The pathologic spectrum of adult T-cell leukemia/lymphoma in the United States. Human T-cell leukemia/lymphoma virus-associated lymphoid malignancies

The human T-cell leukemia/lymphoma virus (HTLV) is a novel Type-C retrovirus isolated from patients with post-thymic T-cell malignancies. Thirteen patients diagnosed in the United States were identified as having antibodies to HTLV and a typical clinicopathologic syndrome characteristic of adult T-cell leukemia/lymphoma as described in Japan. The most characteristic diagnostic feature in our series was the presence of highly pleomorphic and lobated lymphoid cells in the peripheral blood. Also notable was acid phosphatase activity which was partially tartrate-resistant in the neoplastic cells. The pathologic spectrum of the associated lymphomas was broad and encompassed several diffuse histologic subtypes in the Rappaport classification, the working formulation, and the classification of the Japanese lymphoma study group. However, differences in survival could not be correlated with differences in histologic subtype. All patients presented with Ann Arbor Stage IV lymphoma. Other common clinical features were generalized lymphadenopathy, hepatosplenomegaly, skin and peripheral blood involvement, hypercalcemia, and lytic bone lesions. The clinical course was aggressive with a median survival of 9 months. In two-third of patients with cutaneous involvement, epidermal infiltration resembling Pautrier microabscesses was observed. However, most cases can be readily distinguished from mycosis fungoides/Sézary syndrome on clinical and epidemiologic grounds. The presence of HTLV-antibodies in patients with lymphoid malignancies appears to define a distinct clinicopathologic syndrome which tends to occur in geographic clusters. Adult T-cell leukemia/lymphoma is favored as the diagnostic term for this clinicopathologic entity.     

Primary central nervous system mucosa-associated lymphoid tissue lymphoma--case report

A 55-year-old woman presented with an extremely rare primary central nervous system mucosa-associated lymphoid tissue (MALT) lymphoma manifesting as seizure and was subsequently diagnosed with dural MALT lymphoma in the cranium. Magnetic resonance imaging revealed a left frontal dural mass with peritumoral edema. Histological examination of the dural mass confirmed MALT lymphoma and revealed infiltration of small cells with irregular nuclear borders and expression of a B cell marker (CD20) but absence of CD5, CD10, CD23, and cyclinD1. Reactive T-cell infiltration was also seen. Subsequently, local irradiation (40 Gy/20 fractions) was performed. Magnetic resonance imaging showed complete remission just after irradiation was completed. There was no evidence of systemic MALT lymphoma. There has been no recurrence for 3 years without additional therapy.     

Une étiologie exceptionnelle de l’insuffisance rénale aiguë : le lymphome de Burkitt

IntroductionBurkitt's lymphoma (BL) is an exceptional cause of acute renal failure (ARF). The origin of the tumor clone may be lymphoid follicles secondary to renal Epstein-Barr virus (EBV) infection. With the presentation of this clinical case, the pathogenesis, diagnostic criteria and evolution of this extremely rare affection will be discussed.ObservationA 4-year-old patient with a recent history of acute osteomyelitis of the right thigh presented an ARF without indications of post-infectious glomerulonephritis. Ultrasound showed enlarged kidneys without dilation of the excretory cavities. Diffuse interstitial infiltration of atypical lymphoid cells of medium size were noted upon renal biopsy. The tumor cells expressed antibodies against CD20, CD10, Bcl6, and Ki67 but not against Bcl2 or CD3. The search for an EBV infection was positive. A few days after diagnosis, the evolution was spontaneously fatal.Discussion/conclusionBL of the kidney is a rare condition that accounts for less than 1 % of kidney tumors, associated almost invariably with EBV infection. The diagnosis is confirmed histologically by renal biopsy and the criteria of Malbrain affirms the primitive character of the lymphoma. BL of the kidney is a diagnostic and therapeutic emergency and may be fatal.     

Primary renal lymphoma presenting as acute renal failure

Diffuse bilateral infiltration of the kidneys by lymphoma cells is a rare but well-documented cause of acute renal failure (ARF). Only 51 such cases have been reported, 15 of which had ARF as the initial presentation of lymphoma. The clinical and pathologic features of these 15 cases and of two additional cases reported herein are reviewed. The diagnosis should be suspected in a patient with ARF, bilateral enlargement of the kidneys, minimal proteinuria, nonspecific findings on urinalysis, and absence of features of allergic tubulointerstitial nephritis. Renal imaging techniques may suggest the possibility of lymphomatous infiltration, but only renal biopsy or autopsy can provide a definitive diagnosis. Although modern chemotherapy and/or radiation therapy usually leads to a dramatic normalization of renal function, almost all patients eventually die of widespread recurrent lymphoma, despite the absence of clinical or pathologic involvement of the kidneys at the time of death.     

