The applicability of the new WHO-EORTC classification of primary cutaneous lymphomas to a single referral center

Recent years have witnessed differences between the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC) classification systems of primary cutaneous lymphomas (PCLs). Recently, a joint WHO-EORTC classification system for PCLs has been reached. This study was performed to assess the applicability of this new classification to a single referral center. All new PCL cases, excluding mycosis fungoides and Sezary syndrome, who were referred from 1999 to 2005 were included. The histological, immunohistochemical stainings and molecular studies were reviewed, and additional stains were performed as needed. The cases were then reclassified according to the WHO-EORTC classifications. The clinical files were also studied, and the patients were followed up clinically. There were 43 new non-mycosis fungoides/Sezary syndrome PCLs, including 29 B-cell lymphomas of which 14 were follicle center lymphoma, 10 marginal zone lymphoma, 4 diffuse large-B-cell lymphoma, leg type, and 1 diffuse large-B-cell lymphoma, other. The 14 T-cell lymphomas included 5 cases of lymphomatoid papulosis, 2 CD30+ anaplastic large-cell lymphomas, 1 NK/T-cell lymphoma, and 6 peripheral T-cell lymphomas, unspecified. Of the 6 "unspecified" T-cell lymphomas, 3 were CD4+ small/medium-sized pleomorphic T-cell lymphoma, which is considered currently a provisional entity under the unspecified T-cell category. The remaining 3 cases could not be classified beyond the unspecified T-cell category, of which 2 cases had an aggressive course. The new WHO-EORTC classification is applicable to most non-mycosis fungoides/Sezary syndrome PCL cases, especially the B-cell lymphomas. However, there is still a substantial subset of T-cell PCLs which cannot be classified beyond the unspecified peripheral T-cell category, some of which may have an aggressive course.     

Cutaneous lymphomas other than mycosis fungoides in Singapore: a clinicopathological analysis using recent classification systems

BACKGROUND: Cutaneous lymphomas other than mycosis fungoides (MF) are a heterogeneous group with wide variations in clinical presentation, biological behaviour and prognosis. New classification systems have been designed or proposed in recent years, with well-defined disease entities and emphasis on the importance of site. OBJECTIVES: This study aims to analyse a series of non-MF lymphomas in an institution-based dermatological setting in Singapore, based on the European Organization for Research and Treatment of Cancer (EORTC) classification and the World Health Organization (WHO) classification. A secondary objective is to highlight the clinical utility of both classification systems. PATIENTS AND METHODS: Forty cases diagnosed over a 12-year period were examined by immunohistochemistry with antibodies targeting CD3, CD4, CD5, CD8, CD20, CD30, CD43, CD45RO, CD56 and CD68 in paraffin-embedded specimens. The immunohistological diagnosis was correlated with the clinical presentation and staging investigations for the final diagnosis and the course of disease recorded. RESULTS: Non-MF T-cell lymphomas presenting in the skin comprised 31 cases (78%) and were 3(1/2) times more common than B-cell lymphomas, which comprised nine cases (22%). The common subtypes were lymphomatoid papulosis, CD30+ large cell cutaneous T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma. The commonly ascribed B-cell pattern with infiltrates in the mid and deep dermis and perivascular spaces was seen in 60% of T-cell lymphomas. Overall, there were equal numbers of primary cutaneous T-cell lymphomas and those due to concurrent or secondary cutaneous lymphoma. Five of six cases of subcutaneous panniculitis-like T-cell lymphoma had concurrent cutaneous and systemic involvement and their median survival was 7 months. CONCLUSIONS: The predominance of cutaneous T-cell lymphomas in this case series closely matched that reported from east Asia; cutaneous B-cell lymphomas are much less common than in Europe. The EORTC classification, which is designed only for primary cutaneous lymphomas, should be used in conjunction with the WHO classification because of the high prevalence of cutaneous lymphomas as the secondary site of disease from systemic lymphoma. In addition, subcutaneous panniculitis-like T-cell lymphoma is a primary cutaneous lymphoma where systemic involvement is common at initial presentation. We propose full immunophenotyping and complete clinical evaluation with staging investigations for all patients presenting with cutaneous lymphomas other than MF.     

