Staging and Prognosis of Mycosis Fungoides and Sézary Syndrome - UpToDate

Staging and prognosis of mycosis fungoides and Sézary syndrome - UpToDate 12/11/2022 16'57
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Staging and prognosis of mycosis fungoides and

Sézary syndrome
Authors: Richard T Hoppe, MD, Youn H Kim, MD
Section Editors: Timothy M Kuzel, MD, FACP, John A Zic, MD
Deputy Editors: Alan G Rosmarin, MD, Rosamaria Corona, MD, DSc
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2022. | This topic last updated: May 18, 2021.
INTRODUCTION
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of
cutaneous T cell lymphoma (CTCL).
● MF is a mature T cell non-Hodgkin lymphoma that presents in the skin with localized
or widespread patches, plaques, tumors, and erythroderma, but it may also involve
lymph nodes, blood, and viscera.
● SS is a distinctive erythrodermic CTCL with a leukemic involvement of malignant T

cells that clonally match those in the skin.
MF and SS differ from other primary CTCLs by virtue of unique clinical features and
histopathology.
This topic discusses the staging, severity, response criteria, and prognosis of MF and SS.
Diagnosis and management of MF and SS are discussed separately.
● (See "Clinical manifestations, pathologic features, and diagnosis of mycosis

fungoides".)
● (See "Clinical presentation, pathologic features, and diagnosis of Sézary syndrome".)
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● (See "Treatment of early stage (IA to IIA) mycosis fungoides".)
● (See "Treatment of advanced stage (IIB to IV) mycosis fungoides".)
TNMB STAGING
The TNMB system is the standard method for staging MF and SS. TNMB staging is based
on an evaluation of the skin (T), lymph nodes (N), visceral involvement (M), and blood (B)
( table 1A-B) [1].
Staging evaluation — The staging evaluation includes a careful examination of the skin,
skin biopsy, a complete blood count (CBC) with differential, flow cytometry and/or Sézary
cell analysis, screening serum chemistries (including lactate dehydrogenase [LDH]), and a
chest x-ray ( table 2). If lymphadenopathy is present, computed tomography (CT) of the
chest/abdomen/pelvis or an integrated positron emission tomography (PET)/CT scan is
performed. If there are involved lymph nodes, an excisional biopsy is needed for staging
and diagnosis.
Skin (T)
Total body skin examination — Patients should undergo a total body skin examination
(TBSE), including the scalp, face, neck, oral mucosa and cavity; all four extremities,
including hands and feet, palms and soles; trunk, abdomen, buttocks; and perineum and
genitalia. (See "Screening for melanoma in adults and adolescents", section on 'Clinician
total body skin examination'.)
When performing TBSE, skin lesions should be classified as patches, plaques, or tumors
according to the following definitions [2]:
● Patch – Any size lesion without induration or significant elevation above the
surrounding uninvolved skin; poikiloderma (ie, mottled pigmentation, epidermal
atrophy, and telangiectasia associated with slight infiltration) may be present.
● Plaque – Any size lesion that is elevated or indurated; crusting, ulceration, or

poikiloderma may be present.
● Tumor – Any solid or nodular lesions ≥1 cm in diameter with evidence of deep
infiltration in the skin and/or vertical growth.
Clinicians should make special note of signs of follicular/folliculotropic disease (eg,

follicular prominence/accentuation, hair loss/alopecia, comedonal/cystic lesions),
ulceration, and if any pigment alteration is due to active disease (eg, hypopigmented or
vitiliginous variant of MF) or from post-inflammatory discoloration associated with
inactive disease. (See "Clinical presentation, pathologic features, and diagnosis of Sézary
syndrome".)
Body surface area involvement — The percentage of body surface area (BSA) involved
by each type of lesion (eg, patch, plaque, tumor) should be estimated and recorded. Areas
of alopecia are included in the BSA estimate only if they are thought to be manifestations
of disease (eg, in the folliculotropic variant of MF). If tumors are present, the total number,
aggregate volume, size of the largest lesion, and involved body regions should be noted.
Methods of measuring the percentage of BSA involved with MF/SS have been adapted
from management of patients with burns. (See "Assessment and classification of burn
injury", section on 'Extent of burn injury'.)
● Smaller areas of involvement are readily estimated using the "palm method," in
which the palm of the patient's hand, excluding the fingers, is approximately 0.5
percent of total BSA, and the entire palmar surface, including fingers, is 1 percent
BSA in children and adults [3].
● Larger areas of involvement should be estimated based on the "rule of nines" or

Lund-Browder chart:
• Rule of nines – This quick method of estimating total BSA for adults assigns 18
percent total BSA to each leg, 9 percent to each arm, 18 percent each to the
anterior and posterior trunk, and 9 percent to the head [4].
• Lund-Browder chart – The Lund-Browder chart is the most accurate method for
estimating the percentage BSA involvement for adults and children ( figure 1)
[5].
The extent of involvement may be underestimated in women with large breasts and
involvement of the anterior trunk; for every increase in brassiere cup size, the total
BSA of a woman's anterior trunk increases by a factor of 0.1, relative to the posterior
trunk [6].
Nodes (N) — Lymph node involvement can be documented by imaging and/or lymph
node biopsy.
Lymph node biopsy — Lymph node biopsy is generally reserved for patients in whom
clinical examination or imaging suggests lymphadenopathy. An excisional biopsy is
preferred, but good core needle biopsies are acceptable; fine needle aspirate alone is not
adequate for diagnosis and staging.
● Selection of a node – Biopsy should involve a lymph node ≥1.5 cm in diameter; a

firm, irregular, clustered, or fixed lymph node; or a node with significant metabolic
activity by PET [1].
If there is more than one suspicious lymph node, preference is given to lymph nodes
draining an area of involved skin or the node with the highest standardized uptake
value on fluorodeoxyglucose (FDG) PET scan. For nodes that are similar based on
these criteria, the order of preference for biopsy should be cervical, axillary, and then
inguinal lymph nodes.
● Type of biopsy – Excisional biopsy is generally preferred. However, in selected cases

an image-guided core biopsy may be acceptable to reduce morbidity of an excisional
biopsy [7]. Fine needle aspirate is not adequate to document lymph node
involvement by MF/SS.
● Node involvement – The International Society for Cutaneous Lymphomas/European

