The Reason Why We Should Differentiate Monomorphic Epitheliotropic T Cell Lymphoma and Intestinal T Cell Lymphoma, NOS - a Retrospective Study about the Experience of a Single Tertiary Hospital in Korea
Authors: Hyeon Jiyeon , Kim Changgon , Yoon Sang Eun , Kim Seok Jin , Ko Young Hyeh , Cho Junhun , Kim Won Seog 
Published: December 2024

Primary T or NK cell lymphoma of the gastrointestinal tract (GI-TNKL), including Monomorphic Epitheliotropic Intestinal T-cell Lymphoma (MEITL), Intestinal T-cell Lymphoma, NOS (ITCL-NOS), and Extranodal NK/T-cell Lymphoma (ENKTCL), is a rare and aggressive disease entity most commonly reported in Asia.

To investigate their clinicopathologic characteristics and clinical outcomes, we retrospectively collected a total of 215 cases of T or NK cell lymphoma involving the gastrointestinal tract from January 1, 2000, to December 31, 2023, at Samsung Medical Center, Seoul, Korea. Among these, 95 cases were considered to be primary gastrointestinal lymphoma rather than secondary involvement.

We conducted a comprehensive clinical and pathological study of 91 primary GI-TNKL cases, including ITCL-NOS (n=28), MEITL (n=44), and ENKTCL (n=19), excluding 4 cases of anaplastic large cell lymphoma.

Primary GI-TNKL occurred predominantly in adults, with a median age of 57.1 years and a slight male predominance (58 males, 33 females). The most common histologic type was MEITL (48.4%), followed by ITCL-NOS (30.8%) and ENKTCL (20.8%). The small intestine was the most frequently affected region in MEITL (72.7%) and ENKTCL (47.4%), while the stomach was the most common site in ITCL-NOS (50.0%). MEITL and ENKTCL frequently presented with intestinal perforation (MEITL: small intestine, 61.4%; large intestine, 4.5%; ENKTCL: small intestine, 47.4%; large intestine, 10.5%) and required emergency surgery.

B symptoms were slightly more common in ENKTCL (36.8%) compared to ITCL-NOS (10.7%) and MEITL (22.7%). Bone marrow and CNS involvement were rare across all types of GI-TNKL (14.3% and 12.1%, respectively). ITCL-NOS predominantly presented as localized disease (Lugano stage I/II, 78.6%; stage IV, 21.4%), whereas MEITL and ENKTCL often involved multiple intestinal sites, leading to more unfavorable characteristics such as advanced stage at diagnosis. Consequently, the 3-year overall survival (OS) rate was significantly lower for MEITL (23.8%) and ENKTCL (26.3%) compared to ITCL-NOS (53.8%; P &lt; 0.05). There was no significant difference in the 3-year OS rate between MEITL and ENKTCL, although the median OS of MEITL (16.3 months) was longer than that of ENKTCL (7.1 months).

The median overall survival (OS) was 69 months for ITCL-NOS, 16.3 months for MEITL, and 7.1 months for ENKTCL. The median progression-free survival (PFS) was 19.2 months for ITCL-NOS, 4.4 months for MEITL, and 2.1 months for ENKTCL.

Patients who underwent hematopoietic stem cell transplantation (HSCT) had better OS compared to those who did not (1-year OS rate: 85.7% vs. 50.9%, P = 0.0003; 2-year OS rate: 61.2% vs. 34.0%, P = 0.0283). Independent poor prognostic factors included histologic diagnosis (MEITL, ENKTCL), fever as an initial symptom, presence of life-threatening manifestations (GI perforation, bleeding, GI sepsis/peritonitis), involvement of multiple intestinal sites (especially more than 4 lesions), performance status ≥ 2, elevated serum lactate dehydrogenase, and Lugano stage IV. Multivariate analysis identified histologic diagnosis (MEITL, ENKTCL), fever as an initial symptom, presence of massive GI bleeding, primary small intestinal lymphoma, and involvement of multiple intestinal sites as having a strong negative impact on treatment outcomes.

Patients with gastric involvement had better survival outcomes compared to those with involvement in other sites, which may be related to anatomical and histologic characteristics, the proportion of life-threatening manifestations, and the need for surgical resection or intervention.

Targeted sequencing performed on 11 MEITL and 4 ITCL-NOS cases revealed that 8 of 11 MEITL cases (72.7%) and 2 of 4 ITCL-NOS cases (50%) harbored deleterious mutations in the SETD2 gene.

GI-TNKL is characterized by aggressive behavior with short progression-free survival and overall survival. This comprehensive clinical and pathological analysis will aid in the accurate understanding, diagnosis, and treatment of this disease.