小细胞性非特指外周T细胞淋巴瘤病理形态和免疫表型分析

目的 探讨小细胞性非特指外周T细胞淋巴瘤(PTCL,NOS)的临床病理与免疫表型及其病理诊断和鉴别诊断.方法 对5例小细胞性PTCL,NOS进行临床病理回顾性研究和随访,免疫表型检测(SP和EnVision法),以及EBER原位杂交和T细胞受体(TCR)基因重排分析.结果 5例均为男性,平均年龄52.6岁.中位病程1个月.5例中3例为临床Ⅳ期,2例为临床Ⅲ期.4例有全身浅表淋巴结及脾脏肿大,1例有肝肿大.2例有浆膜腔积液.行骨髓检查的4例中,3例有肿瘤累及.1例有外周血自细胞总数和淋巴细胞分类计数升高.主要病理改变为淋巴结结构的破坏和单一形态的小淋巴细胞弥漫性浸润,4例可见少数大的异形细胞散在分布,2例见小血管增生现象.5例之肿瘤细胞均表达两种以上T细胞分化抗原和CD43,表达CD99(3/4),均不表达CD20、末端脱氧核苷酸转移酶、CD56和粒酶B.Ki-67指数为5%-15%.4例行TCR基因重排分析,均存在TCRy基因克隆性重排,1例检出TCRβ基因克隆性重排.EBER原位杂交检测均为阴性.获得3例随访资料,且患者均死亡,平均生存时间21.7个月.结论 小细胞性PTCL,NOS少见,呈高临床分期,预后差,组织形态表现为惰性淋巴瘤.     

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.     

Bone marrow histologic and immunohistochemical findings in peripheral. T-cell lymphoma: A study of 38 cases

The histologic and immunohistochemical findings in bone marrow (BM) biopsies from 38 patients with peripheral T-cell lymphoma (PTCL) are reported. Routine light microscopy showed that BM involvement was unequivocal in 12 cases and questionable in 14 cases. There was no histologic evidence of lymphoma in the remaining 12 cases. Immunohistochemistry performed on BM frozen sections demonstrated the T-cell origin of the infiltrating lymphoid cells in 24 of the 26 patients with unequivocal or questionable involvement. The malignant nature of these cells was suggested by demonstration of an aberrant T-cell phenotype identical to that observed in the other sites of involvement. In addition, in four of the 12 cases with apparently normal BM at routine light microscopy, immunohistochemistry revealed a minimal but phenotypically abnormal T-cell population, suggesting mild infiltration by lymphoma. These combined histologic and immunohistochemical data documented a high incidence (73%) of BM involvement by PTCL. In addition, a very peculiar sinusal pattern of BM involvement was found in five patients who presented an unusual type of hepatosplenic T-cell lymphoma expressing the gamma delta T-cell receptor. The present study demonstrates the high incidence of BM involvement by PTCL and emphasizes the value of frozen section immunohistochemistry to establish this diagnosis, especially when routine light microscopy findings are questionable.     

淋巴浆细胞性淋巴瘤的临床病理特点分析

目的 探讨淋巴浆细胞性淋巴瘤(LPL)的临床及病理学特点及其鉴别诊断和与Waldenstr(o)m巨球蛋白血症的关系.方法 24例骨髓活检标本,6例同时行淋巴结活检,行石蜡包埋切片、HE染色形态观察及免疫组织化学EliVision法检测分析.结果 男17例,女7例(男:女=2.4:1).中位年龄59.5岁(42～75岁).临床表现以乏力最多见,为83.3%(20/24).高黏滞血症20.8%(5/24),B症状8.3%(2/24),浅表淋巴结肿大41.7%(10/24).贫血79.2%(19/24),白细胞增高8.3%(2/24),血小板减少37.5%(9/24).血清免疫固定电泳显示23例(95.8%)出现单克隆性免疫球蛋白轻链条带,IgM型20例、IgG型2例、IgA型1例.22例骨髓活检和2例淋巴结活检均经病理组织形态和免疫组织化学诊断为LPL,骨髓及淋巴结瘤细胞由小淋巴细胞、浆细胞样淋巴细胞及浆细胞组成;侵犯骨髓的方式多为弥漫型(63.6%,14/22),结节型及间质型少见分别为22.7%(5/22)及13.6%(3/22).淋巴结瘤细胞呈弥漫性分布.瘤细胞表达Pax5、CD20、CD38、CD138,不表达CD5、CD10、CD23、细胞周期蛋白D1、CD3、CD7、髓过氧化物酶.结论 LPL具有明确的临床及病理学特点,诊断应主要结合组织形态和免疫表型与慢性淋巴细胞白血病/小细胞淋巴瘤、脾脏边缘区淋巴瘤及滤泡性淋巴瘤等小淋巴细胞肿瘤鉴别.Waldenstr(o)m巨球蛋白血症的本质为LPL.     