CD200 (OX-2 membrane glycoprotein) is expressed by follicular T helper cells and in angioimmunoblastic T-cell lymphoma

CD200, an immunoglobulin superfamily membrane glycoprotein, is expressed in B cells, a subset of T cells, and in a range of B-cell lymphoproliferative disorders. We recently found, by immunohistochemical staining, that follicular helper T cells associated with neoplastic L and H cells in nodular lymphocyte predominant Hodgkin lymphoma, express CD200. Here we show that CD200 is expressed by follicular helper T cells in reactive lymphoid tissue, using single-color and 2-color immunohistochemical staining. Immunohistochemical staining of a range of T-cell lymphoproliferative disorders shows that the neoplastic cells in angioimmunoblastic T-cell lymphoma are immunoreactive for CD200, and the pattern of expression is similar to that of other follicular helper T-cell markers, PD-1 and CXCL13. In contrast, only a minority of cases of T-cell neoplasms other than angioimmunoblastic T-cell lymphoma are immunoreactive for CD200. A subset of CD200-positive peripheral T-cell lymphoma, not otherwise specified, cases may represent evolving angioimmunoblastic T-cell lymphoma or another neoplasm derived from follicular T helper cells. We conclude that CD200 is a useful immunophenotypic marker of angioimmunoblastic T-cell lymphoma and may be a suitable therapeutic target for an anti-CD200 immunotherapy undergoing clinical trial.     

Malignant lymphoma of T-cell origin in a Humboldt penguin (Spheniscus humboldti) and a pink-backed pelican (Pelecanus rufescens)

Multicentric T-cell lymphomas were diagnosed in two birds from separate zoological collections: one in a 27-year-old female Humboldt penguin (Spheniscus humboldti) and the second in an adult pink-backed pelican (Pelecanus rufescens). The main clinical sign in the penguin was dysphagia caused by lymphoma formation in the esophagus. Besides the esophageal lymphoma, neoplastic lymphoid cells were observed in the adrenal glands, liver, kidneys, lung, proventriculus, and gizzard. The pelican was found dead without a clinical history. Neoplastic lymphoid cells were observed in the kidneys, liver, pancreas, spleen, ventriculus, and small intestine. Neoplastic cells of the penguin as well as of the pelican were immunoreactive to CD3 antigen, suggesting the lymphomas were of T-cell origin. In both cases, test results were negative for Marek's disease virus, avian leukosis virus, and reticuloendotheliosis virus. In the pelican, a skin melanoma was diagnosed on the left throat pouch in addition to the multicentric T-cell lymphoma.     

Adult T-cell lymphoma/leukemia with angioimmunoblastic T-cell lymphomalike features: Report of 11 cases

In adult T-cell lymphoma/leukemia (ATLL), the neoplastic lymphoid cells are usually medium-sized to large, often with pronounced nuclear pleomorphism compatible with the diagnosis of diffuse pleomorphic peripheral T-cell lymphoma. We describe here 11 patients with the rare morphologic variant of ATLL, angioimmunoblastic T-cell lymphoma (AILT)-like type. The examined lymph nodes showed proliferation of high endothelial venules and presence of various infiltrating inflammatory cells including plasma cells and eosinophils. The lymphoma cells were medium-to-large size with clear cytoplasm. These findings were suggestive of AILT. However, immunohistochemical features of AILT, namely, CD10 and CXCL13 expression in lymphoma cells and proliferation of CD21-positive follicular dendritic cells, were not detected. Two cases were CXCR3-positive, whereas 9 expressed CCR4, which are usually positive in ATLL. All patients were positive for antiadult T-cell leukemia/lymphoma-associated antigen, which is a specific antibody for human T-cell lymphotropic virus type-I. Southern blot analysis revealed proviral DNA integration in lymphoma cells in 9 patients. The latter was not evident in the first biopsy of 2 patients but in the second biopsy obtained within several months after the first biopsy revealed definite proviral integration. Almost all patients showed aggressive clinical course and poor survival (median survival: 5 mo). This is the first report of ATLL with AILT-like morphologic features.     

Lennert's lymphoma: a variant of cytotoxic T-cell lymphoma?

