Chinese Journal of Practical Internal Medicine
Deserving its name is still
Keywords:monomorphic epitheliophilic intestinal T-cell lymphoma; small intestinal ulcer; small intestinal villous atrophy
Keywords: monomorphic epitheliotropic intestinal T-cell lymphoma; small bowel ulcers; small bowel
monomorphic intestinal epithelium T Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) originates from malignant tumors of intestinal intraepithelial T lymphocytes. This disease is relatively rare in clinic, with an incidence rate of less than 0.1/100,000, accounting for less than 5% of intestinal lymphomas. The typical endoscopic manifestations are multiple deep and large ulcers, which can show penetrating changes, while MEITL with mild lesions Diagnosis is more difficult. Here is a summary and discussion of the diagnosis and treatment process of a MEITL patient with diarrhea as the first symptom and mild lesions under endoscopy in our hospital.
1Case data
Female patient, 67 years old , was admitted to hospital due to “diarrhea for more than 9 months”. The patient developed diarrhea without obvious incentives since July 2020, 4-5 times a day, watery stools, no mucus, pus and blood, no black stools, no abdominal pain, abdominal distension, and no chills and fever. In August, he visited a local hospital and completed the colonoscopy examination prompt: colon polyps, and underwent intestinal EMR treatment. The postoperative diarrhea symptoms did not improve. In October, the symptoms of diarrhea worsened, about 10 times per day, up to 20 to 30 times per day, and the nature was the same as before. He went to the local hospital again to complete the small bowel CT (unenhanced scan + enhanced): no obvious abnormality was found. He was then treated with montmorillonite powder, probiotics, berberine, compound glutamine, and traditional Chinese medicine prescriptions, but the symptoms did not improve. By the time of admission, the patient had been suffering from diarrhea for more than 9 months and lost about 20 pounds in weight.
The patient had a history of hypertension for 10 years, type 2 diabetes for 2 years, and a history of cerebral infarction for more than 5 years, with no obvious sequelae. No history of other chronic diseases, infectious diseases, other surgical trauma, no history of blood transfusion, and history of food and drug allergies. Physical examination on admission: T 36.7°C, P 84 times/min, R 18 times/min, Bp 130/78 mmHg, conscious, height 164 cm, weight 51 kg, BMI 18.9 kg/m2 , no lower extremity edema. Cardiopulmonary examination was negative. Abdominal examination: Abdominal soft, no tenderness, rebound tenderness, no muscle tension. No hepatosplenomegaly. Bowel sounds are active, 8 to 10 times/min. Nervous system examination: normal physiological reflexes, normal muscle strength and muscle tone, and negative pathological signs.
Routine examination after admission: fecal occult blood test was positive; fecal calprotectin 193.52 μg/g; biochemistry: total protein 40.2 g/L, albumin 23.8 g/L, globulin Protein was 16.4 g/L; no obvious abnormality was found in blood routine, urine routine, coagulation function, and transfusion. Tumor and immune-related indicators: five immune items: IgG 5.32 g/L, IgM 0.211 g/L; serum KAP light chain 4.01 g/L, LAM light chain 1.81 g/L, urinary KAP 29.0 mg/L; tumor markers, The three items of rheumatism, serum protein electrophoresis, and serum immunofixation electrophoresis showed no abnormality; antinuclear antibody, anti-ENA antibody, anticardiolipin antibody, anticentrocyte cytoplasmic antibody, and chronic inflammatory bowel disease antibody were all negative. Infection-related indicators: PCT 0.064 ng/mL, serum EBV-DNA 7.72×103copies/mL, stool Clostridium difficile positive; T-SPOT positive, tuberculosis antibody negative , CRP was normal, CMV, fecal bacterial/fungal smear and culture were negative. Thyroid function FT3 was 3.07 pmol/L, VitB12 was 81 pmol/L, BNP and myocardial markers were normal.
Peroral double-balloon enteroscopy showed obvious atrophy of duodenum and jejunum villi with scallop-like changes, and an irregular ulcer at the level of the duodenum with local Circumferential stenosis of the lumen (see Figures 1a-c). Transanal double-balloon enteroscopy revealed ileal villous atrophy and diffuse lymphangiectasia (Fig. 1d–f).
（The picture in the text, click to see the big picture↓↓↓）
Figure 1 Double-balloon enteroscopy
PET/CT examination: abdominal and pelvic cavity The intestinal tube (including the small intestine and colorectum) has diffusely increased FDG metabolism, and the intestinal wall of some lesions is thickened, and the possibility of intestinal malignant lesions is considered (see Figure 2).
Figure 2 PET/CT
Pathology of small bowel biopsy (duodenum, jejunum) with villous atrophy and crypt hyperplasia , crypt and surface intraepithelial lymphocytes increased; tumor cell morphology was single, with small-medium-large nuclei, round nuclei, hyperchromatic, light cytoplasmic staining, showing pro-epithelial appearance (see Figure 3); special staining: PAS (- ), Congo red (-); individual acid-fast stained positive rods were seen under acid-fast staining microscope. T cell receptor gene rearranged clone (+), immunoglobulin heavy chain/light chain gene rearranged clone (-) .(duodenum, jejunum) immunohistochemistry: CD3 (+), CD4 (sporadic +), CD5 (sporadic +), CD8 (+), CD56 (focus +), TIA-1 (+), Granzyme B (stove+), CD79(+) (see Figure 4).
Figure 4 Small intestine immunohistochemistry (×200)
No abnormal lymphocytes were found in bone marrow biopsy, and bone marrow flow cytometry, No abnormality was found in TCR rearrangement and chromosomal analysis, and peripheral lymphoma could be excluded. The diagnosis was confirmed as: monomorphic epitheliophilic intestinal T-cell lymphoma. He was subsequently transferred to the Department of Hematology for further treatment, and has completed the second cycle of CHOP program, specifically: prednisone 45 mg d1-5 + cyclophosphamide 0.8 g + epirubicin 80 mg + vindesine 3 mg, and she is still closely followed up among.
