Large Lymphoid Cells Research Articles

Primary CD56+ NK/T-cell lymphoma of the rectum accompanied with refractory ulcerative colitis

A case of primary NK/T-cell lymphoma of the rectum accompanied with ulcerative colitis (UC) in a 73-year-old man is reported. He had a 6-year history of repeated admission to our hospital for UC. Total colonoscopy performed 4 months after resolution of refractory UC complicated by cytomegalovirus colitis showed a markedly submucosal tumor in the rectum, which was histologically diagnosed as malignant lymphoma. The findings of computed tomography of the chest and abdomen, gallium scintigraphy, abdominal ultrasonography, and upper gastrointestinal endoscopy showed no abnormal lesions. Therefore, based on a diagnosis of localized rectal lymphoma with UC, proctocolectomy was performed. The resected specimen showed three submucosal tumors in the rectum with local nodal involvement. Histologically, the tumors were characterized by diffusely infiltrating sheets of large atypical lymphoid cells, which were negative for CD4, CD8, and CD20 but were positive for CD56, CD3, and granzyme B. The presence of Epstein-Barr virus (EBV) infection in neoplastic cells was shown by in situ hybridization for EBV-encoded early small RNA1 (EBER-1). Based on these findings, the patient was diagnosed with primary CD56+ NK/T-cell lymphoma of the rectum (stage IIE). This is the first case report of primary rectal NK/T-cell lymphoma accompanied with UC.

Pitfalls of Diagnosis Based on Abnormal Flow Cytometry and [18F]Fluorodeoxyglucose Positron Emission Tomography

A 30-year-old, HIV-positive man with a previous history of an atypical nasopharyngeal Burkitt lymphoma developed fluorodeoxyglucose (FDG) avidity on a routine FDG—positron emission tomography (PET)/computed tomography scan performed 10 months after the completion of all treatment. This new FDG-avid disease was in the area of his initial disease. Flow cytometric assessment of a fine needle aspiration showed a CD10-expressing B-cell population with κ predominance. The corresponding cytology smears had large atypical lymphoid cells along with smaller lymphocytes and macrophages. Because of the patient's previous history of a CD10+, high-grade B-cell lymphoma, the cytologic and flow cytometric findings were considered highly suspicious for a B-cell lymphoma. Because the differential diagnosis included a relapsed Burkitt lymphoma versus a second, unrelated lymphoma (the former with a dismal prognosis) it was deemed prudent to obtain more tissue via an open biopsy for confirmation of diagnosis and exact subclassification. An open biopsy, however, revealed a reactive lymph node with enlarged geographic follicles; no lymphoma was demonstrable and c-Myc studies were negative. The patient remains without evidence of disease. Retrospectively, the original flow cytometric assessment was believed to likely represent sampling of hyperplastic germinal centers with significantly expanded CD10+ B cells. The FDG uptake and the κ predominance further confounded the interpretation. This case illustrates the pitfalls of standard diagnostic techniques, including PET scanning, cytology, and flow cytometry, particularly in the setting of HIV. It further underscores the importance of adequate clinical correlation and a low threshold for performing open biopsies in such patients.

Atypical B‐cell infiltrate in a pediatric patient: diagnostic and pathogenetic considerations

