Large Lymphoid Cells Research Articles

Polymorphous lymphoproliferative disorder: a clinicopathological analysis

Lymphoproliferative disorder (LPD) with polymorphous composition of proliferation (polymorphous LPD), containing large lymphoid cells together with small lymphocytes, plasma cells, macrophages, and/or eosinophils, is found in individuals with immunodeficiency conditions. Clinicopathological findings in 19 cases of polymorphous LPD registered with the Osaka Lymphoma Study Group, Osaka, Japan, were analyzed; they represented 0.4% of the registered cases. In six cases, there was a history of rheumatoid arthritis; five of them had received immunosuppressive agents. There were no acquired immunodeficiency syndrome cases or organ transplant recipients. Southern blotting and/or polymerase chain reaction (PCR)-based clonality analysis revealed monoclonal B cell and T cell proliferation in eight and six cases (B- and T-LPD), respectively, and polyclonality in one. In B-LPD, there was polymorphous proliferation, containing large B-lymphoid cells, while medium-to-large T lymphoid cells with occasional eosinophilic infiltration were seen in T-LPD. Epstein-Barr virus (EBV) was detected in three of eight B-LPD, four of six T-LPD, and one of one polyclonal LPD. The prognosis was not favorable; the 3-year overall survival rate was 49.7 +/- 17.3%. Thus, polymorphous LPD is relatively rare in Japan and is a heterogeneous disease with monoclonal proliferation of B or T cells; additionally, it is occasionally EBV-associated, and behaves as an aggressive lymphoma.

Diffuse large B-cell lymphoma of non-germinal center B-cell type of the heart in an immunocompetent woman: an autopsy case

Primary lymphoma of the heart is extremely rare and almost always occurs in immunodeficient persons. The author reports a very rare autopsy case of primary diffuse large B-cell lymphoma in an immunocompetent woman. A 55-year-old woman presented with chest pain and arrhythmia. Various imaging modalities including US, CT, MRI, and gallium-scintigraphy revealed a mass in the right atrium and pericardial effusion. No tumor formations were recognized in other organs. Pericardial effusion cytology revealed malignant large lymphoid cells of B-cell type positive for CD20. Laboratory data did not reveal immunosuppression, and human immunodeficiency virus was negative. Therefore, a clinical diagnosis of primary heart lymphoma was made. The patient was treated with chemo-radiation, but died of heart failure 4 years after the first presentation. An autopsy revealed a tumor formation (4 × 5 × 6 cm) in the right atrium and ventricle of the heart. No tumor formation was recognized in other organs. Histological and immunohistochemical studies showed that the cardiac tumor was diffuse large B-cell lymphoma of non-germinal center B-cell type; tumor cells were positive for CD45, CD20, CD79α, bcl-2, and λ-chain, but negative for EBV latent membrane antigen 1, CD10, bcl-6 and MUM1. Epstein-Barr virus protein and DNA were negative by immunohistochemistry and in situ hybridization. It was suggested that primary lymphoma of the heart may occur in immunocompetent persons. This is the first report of diffuse large B-cell lymphoma of the heart with a classification of non- or germinal center B-cell type.

Extranodal diffuse non hodgkin lymphoma in the thigh

Diffuse large B-cell lymphoma usually starts as a rapidly growing mass in an internal lymph node and can grow in other areas such as the bone or intestines. About 1/3 of these lymphomas are confined to one part of the body when they are localized. In the case of a 78-year-old man, an extensive tumour was located on the right thigh. Biopsies of the tumour revealed diffuse proliferation of large lymphoid cells which have totally affected the normal architecture of striated muscle. The patient received multimodality treatment including chemotherapy of the CHOP regimen and adjuvant radiotherapy. Despite this being a fast growing lymphoma, about 3 out of 4 people will have no signs of disease after initial treatment, and about half of all people with this lymphoma are cured with therapy.

Utility of Chimerism Analysis to Determine Tissue of Origin in Post Transplant Lymphoproliferative Disorder (PTLD).

