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° 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.     

CD10 expression in peripheral T-cell lymphomas complicated by a proliferation of large B-cells.

CD10 expression by the neoplastic T cells in angioimmunoblastic T-cell lymphoma was recently described. As cases of peripheral T-cell lymphoma, unspecified, fail to show similar CD10 expression, this feature helps discriminate between these two entities, particularly in cases exhibiting morphologic overlap. Given these findings, we studied CD10 expression in a subtype of peripheral T-cell lymphoma known as peripheral T-cell lymphoma complicated by a proliferation of large B cells and compared it with angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation. A total of 33 cases were identified including peripheral T-cell lymphoma complicated by a proliferation of large B cells (10), angioimmunoblastic T-cell lymphoma (10) and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (13). Diagnoses were established by hematoxylin and eosin (H&E) stain, immunohistochemistry and/or molecular findings (polymerase chain reaction for T-cell receptor-gamma gene rearrangement). Two of 10 cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells showed aberrant CD10 expression (20%) compared to 9/10 cases of angioimmunoblastic T-cell lymphoma (90%) and 8/13 of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (62%). One case each of angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation showed a rare, but not unequivocal, CD10+ atypical cell. Four cases of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation were CD10 negative. Of the 2 CD10+ peripheral T-cell lymphoma complicated by a proliferation of large B cells, one had no H&E or IHC features of angioimmunoblastic T-cell lymphoma and showed only a rare positive cell. The second case, a lung biopsy, exhibited diffuse CD10 tumor cell positivity. The predominant staining pattern in the CD10+ cases was characterized by scattered, mostly individual, morphologically neoplastic cells. A rare case showed clusters of positive cells. Our data indicate that only 20% of cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells show CD10 expression by the neoplastic T cells in contrast to angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation which exhibit CD10 staining in 90 and 62% of cases, respectively. This finding does not reach statistical significance with a P-value of 0.57 (Fisher's exact test). As these entities appear to be biologically distinct and may portend different overall survivals, CD10 expression may serve as an additional discriminating criterion.     

Peripheral T-cell lymphoma with a nodular growth pattern

Peripheral T-cell lymphomas (PTCL) with nodular growth patterns are very rare, with only 17 cases reported previously. Here, we report a case of PTCL with a nodular growth pattern. The patient was an 81-year-old Japanese woman who complained of malaise, fever and generalized lymph node swelling. Cervical lymph node biopsy was performed, and histological examination revealed proliferation of medium- to large-sized atypical lymphoid cells with indented to irregular nuclei, distinct nucleoli and clear cytoplasm. The nodular growth pattern of the lymphoma cells was obvious. On immunohistochemistry, the atypical lymphoid cells proved to be of T-helper cell origin (CD2+CD3CD4+CD5+CD7+ CD8-CD10-CD25-CD30-CD57-). Polymerase chain reaction analysis of the T-cell receptor gamma-chain revealed a monoclonal rearrangement band. This unusual growth pattern should be distinguished among PTCL, as such cases could be confused with reactive nodular hyperplasia, nodular lymphoma, mantle cell lymphoma and marginal zone lymphoma with nodular colonization.     

Peripheral T-cell lymphoma mimicking marginal zone B-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) may assume a variety of histologic and cytologic appearances. We describe eight cases of PTCL morphologically simulating marginal zone B-cell lymphoma. We reviewed PTCL cases diagnosed in our institution between 1990 and 2000 and selected eight cases for study based on the following criteria: small-cell morphology with abundant, clear cytoplasm and either marginal zone involvement by the neoplastic infiltrate in lymph node biopsies or lymphoepithelial lesions in extranodal biopsies. Histologic features and ancillary studies were reviewed. Patients included six women and two men with a median age of 53 years (range, 35 to 74 years). Six patients were diagnosed with primary nodal PTCL, and two presented with primary extranodal disease. The original diagnosis was PTCL in only four cases; three cases were diagnosed as atypical lymphoid infiltrate, and one case as benign lymphoepithelial lesion. Lymph node biopsies revealed partial effacement of the architecture with residual follicles surrounded by the neoplastic small cells. Extranodal sites included hard palate, tongue, tonsil, and submandibular glands; all but one case demonstrated lymphoepithelial lesions. Monoclonality was demonstrated in six of eight cases (rearrangement of T-cell receptor gene), and three of eight had an aberrant T-cell population by flow cytometry. The differential diagnosis of atypical lymphoid infiltrates with morphologic features of marginal zone B-cell lymphoma should include PTCL. This uncommon morphological mimicry should be recognized, because PTCL is an aggressive disease regardless of morphology and should be treated accordingly.     