Primary cutaneous diffuse large B-cell lymphoma of the leg according to the new WHO-EORTC classification. Two cases

Primary cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders characterized by skin involvement with no evidence of systemic disease at the time of diagnosis. Their clinical behavior is generally indolent, and only occasionally is the development of extracutaneous disease observed. Since the 1980s, primary cutaneous B-cell lymphomas have been considered a specific group of lymphomas, differentiated from both T-cell lymphomas and from secondary cutaneous B-cell lymphomas. Both the EORTC and the WHO have proposed alternative classifications for these entities, with significant discrepancies that were finally resolved through the development of a new classification (WHO-EORTC classification for cutaneous lymphomas), which standardizes criteria that had previously been different. We present two new cases of primary cutaneous diffuse large B-cell lymphoma of the leg according to the new classification.     

Characteristics of cutaneous lymphomas in Osaka, Japan (1988-1999) based on the European Organization for Research and Treatment of Cancer classification

Based on accumulating information, European investigators proposed a new classification for primary cutaneous lymphomas known as the European Organization for Research and Treatment of Cancer (EORTC) classification. The clinical utility of this classification in Japanese cases has not been evaluated. Material from 65 patients with cutaneous lymphomas (48 with primary disease and 17 with secondary disease) who were admitted to Osaka University Hospital during the period 1988 through 1999 was reviewed. Immunohistochemical analysis was performed in all cases. Cutaneous T-cell lymphoma (CTCL) comprised mycosis fungoides (15 cases), Sézary syndrome (1 case), lymphomatoid papulosis (5 cases), large cell CTCL (13 cases), pleomorphic small- or medium-sized CTCL (2 cases), and cutaneous natural killer /T-cell lymphoma (4 cases). B-cell lymphomas comprised 7 cases of follicle center cell lymphoma and 1 case of diffuse large B-cell lymphoma of the leg. Each category of disease in the EORTC scheme showed its characteristic features in our series. Five of 13 large cell CTCL cases were positive for CD30, and 5 were negative. The 5-year survival rate of patients with large cell CTCL CD30+ disease was 100% and that of patients with CD30- disease was 0%. (p > 0.1). Only 1 of 7 CTCL cases expressing CD30 was ALK-1+, and all 7 cases showed a favorable clinical course. The EORTC classification is effective in dealing with Japanese cases of cutaneous lymphomas.     

The protean spectrum of non-Hodgkin lymphomas with prominent involvement of subcutaneous fat

BACKGROUND: Subcutaneous T-cell lymphoma (STCL) represents a controversial entity and a confused concept in the field of cutaneous T-cell lymphomas (CTCLs). Recently, alpha/beta+/CD8+ STCL has been recognized by the new World Health Organization (WHO)-European Organization for Research and Treatment of Cancer (EORTC) classification of primary cutaneous lymphomas as a distinct entity in the group of CTCLs. OBSERVATIONS: We reviewed a series of 53 biopsies from 26 patients (F : M = 19:7; median age: 48; range 18-87) of cutaneous B- and T-cell lymphomas characterized by prominent involvement of the subcutaneous tissue. We could classify our cases according to the following seven categories--(i) STCL: n = 16; (ii) extranodal NK/T-cell lymphoma, nasal type: n = 2; (iii) cutaneous gamma/delta T-cell lymphoma: n = 2; (iv) anaplastic CD30+ large T-cell lymphoma: n = 1; (v) diffuse large B-cell lymphoma, secondary cutaneous: n = 3; (vi) lymphoplasmacytic lymphoma, secondary cutaneous: n = 1; (vii) specific cutaneous manifestations of myelogenous leukemia: n = 1. CONCLUSIONS: We demonstrated the protean nature of lymphomas with prominent involvement of the subcutaneous fat tissues. The term STCL should be restricted to a homogeneous group of cases characterized morphologically by an exclusive involvement of subcutaneous tissues, immunohistochemically by a T-cytotoxic alpha/beta phenotype, and biologically by a relatively good prognosis.     