Peripheral T-cell lymphomas: a clinicopathologic study of 75 cases

Seventy-five peripheral T-cell lymphomas (PTLs) were classified according to the recently proposed "Updated Kiel Classification of Non-Hodgkin's Lymphomas" (mycosis fungoides and Sezary's syndrome excluded). Thirty-seven PTLs belonged to the low-grade category (T-cell chronic lymphocytic leukemia [T-CLL], 3; lymphoepithelioid, 4; angioimmunoblastic, 22; T-zone, 6; pleomorphic small cell, 2) and 38 belonged to the high-grade category (pleomorphic medium and large cell, 24; immunoblastic, 1; large-cell anaplastic Ki-1-positive, 13). Loss of pan-T antigens occurred exclusively in high-grade PTLs; on paraffin sections UCHL 1 was slightly more sensitive than MT 1. Sixty patients presented with lymphadenopathy and 15 patients (20%) presented with extranodal disease most frequently affecting the skin and upper aerodigestive tract. B-cell lymphoma symptoms were found in 43 cases (57%) and bone marrow involvement (T-CLL excluded) was found in 12 cases (17%). Staging (T-CLL excluded) revealed stage I in 13%, stage II in 15%, and stages III and IV in 72% of the cases. Among the intensively treated patients, 37% achieved complete remission and 15 are still in complete remission after 4 to 79 months (median: 24 months). The overall median survival (MS) rate was 23 months. Peripheral T-cell lymphoma of pleomorphic medium and large-cell type was the most aggressive lymphoma (MS: 8 months). B-cell lymphoma symptoms, bone marrow involvement, and Ki-67 positivity 60% or greater significantly shortened survival times, whereas age (under 60 versus over 60 years), stage (I and II versus III and IV), and grade had no significant influence. Ki-67 reactivity was found to be a prognostic factor which allows prediction of probable poor outcome, especially in cases with limited stage of disease.     

Prevalence of bone marrow involvement in systemic anaplastic large cell lymphoma: are immunohistochemical studies necessary?

The frequency of bone marrow involvement in anaplastic large cell lymphoma has been reported with great variation. A prior study found that anaplastic large cell lymphoma involvement of bone marrow was often not evident on routine stains and advocated using immunohistochemical studies. We evaluated 70 bone marrow biopsies from 41 patients with anaplastic large cell lymphoma and found 10 morphologically involved cases (14% of all biopsies, 22% of all patients). In most cases (9/10 biopsies), the involvement of the bone marrow by anaplastic large cell lymphoma was massive and, thus, was evident on the hematoxylin and eosin section. In only 1 biopsy (1% of all biopsies, 2% of all patients), the involvement was minimal and more difficult to detect. To determine if the hematoxylin and eosin evaluation missed bone marrow involvement, we used a panel of antibodies including CD30, ALK-1, epithelial membrane antigen, and granzyme. Only the 10 morphologically involved cases showed anaplastic large cell lymphoma cells with distinct CD30 expression. Other stains highlighted only a subset of the CD30-positive cases. Clinical follow-up was available for 30 patients and shows correlation of marrow involvement with lower overall survival (P = .033). Overall, marrow involvement in anaplastic large cell lymphoma was relatively uncommon, and when present, it was identified on hematoxylin and eosin sections.     

