Triple-Double: A Triple Hit Lymphoma Hits the Kidneys Twice

Case Report

Ann Hematol Oncol. 2016; 3(9): 1113.

Triple-Double: A Triple Hit Lymphoma Hits the Kidneys Twice

Carney BJ¹, Malvar G², Freed JA¹, Pihan G², Bryke CR² and Joyce RM¹*

¹Division of Hematology & Oncology, Beth Israel Deaconess Medical Center, USA

²Department of Pathology, Beth Israel Deaconess Medical Center, USA

*Corresponding author: Joyce RM, Division of Hematology & Oncology, Beth Israel Deaconess Medical Center, Kirstein 121, 330 Brookline Avenue, Boston MA 02215, USA

Received: August 17, 2016; Accepted: October 04, 2016; Published: October 06, 2016


Triple hit lymphoma (THL) is a rare form of non-Hodgkin lymphoma characterized by gene rearrangements involving c-MYC, BCL-2, and BCL-6. These genetic aberrations result in a promotion of growth and suppression of apoptosis, giving rise to a profoundly aggressive lymphoma. The typically rapid progression of THL often results in a high tumor burden at the time of diagnosis, and this creates a significant risk of treatment-related tumor lysis syndrome. Here, we report a case of THL that initially presented with obstructive nephropathy in the setting of spontaneous tumor lysis syndrome. To our knowledge, this is the first case reported in the literature of THL presenting in this manner.

Keywords: Triple hit lymphoma; Tumor lysis syndrome; Obstructive nephropathy


BEAM: Carmustine, Etoposide, Cytarabine, and Melphalan; CNS: Central Nervous System; CT: Computed Tomography; DLBCL: Diffuse Large B- Cell Lymphoma; FDG-PET: Fludeoxyglucose- Positron Emission Tomography; R-EPOCH; THL: Triple Hit Lymphoma

Case Presentation

A previously healthy 67-year-old man presented to an outside hospital with a two week history of bilateral flank pain and acute-onset oliguria. Labs were remarkable for a serum creatinine of 1.78 mg/dL from a baseline of 0.8 mg/dL several months prior to presentation. Urinalysis was positive for leukocyte esterase although a urine culture returned with no growth. A computed tomography (CT) scan of his abdomen and pelvis revealed a 7 mm non-obstructing right renal calculus but was otherwise unremarkable. A Foley catheter was placed with good drainage of urine and the patient was started on empiric ceftriaxone and admitted for observation. His acute kidney injury was attributed to a combination of a urinary tract infection and non-steroidal anti-inflammatories that he had been using for the flank pain. Despite the above management, the patient’s renal function continued to deteriorate. Over the next six days, he became anuric and his creatinine trended up to 6.73 mg/dL on the day of transfer. During his admission at the outside hospital, labs were also notable for a steadily up-trending leukocytosis, reaching 31,500/μL with 10% band forms, and a lactate dehydrogenase (LDH) of 450 IU/L (normal range 94-250 IU/L). The patient was transferred to our center for further evaluation and management of anuric renal failure.

On admission to our hospital, labs were remarkable for urea nitrogen 68 mg/dL and creatinine 8.6 mg/dL. With the exception of mild hyponatremia and an anion gap metabolic acidosis, chemistries were otherwise unremarkable. Complete blood count revealed persistent leukocytosis to 34,700/μL. The differential was with 20% band forms and 9% atypical cells. Renal ultrasound showed moderate to severe bilateral hydronephrosis and a possible 7 mm calculus in the right ureter. Nephrology and Urology were consulted. Both consulting services felt that the patient’s presentation was most consistent with an obstructive etiology. Interventional Radiology was consulted and the patient underwent bilateral percutaneous nephrostomy tube placement. This resulted in rapid normalization of his renal function. Despite this, his leukocytosis, initially attributed to a brisk leukemoid reaction in the setting of a urinary tract infection, persisted and worsened to 51,800/μL by his second hospital day. LDH and uric acid obtained at that time returned markedly elevated at 2,422 IU/L and 17.6 mg/dL, respectively. After conferring with Nephrology, the patient was given rasburicase due to high clinical suspicion for urate nephropathy. Medical Oncology was consulted given concern for a hematologic malignancy.

Peripheral blood smear showed lymphoid cells with punchedout vacuoles and irregular nuclear contours (Figure 1). The patient underwent a bone marrow biopsy. Flow cytometry revealed a clonal population of cells expressing CD10, CD19, CD20, and CD45 comprising 52% of total events. A high grade lymphoma FISH panel was performed on uncultured mononuclear interphase peripheral blood cells (Figure 2). The IGH (14q32) and BCL-2 (18q21) dual fusion probe set showed two fusion signals positive for IGH/BCL- 2 gene rearrangement and an extra IGH signal. The MYC (8q24.1) break apart probe set showed a split signal positive for rearrangement of MYC and an extra 3' MYC signal. The BCL-6 (3q27) break apart probe set showed a split signal consistent with rearrangement of BCL-6. These rearrangements in c-MYC, BCL-2, and BCL-6 were consistent with a “triple hit” lymphoma. Metaphase chromosome analysis of circulating lymphoma cells from a direct preparation and a 24 hour unstimulated culture revealed a 46,XY,inv(3)(q25q27),t(8;14) (q24.1;q32),del(10)(p11.2), t(14;18)(q32;q21) karyotype in all 20 cells examined (Figure 3). Metaphase FISH analysis revealed that in addition to the identified chromosome rearrangements, the abnormal karyotype harbored two copies of the derivative chromosome 14 of the t(8;14)(q24.1;q32), likely resulting in further upregulation of MYC. Fludeoxyglucose-positron emission tomography (FDG-PET) scan immediately prior to initiation of treatment revealed diffuse heterogeneous FDG avidity within the bone marrow and spleen as well as extensive uptake throughout the peritoneum and surrounding the bladder.