Case Report

Jejunal Intussusception from Polypoid Formation of Primary Intestinal Lymphoma in Crohn’s Disease: Case Report and Literature Review

Giungato S*, De Luca GM, Borrello G, Mazzoccoli G, Marangi G, Piscitelli D, Scoletta C and Pepe AS

Giungato S1*, De Luca GM2, Borrello G3, Mazzoccoli G3, Marangi G4, Piscitelli D5, Scoletta C1 and Pepe AS1
1Unit of Surgery and Endoscopy, Department of Emergency Surgery, San Pio Hospital, Italy
2Unit of Surgery, Department of Emergency Surgery, Camberlingo Hospital, Italy
3Unit of Radiology, Department of Emergency, San Pio Hospital, Italy
4Unit of Pathology, Department of Emergency Surgery, SS. Annunziata Hospital, Italy
5Unit of Pathology, Department of Emergency Surgery and Organ Transplantation, University Medical School, Italy

Background: Crohn’s disease is a type of clinical form of inflammatory bowel disease represented by chronic gastrointestinal disorder caused by an inappropriate immune-mediated response and primary gastrointestinal lymphoma accounts for 4% to 20% of all non-Hodgkin’s lymphoma cases, above all B-cell lymphoma, in CD patients.
Case report: A 49-year-old woman, affected by Crohn’s disease, was admitted for the second time, after 21 months, at our Surgical Emergency Unit for acute abdomen for bowel occlusion. The patient had not been submitted to biological therapy. She was submitted to CT-Scan and PET-CT that showed pseudo-aneurismatic dilatation of bowel. Jejunal-jejunal intussusception in the site of previous anastomosis was observed with histological diagnosis of T-cell Non-Hodgkin Intestinal Lymphoma. Discharged after 16 days and she died after 3 months.
Methods: We have compared our case with the literature for the presence of intestinal lymphoma in CD that has not been submitted to biological therapy, matching terms: Crohn’s disease and intestinale lymphoma case report; Crohn’s disease and intestinal lymphoma; Crohn’s disease and bowel lymphoma; Crohn’s disease and primary intestinal lymphoma.
Results: Analysis of 58 cases (including the present study) showed these characteristics: 41 male (70%) and 17 female (30%); middle age: 46,9 yr (range 12 – 84); Patients submitted to surgery: 13/32 (40%), not all studies reported this date; History of CD: 7,7 yr (range 1 – 48); palpable mass at admission: 6/28 (21%).
Conclusions: The association between CD and intestinal lymphoma is rare, but during the follow-up of the patient, the development of this serious complication must never be excluded. This kind of pathological association is not related to biological therapy but to the disease itself and, surely, to the long duration of the Thiopurine therapy.


Keywords: lymphoma; Intussusception; Crohn’s disease; Surgery

Introduction
Crohn’s Disease (CD) is a type of clinical form of Inflammatory Bowel Disease (IBD) represented by chronic gastrointestinal disorder caused by an inappropriate immune-mediated response. 

The overall prevalence of inflammatory bowel disease (IBD) is approximately 0.4% in Europeans and North Americans [1]. Over the last years, the treatment of IBD patients has changed with the birth of new drugs as immunomodulator and biological therapy.

The advent of biological therapy has represented an important achievement in the management of the CD but a close correlation between the same therapy and the development of lymphoproliferative disorders seems to be reported in the literature.
The incidence of lymphoma in the general population ranges from 15 to 100 cases/100,000 person-years, increasing the risk with age and family history [2].

Primary gastrointestinal lymphoma accounts for 4% to 20% of all non-Hodgkin’s lymphoma cases, above all B-cell lymphoma [3]. 

There have been several small population-based studies which could not detect an increased risk of lymphoma in the IBD population but we present a case report of a young woman affected by CD presenting an occlusive syndrome by jejunal intussusception caused by polypoid formation in intestinal lymphoma. We have compared our case with the literature for the presence of intestinal lymphoma in CD that has not been submitted to biological therapy.