Bone marrow involvement by non-Hodgkin's lymphom.

We retrospectively studied 156 patients with non-Hodgkin''s; ymphoma (NHL) in order to evaluate the incidence of bone marrow (BM) involvement at the time of diagnosis. The incidence of marrow involvement in NHL was 35% (55 patients). The most common histologic type of lymphoma was diffuse large cell lymphoma with 30% of the cases having bone marrow involvement. The highest incidence of marrow involvement was seen in immunoblastic lymphoma & the lowest incidence in diffuse mixed cell lymphoma. Bone marrow lymphoma was present in 50% of low-, 34% of intermediate-, and 55% of high-grade lymphomas. B-cell vs T-cell lymphoma in cases of marrow involvement was 56% to 42%. The most frequent pattern of marrow involvement was interstitial & diffuse (56% & 31%). The paratrabecular pattern was rare (4%). Most lymphomas (42%) extensively involved marrow space greater than 76% of the total marrow space. Discordant histology between lymph node and BM was seen in 10 cases (18%). Biopsy was the best method compared to smear & clot section (sensitivity 82% vs 72% vs 69%). In conclusion, our study revealed that the most common histologic type of marrow lymphoma was diffuse large cell type with frequent interstitial and diffuse pattern and extensive involvement of the marrow space. No predilection for a trabecular pattern was found. This result was in contrast to that in the Western literature.     

Isolated bone marrow manifestation of HIV-associated Hodgkin lymphoma.

Human immunodeficiency virus-associated Hodgkin lymphoma frequently involves the bone marrow and is usually recognized at staging after Hodgkin lymphoma diagnosis on a lymph node or other tissue biopsies, but occasionally the marrow involvement is the only apparent manifestation of disease. In the latter setting, diagnosis can be problematic. From a total of 42 patients with newly diagnosed human immunodeficiency virus-associated Hodgkin lymphoma, 22 subjects had positive marrow involvement at diagnosis; 16 of them had additional substantial histological and/or clinical extramedullary Hodgkin lymphoma. In the remaining 6 patients the bone marrow was the only site of disease at diagnosis. In all six cases, bone marrow biopsy revealed obvious lymphomatous involvement. Reed-Sternberg cells were identified both morphologically and immunophenotypically in all cases. Spared marrow tissue consistently showed fibrosis. All patients were males with a median age of 35 years (range, 31-58 years). All presented with fever, blood cytopenias, and severe CD4+ lymphocyte depletion (median, 70 cells/mm(3)). After diagnosis, all staging procedures were negative, and all patients were treated with chemotherapy. Median survival was 4 months (range, 2-118 mo). Longer survival was achieved in the patients who completed chemotherapy regimens; three subjects, however, died shortly before the full completion of chemotherapy, two of them from Hodgkin lymphoma. Isolated bone marrow HIV-associated Hodgkin lymphoma may be an underestimated condition in HIV-infected patients; in those individuals with unexplained fever and blood cytopenias, bone marrow biopsy should be performed with the aim of assessing for Hodgkin lymphoma, even in the absence of nodal and visceral lymphomatous involvement. A rapid diagnosis of isolated bone marrow HIV-associated Hodgkin lymphoma could expedite therapy.     

Reed-Sternberg-like cells in nodular lymphoma involving the bone marrow.

McKenna, Robert W., and Brunning, Richard D. Reed-Sternberg-like cells in nodular lymphoma involving the bone marrow. Am JClin Pathol 63: 779-785, 1975. Two patients with cells indistinguishable from Reed-Sternberg cells in bone marrow lesions of nodular poorly differentiated lymphocytic lymphoma are described. Both patients had lymph node biopsies showing nodular lymphoma. Bone marrow and blood involvement with the lymphoma was demonstrated at the time of initial diagnosis. Reed-Sternberg-like cells were not demonstrated in either case until later in the course of the disease, after the patients had been treated with numerous chemotherapeutic agents. Other similarities of bone marrow involvement with nodular lymphoma to Hodgkin's disease of the bone marrow are noted. The origin of the Reed-Sternberg-like cells in nodular lymphoma is not clear, but they could result from morphologicalteration of lymphoma cells by chemotherapy. The finding of Reed-Sternberg cells in bone marrow lesions should be interpreted with caution unless diagnostic biopsy material from other sites is available for study. (Key words: Bone marrow lymphoma' nodular lymphoma; Reed-Sternberg cells).     

