EBV associated T/NK cell lymphoma presenting as Acute Spontaneous Tumor

Lysis Syndrome – A case report and review of literature.

Abstract:

Tumor Lysis Syndrome (TLS) is a potentially lethal complication of hematological

tumors or their treatment. It results from rapid destruction of tumor cells with
release of cellular breakdown products into the systemic circulation. It commonly
occurs following chemotherapy for malignancies such as acute leukemias and
lymphomas. However, acute spontaneous TLS presenting prior to chemotherapy is
a rare occurrence. TLS is a true oncological emergency that can lead to significant
morbidity and mortality if overlooked. Here we present a case of a young
immunocompetent individual who presented with acute febrile illness who then
developed TLS during hospital stay and later diagnosed to have EBV associated
T/NK T cell lymphoma.

Keywords: Tumor Lysis Syndrome, EBV associated T/NK cell lymphoma,

Oncological emergency.

Introduction:

Tumor Lysis Syndrome (TLS) results from rapid cell turnover rates of highly
proliferating tumors and is characterized by marked hyperuricemia, hyperkalemia,
hyperphosphatemia, clinical complications such as seizures, acute renal insult,
cardiac arrhythmias and death. Significant TLS, with end-organ compromise,
occurs in approximately 5% of all patients with hematologic malignancies and in
up to 25% of high risk patients, including those with T-cell acute lymphoblastic
leukemia and Burkitt’s lymphoma. TLS commonly occurs after the initiation of
chemotherapy, while spontaneous TLS occurring in the absence of chemotherapy,
is rare but might end up in a worse prognosis [1]. Non-Hodgkin’s lymphoma,
Burkitt’s lymphoma, other aggressive B-cell lymphomas, acute lymphoblastic
lymphoma and other hematological malignancies are associated with higher risk of
the occurrence of the acute TLS [2]. We report the first case of EBV associated
T/NK cell lymphoma presenting as Acute Spontaneous Tumor Lysis Syndrome in
a young immunocompetent individual.

Case report:

We report a 28 year old gentleman a known case of hypothyroidism, who was

admitted in our hospital for evaluation and management of acute febrile illness.
On admission he was febrile (103.8 F) and tachycardic (110/min). Clinical
examination was notable for hepatosplenomegaly and bilateral cervical
lymphadenopathy (left> right). Blood work up revealed pancytopenia, Hb-7.6
gm% (13-18 gm %) WBC count-2.6*10^3/mm3 (4-11*10^3/mm3), Platelet count-
60000*10^3/mm3 (150-450*10^3/mm3). Renal function test and coagulation
profile at the time of admission were normal. Ultrasound Abdomen showed
Hepatosplenomegaly with mild ascites and bilateral mild pleural effusion.
Fibrinogen was 236 (200-400 mg %). He was started on prophylactic antibiotics
and other supportive care.

On day 2 he developed sudden de-saturation (Spo2 84% at Room air), tachycardia

(114/min), with worsening lab parameters. Lab workup showed features of tumor
lysis syndrome with hypocalcaemia 7 mg/dl(8.6-10.2 mg/dl) , hyperurecemia 11.7
mg/dl(3.5-7.2 mg/dl), hyperphosphatemia 7 mg/dl(2.5-4.5 mg/dl) , hyperkalemia 6
mEq/L (3.5-5.1 mEq/L). Urea was 108 mg/dl (13-43 mg/dl), creatinine 3 mg/dl
(0.9-1.3 mg/dl). Liver function test showed a predominantly cholestatic pattern.
Aggressive hydration and electrolytes correction were done. Febuxostat 40 mg
twice a day was administered. Serum Procalcitonin (PCT) was 6.65 ng/ml (< 0.5
mg/ml low risk of progression to severe systemic infection); however blood culture
and sensitivity showed no growth.

His fibrinogen level was 42.8 mg %( 200-400 mg %), 2 units Fresh Frozen Plasma
(FFP) was transfused. Hemophagocytic Lymphohistiocytosis (HLH) was suspected
and HLH workup was done. It revealed an elevated ferritin 1635 ng/ml (20-250
ng/ml) and triglycerides 285 mg/dl (<150 mg/dl). In a background of severe
pancytopenia and fever favored a diagnosis of secondary HLH n (5/7 HLH 2004
criteria fulfilled). LDH was 412 U/L (125-220 U/L). He also developed few
episodes of hypothermia (93 F) which was managed conservatively.

Bone marrow biopsy showed hypercellular marrow with evidence of infiltration of

atypical lymphoid cells. Lymph Node biopsy from left cervical lymph node
showed features suggestive of High Grade Non Hodgkin’s Lymphoma. His tumor
lysis syndrome and hemodynamic instability was settled and he was shifted to
ward on Day 5.

Cervical lymph node sample was sent for Immunohistochemistry (IHC). It

revealed CD3+,CD20+(few residual follicles), Ki-67 85-90%, CD4+, CD7+,
Granzyme+, CD56+ ( Diffuse), EBER- ISH + (> 95%) features consistent with
EBV associated T/NK cell lymphoma. TCD gene re-arrangement was done in
order to rule out Hepatosplenic gamma-delta T cell lymphoma, and it was non-
contributory. EBV DNA ------

He underwent chemotherapy with ………………………..

Discussion:

Conclusion:

TLS is an oncometabolic emergency resulting from rapid cell death. The

mechanism behind spontaneous TLS in our patient still remains unknown. Certain
unique features about our case are (a) development of hypothermia after setting in
of TLS. There are various postulates stating increased production of
glucocorticoids and hyperthermia which leads to increased tumor cell death
thereby leading to spontaneous TLS did not correlate in our patient. (b)
Hyperphosphatemia is less common in spontaneous than nonspontaneous TLS,
possibly because phosphate release in lysis is less achievable when cytotoxic
therapy has taken place. However in our case there was marked
hyperphosphatemia. This marks the diverse presentations of spontaneous TLS.
More research and increased awareness among treating physicians is needed for
the better understanding of spontaneous TLS and to prevent its occurrence thereby
improving patient survival. Close monitoring of clinical status and laboratory
values is essential, not only to diagnose and treat spontaneous TLS, but also to
prevent this catastrophic condition.
References:

1. Liu JH, Zhou F, Zhang XL, Liu YQ, Wang JG, et al. (2014) Spontaneous Fatal
Tumor Lysis Syndrome in a Patient with T-Cell Lymphoblastic Lymphoma/
Leukemia: Successful Treatment with Continuous Renal Replacement Therapy and
Increasing-Dose Gradually Chemotherapy. J Clin Case Rep 4: 361.

2. K. R.Hande and G. C. Garrow, “Acute tumor lysis syndrome in patients with

high-grade non-Hodgkin’s lymphoma,” American Journal of Medicine, vol. 94,
no.2, pp. 133–139, 1993.