Imaging findings of primary monomorphic epitheliotropic intestinal T-cell lymphoma: A case report

Abstract

BACKGROUND

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is an uncommon and highly aggressive form of lymphoma that represents less than 1% of all non-Hodgkin’s lymphomas. At present, few reports have focused on the imaging findings of MEITL, which poses significant challenges for clinical diagnosis.

CASE SUMMARY

A 78-year-old female with recurrent vomiting and abdominal distension was admitted to our hospital. Magnetic resonance and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) examinations revealed multiple segmental malignant tumors in the small intestine with mesenteric lymph node metastasis. An endoscopic biopsy revealed MEITL. After three cycles of reduced-dose cyclophosphamide, vinorelbine, and prednisone chemotherapy, follow-up ¹⁸F-FDG PET/CT demonstrated a partial response to treatment. The patient was still alive after 6 months of follow-up.

CONCLUSION

Magnetic resonance imaging serves as a valuable tool in detecting malignant tumor lesions of MEITL, whereas ¹⁸F-FDG PET/CT offers additional assistance in tumor staging and assessing treatment efficacy.

Key Words: Intestinal cancer; T-cell lymphoma; Imaging findings; ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography; Case report

Core Tip: Monomorphic epitheliotropic intestinal T-cell lymphoma is an uncommon and highly aggressive form of lymphoma, making it challenging to distinguish this disease from other intestinal-related disease in clinical practice. In this case, we present the magnetic resonance and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography details of a 78-year-old female patient who presented with recurrent vomiting and abdominal distension. After completing three cycles of reduced-dose cyclophosphamide, vinorelbine, and prednisone regimen chemotherapy, the follow-up ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography revealed partial response in treatment efficacy. We further summarized the imaging findings of monomorphic epitheliotropic intestinal T-cell lymphoma reported previously in the literature.

INTRODUCTION

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is an uncommon and highly aggressive form of lymphoma originating in the intraepithelial lymphocytes of the gastrointestinal tract and accounts for less than 1% of all non-Hodgkin’s lymphomas[1]. In accordance with the 2022 5^th edition of the World Health Organization classification of hematologic malignancies, intestinal T-cell and natural killer cell lymphoid proliferations and lymphomas are classified into five subtypes: Enteropathy-associated T-cell lymphoma (EATL), MEITL, indolent clonal T-cell lymphoproliferative disorder of the gastrointestinal tract, indolent natural killer cell lymphoproliferative disorder of the gastrointestinal tract, and intestinal T-cell lymphoma not otherwise specified[2]. MEITL, previously referred to as type II EATL, is more prevalent among Asian populations and is not associated with celiac disease[3]. However, type I EATL is more common in Western regions and is linked to celiac disease[3]. The early clinical symptoms of MEITL are insidious, with most patients being diagnosed at an advanced stage and having a median survival time of only 7 months[4]. Treatment options for non-Hodgkin’s lymphomas include: Chemotherapy, radiation therapy, immune checkpoint inhibitors, bispecific T-cell engagers, chimeric antigen receptor T cell therapy and allogeneic hematopoietic stem cell transplantation[5]. Owing to the rarity of MEITL, only a handful of medical imaging reports exist in the literature, which poses significant challenges for clinical diagnosis. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is considered the standard imaging modality for the diagnosis, staging and response assessment of lymphoma. Under these circumstances, we present a patient with MEITL who underwent ¹⁸F-FDG PET/CT, magnetic resonance (MR) and gastroduodenoscopy examinations. We further discuss the differential diagnosis and therapeutic approaches of MEITL, aiming to foster a deeper understanding of the disease.

CASE PRESENTATION

Chief complaints

A 78-year-old female patient was admitted with recurrent vomiting and abdominal distension for more than 20 days.

History of present illness

The patient developed discomfort with vomiting 20 days prior, usually 1-2 hours after eating. The vomit consisted of gastric contents accompanied by abdominal distension without fever, chills, diarrhea, abdominal pain or other discomfort. Her recent weight loss was 10 kg. For the past six months, the patient had a decreased appetite and intermittent diarrhea.

History of past illness

There was no special abnormality in the patient’s past medical history.

Personal and family history

The patient reported no family history of malignant tumors.

Physical examination

Her vital signs were as follows: Temperature 36.8 °C, blood pressure 117/65 mmHg, heart rate 76 bpm, and respiratory rate 20 rpm. Physical examination revealed no abnormal signs.

