Clusterin expression in malignant lymphomas: a survey of 266 cases.

Clusterin expression has been reported to be characteristic of systemic anaplastic large cell lymphoma and usually negative in cutaneous anaplastic large cell lymphoma as well as other lymphoma types. We surveyed clusterin expression using immunohistochemical methods in 266 cases of non-Hodgkin's lymphoma and Hodgkin's disease to further assess the diagnostic utility of this marker. Clusterin immunostaining was observed in 40 of 49 (82%) systemic anaplastic large cell lymphomas and 12 of 29 (41%) cutaneous anaplastic large cell lymphomas. Clusterin also was expressed in 5 of 43 (12%) diffuse large B-cell lymphomas (4 of 5 CD30+), 1 of 14 (7%) peripheral T-cell lymphomas, 1 of 32 (3%) cases of nodular sclerosis Hodgkin's disease, and 1 case of mycosis fungoides in large cell transformation. Clusterin was negative in all other neoplasms assessed including follicular lymphoma of all grades (n = 24), mantle cell lymphoma (n = 13), marginal zone B-cell lymphoma (n = 12), precursor T-cell or B-cell lymphoblastic leukemia/lymphoma (n = 10), mixed cellularity Hodgkin's disease (n = 8), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 7), Burkitt lymphoma (n = 7), mycosis fungoides (n = 4), nodular lymphocyte predominant Hodgkin's disease (n = 3), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (n = 2), and plasmacytoma (n = 2). We conclude that clusterin is a marker of anaplastic large cell lymphoma and that addition of clusterin to antibody panels designed to distinguish systemic anaplastic large cell lymphoma from classical Hodgkin's disease is useful. However, clusterin is also positive in a substantial subset of cutaneous anaplastic large cell lymphomas, a smaller subset of diffuse large B-cell lymphomas, and rarely in cases of peripheral T-cell lymphoma and nodular sclerosis Hodgkin's disease.     

T-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive neoplasm: differential diagnosis from Hodgkin's lymphoma

AIMS: An accurate diagnosis of T-cell/histiocyte-rich large B-cell lymphoma needs to take into consideration those forms of Hodgkin's lymphoma also characterized by a predominance of small lymphocytes and histiocytes, i.e. nodular lymphocyte predominance Hodgkin's lymphoma and lymphocyte-rich classical Hodgkin's lymphoma. We have studied the clinical, phenotypic and genetic features of a series of 12 cases of T-cell/histiocyte-rich large B-cell lymphoma along with 18 cases of Hodgkin's lymphoma for comparative purposes. METHODS AND RESULTS: Of the Hodgkin's lymphoma cases, there were 11 lymphocyte predominance type and seven classic type. T-cell/histiocyte-rich large B-cell lymphomas presented usually in advanced stages (III or IV in 11/12 cases), frequently with 'B' symptoms (6/9 cases), and followed a more aggressive course than Hodgkin's lymphoma (4/8 patients died due to the tumour in T-cell/histiocyte-rich large B-cell lymphoma versus 0/15 in Hodgkin's lymphoma). T-cell/histiocyte-rich large B-cell lymphoma cases showed diffuse effacement of the nodal architecture by a proliferation of scattered large atypical B-cells obscured by a background of small T-lymphocytes (more CD8+, TIA1+ than CD57+). Five cases showed also a prominent histiocytic component. The large B-cells expressed CD45 and often EMA (6/10 cases). On the other hand, CD 30, CD15 and latent infection by Epstein-Barr virus (EBV) were generally lacking. bc l6 and CD10 were, respectively, detected in 6/6 and 1/5 cases. Conventional polymerase chain reaction (PCR) showed monoclonal immunoglobulin heavy chain (IgH) gene rearrangements in all T-cell/histiocyte-rich large B-cell lymphomas studied (5/5), but did not detect any case with t(14;18) involving the major breakpoint region (0/4). CONCLUSIONS: The differential diagnosis of T-cell/histiocyte-rich large B-cell lymphoma from Hodgkin's lymphoma is facilitated by the integration of different immunophenotypic, molecular and clinical findings. T-cell/histiocyte-rich large B-cell lymphoma is a monoclonal neoplasm of bc l6+ B-cells with a phenotypic profile similar to lymphocyte predominance Hodgkin's lymphoma, suggesting a germinal centre origin and a possible relation to this disease. Therefore, in order to distinguish it from lymphocyte predominance Hodgkin's lymphoma, characterization of the reactive background, IgH gene rearrangement studies by conventional PCR and clinical features are more useful. In contrast, T-cell/histiocyte-rich large B-cell lymphoma can be distinguished from classical Hodgkin's lymphoma thanks to the presence of monoclonal IgH rearrangement and the CD 30-CD15-CD45+EMA+ immunophenotypic profile of the neoplastic cells in T-cell/histiocyte-rich large B-cell lymphoma.     