World Health Organization classification of hematopoietic and lymphoid tissues: implications for dermatology

The new World Health Organization (WHO) classification of hematopoietic and lymphoid malignancy represents the first worldwide consensus document on the classification of lymphoma/leukemia. Its aim is to supercede all existing classification systems, including the Revised European American Classification (REAL), and the organ-based classification of cutaneous lymphoma proposed in 1997 by the European Organization for Research and Treatment of Cancer (EORTC) cutaneous lymphoma project group. This article compares the REAL, EORTC, and WHO classifications with particular reference to cutaneous lymphoma. It identifies those entities that have been adopted from the EORTC classification, and illustrates important new entities in the category of cytotoxic T-/NK-cell lymphomas that characteristically present in the skin or subcutaneous tissue. However, WHO is not an organ-based classification and some categories (eg follicular B-cell lymphoma and peripheral T-cell lymphoma) include both cutaneous and systemic diseases, and these may have very different prognoses. It is, therefore, important that cancer registries are capable of recording sites of involvement for both B- and T-cell lymphomas so that the incidence and prognosis of cutaneous lymphomas can be established from national data sets in future years.     

Relative frequency of the different types of cutaneous T cell and natural killer cell lymphomas in Korea based on the proposed WHO classification and the EORTC classification

The R.E.A.L. classification was largely adopted recently by the proposed WHO classification. The usefulness of this classification in cutaneous T cell and natural killer (NK) cell lymphomas in Korea was evaluated compared to that of the European Organization for Research and Treatment of Cancer (EORTC) classification. Overall, 78 patients with cutaneous T cell and NK cell lymphomas were diagnosed in Asan Medical Center in the 1990's. The clinical records, slides of H&E and immunohistochemical stainings were reviewed. By the proposed WHO classification, mycosis fungoides (20 cases), lymphomatoid papulosis (13 cases), nasal type NK/T-cell lymphoma (10 cases), CD30+ anaplastic large cell lymphoma (8 cases), subcutaneous panniculitis-like T-cell lymphoma (6 cases), peripheral T-cell lymphoma, unspecified (3 cases), Sézary syndrome (1 case) and blastic NK cell lymphoma (1 case) comprised the primary cases. Secondary or undetermined cases included peripheral T-cell lymphoma, unspecified (10 cases), nasal type NK/T-cell lymphoma (5 cases), and angioimmunoblastic T-cell lymphoma (1 case). EORTC classification for cutaneous T cell and NK cell lymphomas did not include nasal and nasal type NK/T-cell lymphomas, unspecified non-pleomorphic T-cell lymphoma, undetermined cases among primary or secondary ones and some rare types of skin lymphomas which can be classified by WHO. The WHO classification is more useful for skin lymphomas in Korea since it encompassed all the various types of skin T cell and NK cell lymphomas in Korea.     

Solitary primary cutaneous CD30+ large cell lymphoma of natural killer cell phenotype bearing the t(2;5)(p23;q35) translocation and presenting in a child

Primary cutaneous CD30+ large cell lymphoma is an unusual tumor most commonly seen in adults. Most of these lymphomas are of T-cell origin and carry a good prognosis. We present the case of a 4-year-old girl with stage IEA CD30+ large cell lymphoma with a CD56+ natural killer cell phenotype and the t(2;5)(p23;q35) translocation. After excision, the patient has been free of disease for 44 months. Primary cutaneous CD30+ large cell lymphoma is uncommon in children. To our knowledge, primary cutaneous CD30+ natural killer type lymphoma has not been reported previously. The indolent behavior of this tumor indicates its similarity to other primary cutaneous CD30+ large cell lymphomas and its difference from other CD56+ lymphomas involving the skin, which often exhibit an aggressive clinical course. Cases such as this one illustrate why the use of a single, or even a few, immunohistochemical stains can be misleading in regard to lymphoma classification and prognostication.     

Linfomas cutáneos. Parte II: otros linfomas cutáneos

Primary cutaneous T-cell lymphomas other than mycosis fungoides, Sézary syndrome, and lymphoproliferative CD30⁺ disorders are few, accounting for less than 5% of all cutaneous lymphomas. A cytotoxic phenotype is characteristic of these tumors, and their clinical behavior is usually aggressive. Patients often present with extracutaneous symptoms or develop them shortly after diagnosis. Management is usually multidisciplinary, and intensive systemic therapy and bone marrow transplantation should be considered. Cutaneous B-cell lymphomas account for approximately 30% of primary cutaneous lymphomas. They make up a heterogeneous group of tumors that have different clinical and pathological features. Clinical course also varies. Presenting as papules, nodules, or tumors of variable reddish–violaceous coloring, the lesions may be solitary or multiple and occasionally form clusters. There may also be generalized lesions, present at multiple sites on the trunk, head, or extremities. Three well-defined groups of primary cutaneous lymphoma have been reported: follicle center lymphoma; marginal zone lymphoma, which follows an indolent course; and a diffuse large B-cell lymphoma, leg type, which follows an aggressive course.     