Laboratory examinations

Laboratory tests revealed increased white blood cells (11.64 × 10⁹/L), β2-microglobulin (3.26 μg/mL) and platelet count (466 × 10⁹/L); decreased red blood cells (3.77 × 10¹²/L) and hemoglobin (101 g/L); and a positive fecal occult blood test. β2-microglobulin is abundant in lymphocytes and therefore considered a major marker of lymphocyte proliferative diseases. In clinical practice, elevated levels of β2-microglobulin associated with poor prognosis in lymphoma patients[6].

Imaging examinations

¹⁸F-FDG PET/CT revealed multiple segmental thickening in the descending and horizontal segments of the duodenum, jejunum, and ileum. The horizontal segment of the duodenum had the largest lesion, approximately 5 cm × 4 cm in size. The intestinal tract showed aneurysmal dilatation with stenosis and obstruction of the intestinal lumen, and the maximal standardized uptake value (SUV_max) was 9.2 (Figure 1). The SUV_max reflects the uptake of ¹⁸F-FDG and the metabolic activity of the lesion. Multiple enlarged lymph nodes were found in the abdominal and pelvic mesentery. The largest lesion was 0.9 cm × 0.7 cm in size, with an SUV_max of 3.1 (Figure 1). A plain MR scan of the upper abdomen revealed that the larger lesion in the horizontal segment of the duodenum presented an iso-signal on T₁ weighted imaging (T₁WI) and an iso- or hypo-signal on T₂WI. It was hyperintense on diffusion-weighted imaging, and the apparent diffusion coefficient was 0.8 × 10^-3 mm²/second. Post-contrast MR imaging (MRI) demonstrated delayed and homogeneous enhancement (Figure 2). Gastroduodenoscopy revealed cauliflower-like masses in the duodenal lumen, marked narrowing and obstruction of the intestinal lumen (Figure 3).

Figure 1 ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography findings of monomorphic epitheliotropic intestinal T-cell lymphoma. A-L: Multiple segmental thickenings were observed in the descending and horizontal segments of the duodenum, jejunum, and ileum, accompanied by enlarged lymph nodes scattered throughout the abdominal and pelvic mesentery; M: Functional images of the abdomen at the positron emission tomography level before treatment; N: After completing three cycles of chemotherapy, the patient underwent a follow-up ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography scan, which revealed a decrease in multiple lesions in the small intestine as well as a reduction in enlarged mesenteric lymph nodes.

Figure 2 Magnetic resonance imaging findings of monomorphic epitheliotropic intestinal T-cell lymphoma. A: The lesion in the horizontal segment of the duodenum showed an iso-signal on T₁ weighted imaging; B: Iso- or hypo-signals on T₂ weighted imaging; C: Limited diffusion on diffusion-weighted imaging; D: Apparent diffusion coefficient value of 0.8 × 10^-3 mm²/second; E and F: Delayed enhancement on an enhanced scan.

Figure 3 Gastroduodenoscopy of monomorphic epitheliotropic intestinal T-cell lymphoma. A cauliflower-like mass was found in the duodenal lumen, resulting in significant stenosis and obstruction of the intestinal lumen.

An endoscopic biopsy of the lesion located in the descending segment of the duodenum suggested a T-lymphoproliferative lesion. Microscopically, the atypical lymphoid cells were diffusely proliferated, with round or irregular nuclei, thick chromatin, and scattered plasma cells. The immunohistochemical marker results were as follows: CD2 (+), CD3 (+), CD5 (+), CD7 (+), CD8 (+), CD56 (+), CD4 (-), CD20 (-), cytokeratin (-), T-cell intracellular antigen 1 (+), granzyme B (+), Epstein-Barr virus-encoded small RNA (-), and Ki-67 (60%+) (Figure 4). Gene rearrangement suggested that T cell receptor β and T cell receptor γ were positive. Bone marrow aspiration biopsy did not reveal evidence of neoplastic involvement.

Figure 4 Histopathological and immunohistochemical examination of monomorphic epitheliotropic intestinal T-cell lymphoma. A: Atypical lymphoid cells were diffusely proliferated, with round or irregular nuclei, thick chromatin, and scattered plasma cells (hematoxylin eosin × 40); B: Positive in CD3 (× 40); C: Positive in CD8 (× 40); D: Positive in CD56 (× 40); E: Positive in granzyme B (× 40); F: Positive in T-cell intracellular antigen 1 (× 40).

