JOURNAL OF PATHOLOGY, VOL. 179: 138-144 (1996)

HOW TO DIFFERENTIATE BETWEEN T-CELL-RICH B-CELL LYMPHOMA AND LYMPHOCYTE-

PREDOMINANT HODGKIN’S DISEASE. EVIDENCE FOR THE VALUE OF MBl AND 4KB5 IMMUNOSTAINING

U. SCHMIDT, J. IIFKBST, K. A. METZ AND L.-D. LPDEK

Department of Pathology, University of Essen, Germany

SUMMARY

Striking morphological similarities exist between T-cell-rich B-cell lymphoma and lymphocyte-predominant Hodgkin’s disease (Hodgkin’s paragranuloma), making the distinction between them extremely difficult. Immunohistochemistry proFides a means of overcoming this difficult!. lmmunostaining with UCHLl, L26, MB1, and 4KB5 was performed on five T-cell-rich B-cell lymphomas and 11 Hodgkin’s paragranulomas (7/11 nodular, 4/11 diffuse). L26 stained the tumour cells not only of T-cell-rich B-cell lymphomas, but also of L + H Hodgkin’s disease. In contrast, MB1 as well as 4KB5 identified all of the neoplastic cells in 315 T-cell-rich B-cell lymphomas, but did not react with the L + H cells in 811 I Hodgkin’s paragranulomas. Some overlap of staining patterns became apparent in the remaining cases, with 2/5 T-cell-rich B-cell lymphomas showing the MBl’14KB5’ phenotype in a tumour cell subset only. Similarlj, in 3/11 Hodgkin’s paragranulomas, some MBlI4KBS-positive L + H cells occurred in addition to MBlI4KBS-negative L+H cells. These cases, nevertheless, could be distinguished from one another by the numbers of MBlI4KBS-positive background lymphocytes, which were scanty or absent in T-cell-rich B-cell lymphomas and more numerous in Hodgkin’s paragranulomas.

KEY U oRDs-T-cell-rich &cell lymphoma; Hodgkin’s disease; immunohistochemistry

INTRODUCTION

T-cell-rich B-cell lymphoma is a newly recognized unusual variant of non-Hodgkin’s lymphoma.’ It is characterized by a neoplastic population of large B-cells scattered in a reactive background of T-lymphocytes and histiocytes.’.’ Whether T-cell-rich B-cell lymphoma represents a distinct clinicopathological entity is still open for discussion.

T-cell-rich B-cell lymphoma may occur de novo, or inay be related to follicular lymphoma and diffuse large B-cell lymphoma. Moreover, a special relationship to lymphocyte-predominant Hodgkin’s disease (Hodgkin’s paragranuloma) is evident. Firstly, morphological simi- larities exist between T-cell-rich B-cell lymphoma and lymphocyte-predominant Hodgkin’s d i ~ e a s e . ~ Sec- ondly, the developmcn t of T-cell-rich B-cell lymphoma has been observed in the context of lymphocyte- predominant Hodgkin’s d i ~ e a s e , ~ supporting the view that T-cell-rich B-cell ‘lymphoma may be an evolution- ary phase of L + H-type Hodgkin’s disease.* Conse- quently, thc differential diagnosis between T-cell-rich B-cell lymphoma and L + H-type Hodgkin’s disease, especially of the diffuse variety (diffuse paragranuloma), may be extremely difficult.

We report the results of an immunohistochemical analysis of fivc T-cell-rich B-cell lymphomas and 11 Hodgkin‘s paragranulomas. The purpose of this study was to show that immunostaining with MB1 or, alter- natively, with 4KB5 enables T-cell-rich B-cell lymphoma to be distinguished from lymphocyte-predominant

Addreac for correspondence U Schmidt, MD, Pathology/ Uni\crsit) of Essen, Hufel,indatr 55. D-45122 Essen, Germany

CCC 0022 34 17/96/0601 38-07 ( 1996 by John Wiley & Sons, Ltd.

Hodgkin’s disease in the majority of cases. This may have important therapeutic implications.