We studied 10 cases of Lennert's lymphoma (lymphoepithelioid lymphoma) to evaluate the cellular origin of the neoplastic cells. There were six men and four women, aged 38 to 75 years (median, 56 yrs; mean, 59 yrs). The lymphoma cells tended to remain confined to lymph nodes, and extranodal involvement was rare. The mean overall survival was 42.2 months, which is relatively good compared with other peripheral T-cell lymphomas. Morphologically, the lymph node was occupied by small to large clusters of epithelioid cells interspersed with medium to large atypical lymphoid cells. In seven cases, large atypical lymphoid cells resembling Hodgkin's or Reed-Sternberg cells were observed. The phenotypes of these neoplastic cells were CD3+ CD4- CD8+ in five cases, CD3+ CD4+ CD8- in four cases, and CD3+ CD4- CD8- in one case. TIA-1 was positive by immunohistochemical staining in seven cases, whereas four cases were positive for granzyme B. Clonal rearrangement of the T-cell receptor gene was confirmed in all cases by either Southern blot hybridization or a polymerase chain reaction-based denature gradient gel electrophoresis method. Epstein-Barr virus was negative by in situ hybridization in all but one case. Lennert's lymphoma was formerly known as a CD4+ helper T-cell neoplasm. Our results suggest that, at least in some cases, the neoplastic cells are of cytotoxic T-cell origin.     

Peripheral CD4 T-cell depletion is not sufficient to prevent ischemic acute renal failure

BACKGROUND: Ischemia reperfusion injury leading to acute renal failure (ARF) and delayed graft function is an important problem in organ transplantation. CD4+ T cells, essential for transplant rejection, may mediate ischemic ARF. We have demonstrated that the caspase-1 mediated production of IL-18 is pathogenic in ischemic ARF in mice. A potential source of IL-18 in ischemic ARF is the CD4+ T cell. We therefore examined the effect CD4+ T cell depletion on the development of ischemic ARF and the activation of IL-18. METHODS: Functional and histological correlates were examined in two groups of mice with ischemic ARF: 1) CD4 T-cell depleted with the antibody GK1.5, and 2) T-cell receptor alpha-chain deficient (TCRalpha -/-) mice. TCRalpha -/- mice lack the alpha chain of the T-cell receptor and therefore lack functional CD4+ and CD8+ T cells. RESULTS: Flow cytometry of lymph nodes and immunohistochemistry of kidneys demonstrated complete depletion of CD4+ T cells in mice with ischemic ARF treated with GK 1.5. CD4+ T-cell depletion did not confer functional (serum creatinine, BUN and FITC-labeled inulin clearance) or histological protection against ischemic ARF. Likewise, TCRalpha -/- mice were not protected against ischemic ARF. Renal caspase-1 activity and IL-18 protein were similar in CD4+ T-cell depleted and wild-type postischemic reperfusion. CONCLUSIONS: Ischemic ARF can occur in the absence of classical T-cell function. The evaluation of other inflammatory mediators (e.g., macrophages or NK cells) as a source of IL-18 and mediator of ischemic ARF warrants further investigation.     

Peripheral T-cell lymphoma with Reed-Sternberg-like cells of B-cell phenotype and genotype associated with Epstein-Barr virus infection.

We report three cases of nodal peripheral T-cell lymphoma (PTCL) with Reed-Sternberg-like (RS-like) cells of B-cell pheno- and/or genotype. Histologic analysis in all cases revealed diffuse nodal effacement by atypical lymphoid cells of variable size. Two of the three cases had features of angioimmunoblastic T-cell lymphoma (AILT). Large mononuclear and binucleated cells with prominent eosinophilic nucleoli and abundant cytoplasm resembling classic RS cells and mononuclear variants were scattered throughout all biopsies. The lymphoma cells in the three cases were of T-cell lineage (CD3+, CD43+, and CD45RO+). The RS-like cells from all cases were CD30 and CD15 positive. In contrast to the neoplastic T cells, the RS-like cells lacked all T-cell markers and in two cases were positive for CD20. Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) and EBER 1 (2/2) were detected in the RS-like cells in all cases. The neoplastic T cells were negative for EBV. Polymerase chain reaction (PCR) analysis demonstrated clonal rearrangements of the T-cell receptor gamma chain gene in the three cases. PCR analysis of microdissected RS-like cells for immunoglobulin heavy chain gene rearrangements in cases 1 and 3 showed an oligoclonal pattern. The presence of RS-like cells in PTCL represents a diagnostic pitfall, because in one case this observation led to a misdiagnosis of Hodgkin's disease (HD). The oligoclonal expansion of EBV-infected cells may be related to underlying immunodeficiency associated with T-cell lymphomas and AILT in particular. This phenomenon may provide the basis for some cases of Hodgkin's disease after T-cell lymphomas and suggests that they are clonally unrelated neoplasms. The expression of LMP1 appears to be crucial for the immunophenotype and probably for the morphology of the RS and RS-like cells appearing in diverse lymphoid malignancies, including HD, chronic lymphocytic leukemia, and PTCL.     