Abstract 4305Post-transplant lymphoproliferative disorder (PTLD) is one of the major complications of organ transplantation. Most PTLDs are associated with Epstein-Barr virus (EBV) infection of B-lineage lymphocytes. Central nervous system (CNS) involvement is rare. Although most PTLDs following solid organ transplants is of recipient origin, PTLDs following bone marrow or stem cell transplant are mostly of donor cell origin. Origin of the tumor cells are of crucial importance in deciding treatment and predicting prognosis. Here we report a case of PTLD of diffuse large B cell Lymphoma of donor tissue origin determined by chimerism analysis. The patient was a 52-year-old woman with myelofibrosis (Myeloproliferative disorder) who received unrelated donor peripheral blood stem cell transplantation. The donor was an ABO compatible, HLA matched unrelated donor. Post transplant immunosuppression therapy was administered. The post transplant history was complicated by multiple viral infections, including BK, CMV and EB virus. Four months after transplantation, the patient developed fever and mental status changes, MRI of brain showed multiple enhancing lesions. Brain biopsy revealed brain tissue with dense infiltration of large atypical lymphoid cells predominantly perivascular in location. Immunohistochemical stains reveal that the large atypical lymphoid cells are of B-cell origin and these cells are 100% positive for Ebstein Barr virus by EBV encoded RNA by in-situ hybridization. The flowcytometry study revealed a monoclonal population of B cells with Kappa light chain restriction. These findings support the diagnosis of post transplant lymphoproliferative disorder (PTLD) of diffuse large B-cell lymphoma type. To determine the origin of tumor cells, chimerism analysis of the host DNA (buccal) and tumor DNA were performed. Short tandem repeat (STR) multiplex PCR assay were performed using the AmpFlSTR Identifiler PCR amplification kit (Applied Biosystems, Foster City, CA). After amplification, samples were analyzed on an ABI 310 DNA Sequencer (Applied Biosystems). The allele distribution was significantly different between the recipient DNA (from buccal swab) compared to tumor DNA indicating donor origin of the tumor (PTLD). The patient was then placed on high dose methotrexate and dexamethasome, however her condition deteriorated dramatically and the patient expired shortly following the diagnosis. It is known that the major pathogenetic defect of PTLD is the insufficient EBV-specific cytotoxic T-cell control of EBV-driven B-cell proliferations. Despite this understanding, determining the right therapy for any given patient with PTLD remains a major clinical issue. It is important to identify patients who will benefit from reduction of immunosuppression, who will benefit from Rituximab. It is also important to develop more effective, less toxic chemotherapies for resistant or aggressive disease. The chimerism analysis performed on our patient to identify tumor cell origin is an unique and reliable method to help directing clinical management of PTLD. Disclosures:No relevant conflicts of interest to declare.

Lymphoma‐Associated Polymyositis in Dogs

Lymphoma‐Associated Polymyositis in Dogs

Peripheral T-cell lymphoma developing at ileocolonic anastomosis site after colectomy for adenocarcinoma

A 69-year-old man underwent right hemicolectomy for colon cancer in the transverse colon in 2005. Two years after surgery, he was admitted with abdominal pain. Colonoscopy revealed a submucosal tumor of approximately 4 cm in size at the ileocolonic anastomosis site. In the biopsied samples from the anastomosis site, there was diffuse proliferation of large lymphoid cells, which were immunohistochemically positive for CD3 and CD4, but negative for CD8 and CD20. Clonality analysis of T-cell receptor-beta gene rearrangement revealed a single band, indicating monoclonal proliferation of the T- lymphocytes. Epstein–Barr virus in situ hybridization did not reveal any positive signals in any of the tumor cells. Anti-human T-lymphotropic virus-I was negative. Based on these findings, the recurrent tumor was diagnosed as peripheral T-cell lymphoma-unspecified (PTCL-u).

Synchronous meningioma and anaplastic large cell lymphoma

Synchronous primary brain tumors are exceedingly rare. When they occur, most cases are associated with metastatic disease. To the best of our knowledge, we report the first case of an atypical meningioma infiltrated by a T-cell-primary central nervous system lymphoma (PCNSL), specifically anaplastic large cell lymphoma (ALCL). We present a novel, unifying, plausible mechanism for its origin based on theories in the current literature. A 65-year-old man with a history of near-total resection of atypical meningioma presented with a complaint of progressive headaches. Imaging revealed recurrent tumor. Left frontal-temporal craniotomy with near-total tumor resection followed by radiation was performed. Recurrent symptomatic tumor led to repeat left frontotemporal craniotomy with tumor resection and partial anterior temporal lobectomy. Part of the specimen showed predominantly fibrotic neoplasm composed of nests and whorls of meningothelial cells, highlighted by epithelial membrane antigen (EMA) staining. The remainder of the specimen consisted of densely cellular neoplasm centered in connective tissue, including areas involved by meningioma. This tumor was composed of moderately large lymphoid cells with large nuclei, prominent nucleoli, and amphophilic cytoplasm. These cells were strongly immunoreactive for CD3 and CD30 but remained unstained with EMA, anaplastic lymphoma kinase-1 (ALK-1), CD15 or cytotoxic associated antigen TIA-1. Smaller mature lymphocytes, chiefly T-cells, were intermixed. The morphologic and immunohistochemical features were considered typical of anaplastic large T-cell lymphoma. The pathogenesis of this association may have been due to radiation-mediated breakdown of the blood-brain barrier with subsequent T-cell infiltration and proliferation. We advocate aggressive resection and long-term surveillance for individuals with metastasis, especially higher-grade neoplasms that receive radiotherapy.

