Plasma Cell Myeloma Type Posttransplant Lymphoproliferative Disorder in an 18-Month-Old Heart Transplant Recipient: Case Report and Review of the Literature.

Plasma cell myeloma type posttransplant lymphoproliferative disorder (PTLD) is a rare subtype of monomorphic B-cell/plasmacytic-type PTLD. Only 10 cases of monomorphic plasmacytic-type PTLD have been previously reported in pediatric transplant recipients (kidney, liver, small bowel-liver, and heart). We present a case of Epstein-Barr virus positive monomorphic plasma cell myeloma type PTLD that developed 10 months after cardiac transplant in an 18-month-old boy. The bone marrow showed replacement by about 20% to 40% lambda-restricted plasmacytoid lymphocytes and plasma cells (by immunohistochemistry and flow cytometry, respectively). His serum free lambda to kappa light chain ratio was >300, comparable to that seen in myeloma in nontransplant patients. The neoplastic cells were Epstein-Barr virus small RNA positive by in situ hybridization. He was treated with rituximab in combination with ganciclovir, intravenous immune globulin, and discontinuation of immunosuppressants. However, he succumbed to septic shock and multiorgan failure 1 month after diagnosis.

Cytotoxic Molecule-positive Epstein-Barr Virus-associated Peripheral T-cell Lymphoma in a 20-Month-old Child: A Case Report and Review of the Literature.

Peripheral T-cell lymphoma (PTCL) is rare in children. Expression of cytotoxic molecules (CM) in nodal PTCL has unique clinicopathologic features, including an Epstein-Barr virus (EBV) association. However, CM+, EBV-associated PTCL is extremely rare in the childhood, with only 1 study having been reported to date, including both pediatric and adult patients. We report a case of CM+ PTCL in a 20-month-old boy with left neck lymphadenopathy as well as multiple visceral lesions. A biopsied lymph node was diffusely infiltrated by atypical lymphoid cells with a CD4/CD8, granzyme B+, perforin+, and TIA-1+ phenotype, and EBV positivity by in situ hybridization. Rearrangements of the TCR γ-chain and ß-chain genes were demonstrated by polymerase chain reaction. Ancillary genetic studies detected trisomy 2, trisomy 10, a structurally abnormal 6p, and additional copies of the IRF4 gene. Multiple bone marrow biopsies failed to show any evidence of tumor, histiocytic hyperplasia, or hemophagocytosis. This lesion was therefore diagnosed as "CM+, EBV-associated high-grade peripheral T-cell lymphoma." After 5 cycles of chemotherapy, the patient was in remission 8 months following initial diagnosis. To our knowledge, this represents the youngest child with this rare tumor in the published literature, and showing an unusually favorable initial response to therapy.

Mast cell sarcoma in an infant: a case report and review of the literature.

Mast cell diseases comprise a spectrum of disorders including cutaneous mastocytosis, indolent or aggressive systemic variants including leukemia, and unifocal tumor formations such as benign extracutaneous mastocytoma or aggressive mast cell sarcoma (MCS). Many mast cell diseases are associated with aberrancy of c-KIT proto-oncogene resulting in tyrosine kinase activity, typically exhibiting point mutation in codon 816. MCS is an exceedingly rare clinicopathologic entity characterized by a unifocal accumulation of neoplastic mast cells that grow in a locally destructive manner. We report a case in a 2-year-old boy who was initially diagnosed at 8 months of age with atypical cutaneous mastocytoma of the right ear with subsequent aggressive, destructive growth pattern; features that were most consistent with MCS. So far, MCS has been documented in the literature in at least 6 human cases. To the best of our knowledge, our case represents the first MCS in an infant. Thorough multimodal approach with strict follow-up is relevant in appropriately diagnosing this rare entity, particularly in differentiating this lesion from other neoplasms that are more likely to occur in infancy.

Complete absence of KSHV/HHV-8 in posttransplant lymphoproliferative disorders: an immunohistochemical and molecular study of 52 cases.