Organization of Research and Treatment of Cancer (ISCL/EORTC) lymph node
classification schema should be used to score the extent of lymph node replacement
by atypical cells [8]. Nodal involvement is further subclassified according to the
absence (a) or presence (b) of clonal cells.
• Extent of involvement – Lymph node involvement is scored from N0 (no atypical

lymphocytes present) through N3 (complete replacement of nodal architecture by
atypical lymphocytes or frank neoplastic cells).
• Clonality – Lymph node involvement is further subclassified by the absence (a) or

presence (b) of clonal cells, based on T cell receptor (TCR) gene rearrangement by
polymerase chain reaction (PCR).
A clinically abnormal lymph node that is not biopsied (eg, due to skin ulcerations or
concerns for poor healing) should be characterized as "Nx."
Imaging — Imaging should be performed to define lymph node and visceral

involvement in selected patients [2].
● Asymptomatic, early stage disease – Decisions regarding imaging for

asymptomatic, otherwise healthy patients should be individualized, but imaging is
not required for apparently early stage MF (eg, T1N0B0 or T2aN0B0).
● Symptomatic or more advanced disease – Imaging is usually reserved for patients

with ≥T2b skin lesions, palpable adenopathy, abnormal laboratory studies, or
pathology that is consistent with large-cell transformed MF or folliculotropic MF [9].
We generally perform diagnostic (ie, contrast-enhanced) CT of the neck, chest,

abdomen, and pelvis or a whole-body integrated PET/CT. Care should be taken to
limit radiation exposure, particularly in younger individuals, given concerns
regarding the risk for second malignancies.
There is a paucity of data regarding the sensitivity and specificity of CT and PET for staging
MF and SS. In a case series of 13 patients with MF or SS who were at risk for secondary
lymph node involvement, whole-body PET/CT was more sensitive in detecting lymph node
involvement than physical examination or CT; the intensity of PET activity roughly
correlated with the histologic grade of nodal involvement and was highest in those with
large-cell transformation. [10]. Visceral disease is highly unusual in the absence of
significant blood or nodal involvement [10,11].
Viscera (M) — Visceral involvement (ie, M1) is usually suspected based on imaging (eg,
PET and/or CT).
● Liver or spleen – For suspected liver or spleen involvement, imaging is usually

sufficient, given the potential morbidity associated with biopsy.
● Bone marrow – Bone marrow examination is not routinely employed for initial
staging in patients with MF, but it may be useful in selected cases if marrow
involvement is suspected (eg, B2 blood involvement or an unexplained hematologic
abnormality) [1].
A bone marrow core biopsy that demonstrates nodular, diffuse, or interstitial

involvement by SS is considered stage M1.
● Other organs – Suspected involvement of other viscera should be confirmed

histologically, when possible.
Blood (B) — Blood involvement is usually documented by flow cytometry, which has
largely supplanted the Sézary cell preparation (ie, microscopic examination of the buffy
coat of peripheral blood). Staging of blood involvement is described below. (See 'Flow
cytometry' below.)
Note that a bone marrow examination is not routinely employed for initial staging in
patients with MF, but it should be performed in patients with B2 blood involvement or an
unexplained hematologic abnormality [1]. Morphologic findings from a bone marrow
biopsy that constitute stage M1 are described above. (See 'Viscera (M)' above.)
Stage B1 or B2 involvement generally correlates with more extensive skin lesions (usually
T4) and the presence of extracutaneous disease. As an example, in a study of 1263
patients with MF or SS, which included 199 patients with B1 or B2 disease, patients with a
significant number of Sézary cells in peripheral blood had inferior overall survival (OS) and
disease-specific survival [12]. Patients with B2 disease had inferior OS compared with
those with B1 disease (median OS, 4.6 years versus not reached, respectively; hazard ratio
0.11, 95% CI 0.01-0.80). Significant bone marrow involvement with an infiltrative histologic
pattern is most often present in patients who meet the clinical criteria for SS. (See 'Viscera
(M)' above.)
Flow cytometry — Flow cytometry is a standardized, objective method for defining