MATERIALS AND METHODS

From our files, there were 11 cases available classified as L+ H-type Hodgkin’s disease (Hodgkin’s paragranu- loma) according to commonly accepted and applied criteria.8 Seven tumours presented as Hodgkin’s para- granulomas of the nodular variety and four as difhise paragranulomas. A further five cases from our files fulfilled the published diagnostic criteria for T-cell-rich B-cell l ymph~ma . ’ .~~-~ I These lymphomas were charac- terized by striking similarities to Hodgkin’s paragranu- loma of the diffuse variety and to this cxtcnl rcscmbled a subset of T-cell-rich B-cell lymphoma described by Ng et ul.,’ Chittal et uL4 and Krishnan ct The five T-cell-rich B-cell lymphomas had been previously reported (see ref. 7, cases 2-5, 7) and one of them at that time was shown to coexist with nodular Hodgkin’s paragranuloma (see ref. 7, case 3). In a further case (case 2, Table I), a mediastinal mass had been present since 1984, but without clinical progression (ref. 7, case 7); a biopsy of this mass had therefore not been performed.

Briefly, the diagnosis of T-cell-rich B-cell lymphoma was based on the recognition of the following pattern: ( 1) nodal architecture diffusely obliterated; (2) T-lymphocytes predominant; (3) histiocytes admixed singly or in small clusters; (4) neoplastic population comprising large B-cells similar to centroblasts and to immunoblasts, as well as a minority of cells resembling the L+ H-variant of Reed-Sternberg cells; ( 5 ) diagnostic Reed-Sternberg cells completely absent; (6) epitheloid

Rccciivd 24 .July 1995 Ac,ceptcd 8 Fehrticirj, 1496

T-CELLRICH B-CELL LYMPHOMA OR HODGKIN’S PARAGRANULOMA?

Table I-Clinical data

139

Sexlage Case (years) Site of disease

I F, 79 LN, multiple 2 M, 57 (a) Mediastinal mass (since 1984, no biopsy

performed)

3 M, 33 LN; multiple 4 M, 29 LN, cervical, supraclavicular, paraaortic,

5* M, 63 LN , cervical, axillar, paravertebral

(b) LN, mediastinal; lung, spleen (1994)

pelvic; spleen, bone marrow

L+ H-type Hodgkin’s disease 6 F, 55 LN, cervical 7 M, 45 (a) Spleen (1977)

marrow (1995) (b) LN. cervical. supraclavicular, axillar; bone

8 M, 44 LN, cervical, supraclavicular 9 F, 16 LN, inguinal

10 M, 51 LN, intraabdominal; spleen, bone marrow 1 1 F, 27 LN, cervical, mediastinal; spleen 12 M, 36 LN, cervical. axillar, paraaortic, inguinal 13 M, 37 (a) LN, axillar, inguinal (1984)

14 M, 44 LN, cervical 15 F, 37 LN, pelvic 16 M, 44 (a) LN inguinal (1986)

(b) LN, inguinal (1994)

(b) LN, cervical (1995)

Response to therapy Survival

PR No therapy

PR CR PR

CR

CR

PR

CR CR CR PR CR CR

No therapy CR

No therapy No therapy

DFD, 9 months

DFD, 15 months AW, 58 months

DFD, 18 months

AW, 40 months

AW, 21 months

AW, 8 months

Lost to follow-up AW, 14 months AW, 31 months AW, 13 months AWD, 6 months

AW, 9 months AW, 21 months AW, 18 months

AW, 16 months

Case 5* =T-cell-rich B-cell lymphoma coexisting with Hodgkin’s paragranuloma. LN=lymph node; CR=complete remission; PR=partial remission; AW=alive and well; AWD=alive with disease;

DFD=dead from disease.

Table 11-Antibodies used

Antibody ~ ~~ ~

Relevant reactivity Dilution Source

L26 CD20 B-cells 1:50 Dakopatts UCHLl CD45RO T-cells 1:125 Dakopatts MB 1 CD45RA B-cells, T-cell subpopulation 1 : l O Quartett 4KB5 CD45R B-cells, T-cell subpopulation 1:50 Dakopatts BerH2 CD30 RS cells 1:lO Dakopatts Leu-M I CD15 RS cells 1:lOO Dakopatts

venules numerous; (7) immunostaining of the neoplastic cells positive with L26, but negative with UCHLI , BerH2, Leu-M1, and EMA. The clinical data of our patients are summarized in Table I.

Paraffin sections from 1-4 blocks per case of formalin- fixed and routinely processed tissue were stained with haematoxylin and eosin, and Giemsa. In addition, the periodic acid-Schiff (PAS) reaction and Gomori’s silver impregnation were undertaken. Inimunohistochemical analyses of paraffin sections from 1-2 blocks per case with L26, UCHLI , BerH2, Leu-M1, EMA, MBI , and 4KB5 were carried out using the APAAP-complex method. For all markers, immunostaining was per- formed without microwave assistance. The antibodies used are listed in Table IT.