The distribution of non-Hodgkin's lymphoma in the lymphoid compartments of the human spleen

In a series of 139 spleens involved by non-Hodgkin's lymphoma, we found that each type of lymphoma (as classified according to the Kiel classification) has a specific pattern of infiltration in the red and white pulp. Tumor infiltration in preexistent follicles was not a feature of B-cell lymphomas, but tumor nodules were found in the red pulp nonfiltering areas in cases of immunocytoma (small lymphocytic plasmacytoid) and centroblastic-centrocytic lymphoma (follicle center-cell lymphoma). B-chronic lymphocytic leukemia and centrocytic-centroblastic lymphoma were located along central arteries of T-cell areas. T-cell areas were infiltrated by B-prolymphocytic leukemia, immunocytoma, centrocytic lymphoma (lymphocytic lymphoma of intermediate differentiation), and T-cell lymphoma/leukemia. The red pulp showed diffuse involvement in leukemic cases. Additionally, there was pericapillary growth in all cases of low-grade B-cell lymphoma. The findings, which are related to the physiological counterparts of the lymphoma cells, contribute to our knowledge of the routes of circulation as well as the homing areas of lymphocytes in the human spleen.     

Hepatosplenic alphabeta T-cell lymphoma: an unusual case with clinical, histologic, and cytogenetic features of gammadelta hepatosplenic T-cell lymphoma

Hepatosplenic gammadelta T-cell lymphoma is a recently identified entity in which lymphoma cells bearing the gammadelta T-cell receptor (TCR) infiltrate the sinusoids of the liver and the sinuses of the splenic red pulp and bone marrow, without lymph node involvement. It is also characterized by a recurrent cytogenetic finding, isochromosome 7q (i7q10). The authors report a case of hepatosplenic lymphoma of alphabeta T-cell phenotype that shares the same clinical, histologic, and cytogenetic characteristics of the previously described hepatosplenic gammadelta T-cell lymphoma. Fluorescent in situ hybridization performed with chromosome 7 probes showed the typical pattern of isochromosome 7q. Genomic analysis of the TCR gamma locus failed to detect a clonal rearrangement. This unique case of hepatosplenic lymphoma of alphabeta T-cell phenotype supports the possibility that lymphoid populations of different alphabeta or gammadelta phenotype that share similar homing and presumably functional properties could give rise to lymphomas displaying similar clinical and pathologic findings.     

Acute renal failure due to malignant lymphoma infiltration

We present two cases of renal lymphoma revealed by acute renal failure (ARF), which remains a rare clinical entity. Case 1 was a 29-year-old man with an ARF. The diagnosis was a primitive kidney immunophenotype B lymphoma. The patient died after three courses of chemotherapy due to rapid spread lymphoma. The second case was a high-grade renal lymphomatous infiltration, with an unusual computer tomography image of two large kidneys compressing the stomach. Death happened early before initiating therapy. In both cases the diagnosis has been established by renal pathology. Early diagnosis is a key component of therapeutic success, however, the rapid spread of lymphoma worsened renal and vital prognosis.     

Acute renal failure due to non-Hodgkin lymphoma infiltration of the kidneys detected by ultrasonography and confirmed by positron emission tomography

Acute renal failure (ARF) as a consequence of non-Hodgkin lymphoma infiltration of the kidneys (LIK) is an uncommon complication of non-Hodgkin lymphoma. In literature, ARF due to LIK is reported in progressive disease. A case of non-oliguric acute renal failure secondary to relapse of large B cell non-Hodgkin lymphoma primarily localized in the mediastinum is reported. LIK of both kidneys was diagnosed by ultrasonography, computer tomography scan and 18-fluorodeoxyglucose positron emission tomography. No other causes for renal failure were found. The prognosis of renal involvement in relapsed non-Hodgkin lymphoma is poor, as is demonstrated by our case.     

