Early lymph node involvement by mantle cell lymphoma limited to the germinal center: report of a case with a novel "follicular in situ" growth pattern

Recently, several reports have described cases of "in situ" mantle cell lymphoma (MCL) in which scattered cyclin D1+ cells were present within the mantle zones of reactive-appearing lymphoid follicles. In this report, we describe an unusual histologic pattern of in situ MCL that was identified in a staging lymph node for colonic adenocarcinoma resected 4 years before a diagnosis of symptomatic MCL. Retrospective immunohistochemical studies showed scattered cyclin D1-expressing cells within otherwise reactive germinal centers but not in the surrounding mantle zones. The presence of early MCL cells limited to reactive germinal centers represents a novel "follicular in situ" growth pattern for MCL, which overlaps morphologically with reactive follicular hyperplasia and follicular lymphoma and which could have implications for MCL pathogenesis.     

Lymphoid variant of hyaline vascular Castleman's disease containing numerous mantle zone lymphocytes with clear cytoplasm

We report two unusual cases of hyaline vascular type Castleman's disease showing a pale clear cuff of mantle zone lymphocytes presenting a marginal zone distribution pattern. These cells had medium-sized round or slightly indented nuclei and a moderate amount of clear cytoplasm. The histopathologic findings in our cases were similar to those of nodal marginal zone B-cell lymphoma. However, immunohistochemistry demonstrated that both the mantle zone lymphocytes and the pale cuff of the lymphoid cells were CD20+, CD79a+, sIgM+, sIgD+, CD5-, CD10-, CD43-, CD45RO-, Bcl-2+, Bcl-6- and cyclin D1-. The polytypic nature of these cells was demonstrated by immunohistochemistry and polymerase chain reaction. Reactive lymph node lesions only rarely show mantle cell hyperplasia with clear cytoplasm. This unusual mantle cell hyperplasia with clear cytoplasm associated with a hyaline vascular type of Castleman's disease should be differentiated from nodal marginal zone B-cell lymphoma, mantle cell lymphoma and follicular lymphoma. To avoid overdiagnosis and overtreatment, it is suggested that immunophenotypic and genotypic studies might be required, and furthermore careful attention should be paid to the morphologic examination.     

套细胞淋巴瘤的临床病理特征和细胞周期蛋白D1在诊断中的意义

目的 观察套细胞淋巴瘤的临床病理学特征及细胞周期蛋白D1染色在诊断中的意义。方法 对8例淋巴结套细胞淋巴瘤作临床病理观察及随访,LSAB法做免疫表型分析（CD45RO、CD5、CD20、细胞周期蛋白D1、Ki-67、bcl-2）。结果 患者年龄43-78岁（平均年龄57岁）,男女3：1。组织学特点为：（1）淋巴结结构破坏并被单一的淋巴样细胞所取代,淋巴细胞以套区增生性、结节性、弥漫性三种模式增生。（2）淋巴样细胞核有一定的不规则性,染色质中等致密,核分裂象少见,类似中心细胞。其中有3例转变为高度侵袭性的母细胞样变型。所有的病例都呈cyclinD1与bcl-2阳性、CD20阳性、CD45RO阴性、CD5阳性。结论 套细胞淋巴瘤有其特征的形态改变及免疫表型。根据组织病理学特征及cyclin D1阳性,可与其它类型的小B细胞淋巴瘤相鉴别。套细胞淋巴瘤的母细胞样变型也应当与其它变型区别。     

CD5-positive mucosa-associated lymphoid tissue (MALT) lymphoma of ocular adnexal origin: usefulness of fluorescence in situ hybridization for distinction between mantle cell lymphoma and MALT lymphoma

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) usually lacks CD5 expression. Herein is described two cases of CD5-positive MALT lymphoma of ocular adnexal origin. The differential diagnosis between CD5-positive MALT lymphoma and mantle cell lymphoma (MCL), notably cyclin D1-negative MCL, was difficult because both cases consisted histologically of small to medium-sized cells with diffuse or vaguely nodular growth pattern, and the neoplastic cells were positive for CD5 and negative for cyclin D1. Somatic mutation analysis of the immunoglobulin heavy chain variable region (VH) gene in case 1 found a relatively higher mutation frequency (5.0%), which was not definitive to rule out MCL. Interphase fluorescence in situ hybridization (FISH) on paraffin-embedded section using IgH/cyclin D1 (CCND1) probe showed that in both cases there was no molecular evidence of t(11;14), finally leading to the diagnosis of CD5-positive MALT lymphoma. Although the present two patients had no recurrence over 34 months after initial diagnosis, careful observation is needed because the clinicopathological significance of MALT lymphoma with this rare phenotype remains obscure.     