Pediatric primary central nervous system lymphoma (PCNSL) represents1–1.5% of all PCNSL. Pediatric PCNSL are usually high grade B‐cell lymphoma (30%) or anaplastic large cell lymphomas. Herein we report a 15 year‐old male with a well‐circumscribed, enhancing mass centered on the right thalamus with mass effect on the 3rd ventricle and obstructive hydrocephalus. Endoscopic biopsy produced only hemorrhage; repeat biopsy three months later produced multiple fragments of pink‐tan soft tissue including pineal gland, grey matter, granulation tissue, choroid plexus, and a diffuse mononuclear cell infiltrate composed of a mixture of small round and large atypical lymphoid cells with irregular vesicular nuclei, 2 to 3 nucleoli attached to the nuclear membrane, and moderately abundant eosinophilic cytoplasm. The large lymphoid cells showed immunoreactivity for CD20, PAX‐5, and CD79a (B‐cell markers) but were negative for epithelial and germ cell markers; small T lymphocytes were also present. The lymphocytic process infiltrated brain tissue containing atypical astrocytes and large binucleated neurons. Immunoglobulin heavy chain (Ig‐VDJ; B‐cell) and T‐cell receptor (TCR) beta and gamma gene rearrangement studies showed a monoclonal B‐cell population. This atypical B‐cell infiltrate with features of lymphoma may have arising in an inflammatory infiltrate accompanying a pre‐existing glio‐neuronal tumor.

Bilateral Simultaneous Primary Orbital Lymphoma Presenting With Unilateral Enophthalmos

A 73-year-old woman was examined for palpable orbital masses behind the right upper eyelid and left lower eyelid leading to entropion. Hertel exophthalmometry readings were 6.0 mm in the right eye and 11.0 mm in the left eye with a base of 102 mm. MRI revealed bilateral hypointense orbital soft-tissue masses. Pathologic evaluation of incisional biopsy specimens revealed malignant tissue composed of diffuse, mitotically active, atypical large lymphoid cells positive for CD-20 with immunohistochemical staining, confirming the diagnosis of malignant diffuse large B-cell lymphoma. Systemic survey was negative for extraorbital involvement. After R-CHOP chemotherapy (Rituximab 375 mg/m2 intravenously, Cyclophosphamide 750 mg/m2 intravenously, Doxorubicin 50 mg/m2 intravenously, Vincristine 1.4 mg/m2 intravenously, Prednisolone 100 mg orally), Hertel measurements were 9.0 mm in the right eye and 11.0 mm in the left eye. The mass lesions were totally regressed in follow-up MRI. Although rare, non-Hodgkin lymphoma may present bilaterally as primary orbital lesions and can unexpectedly cause enophthalmos instead of proptosis.

Non-Hodgkin lymphoma as a cause of obstructive jaundice with simultaneous extrahepatic portal vein obstruction: A case report

Non-Hodgkin lymphoma is a rare cause of biliary obstruction. To the best of our knowledge, non-Hodgkin lymphoma in the peripancreatic region causing obstructive jaundice with simultaneous portal vein (PV) invasion has not yet been reported. We present a 50-year-old patient with obstructive jaundice whose extrahepatic portal vein was obstructed by the invasion of a peripancreatic non-Hodgkin lymphoma. The patient denied any other symptoms such as recurrent fever, night sweat and loss of body weight. Computed tomography (CT) revealed a 10 cm mass in the retroperitoneal space behind the head of the pancreas causing obstruction of the distal bile duct and the PV. A pylorus-preserving pancreaticoduodenectomy combined with a PV resection was performed. The PV was reconstructed using an autologous right internal jugular vein graft. The resected specimen showed endoluminal invasion of both the bile duct and the PV. Histological examination showed the mass consisting of diffuse sheets of large malignant lymphoid cells. These cells were positive for CD20 and CD79a, partially positive for CD10, and negative for CD3, CD4, CD5, CD8 and CD30. The pathologic diagnosis was diffuse large B-cell type non-Hodgkin lymphoma and the patient was transferred to the Department of Hematology and Oncology for chemotherapy. He received four cycles of combined chemotherapy including cyclophosphamide, doxorubicin, vincristine and prednisone plus rituximab, and three cycles of intrathecal chemoprophylaxis including methotorexate, cytosine arbinoside and prednisone. The patient is alive with no evidence of the disease for 7 mo after operation and will receive additional courses of chemotherapy.