Clinical Case Description

In February 2015 a 49-year-old woman was admitted at our Surgical Emergency Unit for acute abdomen. CT-scan showed bowel obstruction, for this reason the patient was submitted to surgical operation in emergency. Occlusion was caused by 10 cm stenotic tract of bowel at one meter from Treitz’ ligament. A bowel resection of 75 cm was performed with jejunal-jejunal anastomosis. Patient was discharged after 10 days with oral feeding. The patient didn’t have post-operative complications.

Histology showed extensive full thickness mucosal ulceration, with massive widespread chronic inflammatory lymphoplasmacellular infiltrate with histiocytic, granulocyte neutophilic and eosinophilic co-participation, and fibroblastic reaction of all the stenotic tract of the bowel. Crohn’s disease was diagnosed.

The patient was treated with 5-ASA (Mesalazine) at 4.8 g/day for 16 weeks and after with maintenance dosage, thiopurine at dosage of 1.5 mg/kg/day for 6 months.

After 21 months of well-being, the patient was re-admitted to our Hospital in emergency for abdominal pain, fever and palpable mass at left side of abdomen with two episodes of diarrhea in the same week (CDAI: 281,89). She was submitted to CT-Scan and magnetic resonance of the abdomen that revealed suspected anastomotic recurrence with a pseudoaneurismatic jejunal dilatation and for this reason was administered high dosage (4.8 g/day) of 5-ASA and 30 mg/Kg/day of corticosteroids endovenous therapy. Patient presented remission of abdominal pain, normal bowel canalization, no fever and the presence of the abdominal mass was reduced. She was discharged after 15 days (CDAI: 243,29) and she continued home therapy with 5-ASA and Prednisone 2.4 mg/Kg/day.

After 3 months the patient was re-admitted to our Operating Unit for abdominal pain, fever and palpable mass. No canalization of bowel and she was submitted to a PET-CT scan that confirmed pseudo-aneurismatic dilatation of bowel (Figures 1 and 2). She was submitted to surgical operation after enteral feeding equal to 900 kcal/day and total parenteral nutrition equal to 1700 kcal/day for one week.

Jejunal-jejunal intussusception in the site of previous anastomosis was observed. Transverse mesocolon ligament near the left colic flexure was occupied by a great neoplastic lesion of 20 cm diameter localized in the left hemiabdomen involving epiploon, Treitz’s ligament and descending colon (Figures 3-5). Multiple tough lymphnodes and ascitic fluid were highlighted. Jejunal intussusception was resected, approximately 30 cm of jejunum, and L-L jejunal-jejunal anastomosis was performed to solve bowel obstruction and cytological examination of ascitic fluid was drawn.

Histological findings showed “jejunal intussusception with polypoid formation of 6.5 cm diameter, hard consistency, compatible with T-cell Non-Hodgkin Intestinal Lymphoma” (Figures 6-8).

The patient had no post-operative complications and was discharged after 16 days. She was submitted to chemotherapy but she died after 3 months.

Materials and Methods

Literature analysis for systematic review was performed using main databases (Pubmed; Medline) matching terms: Crohn’s disease and intestinale lymphoma case report; Crohn’s disease and intestinal lymphoma; Crohn’s disease and bowel lymphoma; Crohn’s disease and primary intestinal lymphoma. Inclusion criteria of studies were: Paper written in English language; clinical cases of patients not submitted to biological therapy; case reports of patients affected by Crohn’s disease and intestinal lymphoma. Exclusion criteria were: Studies not written in English language; studies reporting only phisiopathological mechanisms; case reports of patients submitted to biological therapy; clinical cases reporting patients with other comorbidities.

Results

881 studies have been analysed: Crohn’s disease and intestinal lymphoma case report (88 studies); Crohn’s disease and intestinal lymphoma (319 studies); Crohn’s disease and bowel lymphoma (408 studies); Crohn’s disease and primary intestinal lymhoma (66 studies). After removing duplicate studies, we have analysed 200 studies: 143 were removed because did not report clinical cases but fisiopathological mechanisms only; 4 studies were removed because reported patients submitted to biological therapy; 15 studies were excluded because reported patients affected by Crohn’s disease and intestinal lymphoma but with other associated immune-mediated pathology; 2 studies were excluded because reported association between Crohn’s disease and intestinal adenocarcinoma; 2 studied were excluded because were not written in English language. We resume literature analysis using Prisma flow diagram (Table 1).

