Survival Determinants in Primary Intestinal NK/T-Cell Lymphoma (PINKTCL): Analysis of a Pooled Database

Introduction: PINKTCL is a less common presentation of extranodal, extranasal NK/T-cell lymphoma which arises along any segment of the gastrointestinal tract. PINKTCL is a rare and rapidly progressive disease with a poor prognosis. It is commonly associated with EBV infection and displays angiotropism and necrosis. PINKTCL affects younger adults and is not associated with pre-existing enteropathy. We conducted this exploratory analysis to delineate key disease characteristics and clinicopathologic determinants of survival in this rare NK/T-cell entity.

Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 126 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS).

Results: A total of 126 patients with confirmed PINKTCL were identified and analyzed. The median age of the sample was 39 years, with a peak incidence occurring between ages 34 and 48. Males were predominantly afflicted with an M:F ratio of 2.7. The colorectum and ileocecum were the most involved sites. The median overall survival (OS) of the whole group was 6 months. PINKTCL commonly presented with abdominal pain, GI bleeding, and perforation. The majority of cases were at stages I&IE (56%). The median duration of symptoms prior to diagnosis was 6 months. The median OS of surgery alone, chemotherapy alone, and surgery and chemotherapy were 2, 6, and 10 months respectively (p=0.002). OS was not impacted by age, sex, presentation with obstruction, anatomic site involvement, or stage. While constitutional symptoms, perforation, non-ileocecal GI involvement, EBER+, and CD56+ seemed to impact OS negatively, they did not reach statistical significance. Surprisingly, CD4 expression despite CD56+ conferred a significantly longer overall survival (18 vs. 6 months), raising the possibility of a separate and less aggressive entity.

Conclusions: This study presents an updated clinicopathologic data from a pooled cohort of patients with PINKTCL. It identifies CD4+ status and surgical resection in conjunction with chemotherapy as major determinants of OS in this rare disease.