t (1;12) (p31; q13) cytogenetic abnormality in a patient of idiopathic hypereosinophilic syndrome: A case report

INTRODUCTION

Hypereosinophilia is defined by an absolute eosinophil count (AEC) of more than ≥1.5 × 10⁹/L.^[1,2] Eosinophils and their derived mediators cause various organ damage ranging from asymptomatic to life-threatening.^[1-4] Predominant complications associated with hypereosinophilic syndrome (HES) are fibrotic and thrombotic.^[1] There are many subtypes under HES, and a panel of investigations which are required to prove clonality. Next-generation sequencing (NGS) and karyotyping remain important investigations in these patients,^[4] and here, we are presenting a case with a rare cytogenetic abnormality detected on conventional karyotyping.

CASE REPORT

Management

On admission, all relevant hematological and biochemical investigations were done [Table 1]. A hemogram and peripheral smear revealed an AEC of 235610/μL. Kidney function and liver function tests were within normal limits. Cardiac troponin I was normal. The patient was started methylprednisolone pulse therapy 1000 mg once daily intravenously for 3 consecutive days, followed by oral prednisolone 1 mg/kg along with cytoreductive therapy with oral hydroxyurea, considering significantly increased eosinophil counts. Peripheral blood breakpoint cluster region: ABL proto-oncogene 1 (BCRABL1) by real-time polymerase chain reaction was negative. Ultrasound sonography venous color Doppler was done in view of asymmetrical left lower limb swelling, revealing acute thrombosis of the left common femoral vein and saphenofemoral vein. The patient was started on subcutaneous enoxaparin injection followed by oral apixaban on discharge. Contrast-enhanced computerized tomography thorax, abdomen, and pelvis, along with computed tomography pulmonary angiogram, were done to rule out underlying occult malignancy and to look for evidence of pulmonary embolism with background deep vein thrombosis, which showed mild bilateral pleural effusion and mild ascites. 2D transthoracic echocardiogram was suggestive of the presence of regional wall motion abnormalities (RWMA), moderate eccentric mitral regurgitation, and grade 1 left ventricular diastolic dysfunction (LVDD) with ejection fraction (EF) of 45%. The stool routine for parasites examination and occult blood was negative, and upper and lower gastrointestinal (GI) endoscopy was planned in view of suspected GI involvement by eosinophilia. Later patient refused the same. Bone marrow examination revealed cellular marrow with a marked increase in eosinophilic precursors with evidence of dyspoiesis in eosinophilic and megakaryocytic lineages. Conventional karyotyping [Figure 1] by unstimulated culture and GTG banding showed t (1;12) (p31; q13). The NGS panel for hypereosinophilia syndrome did not detect any clinically relevant gene fusions. The patient was started on oral imatinib 100 mg once daily, along with oral steroid therapy.^[5,6] The dose of imatinib was increased on the follow-up visit based on eosinophil count, and currently, the patient is on oral imatinib 400 mg once daily dose. The patient in the last follow is symptomatically better, and the latest eosinophil count is 570/μL.

Table 1: Hematological and biochemical parameters on admission.

Hemoglobin	10.5 g/dL
Total leucocyte counts	235610/μL
AEC	212400/μL
Platelet counts	351000/μL
Peripheral blood smear	RBCs: Normocytic normochromic to few microcytic hypochromic RBCs. WBCs: Marked leucocytosis with severe eosinophilia (AEC 2,12,400/μL), 90% eosinophils in the peripheral blood. Many of them are monolobulated, bilobulated, and multilobulated, and many show hypo granulation. DLC: Eosinophils – 90%, monocytes – 04%, lymphocytes – 05%, neutrophils – 01%, Platelets: Adequate. No hemoparasites were seen.
Liver function test	Total bilirubin: 0.64 mg/dL (0.3–1.2) Direct bilirubin: 0.05 mg/dL (0–0.2) SGPT: 34.0 U/L (0–35) SGOT: 28.0 U/L (0–35) ALP: 263.0 U/L (30–120) GGT: 54.0 U/L (0–38) Serum total protein: 6.9 g/dL (6.6–8.3) Serum albumin: 2.9 g/dL (3.5–5.2) Serum globulin: 4.0 g/dL (2.5–3.2)
Kidney function test	Blood urea: 27.0 mg/dL (17–43) Serum creatinine: 0.60 mg/dL (0.55–1.02) Serum Na+: 136.0 mmol/L (136–146) Serum K+: 3.89 mmol/L (3.5–5.1) Serum Cl: 98.0 mmol/L (101–109) Serum total calcium: 9.66 mg/dL (8.8–10.6) Serum uric acid: 4.0 mg/dL (2.6–6) Phosphorus: 1.4 mg/dL (2.5–4.5)
yroid profile	TSH: 0.70 μIU/mL (0.13–6.33) T4: 6.33 μg/dL (4.5–12.6)

RBCs: Red blood cells, WBCs: White blood cells, AEC: Absolute eosinophil count, TSH: Thyroid-stimulating hormone, SGPT: Serum glutamic pyruvic transaminase, SGOT: Serum glutamic oxaloacetic transaminase, ALP: Alkaline phosphatase, GGT: Gamma-glutamyl transferase, Cl: Chloride, Na: Sodium, K: Potassium, T4: Thyroxine, DLC: Differential leucocyte count

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Figure 1:

Chromosome analysis revealed 46, XX with the presence of balanced translocation between the short arm of chromosome #1 and the long arm of chromosome #12, between the regions 1p31 and 12q13, respectively, found in all the metaphases studied.

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DISCUSSION

HES is a heterogeneous group of disorders, and molecular and genetic study is required to reach a particular diagnosis. HES is a diagnosis of exclusion.^[7] NGS and karyotyping or fluorescence in situ hybridization (FISH) remains a very helpful diagnostic modality.^[8] There are various chromosomal abnormalities described with regard to HES.

HES can involve various organ systems with varying severity which needs to be evaluated and managed.^[9]

In the present case, the chromosomal abnormality detected was t (1;12) (p31; q13), and from my knowledge, it is not mentioned so far in the literature.

CONCLUSION

t (1;12) (p31; q13) chromosomal abnormality in conventional karyotyping in HES is a rare finding. Along with other investigations, including immunophenotyping by flow cytometry and NGS for mutation study, karyotyping and FISH are important and recommended.