Hodgkin's disease: classification and differential diagnosis.

During the past decade, there have been many advances in our understanding of Hodgkin's disease. Among the most important is the discovery that the Reed-Sternberg cell is a lymphoid cell, in most cases a B cell, and that it is clonal. Hodgkin's disease is thus a true lymphoma, deserving of a name change to Hodgkin's lymphoma (HL). On the basis of a combination of immunophenotype and morphologic features, the Revised European-American classification system recognizes two main types of HL: classical types (nodular sclerosis, mixed cellularity, lymphocyte-rich classical HL, and lymphocyte depletion) and nodular lymphocyte-predominant type. These two types probably are distinct biologic entities. The immunophenotype and genetic features of the classical HL and the nodular lymphocyte-predominant type have been defined. These are useful in the subclassification of HL and in distinguishing HL from two recently described, aggressive lymphomas that were in the past often diagnosed as HL, i.e., anaplastic large-cell lymphoma, T-cell type, and T-cell/histiocyte-rich large B-cell lymphoma. Epstein-Barr virus has been detected in approximately 40% of the cases of classical HL, and it is clonal; this suggests that this virus might play a role in the pathogenesis of at least some types of HL. Alternatively, its presence might simply reflect the prevalence of Epstein-Barr virus-infected B cells in the individual. Despite the advances of the past 10 years, many questions remain to be answered; these will provide the challenges of the next decade.     

Composite lymphoma: the interface between Hodgkin's and non-Hodgkin's lymphoma

Hodgkin's lymphoma is a rare neoplasm mainly affecting young people. Within the last decade, nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) has been separated from all other cases of the so-called classical type. Moreover, the derivation of Hodgkin's lymphoma from germinal centre B-cells has been established, giving rise to a possible clonal relationship between Hodgkin's lymphoma and the non-Hodgkin's lymphomas (NHLs). The interface between them therefore has both diagnostic and biological aspects. Diagnostic difficulties arise, due to overlapping definitions, between biologically unrelated entities, e.g. classical Hodgkin's lymphoma and NLPHL or anaplastic large cell lymphoma, respectively. On the other hand, there is a biological grey zone regarding composite lymphomas consisting of Hodgkin's lymphoma and any NHL. This simultaneous or subsequent occurrence of Hodgkin's lymphoma and non-Hodgkin's lymphomas may, or may not, be clonally related. For management purposes lymphomas, e.g. NLPHL and T cell-rich B-cell lymphoma, must be distinguished along a continuous spectrum of progression.     

CD20-Positive peripheral T-cell lymphoma: report of a case after nodular sclerosis Hodgkin's disease and review of the literature.

We present a case of peripheral T-cell lymphoma co-expressing CD3 and CD20, as well as demonstrating T-cell receptor gene rearrangement, in a patient who had been diagnosed with nodular sclerosis Hodgkin's disease 5 years previously. Although 15 cases of CD20-positive T-cell neoplasms have been previously reported in the literature, this is the first report of CD20-positive T-cell lymphoma occurring subsequent to treatment of Hodgkin's disease. The current case affords an opportunity to review the rarely reported expression of CD20 in T-cell neoplasms as well as the relationship between Hodgkin's disease and subsequently occurring non-Hodgkin's lymphomas. In addition, the identification of this case supports the suggestion that the use of CD20 antibodies alone in paraffin sections may lead to an incorrect determination of cell lineage in some cases.     

Specific phenotyping of T-cell proliferations in formalin-fixed paraffin-embedded tissues. Use of antibodies to the T-cell receptor beta F1.