Marginalzonenlymphome: extranodale vom MALT-Typ, nodale und splenische

Marginal zone B-cell lymphomas (MCL) of extranodal, nodal and splenic origin appear to be different lymphoma entities with a similar growth pattern in the marginal zone of the B-follicles. Decisive for the detection of MCL as a distinct lymphoma entity was the "MALT concept" for lymphoid infiltrates in the gastric and intestinal mucosa as described by Isaacson et al. in the 1980's. Immunohistological stainings for the immunoglobulin light and heavy chains and molecular pathological studies of the immunoglobulin heavy chain gene configuration have subsequently confirmed the neoplastic nature of the extranodal infiltrates and differentiated marginal zone cells from mantle zone cells. In 1994, the MCL of MALT type as well as of nodal and splenic origin were included in the REAL classification and in 1998 in the new WHO classification for lymphomas. Meanwhile extranodal MCL of MALT-type have been observed in almost every organ and site of the body, by far most frequently in the gastric mucosa. Beside the typical growth pattern, lymphoepithelial lesions are a distinct diagnostic feature of extranodal MCL. Clinically, the small cell extranodal MCL show a very good prognosis with regression after treatment. As for nodal and splenic MCL, we need further studies to evaluate the prognostic aspects and to compare them with other B-cell lymphomas. The same is true for primary extranodal large B-cell lymphomas or blastic transformation to a large cell lymphoma; in these tumors the diagnosis of a MALT type lymphoma should only be made if a small cell component with MALT-specific criteria can be proved.     

Mantle cell lymphoma with partial involvement of the mantle zone: an early infiltration pattern of mantle cell lymphoma?

Most patients with mantle cell lymphoma present with a diffuse or nodular infiltration of the involved organs at diagnosis. We present two patients with a rare morphological variant, displaying a partial involvement of the mantle zone. Patient 1 presented with an enlarged inguinal lymph node, which showed marked follicular hyperplasia with singly spread Cyclin D1+ small lymphoid cells in the mantle zones. An additional lymph node biopsy taken 3 months later showed the same pattern. Patient 2 presented with a classical mantle cell lymphoma with lymph node, bone marrow and gastro-intestinal involvement. However, revision of an appendectomy specimen taken 4 years earlier showed pronounced follicular hyperplasia with singly spread Cyclin D1+ small lymphoid cells in the mantle zones. Mantle cell lymphoma with partial involvement of the mantle zone has rarely been reported and many represent an early manifestation of mantle cell lymphoma. Our cases also illustrate that the inclusion of an anti-cyclin D1 antibody in the diagnostic panel of antibodies to study unexplained follicular hyperplasia, might be advised.     

原发淋巴结套细胞淋巴瘤临床病理分析

目的：探讨原发淋巴结套细胞淋巴瘤（MCL）的临床病理与免疫组化特点。方法：收集6例淋巴结MCL,免疫组化ABC法确定肿瘤细胞特征,使用的抗体有CD45、CD20、CD79、CD45RO、CD30、CD68、TdT、CD43、CD5、cyclinD1、c-myc,IgD,IgM等。结果：光镜可将MCL分为4种亚型：套区型1例,结节型1例,弥漫型2例,母细胞化型2例。肿瘤细胞表达全B细胞标记,IgD CD43 ,cyclinD1(5/6),CD5(4/6) 。结论：MCL是一种具有特殊免疫表型的B细胞淋巴瘤,不同的组织学构型其预后可能不同,临床应与其它类型B细胞淋巴瘤鉴别,如淋巴结边缘区B细胞淋巴瘤（MZL）,滤泡性淋巴瘤（FL）及CLL／SLL等鉴别。     