subsets of lymphocytes. For staging SS by flow cytometry, cells that are CD4+, CD7- or
CD4+, CD26- are considered to be Sézary cells [1,2,13]. (See "Clinical presentation,
pathologic features, and diagnosis of Sézary syndrome".)
In addition to assessing the burden of blood involvement, B staging should also describe
the absence or presence of TCR clonality; the peripheral blood T cell clone should be
identical to that of involved skin; as an example, stage B2 disease should be categorized
as B2a (negative for TCR clonality) or B2b (TCR clonality present).
● B0 – Normal peripheral blood counts and either:
• <250 Sézary cells/microL
or
• <15 percent of total CD4+ lymphocytes are Sézary cells
● B1 – Not meeting criteria for B0 or B2
● B2 – TCR clonal rearrangement in blood and one of the following:
• ≥1000 Sézary cells/microL
• Increased CD4+ or CD3+ cells with CD4/CD8 ≥10
• Increase in CD4+ cells with an abnormal phenotype (>40 percent CD4+, CD7- or
>30 percent CD4+, CD26-)
The CD4+, CD7- or CD4+, CD26- phenotype may not be apparent in some patients, as
Sézary cells can lose CD3 or CD4 and/or gain CD26 expression after treatment or in
association with large-cell transformation. Moreover, an increase of cells with an aberrant
immunophenotype may reflect worsening disease, even if the population does not exceed
the percentages above.
Sézary cell preparation — Sézary cell preparations have largely been supplanted by flow
cytometry (described above). Evaluation of peripheral blood for SS is described separately.
(See "Clinical presentation, pathologic features, and diagnosis of Sézary syndrome".)
Blood involvement is categorized as:
● B0 – ≤5 percent of peripheral blood lymphocytes (PBL) are atypical (ie, Sézary) cells
● B1 – >5 percent of PBLs are Sézary cells, but criteria for B2 are not met
● B2 – Sézary count ≥1000/microL and TCR rearrangement is detected
Each B stage should also be categorized according to clonality, as described above. (See
'Flow cytometry' above.)
DISEASE SEVERITY
Scoring systems can be used to document disease burden and the response to treatment,
but they are not widely adopted in routine clinical practice. There is substantial
interobserver variability due to the subjectivity of many of the measures in the scoring
systems; ideally, the same clinician should determine serial scores for an individual
patient.
Overall disease burden can be estimated using a global scoring system, while local
disease burden can be assessed using a local skin scoring system (to measure the severity
of an individual lesion).
Global scoring (SWAT and mSWAT) — The Severity Weight Assessment Tool (SWAT) score
and the modified SWAT (mSWAT) score provide a global measure of disease severity by
incorporating the estimated percentage of total body surface area (BSA) involved by each
type of skin lesion ( table 3) [2]. The percentage of involved BSA is then multiplied by a
weight according to lesion type (ie, patch = 1, plaque = 2, tumor = 3 or 4). These scores
were designed to reflect the increase in dermal infiltrate thickness (and disease burden)
with tumor versus plaque versus patch lesions.
Skin scoring (CAILS) — The Composite Assessment of Index Lesion Severity (CAILS) score
is used to assess disease severity of an individual lesion. This method rates each of five
characteristics (ie, erythema, scaling, plaque elevation, hypo- or hyperpigmentation if
reflective of active disease, and size) on a scale from 1 to 5 [14]. The CAILS score is a sum
of the rating given to each of these criteria ( table 4).
SWAT and mSWAT can also be used to assess individual lesions by multiplying the
percentage of total BSA involved by a lesion by the weight assigned to the lesion type.
PROGNOSIS
The course of MF and SS is variable. Some patients have limited skin-only disease that
waxes and wanes over decades. Others with more generalized thick skin involvement,
true folliculotropic disease, or multiple tumors are more prone to disease progression or
extracutaneous involvement. Features that are associated with outcomes are described in
the sections that follow, but most prognostic factors for MF have not been evaluated in
prospective trials.
Proposed cutaneous lymphoma prognostic indices require further validation in

prospective studies before they should be routinely applied to the general population.
(See 'Prognostic indices' below.)
Prognostic factors — Patients with more advanced stage disease (especially generalized
skin involvement with patches or plaques on >80 percent skin surface), multiple tumors,
and significant blood or nodal burden are consistently associated with a higher risk of
disease progression and shorter median overall survival (OS).
In an international cohort study of 1275 patients with advanced stage MF or SS, the
following variables were independently associated with worse OS [15]:
● Extracutaneous disease (stage IV)
● Age >60 years
● Transformation to large-cell histology (LCT)
● Increased lactate dehydrogenase (LDH)
Combining these factors in a prognostic index model identified three risk groups across
stages associated with significantly different outcomes:
● Low-risk – 68 percent five-year OS
● Intermediate – 44 percent five-year OS
● High-risk – 28 percent five-year OS
Disease stage — Disease stage is the strongest prognostic factor in MF. Disease stage is
determined by the TNMB classification, which describes involvement of the skin (T), lymph
nodes (N), viscera (M), and blood (B) ( table 1A-B), as described above. (See 'TNMB
staging' above.)
The extent and type of skin involvement (T-stage) and presence of extracutaneous disease
are the most important features associated with OS [15,16]. Consistent with this, patients
with SS have a worse prognosis than patients with erythrodermic disease who do not
have the other findings of SS [17].
● A multicenter retrospective analysis of 1412 patients with MF and SS described the
stage at diagnosis, risk of progression to a higher stage, and OS, after >14 year
median follow-up [18]. Most patients presented with early stage disease, as follows:
IA (39 percent), IB (39 percent), IIA (9 percent), IIB (6 percent), IIIA (6 percent), IIIB to
IVB (<1 percent each). Estimated 5-year and 10-year OS were associated with stage at
diagnosis: IA (97 and 93 percent), IB (91 and 86 percent), IIA (72 and 72 percent), IIB
to IIIB (69 and 51 percent), and IVA to IVB (24 percent). The risk of progression was
associated with the stage at diagnosis; progression from stage IA, IB, and ≥IIA
disease was seen in 25, 29, and 40 percent of patients, respectively.
● In a study of 1502 patients with MF and SS, median OS was 18 years, disease
progression occurred in 34 percent, and 26 percent of patients died due to MF and
SS [16]. A significant difference in OS and risk of disease progression was reported
for patients with early stage disease and patches alone (T1a/T2a) compared with
those having patches and plaques (T1b/T2b). Advanced skin (T) stage, detection of
the tumor clone in peripheral blood without Sézary cells (B0b), increased LDH, and
folliculotropic MF were independent predictors of poor survival and increased risk of
disease progression. Tumor distribution at diagnosis and LCT were independent
predictors of increased risk of disease progression. N, M, and B stages, age, and
male sex were predictors of poor survival, but they were not associated with risk of
disease progression. In contrast, poikilodermatous MF was associated with superior
disease-specific survival (DSS).
● For patients with stage IA MF, long-term survival is similar to that of a race-, age-,
and sex-matched control population; in one study, median OS was not reached after
>32 years [19].
Folliculotropic variant — Folliculotropic MF is an uncommon variant of MF

