Mycosis Fungoides (MF), the most common subtype of CTCL, may be indolent with skin-only symptoms, but may progress to involve blood, lymph nodes, and viscera.5,6
Sézary Syndrome (SS), an aggressive subtype of CTCL, presents with high (B2) blood involvement and is associated with poor prognosis. Patients with Sézary Syndrome typically have erythroderma and intense pruritus. Lymph nodes may also be involved.5,7,8
CTCL can affect multiple disease compartments
NCCN Guidelines recommend consulting with multiple specialists with CTCL expertise (including hematologist-oncologists, dermatologists, and pathologists) for diagnosis and optimal patient management.1
Up to 1 in 3 patients with Mycosis Fungoides may experience disease progression within skin or to other compartments, including blood8,a
aBased on a survival outcomes and prognostic factors study that included 1502 patients with Mycosis Fungoides/Sézary Syndrome.
CTCL diagnosis & TNMB criteria
Blood classification is integral to diagnosis & staging
To determine a patient’s diagnosis and clinical stage, levels of involvement in 4 compartments are assessed: skin, lymph node, viscera, and blood. This is referred to as the TNMB classification.1
TNMB criteria are used to derive clinical stage1
Classifications omitted above: T0=absence of clinically significant skin lesions; Nx=clinically abnormal LN but no pathologic determination of representative LN; Mx=unable to determine by pathologic or imaging assessment; Bx=unable to quantify blood involvement according to agreed upon guidelines.
Blood classification for each level (B0, B1, B2, Bx) can further be characterized by TCR clone status, with A=clone negative or equivocal and B=clone positive with identical clone in the skin.
Atypical cells are defined as CD4+/CD26- or CD4+/CD7- cells.
Images for T1 and T2 courtesy of Oleg Akilov, MD, PhD. Images for T3 and T4 courtesy of Joan Guitart, MD.
Previously, only skin, lymph node, and viscera assessment were the recommended diagnostic criteria for Mycosis Fungoides and Sézary Syndrome. But in 2007, blood classification was added as an independent prognostic factor.9
Currently, blood is categorized into 3 levels based on the quantity of abnormal T-cells (Sézary cells) found. Blood can further be categorized by T-cell receptor (TCR) clone status to inform whether the predominant T-cell clone found in the blood and skin is identical.1
It is expected that patients with high blood tumor burden (B2) will have a clone in the blood that is identical to that in the skin. Nonidentical T-cell clones are often detected in peripheral blood with increasing age and are of unknown clinical significance.
Clinical staging of patients6
Blood can be involved even at early stages of Mycosis Fungoides
Blood involvement is always present in Sézary Syndrome, but it can occur even at early stages of Mycosis Fungoides. Because blood involvement is an independent prognostic factor, it is important to determine the baseline level at diagnosis—classified as B0-B23:
- B0: No blood involvement
- B1: Low blood involvement – may occur at any stage (except for IIIA)
- B2: High blood involvement – advanced disease, regardless of compartment involvement
TNMB classification for Mycosis Fungoides / Sézary Syndrome1
1 in 5 patients with early-stage (IA-IIA) Mycosis Fungoides have B1 blood involvement6
Based on a PROCLIPI database study that analyzed hematological data from 348 patients with early-stage Mycosis Fungoides.
Survival by blood involvement8,10
Blood involvement is associated with poorer outcomes
With increasing blood involvement, overall survival and disease-specific survival are reduced. And in patients with B2 blood involvement, there is a 4.6x greater risk of progression.8
The full significance of B1 level blood involvement remains the subject of further research.2
Median overall survival (years)
by blood classification, Talpur et al (N=1263)10
Accurate staging is essential for guiding treatment approach
For patients with Mycosis Fungoides or Sézary Syndrome, 5-year disease-specific survival drops considerably in advanced stages of disease. Accurately assessing disease stage can help inform prognosis.8
High blood involvement (B2) is always considered advanced disease, regardless of other compartment involvement, and must be staged accurately to inform prognosis and determine treatment approach.9
Factors that contribute to negative prognosis11:
- Higher level of blood involvement
- Higher T-stage
- Extracutaneous disease
- Identical T-cell clone in the skin and in the blood
- Male gender
- Older age
- Eosinophilia and lymph node involvement >N1/Nx
- Elevated LDH level
- Large-cell transformation
Can occur even in early stages
Mycosis Fungoides and Sézary Syndrome are lymphomas that present in skin. Blood may be involved in Mycosis Fungoides; Sézary Syndrome is defined by high blood involvement.1,7
Blood involvement is associated with shorter survival.8,10
Guides treatment approach
Blood involvement must be assessed for accurate diagnosis, staging, and optimal patient management.1,3
Consultation and/or referral to a specialist with CTCL expertise is recommended1
Watch expert perspectives on CTCL
Mara Haseltine, MD, a Dermatologist in private practice and Director of the University Medical Center Cutaneous T Cell Lymphoma Clinic explains why blood matters in Mycosis Fungoides and Sézary Syndrome. She explores the multicompartmental nature of the disease; diagnosis and staging; and assessing blood involvement via flow cytometry.
References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Primary Cutaneous Lymphomas V.1.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed March 5, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. 2. Scarisbrick JJ, Hodak E, Bagot M, et al. Blood classification and blood response criteria in mycosis fungoides and Sezary syndrome using flow cytometry: recommendations from the EORTC cutaneous lymphoma task force. Eur J Cancer. 2018;93:47-56. 3. Vermeer MH, Moins-Teisserenc H, Bagot M, et al. Flow cytometry for the assessment of blood tumour burden in cutaneous T-cell lymphoma: towards a standardized approach. Br J Dermatol. 2022;187(1):21-28. 4. Olsen EA, Whittaker S, Willemze R, et al. Primary cutaneous lymphoma: recommendations for clinical trial design and staging update from the ISCL, USCLC, and EORTC. Blood. 2022;140(5):419-437. 5. Willemze R, Cerroni L, Kempf W, et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019;133(16):1703-1714. 6. Scarisbrick JJ, Quaglino P, Prince HM, et al. The PROCLIPI international registry of early-stage mycosis fungoides identifies substantial diagnostic delay in most patients. Br J Dermatol. 2019;181(2):231-232. 7. Willemze R, Cerroni L, Kempf W, et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019;133(16):1703-1714. 8. Agar NS, Wedgeworth E, Crichton S, et al. Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol. 2010;28(31):4730-4739. 9. Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110(6):1713-1722. 10. Talpur R, Singh L, Daulat S, et al. Long-term outcomes of 1,263 patients with mycosis fungoides and Sézary syndrome from 1982 to 2009. Clin Cancer Res. 2012;18(18):5051-5060. 11. Farabi B, Seminario-Vidal L, Jamgochian M, et al. Updated review on prognostic factors in mycosis fungoides and new skin lymphoma trials. J Cosmet Dermatol. 2021;21(7):2742-2748.