Large cell variants of CD5+, CD23- B-cell lymphoma/leukemia

CONTEXT: Mantle cell lymphoma (MCL), and its leukemic phase, constitute a well-studied hematologic malignancy with known overall survival, prognostic indicators, morphologic findings at diagnosis and in bone marrow, and known incidence of the bcl-1 immunoglobulin gene rearrangement. Large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype (CD5+, CD23-), including but not limited to blastic MCL, prolymphocytoid MCL, blastic mantle cell leukemia, and prolymphocytic mantle cell leukemia, are not as well characterized. Although blastic MCL is known to be associated with a shorter overall survival than conventional MCL, the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype have not been described as fully as conventional MCL. OBJECTIVE: The purpose of the present study was to describe the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype. DESIGN: Nineteen cases of large cell variants of CD5+, CD23- B-cell lymphoma/leukemia are reviewed and described in regard to morphology, bone marrow morphological findings, Cyclin D1 immunostaining, and bcl-1 analysis. Clinical data were not available owing to the varied clinical sources of the specimens. SETTING: Tertiary-care academic institution. RESULTS: Lymph node involvement in blastic CD5+, CD23- B-cell lymphoma was diffuse (100%) with a nodular component (33%) or focal mantle zone pattern (10%). Bone marrow involvement in blastic CD5+, CD23- B-cell lymphoma was seen in only 27% of cases and was composed predominantly of small, slightly irregular lymphocytes. Cyclin D1 was demonstrated in 60% of the 15 cases analyzed and more sensitive in B5-fixed tissue. Bcl-1 (performed in 5 cases) was not detected in the 4 cases of blastic CD5+, CD23- B-cell lymphoma analyzed and was detected in the case of the prolymphocytoid MCL. Cyclin D1 was demonstrated in all 4 bcl-1 negative cases and was negative in the bcl-1 positive prolymphocytoid MCL. CONCLUSION: Careful analysis of clinical data, morphology, immunophenotype, Cyclin D1 expression, and molecular analysis are required to differentiate the unusual large cell variants of MCL from other processes.     

Variability in morphology and cell proliferation in sequential biopsies of mantle cell lymphoma at diagnosis and relapse: clinical correlation and insights into disease progression

Aims: The variable morphology of mantle cell lymphoma (MCL) is assumed to reflect progression from an early form with classical cytology and mantle zone or nodular growth to a later, more aggressive variant of the disease with blastoid cytology and a diffuse growth pattern. However, studies of sequential biopsies of MCL are very limited, and we therefore undertook to carry out such a study. Methods and results: We analysed a cohort of 47 MCLs at primary diagnosis and relapse for cytology, growth pattern, and Ki67 index, and correlated the findings with outcome. In the majority of cases, the mantle zone growth pattern was lost, but it had been reacquired in a small subset of MCLs at relapse. Twenty‐two per cent of MCLs with classical/small cell cytology acquired blastoid features during the course of the disease. However, 50% of MCLs with blastoid cytology at primary diagnosis recurred as a classical variant. The Ki67 index increased over time, and was associated with prognosis in the primary and the relapse biopsy specimens. Conclusions: This is the first study to show, in a large cohort of MCLs, that the Ki67 index increases over time in MCL. Assessment of the Ki67 index remains a useful prognostic tool if assessment is performed in the relapse situation.     

逆转录聚合酶链反应检测石蜡包埋组织中细胞周期蛋白D1 mRNA对套细胞淋巴瘤的诊断价值

目的 探讨用逆转录聚合酶链反应（RT-PCR）法和竞争性RT-PCR法检测套细胞淋巴瘤（MCL）石蜡包埋组织中细胞周期蛋白D1（cyclin D1）蛋白和mRNA在常规病理工作中的可行性及其诊断和鉴别诊断价值。方法 收集淋巴结内MCL38例、对照组包括结内小B细胞淋巴瘤58例（B小淋巴细胞性淋巴瘤14例,淋巴浆细胞性淋巴瘤3例,滤泡性淋巴34例,淋巴结边缘区B细胞淋巴瘤7例）和淋巴结反应性增生病例20例,用免疫组织化学EnVision法和RT-PCR法、竞争性RT-PCR法检测cyclin D1蛋白及其mRNA的表达,以看家基因PGK作为内对照检测RNA。结果 （1）38例结内MCL中,cyclin D1蛋白阳性率为71．1％（27／38）,对照组均为阴性。（2）116例标本中,可检出内对照PGK基因mRNA表达103例（88．8％）。38例MCL中PGK阳性36例（94．7％）。（3）38例结内MCL中,34例可检出cyclin D1 mRNA表达,去除PGK和cyclin D1 mRNA均阴性的2例,MCL中cyclin D1 mRNA表达的阳性率为94．4％（34／36）。对照组中B小淋巴细胞性淋巴瘤1例检出cyclin D1 mRNA表达,其余病例均未检出cyclin D1 mRNA表达。PCR结果全部经测序证实。（4）用竞争性RT-PCR,38例结内MCL中27例可检出cyclin D1 mRNA高表达,去除2例PGK也为阴性的病例,MCL中cyclin D1 mRNA高表达率为75．0％（27／36）。对照组小B细胞恶性淋巴瘤及淋巴结反应性增生无1例有cyclin D1 mRNA高表达。结论 RT-PCR方法和竞争性RT-PCR方法可在石蜡包埋组织中检测cyclin D1 mRNA的表达,均可用于MCL的诊断。     