RESULTS

In the following, only the staining patterns of UCHL1, L26, MB1, and 4KB5 are described. This is because ( I ) UCHLl and L26 are essential for the recog- nition of T-cell-rich B-cell lymphoma and (2) MBl and 4KB5 are the reagents found to be useful in the differen- tial diagnosis of T-cell-rich B-cell lymphoma and L + H- type Hodgkin’s disease. Details are given in Table 111.

T-cell-rich B-cell lymphomas

In T-cell-rich B-cell lymphoma, the majority of small background lymphocytes were positive with U C H L l (Fig. 1). In all cases, L26 imniunostaining labelled the

140 U. SCHMIDT ET AL.

Table 111-lmmunoreactivity of the neoplastic cells and of the background lymphocytes in T-cell-rich B-cell lymphoma (TCRBCL) and L + H Hodgkin's disease

UCHLl L26 MB 1 4KB5

TCRBCL Case 1 Neoplastic cells - + + + + + + +

Case 2 Neoplastic cells - + + + + + + +

Backgr. lymphocytes + + +, diffuse - +, diffuse +, diffuse

Backgr. lymphocytes + + + , diffuse +, focal +, diffuse +. diffuse

Case 3 Neoplastic cells - +++ + + + + + + Backgr. lymphocytes + + , diffLw - - -

Case 4 Neoplastic cells - + + + + + + + + + Backgr. lymphocytes + + +, diffuse - +, diffuse +, diffuse

Case 5" Neoplastic cells - + + + + + + + + + - Backgr. lymphocytes + + + , diffuse +, focal ~

L + H Hodgk in's disease, diffuse Case 6 L + H cells - + + + + +

Backgr. lymphocytes + + , meshwork + +, focal + + + , focal + + + , focal

- - Case 7 L + H cells - +++ Backgr. lymphocytes + +, diffuse - +. diffuse +. difuse

- Case 8 L + H cells - + + + ~

Rackgr. lymphocytes + +, diffuse +, focal + + + , f o c a l : +++, focal

__ - Case 9 L + H cells - + + + Backgr. lymphocytes + +, diffuse +, diffuse + + +, diffuse + + + , diffuse

L+ H Hodgkin's disease, nodular Case 10 L + H cells - - + + + -

Backgr. lymphocytes + +, diffuse +, focal + +, focal + + +, focal

- + + - Case 11 L + H cells ~

Backgr. lymphocytes + +, meshwork + +, focal + + +. focal + + +, focal

+ - + + + - Case 12 L+H cells Backgr. lymphocytes + +, diffuse +, diffuse +, focal +, focal

- - Case 13 L + H cells - + + + Backgr. lymphocytes + +, meshwork + +, focal + + +, focal + + +, focal

- + + - Case 14 L + H cells ~

Backgr. lymphocytes +, focal + + , f o c a l +++, focal +++. focal

Case IS L + H cells - + + + + + Backgr. lymphocytes + + +, focal + + , f o c a l +++, focal + + + . rocai

- __ + + - Case 16 L+H cells Backgr. lymphocytes + +, meshwork + + +, focal + + +. focal + + +. focal

Case 5* Paragranuloma part - - + + + - L+H cells

Backgr. lymphocytes + +, diffuse + + , f o c a l +++. focal +++ , focal

Case 5* =T.-cell-rich B-cell lymphoma coexisting with Hodgkin's paragranuloma. linmunostaining without microwave assistance. The symbols indicate the proportions of immunoreactive neoplastic cellslbackground lymphocytes. + + + = a majority

of cells staining. + + = a minority of cells staining; +=few cells staining; - =no cells staining.

T-CELL-RICH B-CELL LYMPHOMA OR HODGKIN’S PARAGRANULOMA? 141

Fig. 1-UCHLI-positive lymphocytes in T-cell-rich B-cell lymphoma (case 1)

Fig. 3-MB1 positivity of the neoplastic cells in T-cell-rich B-cell lymphoma (case 1). Although rare MBI-positive background lym- phocytes were observed in this case, the staining pattern is completely different from Hodgkin’s paragranuloma; compare with Fig. 5

Fig. 2-T-cell-rich B-cell lymphoma coexisting with Hodgkin’s uara- granuloma (case 5*). L26 positivity of the neoplastic cells in the T-cell-rich B-cell lymphoma part Fig. 4-UCHLI-positive lymphocytes in Hodgkin’s paragranuloma

(case 6). Non-reactive L + H cells (t)

neoplastic population, comprising centroblast-like, immunoblast-like, and L+H-like cells (Fig. 2 and Table 111). In 2/5 T-cell-rich B-cell lymphomas, occasional small foci of lymphocytes also reacted with L26, whereas L26-positive lymphocytes were not observed in 3/5 T-cell-rich B-cell lymphomas.