Peripheral T-cell lymphoma: a clinicopathologic study of nine cases

The clinicopathologic features of nine cases of peripheral T-cell lymphoma were analyzed. Although the youngest patient was 18 years old, the median age was 59.8 years. They usually presented with widespread disease and had an aggressive course. Seven have died with a median survival of 10.9 months. Five cases were of mixed cell type, sharing certain histopathologic features that we believe are characteristic of peripheral T-cell lymphomas. Three cases were of large cell type; one was a small cell (PDL) type. This latter patient lived symptom-free without treatment for over 3 years, despite stage III disease. Another patient, whose tumor had nodular sclerosis-like fibrosis, is in complete remission two years after chemotherapy for stage III B disease. Because peripheral T-cell lymphoma is morphologically heterogeneous, it may be clinically heterogeneous as well. We believe that classification according to a modified Rappaport system may clarify possible variations in biologic behavior.     

Peripheral T-cell lymphoma arising in the liver

We report 3 cases of primary hepatic peripheral T-cell lymphoma (PTCL). All patients were men, 50 to 57 years of age, who sought care because of systemic symptoms including fever, fatigue, and weight loss. Physical examination revealed hepatomegaly in 2 patients, associated with jaundice in 1. Two patients had abnormal serum liver enzyme levels and coagulation profiles. Imaging studies demonstrated marked hepatomegaly without focal lesions in 1 patient and multiple discrete tumor masses in 2 patients. Tumor infiltrates in biopsy specimens were heterogeneous with a large cell component in 2 cases. An inflammatory background was present in all cases, complicating the histologic recognition of PTCL Immunohistochemical studies showed that all tumors were of T-cell lineage, and 2 cases had monoclonal T-cell receptor gamma chain gene rearrangements. One patient died of disease shortly after diagnosis, and 2 patients treated with multiagent chemotherapy are in clinical remission with 12 and 84 months of clinicalfollow-up, respectively. PTCL may rarely arise in the liver. These neoplasms respond to chemotherapy, suggesting that this disease is curable if diagnosed at an early stage.     

Peripheral T-cell lymphoma presenting as a soft-tissue mass of the extremity

An 87-year-old man was found to have a lymphoma in the deep soft tissue of the right shoulder with concomitant central nervous system involvement. There was no evidence of cutaneous, peripheral lymph node, mediastinal, abdominal, or bone marrow involvement. Light microscopic, ultrastructural, and immunohistochemical evaluation characterized the neoplasm as a peripheral T-cell lymphoma. Lymphomas presenting in soft tissue are rare, and the few well-documented cases in the literature are of B-cell origin. We report a T-cell lymphoma presenting in the soft tissue of the extremity, and delineate its clinicopathologic features.     

Sequential development of diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma

Lymphoma of different histologic type can occur in the same patient. Here, we describe a 64-year-old male patient with angioimmunoblastic T-cell lymphoma (AITL) who subsequently developed diffuse large B-cell lymphoma (DLBCL). At the time of initial diagnosis, histologic examination of a left inguinal lymph node of the patient and a monoclonal pattern of TCRβ gene rearrangement showed typical features of AITL, and there was no evidence of a monoclonal B-cell population. Twenty-six months later, he had generalized lymphadenopathy and organs involvement by DLBCL. A monoclonal IgH gene rearrangement proved de novo development of secondary B-cell lymphoma and excluded relapse of a primary composite lymphoma. The in situ hybridization analysis showed Epstein-Barr-encoded RNA (EBER) sporadic positivity in sample collected from AITL but extensive positivity in the immunoblasts collected from DLBCL. Our observation supports the hypothesis that Epstein-Barr virus (EBV) is etiologically related to AITL in this case. Clonal expansion of EBV-associated DLBCL is a secondary event in AITL via EBV infection or reactivation.     

Peripheral eosinophilia camouflaging anaplastic large cell lymphoma

Eosinophilia is a nonspecific laboratory finding, often noted incidentally during routine blood analysis. When persistent, eosinophilia can herald an underlying parasitic infection, drug reaction or less commonly, a neoplastic process. Anaplastic large cell lymphoma (ALCL) and tissue eosinophilia has been described; however, such cases have not displayed marked leukocytosis with eosinophilia. This article reports a patient presenting with marked leukocytosis with profound peripheral eosinophilia initially thought to be related to a chronic myeloproliferative disorder, likely chronic eosinophilic leukemia. After further diagnostic evaluation, ALCL was noted in the bone marrow, masked by the myeloid hyperplasia and eosinophilia. This case emphasizes the importance of a full diagnostic workup for T-cell malignancies, including ALCL rather than focusing on the far less common eosinophilia-associated myeloid malignancies in the clinicopathologic setting of marked eosinophilia. Moreover, bone marrow involvement by ALCL is exceedingly rare and when noted, presents as one or more localized lytic lesions. This is the first reported case of ALCL primarily involving bone marrow without radiographic evidence of lytic bone lesions.     