Clinicopathologic features of systemic EBV-positive T-cell lymphoproliferative disease of childhood

To study the clinicopathologic features, diagnosis and differential diagnosis of systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood (CSEBV(+)T-LPD). Thirty cases of CSEBV(+)T-LPD were retrospectively studied by light microscopy, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The clinical information and follow-up data were analyzed. Nineteen of the 30 patients were males and 11 females. The median age of disease onset was 9 years (range = 1.5 to 32 years). The average duration between disease onset and diagnosis was 14 months. The major clinical manifestations were fever (96.7%), lymphadenopathy (83.3%) and hepatosplenomegaly (66.7%). Cutaneous manifestations were not uncommon, which included hypersensitivity to mosquito bite (13.3%) and skin rash (20.0%). Six of the 20 patients died on follow up. Histologically, the lymph nodes showed expansion of T zone, with diminished or effaced lymphoid follicles. The lymphoid cells were of small to medium size. Scattered large lymphoid cells were also identified in the expanded T zone. Furthermore, the liver and spleen showed mild to marked sinusoidal infiltration. In some cases, various degrees of sinus histiocytosis with erythrophagocytosis were present. Skin biopsies showed mild to marked degree of lymphocytes infiltration in dermis. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T lineage and CD3 positive. They also expressed cytotoxic molecules granzyme B and TIA-1. Seven of the 8 cases examined were CD8 positive, while the remaining case was mainly CD4 positive. Thirteen of 15 cases were shown to be CD56 negative. The number of EBER-positive cells ranged from 5 to more than 500 per high-power field. These cells included small to large lymphoid cells located mostly in the expanded T zone and sometimes in the germinal centers. Nine of the 30 cases, which consisted mainly of medium to large-sized lymphoid cells, were also EBER positive. Systemic EBV-positive T-cell lymphoproliferative disease of childhood occurs most often in children and young adults, with a median age of 9 years. It has a subacute or chronic clinical course. Most of the patients have evidence of systemic disease, often with lymph node, liver, spleen and skin involvement. It carries a poor clinical outcome and can be life-threatening. The disease is characterized by a clonal proliferation of EBV-infected T cells with cytotoxic immunophenotype. Definitive diagnosis requires correlation between clinical, pathologic and ancillary investigation findings.

Diffuse large B-cell lymphoma with a high number of epithelioid histiocytes (lymphoepithelioid B-cell lymphoma): a study of Osaka Lymphoma Study Group

The aim of this study was to clarify whether diffuse large B-cell lymphoma (DLBCL) with a high number of epithelioid histiocytes (DLBCL-EH) could have distinctive clinicopathological characteristics. Clinicopathological findings in 22 cases with DLBCL-EH and, as a control, 96 cases with ordinary type of DLBCL were analyzed. There were ten men and 12 women with ages ranging from 38 to 91 (median, 64) years. The primary site was lymph node in 16 cases, extranodal organs in three, and unknown in three. Stage of disease was I in five cases, II in three, III in nine, and IV in five. Histologically, there was a diffuse proliferation of large lymphoid cells admixed with numerous clusters of epithelioid histiocytes sprinkling throughout the lesions. Immunohistochemically, the large lymphoid cells were CD20(+), CD15(-), and CD3(-) and positive for CD10, bcl-6, and MUM1 in nine (41%), eight (36%), and 12 (55%) of 22 cases, respectively. Epstein-Barr virus positive rate was higher in DLBCL-EH (23.8%) than that in ordinary DLBCL (4.5%; P<0.05). Clonality analysis revealed monoclonal bands in all of the examined 20 cases with DLBCL-EH. Multivariate analysis revealed the prominent epithelioid reaction to be an independent factor for favorable prognosis. These findings suggest that DLBCL-EH could be a specific morphological variant of DLBCL associated with a better prognosis.

