Adult T-type Lymphoblastic Lymphoma Presenting as Hypercalcemic Crisis and Aplastic Anemia

Journal of Medical Case Reports
08 Oct, 2019 ,

Mickael Essouma et al report a case of a 52-year-old Cameroonian man with acute kidney injury who presented with confusion, abdominal pain, constipation, polyuria, polydipsia, calciphylaxis, enlarged lymph nodes, tachycardia, and a blood pressure of 170/88 mmHg. Laboratory investigations revealed hypercalcemia (total/ionized 199.5/101.75 mg/L), normal serum phosphorus (40.20 mg/L), and a low intact parathyroid hormone (9.70 pg/ml). Complete blood count revealed pancytopenia. Peripheral blood smear confirmed thrombocytopenia but showed neither blasts nor flower cells. Bone marrow aspirate revealed hypocellularity with no blasts or fibrosis. Lymph node biopsy was suggestive of T-cell precursor lymphoma. T-lymphoblastic lymphoma presenting with hypercalcemic crisis and aplastic anemia was diagnosed, and the patient received the cyclophosphamide-doxorubicin-vincristine-prednisone protocol of chemotherapy together with filgrastim and whole-blood transfusion for aplastic anemia. The short-term outcome was fatal, however.

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A 52-year-old Cameroonian man, married and a car driver, was admitted to our nephrology inpatient ward for acute kidney injury. He had no relevant past history regarding disease or toxic exposure. He occasionally consumed alcohol and was not a smoker. He had been well until 8 weeks prior to admission, when he developed progressive fatigue, anorexia, involuntary weight loss (~ 12% of his usual body weight), and intermittent nocturnal fever that had been treated twice as malaria and typhoid fever. The malaria and typhoid fever treatments received were parenteral quinine and ofloxacin (doses and duration of treatment not described for both), and both were unsuccessful. A few days before consultation in our hospital, he developed polyuria, polydipsia, constipation, and diffuse abdominal pain that rapidly worsened, prompting consultation at the emergency service of our hospital.

The findings of a serum creatinine level of 36.7 mg/L (normal range, < 15 mg/L) and a blood urea nitrogen level of 1.23 g/L (normal range, 0.15–0.45) led to his transfer to the nephrology unit. Upon admission, further questioning revealed that a few days prior to consultation, the patient had inconsistent verbalizations and hallucinations. He was very ill-looking, severely dehydrated, with nontender fixed bilateral inguinal lymph node enlargement (4 cm for the largest), nonreactive urine dipstick, and a fecaloma. His Glasgow Coma Scale score was E4V2M6, blood pressure was 170/88 mmHg, pulse rate was 102/minute, respiratory rate was 17/minute, temperature was 37.7 °C, body surface area was 1.66 m2, and random capillary glucose was 0.91 g/L.

Apart from the impaired verbal response (in the Glasgow Coma Scale) that limited cognitive function examination, no cranial palsy, meningeal signs, motility abnormalities, sensitivity abnormalities, or coordination abnormalities were found on neurological examination. Cardiac auscultation revealed regular tachycardia. Abdominal examination revealed diffuse tenderness and increased bowel sounds but no defense, contracture, abdominal distention, or visceral enlargement. The result of the rest of the physical examination was normal. Laboratory tests revealed red blood cells 5.4 × 1012/L, hemoglobin 14.3 g/dl, white blood cells 6.2 × 109/L, neutrophils 2.6 × 109/L, eosinophils 0, basophils 0, lymphocytes 2.7 × 109/L, monocytes 6.2 × 109/L, platelets 137 × 109/L, total calcium 199.5 mg/L (normal range, 84–105), ionized Ca2+ 101.75 mg/L (normal range, 46–54), serum phosphorus 40.20 mg/L (normal range, 25–50), plasma sodium 152 mmol/L (normal range, 135–145), serum potassium 3.1 mmol/L (normal range, 3.5–5), serum chloride 110 mmol/L (normal range, 96–107), and serum magnesium 19.80 mg/L (normal range, 18–26).