Angioimmunoblastic T-cell lymphoma with supervening Epstein-Barr virus-associated large B-cell lymphoma

Patients with angioimmunoblastic T-cell lymphoma can have profound immune dysfunction and immunodeficiency. Epstein-Barr virus-driven B-cell lymphoid proliferation can occur in angioimmunoblastic T-cell lymphoma, as in other immunodeficiency states. However, few cases of Epstein-Barr virus-positive B-cell lymphoma arising in patients with preexisting angioimmunoblastic T-cell lymphoma have been reported. We report a case of angioimmunoblastic T-cell lymphoma in which diffuse large B-cell lymphoma developed 56 months after the diagnosis of angioimmunoblastic T-cell lymphoma. The patient survived for 9 years after the initial diagnosis of angioimmunoblastic T-cell lymphoma, and molecular studies performed on multiple biopsy specimens during this period revealed the dynamic nature of clonal lymphoid expansion. Epstein-Barr virus latent membrane protein 1 and Epstein-Barr virus-encoded RNA were detected in the diffuse large B-cell lymphoma, suggesting that Epstein-Barr virus may have played a role in the pathogenesis of the diffuse large B-cell lymphoma.     

原发于骨骼肌的间变性大细胞T细胞淋巴瘤

目的：探讨骨骼肌原发的间变性大细胞淋巴瘤的临床病理特征和免疫表型。方法：采用常规制片和免疫组化(S-P)法检测1例（14岁）骨骼肌原发的间变性大细胞淋巴瘤。结果：肿瘤细胞CD30、ALK-1、CD45RO和CD45阳性；而CD20、EMA、S-100蛋白、desmin和CD68阴性。结论：本例为间变性淋巴瘤激酶（ALK）阳性的间变性大细胞淋巴瘤。骨骼肌原发的间变性大细胞淋巴瘤非常少见，诊断旱应先排除其它肿瘤和其它部位淋巴瘤累及骨骼肌。     

Peripheral T-cell lymphoma: aggressive disease with heterogeneous immunotypes

Eleven patients with mature or peripheral T-cell lymphoma (PTL), other than mycosis fungoides, were identified using an extensive battery of T- and B-cell markers. Eight cases had a histologic diagnosis of either diffuse large cell or mixed lymphoma, three of small cell type. All cases had one or more "mature" T-antigens and an absence of B- and immature T-antigens. Assessment of T-antigens included E-rosettes (Er), anti-Leu 1-7 and Tdt. The authors delineated striking heterogeneity of T-antigen expression: 9 different immunotypes in 11 cases. Subset T-antigen assessment indicated T-helper neoplastic cells in five cases and T-suppressor in two. The remaining four had universal T-antigens alone. Seven cases appeared to have "novel" T-phenotypes not corresponding to normal T-ontogeny phenotypes. Novel or idiosyncratic phenotypes may be a key characteristic of PTL. Since no single T-antigen, including Er and Er receptor (Leu-5), was expressed in all cases, a battery of monoclonal antibodies is necessary to detect PTL. Clinically, the authors found PTL unexpectedly aggressive, despite mature immunotype. Most patients were elderly (median age 69); all had extranodal disease with cutaneous involvement (six cases) most frequent. Responses to chemotherapy frequently proved transient, with median survival of nine months. A fulminant course was noted even with localized presentation. Clinical outcome suggests PTL requires new therapeutic strategies.     

Peripheral T-cell lymphoma with helper T-cell phenotype (Leu 3a+ Leu 8-)

Eleven cases of Leu 3a+ Leu 8- peripheral T-cell lymphoma (PTCL), excluding adult T-cell leukemia/lymphoma, were studied by immunostaining with monoclonal antibodies and enzyme histochemistry in order to clarify the histogenesis of PTCL. Seven of the eleven cases had varying degrees of polyclonal hypergammaglobulinemia. All cases were histologically characterized by neoplastic proliferation of clear cells and some cases showed a histologic background similar to IBL or AILD lesions with proliferation of immunoblasts or plasmacytoid cells and vascular proliferation. Immunohistologic analysis of PLP-fixed frozen tissues revealed that neoplastic clear cells expressed a Leu 3a+ Leu 8- phenotype (helper T-cell subset). The distribution of Leu 3a+ Leu 8- neoplastic cells corresponded closely to that of DRC-1+ cells, which are localized in the lymphatic follicles, but hardly at all with that of beta-glucuronidase+ vessels, termed PCV or HEV, which are usually present in T-cell areas. One case only progressed from Leu 3a+ Leu 8- IBL-like T-cell lymphoma (IBL-T), with proliferation of immunoblasts or plasmacytoid cells and vascular proliferation, to diffuse lymphoma of the large cell type showing none of these lesions. From these observations it is suggested that IBL-T might progress to T-cell-type monomorphous diffuse lymphoma.     