Spontaneous regression of primary breast lymphoma

Described herein is a case of primary breast lymphoma (PBL) that underwent spontaneous regression (SR). A 71-year-old woman visited hospital because of the rapid growth of a tumor in her left breast. On imaging, including magnetic resonance imaging (MRI), a discrete solid nodule was detected, which suggested malignant tumor. Histology of the following core needle biopsy (CNB) specimen indicated diffuse large B-cell lymphoma (DLBCL). The patient had no past history of lymphoma and there was no evidence of systemic lymph nodes enlargement. After CNB, however, the patient noticed that her breast nodule gradually decreased in size without any specific treatment. Subsequent MRI showed an ill-defined nodular area suggesting a regressing tumor. Excisional biopsy indicated fibrotic mammary tissue devoid of large neoplastic lymphoid cells. The patient has remained well without evidence of recurrent lymphoma more than 18 months after her original diagnosis. This case is considered to be unique in a PBL showing SR, probably induced by an intervention of CNB and histologically confirmed on sequential examinations in addition to illustrative before-and-after imaging. To the best of the authors' knowledge no other PBL of DLBCL has been reported as undergoing a complete SR in the English-language literature.

Composite gastrointestinal lymphoma consisting of diffuse large B-cell lymphoma and peripheral T-cell lymphoma

Composite lymphomas are defined as two different types of lymphomas presenting in the same anatomic site [1]. A rare case of a composite gastrointestinal lymphoma consisting of diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL) is presented. A 65-year-old woman was diagnosed with mucosaassociated lymphoid tissue lymphoma of the duodenum in 2001. Eradication therapy for Helicobacter pylori resulted in complete remission of the lymphoma. After 4 years, she was admitted to our hospital due to hematemesis in December 2005. The levels of hemoglobin and soluble interleukin-2 receptor were 10.4 g/dL and 938.1 U/mL, respectively. Endoscopic examination revealed multiple ulcers in the stomach and ileum. On microscopy, both gastric and ileal ulcers showed diffuse proliferation of large lymphoid cells, which were positive for CD20, CD79a, and Epstein–Barr virus (EBV) encoded RNA-1 (EBER-1) in situ hybridization (ISH) and negative for CD3 and CD45RO (Fig. 1a–d). These findings were compatible with EBV-positive DLBCL of the elderly, according to the new WHO classification [2]. After 3 courses of combination chemotherapy (pirarubicin, vincristine, cyclophosphamide and prednisolone; THP-COP) with rituximab, the ileal ulcers disappeared, but the area of the gastric lymphoma enlarged. A partial gastrectomy was performed with a diagnosis of perforation of the stomach in April 2006. Unexpectedly, pathological examination of the resected specimen demonstrated diffuse proliferation of smallto large-sized lymphocytes with T-cell markers (positive for CD3, CD4, CD45RO, CD56 and TIA-1, and negative for CD8, CD20, CD79a and EBER-ISH, Fig. 1e–h). The diagnosis of PTCL was made, and the distribution of the disease and strong positivity of TIA-1 suggested enteropathyassociated T-cell lymphoma. Since the size of the lymphoma cells was mainly small to medium and they were positive for CD56, we speculated that the lymphoma could be classified into enteropathy-associated T-cell lymphoma type 2 [3, 4]. However, the mucosa of the specimen was almost destroyed and the distribution pattern was not clear. Retrospectively, we performed PCR analysis of T-cell receptor (TCR) gamma chain gene in the gastric specimen at the DLBCL stage in 2005 and PTCL stage in 2006 (Fig. 2). Although scattered T cells were present in the specimen, rearrangement of TCR was not detected. On the other hand, strong rearranged band was detected at the PTCL stage. Since PTCL was diagnosed during the course of chemotherapy against DLBCL and residual B-cell disease could not be denied after gastrectomy, the patient was given 2 courses of consolidation chemotherapy (etoposide, methylpredonisolone, cytarabine and cisplatin; ESHAP) with rituximab. Achievement of complete remission was confirmed by 18[F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan in June 2006. However, Y. Tachikawa M. Shiratsuchi E. Sada K. Idutsu J. Kiyasu R. Takayanagi Y. Abe (&) Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan e-mail: abey@intmed3.med.kyushu-u.ac.jp