Monocytoid B-cell lymphoma in patients with Sj?gren's syndrome: a clinicopathologic study of 13 patients.

A recent clinicopathologic study of a series of patients with monocytoid B-cell lymphoma (MBCL) indicated that there is a frequent association between MBCL and Sj?gren's syndrome (SS) and raised the possibility of a relationship between these two disease entities. To further investigate the possible relationship of MBCL and SS, we studied pathologic and clinical characteristics of 13 patients with MBCL who had clinically documented SS. In all patients, the lymphoma had the characteristic morphologic features of MBCL, and immunologic and molecular hybridization studies confirmed the B-cell nature of the lymphoma. Twelve of the 13 patients were female, with a median age of 66 years at diagnosis. Eleven had localized disease and presented with either salivary gland or cervical lymph node enlargement; one patient presented with a breast mass, and another with generalized lymphadenopathy and hepatosplenomegaly. In five of 13 patients, the MBCL was associated with or progressed to large cell lymphoma. In two patients, there was bilateral involvement of the parotid gland; one had a synchronous high-grade lymphoma in both parotid glands. In two patients, bone marrow biopsies showed involvement by MBCL. Eleven patients are alive 2 to 55 months after the diagnosis of MBCL. One patient died with the disease 8 months after the initial diagnosis. Another patient died of an unrelated cause without evidence of disease 16 months after the diagnosis of MBCL. We conclude that there is a more than fortuitous association between MBCL and SS. This concept is consistent with previously reported observations of reactive monocytoid B cells in patients with benign lymphoepithelial lesions of salivary glands, which may result from selective homing of reactive monocytoid B lymphocytes to the benign lymphoepithelial lesions and their subsequent neoplastic transformation.     

Prominent intrasinusoidal infiltration of the bone marrow by mantle cell lymphoma

Intrasinusoidal infiltration of bone marrow (BM) may accompany several malignant lymphoproliferative disorders. In small B-cell lymphomas, this pattern is considered specific for splenic marginal zone lymphoma (SMZL) when exclusive or prominent, although it may occur in other subtypes of non-Hodgkin's lymphomas (NHLs) as a minor feature. Here we report 2 cases of mantle cell lymphoma (MCL) with a prominent intrasinusoidal BM infiltration pattern. Both patients presented with massive splenomegaly and peripheral blood involvement characterized by markedly atypical lymphocytes, but no lymphadenopathy. The cytological features and the phenotype of the lymphoma cells were diagnostic of MCL. The malignant B cells showed coexpression of B-cell markers (CD20+ and CD79a+), CD5 antigen, and cyclin D1 by immunohistochemistry. We discuss the specificity of an intrasinusoidal growth pattern in the bone marrow, emphasizing the importance of using a broader immunohistochemical panel in the differential diagnosis of intrasinusoidal BM infiltration by NHL.     

Blastic mantle cell leukemia: an unusual presentation of blastic mantle cell lymphoma.