characterized by infiltration of follicles [20,21]. Folliculotropic MF is generally associated
with greater risk for disease progression and worse prognosis compared with other MF
variants (especially in the early stages of MF), but this is a heterogeneous category with
variable natural history. Details of the diagnosis, management, and outcomes with
folliculotropic MF are presented separately. (See "Variants of mycosis fungoides", section
on 'Folliculotropic mycosis fungoides'.)
Transformation to large-cell histology (LCT) — LCT is reported in 10 to 25 percent of

patients with MF [22-24]. Patients with LCT have heterogeneous outcomes with some
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experiencing rapid deterioration and others having a more indolent clinical course [25,26].
Clinical findings are variable, but they may include new solitary nodules within a long-
standing patch or plaque, rapid development of multiple pink scattered nodules without
spontaneous resolution, or new or enlarging tumors [27]. Suspicious new papules,
nodules, and/or tumors should be biopsied because a diagnosis of LCT may result in a
change of therapy. LCT is diagnosed if >25 percent of the lymphoid infiltrate is composed
of large cells (by definition, >4 times larger than a small lymphocyte) or these large cells
create microscopic nodules.
LCT most often arises from plaque-type or erythrodermic MF, but LCT also varies
according to the stage at presentation.
● Incidence of LCT – The incidence of LCT varies among studies. A study of 419
patients with MF reported that 11 percent underwent LCT, a median of 6.5 years
after initial diagnosis [28]. In multivariate analysis, only age ≥60 and extracutaneous
spread were associated with a poor prognosis. A single-institution study of 70
patients with LCT reported a median survival of 8.3 years and rates of disease
progression at 5, 10, and 20 years were 49, 75, and 87 percent, respectively [16].
● Stage-dependence – The rate of LCT varies with disease stage. A retrospective

analysis of 297 patients reported that the rate of transformation ranged from 1.4
percent for patients with stage IA through IIA disease to 67 percent in patients with
stage IVB disease [29]. A retrospective study of 100 patients with transformed MF
reported a median survival after transformation of 24 months [25]. DSS rates at 2, 5,
and 10 years were 62, 38, and 36 percent, respectively. Corresponding rates of OS
were 57, 33, and 24 percent. The following four clinicopathologic features were
independently predictive of a worse outcome: generalized skin lesions, negative
staining for CD30, folliculotropic MF, and extracutaneous disease. Using these
prognostic factors, patients could be stratified into two cohorts with significantly
different disease trajectories. DSS was approximately 60 percent in patients with
zero or one unfavorable prognostic factor. In comparison, DSS was less than 20
percent in patients with two or more unfavorable prognostic factors. Further studies
are needed to determine whether this prognostic information may be used to alter
the treatment approach for these patients.
Age — MF most commonly presents in older adults (peak incidence in the sixth to
seventh decade), but MF that presents before age 30 may be associated with more
favorable outcomes [30,31].
A retrospective study of two cancer registries evaluated outcomes of 399 patients who
were diagnosed before age 30 [32]. Estimated rates of 10-year OS were 94 and 89 percent
in the two registries. The most common causes of death were non-Hodgkin lymphoma
and infection. Compared with the general population, these younger patients with MF had
an excess risk of second cancers (standardized incidence ratio [SIR] 3.40; 95% CI 1.55-
6.45), especially lymphoma and melanoma.
A single-institution retrospective study included 74 patients <30 years old with MF, 88
percent of whom presented with early stage disease [33]. Rates of OS at 5 and 10 years
were 97 and 96 percent, respectively; all deaths were due to progressive lymphoma. With
median follow-up of 3.5 years, progressive disease occurred in 26 percent and
progression was associated with advanced stage disease, age >20 years, African American
patients, and poikilodermatous presentation.
Biomarkers — No biomarkers have been validated as having prognostic value in

patients with MF/SS. Immunophenotypic features and molecular biomarkers for
evaluating disease progression or for distinguishing MF/SS from other cutaneous
processes have not yet been tested for independent prognostic value [34-36]. (See
"Clinical presentation, pathologic features, and diagnosis of Sézary syndrome".)
RNA sequencing analysis from samples of lesional cutaneous T cell lymphoma (CTCL) skin
from 110 patients indicated that high expression of TOX (which encodes a protein
implicated in T cell development through chromatin regulation), FYB (which encodes a T
cell adapter protein involved in T cell activation), and CD52 (a glycosylphosphatidylinositol-
anchored glycoprotein with potential roles in T cell migration and co-stimulation of the
immune response) were associated with disease progression and decreased DSS [37].
Among patients with early stage disease (≤IIA), overexpression of CCR4 (which encodes CC
chemokine receptor 4) was also a predictor of disease progression. The value of these
markers as prognostic indicators in early stage MF needs further validation in other
patient populations.
MicroRNAs (miRNAs) are small, non-coding, regulatory molecules that may be associated
with progression of MF [38]. Expression of three miRNAs in diagnostic skin biopsies from
154 Danish patients was used to stratify patients into high- and low-risk groups for
disease progression [39]. This 3-miRNA classifier was stronger than existing clinical
prognostic factors and remained an independent prognostic tool after adjustment for
clinical factors. Quantitation of these three miRNAs (miR-106b-5p, miRNA148a-3p, miR-
338-3p) by reverse transcription polymerase chain reaction (RT-PCR) must be validated in
other patient populations before it is adopted for clinical use.
Prognostic indices — Prognostic indices for MF/SS have been developed using large
retrospective cohorts of patients, but they require validation in prospective studies before
they should be routinely applied to clinical practice.
● The Cutaneous Lymphoma International Prognostic Index (CLIPi) was developed