Antibody beta F1 to a common framework determinant of the beta subunit of the T-cell receptor (TCR) was used as a specific phenotypic marker for T-cell differentiation in malignant lymphomas. Sensitivity of immunoperoxidase staining in paraffin sections was enhanced by pronase pretreatment, overnight incubation of primary antibody in Tween 20, and use of streptavidin horseradish peroxidase complexes to amplify the reaction. All 43 cases of B-cell lymphoma were negative for TCR. Reed Sternberg (RS) cells in 3 of 20 cases of Hodgkin's disease exhibited cell membrane staining for TCR (all nodular sclerosis type), further evidence that some RS cells may be T-cell derived. Twenty-nine of 44 cases of T-cell lymphoma expressed TCR (66%). These included 11 of 12 cases of peripheral T-cell lymphoma (PTCL) of small and mixed cell type, 8 of 9 cases of lymphoepithelioid cell (Lennert's) lymphoma, and 2 of 4 cases of T-cell lymphoblastic lymphoma. Loss of immunoreactivity for TCR occurred in lymphomas of large or activated T-cell type, including 7 of 9 cases of T-cell immunoblastic lymphoma and 3 of 4 cases of large cell PTCL. Antibody beta F1 is a specific and relatively sensitive marker of T-cell phenotype in formalin-fixed paraffin sections of malignant lymphomas.     

T-cell rich B-cell non-Hodgkin's lymphoma: a progressed form of follicle centre cell lymphoma and lymphocyte predominance Hodgkin's disease

T-cell rich B-cell non-Hodgkin's lymphoma (T-cell rich B-cell lymphoma) is a morphological variant of diffuse large B-cell lymphoma. It is important to recognize this variant in the differential diagnosis of T-cell non-Hodgkin's lymphoma. The main differential diagnosis of T-cell rich B-cell lymphoma, nodular and diffuse lymphocyte predominance Hodgkin's disease (lymphocyte predominance Hodgkin's disease), is, however, even more difficult and differentiating criteria are still not satisfactorily defined. Moreover, T-cell rich B-cell lymphoma may not represent a clinicopathological entity. Twelve cases of T-cell rich B-cell lymphoma, selected on the basis of morphology and limited immunohistochemistry without previous knowledge of clinical data, were studied by immunohistochemistry and polymerase chain reaction for bcl-2 rearrangements to investigate the histogenetic background. In three of 12 cases, bcl-2 rearrangements were found, strongly suggesting a follicle centre cell origin. In three other cases, a documented history of definite nodular lymphocyte predominance Hodgkin's disease 29 months to 20 years prior to the diagnosis of the lymphoma was present. No differences in growth pattern, residual nodularity, tumour cell distribution, cellular morphology and composition, or immunophenotypical differences were noted in these six cases as compared to the remaining cases. These data underscore the histogenetic diversity in T-cell rich B-cell lymphoma and identify it as a progressed form of lymphoma derived from entities as diverse as follicle centre cell lymphoma and nodular lymphocyte predominance Hodgkin's disease. Moreover, it shows a complete morphological overlap with the diffuse form of lymphocyte predominance Hodgkin's disease and may actually encompass this disease entity.     

The interrelationship of Hodgkin's disease and non-Hodgkin's lymphomas--lessons learned from composite and sequential malignancies.

While Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) have long been regarded as distinct disease entities, recent observations suggest a closer association. The analysis of cases in which these diagnoses are made in the same anatomic site (composite lymphomas) or in separate sites (simultaneous or sequential HD and NHL) indicates that this phenomenon occurs more frequently than would be expected by chance alone. The most common form of composite lymphoma is coexistent nodular lymphocyte-predominant Hodgkin's disease (NLPHD) and large cell lymphoma (LCL) of B cell phenotype. This finding is consistent with a B cell origin for the abnormal cells in NLPHD, suggesting that LCL represents a form of histologic progression, with the existence of a clonal relationship between the two components. The association of other forms of HD (nodular sclerosis or mixed-cellularity) and NHL is less common, but still significant. As with NLPHD and LCL, one may observe composite lymphomas, or the diagnosis of HD may precede or follow the diagnosis of NHL. The vast majority of NHLs associated with HD are of B cell origin, most commonly follicular lymphomas. An association between HD and B cell chronic lymphocytic leukemia (CLL) is also observed. In selected cases, Reed-Sternberg (RS) cells are seen in a background of otherwise typical CLL, and some of these patients have progressed to disseminated HD. These findings suggest that, at least in some cases, HD may be clonally related to an underlying B cell malignancy, and that the RS cell may be an altered B lymphocyte.(ABSTRACT TRUNCATED AT 250 WORDS)     

The distinction of Hodgkin's disease from B cell lymphoma.

