Transformation of Mycosis Fungoides/Sezary Syndrome: Clinical Characteristics and Prognosis

Abstract

The occurrence of large cell transformation has been well documented in a subgroup of patients with mycosis fungoides/Sezary syndrome (MF/SS). However, because of the rarity of MF/SS, little is known about the influence of clinicopathologic features in predicting large cell transformation and about outcome in the transformed cases. We evaluated all patients with MF/SS who were registered in our clinic during the study period and for whom pathologic slides for review were available or could be obtained. Disease was classified as transformed if biopsy showed large cells (≥4 times the size of a small lymphocyte) in more than 25% of the infiltrate or if they formed microscopic nodules. Twenty-six patients with transformation were identified from a total of 115 evaluable cases with a diagnosis of MF/SS. The actuarial cumulative probability of transformation reached 39% in 12 years. The median time from diagnosis of MF/SS to transformation was 12 months (range, 0 to 128 months). Thirty-one percent of all patients with stage IIB-IV disease at presentation eventually transformed versus 14% of those with stage I-IIA (P= .03), with transformation being especially common in patients with tumors (T3), 46% of whom transformed. Combining elevated β2 microglobulin and lactic dehydrogenase (neither elevated v one or both elevated) was also predictive for transformation (P = .009). The median survival from initial diagnosis of MF/SS for the transformed patients was 37 months versus 163 months for the untransformed group (P = .0029). The median survival from transformation was 19.4 months (range, 2+ to 138 months). The following characteristics were associated with an inferior survival in transformed patients: (1) early transformation (<2 years from the diagnosis v ≥2 years; P = .011) and (2) advanced stage (IIB-IV v I-IIA; 2-year survival, 23% v 86%;P = .0035). We conclude that MF/SS patients with stages IIB-IV disease and, in particular, those with tumors have a high incidence of large-cell transformation. Patients with transformation have a relatively poor survival, especially if transformation occurs early (within 2 years) in the course of disease or if they are staged as IIB or higher. © 1998 by The American Society of Hematology.

Time course, clinical pathways, and long‐term hazards risk trends of disease progression in patients with classic mycosis fungoides

“…The development of SS (secondary SS13) during follow‐up was defined in the presence of erythroderma, palpable adenopathies, and peripheral blood involvement according to ISCL recommendations 3, 6, 15. Transformation into high‐grade lymphoma was defined based on the presence of > 25% of large cells in skin lesions 6, 9‐11. The pathologic diagnosis was made on the basis of the (dermato)pathologist report; no review of biopsy specimens was performed.…”

“…Clinical features are represented by long‐standing, scaly, patch lesions preferentially involving the buttocks and body areas infrequently exposed to sunlight (“bathing trunk”) and by a slow evolution over years from patches to plaques and eventually tumors or erythroderma 1‐3, 6‐8. Lymph node and visceral involvement, as well as large cell transformation,9‐11 usually occur in the late stages of the disease; moreover, patients with MF can develop typical manifestations of Sezary syndrome (SS),1‐3, 12 so‐called “secondary” SS 13. The prognostic relevance of the extent of skin involvement and extracutaneous localizations has been known since the 1970s, when the Mycosis Fungoides Cooperative Group classification was developed 7, 14.…”

Management of the primary cutaneous lymphomas

“…In one series of 115 patients (of which 26 transformed), the cumulative risk of MF large‐cell transformation was 39% at 12 years, with the risk of transformation related to the presence of stage IIB–IV (31% compared with 14%), tumour‐stage disease, elevated β2 microglobulin and elevated lactate dehydrogenase (LDH). In this study, the median survival from the diagnosis of transformation was only 19.4 months 14 . In another series of 45 patients with transformed disease, the median survival was 22 months; older patients (>60 years) and systemic spread following transformation was associated with a worse prognosis 15 .…”

“…Cutaneous tumours can develop either as increasing depth of the small atypical lymphocytes of MF or as a result of large‐cell transformation. Large‐cell transformation is defined as large cells (≥4× the size of a small lymphocyte) in more than 25% of the infiltrate or if these cells form microscopic nodules 14,15 . There is a variable incidence of 8–39% reported and it is associated with a very poor prognosis 14–16 .…”

“…Large‐cell transformation is defined as large cells (≥4× the size of a small lymphocyte) in more than 25% of the infiltrate or if these cells form microscopic nodules 14,15 . There is a variable incidence of 8–39% reported and it is associated with a very poor prognosis 14–16 . In one series of 115 patients (of which 26 transformed), the cumulative risk of MF large‐cell transformation was 39% at 12 years, with the risk of transformation related to the presence of stage IIB–IV (31% compared with 14%), tumour‐stage disease, elevated β2 microglobulin and elevated lactate dehydrogenase (LDH).…”