Successful treatment of IgA nephropathy in association with low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue type

Kidney and the urogenital tract are among the various mucosal sites involved in mucosa-associated lymphoid tissue (MALT) lymphoma. We report a case with simultaneous onset of crescentic immunoglobulin (Ig) A nephropathy and gastrointestinal low-grade B-cell lymphoma of the MALT type with kidney infiltration. M-component of IgM lambda was detected in the serum, and the renal biopsy specimen showed monotypic lambda light chain staining in the lymphoma cells but not the glomeruli. The heavy proteinuria and impaired creatinine clearance returned to normal, and microscopic hematuria disappeared 20 months after treatment with chlorambucil as single-agent chemotherapy. This coincided with a complete resolution of the gastric and renal lymphoma infiltration. The close association of both the onset and successful outcome of the two entities thus support their possible causal relationship, and we discuss the possibility of an association of the disturbance of the MALT by the lymphoma cells with the pathogenesis of IgA nephropathy.     

Marginal Zone B-cell Lymphoma Arising from Buccal Mucosa Resembling Inflammatory Myofibroblastic Tumor of the Soft Tissue

We report here a case of marginal zone B-cell lymphoma (MZBL) arising from buccal mucosa resembling inflammatory myofibroblastic tumor (IMT) of the soft tissue. On a low-power field, the lesion is characterized by fibrous granulation tissue and numerous lymphoid follicles with or without atrophic small germinal center. A portion of the lymphoid follicles were surrounded by partial and/or complete thin pale cuff of centrocyte-like (CCL) cells on high power field. The thin rim of the lymphoid follicles contained CCL-cells, plasma cells, cells showing plasma cell differentiation and mature eosinophils. In contrast, the granulomatous areas contained were characterized by haphazardly arranged spindle cells, mature plasma cells, mature eosinophils, small-to-medium lymphocytes and histiocytes. Histologically, IMT was suspected. However, flow cytometry and immunohistochemical study demonstrated a monotypic nature of centrocyte-like cells, plasma cells and their precursor and confirmed the diagnosis of MZBL arising from the buccal mucosa. The differential diagnostic problems between IMT of the soft tissue and classical Hodgkin lymphoma and T-cell lymphoma have been discussed previously. However, the present case indicated that MZBL should be added to the differential diagnosis of IMT of the soft tissue.     

Histological and immunohistological findings in lymphoepithelioid cell lymphoma (Lennert's lymphoma)

Four hundred and two cases considered or suspected to be lymphoepithelioid cell lymphoma (Lennert's lymphoma) were analyzed morphologically, immunohistochemically, and clinically. One hundred and eight of these cases, investigated in 180 biopsies, fulfilled the morphological and immunohistochemical criteria for lymphoepithelioid cell lymphoma and are herein reported. Cellular composition and histological structure are described in detail as a basis for discriminating Lennert's lymphoma from similar lymphomas with a high content of epithelioid cells (Hodgkin's disease, AILD type of T-cell lymphoma, lymphoplasmacytic lymphoma) and from inflammatory epithelioid cell reactions. Single typical Hodgkin cells were found in only 3.8% of biopsy specimens examined, and single typical Sternberg-Reed cells were found in only 2.2% of the biopsy specimens examined. Because these single Hodgkin and Sternberg-Reed cells were situated in a relatively monotonous lymphoid cellular pattern and because both these cells types also may occur in peripheral T-cell lymphomas, we include cases with such cells in the category of Lennert's lymphoma. Eight percent of the patients with lymphoepithelioid cell lymphoma showed transformation into a large-cell T-cell lymphoma without the prominent focal epithelioid cell component previously observed. Immunohistochemically, seven of the 69 biopsy specimens with detectable giant cells stained positively for the granulocyte-specific monoclonal antibody 3C4 (approximately CD15). Plasma cells were rare and always showed a polytypic immunoglobulin pattern. Lymphoepithelioid cell lymphoma, defined as a lymphoma of CD4+ T lymphocytes, marks the border between Hodgkin's disease and the non-Hodgkin's lymphomas. Today, absolute criteria for distinguishing between these two classes of lymphoma are lacking.     