from a retrospective analysis of 1502 patients with MF and SS in the United Kingdom
and applied to an independent group of 1221 patients with MF and SS [40]. Adverse
prognostic factors identified in early (IA to IIA) stage MF and SS were male sex, age
>60, plaques, folliculotropic disease, and stage N1/Nx, while adverse factors those in
advanced stage (IIB to IVB) disease included male sex, age >60, stages B1/B2, N2/3,
and visceral involvement. Male sex, age >60, plaques, folliculotropic disease, and
stage N1/Nx were used to define three prognostic groups among patients with early
and advanced stage MF and SS. Patients with early stage MF had estimated 5-year
OS rates from 82 to 97 percent and 10-year OS rates from 65 to 93 percent.
Corresponding rates for advanced stage MF ranged from 42 to 61 percent and 20 to
46 percent.
● The Cutaneous Lymphoma International Consortium (CLIC) was developed from a

retrospective analysis of 1275 patients at 29 international centers with advanced (IIB
to IVB) stage MF and SS [15]. Stage IV disease, age >60 years, elevated LDH, and LCT
in the skin were used to classify three prognostic groups:
• Low risk (0 to 1 risk factor) – Median survival not reached; estimated survival rates
at one, two, and five years were 94, 87, and 68 percent, respectively.
• Intermediate risk (2 risk factors) – Median survival 46 months; estimated survival

rates at one, two, and five years were 84, 72, and 43 percent, respectively.
• High risk (3 to 4 risk factors) – Median survival 34 months; estimated survival

rates at one, two, and five years were 85, 62, and 28 percent, respectively.
RESPONSE ASSESSMENT
Evaluation — Outside of a clinical research protocol, response to treatment should

always include the following [2]:
● Complete skin examination, including a determination of the type of skin lesions and
the estimated percentage of total body surface area involved by patches, plaques,
and tumor lesions
● Survey of the lymph nodes and assessment for organomegaly
● Complete blood count with differential count
● Flow cytometry (for assessment for Sézary cells and/or clonality)
● Repeat imaging studies that were previously abnormal
For patients treated as part of a research protocol, response assessment should include
all of the features listed, but it may also entail measures of disease severity (eg, mSWAT
score) and additional imaging.
Response criteria — A consensus statement regarding response criteria was published

by the International Society for Cutaneous Lymphomas, the United States Cutaneous
Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European
Organisation for Research and Treatment of Cancer ( table 5) [2]. All responses should
be documented to have persisted for ≥4 weeks. If there is clinical uncertainty, possible
disease progression and/or relapse should be re-evaluated after four weeks.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links: Primary
cutaneous lymphoma".)
SUMMARY
● Mycosis fungoides (MF) is an extranodal non-Hodgkin lymphoma of T cell origin
that is characterized by skin involvement, but it may also involve lymph nodes,
blood, and viscera. The clinical course of MF varies from indolent to aggressive
behavior.
Sézary syndrome (SS) is a more aggressive leukemic variant of cutaneous T cell

lymphoma in which a significant number of circulating malignant (Sézary) cells are
present in peripheral blood.
● TNMB Staging – TNMB staging is the standard method used for MF and SS and is
based on evaluation of skin (T), lymph nodes (N), viscera (M), and blood (B)
( table 1A-B). (See 'TNMB staging' above.)
Staging evaluation includes a total body skin examination (TBSE) and biopsy,
complete blood count, flow cytometry for Sézary cell analysis, screening chemistries,
and lactate dehydrogenase (LDH) ( table 2). Computed tomography (CT) with or
without positron emission tomography (PET) is indicated for patients with more
advanced clinical disease, lymphadenopathy, or with adverse histologic factors (eg,
suspected large-cell transformation). Lymph node biopsies should be obtained if
lymphadenopathy is present and bone marrow biopsy may be useful in selected
cases to document visceral disease. (See 'Staging evaluation' above.)
• Skin – A TBSE forms the basis of an estimate of the extent of body surface area
(BSA) involvement by patches, papules, plaques, and tumors. The preferred tool
for estimation of BSA involvement depends on the extent and sites of
involvement, as described above. (See 'Skin (T)' above.)
• Nodes – Lymph node involvement may be suspected by imaging but should be

documented by excisional lymph node or good core biopsies; fine needle aspirate
is not acceptable for staging and diagnosis. (See 'Nodes (N)' above.)
• Viscera – Visceral involvement is usually suspected based on imaging (eg, PET

and/or CT). For suspected liver or spleen involvement, imaging is usually
sufficient (given the potential morbidity associated with biopsy), but suspected
involvement of other viscera, including bone marrow, should be confirmed
histologically, when possible. (See 'Viscera (M)' above.)
• Blood – Blood involvement is generally documented by flow cytometry of
peripheral blood and is staged as described above. (See 'Flow cytometry' above.)
● Prognosis – Prognosis of MF and SS varies with disease stage. Patients with more
advanced stage disease (especially generalized skin involvement with patch or
plaques on >80 percent skin surface), multiple tumors, and significant blood or nodal
burden are consistently associated with a higher risk of disease progression and
shorter median overall survival. Other factors associated with outcomes in MF/SS
include large cell transformation and the folliculotropic variant of MF. Biomarkers
have not yet been validated for prognostic use in clinical practice. (See 'Prognosis'
above.)
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Topic 83281 Version 22.0
GRAPHICS
Mycosis Fungoides Cooperative Group TNMB classification of