Lymphome B cutané à grandes cellules « de type jambe » sur cicatrice de brûlure

Primary cutaneous B-cell lymphomas form a heterogeneous group of lymphoid proliferations found on the skin. We report a case of primary leg-type cutaneous large B-cell lymphoma occurring on the site a previous leg burn. A few rare cases of cutaneous lymphoma forming on burn scars have been described, but these concern primary cutaneous lymphomas of the T-cell phenotype. An 85-year-old man with a history of a burn to the left leg 17 years ago, previously treated with several skin grafts, presented numerous ulcerative budding lesions on the scar area. Histological examination of the skin biopsy revealed the existence in the skin ulcers of atypical large lymphoid cells having an immunoblastic or centroblastic morphology and shown by immunohistochemistry to be of the B-cell phenotype, thereby evoking a diagnosis of large B-cell lymphoma. The lymphoma cells were positive for MUM1/IRF4 and BCL2, and more weakly for BCL6, but negative for CD10. The staging examination revealed only cortical lysis of the left tibia. Temporary initial regression was achieved by polychemotherapy comprising cyclophosphamide, vincristine and prednisone in combination with rituximab. This case is novel in that it involves primary large B-cell lymphoma, leg type, occurring on burn scar tissue. Venous insufficiency and lymphatic stasis have already been incriminated in the genesis of this type of lymphoma; the prior injury and resulting immune dysregulation at the burn site may have also contributed to the development of this neoplasia.

Loss of tumor cell CCR4 expression upon leukemic change in adult T-cell leukemia/lymphoma

Loss of tumor cell CCR4 expression upon leukemic change in adult T-cell leukemia/lymphoma

Peripheral T-cell lymphoma of Lennert type complicated by monoclonal proliferation of large B-cells

A 69-year-old man presented with lymph node swelling in the right inguinal region. A biopsy was made (LN1) and diagnosed as peripheral T-cell lymphoma. The lesion remitted completely over a period of about 51 months after combination chemotherapy, but erythematous papules, systemic lymphadenopathy, and fever of 38 degrees appeared. Skin (S1) and lymph nodes (LN2) were biopsied. Erythematous papules once disappeared spontaneously, but appeared again and were biopsied (S2). LN1 displayed the typical histologic and immunohistochemical features of Lennert lymphoma, i.e., diffuse proliferation of small to large lymphoid cells of CD3+, CD4+, CD8- immunophenotype accompanied by numerous clusters of epithelioid histiocytes. In LN2, the large cells with CD3+, CD4+, CD8- decreased in number, while numerous CD20+ large cells were discernible. Clonality analysis revealed the persistent presence of an identical T-cell clone in LN1 and LN2. Clonal bands of immunoglobulin heavy (IgH) chain gene were detected in LN2 but not in LN1. S1 and S2 showed diffuse proliferation of small to large lymphoid cells of CD20-, CD3+, CD4+, CD8- in the upper dermis, with obvious epidermotropism. Clonality analysis revealed the presence of a T-cell clone identical to LN1 and LN2 with no B-cell clone, indicating the recurrence of PTCL. In situ hybridization (ISH) for Epstein-Barr virus (EBV) genome revealed that positive signals in the nucleus of large B-lymphoid cells appeared only in LN2. Taken together, EBV-positive large B-cell lymphoma appeared transiently in the course of "Lennert lymphoma".

Lymphoproliferative disease of the kidney developing in fibro-inflammatory lesion

An 80-year-old man presented with continuous spike fever and night sweats. Computed tomographic scans revealed a poorly demarcated mass in the upper part of the right kidney, which was resected. At surgery, tumorous lesions were not found in the abdominal cavity. Serum IgG4 level measured after surgery was 40.1 mg/dl. Macroscopically, renal parenchyma of the upper part was replaced by an irregularly shaped grayish-white lesion of elastic, firm consistency. Histologically, the lesion consisted mostly of fibrous tissue in which small lymphoid cells, often with formation of aggregates, were evident. IgG4-positive plasma cells were few in number. Careful macroscopic examination revealed several minute nodules, which histologically consisted of large lymphoid cells, small lymphoid cells, and macrophages. These large lymphoid cells were positive for CD20 and contained Epstein-Barr virus (EBV) genome. Taken together, a diagnosis of EBV-positive B-cell lymphoproliferative disease (LPD) developing in inflammatory pseudotumor (IPT) of the kidney was made. This is the first report of B-LPD in IPT of the kidney. In addition, a presence of EBV in renal lymphoma cells has not yet been reported.