Posttransplant lymphoproliferative disorders (PTLDs), a heterogeneous group of monoclonal or polyclonal lesions, occur in immunosuppressed patients after solid organ or bone marrow transplantation. Although most PTLDs are Epstein-Barr virus (EBV)+ and seem to represent EBV-induced proliferations of monoclonal (or less often polyclonal) B, T, or plasma cells, a subset of PTLDs is EBV-. Because Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) has been described in association with the development of hematolymphoid and nonhematolymphoid neoplasms in HIV+ patients, we investigated whether there is an association between KSHV/HHV-8 and PTLDs. Formalin-fixed, paraffin-embedded tissue from 52 confirmed PTLD cases were analyzed immunohistochemically for expression of KSHV/HHV-8 latent nuclear antigen (LNA)-1 protein and by polymerase chain reaction-hybridization analysis for the KSHV/HHV-8 genome. The PTLD subtypes included 12 with early lesions (1 plasmacytic hyperplasia and 11 infectious mononucleosis-like), 10 polymorphic, 23 monomorphic (5 Burkitt, 14 diffuse large B-cell lymphoma, 1 plasmacytoma, 1 multiple myeloma, and 2 T-cell), 1 Hodgkin lymphoma (HL), 5 HL-like lesions, and 1 unclassified or other. None of the 51 tested specimens showed expression of KSHV/HHV-8 LNA-1. Furthermore, all 46 specimens tested demonstrated complete absence of the KSHV/HHV-8 genome. Our data clearly indicated that KSHV/HHV-8 is not associated with PTLDs.

Frequent expression of CD99 in anaplastic large cell lymphoma: a clinicopathologic and immunohistochemical study of 160 cases.

Originally described as a diagnostically useful marker for Ewing sarcoma, CD99 immunoreactivity has also been documented in a variety of other tumors, including hematopoietic neoplasms. By using conventional paraffin immunoperoxidase staining and tissue microarrays, we retrospectively investigated CD99 expression in a series of 160 anaplastic large cell lymphoma (ALCL) cases. Of the 160 cases, 103 (64.4%) were positive for CD99. The distribution of CD99 positivity was similar for nodal (66/103 [64.1%]), extranodal, (21/32 [66%]), and primary cutaneous lesions (16/25 [64%]). CD99 expression was present in 96 (64.4%) of 149 of the common type, 4 (80%) of 5 of the small cell variant, and 3 (50%) of 6 of the lymphohistiocytic variant cases. CD99 expression was slightly more frequent in anaplastic large cell lymphoma kinase (ALK)+ cases compared with ALK- cases (43/54 [80%] vs 44/81 [54%]). With 2 exceptions, ALK+ ALCL was seen only in patients younger than 41 years. We conclude that CD99 is frequently expressed in ALCL, with a slightly increased frequency in the younger age ALK+ cases. Nodal and extranodal ALCL should be considered in the differential diagnosis when a CD99+ neoplasm is encountered.

CD3-positive large B-cell lymphoma.

It is not uncommon for some B-lineage non-Hodgkin lymphomas (NHLs) to aberrantly coexpress T-cell markers, particularly CD5, as well as CD7, CD2, CD4, and/or CD8 in rare cases. Cases of CD3-positive B-cell NHL, however, have not previously been described in the literature. We present 4 cases of large B-cell lymphoma aberrantly coexpressing T-cell marker CD3 and B-lineage markers as well as demonstrating clonal rearrangement of the immunoglobulin genes but not the gamma T-cell receptor gene. To our knowledge, this represents the first series report of B-cell NHL coexpressing T-lineage-specific marker CD3. The identification of such cases indicates that the use of CD3 antibody alone in paraffin sections may lead to an incorrect determination of cell lineage in some B-cell NHL. Immunohistochemistry using additional cell lineage specific markers or molecular analysis for antigen receptor gene rearrangements are necessary for correct determination of the cell lineage in such cases.

Hodgkin lymphoma-like posttransplant lymphoproliferative disorder (HL-like PTLD) simulates monomorphic B-cell PTLD both clinically and pathologically.