Immunoreactivity of neoplastic and non-neoplastic monocytoid B lymphocytes for DBA.44 and other antibodies.

AIMS--To evaluate the immunoreactivities of neoplastic and non-neoplastic monocytoid B cells (MBC) and compare them with hairy cell leukemia (HCL) and mantle cell lymphoma (MCL). METHODS--An immunohistochemical study of paraffin wax embedded sections was done on surgically resected specimens of spleens with MBC clusters from patients with gastric cancer (14 cases), tonsils (five cases), and lymph node (two cases) showing lymphoid follicular hyperplasia (LFH), submandibular lymph nodes containing MBC in Sjögren's syndrome (one case). Extranodal organs affected by MCL (three cases) and monocytoid B cell lymphoma (MBCL) (seven cases), and spleens from HCL (four cases) were also studied. These specimens were fixed in 10% formalin and routinely processed for paraffin wax embedding. Fresh spleen specimens from patients with liver cirrhosis (one case) and gastric cancer (seven cases) were snap frozen. RESULTS--Mantle zone lymphocytes were DBA.44, CD74 positive and showed a weaker reaction for CDw75 than marginal zone lymphocytes and MBC, which were almost DBA negative. In neoplastic diseases tumour cells in MCL were DBA.44, CD74, and CDw75 positive. MBCL showed a positive reaction for CD74 and CDw75, but positivity for DBA.44 was observed in only one of seven cases. The HCL specimens, all positive for DBA.44, showed a weaker reaction for CD74 and a stronger reaction for CDw75 than either MCL and MBCL specimens. CONCLUSION--These results show that mantle zone lymphocytes and MCL more closely matched HCL for reactivity to DBA.44 than MBC and MBCL. Reactivities for DBA.44 and CDw75 were greater in MBCL compared with its non-neoplastic counterpart, MBC.     

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.     

B-cell lymphoma with hyaline vascular Castleman disease-like features: a clinicopathologic study

Hyaline vascular Castleman disease (HV-CD) is a localized benign mass characterized by follicular hyperplasia with atrophic germinal centers, mantle zone hyperplasia, hyaline deposits, and vascular proliferation. Before establishing a diagnosis of CD, several B-cell lymphomas (BCLs) must be considered, including follicular lymphoma (FL), mantle cell lymphoma (MCL), and nodal marginal zone lymphoma (NMZL). Conversely, BCLs with prominent atrophic germinal centers and hyaline vascular penetration may closely resemble HV-CD, leading to misdiagnosis. We report 6 cases of BCL with prominent HV-CD-like features, including FL (2 cases), MCL, NMZL (2 cases), and interfollicular large B-cell lymphoma. Histologically, all were initially considered to be HV-CD before additional tests revealed a neoplastic B-cell proliferation. We highlight the clinicopathologic features of these cases in comparison with cases diagnostic of HV-CD. In contrast with HV-CD, BCLs with HV-CD-like features are more likely to manifest clinically with systemic symptoms or generalized lymphadenopathy. Careful histopathologic examination, supported with immunohistochemical studies, flow cytometric immunophenotyping, and judicious use of cytogenetic and molecular analyses, allows identification of the masked neoplastic process. A multifaceted approach, integrating clinical, histologic, and ancillary tests, can help avoid this diagnostic pitfall.     

