Large cell transformation is an independent prognostic factor in Sézary syndrome: a retrospective analysis of 117 cases

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.

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

Blood ◽

10.1182/blood.v92.4.1150.416k04_1150_1159 ◽

1998 ◽

Vol 92 (4) ◽

pp. 1150-1159 ◽

Cited By ~ 5

Author(s):

Eleni Diamandidou ◽

Maria Colome-Grimmer ◽

Luis Fayad ◽

Madeleine Duvic ◽

Razelle Kurzrock

Keyword(s):

Mycosis Fungoides ◽

Median Survival ◽

Cell Transformation ◽

Large Cell ◽

Lactic Dehydrogenase ◽

Cumulative Probability ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Large Cell Transformation ◽

American Society

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.

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CD25+ folliculotropic Sézary syndrome with CD30+ large cell transformation

Australasian Journal of Dermatology ◽

10.1111/ajd.12000 ◽

2012 ◽

Vol 55 (1) ◽

pp. e4-e8 ◽

Cited By ~ 4

Author(s):

Min Soo Jang ◽

Dong Young Kang ◽

Sang Hwa Han ◽

Jong Bin Park ◽

Sang Tae Kim ◽

...

Keyword(s):

Cell Transformation ◽

Large Cell ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Large Cell Transformation

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1096P Clinicopathologic risk factors for large cell transformation in patients with Sezary syndrome

Annals of Oncology ◽

10.1016/j.annonc.2020.08.1220 ◽

2020 ◽

Vol 31 ◽

pp. S742

Author(s):

R. Bardhi ◽

N.K. Jairath ◽

R. Jairath ◽

J. Runge ◽

R. Bledea ◽

...

Keyword(s):

Risk Factors ◽

Cell Transformation ◽

Large Cell ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Large Cell Transformation

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Large Cell Transformation of Sézary Syndrome

American Journal of Clinical Pathology ◽

10.1309/4e9v-hby1-tmbm-k3by ◽

2000 ◽

Vol 113 (6) ◽

pp. 792-797 ◽

Cited By ~ 13

Author(s):

Chi-chiu So ◽

Kit-fai Wong ◽

Lisa L.P. Siu ◽

Yok-lam Kwong

Keyword(s):

Cell Transformation ◽

Large Cell ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Large Cell Transformation

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A Case of Refractory Sézary Syndrome With Large-Cell Transformation Responsive to Brentuximab Vedotin

JAMA Dermatology ◽

10.1001/jamadermatol.2013.5741 ◽

2014 ◽

Vol 150 (2) ◽

pp. 210 ◽

Cited By ~ 8

Author(s):

Kristen Corey ◽

Deborah Cook ◽

Jessica Bekker ◽

Emiliano Mugnaini ◽

Julie H. Lin

Keyword(s):

Cell Transformation ◽

Large Cell ◽

Brentuximab Vedotin ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Large Cell Transformation

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Cytogenetic findings in terminal large cell transformation in a case of sézary syndrome

Cancer Genetics and Cytogenetics ◽

10.1016/0165-4608(92)90144-w ◽

1992 ◽

Vol 58 (1) ◽

pp. 100-104 ◽

Cited By ~ 11

Author(s):

Elvira D'Alessandro ◽

Andrea De Pasquale ◽

Claudio Ligas ◽

Maria Luisa Lo Re ◽

Mario Di Cola ◽

...

Keyword(s):

Cell Transformation ◽

Large Cell ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Large Cell Transformation

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Expression of Thymidine Phosphorylase in Lymph Nodes Involved with Mycosis Fungoides and Sézary Syndrome

Advances in Hematology ◽

10.1155/2011/875135 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6

Author(s):

Xingcao Nie ◽

Rekha Bhat ◽

Essel Dulaimi Al-Saleem ◽

Eric C. Vonderheid ◽

J. Steve Hou

Keyword(s):

T Cells ◽

T Cell ◽

Lymph Nodes ◽

Mycosis Fungoides ◽

Thymidine Phosphorylase ◽

Cell Transformation ◽

Large Cell ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Thymidine Phosphorylase Expression