With MB1, the tumour cells were again positive (Fig. 3). Three out of the five T-cell-rich B-cell lymphomas, including the one coexisting with Hodgkin’s paragranu- loma (see the Materials and Methods section), reacted strongly with MBl in all or nearly all tumour cells. In 2/5 T-cell-rich B-cell lymphomas, however, only a minority of tumour cells were positive (cases 1 and 2, Table 111). These two T-cell-rich B-cell lymphomas and one further case also showed few MBl-positive lym- phocytes, which were evenly distributed in the neoplastic tissue. 4KB5 immunostaining was identical with MBl and no significant qualitative or quantitative differences could be detected between the two markers.

L + H-type Hodgkin ’s disease

In L+ H-type Hodgkin’s disease, UCHLl staining marked a proportion of the background lymphocytes (Fig. 4). With the exception of three cases, the distri- bution of the UCHLI -positive lymphocytes correlated well with the nodular or diffuse growth pattern. In L + H nodular Hodgkin’s disease, the T-lymphocytes were distributed in a meshwork pattern (3/7 nodular para- granulomas, cases 11, 13, 16) or focally (2/7 nodular paragranulomas, cases 14, 15) between B-lymphocyte aggregates, whereas in three out of four diffuse para- granulomas the T-lymphocytes were more evenly dis- tributed, similar to their arrangement in T-cell-rich B-cell lymphoma (cases 7, 8, 9, Table 111).

With L26, the L + H cells stained consistently in 8/11 paragranulomas, irrespective of the growth pattern, but were not all positive in three cases. Additionally, small lymphocytes in varying numbers were regularly

142 U. SCHMIDT ET AL. ’

L26-positive in most paragranulomas, as was the case with UCHLl . However, the distribution of the L26-positive lymphocytes did not correlate with either the nodular or the diffuse growth pattern, in contrast to the distribution of the UCHLl-positive lymphocytes. In most cases (8/11 paragranulomas), the L26-positive lymphocytes were arranged focally, but were more diffusely distributed in the remainder (2/11 paragranulomas), and did not react in one case. As regards the T-lymphocyte/B-lymphocyte ratio, it appeared that in nodular paragranuloma, B-lymphocytes predominated or were at least equal in number to the T-lymphocytes in 4/7 cases, but were less numerous in three cases. In diffuse paragranuloma, T-lymphocytes outnumbered the B-lymphocytes (314 cases), as in T-cell-rich B-cell lymphoma (Table 111).

MBI and 4KB5 immunostaining gave identical results in all paragranulomas, irrespective of the subtype: the L + H cells in general did not react with either ME31 or 4KB5 (Fig. 5) . In two cases, however, occasional L + H cells were found to be positive with MB1. These two cases and a further one also contained few L + H cells positive with 4KB5 (Table 111). In addition, a majority of background lymphocytes were consistently positive with MB1 as well as with 4KB5 in 9/11 paragranulomas (Fig. 5). These MB1/4KBS-positive lymphocytes were focally distributed in most paragranulomas, irrespective of whether the growth pattern was nodular or diffuse.

lnimunoreactivities of the paragranuloma part of case 5 (T-cell-rich B-cell lymphoma coexisting with nodular paragranuloma, Table 111) were identical to the above; that is, the L+H cells remained negative with MB1 and 4KB5, whereas numerous MB1- and 4KBS-positive lymphocytes were found to be disseminated in between the neoplastic cells (Fig. 6).