Follicular hyperplasia presenting with a marginal zone pattern in a reactive lymph node lesion

Histologically, the marginal zone pattern of the lymph node is characterized by lymphoid follicles with three distinct layers. The inner layer is composed of follicular center zones, the middle layer of darkly stained mantle zones, and the outer layer of marginal zones. However, the marginal zone pattern is rarely seen in reactive lymph nodes except for mesenteric lymph nodes. We describe the clinicopathologic, immunohistochemical and genotypic findings of six cases of reactive follicular hyperplasia exhibiting the marginal zone pattern. The patients comprised three males and three females (age range 24 to 63 years; medium 56 years). Follow-up data were obtained from five patients. None of them developed malignant lymphomas during the follow-up period of from 5 to 204 months (median 68 months). Histologically, the lesion was characterized by numerous lymphoid follicles and partial distortion of lymph node structure. Varying degrees of progressive transformation of the germinal center (PTGC) were noted in the four cases. The marginal zone pattern was observed in some or most of the lymphoid follicles including PTGC. The marginal zone B cells were small to medium-sized lymphocytes with round or slightly indented nuclei and a broad rim of pale cytoplasm. Some of them had a monocytoid appearance. They were CD20+, CD79a+, sIgM+/-, sIgD-, CD5-, CD10-, CD21-, CD23-, CD43-, CD45RO-, Bcl-6-, cyclin D1-, EMA- and p53-. A portion of them were Bcl-2 positive. Occasional large lymphoid cells with round or indented nuclei and moderate amounts of cytoplasm were observed in the marginal zone in four cases. These large lymphoid cells were usually CD20 positive, but Bcl-6 negative. A small number of them contained polytypic intracytoplasmic immunoglobulins. The polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. Recognition of unusual marginal zone hyperplasia in reactive lymph node lesions is important to avoid confusion with nodal involvement in various low-grade B cell lymphomas presenting a marginal zone distribution pattern.     

Mantle cell lymphoma: recent insights into pathogenesis, clinical variability, and new diagnostic markers

Mantle cell lymphoma (MCL; previously called centrocytic lymphoma or lymphocytic lymphoma of intermediate differentiation) is a distinct subtype of B-cell lymphoma, accounting for approximately 3%-10% of all lymphoma diagnoses. The name refers to the growth pattern in early disease presentation resembling the normal mantle zone that surrounds the germinal center of the B-cell follicle. The hallmark of MCL is the t(11;14)(q13;q32), resulting in aberrant expression of the CCND1 gene and expression of cyclin D1 in the tumor cells. Expression and genomic profiling of MCL have provided new insight into the pathogenesis and will be summarized in this review. Pitfalls in the differential diagnosis versus B-cell chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, cyclin D1-positive diffuse large B-cell lymphoma, hairy cell leukemia, and plasma cell tumors will be discussed, including the usefulness new diagnostic markers SOX11 and CD200. In situ MCL, MCL with an indolent clinical course, and cyclin D1-negative MCL are other topics of this review.     

Classical type and blastoid variant mantle cell lymphoma in the same lymph node: Histology and cytological findings from a touch imprint specimen

Blastoid variant (BV) is one of the aggressive variants of mantle cell lymphoma (MCL). BV‐MCL is defined by its blastic cytomorphology. Previous studies using sequential biopsies in cases with MCL have demonstrated that classical type MCL (C‐MCL) often transforms or relapses as an aggressive variant, but a histopathological transition from C‐MCL to an aggressive MCL variant in the same pathological specimen has been shown in only a limited number of the cases. We present a case of MCL in which a histological transition between C‐MCL and BV‐MCL was observed in the same lymph node. A 53‐year‐old man presented with a submandibular tumor. Touch imprint cytology revealed a monotonous proliferation of large blastic lymphoid cells. Histology revealed a transition between a large lymphoid cell component and small foci of small‐ to medium‐sized cell component within the tumor. Both components were CD5(+), CD10(−), CD20(+), cyclin D1(+), and SOX11(+) on immunohistochemistry. Fluorescent in situ hybridization revealed the translocation of IgH/BCL1 locus. These findings led to a final diagnosis of BV‐MCL with coexistent C‐MCL. The present case suggests the existence of a pathogenetic pathway of MCL from C‐MCL to BV‐MCL. Because it is important to accurately identify BV‐MCL for prognostication, appropriate ancillary diagnostic tools should be used in suspected cases. Diagn. Cytopathol. 2017;45:364–370. © 2016 Wiley Periodicals, Inc.     