Six patients had blood and bone marrow manifestations characterized by the presence of morphologically immature or blastic B-lineage lymphoid cells expressing CD5 antigen. The median patient age was 70 years, and the male-to-female ratio was 5:1. The presence or degree of lymphadenopathy and splenomegaly was variable among this group at staging evaluation, although two patients did not have these features. One patient had an antecedent diagnosis of classical nodal mantle cell lymphoma, without prior morphologic blood or bone marrow involvement. Other patients lacked a history of underlying lymphoproliferative disorders. The median white blood cell count was 120 x 10(9)/L. Most patients had thrombocytopenia, whereas only one patient had neutropenia at presentation. Leukemic peripheral blood cells in these six cases were small to medium in size with fine or granular nuclear chromatin and small or inconspicuous nucleoli. The pattern of marrow involvement was interstitial or diffuse, with cells showing immature nuclear features resembling acute leukemia or blastic lymphoma. All tumors demonstrated a consistent immunophenotype of B-cell lineage, surface immunoglobulin positivity, and CD5 antigen expression. The progenitor cell-associated markers CD34 and TdT were not expressed, and CD23 antigen was either negative (three of four cases) or only weakly present (one of four cases). The presence of a karyotypic t(11;14)(q13;q32) was documented in one tumor, whereas two other cases had BCL-1 gene rearrangements by either polymerase chain reaction or Southern blot analysis. Cyclin D1 mRNA overexpression was noted in three of four cases tested. This patient group was characterized by very poor overall survival (median, 3 months; range, 0.5 to 6 months). The aggregate clinical, pathologic, and genetic data in these unusual cases are consistent with de novo or predominant leukemic presentations of blastic mantle cell lymphoma. Accurate diagnosis in such cases is greatly facilitated by cytogenetic studies or the demonstration of BCL-1/cyclin D1 abnormalities.     

Bone marrow diagnosis in lymphoproliferative disorders: comparison of results obtained from conventional histomorphology and immunohistology

In this study we have investigated 313 bone marrow biopsies from 280 patients with lymphoproliferative disorders. Trephines were sectioned transversely to obtain one cylinder for cryostat sectioning and immunostaining and a second for histomorphological evaluation using a plastic-embedding technique. The results obtained by histomorphological and immunohistological evaluation were compared for their contribution to staging and classification. Using both techniques, bone marrow involvement was seen in 3/43 (7.0%) biopsies from patients with Hodgkin's disease and in 193/270 (71.5%) cases with non-Hodgkin's lymphoma, including multiple myeloma and acute lymphocytic leukaemia. Immunohistology proved superior in detecting minimal mainly interstitial bone marrow infiltration in 15 leukaemia/lymphoma cases. Biopsies showing infiltration with both methods (n = 157) were re-examined for classification of lymphomatous infiltrates. Whereas immunohistology did not provide additional information in cases with Hodgkin's disease and myeloma, this method was crucial for establishing the definitive diagnosis in a number of cases with acute lymphocytic leukaemia and non-Hodgkin's lymphoma. In all of six leukaemia cases, in which no or inadequate material was available for immunophenotyping of cell suspensions, immunohistology clearly defined the subtype. In the 140 cases of non-Hodgkin's lymphoma the majority of cases (76.4%) were identically classified. In some cases, with important prognostic and therapeutic implications, immunohistology alone provided the definitive diagnosis: T-cell lymphoma (n = 2), hairy cell leukaemia (n = 2) and centrocytic non-Hodgkin's lymphoma (n = 3). Bone marrow immunohistology is, therefore, an important supplement for classical lymphoma/leukaemia diagnosis. The differences observed between histomorphology and immunohistology emphasize the importance of lymph node biopsy in lymphoma classification.     

Diffuse large B-cell lymphoma with distinctive patterns of splenic and bone marrow involvement: clinicopathologic features of two cases.

Two unusual cases of large B-cell lymphoma with predominant splenic and bone marrow (BM) involvement and similar clinical and histopathologic features are described. Both patients presented with nonspecific constitutional symptoms, unexplained cytopenias, and splenomegaly. Splenectomy revealed diffuse red pulp involvement by large B-cell lymphoma. The perisplenic lymph nodes were also involved diffusely with effacement of normal nodal architecture, excluding a diagnosis of intravascular large B-cell lymphoma. BM biopsies revealed striking erythroid hyperplasia without overt morphologic evidence of involvement by lymphoma. Immunoperoxidase staining of the marrow biopsies with antibodies to CD20 and erythroid-associated antigens revealed involvement by large B-cell lymphoma morphologically resembling the early pronormoblasts. In both cases there was prominent, but not exclusive, intravascular/intrasinusoidal lymphomatous marrow infiltration. These cases represent an unusual variant of large B-cell lymphoma with distinctive patterns of splenic and BM involvement. Furthermore, they underscore the difficulties in identifying intrasinusoidal marrow infiltration by lymphoma in H&E-stained biopsy slides and demonstrate that this pattern of marrow infiltration may be seen in cases of large B-cell lymphoma distinct from the intravascular variant.     