Workshop C included cases with a differential diagnosis of Hodgkin's disease and B cell lymphoma. In general, the cases could be placed into one of the following four major categories: (1) usual Hodgkin's disease versus T cell-rich B cell lymphoma; (2) syncytial Hodgkin's disease versus B large cell lymphoma; (3) nodular and/or diffuse lymphocyte-predominance Hodgkin's disease (LPHD) versus T cell-rich B cell lymphoma; and (4) LPHD with composite or discordant large cell lymphoma versus T cell-rich B cell lymphoma progressing to large cell lymphoma. A final case illustrated the differential diagnosis of B cell Hodgkin's disease, ie, nodular LPHD versus the cellular phase of nodular sclerosing Hodgkin's disease (NSHD). The cases from this session have been grouped into these five categories and tables have been constructed to highlight features favoring each of the diagnostic possibilities. A brief discussion is given after each case, and selected cases have been illustrated to demonstrate some of the unusual histologic features.     

CD30 distribution. Immunohistochemical study on formaldehyde-fixed, paraffin-embedded Hodgkin's and non-Hodgkin's lymphomas.

Two hundred Hodgkin's and non-Hodgkin's lymphomas were immunohistochemically studied for the presence of the CD30 (Ki-1) activation antigen using a monoclonal antibody BerH2 on paraffin-embedded, formaldehyde-fixed tissue. Immunohistochemistry was performed by using the avidin-biotin complex technique and was preceded by enzymatic digestion with pepsin (0.05% for 20 minutes). Ninety percent (56/64) of cases of Hodgkin's disease, other than lymphocyte predominance type, showed positive tumor cells, although the positivity was often focal. In contrast, lymphocyte predominance type showed CD30 in only two of nine cases. CD30 was commonly seen in non-Hodgkin's lymphomas. Five of 37 large-cell lymphomas showed extensive CD30 positivity and morphologically represented large-cell anaplastic lymphomas ("Ki-1 lymphomas"). Apart from this, occasional CD30-positive cells were seen in nine of 32 large-cell non-Hodgkin's lymphomas. About half of the nodular small cleaved-cell lymphomas contained CD30-positive cells, two of them showing large numbers of positive cells both within and outside the nodules. Lymphocytic lymphoma sometimes (6/17) showed a few CD30-positive cells. Peripheral T-cell lymphomas showed positive cells in three of eight cases. The positive cases were one lymphoma with small groups of epithelioid cells (Lennert's lymphoma) and two immunoblastic lymphadenopathylike peripheral T-cell lymphomas. The results show that CD30 is more widespread than originally thought in non-Hodgkin's lymphomas and that especially nodular small cleaved-cell lymphomas often contain positive cells. These findings have to be considered in the immunohistochemical differential diagnosis of lymphomas. Obviously, CD30 alone cannot be used to differentiate between Hodgkin's and non-Hodgkin's lymphomas. The CD30-positive cells in non-Hodgkin's lymphoma may represent a link between Hodgkin's and non-Hodgkin's lymphomas.     

Recurrent "syncytial variant" of Hodgkin's disease: an immunohistologic diagnosis

A case of recurrent Hodgkin's disease of the "sarcomatoid" or "syncytial variant" type was seen that occurred as an extension from the mediastinum to a previously uninvolved extranodal site (breast) and pericardium after treatment of classical nodular sclerosing Hodgkin's disease based in the lymph nodes. This histologic variant was composed of sheets of large, undifferentiated neoplastic cells with few, if any, diagnostic features of nodular sclerosing Hodgkin's disease. For this reason, the differential diagnosis of this variant was difficult and included non-Hodgkin's lymphoma (peripheral T-cell lymphoma), Ki-1-positive lymphoma, medullary carcinoma, metastatic carcinoma, melanoma, and granulocytic sarcoma. Immunologic analysis by immunoperoxidase technique showed a phenotype consistent with "syncytial variant" Hodgkin's disease: Leu-M1+, Ki-1+, IL-2+, HLA-DR+, T11-, pan B-, K-, lambda-, cytokeratin-, S-100-, muramidase-.     

