J Clin Pathol 1994;47:33-37 33 Relation of CD30 expression to survival and morphology in large cell B cell lymphomas J Clin Pathol: first published as 10.1136/jcp.47.1.33 on 1 January 1994. Downloaded from L A Noorduyn, P C de Bruin, P van Heerde, M M van de Sandt, G J Ossenkoppele, CJLMMeijer Abstract the nerve growth factor receptor superfamily.3 Aims-To investigate whether CD30 Because these CD30 positive lymphomas expression is correlated with anaplastic seemed to present a specific histological pic- morphology, and whether this correlated ture, this group of lymphomas was called with a better survival in large cell B cell anaplastic large cell (Ki-I +) lymphoma, and lymphomas, as has been described for was incorporated in the updated version of T cell lymphomas. the Kiel classification among the high grade Methods-CD30 expression was investi- category of both B cell and T cell gated using frozen sections in a series of lymphomas.4 Several reports have described 146 large cell B cell lymphomas. Clinical cases or series of these anaplastic large cell data and follow up information were col- lymphomas, most of which have concentrated lected from 25 lymphomas with strong on the T cell variety.2 5 Furthermore, CD30 expression, 30 lymphomas with several morphological subtypes have been partial CD30 expression, and a control described.5 7 17-20 group of 25 lymphomas which did not According to the updated Kiel classifica- express CD30. tion, a lymphoma should not only express Results-Morphological distinction between CD30, but also exhibit a so-called "anaplas- anaplastic and non-anaplastic tumours tic" morphology, to qualify as an anaplastic was difficult. Of the cases with an large cell lymphoma. Some studies mention anaplastic morphology, 50% were CD30 the expression of CD30 in non-anaplastic positive, as were 24% of the polymorphic lymphomas,2782' but none of these studies centroblastic B cell lymphomas. Only has systematically addressed the question of 65% of the morphologically non-anaplas- how frequently CD30 expression occurs in tic tumours were completely CD30 nega- different morphological subtypes of large cell tive. There was no difference in survival non-Hodgkin's lymphoma. In T cell among patients with lymphomas express- lymphomas the relation between anaplastic ing CD30 and those that did not. Patients morphology and CD30 expression seems to http://jcp.bmj.com/ with morphologically anaplastic B cell be fairly good,22 and CD30 expression is lymphomas did not differ in their sur- associated with a relatively benign clinical vivals from those with other high grade B course.22 23 Whether this also holds true for B cell lymphomas. Clinical stage at presen- cell lymphomas is presently unknown. tation was the only variable that was sig- nificantly associated with survival. Department of Conclusions-CD30 expression occurs Methods on October 2, 2021 by guest. Protected copyright. Pathology, Academic frequently in large cell B cell lymphomas In a pilot experiment of 44 large cell B cell Medical Centre, Amsterdam and is poorly related to anaplastic lymphomas CD30 expression, as demon- L A Noorduyn morphology. Morphological distinction strated by Ber-H224 on formalin fixed, paraf- Department of between anaplastic and non-anaplastic fin wax embedded tissue, gave many false Pathology, Free tumours is difficult. In contrast to T cell negative results when compared with frozen University Hospital, B sections we decided to use Amsterdam lymphomas, CD30 positive cell lym- (fig 1). Therefore, P C de Bruin phomas do not show a relatively only those large cell lymphomas from which CJLMMeijer favourable clinical course. The results frozen tissue was available. We therefore col- Netherlands Cancer presented here raise serious doubts as to lected 146 cases of large cell lymphoma from Institute whether large cell B cell lymphoma, the files of the Comprehensive Cancer Centre P van Heerde based on the expression of CD30 or Amsterdam (CCCA). Routinely stained Slotervaart Hospital, and Amsterdam anaplastic morphology, can really be slides (haematoxylin eosin, reticulin, M M van de Sandt termed a separate entity. Giemsa, and periodic acid Schiff), and data Department of on immunohistochemistry were also collected Haematology, Free (3 Clin Pathol 1994;47:33-37) from all cases. University Hospital, Staining with Ber-H2 on frozen sections Amsterdam G J Ossenkoppele was performed according to standard proce- as Correspondence to: In 1982 a monoclonal antibody that reacted dures. Tumours were scored positive (+) Dr L A Noorduyn, selectively with Hodgkin and Reed-Stemnberg if at least 50% of the tumour cells were Department of Pathology, Academic Medical Centre, cells was described by Schwab et al.' Ki-i stained clearly and dubious (+ /-) if less Meibergdreef 9, 1105 AZ (CD30) was subsequently shown to react than 50% of the tumour cells were stained or Amsterdam, The Netherlands with a number of large cell non-Hodgkin's if staining was weak. Morphological investiga- Accepted for publication lymphomas. Recently, it has been shown that tion of the tumours was performed with the 18 August 1993. Ki-i detects an antigen that is a member of help of routinely stained slides, without prior 34 Noorduyn, Bruin, Heerde, Sandt, Ossenkoppele, Meijer .... V4, knowledge of the results of Ber-H2 staining. 