A provisional diagnosis of a lymphoproliferative disorder or a granulomatous disease causing acute kidney injury was made. Further laboratory tests showed parathyroid hormone (PTH) level 9.70 pg/ml (normal range, 17–73), PTH-related peptide (PTH-rp) level < 8.5 pg/ml (normal range, < 13.0), 1.25(OH)2D3 level 32 ng/ml (normal range, 18–71 ng/ml for nondialysis subjects), erythrocyte sedimentation rate 50 mm (normal range, < 20 mm), C-reactive protein (CRP) 148.72 mg/L (normal range, < 6 mg/L), and prostate-specific antigen 0.21 ng/ml (normal range, < 4 ng/ml).

Twenty-four hours following admission to the nephrology unit, specific hypercalcemia management was initiated with 4-mg zoledronate once and hydration using intravenous liquids (isotonic saline, 2 L/24 hours and 5% dextrose, 1 L/24 hours) for 3 consecutive days before introduction of oral furosemide 40 mg once daily to correct consequential fluid overload. A symmetric purpura limited to the lower limbs progressively developed from the fourth to sixth days of hospitalization, with temperatures reaching a plateau at 40–40.5 °C. On evaluation 9 days after initiation of specific hypercalcemia management, serum calcium and sodium returned to normal values, with complete recovery of related symptoms and signs, as well as renal function.

On the 14th day of hospitalization, although the purpura completely regressed, fever persisted, and lymph node enlargement extended beyond the groins to the cervical region. At this time, results of bacteriological cultures, including urine culture and three serial hemocultures, were all negative, and CRP was 115.61 mg/L. Complete blood count showed red blood cells 2.5 × 1012/L, hemoglobin 6.6 g/dl, white blood cells 2 × 109/L, neutrophils 0.6 × 109/L, eosinophils 0.06 × 109/μl, basophils 0, lymphocytes 1.3 × 109/L, monocytes 0.4 × 109/L, and platelets 44 × 109/L. Peripheral blood smear confirmed a low platelet count but showed neither blasts nor flower cells. The reticulocyte count was 22,640/mm3. The bone marrow aspirate showed 8.3% normal cellularity with no abnormal infiltrate (including blast cells) or fibrosis.

This marrow hypocellularity together with pancytopenia led to the diagnosis of nonsevere aplastic anemia according to the revised Camitta criteria. Inguinal lymph node biopsy showed large cells with distinct nucleoli, dispersed chromatin, and scant cytoplasm with intracytoplasmic CD3 and Ki67 markers, all suggestive of aggressive precursor T-cell lymphoma. Because lymphoblasts were not observed either in bone marrow analysis or in the peripheral blood smear, and considering histopathologic findings of the lymph node biopsy, T-ALL was ruled out, and the diagnosis of T-LBL was retained.

An abdominal ultrasound obtained to assess T-LBL extension showed no organ (spleen, liver, kidney) enlargement. Additional examinations evaluating disease prognosis showed serum lactate dehydrogenase 1145.2 IU/L (normal range, 200–400), uric acid 148 mg/L (normal range, < 70 mg/L), serum glutamic oxaloacetic transaminase 72.3 IU/L (normal range, < 37), and serum glutamic pyruvic transaminase 27.6 IU/L (normal range, < 45). The patient was then transferred to the oncology unit, where he immediately received transfusion of 3 U of whole blood within 2 days prior to chemotherapy. The chemotherapy, which was based on the standard cyclophosphamide-doxorubicin-vincristine-prednisolone (CHOP) protocol for NHL, consisted of a 15-minute intravenous infusion of 1250 mg of cyclophosphamide on day 1, a 2-minute intravenous bolus of 80 mg doxorubicin on day 1, a 2-minute intravenous bolus of 2 mg vincristine on day 1, and 100 mg of oral prednisolone once daily on days 1 to 5 of the cycle.

Following this CHOP cycle, 1 ml of filgrastim was administered subcutaneously once daily for 3 consecutive days as supportive treatment for aplastic anemia. Resolution of fever and recovery from fatigue and anorexia were noted from the third day of the CHOP cycle. The patient was discharged at the end of the cycle. One week following hospital discharge, he died at home a few hours after fever recurrence.