cutaneous T cell lymphoma (CTCL)
Skin (T)
T1 Limited patches*, papules, and/or plaques ¶ covering <10 percent of the skin surface;
may further stratify into T 1a (patch only) versus T 1b (plaque ± patch)
T2 Patches, papules, or plaques covering ≥10 percent of the skin surface; may further
stratify into T 2a (patch only) versus T 2b (plaque ± patch)
T3 One or more tumors Δ (≥1 cm diameter)
T4 Confluence of erythema covering ≥80 percent body surface area
Node (N)
N0 No clinically abnormal lymph nodes ◊ ; biopsy not required
N1 Clinically abnormal lymph nodes; histopathology Dutch grade 1 or NCI LN0-2
N 1a Clone negative §
N 1b Clone positive §
N2 Clinically abnormal lymph nodes; histopathology Dutch grade 2 or NCI LN3
N 2a Clone negative §
N 2b Clone positive §
N3 Clinically abnormal lymph nodes; histopathology Dutch grades 3-4 or NCI LN4; clone
positive or negative
NX Clinically abnormal lymph nodes; no histologic confirmation
Visceral (M)
M0 No visceral organ involvement
M1 Visceral involvement (must have pathology confirmation ¥ and organ involved should
be specified)
Blood (B)
B0 No significant blood involvement: ≤5 percent of Sézary cells. For clinical trials, B 0
may also be defined as <250/microL Sézary cells; CD4+CD26- or CD4+CD7- cells or
CD4+CD26- and CD4+CD7- cells <15 percent by flow cytometry.
B 0a Clone negative
https://www.uptodate.com/contents/staging-and-prognosis-of-m…earch=syndrome%20de%20sezary&topicRef=16193&source=see_link Página 20 de 35
B 0b Clone positive
B1 Low blood tumor burden: Does not meet the criteria of B 0 or B 2
B 1a Clone negative
B 1b Clone positive
B2 High blood tumor burden: Positive clone ‡ plus one of the following:
≥1000/microL Sézary cells; CD4/CD8 ≥10; CD4+CD7- cells ≥40 percent; or CD4+CD26-
cells ≥30 percent. For clinical trials, B 2 may also be defined as >1000/microL
CD4+CD26- or CD4+CD7- cells.
* For skin, patch indicates any size lesion without significant elevation or induration.
Presence/absence of hypo- or hyperpigmentation, scale, crusting, and/or poikiloderma should
be noted.
¶ For skin, plaque indicates any size skin lesion that is elevated or indurated. Presence or
absence of scale, crusting, and/or poikiloderma should be noted. Histologic features such as
folliculotropism or large-cell transformation (>25 percent large cells), CD30+ or CD30-, and
clinical features such as ulceration are important to document.
Δ For skin, tumor indicates at least one 1 cm diameter solid or nodular lesion with evidence of
depth and/or vertical growth. Note total number of lesions, total volume of lesions, largest
size lesion, and region of body involved. Also note if histologic evidence of large-cell
transformation has occurred. Phenotyping for CD30 is encouraged.
◊ For node, abnormal lymph node(s) indicates any lymph node that on physical examination
is firm, irregular, clustered, fixed, or 1.5 cm or larger in diameter or on imaging is >1.5 cm in
the long axis or >1 cm in the short axis. Node groups examined on physical examination
include cervical, supraclavicular, epitrochlear, axillary, and inguinal.
§ A T cell clone is defined by polymerase chain reaction or Southern blot analysis of the T cell
receptor gene.
¥ For viscera, spleen and liver may be diagnosed by imaging criteria alone.
‡ The clone in the blood should match that of the skin. The relevance of an isolated clone in
the blood or a clone in the blood that does not match the clone in the skin remains to be
determined.
This research was originally published in Blood. Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging
and classification of mycosis fungoides and Sezary 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; 110:1713. Copyright © the American Society of Hematology.
Additional data from: Olsen EA, Whittaker S, Kim YH, et al. Clinical end points and response criteria in mycosis
fungoides and Sézary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the
United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European
Organisation for Research and Treatment of Cancer. J Clin Oncol 2011; 29:2598.
Graphic 75768 Version 5.0
Clinical staging system for mycosis fungoides
Clinical stage TNMB classification
IA T1 N0 M0 B 0 or B 1
IB T2 N0 M0 B 0 or B 1
IIA T 1 or T 2 N 1 or N 2 M0 B 0 or B 1
IIB T3 N 0 to N 2 M0 B 0 or B 1
IIIA T4 N 0 to N 2 M0 B0
IIIB T4 N 0 to N 2 M0 B1
IVA1 T 1 to T 4 N 0 to N 2 M0 B2
IVA2 T 1 to T 4 N3 M0 B 0 to B 2
IVB T 1 to T 4 N 0 to N 3 M1 B 0 to B 2
To be used in conjunction with the TNMB classification system for mycosis fungoides.
Modified from: Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging and classification of mycosis
fungoides and Sezary 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; 110:1713.
Recommended evaluation/initial staging of the patient with mycosis

