Dina Sameh Soliman

Concomitant Classic Hodgkin Lymphoma of Lymph Node and cMYC-Positive Burkitt Leukemia/Lymphoma of the Bone Marrow Presented Concurrently at the Time of Presentation: A Rare Combination of Discordant Lymphomas:

Discordant lymphoma is rare condition in which different types of malignant lymphomas occurring in different anatomic sites. The two diseases may present clinically as concurrent or sequential disease (10). Herein we are reporting a Pakistani female in her 60s, a carrier of hepatitis B virus with multiple comorbidities presented with cervical lymphadenopathy, diagnosed as Hodgkins lymphoma, mixed cellularity. During the staging workup, the patient was discovered to have extensive bone marrow (BM) involvement by Burkitt leukaemia/lymphoma (BL). Cytogenetic analysis revealed positivity for t(8;14)(q24;q32) confirmed by Fluorescence In Situ Hybridization (FISH) for IGH/MYC. Epstein-Barr virus (EBV) was demonstrated heavily in our case, with (EBV) DNA of 24,295,560 copies/ml by PCR at time of presentation, in addition, the neoplastic cells in both diagnostic tissues (cervical lymph node and BM) demonstrated positivity for EBV. A diagnosis of concomitant EBV related discordant lymphoma (classical Hodgkin lymphoma (cHL) and Burkitt lymphoma (BL) in leukemic phase was made. Among all reported cases, this case is highly exceptional because it is the first case of discordant/composite lymphoma, with this combination and concomitant presentation. Since we are dealing with a case with an exceptionally rare combination, we found it significant to elaborate more on its clinical features, contributing factors including EBV role, response to treatment, complications, and prognosis.

De Novo Precursor B-Lymphoblastic Leukemia/Lymphoma With Double-Hit Gene Rearrangements ( MYC/BCL-2 ) Presented With Spinal Cord Compression and Acquired Factor XIII Deficiency

Double-hit lymphomas (DHLs) are aggressive mature B-cell neoplasms associated with rearrangements involving MYC and B-cell lymphoma-2 (BCL-2). Such DH events are extremely rare in B-cell precursor acute lymphoblastic leukemia (B-ALL), especially in young adults. A 29-year-old male patient initially presented to emergency department with right mandibular mass of 2 months duration associated with intermittent fever. Laboratory workup revealed very high lactate dehydrogenase at 2,026.0 U/L. Peripheral blood revealed pancytopenia with many circulating blasts (about 77%). Bone marrow (BM) aspirate revealed infiltration with many small sized blasts of very high nucleocytoplasmic ratio, finely dispersed nuclear chromatin and prominent nucleoli. The BM biopsy reflected marked hypercellularity with diffuse replacement by sheets of blasts, positive for TdT, PAX-5, CD10, cMYC, BCL-2 and CD20 with Ki-67 > 90%. Flow cytometry on BM revealed a precursor B-immunophenotype (CD45 (dim), CD19, CD10, Tdt and CD20). The blasts are negative for cytoplasmic and surface IgM. Cytogenetics revealed complex karyotype: 46,XY,del(6)(q21q23),t(8;22)(q24.1;q11.2),t(14;18)(q32;q21)(20). A diagnosis of B-lymphoblastic leukemia/lymphoma with t(8;22)(q24.1;q11.2) and t(14;18)(q32;q21) was made. Fluorescent in situ hybridization (FISH) analysis revealed an abnormal hybridization signal pattern for CDKN2A probe, indicating biallelic (homozygous) deletion of the short arm of chromosome 9 (9p) in 94% of the cells analyzed. The patient had severe life-threatening bleeding despite of normal prothrombin time (PT) and activated partial thromboplastin time (APTT) due to acquired factor XIII deficiency, an overlooked rare coagulopathy disorder. In addition, the patient developed acute sudden onset paraplegia, and magnetic resonance imaging (MRI) of spine showed acute cord compression which necessitated emergency radiotherapy after which chemotherapy was started on hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone) protocol. MRI showed dramatic resolution of the mass. Very few cases of B-ALL with DH rearrangement with true precursor B-cell phenotype (positivity for TdT with negativity for surface light chain) have been reported. Many of these had frequent central nervous system (CNS) involvement, with complex karyotypes, highly aggressive course, with short survival of less than 1 year. This case however showed very good response to treatment. In contrary to DHL, de novo B-ALL with double-hit rearrangements is more prevalent in pediatrics and young adults. Although most of reported cases represent transformation of follicular lymphoma, our patient’s young age, acute onset and absent lymphadenopathies all support de novo ALL.