DlSCUSSION

Putative T-cell-rich B-cell lymphomas comprise a het- erogeneous group with a wide spectrum of phenotypes,

of which only a subset of cases is described as proto- t y p i ~ . ~ , ~ , ~ , ’ This subset is distinguished by features mimicking lymphocyte-predominant Hodgkin’s disease. We believe that this particularly holds true for the diffuse variety of L + H Hodgkin’s disease (diffuse para- granuloma). Prototypic T-cell-rich B-cell lymphoma and diffuse paragranuloma have in common the following features: (1) a diffuse growth pattern; (2) a predomi- nance of T-lymphocytes in the reactive background;12 (3) histiocytes interspersed singly or in small clusters; (4) a neoplastic population of large atypical B-cells, inter- mingled with some L+ H-like elements in T-cell-rich B-cell lymphoma and comprising typical L+H cells in Hodgkin’s disease; and (5) an identical imrnunopheno- type of the L+H-like cells in T-cell-rich B-cell lym- phoma and of the L + H cells in Hodgkin’s disease, which all are positive with L26 and LCA and negative with Leu-M1 and EMA.8 Moreover, T-cell-rich R-cell lymphoma has been shown to coexist with, or arise secondary to, lymphocyte-predominant Hodgkin’s dis- ease.7 One may therefore speculate whether T-cell-rich B-cell lymphoma simply represents a phenotypically different manifestation of lymphocyte-predominant Hodgkin’s disease, as believed by Lukes and C o l l k 8

Krishnan et 0 1 . ~ recently stated that ‘even with the help of immunoperoxidase and genotypic results . . . the distinction of T-cell-rich B-cell lymphoma from lym- phocyte predominant Hodgkin’s disease . . . may remain unclear’. Indeed, immunostaining with LeuM 1, BerH2, L26, and UCHLl discloses a high degree of con- cordance between T-cell-rich B-cell lymphoma and lymphocyte-predominant Hodgkin’s disease.’ For example, UCHLl does not label tumour cells of either T-cell-rich B-cell lymphoma or Hodgkin’s paragranu- loma, which are both B-cell neoplasms, whereas many background lymphocytes are UCHLl -positive in the two entities. Conversely, L26 labels all the neoplastic cells not only of T-cell-rich B-cell lymphoma, but also of lymphocyte-predominant Hodgkin’s disease, whereas background lymphocytes, which are L26-positive, tend

T-CELL-RICH B-CELL LYMPHOMA OR HODGKIN’S PARAGRANULOMA? 143

to be absent in T-cell-rich B-cell lymphoma and to be relatively few in number in many Hodgkin’s para- granulomas (Table 111).

The findings presented here, however, illustrate that MBl or, alternatively, 4KB5 immunostaining can resolve the problems of differential diagnosis. MBl (CD45RA) stains B-cells and a T-cell subpopulation and identifies a majority of high-grade B-cell lymphomas. In contrast, classical Reed-Sternberg cells, as well as the L + H Reed-Sternberg variants, are found to be positive in only a minority of c a s e ~ . ~ ~ J ~ 4KB5 (CD45R), also a B-cell marker, reacts with most B-cells in tissue sections as well as with a small subset of T-cells and monocytes and its specificity is thus similar to that of MBI. In malignant lymphomas, most B-cell tumours are recog- nized by this reagent,lS whereas all variants of Reed- Sternberg cells, including the L + H type, fail to react.I4

From our results, it appears that in T-cell-rich B-cell lymphoma, and with respect to the neoplastic popu- lation, MB1 and 4KB5 gave results identical to L26; namely, an intense staining of the large neoplastic cells. In L+ H-type Hodgkin’s disease, however, tumour cell behaviour is different, since the L + H cells, although positive with L26, remain negative with MB 1 and 4KB5.

Concerning the background lymphocytes, we observed that MB1- and 4KB5-positive cells are absent or scanty in all the T-cell-rich B-cell lymphomas (Table 111). This is in accordance with the fact that MB1 and 4KB5 are B-cell markers and, by definition, the majority of background lymphocytes in T-cell-rich B-cell lympho- mas are of the T-phenotype. In contrast, MB1- and 4KB5-positive lymphocytes were found to be numerous in all cases of Hodgkin’s paragranulomas (Table 111). Unexpectedly, no significant differences were seen between their numbers in the nodular and in the diffuse subtypes, although it is well known that B-lymphocytes tend to exceed T-lymphocytes in nodular para- granuloma, but, conversely, tend to be less numerous in diffuse paragranuloma, where T-cells may predominate.lGls

