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Notes: In April 1998, The European Association for Haematopathology organized the IXth workshop on peripheral T-cell and NK-cell lymphomas and leukaemias. The workshop focused on unusual subtypes of these rare malignancies, allowing evaluation of the recently published WHO classification of neoplastic diseases of the lymphoid tissues.  One-hundred and three cases were centrally immunophenotyped and hybridized for EBER1/2 of Epstein–Barr virus. All cases were reviewed by a panel of experienced haematopathologists and classified according to the new WHO classification for lymphoid neoplasms. Three cases were considered as precursor T-cell and 95 cases as peripheral T/NK-cell lymphoma/leukaemia. Although the cases represented a selected series of unusual cases, the following conclusions could be made: (i) Most lymphomas except the hepatosplenic γ/δ T-cell lymphomas showed a rather broad morphological spectrum, with differences both between and within individual tumours. (ii) This heterogeneity was also reflected by the immunophenotype, for instance a variable expression of CD30 was found in many enteropathy type T-cell lymphomas. (iii) Exceptions in phenotype were regularly found in almost all categories, indicating that phenotype should not be the final determining factor in classification. (iv) The great majority of T-cell lymphomas expressed the α/β T-cell receptor, with the exception of all but one hepatosplenic T-cell lymphomas and a few other extranodal peripheral T cell lymphomas. (v) Malignancies of precursor cells, blastic NK-cell lymphoma/leukaemia, adult T-cell lymphoma/leukaemia and most AIL-type T-cell lymphomas did not express cytotoxic molecules such as TIA1 and granzyme-B. In contrast, all five aggressive NK/T-cell lymphomas/leukaemias, a single case of large granular lymphocyte leukaemia and 40 of 47 primary extranodal lymphoma/leukaemias expressed these molecules. In hepatosplenic γ/δ T-cell lymphoma, five of six cases showed expression of TIA1 but not of granzyme-B. (vi) Seven tumours developed after organ-transplant, four cases being EBV-positive. No distinct phenotype could be attributed to these cases.Most peripheral T/NK cell lymphomas could be categorized as distinct entities as described in the recently proposed WHO classification for lymphoid neoplasms.

Notes: Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases Neoplasms of histiocytes and dendritic cells are rare, and their phenotypic and biological definition is incomplete. Seeking to identify antigens detectable in paraffin-embedded sections that might allow a more complete, rational immunophenotypic classification of histiocytic/dendritic cell neoplasms, the International Lymphoma Study Group (ILSG) stained 61 tumours of suspected histiocytic/dendritic cell type with a panel of 15 antibodies including those reactive with histiocytes (CD68, lysozyme (LYS)), Langerhans cells (CD1a), follicular dendritic cells (FDC: CD21, CD35) and S100 protein. This analysis revealed that 57 cases (93%) fit into four major immunophenotypic groups (one histiocytic and three dendritic cell types) utilizing six markers: CD68, LYS, CD1a, S100, CD21, and CD35. The four (7%) unclassified cases were further classifiable into the above four groups using additional morphological and ultrastructural features. The four groups then included: (i) histiocytic sarcoma (n=18) with the following phenotype: CD68 (100%), LYS (94%), CD1a (0%), S100 (33%), CD21/35 (0%). The median age was 46 years. Presentation was predominantly extranodal (72%) with high mortality (58% dead of disease (DOD)). Three had systemic involvement consistent with `malignant histiocytosis'; (ii) Langerhans cell tumour (LCT) (n=26) which expressed: CD68 (96%), LYS (42%), CD1a (100%), S100 (100%), CD21/35 (0%). There were two morphological variants: cytologically typical (n=17) designated LCT; and cytologically malignant (n=9) designated Langerhans cell sarcoma (LCS). The LCS were often not easily recognized morphologically as LC-derived, but were diagnosed based on CD1a staining. LCT and LCS differed in median age (33 versus 41 years), male:female ratio (3.7:1 versus 1:2), and death rate (31% versus 50% DOD). Four LCT patients had systemic involvement typical of Letterer–Siwe disease; (iii) follicular dendritic cell tumour/sarcoma (FDCT) (n=13) which expressed: CD68 (54%), LYS (8%), CD1a (0%), S100 (16%), FDC markers CD21/35 (100%), EMA (40%). These patients were adults (median age 65 years) with predominantly localized nodal disease (75%) and low mortality (9% DOD); (iv) interdigitating dendritic cell tumour/sarcoma (IDCT) (n=4) which expressed: CD68 (50%), LYS (25%), CD1a (0%), S100 (100%), CD21/35 (0%). The patients were adults (median 71 years) with localized nodal disease (75%) without mortality (0% DOD). In conclusion, definitive immunophenotypic classification of histiocytic and accessory cell neoplasms into four categories was possible in 93% of the cases using six antigens detected in paraffin-embedded sections. Exceptional cases (7%) were resolvable when added morphological and ultrastructural features were considered. We propose a classification combining immunophenotype and morphology with five categories, including Langerhans cell sarcoma. This simplified scheme is practical for everyday diagnostic use and should provide a framework for additional investigation of these unusual neoplasms.