Thymidine phosphorylase may be overexpressed in both neoplastic cells and tumor stromal cells in a variety of malignancies. Our study explores thymidine phosphorylase expression in lymph nodes (LNs) from patients with mycosis fungoides (MF) or Sézary syndrome (SS). In MF/SS, the LNs may have a pathologic diagnosis of either dermatopathic lymphadenopathy (LN-DL) or involvement by MF/SS (LN-MF). We performed immunohistochemical staining on MF/SS lymph nodes using antibodies to thymidine phosphorylase, CD68, CD21, CD3, and CD4. In both LN-DL and benign nodes, thymidine phosphorylase staining was noted only in macrophages, dendritic cells, and endothelial cells. In LN-MF, thymidine phosphorylase expression was also noted in subsets of intermediate to large neoplastic T cells. Concurrent CD68, CD21, CD3, and CD4 staining supported the above observations. Similar results were noted in the skin and in LN-MF with large cell transformation. Other T-cell lymphomas were also examined (total 7 cases); only enteropathy-type T-cell lymphoma (1 case) showed TP positivity in neoplastic T lymphocytes. We demonstrated that thymidine phosphorylase staining is present in neoplastic T cells in mycosis fungoides. The exact mechanism needs further investigation.

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Risk Factors for Large Cell Transformation in Patients with Sezary Syndrome

10.1101/2020.06.01.20119669 ◽

2020 ◽

Author(s):

Neil K. Jairath ◽

Ruple Jairath ◽

Redina Bardhi ◽

John S. Runge ◽

Ramona Bledea ◽

...

Keyword(s):

Risk Factors ◽

Flow Cytometry ◽

Cell Count ◽

Cell Transformation ◽

Large Cell ◽

Langerhans Cell ◽

Sézary Syndrome ◽

Cell Hyperplasia ◽

Unit Increase ◽

Large Cell Transformation

AbstractObjectivesLarge cell transformation (LCT) of Sezary Syndrome (SS) is associated with an aggressive clinical course. To date, there are no rigorous studies identifying risk factors for the development of this phenomenon. We aim to characterize the clinicopathologic risk factors that may predispose patients with SS to develop LCT in the largest such study to date that the authors have identified.Materials/MethodsWe retrospectively evaluated all SS patient records available in the Michigan Medicine Cancer Registry from 2010–2019. The Mann-Whitney U test and Fisher exact test were used to compare age, sex, race, time to diagnosis, stage, total body surface area (TBSA) involvement, pathologic features, complete blood counts, flow cytometry data, and T cell receptor rearrangements. The Kaplan-Meier method and log-rank test were used to assess overall survival (OS). Univariate analyses were conducted for endpoints of LCT and OS and visualized with Forest plots using the “survival” and “forestplot” packages in R.ResultsOf the 28 SS patients included in the analysis, eight patients with LCT were identified, and 20 without nonlarge cell transformation (NLCT). Mean peak LDH before LCT (p = 0.0012), mean maximum TBSA involvement before diagnosis of LCT (p = 0.0114), absolute CD8+ cell count on flow cytometry or on biopsy at diagnosis of SS (p = 0.0455), presence of Langerhans cell hyperplasia (p = 0.0171), and presence of ulceration on biopsy (p = 0.0034) were clinicopathologic variables identified as differing significantly between the two groups. On univariate analysis, increased TBSA involvement (HR 1.043 per unit increase, 95% CI 1.001 – 1.081, p = 0.018) and increased peak LDH prior to LCT diagnosis (HR 1.002 per unit increase, 95% CI 1.001 – 1.003, p = 0.002) were identified as poorly prognostic, while unit increase in CD8+ absolute cell count at diagnosis of SS (HR 0.988, 95% CI 0.976 – 0.999, p = 0.041) was identified as protective for development of LCT. There was no survival difference identified between patients with “High” vs. “Low” CD8+ cell counts, or between LCT and NLCT groups.ConclusionsMaximum TBSA involvement, peak LDH, presence of ulceration, Langerhans cell hyperplasia, and decreased levels of CD8+cells in the peripheral blood may predict the development of LCT in patients with SS.

