A 45-year-old Hispanic male who underwent cadaveric renal transplant in the right lower quadrant 17 years earlier, presented to the hospital with a three-month history of generalized abdominal pain with localization to the right side for two weeks. He was on chronic immunosuppression with tacrolimus, azathioprine, sirolimus and prednisone. The pain was more pronounced in the right upper quadrant, and the ultrasound imaging of the abdomen was suggestive of cholecystitis. Laboratory studies did not reveal any abnormalities. He could not confirm if he had had any problems or surgeries on his gall bladder. Hence, he underwent laparoscopic exploration of the gall bladder fossa. During surgery, adhesions of the omentum were found in the gall bladder fossa in the absence of the gall bladder, and an inflamed appendix was found elevated due to the transplanted kidney in the right lower quadrant. Laparoscopic appendectomy was performed and the tissue underwent pathological examination. He was discharged after an uneventful post-operative course.
Pathology of his appendix by immunostaining revealed anaplastic cells strongly positive for CD3, CD56 together with strong focal EBV-encoded RNA (EBER) staining (Figures , , and ). The malignant cells were negative for CD20, CD30, CD45, CD5, Alk-1 and TCK. The tissue was found to be positive for the T-cell receptor (TCR) by gamma gene rearrangement studies by PCR analysis (Figure ). Immunoglobulin heavy chain rearrangement (IgH) by PCR analysis did not detect a clonal B-cell population, thereby confirming T-cell lymphoma. A bone marrow examination revealed no involvement with negative flow cytometry and showed normal male karyotype (46, XY). A staging positron emission tomography (PET) scan showed increased radiotracer uptake in the right cervical and left groin lymph nodes along with the 3.3 cm liver mass. Non-specific uptake in the stomach was also observed.
Appendix biopsy showing large, pleomorphic lymphocytes with irregular nuclear contours and large nucleoli. (400 X).
Positive staining of lymphoid infiltrate for CD3 (400 X).
Gastric biopsy showing atypical lymphoid infiltrate (200 X).
Appendiceal infiltrate showing scattered Epstein Barr Virus-positive cells (100 X).
T cell receptor gene rearrangement by PCR analysis showing monoclonal spike.
The patient was re-admitted to the hospital 10 days later, with increasing abdominal pain, symptoms of gastric outlet obstruction, weight loss, headaches and fever. A lumbar puncture was negative for infection or lymphoma. Cranial imaging with a computed tomography (CT) scan was also negative. An esophagogastroduodenoscopy (EGD) was performed revealing multiple ulcerated nodular masses in the stomach and duodenum (Figures and ). A stomach biopsy gave similar results as the appendix with large anaplastic cells with irregular nuclei. Immunostaining of the gastric specimen confirmed T-cell lymphoma as well as positive EBER staining.
EGD showing large ulcerated gastric nodule together with large nodules in the duodenum.
EGD showing multiple large gastric nodules with central ulceration.
Initial treatment management involved reducing the dose of the patient's immunosuppressive agents and starting chemotherapy. Administration of azathioprine, prednisone and tacrolimus was stopped and low dose sirolimus at 1 mg was given daily. The first cycle of chemotherapy (PEGS) included cisplatin 25 mg/m2, etoposide 40 mg/m2 and solumedrol 250 mg administered on days one, two and three, and gemcitabine (Gemzar) 1000 mg/m2 on day one (ongoing Phase II trial SWOG 0350). Our patient had a positive and rapid clinical response to this regimen. Thus, the chemotherapy was changed to a standard CHOP regimen (cyclophosphamide, doxorubicin [Adriamycin], vincristine, prednisone). His gastric outlet obstruction was supported with total parenteral nutrition (TPN) for a few weeks, after which the patient was able to eat well. A repeat PET scan after the second cycle of CHOP showed a significant response.
The main complications during the therapy were pancytopenia, febrile neutropenia and pneumonia. These were managed successfully. He recovered well and is presently receiving treatment as an outpatient. His allo-grafted kidney is also fully functional. Restaging is planned after a total of six cycles of CHOP with a PET scan and EGD.