fungoides/Sézary syndrome
Evaluation and staging
Complete physical examination, including:
Determination of type(s) of skin lesions
Estimate percentage of BSA involved by patches, plaques, and tumor lesions and note any
ulceration or folliculocentricity of lesions. The patient's palm (including all fingers) is
approximately 1 percent of BSA.*
Identification of any palpable lymph node, especially those ≥1.5 cm in largest diameter or
firm, irregular, clustered, or fixed
Identification of any organomegaly
Skin biopsy
Essential: At least two skin biopsies should be obtained of different anatomic areas and
morphology for H&E evaluation. If only one biopsy can be obtained, then the lesion that has
the most scaling and induration should be chosen.
If needed: Immunophenotyping to include at least the following markers: CD2, CD3, CD4,
CD5, CD7, and CD8, beta-F1 (to confirm alpha-beta TCR), and a B cell marker, such as CD20;
CD30 may also be indicated in cases where lymphomatoid papulosis, anaplastic lymphoma,
or large-cell transformation is considered.
If needed: Evaluation for clonality of TCR gene rearrangement.
Blood tests
CBC with manual differential (assess for Sézary cells), comprehensive chemistries, LDH
Analysis for abnormal lymphocytes by either Sézary cell count with determination of the
absolute number of Sézary cells and/or flow cytometry (including CD4 + / CD7 - or CD4 + /
CD26 - )
If needed: TCR gene rearrangement and relatedness to any clone in skin
Radiologic tests
Radiologic tests are not necessary in patients with T 1 N 0 B 0 or T 2a N 0 B 0 stage disease who
are otherwise healthy and without complaints directed to a specific organ system.
In all other patients, contrast-enhanced CT scan of chest, abdomen, and pelvis (neck
included if clinically indicated) or whole body integrated PET-CT is recommended to further
evaluate any potential lymphadenopathy, visceral involvement, or abnormal laboratory
tests; in patients unable to safely undergo CT scans, MRI may be substituted.
Lymph node biopsy
Excisional biopsy is indicated in those patients with a node that is at least 1.5 cm (confirmed
by imaging) in diameter; and/or is firm, irregular, clustered, or fixed; and/or significantly PET
avid.
Site of biopsy: Preference is given to the largest lymph node draining an involved area of the
skin or if FDG-PET scan data are available, the node with highest standardized uptake value.
Analysis: Pathologic assessment by light microscopy, flow cytometry, and TCR gene
rearrangement.
BSA: body surface area; TCR: T cell receptor; CBC: complete blood count; LDH: lactate
dehydrogenase; CT: computed tomography; PET-CT: positron emission
tomography/computed tomography; MRI: magnetic resonance imaging; FDG-PET: 18 F-fluoro-
2-deoxyglucose positron emission tomography.
*A more specific BSA calculation can be calculated using the "mSWAT" system: mSWAT =
(percent BSA of patches) (1) + (percent BSA of plaques) (2) + (percent BSA of tumor) (4).
Adapted from:
1. 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; 110:1713.
This table was created using research originally published in Blood. Modified from: Prince HM, Whittaker S, Hoppe
RT. How I treat my mycosis fungoides and Sézary syndrome. Blood 2009; 114:4337. Copyright © 2009 American
Society of Hematology.
Modified Lund-Browder chart
Numbers refer to the percentage body surface area burned.
Modified Severity Weighted Assessment Tool for Mycosis Fungoides

and Sezary Syndrome
Percent BSA Assessment of involvement in patient's skin

Body region in body
region Patch* Plaque ¶ Tumor Δ
Head 7
Neck 2
Anterior trunk 13
Arms 8
Forearms 6
Hands 5
Posterior trunk 13
Buttocks 5
Thighs 19
Legs 14
Feet 7
Groin 1
Subtotal of
lesion BSA:
Weighting x1 x2 x4
factor:
Subtotal lesion
BSA x
weighting
factor:
Modified Severity Weighted Assessment Tool score equals summation of each column line.
BSA: body surface area; mSWAT: modified Severity Weighted Assessment Tool.
* Any size lesion without induration or significant elevation above the surrounding uninvolved
skin; poikiloderma may be present.
¶ Any size lesion that is elevated or indurated; crusting, ulceration, or poikiloderma may be
present.
Δ Any solid or nodular lesion ≥1 cm in diameter with evidence of deep infiltration in the skin
and/or vertical growth.
From: Olsen EA, Whittaker S, Kim YH, et al. Clinical end points and response criteria in mycosis fungoides and Sézary
syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States
Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for
Research and Treatment of Cancer. J Clin Oncol; 29(18), 2011:2598-2607. Reprinted with permission. Copyright ©
2011 American Society of Clinical Oncology. All rights reserved.
Composite Assessment of Index Lesion Severity for Mycosis Fungoides

and Sezary Syndrome
Index lesion
Clinical sign and degree or size (scale of 0 to 8)
1 2 3 4 5
Erythema
Scaling
Plaque elevation
Hypo- or hyperpigmentation
Lesion size*
Subtotal:
Total (sum of subtotals):
Composite Assessment of Index Lesion Severity cannot be used as skin assessment in global
response score. Suggestions for improvement include using actual size of lesion versus
categorical score for size and eliminating pigmentation as a clinical parameter.
* Lesion size (cm 2 ): 0: no measurable area; 1: >0 to ≤4; 2: >4 to ≤10; 3: >10 to ≤16; 4: >16 to
≤25; 5: >25 to ≤35; 6: >35 to ≤45; 7: >45 to ≤55; 8: >55 to ≤70; 9: >70 to ≤90; 10: >90 to ≤110;
11: >110 to ≤130; 12: >130 to ≤155; 13: >155 to ≤180; 14: >180 to ≤210; 15: >210 to ≤240; 16:
>240 to ≤270; 17: >270 to ≤300; 18: >300.
Research and Treatment of Cancer. J Clin Oncol; 29(18), 2011:2598-2607. Reprinted with permission. Copyright ©
2011 American Society of Clinical Oncology. All rights reserved.
Response criteria in mycosis fungoides and Sézary syndrome
Response in specific tissues
Location Response Definition
Skin* CR 100 percent clearance of skin