The background lymphocyte reactivity may be important in those few paragranulomas showing an immunophenotypical overlap with T-cell-rich B-cell lymphoma, with the L + H cell subset positive for MB1 and 4KB5 (311 1 Hodgkin’s paragranulomas, cases 6, 12, 15). This is similar to the behaviour of 215 T-cell-rich B-cell lymphomas, in which only a proportion of the tumour cells stained MB1 and 4KB5-positive (cases 1, 2). In such cases, high numbers of immunoreactive MB 1 +/4KB5 + background lymphocytes indicate Hodgkin’s disease, whereas low numbers indicate T-cell- rich B-cell lymphoma. Similar findings were recently described by Kame1 et al., who observed more numerous CDS7-positive background lymphocytes in Hodgkin’s paragranuloma than in T-cell-rich B-cell lymphoma. l8

One of the T-cell-rich B-cell lymphomas included has previously been shown to coexist with Hodgkin’s para- granuloma (case 5*, Tables I and 111). This case, with MBl and 4KB5, presented as typical T-cell-rich B- cell lymphoma, but in addition showed the pattern of Hodgkin’s paragranuloma in some small areas. Its clini- cal course appears to be distinctly favourable: 40 months

Table IV-Clinicopathological clues to differential diagnosis between T-cell-rich B-cell lymphoma and L + H-type Hodgkin’s disease

T-cell-rich B-cell lymphoma L+ H-type Hodgkin’s disease

Centroblast-like cells Immunoblast-like cells

L+ H-like cells Reed Sternberg cells (rare)

L+H cells (frequent) L26 + L26 + MBl+ MB1- 4KB5 + 4KB5 - EMA - EMA+/ -

Light chain restriction Ig gene rearrangements Advanced clinical stage with

frequent bone marrow and spleen involvement

Less aggressive course

Immunostaining without microwave assistance.

after primary diagnosis, the patient remains stable and in complete remission (Table 111). This is in contrast to 3/5 patients with T-cell-rich B-cell lymphoma, who died from disease at intervals of 9, 15, and 18 months, respectively. T-cell-rich B-cell lymphoma, in general, may behave a g g r e ~ s i v e l y , ~ ~ , ~ ~ but cases have also been observed with a highly variable or following an indolent clinical c o ~ r s e . ~ In contrast, Hodgkin’s paragranuloma follows the least aggressive course of all Hodgkin’s subtypes and most of the paragranuloma patients included here are still in complete remission (Table I).

Case 2 of the T-cell-rich B-cell lymphomas was diag- nosed from a mediastinal mass that had been present for 10 years without being resected, since there was no clinical progression (see also ref. 7, case 7). This long- standing course is consistent with, for example, lymphocyte-predominant Hodgkin’s disease. One may therefore speculate whether the T-cell-rich B-cell lym- phoma of this patient arose from an unrecognized Hodgkin’s paragranuloma. Coexistence with Hodgkin’s paragranuloma, as in case 5*, was not evident.

In this study, immunostaining was performed without microwave assistance. This fact has to be emphasized, since it seems conceivable that a heating step might improve the MBl and 4KB5 sensitivities of Hodgkin’s L+ H cells. If so, the immunophenotypical differences between T-cell-rich B-cell lymphoma and Hodgkin’s paragranuloma with respect to MB1 and 4KB5 as described here would decrease. In other words, Hodgkin’s L+ H cells would become MB114KB5- positive, as with the tumour cells of T-cell-rich B-cell lymphoma, and these markers would no longer be helpful in distinguishing between T-cell-rich B-cell lymphoma and Hodgkin’s paragranuloma.

In conclusion, MB114KB5 immunostaining may fur- ther improve the differential diagnosis between T-cell- rich B-cell lymphoma and lymphocyte-predominant Hodgkin’s disease. The distinction between the two can be made by analysing tumour cell and background

144 U. SCHMIDT E T ’ A L .

lymphocyte reactivities: in T-cell-rich B-cell lymphoma, MBl and 4KB5 label the whole or a subset of the neoplastic population and none or few of the back- ground lymphocytes; in Hodgkin’s paragranuloma, MBI and 4KB5 label none or few L+H cells and consistently numerous background lymphocytes. Ad- ditional criteria which have been proven useful are listed in Table IV.

The exact nature of the relationship between T-cell- rich B-cell lymphoma and lymphocyte-rich Hodgkin’s disease is not yet known and the same holds true for the association of T-cell-rich B-cell lymphoma with certain non-Hodgkin’s lymphoma entities. The nosological dis- tinctiveness of T-cell-rich B-cell lymphoma thus needs further study.