34 studies have been included in our study and 57 cases presented Intestinal lymphoma in CD, not submitted to biological therapy, from 1955 up to now.

Analysis of 58 cases (including the present study) showed these characteristics: 41 male (70%) and 17 female (30%); middle age: 46,9 yr (range 12–84); Patients submitted to surgery: 13/32 (40%), not all studies reported this date; History of CD: 7,7 yr (range 1–48); palpable mass at admission: 6/28 (21%), not all studies reported this date (Table 2).

Discussion

CD is an important clinical form of IBD, representing around 25% of patients with IBD, diagnosed in the first 2 decades of their life.

Currently, the highest annual incidence of CD in Europe is 12.7 per 100,000 person-years and primary intestinal lymphoma in CD patients is described as uncommon even if it is reported in many cases by now.

Treatment of CD, during these last decades has been revolutionized by the development of biological therapy. In fact, until the last century patients with CD were more often submitted to surgery, above all for bowel occlusion.

During the last decades some drugs have been developed to oppose autoimmunity, as thiopurines, and inflammation of mucosa, as 5-ASA.

At the end of the last decades were developed biological drugs (Infliximab, Adalimumab, Vedoluzimab, Natalizumab) that have improved the course of the disease. But in 1999, Bickston, et al. described 3 cases of CD patients, who underwent biological therapy with lymphoma disease [38].

Conversely in 2013 Burmester, et al. published a randomized study literature review with 4.000 patients affected by CD, proving an incidence rate of lymphomatous diseases in CD of 0.7% patient/ year [39].

In 2016 Van Den Heuvel et al. showed a Cohort study analyzing neoplastic correlations in patients affected by IBD, describing that the development of neoplasm in patients affected by IBD is not related to biological therapy but to duration of immunosuppressive therapy (Thiopurine) for more than 12 months [40].

There is reason to believe that thiopurines themselves have an effect as well. Thiopurines are suppressing the immune system and have specific procarcinogenic effects. In case of haematologic cancers, for instance, aziathioprine promotes clonal expansion of rare mismatch repair-defective myeloid cells. A potential mechanism in NMSC carcinogenesis is the accumulation of 6-thioguanine in DNA. Thiopurine exposure may also cause PTCH mutations, a candidate tumor suppressor gene, particularly in cancers from non-sun-exposed skin, such as BCC [40].

There have been several studies estimating the risk of lymphoma in the IBD population. A British study performed by Lewis, et al. included 6000 Crohn’s disease patients, 10000 ulcerative colitis patients, and 60000 matched controls, and did not show a significantly increased risk of lymphoma (risk ratio, 1.2) [41]. A Swedish population-based study by Askling, et al. which included 47000 IBD patients, showed that the risk of any malignant lymphoma was 0.8 [42].

There have been several other small population-based studies which could not detect an increased risk of lymphoma in the IBD population. A 2011 Dutch nationwide study which included 17834 patients concluded that there was no increased risk for lymphoma in IBD (Risk Ratio 1.27) [43].

Our literature analysis reported a correlation between CD and Intestinal lymphoma with poor prognosis, therefore it is important to perform a quick diagnosis to immediately submit patients to chemotherapy. Radiological diagnosis is the most important method to make a fast diagnosis, as in 1976 Shapira, et al. already showed through the description of bowel aneurismatic dilatation in patients affected by intestinal lymphoma [44].

Conclusions

The association between CD and intestinal lymphoma is rare, but during the follow-up of the patient, the development of this serious complication must never be excluded, above all when the patient does not respond to the traditional therapy and when there is the presence of palpable abdominal mass. This kind of pathological association is not related to biological therapy but to the disease itself and, surely, to the long duration of the Thiopurine therapy.

 

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