Localized lymphoid hyperplasia of the rectum representing progressive transformation of the germinal center

Histologically, benign lymphoid hyperplasia (BLH) of the rectum is usually characterized by large lymphoid follicles with active germinal centers, and a narrow surrounding mantle zone and marginal zone. We present two cases of BLH of the rectum demonstrating progressive transformation of the germinal center (PTGC). The patients were 50- and 71-year-old Japanese women. Colonoscopy demonstrated small sessile polyps in both cases. The resected specimen contained numerous lymphoid follicles with active germinal centers and a portion of the lymphoid follicles exhibited PTGC. The area showing PTGC contained a few large lymphoid cells resembling lymphocytic and histiocytic Reed-Sternberg cells of nodular lymphocyte-predominant Hodgkin lymphoma. These PTGC contained small- to-medium clusters of epithelioid cells in both cases. In situ hybridization studies demonstrated scattered Epstein-Barr virus (EBV)-encoded small RNA-positive medium and large lymphoid cells and crypt epithelium in both lesions. EBV may be involved in the etiology of a subset of BLH of the rectum. However, reactivity of lymphoid cells for EBV has been reported in lymphoid tissues in a high percentage of "normal" individuals. The etiology of BLH of the rectum remains unclear.

Burkitt Transformation of Mantle Cell Lymphoma.

MYC rearrangements are not included as a genetic change in the blastoid variants of mantle cell lymphoma (Jaffe, et al (2001) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press.). We present two cases both with CCND1/IGH and MYC rearrangements. Case 1. An 82-year-old male with no known history of lymphoma presented with thrombocytopenia, loss of appetite and “abdominal fullness.” Imaging studies showed enlarged retroperitoneal lymph nodes. The peripheral blood smear had 18,000 WBC with approximately 30% circulating atypical lymphocytes. Flow cytometric studies of the bone marrow revealed a surface kappa light chain restricted CD10+ B-cell population. A bone marrow biopsy showed >90% of marrow cellularity comprised of neoplastic lymphocytes. The neoplastic lymphocytes were small to intermediate in size with minimal amounts of dark blue cytoplasm and several cytoplasmic vacuoles (Burkitt like morphology). By immunohistochemical stains, the neoplastic cells were positive for CD20, CD43, CD10, BCL-6, and cyclin D1, weakly and focally positive for BCL-2, and negative for CD23. The Ki-67 proliferation fraction was ∼100%. An immunohistochemical stain for CD5 was predominantly negative with a possible very faint blush on a subset of neoplastic B-cells. The FISH tests on bone marrow interphases were positive for a CCND1/IGH, a variant MYC/IGH, a variant MYC-BA rearrangements and negative for BCL6-BA and BCL2/IGH rearrangements. The variant MYC/IGH pattern was 3xMYC, 3xIGH, 1xFusion signals and MYC-BA pattern was 2x5′MYCcon3′MYC, 1x3′MYC. rearrangements. The karyotype was 44∼45,XY,del(2)(q11.2q21),der(3;17)(p10;q10), der(5)t(3;5)(q12;q15), t(11;14) (q13;q32) [cp6]/46,XY[14]. Since the karyotype had a t(11;14) and two normal 8 chromosomes, a metaphase FISH was analyzed to localize the signals for the MYC/IGH probe. The MYC signal were on both normal 8 chromosomes, a fusion signal was on a F-G sized chromosome. While the IGH signals were on the normal 14, der(14) and der(11). This was consistent with a cryptic MYC/IGH fusion in a three way rearrangement between chromosomes 8, 11 and 14. Case 2. A 69-year-old male having had a kidney transplant in 2001 was on immunosuppressive therapy. He presented with severe leukocytosis, anemia and thrombocytopenia and weight loss of about 12 pounds over several months. A peripheral blood smear showed 74,000 WBC with approximately 30% blasts. Bone marrow biopsies revealed normocellular bone marrow (50% cellularity). Interspersed large neoplastic lymphoid cells were shown by immunohistochemical stains to be positive for CD20, BCL-1, weak positive for BCL-2 and a Ki-67 staining > 90%. Flow cytometry indicated that the neoplastic cells were positive for kappa and CD5 but negative for CD11c and CD23. Interphases FISH on peripheral blood was positive for a CCND1/IGH rearrangement. The karyotype was 42∼44,X,-Y,add(1)(p13), t(2;8)(p12;q24), der(2)t(2;15)(p25;q11.2),+3,del(9)(p22p24),+del(9)(p22p24), − 10, del(11)(q21q23), t(11;14)(q13;q32) , − 13, − 15, − 17,add(17)(p11.2)[cp7]/46,XY[17]. FISH confirmed a MYC rearrangement. Therefore, this case had both CCND1/IGH and MYC/IGK rearrangement. Concomitant occurrence of a CCND1/IGH and a MYC rearrangement is rare in lymphomas. In Mitelman database of chromosome aberrations in cancer 2007, Four cases had both a t(11;14) and a t(8;14) translocation and two cases had both a t(11;14) and a t(2;8) translocation. This study expands the repertoire of abnormalities seen in blastoid transformation of mantle cell lymphoma. Being cognizant of a possible MYC involvement in the transformation of mantle cell lymphoma and its exploration would influence therapy.