RE,FERENCES Ramsay AD, Smith WJ, lsaacson PG. T-cell-rich B-cell lymphoma. A m J

Ng CS. Char) JKC, Hui PK, Lau WH. Large B-cell lymphomas with a high content of reactive T cells. Hum Ptrrhol 1989; 2 0 1145 -1154. Macon WR. Williams ME, Greer JP, Stein RS, Collins R D , Cousar JB. T-cell rich B-cell lymphomas. A m J Surg Puthol 1992; 1 6 351-363. Chittal SM, Brousset P, Voigt JJ, Delsol G. Large B-cell lymphoma rich in T-cells and simulating Hodgkin’s disease. F f i ~ f ~ p ~ / / i ~ ~ l o g , ~ 199 1; 19: 211 210. Krishnan J, Wallberg K. Frirzera G . T-cell-rich large B-cell lymphoma. Anz J Sirrg Potliol 1994: 18: 455 465. I k Wolf-Peeters C, Pittaliiga S. T-cell-rich B-cell lymphoma: a mor- phological variant of a n r i e t y of non-Hodgkin’s lymphomas or a clinicopathological entity? IIi,vfopn/holo~~ 1995; 2 6 383-385.

sir,.g Pothol 1988; 12: 433443.

7

8.

Y.

10.

I I .

12.

13.

14.

15.

16.

17.

18.

19.

Schmidt U, Metr KA, Leder LD. T-cell-rich B-cell lymphoma and lymphocyte-predominant Hodgkin‘s disease: two closely related entities? Rr J Hmmutol 1995; 9 0 398403. Lukes K, Collins RD. Tumors of the Hematopoietic system. Atla, of Tumor Pathology, 2nd Series, Vol. 28. Armed Forces Institute of Pathology, 1992: 250~259. Jaffe ES, Longo DL, Cosmaii J, Hsu SM, Arnold A, Korsmeyer S J . Diffuse B cell lymphomas with T cell predominance in patients with follicular lymphoma or ‘pseudo T cell lymphoma’. Lnh lnvesi 1984; 50: 27A 28A. Osborne BM, R u t h JJ, Pugh WC. The value of immunophenotyping on paraffin sections i n the idcnlification of T-cell rich B-cell large-cell lympho- mas. Am J Suug Puthnl 1990; 14: 933 938. Baddoura FK, Chan WC. T-cell rich B-cell lymphoma: a clinicopathologic study. Luh Invest 1991; 64 68A. Hansmann ML, Stein H, Dallenbach F , Fellbaum C. DiRuse lymphocyte- predominant Hodgkin’s disease (diRuse paragranuloma). Am J P ~ t h ~ l 1991: 138: 29-36. Ng CS, Chan JKC. Lo STH, Lo DSY. Critical assessment of four monoclonal antibodies reactive with B-cells in Ibrmalin-fixed parafin- embedded tissues. HiJtoputhologj, 1987; 11: 1243 1258. Norton AJ. Isaacson PH. Lymphoma phenotyping in formalin-fixed and paraffin-embedded tissues: 11. Profiles of reactivity in the various tumour types. Hisroputholofiy 1989; 1 4 557-579. Davey FR, Gatter KV, Ralfkiacr E, Pulfvrd KA. Krissansen GW. Mason DY. Immunophenotyping of non-Hodgkin’s lymphomas using a panel of antibodies on paraffin-cmbedded tissues. An1 .I Puihol 1987: 129: 54 ~ 6 3 . Poppema S. The nature of thc lymphocytes surrounding Reed Sternberg cells in nodular lymphocyte predominance and in other types of Hodgkin’s disease. A m J Puthnl 1989; 135: 351 357. Schmid C, Sargent C, lsaacson PG. L and t1 cells of nodular lymphocyte predominant Hodgkin’s disease show immunoglobulin light-chain restric- tion. Am J Puthnl 1991; 139 1281 1289. Kame1 OW, Gelb AB, Shibuya RB, Warnkc RA. Leu 7 (CD 57) reactivity distinguishes nodular lymphocyte predominance Hodgkin‘s disease from nodular sclerosing Hodgkin’s disease. T-cell-rich R-cell lymphoma and follicular lymphoma. An7 J Putlid 1993: 142 541 ~546. Delabie J, Vandenberghe E, Kennes C. C’I rrl. Histiocytc-rich B-cell lyn- phoma. Am J PLL~/Z(J/ 1992; 1 6 3 7 4 8 .