B-Cell Precursor Acute Lymphoblastic Leukemia/ Lymphoma with MYC and BCL-2 Rearrangements, a Case Report of an Unclassified "New" Entity

Case Report

Ann Hematol Oncol. 2020; 7(5): 1302.

B-Cell Precursor Acute Lymphoblastic Leukemia/ Lymphoma with MYC and BCL-2 Rearrangements, a Case Report of an Unclassified “New” Entity

Secchi R¹*, Meconi F¹, Esposito F¹, Zizzari A¹, Rapisarda VM¹, Provenzano I¹, Rizzo M¹, Anemona L² and Cantonetti M¹

¹Department of Biomedicine and Prevention, Hematology Division, University of Tor Vergata, Viale Oxford 81, Italy

²Anatomic Pathology, Department of Biomedicine and Prevention, University of Tor Vergata, Viale Oxford 81, Italy

*Corresponding author: Roberto Secchi, Policlinico Tor Vergata, Viale Oxford 81, Rome 00133, Italy

Received: May 12, 2020; Accepted: June 17, 2020; Published: June 24, 2020


Lymphomas with MYC and BCL-2 and/or BCL-6 rearrangements, commonly defined Double Hit Lymphomas (DHI) or Triple Hit Lymphomas (THI) are included in the category “High grade B-cell Lymphomas (HGBLs)” of 2016 revised World Health Organization (WHO) classification of lymphoid neoplasms [1].

Patients with DHI and THI have a poorer prognosis than those with Diffuse Large B-Cell Lymphoma (DLBCL) NOS [2]. Combined MYC and BCL-2 and BCL-6 rearrangements have been recently also found in rare cases of Follicular Lymphoma (FL) and Acute lymphoblastic B-Cell Precursor Leukemia/Lymphoma (BCP-ALL) [3].

BCP-ALL with combination of MYC and BCL-2 and/or BCL-6 rearrangements named “De novo DH-BCP-ALLs” have to be classified as a separate entity although they are rare and their clinic immune-phenotypic and cytogenetic features are not well characterized. A recent review in literature identified 6 patients in the German Multicenter Study Group for Adult LL (GMALL) registry and 11 patients published between 1983 and 2018 with De novo DH-BCP-ALLs, analyzing their common features, therapy approaches and poor outcomes [4].

Here in, we report a case of a fifty year-old man, who was referred to our hospital after being diagnosed with de novo DH-BCP-ALL, presenting with both diffuse cranial and spinal meningeal involvement and multiple other extra-nodal localizations (cutaneous, testicular, gastro-enteric and skeletal), in addition to nodal localizations such as para-cardiac and para-renal. After reaching Partial Response (PR) with first line treatment, the patient early relapsed and was refractory to new lines of therapy with an OS of 7 months.

Keywords: C-MYC translocation; BCL-2 translocation; High grade lymphoma; Acute lymphoblastic lymphoma; B-cell lymphoma

Case Presentation

In April 2019, the patient presented progressive brachialgia, paresthesia, and hypotrophy of the right upper limb, associated with loss of function of the ipsilateral hand. A Magnetic Resonance (MR) of the spine showed an extradural hourglass mass, extended from C6 to D1 and displacing the spinal cord.

The pathological evaluation of the lesion showed proliferation of medium lymphoid cells with “starry sky” appearance and frequent mitoses (Ki67 proliferation index 95%). Immuno-phenotype analysis showed rare Tdt positivity (10-15%), CD45/LCA+, CD79a+, PAX5+, CD20 +/-, CD34-, CD99-/+, CD10+, BCL-6-, IRF4 +/-, BCL-2+, IgM+, C-MYC+. BothMYC and BCL-2 were rearranged in FISH analysis, cytogenetic analysis showed a normal karyotype. The findings were consistent with B-ALL with mature phenotype.

Initial Positron Emission Tomography (PET) Computed Tomography (CT) (Figures 1 and 2) scan revealed marked diffuse FDG activity involving the pericardium (SUV max 10), the palatine tonsils and the tongue (SUV max 10), the stomach (SUV max 18), the right kidney (SUV max 5), both homers (SUV max 9), the left femur, the right scapula, the right testicle (SUV MAX 13) and two cutaneous regions, one on the right gluteus (SUV max 13) and the other localized above the VIII left rib (SUV max 3.7).Spinal cord was involved in both the previous analyzed mass and on a second level, from L5 to S1 (SUV max 15). Atadmission, laboratory studies showed a normal level of hemoglobin, platelets and White Blood Cells (WBC) and Lactate Dehydrogenase (LDH) was on range. The patient suffered from a severe hyponatremia (lowest of 110 mEq/L). Esophago Gastroduo Denoscopy (EGD) with biopsy (Figure 1) and testicular echography were performed, confirming the disease localizations. Bone marrow biopsy and aspirate showed no disease infiltration.

Citation: Secchi R, Meconi F, Esposito F, Zizzari A, Rapisarda VM, Provenzano I, et al. B-Cell Precursor Acute Lymphoblastic Leukemia/Lymphoma with MYC and BCL-2 Rearrangements, a Case Report of an Unclassified “New” Entity. Ann Hematol Oncol. 2020; 7(5): 1302.