Primary cutaneous CD30+ anaplastic large-cell lymphomas mimicking keratoacanthomas

Primary cutaneous anaplastic large cell lymphoma (ALCL) may be associated with keratoacanthoma (KA)-like epithelial hyperplasia and dense eosinophilic and neutrophilic infiltrates. Diagnosis in such cases is challenging both clinically and histologically, because the large atypical lymphoid cells may be obscured by the massive infiltrate of eosinophils and neutrophils, or confused with invasive squamous cell carcinoma or KA. We recently encountered two cases of CD30+ ALCL presenting with a KA-like tumour on the eyelid and nose, respectively. One showed features of KA histologically, with marked tissue eosinophilia and neutrophilia.

Primary bone marrow T-cell anaplastic large cell lymphoma with triple m gradient

We present a case of a 60-year-old male patient with primary bone marrow anaplastic large cell lymphoma. He was admitted to the hospital with the symptoms of anemia and fever. There was no evidence of lymphadenopathy or splenomegaly. Immunoelectrophoresis showed the presence of a triple M gradient (double IgM and an IgG), with the IgG and one of the IgM paraproteins functioning as a cryoglobulin. The patient had no hepatitis C virus infection. Bone marrow biopsy showed massive CD30-positive, ALK-negative large lymphoid cell infiltration of T-cell origin with anaplastic morphology. PCR analysis of lymphoid cells separated from the bone marrow demonstrated the presence of a B/T hybrid genotype disorder with no evidence of the t(2;5), nor t(1;2) translocations. The patient entered a period of remission following CHOP chemotherapy. The patient subsequently died of sepsis as a consequence of serious humoral immunodeficiency.

T(6;14)(q15;q32) in a Patient with CD5+CD10+ Diffuse Large B-Cell Lymphoma

A 68-year-old man presented with systemic lymph node swelling. A biopsy specimen taken from the right cervical lymph node showed that the normal architecture was replaced by a diffuse proliferation of large lymphoid cells with large atypical nuclei. Immunohistochemical analysis showed that the atypical lymphoid cells were positive for CD5, CD10, CD20, CD79a, and Bcl2, and negative for CD3 and cyclin D1. A diagnosis of diffuse large B-cell lymphoma was made. Karyotypic findings included add(5)(q13), del(6)(q13), add(17)(p11), add(19)(p11), add(19)(p13), and t(6;14)(q15;q32). The serum lactate dehydrogenase level and indirect bilirubin level were slightly elevated. Elliptocytosis was observed in the peripheral blood, and a diagnosis of hereditary spherocytosis was made from the family history. Regarding CD5+CD10+ diffuse large B-cell lymphoma with a non-random chromosomal translocation of t(6;14)(q15;q32), studies on the mechanism of lymphomagenesis are needed.