Small cell variant of peripheral T-cell lymphoma, not otherwise specified: a clinicopathologic and immunophenotypic analysis

To study the clinicopathologic features and differential diagnosis of small cell variant of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS). The clinicopathologic features of 5 cases of small cell variant of PTCL, NOS were retrospectively reviewed, with immunohistochemical study, T-cell receptor (TCR) gene rearrangement analysis and evaluation for Epstein-Barr virus (EBV) status. All the 5 patients were males. The mean age was 52.6 years. The median duration before diagnosis was 1 month. Clinically, 3 patients presented in stage IV and 2 in stage III. Four of them had generalized lymphadenopathy and splenomegaly. Hepatomegaly and massive effusion were found in 1 and 2 cases, respectively. Marrow involvement was detected in 3 of the 4 patients with bone marrow biopsy performed and one of them also accompanied by lymphocytosis. Histologically, the involved lymph nodes showed partial or complete effacement of nodal architecture and replacement by a monomorphous population of small lymphoid cells. Scanty large lymphoid cells were also identified in 4 cases. Increase in number of blood vessels was noticed in two of them as well. Immunohistochemically, the lymphoma cells in all cases expressed two or more of the T-cell markers and CD43. The staining for CD20, TdT, CD56 and granzyme B was negative. CD99 expression was noted in 3 of the 4 cases. The Ki-67 index ranged from 5% to 15%. Clonal TCRgamma gene rearrangement was detected in the 4 cases studied and one of them also showed TCRbeta gene rearrangement. In-situ hybridization for EBV-encoded RNA was negative in the 4 cases studied. Follow up information was available in 3 of the 5 cases. All of the 3 patients died of the disease, with an average survival of 21.7 months. Small cell variant of PTCL, NOS represents a rare disease entity which often presents in advanced tumor stage and carries a poor prognosis.

Metastatic Angioinvasive Lymphoma (Lymphomatoid Granulomatosis) in a Cat

A subcutaneous mass removed from the right rear leg of a 17-year-old, spayed, female Domestic Shorthair cat was characterized histopathologically by granulomatous inflammation, sheets of large atypical lymphoid cells, and necrosis. The walls of the small and medium caliber blood vessels were invaded transmurally by atypical lymphoid cells. A diagnosis of angioinvasive lymphoma (AIL), or lymphomatoid granulomatosis, was made based on histopathologic findings. The cat was euthanized 2 months later because of recurrence of the mass and elevated serum alanine aminotransferase activity, and a necropsy was performed. The histopathologic lesion of AIL was seen in the skin and subcutis of the right rear leg, and neoplastic cell infiltrates were seen in adjacent skeletal muscle, right superficial inguinal lymph node, liver, and spleen. By immunohistochemistry, variable numbers of neoplastic cells expressed B-lymphocyte antigen 36 (BLA36) or cluster of differentiation (CD)3 markers, indicative of B- and T-cell lineages, respectively. Neoplastic cells were uniformly positive for vimentin and uniformly negative for cytokeratins and myeloid/histiocytic antigen. Although the cat had received a Rabies virus vaccine subcutaneously in the right rear leg 6 months earlier, the AIL lesion was not typical of vaccine-induced sarcomas. The AIL in this cat was unusual because the extrapulmonary metastases involved the skin and subcutis.

Plasmacytoid Dendritic Cell Leukemia in Children

CD4/CD56 malignancies are rare hematologic neoplasms, which have recently been shown to represent the malignant counterpart of plasmacytoid dendritic cells (pDC). A 5-year-old boy initially presented with multiple subcutaneous lesions on his upper and lower extremities. Skin biopsy results showed large atypical lymphoid cells in the dermis. The blast cells were stained with CD4 and CD56. In the bone marrow aspirate, 20% of the blast cells were found. The patient was diagnosed as acute unclassified leukemia and received chemotherapy designed for the treatment of acute myeloid leukemia. He achieved a complete remission that lasted for 8 months. However, multiple subcutaneous lesions recurred 1 month after the end of the therapy, with increasing blast cells in his blood. Immunophenotypically, the blast cells were positive for CD2, CD4, CD7, and CD56, and negative for CD3, CD13, CD19, CD33, and CD34 antigens. The blast cells were positive for CD123 (interleukin-3 receptor alpha chain) and blood dendritic cell antigen-2, which are expressed on pDC. The patient was diagnosed as acute leukemia derived from pDC. The CD4, CD56, CD3, CD13, CD19, CD33 profile is highly suggestive of this disease, and the CD123 and blood dendritic cell antigen-2 markers are useful in helping to diagnose pDC leukemia.