Peripheral T-cell lymphoma with involvement of the expanded mantle zone

Peripheral T-cell lymphoma (PTCL) with a nodular architecture is rare. Recently, two variants have been described with infiltration of the B-cell follicle, one variant that localizes to the marginal zone with a so-called perifollicular growth pattern, and a variant that localizes to the germinal center. These lymphomas have a CD4+ phenotype and may express Bcl-6. We have studied five similar cases of PTCL with involvement of the B-cell follicle. However, our cases differ from the cases previously described by their predominant and frequently patchy involvement of the expanded mantle zone of the B-cell follicle at onset. Later biopsies in three of the cases show diffuse infiltration of the lymph node, without features of angioimmunoblastic TCL (AILT). All cases expressed Bcl-6 in addition to CD4. Cytogenetics was available in four of the cases but revealed no recurrent chromosomal aberrations or changes associated with other types of PTCL. No mutations of the BCL-6 gene were observed. Together, the cases seem to have an intermediately aggressive clinical behavior. Whether our cases are part of a spectrum of PTCLs that encompasses previously described variants with predominant marginal zone or germinal center infiltration or they represent a separate T-cell lymphoma type remains to be demonstrated by a study of more of such cases.     

Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma

A case showing the typical clinical and pathological features of splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma is presented. Since the series recorded by Dogan et al (Am J Surg Pathol 2003;27:903-911), there have been very few reports on this lymphoma variant. Our case presents minor variations on the recorded features. Possible reasons for the scarcity of reports and for the confirmation of this lymphoma as a variant of T-cell-rich large B-cell lymphoma are discussed.     

Contact-dependent suppression of CD4 T-cell activation and proliferation by B cells activated through IgD cross-linking

Although the co-stimulatory interaction between B and T cells is well defined, recent evidence suggests that B cells also have a regulatory role. Here, we show that B cells activated using anti-IgD conjugated to dextran (α-δ-dex) directly inhibit T-cell receptor-induced CD4 T-cell activation, proliferation and cytokine production. This effect was observed in CD4 T cells activated both with and without CD28 co-stimulation. T-cell viability was unaffected, and the T-cell suppressive effect was mediated by contact with IgD-activated purified B cells and not by interleukin-10 or other soluble factors. This is the first evidence of IgD-activated B cells mediating inhibition of activation and proliferation of CD4 T cells in humans.     

腺淋巴瘤淋巴组织恶变为非特殊性外周T细胞淋巴瘤一例

患者男,62岁.主因发现左侧腮腺肿物3年,生长加快1年于2007年1月5日入院.体检:左腮腺后极触及一个直径3.5 cm的肿物,边界清楚,表面光滑,无压痛,活动度较好,与周围组织无粘连,全身浅表淋巴结无肿大.B超示左侧颈上部近圆形低回声区,与周围组织分界尚清.     

Apoptosis and proliferation in subcutaneous panniculitis-like T-cell lymphoma.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL), designated recently as a distinct clinicopathologic entity in the World Health Organization Classification, is a neoplasm composed of cytotoxic T-cells that preferentially involves subcutaneous adipose tissue. Histologically, SPTCL is characterized by extensive karyorrhectic debris and tumor necrosis suggesting that apoptotic mechanisms are involved in its pathogenesis. We assessed the apoptotic index (AI) and proliferation rate (PR) of 13 cases of SPTCL by TUNEL test and Ki-67 immunostaining, respectively. We also immunohistochemically assessed for expression of BCL-2 (anti-apoptosis), BAX (pro-apoptosis), and P53 and correlated the results with apoptosis and proliferation. We detected a high AI (median 8.1%) in 11 cases of SPTCL, and 12 cases had low BCL-2 and high BAX expression. BCL-2 expression inversely correlated with AI (P <.001) and BAX (P <.001). We found a low PR (cutoff > or = 25%) in eight (61%) cases. There was an inverse correlation between AI and PR (r = -.58, P =.04). Ten cases were assessed for P53; immunostaining results were heterogeneous but P53 expression correlated with large cell cytologic features. Our findings demonstrate that SPTCLs have a high AI that may be explained by differential expression of BCL-2 and BAX in the neoplastic cells.