Acute Myeloid Leukemia With Inv(16)(p13q22) Associated With Hidden Systemic Mastocytosis: Case Report and Review of Literature

Systemic mastocytosis (SM) is a condition associated with clonal neoplastic proliferation of mast cells. In up to 40% of systemic mastocytosis cases, an associated clonal hematological disease of non–mast cell lineage, such as acute myeloid leukemia (AML), is diagnosed before, simultaneously with, or after the diagnosis of SM. Herein, we report a case of a 30-year-old man diagnosed with AML with inv(16)(p13;q22) CBFB:MYH11. Associated mastocytosis was not noted at diagnosis and was only detected in the bone marrow at time of remission after successful chemotherapy. The diagnosis of mastocytosis was based on the demonstration of a multifocal dense mast cell infiltrate in the marrow biopsy with aberrant immunophenotype, with coexpression of tryptase, CD117, and CD25. The mast cells showed atypical morphology mostly with irregular nuclear contour, bilobed or multilobed nuclei with cytoplasmic hypogranulation or irregular metachromatic granule distribution, and some cells with eccentric nucleus or spindle shape. Reexamination of the pretherapeutic bone marrow with immunostain for tryptase and CD25 revealed that mastocytosis was present from the start but masked by extensive blast proliferation. This case indicates that mast cell infiltrates are sometimes underappreciated at the original diagnosis of AML with inv(16) and that the concurrent diagnosis of SM with AML requires a high index of suspicion supported with comprehensive morphologic and immunohistochemical evaluation for a neoplastic mast cell proliferation.

High-Grade B-Cell Neoplasm with Surface Light Chain Restriction and Tdt Coexpression Evolved in a MYC-Rearranged Diffuse Large B-Cell Lymphoma: A Dilemma in Classification

According to World Health Organization (WHO) classification (2008), B-cell neoplasms are classified into precursor B-cell or a mature B-cell phenotype and this classification was also kept in the latest WHO revision (2016). We are reporting a male patient in his fifties, with tonsillar swelling diagnosed as diffuse large B-cell lymphoma (DLBCL), germinal center. He received 6 cycles of RCHOP and showed complete metabolic response. Two months later, he presented with severe CNS symptoms. Flow cytometry on bone marrow (BM) showed infiltration by CD10-positive Kappa-restricted B-cells with loss of CD20 and CD19, and downregulation of CD79b. Moreover, the malignant population showed Tdt expression. BM Cytogenetics revealed t(8;14)(q24;q32) within a complex karyotype. Retrospectively, MYC and Tdt immunostains performed on original diagnostic tissue and came negative for Tdt and positive for MYC. It has been rarely reported that mature B-cell neoplasms present with features of immaturity; however the significance of Tdt acquisition during disease course was not addressed before. What is unique in this case is that the emerging disease has acquired an immaturity marker while retaining some features of the original mature clone. No definitive WHO category would adopt high-grade neoplasms that exhibit significant overlapping features between mature and immature phenotypes.

Spinal cord compression secondary to extramedullary hematopoiesis: A rareness in a young adult with thalassemia major

We report a case of a thalassemia major male patient with back pain associated to severe weakness in lower extremities resulting in the ability to ambulate only with assistance. An urgent magnetic resonance imaging (MRI) of thoracic and lumbosacral spine was requested. A posterior intraspinal extradural mass lesion compressing the spinal cord at the level of thoracic T5-8 was present, suggesting an extramedullary hematopoietic centre, compressing the spinal cord. The patient was treated with blood transfusion, dexamethasone, morphine and paracetamol, followed by radiotherapy in 10 fractions to the spine (daily fraction of 2Gy from T3 to T9, total dose 20 Gy). His pain and neurologic examination quickly improved. A new MRI of the spine, one week after radiotherapy, showed an improvement of the extramedullary hematopoietic mass compression. In conclusion, EMH should be considered in every patient with ineffective erythropoiesis and spinal cord symptoms. MRI is the most effective method of demonstrating EMH. The rapid recognition and treatment can dramatically alleviate symptoms. There is still considerable controversy regarding indications, benefits, and risks of each of modality of treatment due to the infrequency of this disorder. (www.actabiomedica.it)