Aberrant Co-Expression of Key Transcription Factors BCL6, IRF4 and FOXP1 Are Frequently Observed in Diffuse Large B-Cell Lymphoma

Diffuse Large B-cell Lymphoma (DLBCL) is classified into germinal centre (GCB) and activated B-cell (ABC) type by comparison with the phenotype of normal B-cells. Using single-color immunocytochemistry, tumors can be classified using a simple algorithm based on the expression of CD10, BCL6 and IRF4. This classification may have prognostic relevance and correlates with balanced translocations involving the immunoglobulin locus. However, the phenotypic differences between normal and neoplastic cells may be of greater relevance to understanding the pathogenesis of DLBCL and in developing effective diagnostic techniques. To investigate this we examined the co-expression of BCL6, IRF4 and FOXP1. These are key transcription factors that regulate the process of germinal centre and post germinal centre B-cell differentiation. Abnormal co-expression of these molecules would be expected to have major effects on the overall cellular phenotype. A multi-color immunofluorescence (MCIF) technique was developed that allowed the co-expression of these markers to be assessed in relation to the PAX5 positive B-cell population. The use of a multi-color technique allows the distinction between co-expression at the level of individual cells and differentiation within the tumor as a whole. We first determined the pattern of expression of these transcription factors in normal B-cells. In reactive lymph nodes the expression of BCL6, IRF4 and FOXP1 was almost mutually exclusive with only a small proportion of co-expressing cells. In a series of 61 DLBCL co-expression of both BCL6/IRF4 and IRF4/FOXP1 was found in 41/61 (67%) of the cases. In most of these cases the level of co-expression was greater than 50% of the PAX5 positive large lymphoid cells. Co-expression was not present in 11/61 (18%) of the tumors. In the remaining cases there was co-expression of either BCL6/IRF4 or IRF4/FOXP1. There was no correlation between the occurrence of co-expression of these combinations of transcription factors and the expression of CD10 or the classification into GCB and ABC phenotypes. In 16 of the cases the sample used was a small needle core biopsy in which assessment of nodal architecture was impossible. In these cases it was possible to confidently determine the presence of abnormal co-expression in 14/16 (87.5%) of the cases. One explanation for the aberrant co-expression of BCL6 and IRF4 in DLBCL would be the presence of a 3q27 rearrangement leading to dysregulation of BCL6 expression. However, in this series there was no correlation between BCL6/IRF4 co-expression and abnormalities of 3q27 detected by interphase FISH. These results show that in the majority of cases of DLBCL the key transcription factors regulating post germinal centre B-cell differentiation are expressed in combinations not seen in normal B-cells. This is likely to be a central element in the pathogenesis of these tumors. The ability to reliably identify these abnormalities by MCIF has potential value in improving the reliability of diagnosis of DLBCL when only small biopsy samples are available and it is likely that this approach can be extended to other types of lymphoma.

Rapid progression of Epstein-Barr-virus-positive gastric diffuse large B-cell lymphoma during chemoradiotherapy: a case report.

A 61-year-old woman was referred to our hospital with epigastralgia and appetite loss. Barium examination and upper gastrointestinal endoscopy revealed uneven erythematous mucosa with multiple elevated lesions from the gastric fornix to the upper corpus. Abdominal computed tomography showed thickening of the wall of the fornix and swelling of perigastric lymph nodes, but whole-body gallium scintigraphy and bone marrow examination did not indicate further involvement. Biopsy specimens showed diffuse infiltration of large atypical lymphoid cells in which Epstein-Barr virus (EBV) was detected by in situ hybridization. Diffuse large B-cell lymphoma (DLBCL), stage II1, was diagnosed. Combination chemotherapy [cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP)], was given, and this was followed by radiotherapy. Partial remission was achieved by chemotherapy, but the disease progressed rapidly during radiotherapy. Because the reported prognosis of EBV-positive DLBCL is unfavorable, the therapeutic strategy for EBV-positive gastric DLBCL should be considered carefully.