2Discussion
There are many types of intestinal lymphomas , the manifestations are diverse, and the clinical diagnosis is difficult. This case presents a chronic course with progressive aggravation. The clinical symptoms are mainly diarrhea, accompanied by obvious hypoalbuminemia and opportunistic infections. Therefore, the diagnosis should be considered around autoimmune enteritis, celiac disease, lymphoma, and small bowel Crohn’s disease. , Infectious diarrhea for differential diagnosis. Further through enteroscopy, the endoscopic manifestations of small intestinal ulcer, small intestinal villous atrophy, and lymphatic dilatation were found, and the etiology of small intestinal ulcer was further discussed.
In recent years, with the development of enteroscopy technology, the detection rate of small intestinal ulcers has increased significantly. Small intestinal ulcers[1] can be found in a variety of diseases, including Crohn’s disease, non-steroidal anti-inflammatory drug (NSAID)-associated enteritis, nonspecific multiple intestinal ulcer disease (chronic enteropathy associated with SLCO2A1 gene, CAES), cryptogenic Multifocal ulcerative stenosing enteritis (CMUSE), lymphoma, immune-related (vasculitis, primary systemic amyloidosis, systemic lupus erythematosus, etc.), celiac disease, etc. In this case, the small bowel endoscopy showed special findings. PET/CT showed diffusely elevated intestinal FDG metabolism, and malignant lesions were possible. Small bowel biopsy showed high lymphoid tissue hyperplasia and TCR (+). Finally, immunohistochemistry was used to confirm the diagnosis of monocytogenes. Epitheliophilic intestinal T-cell lymphoma.
MEITL[2,3] is a relatively rare peripheral T-cell lymphoma, which is independently classified in the “2016 WHO Guidelines for Lymphoid Hematopoietic System”. It is more common in males, with a male-to-female ratio of 2.25:1, and a median age of 58 years. The main symptoms are abdominal pain, diarrhea, fever, and weight loss. In most cases, typical intestinal lesions can be observed at the time of diagnosis. Endoscopically, they appear as multiple deep and large ulcers, which may show penetrating changes. Thickening of the bowel wall and stiffness of the bowel. Wang Yanan et al. summarized the characteristics of 6 cases of MEITL with mild endoscopic lesions diagnosed and treated in Peking Union Medical College Hospital from 2012 to 2016 [4]. In clinical manifestations, diarrhea was the first symptom, accompanied by weight loss; small bowel CT imaging showed continuous intestinal lesions, symmetric intestinal thickening, abnormal enhancement of mucosal surface, and enlarged lymph nodes; cases of small bowel involvement under endoscopy may manifest as small intestinal villi Shortening, white lymphangiectasia, mosaic sign, and irregular shallow ulcers were not significant; pathologically, there were single, small to medium-sized tumor cells in the lesion area, with crypt epithelial infiltration, and villous atrophy and crypt hyperplasia in the adjacent mucosa. and increased intraepithelial lymphocytes; immunophenotype: CD3, CD8, CD56, Granzyme B, TIA-1, TCR gene rearrangement was positive. Reviewing this case, its clinical symptoms, imaging, and endoscopic findings are consistent with the characteristics of MEITL with mild microscopic lesions. However, this type of cases lacks characteristic manifestations, which brings difficulties and challenges to diagnosis.
Currently, there is no unified standard for MEITL treatment. Chemotherapy alone is more commonly used. The most widely used regimen is CHOP, but the overall prognosis is poor. The latest study revealed potential targets for MEITL therapy through whole-genome sequencing [5]. The study found: a total of 338 non-blind protein-coding mutations in MEITL cases, microsatellite instability and hypermutation were not detected; in CREBBP, Repeated mutations were detected in STAT5B, SETD2, GNAI2, JAK3, and AXSL3; based on sequencing results, we have successfully constructed a PDX tumor model that retains known driver mutations, including STAT5B, JAK3, SETD2, DUSP14, and CREBBP, It is believed that further research on this basis will help to further clarify the mechanism of the disease and develop targeted drugs.
References
[1] KEUCHEL M, KURNIAWAN N, BALTES P. Small bowel ulcers: when is it not inflammatory bowel disease ?[J]. Curr Opin Gastroenterol, 2019, 35(3): 213-222.
[2] SOARDO G, CASTALDO V, DONNINI D, et al. Monomorphic Epitheliotropic Intestinal T Cell Lymphoma of the Appendix: a Case Report and Review of Literature[J]. J Gastrointest Cancer, 2020, 51( 2): 688-694.
[3] HASHIMOTOR R, MATSUDA T. Gastrointestinal: Endoscopic findings of monomorphic epitheliotropic intestinal T-cell lymphoma[J]. J Gastroenterol Hepatol, 2019, 34(2): 311.
[4] Wang Yanan, Li Ji, Ni Yuehui, et al. Monomorphic epitheliophilic intestinal T in mild lesions under endoscopy Clinical characteristics of cell lymphoma[J]. Chinese Journal of Internal Medicine, 2018, 57(2): 112-117.
[5] HUANG D, LIM JQ, CHEAH D , et al. Whole-genome sequencing reveals potent therapeutic strategy for monomorphic epitheliotropic intestinal T-cell lymphoma[J]. Blood Adv, 2020, 4(19): 4769-4774.
< /p>Chinese Journal of Practical Internal Medicine
Real Deserving of the Name< /span>
use < span>Anyone is still
If you like it, click ”