The topic of follicular lymphomas, and more specifically, the relationship of histologic subtypes of follicular lymphomas to outcome, has periodically been the focus of extensive debate.<sup>1 Anderson T. Nodular mixed cell lymphoma: Is there a potential for prolonged disease free survival and cure? Controversies in the Management of Lymphomas 1983 ; 225

Cliccare qui per andare alla sezione Riferimenti, 7 Glick J.H., Orlow E.L. Nodular mixed lymphoma: Failure to demonstrate prolonged disease free survival and cure Controversies in the Management of Lymphomas 1983 ; 239

Cliccare qui per andare alla sezione Riferimenti, 16 Longo D.L. What's the deal with follicular lymphomas? J Clin Oncol 1993 ;  11 : 202

Cliccare qui per andare alla sezione Riferimenti</sup> The results of such discussions are important to practicing clinicians with regard to patient care by setting expectations of prognosis and guiding therapy. Currently, the Working Formulation system of classifying non-Hodgkin's lymphomas provides the framework from which clinicians translate lymphoma histologic subtypes into outcome expectations and therapeutic strategies.<sup>26 The Non-Hodgkin's Lymphoma Pathologic Classification Project National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: Summary and description of a working formulation for clinical usage Cancer 1982 ;  49 : 2112

Cliccare qui per andare alla sezione Riferimenti</sup> According to the Working Formulation, patients with low-grade histologic subtypes are generally thought to be incurable and are treated for palliation of symptoms related to lymphoma.<sup>4 Dana B.W., Dahlberg S., Nathwani B. , e al. Long-term follow-up of patients with low grade malignant lymphomas treated with doxorubicin-based chemotherapy or chemoimmunotherapy J Clin Oncol 1993 ;  11 : 644

Cliccare qui per andare alla sezione Riferimenti, 10 Horning S.J., Rosenberg S.A. The natural history of initially untreated low-grade non-Hodgkin's lymphoma N Engl J Med 1984 ;  311 : 1471  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> Low-grade histologic subtypes of follicular lymphoma include follicular small cleaved-cell and follicular mixed large- and small-cell types.<sup>26 The Non-Hodgkin's Lymphoma Pathologic Classification Project National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: Summary and description of a working formulation for clinical usage Cancer 1982 ;  49 : 2112

Cliccare qui per andare alla sezione Riferimenti</sup> Intermediate and high-grade histologic subtypes, on the other hand, are known to be potentially curable and are treated with aggressive doxorubicin-containing combination chemotherapy.<sup>6 Fisher R.I., Gaynor E.R., Dahlberg S. , e al. Phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate or high-grade non-Hodgkin's lymphoma: Results of SWOG-8516 (Intergroup 0067), the national high priority lymphoma study N Engl J Med 1993 ;  328 : 1002  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 24 Miller T.P., Jones S.E. Initial chemotherapy for clinically localized lymphomas of unfavorable histology Blood 1983 ;  62 : 413

Cliccare qui per andare alla sezione Riferimenti</sup> Follicular large-cell lymphoma is currently classified as an intermediate-grade histology and is usually treated accordingly with curative intent.<sup>2 Bartlett N.L., Dorfman R.F., Helpern J., Horning S.J. Follicular large-cell lymphoma: Intermediate or low grade? J Clin Oncol 1994 ;  12 : 1349

Cliccare qui per andare alla sezione Riferimenti, 6 Fisher R.I., Gaynor E.R., Dahlberg S. , e al. Phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate or high-grade non-Hodgkin's lymphoma: Results of SWOG-8516 (Intergroup 0067), the national high priority lymphoma study N Engl J Med 1993 ;  328 : 1002  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 26 The Non-Hodgkin's Lymphoma Pathologic Classification Project National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: Summary and description of a working formulation for clinical usage Cancer 1982 ;  49 : 2112

Cliccare qui per andare alla sezione Riferimenti</sup> Some investigators have previously argued that follicular mixed large- and small-cell lymphomas also have a potential for cure and should also be treated with doxorubicin-containing chemotherapy.<sup>1 Anderson T. Nodular mixed cell lymphoma: Is there a potential for prolonged disease free survival and cure? Controversies in the Management of Lymphomas 1983 ; 225

Cliccare qui per andare alla sezione Riferimenti, 17 Longo D.L., Young R.C., Hubbard S.M. Prolonged initial remission in patients with nodular mixed lymphoma Ann Intern Med 1984 ;  100 : 651

Cliccare qui per andare alla sezione Riferimenti, 21 McLaughlin P., Fuller L.M., Velasquez W.S. Stage III follicular lymphoma: Durable remissions with a combined chemotherapy-radiotherapy regimen J Clin Oncol 1987 ;  5 : 867

Cliccare qui per andare alla sezione Riferimenti</sup>

Recently, a group of internationally known expert hematopathologists proposed a new classification system, the Revised European-American Lymphoma Classification (REAL).<sup>3 Chan J.K.C., Banks M., Clary M.L. , e al. A revised European-American classification of lymphoid neoplasms proposed by the International Lymphoma Study Group Am J Clin Pathol 1995 ;  103 : 543

Cliccare qui per andare alla sezione Riferimenti, 9 Harris N.L., Jaffe E.S., Stein H. , e al. A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group Blood 1994 ;  84 : 1361

Cliccare qui per andare alla sezione Riferimenti</sup> In that system, the distinction between follicular lymphoma subtypes is minimized. The authors suggest the term grade be used instead of distinct names, to better reflect the reality of a cytologic continuum.<sup>9 Harris N.L., Jaffe E.S., Stein H. , e al. A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group Blood 1994 ;  84 : 1361

Cliccare qui per andare alla sezione Riferimenti</sup> These investigators recognize that pathologists cannot reproducibly determine the proportion of large cells and, therefore, cannot reproducibly determine the histologic subtype of follicular lymphomas. This consensus decision to lump follicular subtypes will surely prompt another debate with regard to outcome relative to histology. In an attempt to test the clinical utility of the REAL proposal to lump follicular lymphoma subtypes, and to provide data for that debate, we have analyzed data from the Southwest Oncology Group (SWOG) including 389 patients with follicular lymphomas followed for up to 25 years.