Monoclonal antibodies reactive in routinely processed tissue sections of malignant lymphoma, with emphasis on T-cell lymphomas

The immunoreactivity of eight monoclonal antibodies was evaluated on 45 routinely processed lymphomas (22 T-cell lymphomas, 11 B-cell lymphomas, and 12 cases of Hodgkin's disease). Two antibodies reactive with leukocyte common (T200) antigens (PD7/26 and 2B11) stained most of the B- and T-cell lymphomas but did not stain the Reed-Sternberg cells and variants in Hodgkin's disease. Two antibodies known to stain B cells (LN-1 and LN-2) reacted with some of the B-cell lymphomas, but LN-2 also reacted with the neoplastic cells in six of 22 T-cell lymphomas and with the Reed-Sternberg variants in eight of 12 cases of Hodgkin's disease. The granulocyte antibody anti-Leu M1 reacted with most cases of Hodgkin's disease but also reacted with two of 11 B-cell non-Hodgkin's lymphomas. An antibody to epithelial membrane antigen (anti-EMA) stained some cases of T-cell lymphoma, B-cell lymphoma, and Hodgkin's disease. Leu 7 was expressed in one T-cell lymphoma and in one case of Hodgkin's disease. A novel antibody reactive with T cells (L60) stained all cases of T-cell lymphoma but also stained some cases of B-cell lymphoma and one case of Hodgkin's disease. We conclude that none of these antibodies, when used alone on routinely fixed paraffin-embedded material, is completely sensitive and specific for T-cell lymphoma, B-cell lymphoma, or Hodgkin's disease. However, a panel of antibodies is useful in distinguishing Hodgkin's disease from non-Hodgkin's lymphoma and in suggesting the B- or T-cell phenotype of non-Hodgkin's lymphomas.     

Pitfalls in diagnostic hematopathology �C Part II

The overlapping features of malignant lymphomas create a diagnostic “grey zone” , and lead to the invention of “grey zone lymphomas”. There are several major grey zone lymphomas: 1) Lymphomas with overlapping features of Hodgkin lymphoma and large B-cell lymphoma; 2) Lymphomas with overlapping features of Burkitt lymphoma and diffuse large B-cell lymphoma; 3) Lymphomas with overlapping features of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte rich large B-cell lymphoma; 4) Lymphomas with overlapping features of Hodgkin lymphoma, anaplastic large cell lymphoma (ALCL) and peripheral T-cell lymphoma (PTCL); 5) T-cell classical Hodgkin lymphoma and ALCL-HL. The second review of this series will be dedicated to discussion of the “grey zone” features of the lymphomas and how to narrow down the “grey zone” between those lymphomas.     

Combination of Hodgkin's disease and diffuse large cell lymphoma: an in situ hybridization study for immunoglobulin light chain messenger RNA

It is not clear whether the rare combination of Hodgkin's disease with non-Hodgkin lymphomas are true composite lymphomas or differentiation stages of one tumour cell clone. We used in situ hybridization and immunohistochemistry for the demonstration of immunoglobulin light chains in order to investigate the relationship between the two lymphoma components. In three cases of nodular lymphocyte predominance Hodgkin's disease combined with diffuse large B-cell lymphoma the Hodgkin cells, as well as the tumour cells in the diffuse large B-cell lymphoma, showed the same messenger RNA for one light chain. Thus, using in situ hybridization in nodular lymphocyte predominance Hodgkin's disease combined with diffuse large B-cell lymphoma in a small number of cases a possible genetic relationship between the two components could be shown. In nodular sclerosis combined with diffuse large B-cell lymphoma, in situ hybridization did not support a common clonal origin of both tumour parts. However, a unique clonal derivation cannot be excluded by the techniques applied.     