Grading of Follicular Lymphoma: Comparison of Routine Histology With Immunohistochemistry

Follicular lymphoma (FL) grading is based on the average number of large transformed cells in 10 neoplastic follicles at x40 high-power field (x10-40 high-power field) examination (grade 1, 0-5 centroblasts per high-power field; grade 2, 6-15 centroblasts per high-power field; grade 3, >15 centroblasts per high-power field). Since there may be significant interobserver variability, we analyzed the usefulness of immunohistochemical stains in grading FLs more reliably. Forty-three FLs initially graded by World Health Organization criteria (grade 1, 12; grade 2, 18; grade 3, 13) were reviewed and stained with CD3, CD20, Ki-67, CD30, CD68, PAX-5, and BCL-6. Retrospective review was performed for the average number of large cells, of large lymphoid cells, of large cells staining with CD3, CD20, BCL-6 (40 cases), and PAX-5, and of all cells staining with CD68, Ki-67, and CD30. By histologic review, 8 of 43 FLs had a significant grade change (4 cases upgraded and 4 cases downgraded). CD3 and CD30 stained only 0 to 3 large cells and 0 to 3 cells, respectively, in neoplastic follicles. CD68+ cells represented the large nonlymphoid cells. Increasing FL grades demonstrated increases in Ki-67+ cells. The original grade showed substantial agreement with CD20 and moderate agreement with PAX-5 and BCL-6. The original histologic grade agreed with immunohistochemical-based grade using 2 or more antibodies in 5 of 8 discordant cases (4 by CD20 or BCL-6 and PAX-5; 1 by CD20, PAX-5, and BCL-6). Interobserver variability of histologic FL grading may be significant; we showed low-end "substantial agreement." Immunohistochemical stains (ie, CD20, PAX-5, and BCL-6) may more reliably determine the number of large transformed cells in neoplastic follicles; Ki-67 staining correlates with higher FL grades. Immunohistochemical stains may be evaluated in clinical trials of FL patients to determine prognostic significance.

Intravascular lymphoma in a patient with systemic lupus erythematosus: a case report

Intravascular lymphoma IVL is a rare and aggressive disorder characterized by proliferation of large lymphoid cells (most commonly B-cells) within the lumen of small vessels of nearly every organ. Obliteration of vessels leads to the different clinical signs, being cutaneous lesions and neurological signs the most frequent presentations, whereas lymph node and reticuloendothelial system involvement is typically absent. No association with SLE has been described up to the present. We report a case of IVL in a patient with systemic lupus erythematosus (SLE) involving skin, central nervous system (CNS) and bone marrow.

Successful treatment of primary cutaneous follicle centre lymphoma with topical 5% imiquimod

Conflicts of interest: none declared. Sir, Imiquimod, a topical immune response modifier, has potent antitumour activity through local augmentation of innate and cell‐mediated immunity.1 It is increasingly being used to treat a wide variety of cutaneous tumours, including cutaneous T‐cell lymphomas.2, 3 It has not previously been shown to be fully efficacious for the treatment of cutaneous B‐cell lymphoma. We report a 59‐year‐old man with primary cutaneous follicle centre lymphoma successfully treated with topical 5% imiquimod. Our patient presented with a 5‐year history of multiple asymptomatic lesions grouped over the lateral surface of his upper right arm. Individual lesions had gradually appeared and enlarged over this time. Examination revealed smooth‐surfaced soft dermal papules and nodules (Fig. 1a). There was no associated palpable lymphadenopathy, nor organomegaly. Skin biopsy showed a lymphoid lesion involving superficial and deep dermis. The epidermis was intact and a Grenz zone was present (Fig. 2). On higher magnification, the infiltrate was noted to be polymorphic and composed of intermixed small and large lymphoid cells, with sparse germinal centres.