t(8;13)-positive bilineal lymphomas: report of 6 cases

The 8p11 myeloproliferative syndrome (EMS) is a rare hematologic malignancy characterized by myeloid hyperplasia, eosinophilia, and precursor lymphoblastic lymphoma, associated with balanced translocations involving chromosome 8p11, most commonly t(8;13)(p11;q12). Approximately 75% of EMS patients present with or develop precursor T-cell lymphoblastic lymphoma, and most subsequently develop acute myeloid leukemia. Here we describe the morphologic and immunophenotypic features of 6 cases of t(8;13)-positive bilineal lymphoma of mixed T-cell and myeloid lineage, 5 in lymph nodes and 1 in breast. The patients, 3 males and 3 females, ranged in age from 6 to 19 years. Histologically, each tumor was composed of 2 distinct cellular components: small to medium-sized T cells with scant cytoplasm that resembled lymphoblasts, and larger immature-appearing cells with more abundant eosinophilic cytoplasm that resembled myeloblasts, a subset of which expressed myeloid antigens. In all cases, the latter component tended to surround residual lymphoid follicles and/or blood vessels. Numerous eosinophils and prominent high endothelial venules were present in all of the lymph node specimens. Interestingly, cells of both components expressed CD3 on immunohistochemical stains. In conclusion, EMS associated with t(8;13) should be suspected in patients with a bilineal tumor that involves lymph nodes or other extramedullary sites. We believe that these bilineal neoplasms of mixed T-cell and myeloid lineages, which present as lymphoma, are analogous to bilineal leukemias. They likely arise from an early hematopoietic cell with potential to differentiate along T-cell and myeloid pathways.     

Acute Renal Failure Secondary to Small Cell Lung Cancer with Tumor Infiltration of the Kidneys

Acute renal failure secondary to tumor infiltration of the kidneys is uncommon and largely described in patients with lymphoma or leukemia. We report a 64-year-old man previously diagnosed with limited stage small cell lung cancer who presented with acute renal failure (ARF). Renal imaging showed bilateral enlargement with features suggestive of an infiltrative process. A kidney biopsy established the diagnosis of metastatic small cell lung cancer with diffuse renal parenchymal infiltration. This case emphasizes the rare potential for cancers to metastasize to the kidneys, which can result in ARF. Early recognition of this cause of ARF is crucial, in particular, when the tumor is amenable to chemotherapy or irradiation.     

Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent γδ T-cell receptor expression

Enteropathy-associated T-cell lymphoma (EATL), an uncommon lymphoma of intestinal intraepithelial T lymphocytes, occurs with a higher frequency in northern Europe due to association with celiac disease. Data on the occurrence of EATL in the Asian population, among whom celiac disease is very rare, are conflicting. This study aimed to characterize EATL encountered in the Chinese population in Hong Kong. Eighteen cases were identified, all fulfilling the criteria of type II rather than classical EATL. The patients, including 13 men and 5 women, had a median age of 62 years. Most presented with small bowel perforation, and there was no history of malabsorption. The clinical course was aggressive, with 14 of 16 patients dying of progressive disease or complications, usually within 1 year. The histologic features were practically identical in all cases. The central zone of the tumor showed ulceration with or without perforation and was characterized by monotonous transmural infiltration of the bowel by small-sized or medium-sized lymphoma cells with few admixed inflammatory cells and no coagulative necrosis. The peripheral zone featured lateral spread of lymphoma cells in the mucosa, accompanied by variable involvement of the submucosa and muscularis. In all cases, there was an intraepithelial lymphocytosis zone contiguous or discontinuous with the peripheral zone, which was characterized by infiltration of the intestinal epithelium by nonatypical small lymphocytes, and not accompanied by other histologic changes of enteropathy. The most common phenotype of the lymphoma cells was CD3+, CD5-, CD4-, CD8+, CD56+, TIA1+, CD30-, and Epstein-Barr virus, and 2 cases showed aberrant expression of CD20. A remarkable finding was that 14 (78%) cases expressed γδ T-cell receptor, and only 6 (33%) expressed αβ T-cell receptor (with 3 cases coexpressing both T-cell receptors and 1 case expressing neither). The immunophenotype of the intraepithelial lymphocytes was either discordant (particularly with respect to CD8 and CD56 expressions) or concordant with the lymphoma cells of the corresponding cases. Thus, this study shows that EATL occurring in the Chinese population is exclusively of type II. In contrast to several studies, intraepithelial lymphocytosis can be consistently demonstrated and this component seems to represent a precursor lesion of EATL rather than a manifestation of celiac disease. In view of the differences in epidemiology and clinicopathologic features, we believe it is justified to separate out type II EATL from the EATL category as a distinct form of lymphoma, for which we propose the designation "monomorphic intestinal T-cell lymphoma."