Localized lymphoid hyperplasia of the rectum resembling polypoid mucosa-associated lymphoid tissue lymphoma: a report of three cases

Histologically, benign lymphoid hyperplasia of the rectum is usually characterized by large lymphoid follicles with active germinal centers and by a narrow surrounding mantle zone and marginal zone (MZ). We report here three cases of benign lymphoid hyperplasia of the rectum associated with prominent marginal zone hyperplasia, which caused serious difficulty in the differential diagnosis from the polypoid type of mucosa-associated lymphoid tissue (MALT) lymphoma. Colonoscopy demonstrated small sessile polyps in all three cases. Histologically, the lesions were characterized by a hyperplastic germinal center and expanded MZs. The expanded MZs contained numerous monocytoid B-cells (MBC) and scattered large transformed B-cells. Initially, combined colonoscopic and histological findings strongly supported a diagnosis of polypoid MALT-type lymphoma of the rectum. However, there were neither colonized lymphoid follicles nor lymphoepithelial lesions in any of the three lesions. MBCs and large transformed B-lymphocytes were CD43- and bcl-2-. Moreover, immunohistochemical and genotypic studies proved the polytypic nature of the B-lymphocytes in all three lesions. The present cases indicated that benign lymphoid hyperplasia of the rectum should be included in the differential diagnosis for polypoid MALT-type lymphoma of the rectum.     

Sensitivity and specificity of immunostaining in the diagnosis of mantle zone lymphoma

The diagnosis of mantle zone lymphoma is sometimes difficult to make solely on the basis of morphology because the mantle zone pattern may be present in other disorders such as benign mantle zone hyperplasia, follicular center cell (FCC) lymphomas, and Castleman disease. To distinguish mantle zone lymphoma from the other disorders mentioned previously, the authors performed immunoperoxidase studies on B-5-fixed, paraffin-embedded sections or cryostat sections of lymph nodes from nine patients with a diagnosis of mantle zone lymphoma. The results then were compared with the immunostaining pattern seen in FCC lymphomas and various benign lymphoid hyperplasias. A monoclonal proliferation of mantle zone cells, as shown by staining for immunoglobulin light chains, was noted in the mantle zones and interfollicular areas in all six cases from which cryostat sections were available. The cells in the residual follicular centers uniformly had a polyclonal light chain marking pattern. Two novel monoclonal antibodies (LN-1 and LN-2) that identify FCCs and B-cells in B-5-fixed, paraffin-embedded tissues also were used in this study. Of the six cases in which the monoclonal antibodies could be used, the cells in the residual follicles were uniformly LN-1 positive, LN-2 positive, while the mantle zone and interfollicular cells were almost completely LN-1 negative, LN-2 positive. The data suggest that mantle zone lymphomas are a distinctive neoplasm of monoclonal B-cells of non-FCC origin. The authors conclude that immunostaining is a sensitive technic for identifying a malignant neoplasm of B-cells in the mantle zone and interfollicular areas. In addition, the method is relatively specific and useful for distinguishing mantle zone lymphoma from similar-appearing disorders such as benign mantle zone hyperplasias and certain FCC lymphomas.     

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.     

Lymphoproliferative diseases of the orbit and appendages of the eye

The results are available of clinical, morphological, cytological and immunological investigations of orbital lymphomas and lymphomas of appendages of the eye. Malignant lymphoma was detected in 17 patients and reactive lymphoid hyperplasia in 3 patients. All the malignant lymphomas had B-cell phenotype. By cell composition, MALT-lymphoma is more polymorphic than lymphoma from mantle zone cells and lymphoma from small lymphocytes and centro follicular lymphoma. The conjunctive is affected primarily with lymphoma from marginal zone cells or mantle zone cells. As a rule, this is a primary local lesion. Other variants of orbital lymphoma and lymphoma of the eye appendages develop more often as secondary lesions in systemic disease and are characterized by more aggressive course. The key in differential diagnosis of reactive lymphoid hyperplasia and small cells lymphomas is immunophenotyping, especially at initial stages of the tumor process.