Immunocytochemical analysis of lymph node aspirates in patients with human immunodeficiency virus infection.

Thirty four patients positive for human immunodeficiency virus (HIV) who had lymphadenopathy were investigated using fine needle aspiration. Cytological analysis included immunocytochemical investigation with the alkaline phosphatase-antialkaline phosphatase (APAAP) method. All patients had confirmation of cytological diagnosis by lymph node biopsy. Fifteen aspirates with follicular hyperplasia were evaluated. Eleven patients showed B cell predominance. The B cell population did not show light chain restriction. Ten patients with B cell non-Hodgkin's lymphoma (five with Burkitt's lymphoma and five with B cell immunoblastic lymphoma) were investigated. Nine out of 10 cases were monoclonal with respect to their light chain determinants; only one case with Burkitt's lymphoma with partial lymph node metastasis did not show light chain restriction. The cytological diagnosis included two mycobacterial infections and four cystic lesions. Histological investigation was necessary to diagnose the extent of lymph node disease caused by Kaposi's sarcoma. These findings indicate that the immunocytological investigation of lymph node aspirates is useful for evaluating lymphadenopathy in HIV positive patients.     

B-chronic lymphocytic leukemia showed triple transformation,to diffuse large B cell,CD20-negative,and T-cell neoplasm during ofatumumab treatment: a case report

Background

Chronic lymphocytic leukemia (CLL) is a mature lymphoid neoplasm currently categorized as an indolent type of malignant lymphoma. CLL progresses slowly over years, but it eventually transforms to a more aggressive lymphoma such as the diffuse large B-cell (DLBCL) type, also known as Richter’s syndrome.

Case presentation

We treated a 69-year-old Japanese male who was histologically diagnosed with Richter’s syndrome after 6 years of CLL. His lymphadenopathy had systemically progressed for years, with lymphocyte counts of less than 10,000 cells/μL and a disease status of Rai classification stage I and Binet classification B. He had high fever and hepatosplenomegaly upon Richter’s transformation. The patient was treated with ofatumumab for refractory CLL, which relieved his febrile lymphadenopathy. He received a total of 11 ofatumumab courses and achieved partial remission. On the day of the 12th course of ofatumumab, his disease relapsed with febrile lymphadenopathy. Computed tomography revealed multiple liver masses and systemic lymphadenopathy, while a liver biopsy confirmed T-cell lymphoma. Concomitantly, CD20-lacking CLL cells were detected in his peripheral blood and bone marrow, and pathological examination of his left cervical lymph node biopsy showed CD20-positive DLBCL. The final diagnosis was three different types of lymphoma pathologies: (1) CD20-positive DLBCL of the lymph nodes, (2) CD20-lacking CLL of the peripheral blood and bone marrow, and (3) peripheral T-cell lymphoma (PTCL) of the liver. He received intravenous and oral dexamethasone therapy as palliative care. He died because of the rapid progression of abdominal masses 2 months after the diagnosis of triple transformation CLL. An autopsy revealed aggressive PTCL with aggressive systemic involvement of the liver, spleen, gall bladder, pericardium, bone marrow, and mediastinal–paraaortic–intraceliac lymph nodes. T-cell receptor study of an autopsy specimen supported the diagnosis of PTCL that spread to the intraceliac organs and lymph nodes. We concluded that his pathogenicity progressed to a mixture of triple lymphoma as a result of double malignant transformations, which included PTCL from CLL, CD20-negative CLL, and CD20-positive DLBCL by Richter’s transformation.

Conclusions

Our case provides information on the biology of CLL, to transform from a low-grade chemosensitive status to a malignant chemoresistant status.