FINAL DIAGNOSIS

The final pathology diagnosis revealed MEITL (Figure 4). ¹⁸F-FDG PET/CT revealed retroperitoneal and mesenteric lymph node metastasis. According to the Lugano staging criteria, version 2014, the stage was II.

TREATMENT

Given the patient's advanced age, we used a reduced-dose cyclophosphamide, vinorelbine, and prednisone (CVP) chemotherapy regimen: Cyclophosphamide 500 mg/m² (day 1), vinorelbine 20 mg/m² (day 1), and prednisone 60 mg/m² (day 1-day 5). The cycle of treatment lasted for 21 days.

OUTCOME AND FOLLOW-UP

After the first course of chemotherapy, the patient’s clinical symptoms were significantly relieved. After completing three cycles of chemotherapy, the patient underwent a follow-up ¹⁸F-FDG PET/CT scan, revealing a decrease in multiple lesions in the small intestine as well as a reduction in the enlarged mesenteric lymph nodes (Figure 1). The efficacy was evaluated as a partial response. The patient was still alive after 6 months of follow-up.

DISCUSSION

According to the 2022 World Health Organization classification of hematologic malignancies, MEITL is a rare subtype of intestinal T-cell proliferative lymphoma formerly known as type II ETAL[2]. To our knowledge, approximately 300 cases have been reported worldwide to date. MEITL is caused by the malignant proliferation of intraepithelial lymphocytes, with an average age of approximately 60 years at first diagnosis and a male to female ratio of approximately 2:1[1,7]. The most common site of MEITL is the small intestine[7]. The early clinical symptoms of MEITL are insidious and can manifest as nonspecific intestinal symptoms, such as abdominal pain and bowel dilatation[1]. Therefore, most MEITLs are found at an advanced stage with an extremely poor prognosis: the median survival time of MEITLs is only 7 months, and the 1-year overall survival rate is only 36%[4].

Currently, there are few imaging reports on MEITL. The previously reported cases are shown in Table 1. According to previous reports, MEITL can involve the whole intestine, with increased FDG uptake in the lesion and an SUV ranged 3.3 to 10.2[8]. Our patient also presented with multiple lesions in the small intestine, with a SUV_max of 9.2, which is consistent with previous reports in the literature. Intestinal lymphoma typically does not involve organ metastasis. However, in rare instances, MEITL may metastasize to the lung, liver, central nervous system and bone marrow[8-11]. MR examination shows iso- or hypo-signals on T₂WI and limited diffusion on diffusion-weighted imaging, which is attributable to the abundance of tumor cells and the diminished concentration of extracellular fluid. On an enhanced scan, MEITL exhibits delayed and homogeneous enhancement, which is similar to the performance in a previous report[8]. These findings suggest that MEITL is generally characterized by the absence of necrosis. A search of the PubMed database found five case reports of MEITL that presented with MRI and/or ¹⁸F-FDG PET/CT findings (Table 1)[8-10,12,13].

Table 1 Previous case reports of magnetic resonance and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography findings in monomorphic epitheliotropic intestinal T-cell lymphoma.

Ref.	Age/sex	Symptom	Location	Imaging findings	Treatment	Outcome, month
[8]	48/F	Abdominal pain, diarrhea, distension, dysuria, frequency, and urgency	Entire small bowel, part of the colon, and rectum. Infiltration of the spleen, skeleton, liver and some mesenteric lymph nodes	Iso or hypo-intensity on T2WI, reduced diffusion on DWI, low signal intensity on ADC map, and markedly homogeneous enhancement. Increased FDG-uptake (SUVmax 4.0-10.2). The spleen, skeleton, liver and some swollen mesenteric lymph nodes were also FDG-avid	Only received anti-infection, nutrition support, and hormone therapy	3 (dead)
[9]	74/M	Acute onset of left hemiparesis and diarrhea	The small intestinal of the pelvic cavity. Involving the lung and brain	PET-MRI revealed high 18F-FDG accumulation in a mass in the pelvic cavity (SUVmax of 12.9), the right cerebral hemisphere with SUVmax of 8.3, bilateral lungs (SUVmax of 11), and mediastinal lymph nodes (SUVmax of 8.6)	Transferred to outpatient clinic for palliative care	Absent
[10]	57/M	Bloody diarrhea, abdominal pain, and urological symptoms, including dysuria, frequency and urgency	The ileocecum, entire colon, and rectum	Increased FDG activity (SUVmax of 14.5). Multiple pulmonary nodules and ground-glass opacities in both lungs with intense FDG uptake (SUVmax of 14.8) and abnormal hypermetabolism in the prostate (SUVmax of 5.6)	Chemotherapy	1.5 (dead)
[12]	56 (ranged 39-70)/8M, 4F	Abdominal pain, abdominal distension, ascites, intestinal obstruction, diarrhea, intestinal perforation, weight loss and gastrointestinal bleeding	The stomach, small bowel and large bowel. Lymph nodes and other organs were involved in 58% of cases. Thoracic and brain were frequently involved	The SUVmax of the stomach, small bowel and large bowel lesions varied from 3.6 to 8.7. The SUVmax of regional lymph nodes varying from 0.9 to 5.3	Chemotherapy	The median survival was 13 (1-136) months
[13]	61/M; 35/F	Upper abdominal pain and intermittent black stool; abdominal distention	Small intestine and upper sigmoid colon	Increased metabolism in 18F-FDG PET/CT. Regional lymph nodes were also metabolically active	CHOP combined with chidamide; surgery combined with ifosfamide, etoposide, and vincristine and chidamide	15 (dead); 17 (alive)

