Differentiating Lymphoblastic Lymphoma and Ewing's Sarcoma: Lymphocyte Markers and Gene Rearrangement

Abstract

We encountered a child with an intraosseous small round cell tumor that was negative for LCA, CD20 (L26), and CD3 and positive for vimentin, CD99 (MIC-2), and periodic acid-Schiff. The tumor exhibited rosette-like formations. This case was initially interpreted as Ewing's sarcoma (ES); however, additional studies revealed positivity for CD79a, CD43, and TdT expression, and an immunoglobulin heavy chain gene rearrangement (IgH-R) by polymerase chain reaction (PCR) established this to be a precursor B-lymphoblastic lymphoma. Because the differential diagnosis of ES and lymphoblastic lymphoma can be difficult and the differential diagnostic value of leukocyte antigens and immunoglobulin heavy chain gene rearrangement studies have not been fully evaluated, we conducted a more extensive investigation on 33 (21 soft tissue and 12 intraosseous) ES cases. Cases were retrieved from the files of the Department of Pathology at Georgetown University and from the Soft Tissue Registry of the Armed Forces Institute of Pathology. The cases were studied by light microscopy, immunohistochemistry, and PCR for IgH-R and T cell receptor gamma chain gene rearrangement (T␥-R). There were 17 females and 16 males; the mean age was 29.3 years. Locations included the extremities (n ‫؍‬ 17) and trunk (n ‫؍‬ 16). All cases fit the ES spectrum by light microscopy and immunohistochemistry, as previously determined, and were negative for lymphoid markers (LCA, CD3, CD20, CD43, CD79a, and TdT), CD10 and CD34. CD99 was positive in 31/33 and bcl-2 was weakly positive in 13/33 cases. All 21 cases studied for gene rearrangements by PCR were negative for IgH-R and T␥-R. Distinction of intraosseous lymphoblastic lymphoma from ES may be difficult because lymphomas may occasionally exhibit unexpected morphologic and immunophenotypic properties including LCA, CD3 and CD20 negativity and cytokeratin positivity. Additional analysis using CD79a, CD43, TdT, and PCR should be performed to avoid misdiagnosis. True ES is negative for lymphoid markers including CD79a, CD43, and TdT, as well as for IgH-R and T␥-R.

Head and Neck Rhabdomyosarcoma: Clinical and Pathologic Characterization of Seven Cases

“…Examples are Ewing's sarcoma, small cell melanoma, and lymphoblastic lymphoma. Immunohistochemistry for markers such as CD99 (diffuse membranous pattern in Ewing's sarcoma [26]), S100, Melan A and HMB-45 (melanoma) and TdT, CD43 and CD79a (lymphoblastic lymphoma [27,28]) will be helpful in the diagnostic work-up. Ancillary tests such as Fluorescent In Situ Hybridization (FISH) or Reverse Transcription Polymerase Chain Reaction (RT-PCR) assays to show the presence of EWS gene rearrangement in Ewing's sarcoma and flow cytometry assay to show clonal lymphoid population will also be useful.…”

Pre‐B‐cell acute lymphoblastic leukemia with bulk extramedullary disease and chromosome 22 (EWSR1) rearrangement masquerading as Ewing sarcoma

“…Despite the great advances in technology, problems still exist with regards to differentiating between similar tumors from that group. This difficulty is evident in the differentiation of the Ewing sarcoma family of tumors (ESFT) from lymphoblastic lymphoma (LBL) (4,5).…”

A Peripheral Primitive Neuroectodermal Tumor with Generalized Bone Metastases in a Puppy

“…3,4,8,11 In children, correct differentiation between a primary osseous lymphoma and EFT is a major diagnostic challenge that additionally requires immunophenotyping, molecular genetic analysis, and ultrastructural evaluation. 2,3,8,10,11,15 In this dog, the consistent negative expression by tumor cells for all canine leukocyte cell-specific markers (see Table 1), together with the ultrastructural findings of intercellular desmosome-like junctions and some cytoplasmic dense core secretory vesicles excluded a diagnosis of an osseous lymphoma. 8,[9][10][11]13 Thus, based on the age, clinical history of orbital swelling with subsequent axial and appendicular skeletal involvement, the histologic and ultrastructural findings, and immunocytochemical profile, the diagnosis of this canine tumor best fits the clinicopathologic criteria of an intraosseous human pPNET (Ewing's sarcoma).…”

“…2,3,8,10,11,15 In this dog, the consistent negative expression by tumor cells for all canine leukocyte cell-specific markers (see Table 1), together with the ultrastructural findings of intercellular desmosome-like junctions and some cytoplasmic dense core secretory vesicles excluded a diagnosis of an osseous lymphoma. 8,[9][10][11]13 Thus, based on the age, clinical history of orbital swelling with subsequent axial and appendicular skeletal involvement, the histologic and ultrastructural findings, and immunocytochemical profile, the diagnosis of this canine tumor best fits the clinicopathologic criteria of an intraosseous human pPNET (Ewing's sarcoma). [2][3][4]8,10,11 Admittedly, because CD99 expression could not be detected in relevant normal dog tissue (lymph node, spleen, and pancreatic islet cells) and the lack of molecular genetic analysis, the diagnosis still depends somewhat on circumstantial evidence.…”

“…However the differential diagnosis of this complex tumor group in young dogs includes at least a rhabdomyosarcoma, neuroblastoma of the PNS, or lymphoma. [2][3][4]10,11,13 A rhabdomyosarcoma was excluded on the basis of the lack of any cytoplasmic striations histologically, further supported both by negative immunocytochemical staining for skeletal myosin and desmin, and by the absence ultrastructurally of myofilaments with Zbands. A neuroblastoma was ruled out based mainly on the distribution of gross lesions, together with histologic absence of Homer-Wright rosettes, and lack of neuritic processes by TEM.…”