Spontaneous ileal perforation in a critically ill adult with aggressive diffuse large B-cell lymphomas.

Sir,

Spontaneous pneumoperitoneum is a rare but life-threatening complication of systemic chemotherapy for non-Hodgkin's lymphoma (NHL), and any part of the gastrointestinal (GI) tract may be affected. There is little data in the medical literature with regards to spontaneous GI perforation during chemotherapy in the absence of intestinal lymphoma involvement.[1] Poor prognostic markers include myeloid toxicity, immunosuppression, and protein malnutrition.[2] Diagnosis may be delayed because of masking effect of steroids on the localized and systemic inflammatory response.[3] We report herein a case of a 80-year-old Cuban male with chronic obstructive pulmonary disease, diabetes mellitus, and dilated cardiomyopathy that required defibrillator placement, and he complained of insidious onset of shortness of breath of 4 months’ duration. Physical examination was unremarkable. Review of systems was significant for early fatigue, 10-pound weight loss, and night sweats. Computed tomography revealed a mediastinal mass, and the patient underwent a mediastinoscopy assisted biopsy of the mass. Histopathologically, the sample showed diffuse populations of pleomorphic lymphoid cells with immunohistochemical positivity for CD10, CD20, and CD79a with overexpression of lambda light chain. Bone marrow biopsy expressed large-cell lymphoma consisting of polyclonal B cells. Fluorescence in situ hybridization (FISH) detected a t(8,14), leading to an IgH/myc fusion protein, and the diagnosis of stage 4 diffuse large B-cell lymphoma (DLBCL), centroblastic variant was made.

He received one cycle of R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) chemotherapy as well as oral allopurinol for acute tumor lysis syndrome (ATLS) prophylaxis. Two days after the first cycle of chemotherapy, laboratory results revealed a normal complete blood count (CBC) and the following: Creatinine 2.1 mg/dL, calcium 6.9 mg/dL, phosphorus 9.5 mg/dL, and uric acid 9.5 mg/dL.

The patient was diagnosed with ATLS and immediately started on aggressive intravenous hydration and continued on oral allopurinol. On day 4 post-chemotherapy, he experienced sudden severe abdominal pain. CT scan of the abdomen revealed pneumoperitoneum [Figure 1] and emergency surgical laparotomy revealed a perforation 2 feet from the ileocecal valve and sigmoid diverticulitis with purulent peritonitis. He had a Hartmann procedure with small bowel resection and primary anastomosis at the level of the ileum. Pathology revealed necrotizing inflammation with areas of granulation consisting predominately of mature lymphocytes, plasma cells, and macrophages. No definitive evidence of a lymphomatous or malignant process was identified. One day later, he developed post-operative hemorrhagic shock and was rushed to the operating room and about 1 L of blood was aspirated from the belly. He clinically improved after surgery, but a month later, he developed methicillin-resistant Staphylococcus aureus endocarditis-related complications and then expired.

Figure 1

CT scan revealing evidence of pneumoperitoneum

There are few cases of spontaneous GI perforation secondary to systemic chemotherapy in the literature.[4] Lymphoma may involve the GI tract and when treated with chemotherapy can result in tumor necrosis and spontaneous perforation.[5] Intestinal involvement with lymphoma can contribute to this complication, but, in our patient, the pathology of the surgically resected bowel specimens rejected this notion since it was negative for lymphoma. The hypothesis may be that the combination of the drugs most likely results in ulcer perforation and the morbidity and mortality of pneumoperitoneum is high if a major medical illness exists concomitantly with the perforation. Diagnosis is often delayed because symptoms are blunted by high dose steroids and it may go unnoticed until septic shock presents. The time that elapses from the time of recognition of peritonitis to the time of surgical intervention can determine the survival outcome.

We recommend that patients with aggressive NHL who complain of abdominal pain during systemic chemotherapy and steroids get immediately evaluated for GI ulcers or even perforation and the clinical index of suspicion should be higher in patients with multiple co-morbidities.