CDK9/CYCLIN T1 expression during normal lymphoid differentiation and malignant transformation

CDK9 is a member of the CDC2-like family of kinases. Its cyclin partners are members of the CYCLIN T family (T1, T2a, and T2b) and CYCLIN K. The CDK9/CYCLIN T1 complex is very important in the differentiation programme of several cell types, controlling specific differentiation pathways. Limited data are available regarding the expression of CDK9/CYCLIN T1 in haematopoietic and lymphoid tissues. The aim of this study was to analyse the expression of the CDK9/CYCLIN T1 complex in lymphoid tissue, in order to assess its role in B- and T-cell differentiation and lymphomagenesis. CDK9/CYCLIN T1 expression was found by immunohistochemistry in precursor B and T cells. In peripheral lymphoid tissues, germinal centre cells and scattered B- and T-cell blasts in interfollicular areas expressed CDK9/CYCLIN T1, while mantle cells, plasma cells, and small resting T-lymphocytes displayed no expression of either molecule. CDK9/CYCLIN T1 expression therefore appears to be related to particular stages of lymphoid differentiation/activation. CDK9 and CYCLIN T1 were highly expressed in lymphomas derived from precursor B and T cells, from germinal centre cells, such as follicular lymphomas, and from activated T cells (ie anaplastic large cell lymphomas). Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma also showed strong nuclear staining. Diffuse large B-cell, Burkitt's lymphomas, and peripheral T-cell lymphomas, among T-cell lymphoproliferative disorders, showed a wide range of values. No expression of CDK9 or CYCLIN T1 was detected in mantle cell and marginal zone lymphomas. However, at the mRNA level, an imbalance in the CDK9/CYCLIN T1 ratio was found in follicular lymphoma and diffuse large B-cell lymphomas with germinal centre phenotype, and in the cell lines of classical Hodgkin's lymphomas, Burkitt's lymphomas, and anaplastic large cell lymphoma, in comparison with reactive lymph nodes. These results suggest that the CDK9/CYCLIN T1 complex may affect the activation and differentiation programme of lymphoid cells. The molecular mechanism through which the CDK9/CYCLIN T1 complex is altered in malignant transformation needs to be elucidated.     

Patterns of spectrin expression in B-cell lymphomas: loss of spectrin isoforms is associated with nodule-forming and germinal center-related lymphomas.

Spectrins are a family of cytoskeletal proteins that organize and link membranes to subcellular motors and filaments. Although traditionally divided into erythroid and non-erythroid forms, the discovery of new spectrin isoforms in various tissues indicates that their distribution is not yet fully characterized. To our knowledge, there is no comprehensive analysis of spectrins in lymphoid malignancies. Using tumor microarrays of paraffin blocks, we immunohistochemically studied 10 lymph nodes with reactive lymphoid hyperplasia and 94 lymph nodes involved by B-cell malignant lymphoma. Expression of spectrins alphaI, alphaII, betaI, betaII, and betaIII was scored using a 20% cutoff for positive immunoperoxidase staining. All spectrin isoforms, except erythroid-specific alphaI spectrin, were detected in lymph nodes with reactive lymphoid hyperplasia. In contrast, various spectrins were lost in particular B-cell malignant lymphomas. Based on the absence of staining for one or more spectrin isoforms in at least 50% of cases, we identified three patterns: (1) loss of alphaII and betaII in follicular lymphoma, grades 2/3 and 3/3; nodular lymphocyte predominance Hodgkin's lymphoma; nodular sclerosis Hodgkin's lymphoma; (2) loss of betaI only in Burkitt lymphoma; and (3) loss of alphaII and betaI in mixed cellularity Hodgkin's lymphoma. In contrast, follicular lymphoma, grade 1/3 and diffuse large B-cell lymphoma retained spectrin in 67-100% of cases. The other lymphoma subtypes retained spectrin in greater than 50% of cases. We identified the loss of particular spectrin isoforms in B-cell malignant lymphomas that have a nodular growth pattern and/or are believed to arise from germinal center B-cells, that is follicular lymphoma, grades 2/3 and 3/3; Burkitt lymphoma; nodular sclerosis Hodgkin's lymphoma; mixed cellularity Hodgkin's lymphoma; and nodular lymphocyte predominance Hodgkin's lymphoma. The absence of particular spectrin isoforms may correlate with transformation or aggressive biologic behavior for some lymphoma subtypes.     

Morphoimmunohistological differential diagnosis between Hodgkin's lymphoma with lymphoid prevalence and large B-cell lymphoma

Morphological and immunophenotypical features of Hodgkin's lymphoma with lymphoid predominance are described: a variant with nodular lymphoid predominance (NLPHL) and variants of large-cell lymphoma including mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma rich with T-cells and/or histiocytes. In view of the fact that these lymphomas enter so-called "gray zone" criteria for immunohistochemical differential diagnosis are suggested.