Notes: Abstract Mature or peripheral T-cell lymphomas are uncommon, accounting for only10%–15% of all non-Hodgkin's lymphomas. The classification of these neoplasms has been controversial. In contrast to B-cell lymphomas, cytologic grade has not been very useful in predicting the clinical course. This finding may result from the generally aggressive clinical course associated with T-cell lymphomas. Prior studies have suggested that stage of disease may be more important than cytologic subtype. Clinical presentation is very important in the classification of T-cell malignancies. For T-cell lymphomas, cytologic features alone are not sufficient to distinguish among disease entities. For example, adult T-cell leukemia/lymphoma (ATLL) often cannot be distinguished morphologically fromHTLV-1-negative T-cell lymphomas. Most extranodal T-cell lymphomas appear to be derived from cytotoxic T cells, which express perforin, TIA-1, and granzyme B. Three broad groups of T-cell malignancies can be identified: (1) leukemicor systemic disease; (2) nodal disease; (3) extranodal disease. Anaplastic large-cell lymphoma (ALCL) is probably the single most common subtype of T-cell lymphoma. Classical ALCL should be distinguished from primary cutaneous ALCL (CD30-positive lymphoproliferative disease of the skin), which is a distinct disease entity.

Notes: Abstract Mature or peripheral T-cell lymphomas are uncommon, accounting for only10%–15% of all non-Hodgkin's lymphomas. Theclassification of these neoplasms has been controversial. In contrast toB-cell lymphomas, cytologic grade has not been very useful in predicting theclinical course. This finding may result from the generally aggressiveclinical course associated with T-cell lymphomas. Prior studies havesuggested that stage of disease may be more important than cytologicsubtype. Clinical presentation is very important in the classification of T-cellmalignancies. For T-cell lymphomas, cytologic features alone are notsufficient to distinguish among disease entities. For example, adult T-cellleukemia/lymphoma (ATLL) often cannot be distinguished morphologically fromHTLV-1-negative T-cell lymphomas. Most extranodal T-cell lymphomas appear tobe derived from cytotoxic T cells, which express perforin, TIA-1, and granzymeB. Three broad groups of T-cell malignancies can be identified: (1) leukemicor systemic disease; (2) nodal disease; (3) extranodal disease. Anaplasticlarge-cell lymphoma (ALCL) is probably the single most common subtype ofT-cell lymphoma. Classical ALCL should be distinguished from primary cutaneousALCL (CD30-positive lymphoproliferative disease of the skin), which is adistinct disease entity.

Notes: Abstract Background:Controversy in lymphoma classification dates back tothe first attempts to formulate such classifications. Over the years, much ofthis controversy arose from the assumption that there had to be a singleguiding principle – a `gold standard' – for classification, andfrom the existence of multiple different classifications. Design:The International Lymphoma Study Group (I.L.S.G.)developed a consensus list of lymphoid neoplasms, which was published in 1994as the `Revised European–American Classification of Lymphoid Neoplasms'(R.E.A.L.). The classification is based on the principle that a classificationis a list of `real' disease entities, which are defined by a combination ofmorphology, immunophenotype, genetic features, and clinical features. Therelative importance of each of these features varies among diseases, and thereis no one `gold standard'. In some tumors morphology is paramount, in othersit is immunophenotype, a specific genetic abnormality, or clinical features.An international study of 1300 patients, supported by the San SalvatoreFoundation, was conducted to determine whether the R.E.A.L. Classificationcould be used by expert pathologists and had clinical relevance. Since 1995,the European Association of Pathologists (EAHP) and the Society forHematopathology (SH) have been developing a new World Health Organization(WHO) Classification of hematologic malignancies, using an updated R.E.A.L.Classification for lymphomas and applying the principles of the R.E.A.L.Classification to myeloid and histiocytic neoplasms. A Clinical AdvisoryCommittee (CAC) was formed to ensure that the WHO Classification will beuseful to clinicians. Results:The International Lymphoma Study showed that the R.E.A.L.Classification could be used by pathologists, with inter-observerreproducibility better than for other classifications (〉85%).Immunophenotyping was helpful in some diagnoses, but not required for manyothers. New entities not specifically recognized in the Working Formulationaccounted for 27% of the cases. Diseases that would have been lumpedtogether as `low grade' or `intermediate/high grade' in the WorkingFormulation showed marked differences in survival, confirming that they needto be treated as distinct entities. Clinical features such as theInternational Prognostic Index were also important in determining patientoutcome. The WHO Clinical Advisory Committee concluded that clinical groupingsof lymphoid neoplasms was neither necessary nor desirable. Patient treatmentis determined by the specific type of lymphoma, with the addition of gradewithin the tumor type, if applicable, and clinical prognostic factors such asthe International Prognostic Index (IPI). Conclusions:The experience of developing the WHO Classificationhas produced a new and exciting degree of cooperation and communicationbetween oncologists and pathologists from around the world, which shouldfacilitate progress in the understanding and treatment of hematologicmalignancies.