Although Hodgkin lymphoma-like posttransplantation lymphoproliferative disorder (HL-like PTLD) has been grouped with classic Hodgkin lymphoma type PTLD (HL-PTLD), controversy remains as to whether it is truly a form of HL or whether it should be more appropriately classified as a form of B-cell PTLD. Because only few cases of HL-like PTLD have been reported, their pathologic nature and clinical behavior have not been well defined. This report characterized 5 cases of HL-like PTLD with respect to their immunophenotype, EBV status, clonality, and clinical outcome. All of the patients were male, with ages ranging from 1.5 to 55 years at diagnosis. PTLD developed from 4 months to 6 years following solid organ transplantation (3 hearts, 1 kidney, 1 liver), and involved both nodal and extranodal sites. All were EBV-related (EBER+) with the large neoplastic cells CD20/CD79a positive but CD15 negative. Immunoglobulin gene rearrangements were detected in 3 of 5 tested. All patients were managed by initial reduction/withdrawal of immunosuppression, with 2 also receiving chemotherapy for non-HL. Three patients died of progressive disease within 2 to 3 months after diagnosis, 1 is alive and well 2 years later, and the fifth was disease free but died of unrelated causes (graft coronary disease) 2 years later. We conclude that, although HL-like PTLD morphologically simulates classic HL PTLD, there are important immunophenotypic, molecular genetic, and clinical differences, suggesting it is in fact most often a B-cell PTLD. Distinction between HL and HL-like PTLD may be important for clinical management and prognosis.

Primary diffuse large B-cell lymphoma of the uterus presenting solely as an endometrial polyp.

We report a primary diffuse large B-cell lymphoma of endometrial polyp in a 44-year-old woman who presented with irregular vaginal spotting and was found to have a polyp protruding from the cervical os. Histology of the polyp showed an atypical diffuse infiltration by large, mononuclear cells within the stroma and between endometrial glands in one of the polypoid fragments. Immunohistochemistry and testing for immunoglobulin heavy chain gene rearrangement showed a B-cell lineage, consistent with diffuse large B-cell lymphoma. Staging procedures including detailed gynecology examination, body computed tomography scan, and bone marrow examination, as well as total hysterectomy, showed no evidence of lymphoma outside of the polyp. To our knowledge, this represents the first well-documented instance of primary lymphoma of the uterus presenting as an endometrial polyp. The differential diagnosis of endometrial biopsies containing an atypical lymphoid infiltrate should include the rather rare possibility of primary uterine lymphoma arising in an endometrial polyp. Immunohistochemistry and/or molecular analysis for antigen receptor gene rearrangements are critical in arriving at the correct diagnosis.

Anaplastic large cell lymphoma associated with Epstein-Barr virus following cardiac transplant.

Posttransplantation lymphoproliferative disorders (PTLDs) eventually occur in approximately 5% of all organ transplant recipients. Most of cases are B-cell proliferations associated with the Epstein-Barr virus (EBV). T-cell PTLDs are relatively rare, although some estimate that up to 14% of posttransplantation malignant lymphomas are T-cell lymphomas even though only a few of these cases are described in the literature. A literature review found only 77 cases of T-cell PTLD, including 1 case following cardiac transplant, 15 cases associated with EBV, and only 1 case of anaplastic large cell lymphoma (ALCL). This single ALCL case followed a liver transplant, was of the T-cell phenotype, and was EBV negative. In this report, we describe a 14-year-old male who developed an EBV-positive, T-cell PTLD of the ALCL subtype after a period of 14 years following cardiac transplant. Immunohistochemical staining established the T-cell origin of the neoplasm with strong expression of CD45, CD3, CD43, and CD2 and also showed expression of CD30 consistent with the histologic features that suggested ALCL. EBER in situ hybridization detected the presence of the EBV. Polymerase chain reaction analysis for T-cell receptor-gamma gene rearrangements confirmed the T-cell lineage of this lymphoma. To our knowledge, this is the first reported case of an EBV-positive T cell lymphoma of the anaplastic large cell subtype following organ transplant.

Primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma of the brain in a patient with acquired immunodeficiency syndrome.

Anaplastic large cell lymphoma is a unique diagnostic subcategory of the T-cell lymphomas in the current World Health Organization classification. Representing approximately 3% of adult and 10% to 30% of childhood non-Hodgkin lymphomas, anaplastic large cell lymphoma classically consists of CD30+ large lymphoid cells with abundant cytoplasm and pleomorphic, often horseshoe-shaped or kidney-shaped nuclei. Among the reported nodal and extranodal sites of occurrence, the gastrointestinal tract and central nervous system have rarely been noted. We report a case of primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma in the brain of a 46-year-old patient with acquired immunodeficiency syndrome. T-cell lineage was confirmed by T-cell receptor gamma chain gene rearrangements using polymerase chain reaction, and extra copies of the anaplastic lymphoma kinase gene of chromosome 2 were demonstrated by fluorescence in situ hybridization analysis. To our knowledge, primary anaplastic large cell lymphoma of the brain has not previously been reported in acquired immunodeficiency syndrome.