Systemische Therapie kutaner Lymphome

The management of patients with primary cutaneous lymphomas requires first of all a diagnostic work-up in order to differentiate between patients with nodal non-Hodgkin lymphomas with cutaneous manifestations and those with primary cutaneous lymphomas. In the latter an exact diagnosis of the type of cutaneous lymphoma has to be determined due to varying prognoses between the types of primary cutaneous lymphomas. In general, cutaneous lymphoma patients in early stages of disease can be treated successfully with skin-directed therapies. More advanced stages and some aggressive types like primary cutaneous diffuse large B-cell lymphoma, leg type or the leukemic variant of cutaneous T-cell lymphoma, the Sézary syndrome, require systemic treatment. The current recommendations regarding systemic therapy of patients with primary cutaneous lymphomas are reviewed.     

Clinicopathologic reassessment of non-mycosis fungoides primary cutaneous lymphomas during 17 years

BACKGROUND: New classification systems have recently been proposed for primary cutaneous lymphomas (PCLs). The aim of our study was to evaluate the applicability and significance of the new classification systems to the diagnosis and management of non-mycosis fungoides (non-MF) PCL. METHODS: Immunohistochemical restaining, histological reclassification, and clinical follow-up of all new non-MF PCL cases during 17 consecutive years were performed. The histological reclassification was performed according to the Revised European-American Lymphoma (REAL) classification, except for lymphomatoid papulosis (Lyp), which was included as an indolent lymphoma, according to the European Organization for the Research and Treatment of Cancer (EORTC) classification. RESULTS: During the period 1983-99, 251 new PCL cases were seen, 213 (85%) of which were MF and Sézary syndrome (eight cases), and 38 (15%) of which were non-MF. Of the latter, 20 (53%) were B-cell lymphomas, including eight (40%) follicle center lymphoma, follicular (FCLF), eight (40%) marginal zone lymphoma (MZL), two (10%) diffuse large cell lymphoma, and two (10%) unclassifiable cases. Most or all of the lesions did not stain for CD10, CD43, and bcl-2 protein, and immunostaining for kappa and lambda immunoglobulin light chain restriction was much more useful diagnostically in MZL. Of the 18 primary non-MF cutaneous T-cell lymphomas, 13 (72%) were Lyp, all of which were type A, four (22%) were CD30+ anaplastic large cell lymphoma, and one (6%) was natural killer (NK)/T-cell lymphoma. Except for the NK/T-cell lymphoma, all the other non-MF PCLs had an indolent course. CONCLUSIONS: A minority of the routinely diagnosed PCLs are non-MF, equally divided between B- and T-cell lymphomas. The REAL classification is applicable to the majority, although it does not include entities such as Lyp; the clinical correlations are not as obvious because most of the non-MF PCLs tend to have a relatively indolent course.     

New aspects in the biology of cutaneous B-cell lymphomas

Immunologic and molecular genetic studies greatly contributed to a better understanding and interpretation of the distinct clinico-pathologic features of primary cutaneous B-cell lymphomas (CBCL), which are the basis for the consensus WHO-EORTC classification. There is increasingly accumulating evidence that these well defined clinico-pathologic entities of CBCL have specific immunologic and molecular features, which further support their nosologic categorization as well as either interesting similarities with other extranodal B-cell lymphomas or definite peculiarities as compared to nodal B-cell lymphomas of similar histotype (specifically, follicle center lymphoma and diffuse large B-cell lymphoma).     