F: Female; M: Male; T₂WI: T₂ weighted imaging; DWI: Diffusion-weighted imaging; ADC: Apparent diffusion coefficient; CHOP: Cyclophosphamide, doxorubicin, vincristine, and prednisone; ¹⁸F-FDG PET/CT: ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography; MRI: Magnetic resonance imaging; SUV: Standardized uptake value.

MEITL should be differentiated from Crohn’s disease (CD), intestinal B-cell lymphoma and intestinal carcinoma in imaging diagnosis. The present patient presented with multiple segmental thickening of the small intestine, similar to the imaging findings of “skip distribution” in patients with CD. Although CD also manifests as intestinal wall thickening and FDG uptake, there is no obvious intestinal dilatation. Epelboym et al[14] reported that the average SUV ratio (SUV_max/liver SUV_mean) in eight patients with CD before treatment was 3.16 (range 1.88-4.6). The SUV ratio in our patient was 5.4, which was greater than that in patients with CD. On contrast-enhanced CT, CD may present enlargement and thickening of the mesenteric vessels. Moreover, the onset of CD is gradual, and the course of the disease is relatively long, CD can be complicated by abscesses and fistula formation and can involve extraintestinal organs, such as the mouth, eyes and joints[15]. The characteristic finding of CD under endoscopy is cobblestone-like ulceration[15]. Most intestinal B-cell lymphomas are localized lesions, and the SUV_max (mean ± SD) of B-cell lymphoma (14.1 ± 6.4) is significantly greater than that of T-cell lymphoma (7.6 ± 3.9)[16], which is helpful for their differentiation. The focus of intestinal carcinoma is relatively limited, causing focal intestinal concentric stenosis or asymmetric intestinal stenosis. Intestinal carcinoma rarely involves multiple segments; however, it is prone to invade the surrounding fat space and adjacent organs and hematogenously metastasize to the liver and lungs. MEITL is more likely to manifest as aneurysmal dilatation at multiple sites and generally does not result in fat space infiltration around the intestine.

The imaging differential diagnosis of MEITL from ETAL is difficult because of their rarity and limited reference data. On PET/CT, EATL typically presents as hypermetabolic lesions (SUV_max of 6.4-8.0), combined with a background of diffuse low FDG uptake (SUV_max of 2.2-4.6) related to celiac disease[17]. However, MEITL lesions present as discrete hypermetabolic lesions without a background of low FDG uptake, as they are not associated with celiac disease[12]. The final diagnosis depends on pathological examination. There is an absence of standard treatment guidelines for MEITL because of its rarity. In previous reports, cyclophosphamide, doxorubicin, vincristine, and prednisone was the most commonly used chemotherapy[18]. For elderly EMITL patients, our reduced-dose CVP chemotherapy regimen also appeared to be an appropriate treatment, and the patient achieved a partial response after treatment. However, further follow-up studies with larger sample sizes are needed.

CONCLUSION

This article comprehensively describes the imaging findings of MEITL. MRI serves as a valuable tool in detecting malignant MEITL lesions, whereas ¹⁸F-FDG PET/CT offers additional assistance in tumor staging and assessing treatment efficacy. For elderly EMITL patients, a reduced dose of the CVP regimen is an alternative therapeutic approach. Given the rarity of MEITL, no standard treatment method for MEITL exists, highlighting the need to establish standardized treatment protocols in future studies.