Notes: Abstract The symposium discussed the pathobiology, classification, and treatment ofcutaneous lymphomas. Drs. Burg and Kadin commented on the pathophysiology ofmycosis fungoides/Sézary syndrome and cutaneous CD30+lymphoproliferative disorders, respectively. A proposed classification ofprimary cutaneous lymphomas from the EORTC was presented by Drs. Kerl andSterry. Dr. Jaffe presented a classification of cutaneous lymphomas based onthe REAL classification. All speakers agreed that primary cutaneous lymphomasare usually distinctive in their clinical behavior and biology, and differfrom their nodal counterparts. The symposium concluded with remarks from Drs.Vonderheid and Hoppe on the therapeutic approach to primary cutaneous lymphoidmalignancies.

Notes: Abstract Background:The classification of cutaneous lymphomas has beencontroversial. The EORTC has proposed that conventional classification schemesare not suitable for cutaneous lymphomas, and that a unique classificationsystem is required. Design:The authors review the suitability of the R.E.A.L.Classification for cutaneous lymphomas, and compare it with the newly proposedEORTC system. The priniciples of the R.E.A.L. Classification have been adoptedby the WHO committees for the classification of hematopoietic and lymphoidneoplasms. Each disease is defined as a distinct entity based on anintegration of morphology, immunophenotypic and genetic features, clinicalpresentation and course, and normal cellular counterpart. If either primaryor secondary involvement of the skin is a constant factor, this aspect isconsidered integral to disease definition. Results:Organ-specific classification schemes may impede therecognition of common features of diseases involving multiple anatomic sites.For example, cutaneous marginal zone B-cell lymphomas (formerly designatedcutaneous immunocytomas) mirror the features of MALT lymphomas in otheranatomic sites. While the EORTC Classification for cutaneous lymphomasattempts to emphasize certain aspects of these neoplasms of importance todermatologists, the use of multiple classification systems is a step backward,and may lead to confusion among hematologists/oncologists, and dermatologists.Nevertheless, cutaneous lymphomas often have a more indolent natural historythan nodal lymphomas, and may require different therapeutic approaches.Clinical features are an important prognostic factor and should be utilizedin guiding therapy. For cutaneous lymphomas the presence or absence ofsystemic spread is particularly important. Additionally, the site of originis often important in the definition of disease entities. Conclusions:Organ-specific classification schemes, such as theEORTC Classification for cutaneous lymphomas, are not required, and indeed mayimpede the recognition of common features of diseases involving multipleanatomic sites. A common classification system, such as the R.E.A.L./WHOClassification, should be utilized for all lymphomas, regardless of the siteof origin.

Notes: Abstract Introduction: Since 1995, the European Association of Pathologists (EAHP) and the Society for Hematopathology (SH) have been developing a new World Health Organization (WHO) Classification of hematologic malignancies. The classification includes lymphoid, myeloid, histiocytic, and mast cell neoplasms. Design: The WHO project involves 10 committees of pathologists, who have developed lists and definitions of disease entities. A Clinical Advisory Committee (CAC) ) of international hematologists and oncologists was formed to ensure that the classification will be useful to clinicians. A meeting was held in November, 1997, to discuss clinical issues related to the classification. Results: The WHO has adopted the ‘Revised European–American Classification of Lymphoid Neoplasms’ (R.E.A.L.), published in 1994 by the International Lymphoma Study Group (ILSG), as the classification of lymphoid neoplasms. This approach to classification is based on the principle that a classification is a list of ‘real’ disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one ‘gold standard’. The WHO Classification has applied the principles of the R.E.A.L. Classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. The CAC meeting, which was organized around a series of clinical questions, was able to reach a consensus on most of the questions posed. The questions and the consensus are discussed in detail below. Among other things, the CAC concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors such as the international prognostic index (IPI). Conclusion: The experience of developing the WHO Classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies.