases. Notably, MMR deficiency was found in 2 of 9 tested cases (22%),⁷ challenging the assumption of uniformly stable microsatellite status. A 2026 study by Fallas et al¹¹ subsequently proposed morphological diagnostic criteria for GALT/dome carcinoma, summarized in Table 3.

Table 2.

Clinicopathologic characteristics of lymphoglandular complex-like carcinoma in 20 cases

Characteristic	n (%) or Value
Demographics
Age, mean ± SD (range)	64.4 ± 13.7 (41-88) years
Female sex	12 (60%)
Lesion characteristics
Median size (range)	1.1 (0.8-5.0) cm
Most common site	Ascending colon/cecum, 7 (35%)
Sessile appearance	12/14 with data (86%)
Surface histology
TA with high-grade dysplasia	10 (50%)
TA without dysplasia	6 (30%)
Sessile serrated lesion	3 (15%)
Histologic features
Germinal centers >50% of infiltrate	15 (75%)
High-grade dysplasia in submucosa	11 (55%)
Angulation	18 (90%)
Fused glands	15 (75%)
Luminal necrosis	13 (65%)
Loss of polarity	11 (55%)
Desmoplasia	10 (50%)
Single-cell infiltration	7 (35%)
Goblet cells	2 (10%)
Pathologic stage
T1	18 (90%)
T3	2 (10%)
Node-positive disease (among those with lymphadenectomy)	4/11 (36%)
Molecular and outcome data
MMR deficiency	2/9 tested (22%)
Alive without disease at follow-up	11/14 (79%)

Adapted from Yilmaz et al⁷.

LGCC, lymphoglandular complex-like carcinoma; MMR, mismatch repair; TA, tubular adenoma.

Table 3.

Proposed diagnostic criteria for GALT-associated carcinoma compared with 2 main mimics: conventional adenocarcinoma invading GALT and inverted colorectal adenoma (misplaced adenomatous glands)

Essential morphological criteria
Gross findings  Submucosal nodule or raised plaque (1 reported case of a pedunculated lesion)
Microscopic findings  Nodule with sharp borders and pushing margins (pushing growth pattern)  Dense lymphoid stroma with germinal centers  Well-formed glands with minimal architectural disruption  Cystic glands filled with amorphous eosinophilic material  Absence of goblet cells (MUC2-negative)  No desmoplasia (presence suggests associated conventional adenocarcinoma)  No tumour budding or small isolated clusters of cells  No lymphovascular invasion  High-grade dysplasia on the mucosal surface
Differential diagnoses
Misplaced adenomatous glands  Invagination of adenomatous glands from surface epithelium into GALT  Lamina propria surrounding/cuffing the displaced glands  Tubular architecture and/or villous projections
Conventional adenocarcinoma invading GALT  Infiltration of GALT by a conventional adenocarcinoma  Presence of desmoplasia  Infiltrative, irregular margins  Small fused glands containing dirty necrosis  Tumour budding or small isolated clusters of cells may be present  Lymphovascular invasion may be present  Extension beyond lymphoid tissue may occur

Adapted from Fallas et al¹¹.

GALT, gut-associated lymphoid tissue.

The present case demonstrates none of the high-risk LGCC features: Lymphovascular invasion, perineural invasion, and desmoplasia were absent, with pT1 staging and clear polypectomy margins, which is clinically reassuring. MLH1 mutations, as confirmed in this patient, are associated with a lifetime CRC risk of 40%-80% and a lifetime endometrial cancer risk of approximately 39%-43%.^12,13 The accelerated adenoma-to-carcinoma sequence in LS underscores that even small polyps may harbor invasive carcinoma, as illustrated by this 9 mm pT1 lesion, reinforcing the importance of complete removal and careful histopathologic evaluation of all lesions identified during LS surveillance.¹⁴

A critical unresolved question is whether this tumor arose via LS-related biallelic somatic MLH1 inactivation or as an independent event. Tumor-specific MMR immunohistochemistry (IHC) and MSI testing of the polypectomy specimen, which could not be performed for our case due to retrospective limitations, may have clarified this and informed immune checkpoint inhibitor (ICI) eligibility in the event of recurrence, given the established role of pembrolizumab in MMR-deficient CRC.¹⁵ We acknowledge this as a limitation. Separately, given the 36% nodal metastasis rate in surgically staged LGCC cases,⁷ cross-sectional staging imaging would have been warranted despite favorable histopathology.

The decision against colectomy was guided by favorable histopathology, complete en bloc resection with clear margins, prior bilateral salpingo-oophorectomy, and patient preference, consistent with NCCN guidance for pT1 CRC with favorable histologic features following curative-intent endoscopic resection.^16,17 Colonoscopy-based surveillance every 1-2 years remains the cornerstone of CRC risk reduction in LS, with current guidelines recommending initiation at the age 20-25 years or 2-5 years before the earliest familial CRC diagnosis.^16,18 Multidisciplinary tumor board review is recommended, and retrospective MMR immunohistochemistry and MSI testing should be pursued if specimen material remains available.

In conclusion, GALT/dome carcinoma is a rare, histologically distinct colorectal entity whose co-occurrence with Lynch syndrome, as illustrated in this case, creates a management challenge not currently addressed in established guidelines. Clinicians should recognize that GALT/dome carcinomas may fall within the broader LGCC spectrum and may, in a subset of cases, exhibit nodal metastasis or other high-risk features. In the setting of hereditary MMR deficiency, tumor-specific MSI and MMR immunohistochemistry testing of the polypectomy specimen is essential and should not be deferred. When high-risk features are absent and resection is complete, endoscopic surveillance is a reasonable management approach, with final decisions individualized through multidisciplinary discussion. Staging cross-sectional imaging could be obtained in cases of GALT/dome carcinoma arising in patients with Lynch syndrome, given the emerging data on nodal disease in the LGCC spectrum.⁷ Future research should focus on histomorphologic and molecular predictors of behavior in GALT/dome and LGCC tumors, with particular attention to the setting of hereditary cancer syndromes.

DISCLOSURES

Previous presentation: The case in the manuscript has been presented as poster at the American College of Gastroenterology Annual Scientific Meeting, October 27, 2025; Phoenix, Arizona.

Author contributions: V. Deshpande: Encountered the case in the topic, Review of literature, part of discussion and entire course of the case. A. Sharma: Majority of discussion, review of literature. A. Tiwari: Tables and Introduction. JS Mupparaju: Critical review and part of discussion. T. Bodla: Abstract and critical review. DS Dahiya: Senior author, guidance and final approval of manuscript. V. Deshpande is the article guarantor.

Informed consent was obtained for this case report.

Financial disclosure: None to report.