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Induction and Maintenance Therapy for Patients with Mycosis Fungoidus (MF) and Sezary Syndrome (SS) in Large Cell Transformation Phase.

Blood ◽

10.1182/blood.v114.22.4758.4758 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4758-4758

Author(s):

Yulia E Vinogradova ◽

Irina Lucenko ◽

Irina Kaplansky ◽

Lyuba Varticovski ◽

Nikita E Shklovskiy-Kordi ◽

...

Keyword(s):

T Cell ◽

Maintenance Therapy ◽

Tumor Cells ◽

Partial Remission ◽

Cell Transformation ◽

Cell Lymphoma ◽

Large Cell ◽

T Cell Lymphoma ◽

Sézary Syndrome ◽

Large Cell Transformation

Abstract Abstract 4758 Aim To determine the frequency of transformation of cutaneous T-cell tumors (CTCL) and effect of different therapies. Materials and methods Retrospective analysis of treatment results for 68 patients with two types of CTCL, MF and SS, selected from 263 patients T-cell lymphoma/leukemia treated at NCH during 9 years. All 68 patients have CD 3 +, CD 4+, CD 7-, CD 8-, CD 30- immunophenotype and T-cell clonality (rearranged genes for T-cell receptor). MF was diagnosed in 48 patients (24 men, 24 women) with median age 52 years (26 - 77), SS in 20 patients (12 men, 8 women), median age 61 years (23 -87). Half of the MF patients started surveillance at III - IV stages, 15 of 20 patients with SS - at stage IV. Treatment of CTCL in the indolent phase was conducted in accordance with their stage: monochemotherapy (leukeran or methotrexate) and biologically active agents (interferons, retinoids, monoclonal antibody) were used. Appearance of transformation to large cell lymphoma was consistent with tumor progression as determined by presence of two or more of the following: 1. rapid growth of tumors in MF or leukemization in SS; 2. presence of large anaplastic cells in blood or tumor biopsy; 3. increase in expression of Ki-67 (10-70%); 4. appearance of activation markers (CD30, CD25) in tumor cells, and 5. loss of certain linear T-cell markers. For treatment of patients in large cell transformation phase Promace-Cytabom or FNC protocols were used in 7 patients. Five patients received A-CHOP-14 (with alemtuzumab) and subsequent maintenance therapy (methotrexate 20 mg per week, 6-mercaptopurine 50-100 mg/day in combination with alpha interferon 3 million daily). Results and Discussion The overall median time of observation (before and during treatment) in 48 patients with MF was 96 months (8-264). For 13 patients who died it was 76 months (8-264), mortality rate was 27%. The overall median observation (before and during treatment) in 20 patients with SS was 60 months (6-123), for 8 who died, it was 62 months (6-94), mortality 40%. The median observation for treatment of MF was 30 months (from 3-122) for the SS, it was 18 months (1 - 85). Restraining aggressive therapy for an indolent process resulted in complete or partial remission, while maintaining a good quality of life. Large cell transformation phase was observed in 12 patients (7 of 48 patients with MF (14.5%) and 5 of 20 patients with SS (25%). Seven of the 12 patients died within 2-4 months due to septic complications during Promace-Cytabom or FNC protocols. The remaining 5 patients received A-CHOP-14 (6-7 courses) which reduced tumor formation and /or leukemization. However, the persistence of patches, plaque or erythrodermia was the reason for maintenance therapy. This combination led to further regression of skin manifestations and full or partial remission within 4-12 months. Conclusion Because of the lack of a generally accepted treatment for GM and SS in Large Cell Transformation phase, even small successes should be discussed. The effectiveness of combining of polychemotherapy with maintenance therapy may be effective due to the presence of several distinct clones of tumor cells with different properties. Keywords: treatment of cutaneous T-cell lymphoma, Mycosis Fungoidus, Sezary Syndrome, Large Cell Transformation Phase, immunohistochemical markers of T-cell lymphomas. Disclosures: No relevant conflicts of interest to declare.

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