Rimming of adipocytes by neoplastic lymphocytes: a histopathologic feature not restricted to subcutaneous T-cell lymphoma

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin presenting with histopathologic features simulating those of a lobular panniculitis. The presence of neoplastic T-lymphocytes forming a rim around the individual fat cells in the subcutaneous lobules, so-called "rimming" of adipocytes, is considered a characteristic morphologic feature of this type of cutaneous lymphoma. In this study we reviewed a series of 45 biopsy specimens of primary and secondary cutaneous B- and T-cell lymphomas and one of myeloid leukemia involving the subcutaneous tissues and showing rimming of adipocytes (subcutaneous panniculitis-like T-cell lymphoma: n = 16; mycosis fungoides, tumor stage: n = 3; aggressive epidermotropic CD8(+) T-cell lymphoma: n = 2; cutaneous gamma/delta T-cell lymphoma: n = 4; extranodal NK/T-cell lymphoma, nasal type: n = 4; cutaneous medium-large pleomorphic T-cell lymphoma, NOS: n = 5; CD4(+)/CD56(+) hematodermic neoplasm (blastic NK-cell lymphoma): n = 7; secondary cutaneous large B-cell lymphoma: n = 3; secondary cutaneous lymphoplasmacytic lymphoma: n = 1; specific cutaneous manifestations of acute myelogenous leukemia: n = 1). We could demonstrate that rimming of adipocytes by neoplastic cells can be recognized not only in subcutaneous panniculitis-like T-cell lymphoma, but also in several different entities of malignant lymphoma with skin involvement. Precise classification of cases with prominent involvement of the subcutaneous tissues can only be achieved upon precise correlation of clinicopathologic and phenotypic features. Rimming of adipocytes should not be considered specific of subcutaneous panniculitis-like T-cell lymphoma.     

Retrospective analysis of 133 patients with cutaneous lymphomas from a single Japanese medical center between 1995 and 2008

In 2008, a revised World Health Organization (WHO) system of hematological neoplasm classification was promulgated. Between January 1995 and December 2008, 133 new patients with cutaneous lymphomas were seen at the dermatology clinic of Okayama University Hospital. All patients were re-classified according to the revised WHO system. The incidence rates were analyzed and the survival was estimated. Of 133 patients, 106 (79.7%) had primary cutaneous lymphomas (PCLs) and 27 (20.3%) were skin invasion from extracutaneous origin of systemic lymphoma. Compared with several reports from western countries, "mature T-cell and NK-cell neoplasms" was frequent in this study (87% vs. 77 or 72%) because of the occurrence of adult T-cell leukemia/lymphoma (ATLL) and "extranodal NK/T cell lymphoma, nasal type", with less frequent occurrence of "mature B-cell neoplasms" (13% vs. 23 or 28%). Estimated survival of patients with mycosis fungoides was favorable (5-year survival rate 90.6%), but that of the patients with primary cutaneous anaplastic large cell lymphoma (C-ALCL) was extremely less favorable than previously reported (5-year survival rate of 47.4%).     

Cutaneous natural killer/T-cell lymphoma

Lymphomas are classified as either Hodgkin's or non-Hodgkin's. The 2 subtypes of non-Hodgkin's lymphoma that can present primarily in the skin are cutaneous T-cell lymphoma and cutaneous B-cell lymphoma, both of which tend to be low-grade malignant neoplasms. Recently another distinct subtype of lymphoma was discovered, the natural killer (NK)/T-cell lymphoma, which can involve the skin in a primary or secondary fashion. The NK/T-cell subtype of lymphoma is characterized by the expression of the NK-cell antigen CD56. These CD56(+) lymphomas are further subdivided into nasal NK/T-cell lymphomas that commonly present as midfacial destructive disease and non-nasal NK/T-cell lymphomas that often arise in extranodal locations, including the skin. We report a case of aggressive NK-cell leukemia/lymphoma with numerous secondary cutaneous lesions and review the clinical and histopathologic spectrum of non-nasal CD56(+) lymphomas, with an emphasis on the dermatologic findings.     