Distinction between lymphoma-like lesions and lymphoma of uterine cervix: a clinicopathologic study of 26 cases

To study the clinicopathologic features and differential diagnosis of lymphoma-like lesions and lymphoma of uterine cervix. Clinical data and hematoxylin and eosin-stained slides of 10 cases of lymphoma-like lesion and 16 cases of lymphoma of uterine cervix were reviewed. Immunohistochemical study for B- and T-cell markers and light chains (kappa, lambda) were performed on paraffin sections. The rearrangement status of immunoglobulin heavy chain (IgH) gene was analyzed with semi-nested polymerase chain reaction in 4 cases lymphoma-like lesion and 4 cases of lymphoma of uterine cervix. The age of patients with lymphoma-like lesion ranged from 24 to 54 years (medium = 43 years). The lesion generally presented with cervical erosion or polyp. Microscopically, it is characterized by focal or diffuse superficial infiltration of immunoblast-like large B cells intermingled with a polymorphic population of inflammatory cells, including plasma cells, eosinophils and neutrophils. Maturation of the transformed large B cells was also noticed. On the other hand, the age of the patients with lymphoma of uterine cervix varied from 28 to 78 years (medium = 58 years). Cervical mass or diffuse enlargement of cervix were the commonest clinical findings. The cases included 12 examples of diffuse large B-cell lymphoma and 4 examples of follicular lymphoma. The former was characterized by a diffuse monomorphic population of large atypical lymphoid cells, while neoplastic follicles were identified in the latter. Neither polymorphic inflammatory infiltrates nor maturation phenomenon was found. The immunostaining for kappa and lambda light chains was inconclusive. Molecular study showed clonal rearrangement of IgH gene in all cases of cervical lymphoma, as well as 2 cases of lymphoma-like lesion. The distinction between lymphoma-like lesion and lymphoma of uterine cervix depends primarily on the clinical and histopathologic features. Assay for rearrangement of IgH gene may be helpful in differential diagnosis, though monoclonality can be detected in some benign lesions as well.

Meningeal recurrence of intravascular large B‐cell lymphoma: early diagnosis with PET‐CT

A 50-year-old woman with a history of pyrexia of unknown origin, weight loss and constitutional symptoms was diagnosed with intravascular large B-cell lymphoma. The trephine biopsy confirmed the presence of CD19, CD20, CD79a large lymphoid cells, with prominent nucleoli, lodged intraluminally. Initial staging with [F]-fluorodeoxyglucose (FDG) combined positron emission tomography – computed tomography (PET/ CT) demonstrated left axillary nodal disease and diffuse increased bone marrow uptake. She was treated with six cycles of R-CEOP (rituximab, cyclophosphamide, epirubicin, vincristine and prednisolone). Early PET-CT re-staging after two cycles of R-CEOP demonstrated a complete metabolic response and bone marrow examination demonstrated complete remission. In view of high-risk disease, consolidation treatment with carmustine, etoposide, cytarabine and melphalan (BEAM) chemotherapy plus autologous stem cell transplantation was undertaken in first remission. The transplant course was uncomplicated with neutrophil engraftment on day 12. Routine restaging at 3 months post-transplant with a bone marrow examination showed no evidence of lymphomatous infiltration. On clinical review 2 weeks later, she was asymptomatic except for a several-day history of a vague intermittent headache. A routine PET-CT at this time demonstrated striking intense uptake in the spinal canal extending from L1 to L5 levels. There was further intense uptake in subcentimetre right axillary lymph nodes, and further focal bony uptake in the right clavicle, sternum, humeri and femora, without abnormality on CT bony windows. Subsequent lumbar puncture revealed heavy infiltration with lymphocytes confirming meningeal lymphoma recurrence. Treatment with salvage chemotherapy was undertaken, with an early re-staging PET study after one cycle demonstrating a complete metabolic response. Intravascular large B-cell lymphoma is a rare subtype of diffuse large B-cell lymphoma. It is characterised by the presence of lymphoma cells in the lumina of small vessels resulting in highly variable end-organ involvement and clinical presentation. It has a very poor prognosis, partly reflecting frequent delays in diagnosis and initiation of therapy due to its unusual presentation. This case demonstrates the utility of functional imaging with PET-CT throughout disease management, including initial staging, early re-staging and response to therapy, which resulted in the early diagnosis of disease recurrence, allowing prompt institution of appropriate salvage chemotherapy.

Lymphoma-like Lesion of the Uterine Cervix

Lymphoma-like lesion of the female genital tract is rare. We report 12 cases of lymphoma-like lesions of the cervix in patients ranging from 27-54 years of age (mean 41). The commonest clinical presentation was post-coital bleeding (8), which was followed by vaginal bleeding (2) and leukorrhagia (4). Grossly, the lesions were either polypoid (8) or ulcerated (4). On histological examination, the lesions were eroded and involved the superficial mucosa 2-12 mm (mean 4 mm) in depth. They comprised sheets of dense populations of predominantly large lymphoid cells admixed with small lymphocytes, plasma cells, and neutrophils. Follicle formation was occasionally seen. Immunostaining revealed the majority of the large cells were B cells (CD20(+), CD79a(+)) with no aberrant CD5 and CD43 expression. The lymphoid cells in the follicle were CD10(+) and bcl6(+) but negative for bcl-2. Cyclin D1 was negative. There was no immunoglobulin light chain restriction and polymerase chain reaction for T cell receptor-gamma chain gene and immunoglobulin heavy chain gene demonstrated polyclonal patterns. In situ hybridization for EBER and high risk HPV 6/11 and 16/18 were negative. All patients were well with one case developing local recurrence in the follow-up period up to 7 years.

Three cases of extranodal NK/T‐cell lymphoma of the nasal type diagnosed by nasal brush cytology

Extranodal natural killer (NK)/T-cell lymphoma of the nasal type is a rare type of malignant lymphoma that is most common in Asian countries. Here we describe cytomorphologic, immunocytochemical, and molecular cytochemical features of three cases of NK/T-cell lymphoma of the nasal type diagnosed by nasal brush cytology. Cytomorphologic findings common among the three cases included the presence of several cell types, including nasal cavity epithelial cells, histiocytes, phagocytic histiocytes, and lymphoid cells, within a necrotic background. Suspected lymphoma cells were medium to large lymphoid cells possessing light blue and abundant cytoplasm. A characteristic feature of these cells was the presence of the tongue-like projections of cytoplasm from one or both sides of the cells. We believe these intriguing cytologic findings are indicators of NK/T-cell lymphoma of the nasal type. Azurophilic granules were observed in all cases, ranging from extremely fine granules to large granular lymphocyte (LGL)-like granules. Immunocytochemical and molecular cytochemical analyses showed staining for natural killer cell antigen CD56 as well as cytotoxic granule-associated proteins granzyme B7 (GrB7) and T-cell-restricted intercellular antigen-1 (TIA-1). EBV (Epstein-Barr virus) encoded small RNAs (EBER) positivity was shown by in situ hybridization, and no rearrangement of the TCRgamma gene was observed. Comparison between cytobrush and cotton swab methodology showed that cytobrush resulted in more cell-rich specimens than did cotton swabs, suggesting that nasal brush cytology with cytobrush is most useful in the diagnosis of NK/T-cell lymphoma of the nasal type.

18F‐Fluorodeoxyglucose positron emission tomography for evaluation of intravascular large B‐cell lymphoma

