Enteropathy associated T cell lymphoma in celiac disease: a large retrospective study

Abstract

Introduction: Prognosis of enteropathy-associated T cell lymphoma is poor but predictors of survival remain ill-defined. How clinical presentation, pathological features and therapies influence outcome was evaluated in 37 thoroughly characterized patients with celiac disease and T-cell lymphoma.

Patients and methods: Medical files were studied retrospectively. Lymphoma and intestinal mucosa were analysed by histopathology, multiplex PCR and intestinal intraepithelial lymphocytes phenotyping. Survival and prognostic factors were analysed using Kaplan-Meier curves with Logrank test and Cox Model.

Results: Lymphoma complicated non clonal enteropathy, celiac disease (n=15) and type I refractory celiac disease (n=2) in 17 patients and clonal type II refractory celiac disease in 20 patients. Twenty-five patients underwent surgery with resection of the main tumour mass in 22 cases. In univariate analysis, non clonal celiac disease, serum albumin level>21.6g/L at diagnosis, chemotherapy and surgical resection predicted good survival (p=0.0007, p<0.0001, p<0.0001, p<0.0001, respectively). In multivariate analysis, serum albumin level>21.6g/L, chemotherapy and reductive surgery were all significantly associated with increased survival (p<0.002, p<0.03, p<0.03, respectively).

Conclusions: Our study underlines the prognostic value of celiac disease type in patients with T-cell lymphoma, and suggests that a combination of nutritional, chemotherapy and reductive surgery may improve survival.

Fig. 1

Histology and immunohistochemistry in intestinal EATL. (A,B) Case 9: HE staining demonstrates trans-parietal infiltration by ulcerative and invasive EATL (A: 16×) that is made of pleomorphic small to large-size lymphoid tumour cells and is associated with apoptotic bodies, eosinophils and plasma cells (B: 400×). (C–F) Case 23: (C) HE staining shows anaplastic-like EATL that contains many large tumour cells associated with some eosinophils and small lymphocytes (400×). (D–F) Immunohistochemical staining indicates that tumour cells express CD3 (D: 200×), Granzyme B (E: 200×) and CD30 (F: 200×) and reveals their immediate proximity to blood vessels.

Fig. 2

Histology and immunohistochemistry in extraintestinal and intramucosal EATL. (A,B) Case 32: (A) HE staining (50×) demonstrates lymph node infiltration by EATL. (B) Interfollicular zones are enlarged and infiltrated by lymphoid cells that stained with Granzyme B (100×). Foci of necrosis are visible (surrounded by arrows). (C,D) Case 37 (C) HE staining (200×) shows spleen infiltration by small to large-size lymphoid cells invading red pulp sinuses. Tumour cells expressed CD30 (D1: 400×), Granzyme B (D2: 400×) and CD103 (D3: 400×). (E,F) Case 15: early stage of transformation with massive infiltration of lamina propria and epithelium by medium to large-size lymphoid cells that express CD30 (E: 200×) and Granzyme B (F: 200×).

Fig. 3

EATL survival. (A) Kaplan–Meier curve of EATL survival according to the type of associated enteropathy. The dashed and solid curves represent the overall survival in patients with EATL associated with non clonal enteropathy (CD/RCDI) and EATL developed on clonal enteropathy (RCDII), respectively. (B) Kaplan–Meier curve of EATL survival according to the serum albumin level at diagnosis. The dashed and solid curves represent the overall survival in patients with serum albumin level > 21.6 g/L and patients with serum albumin level ≤ 21.6 g/L at diagnosis, respectively. (C) Kaplan–Meier curve of survival according to the realization of chemotherapy. The dashed and solid curves represent the overall survival in patients treated with chemotherapy and patients not treated by chemotherapy, respectively. (D) Kaplan–Meier curve of survival according to the realization of tumour resection surgery. The dashed and solid curves represent the overall survival in patients having tumour reductive surgery and patients without tumour reductive surgery, respectively.