Use of an expanded immunohistochemical panel to distinguish cutaneous Hodgkin lymphoma from histopathologic imitators

In lymph nodes, classical Hodgkin lymphoma can typically be distinguished from non-Hodgkin lymphoma (NHL) by the presence of Hodgkin and Reed-Sternberg cells that co-express CD30 and CD15. However, anaplastic large cell lymphoma (ALCL) and diffuse large B-cell lymphoma (DLBCL) can show identical features, and some cases of classical Hodgkin lymphoma lack CD15 expression, rendering them difficult to differentiate from CD30-positive NHL. The differential diagnosis of cutaneous Hodgkin lymphoma similarly includes ALCL and DLBCL, and, additionally, tumors of mycosis fungoides. Recent studies have shown that classical Hodgkin lymphoma is of B-cell origin in virtually all cases, and shows at least focal weak expression of the B-cell marker PAX5 and often focal weak expression and no expression of the B-cell markers Oct-2 and BOB.1, respectively. All three of these markers are almost invariably absent in T-cell lymphomas and are strongly expressed in B-cell lymphomas. We report a 40-year-old man with classical Hodgkin lymphoma who developed cutaneous nodules. A biopsy from one revealed Hodgkin/Reed-Sternberg cells with a similar immunophenotype to the diagnostic lymph node biopsy, namely CD30+/CD15+, diffusely but weakly PAX5+, focally weakly Oct-2+ and lacking BOB.1 expression, thereby confirming a diagnosis of cutaneous Hodgkin lymphoma. To our knowledge, this is the first report of the expression pattern of the combination of PAX5, Oct-2 and BOB.1 in the context of cutaneous involvement by Hodgkin lymphoma.     

Cutaneous peripheral T-cell lymphoma of cytotoxic phenotype mimicking extranodal NK/T-cell lymphoma

Cutaneous peripheral T-cell lymphoma unspecified is a rare neoplasm that is infrequently associated with Epstein-Barr virus (EBV) infection. In contrast, extranodal natural killer (NK)/T-cell lymphoma, although also rare, is known to be strongly associated with EBV and occurs most commonly in the nasal region. We report the case of a 55-year-old male who presented with fever and an indurated cutaneous plaque with ulceration. This cutaneous neoplasm showed diffuse dermal lymphomatous infiltration and tumor necrosis, with neoplastic cells expressing CD2, cytoplasmic CD3 (CD3ε), CD8, CD16, CD30, T-cell intracellular antigen-1, and granzyme B but not CD56, BF1, or T-cell receptor (TCR) δ1. Furthermore, the tumor cells were noted to be diffusely positive for EBV by in situ hybridization. A monoclonal TCR gene rearrangement was demonstrated. The disease showed an aggressive clinical course, and the patient died within 3 weeks of diagnosis without complete staging or chemotherapy. According to the 2005 World Health Organization/European Organization for Research and Treatment of Cancer scheme for cutaneous lymphoma and the 2008 WHO classification for lymphoid neoplasms, our case would have been classified as a nasal type extranodal NK/T-cell lymphoma with T-cell lineage. However, the expressions of CD8 and CD16, in addition to a monoclonal TCR gene rearrangement, are unusual findings in NK/T-cell lymphoma, and we believe such a phenotype/genotype should be more appropriately classified as an EBV-positive peripheral T-cell lymphoma, unspecified with a cytotoxic phenotype. Detailed clinicopathologic and molecular studies of similar cases may shed light on the prognostic impact of NK vs. T-cell lineage on extranodal NK/T-cell lymphomas.     

Kutane Lymphome

Cutaneous lymphomas are a heterogeneous group of clonal proliferations of T and B lymphocytes with various clinical manifestations and prognosis. The new EORTC WHO classification of cutaneous T- and B-cell lymphomas provides a uniform nomenclature based on clinical, histologic, cytologic and molecular biological features. Accurate classification is a prerequisite for uniform therapeutic concepts. For office-based dermatologist, more than 50% of the therapies deal with classic forms of cutaneous T-cell lymphomas, type mycosis fungoides. In recent years the paradigm for the therapy of cutaneous T-cell lymphomas has changed. Since early aggressive treatment with cytostatic agents does not increase the response rate or overall survival, a commonly accepted stage-adapted therapy is recommended. In this review the current status of the therapy of cutaneous lymphoma is described in detail.     

Primary diffuse large B-cell lymphoma of the skin

B-cell lymphomas of the skin represent a wide spectrum of disorders. We present the microscopic and immunohistochemical features of a primary cutaneous B-cell lymphoma and classify it either as a diffuse large B-cell lymphoma or an indolent follicle-center-cell lymphoma according to the updated REAL/WHO system and the EORTC classification respectively. The former system is widely recommended; nevertheless, the EORTC system is also worth considering when planning management, because most data on long-term outcomes are based on it and it is considered to offer remarkable prognostic information.