     

Non-Hodgkin's lymphomas of the sinonasal region: histologic subtypes and their clinicopathologic features

The authors describe 11 patients with non-Hodgkin's lymphoma arising in the nasal cavity or paranasal sinuses. Seven were men and four were women. The median age of the women was 76 years; the median age of the men was 45 years. The most common presenting symptoms were nasal obstruction and unilateral facial swelling. The most frequent sites of disease were maxillary antrum (ten cases), nasal cavity (eight cases), and ethmoid sinus (seven cases). Eight patients had involvement of multiple sinuses. Six patients were clinical stage I E, two were II E, one was stage III E, and two were stage IV. Histologic subtypes included diffuse small cleaved cell (1 case), diffuse large cell (4 cases), and diffuse large cell immunoblastic (6 cases). Three patients having immunoblastic lymphoma had longstanding sinusitis, rhinitis, and allergies. Overall, 55% of patients died of disease. Three of four patients with the diffuse large cell subtype were free of tumor (mean follow-up 50 months). Five of six patients having immunoblastic lymphoma died of disease from 1 to 13 months following diagnosis (mean 6.4 months).     

Comparative study of marginal zone lymphoma involving bone marrow

Few studies have characterized or compared the pathologic features of bone marrow involvement by extranodal (EMZL), splenic (SMZL), and nodal marginal zone lymphoma (NMZL). We evaluated 45 bone marrow biopsy specimens from 39 patients with marginal zone lymphomas. As previously reported, bone marrow involvement was frequent (100%) in patients with SMZL. We also identified lymphoma involving bone marrow in 11 (44%) of 25 patients with EMZL and 1 of 2 patients with NMZL. The patterns of infiltration were mixed in all groups; however, the extent of involvement was greater in SMZL than in EMZL. In addition, germinal centers were present in bone marrow biopsy specimens involved by lymphoma in 4 patients with SMZL. Intrasinusoidal infiltration was common (10/12 [83%]) and prominent in patients with bone marrow involvement by SMZL, but was not invariably present. Intrasinusoidal infiltration of the bone marrow also was not specific for SMZL since similar infiltrates, although subtle, also were found in patients with other small B-cell lymphoproliferative disorders, including 6 (55%) of 11 patients whose bone marrow samples were infiltrated by EMZL.     

Polymerase chain reaction in the diagnosis of T-cell lymphoma in paraffin-embedded bone marrow biopsies: a comparative study

AIMS: In routine histological analysis of bone marrow biopsies, the distinction between reactive T-cell infiltrates and T-cell lymphoma can be difficult, even with the use of extensive immunohistochemistry. The aim of this study was to evaluate the diagnostic contribution of TCR-gamma gene rearrangement analysed by PCR. METHODS and RESULTS: The samples studied consisted of 46 paraffin-embedded bone marrow biopsies (diagnosis, staging and follow-up) from 26 patients with T-cell lymphoma. The bone marrow biopsies were categorized into three groups according to the morphological and immunohistochemical results. Group 1, positive for T-cell lymphoma (24 bone marrow biopsies), group 2, suspicion of T-cell lymphoma (15 bone marrow biopsies) and group 3, negative for T-cell lymphoma (seven bone marrow biopsies). DNA could be amplified in 45/46 bone marrow biopsies (98%). Clonal rearrangement was detected in 30/45 bone marrow biopsies tested (67%) including 15/24 bone marrow biopsies (62.5%) of group 1, 11/14 (78.5%) of group 2 and 4/7 (57%) of group 3. In total, PCR analysis supported a diagnosis of T-cell lymphoma in 15/45 bone marrow biopsies (33%), in which histological and/or immunohistochemical examination provided inconclusive evidence of malignancy. CONCLUSIONS: TCR-gamma PCR is a complementary tool for the assessment of T-cell lymphoma in bone marrow biopsies. Optimal evaluation of bone marrow biopsies requires an integrative approach of all available results from morphology, immunohistochemistry, molecular biology and clinical data.