9-go" .:. Morphologically, the tumours were graded .* according to the updated Kiel classification.4 i .. Tumours were scored as anaplastic if they ... J Clin Pathol: first published as 10.1136/jcp.47.1.33 on 1 January 1994. Downloaded from met the criteria described by Suchi et al and Lennert.526 In short, anaplastic lymphomas 4 were characterised by large or very large cells, 4. * with abundant cytoplasm, with large, often and usually mul- ..... ...... reniform or indented nuclei, w. tiple, medium sized to large nucleoli. The ._: i :. i. tumour often showed an intrasinusoidal '4 growth pattern. ./:O..§. .... w.s., *: °\ ...... ... Of the tumours that were scored as + or * .e:*: .S :> ffiW- A">Z:X:.: '4, if}S%;R:. * u R;iu)+ /-)and from a control group of 25 A1 {:Aj.!. *.*..: *, :& * i # tumours that were scored as -, clinical :' # ..... .: and follow up data were collected from the .. IP e patients' records. This group of 25 patients whose tumours were completely CD30 nega- : *.z .. , g ...- tive was used as a control group for survival analysis. It included three patients with :. ...:: . anaplastic, but immuno- ...., .":o. ....e..:.A morphologically histochemically CD30 negative, tumours. JR-.if>. ... - .: vR* ..^'w bioi.. Statistical analysis of these data was Figure 1 Polymorphic centroblastic B cell lymphoma. Staining with Be? paraffin wax section is negative. Inset: staining with Ber-H2 onfrozen section is I-Ht2ven performed with the help of a BMDP package. Results The numbers of positive tumours for each morphological subtype are shown in the Expression ofCD30 (Ber-H2) in 146 large cell B cell table. In most tumours in the CD30+ cate- lymphomas, according to morphological subtype gory, over 80% of tumour cells were positive, and in the CD30 + / - category generally less CD30 than 20% were positive. Only a few tumours + - Total expressed CD30 in tumour cells close to the B cell lymphomas cutoff point of 50%. Follicular centroblastic 2 5 7 14 Of the B cell lymphomas that were mor- Centrocytoid centroblastic 2 10 29 41 Centroblastic 2 5 22 29 phologically scored as anaplastic (fig 2), 50% Polymorphic centroblastic 9 7 21 37 were positive with CD30, but of the Immunoblastic 2 1 6 9 http://jcp.bmj.com/ Anaplastic 8 2 6 16 immunoblastic and polymorphic centroblastic Total 25 30 91 146 tumours, 22% and 24%, respectively, were + > 50% of the tumour cells positive; + < 50% of the also positive. Even the other groups of large tumour cells positive, or weak staining; - tumour cells cell B cell lymphoma included cases which negative. were positive with CD30, and a considerable percentage of these tumours showed partial or weak staining of the tumour cells. Only 65% of the morphologically non-anaplastic on October 2, 2021 by guest. Protected copyright. tumours were completely negative with CD30. In reviewing the morphology of the tumours, it was often difficult to differentiate anaplastic and non-anaplastic tumours. In particular, the distinction between poly- .S.. : 0, morphic centroblastic lymphomas and X.! t. immunoblastic B cell lymphomas on the one ::: ::. hand, and anaplastic large cell B cell lym- *:::: :.: phomas on the other, was hard to make when the lymph node was completely invaded, and *# ,u.if > >ak therefore, the characteristic intrasinusoidal .:: i:. growth pattern of anaplastic large cell lym- phoma could not be seen. All these types of :*b. .U. ..f e.: f lymphoma were composed of large cells, .Z:z,:2' 'S usually with abundant cytoplasm, and .- :.e t: .: .:.' : anaplastic nuclei were detected in varying !§2 '' amounts in all of them. Therefore, the dis- .: .S.:e,:....w. tinction was made by estimating the propor- tion of anaplastic nuclei, but we felt that ... : placing these tumours in one category or :... '' another was often arbitrary. Of the cases that expressed CD30, 25 4. .'. patients were men, 10 of whom were in ....Figure: S.t,:^:;*t. e |.... r .:....... ::: ae:., .% 's3':.2'....,.... ' :.:.... '° 3..Anaplastic<... : .. ......: nsslt.?.: .X. :e ffly:.:::; .. s::. : large cell lymphoma, B cell type (haematoxylin and eosin). the CD30 + category, with 15 in the Relation ofCD30 expression to survival and morphology in large cell B cell lymphomas 35 Figure 3 Survival curves tumours died of their disease, with a mean ofCD30 +, CD30 +/-, lOOr - CD30 + and CD30 - large cell B 90 It-I --- CD30 +/- survival of 13 months. The other 14 patients cell lymphomas. No .CD30- with CD30- lymphomas were alive with a 80 - significant difference was § mean follow up of 47 months. There was no seen between any ofthe 70 :...'.n = 25 J Clin Pathol: first published as 10.1136/jcp.47.1.33 on 1 January 1994.