A 73-year-old woman was referred to our hospital with a 1month history of recurrent fever, worsening mental state and general weakness. Physical examination showed confusion and mild splenomegaly but no peripheral lymphadenopathy or skin lesions. Her serum lactate dehydrogenase (LDH) and soluble interleukin-2 receptor were elevated to 1110 iu/l and 14 400 U/ml respectively. Computed tomography of the abdomen revealed mild hepatosplenomegaly and a right adrenal mass (top left panel). A bone marrow aspirate from the sternum showed scattered large atypical lymphoid cells (4AE2%) suggesting lymphoma infiltration. Based on our prior experience with intravascular lymphoma (IVL), we performed random skin biopsies from normal appearing skin on the trunk, thigh and upper arms. All specimens showed large lymphoid cells with irregular nuclei filling the small vessels in subcutaneous tissues (middle left panel). These cells were stained positively with CD20 (bottom left panel) and negatively with CD3 monoclonal antibody. A diagnosis of IVL of B-cell origin was made. F-Fluorodeoxyglucose positron emission tomography (F-FDG PET) was performed before treatment. In addition to intense uptake of the adrenal mass, increased F-FDG uptake was observed in the vertebrae, humeri, ulnae, radii and iliac crests (top right panels). After rituximab infusion (375 mg/m), her general condition and mental status improved rapidly. The serum LDH level was elevated transiently but returned to within normal limits over the next few days. After two courses of weekly rituximab and one course of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy, F-FDG PET (bottom right panels) scan was repeated, and no abnormal F-FDG uptake was observed. The patient entered complete remission and continued to receive additional treatment with rituximab and CHOP. IVL is a very rare subtype of non-Hodgkin lymphoma with an aggressive natural course. F-FDG PET scanning appears to be extremely useful for evaluating the early response to the chemotherapy in patients with IVL.

Composite Recurrent Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma: One Clone, Two Faces

We describe a composite lymphoma with recurrent Hodgkin lymphoma and diffuse large B-cell lymphoma components manifesting as a single, perforated small intestinal tumor in a 56-year-old man with a history of classical Hodgkin lymphoma and recent relapse in the bone marrow. The resected mass had 2 morphologically and immunophenotypically distinct components; 1 showed a pleomorphic cellular infiltrate with fibrosis and contained numerous, large Hodgkin/Reed-Sternberg-like cells and variants. The tumor cells were CD30+ and focally positive for CD15 but CD20-, CD79a-, and PAX-5-. In situ hybridization for Epstein-Barr virus (EBV) was strongly positive in the large pleomorphic tumor cells. The adjacent component displayed sheets of relatively uniform, large lymphoid cells with typical morphologic features of diffuse large cell lymphoma. The tumor cells showed uniform expression of tested B-cell antigens, absence of CD30 or CD15, and complete absence of EBV-encoded RNA. Separate molecular studies with immunoglobulin heavy and k light chain gene rearrangements clearly demonstrated an identical rearrangement pattern, indicating derivation from the same clone, which was confirmed by direct DNA sequencing analysis. Such distinctly different morphology, immunophenotype, and EBV status in different components within a clonally related single tumor mass is striking.

Composite Recurrent Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma

We describe a composite lymphoma with recurrent Hodgkin lymphoma and diffuse large B-cell lymphoma components manifesting as a single, perforated small intestinal tumor in a 56-year-old man with a history of classical Hodgkin lymphoma and recent relapse in the bone marrow. The resected mass had 2 morphologically and immunophenotypically distinct components; 1 showed a pleomorphic cellular infiltrate with fibrosis and contained numerous, large Hodgkin/Reed-Sternberg–like cells and variants. The tumor cells were CD30+ and focally positive for CD15 but CD20–, CD79a–, and PAX-5–. In situ hybridization for Epstein-Barr virus (EBV) was strongly positive in the large pleomorphic tumor cells. The adjacent component displayed sheets of relatively uniform, large lymphoid cells with typical morphologic features of diffuse large cell lymphoma. The tumor cells showed uniform expression of tested B-cell antigens, absence of CD30 or CD15, and complete absence of EBV-encoded RNA. Separate molecular studies with immunoglobulin heavy and light chain gene rearrangements clearly demonstrated an identical rearrangement pattern, indicating derivation from the same clone, which was confirmed by direct DNA sequencing analysis. Such distinctly different morphology, immunophenotype, and EBV status in different components within a clonally related single tumor mass is striking.