lesions. ¶
PR 50 to 99 percent clearance of
skin disease from baseline
without new tumors (T3) in
patients with T1, T2, or T4
only skin disease.
SD <25 percent increase to <50

percent clearance in skin
disease from baseline
without new tumors (T3) in
patients with T1, T2, or T4
only skin disease.
PD Δ ≥25 percent increase in skin

disease from baseline; OR
New tumors (T3) in patients

with T1, T2, or T4 only skin
disease; OR
Loss of response: in those

with complete or partial
response, increase of skin
score of greater than the
sum of nadir plus 50 percent
baseline score.
Relapse Any disease recurrence in

those with complete
response.
Lymph nodes ◊ CR All lymph nodes are now

≤1.5 cm in greatest
transverse (long axis)
diameter by method used to
assess lymph nodes at
baseline or biopsy negative
for lymphoma; in addition,
lymph nodes that were N3

classification and ≤1.5 cm in
their long axis and >1 cm in
their short axis at baseline,
must now be ≤1 cm in their
short axis or biopsy negative
for lymphoma.
PR Cumulative reduction ≥50

percent of the SPD of each
abnormal lymph node at
baseline and no new lymph
node >1.5 cm in the diameter
of the long axis or >1 cm in
the diameter of the short
axis if the long axis is 1 to 1.5
cm diameter.
SD Fails to attain the criteria for

CR, PR, and PD.
PD Δ ≥50 percent increase in SPD

from baseline of lymph
nodes; OR
Any new node >1.5 cm in the

long axis or >1 cm in the
short axis if 1 to 1.5 cm in the
long axis that is proven to be
N3 histologically; OR
Loss of response: >50

percent increase from nadir
in SPD of lymph nodes in
those with PR.
Relapse Any new lymph node >1.5 cm

in the long axis in those with
CR proven to be N3
histologically.
Viscera CR Liver or spleen or any organ

considered involved at
baseline should not be
enlarged on physical exam
and should be considered
normal by imaging; no
nodules should be present

on imaging of liver or spleen;
any post treatment mass
must be determined by
biopsy to be negative for
lymphoma.
PR ≥50 percent regression in

any splenic or liver nodules,
or in measureable disease
(SPD) in any organs
abnormal at baseline; no
increase in size of liver or
spleen and no new sites of
involvement.
SD Fails to attain the criteria for

CR, PR, or PD.
PD Δ >50 percent increase in size

(SPD) of any organs involved
at baseline; OR
New organ involvement; OR
Loss of response: >50

percent increase from nadir
in the size (SPD) of any
previous organ involvement
in those with PR.
Relapse New organ involvement in

those with CR.
Blood § CR ¥ B0
PR ‡ >50 percent decrease in

quantitative measurements
of blood tumor burden from
baseline in those with high
tumor burden at baseline
(B2).
SD Fails to attain criteria for CR,

PR, or PD.
PD Δ B0 to B2; OR
>50 percent increase from
baseline and at least 5000

neoplastic cells/microL [1] ;
OR
Loss of response: in those

with PR who were originally
B2 at baseline, >50 percent
increase from nadir and at
least 5000 neoplastic
cells/microL.
Relapse Increase of neoplastic blood

lymphocytes to ≥B1 in those
with CR.
Global response score
Global
Definition Skin Nodes Blood Viscera
score †
CR Complete CR All categories have CR/NI.

disappearance
of all clinical
evidence of
disease
PR Regression of CR All categories do not have a CR/NI and no

measurable category has a PD.
disease
PR No category has a PD and if any category
involved at baseline, at least one has a CR or
PR.
SD Failure to PR No category has a PD and if any category

attain CR, PR, involved at baseline, no CR or PR in any.
or PD
SD CR/NI, PR, SD in any category and no
representative
category has a PD.
of all disease
PD Progressive PD in any category.

disease
Relapse Recurrence Relapse in any category.

disease in
prior CR
CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; SPD:
sum of the maximum linear dimension (major axis) X longest perpendicular dimension (minor
axis); NI: noninvolved.
* Based on modified Severity Weighted Assessment Tool score.
¶ A biopsy of normal appearing skin is unnecessary to assign a complete response. However,

a skin biopsy should be performed of a representative area of the skin if there is any question
of residual disease (persistent erythema or pigmentary change) where otherwise a complete
response would exist. If histologic features are suspicious or suggestive of mycosis
fungoides/Sézary syndrome (see histologic criteria for early mycosis fungoides [2] ), the
response should be considered a partial response only.
Δ Whichever criterion occurs first.
◊ Peripheral and central lymph nodes.
§ As determined by absolute numbers of neoplastic cells/microL.
¥ If a bone marrow biopsy was performed at baseline and determined to unequivocally be

indicative of lymphomatous involvement, then to confirm a global CR where blood
assessment now meets criteria for B0, a repeat bone marrow biopsy must show no residual
disease or the response should be considered a PR only.
‡ There is no PR in those with B1 disease at baseline as the difference within the range of
neoplastic cells that define B1 is not considered significant and should not affect
determination of global objective response.
† It is recommended that not only the proportion of patients who achieve a response or an
unfavorable outcome be calculated but a life table account for the length of the interval
during which each patient is under observation also be generated.
References:
1. Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored Working Group guidelines for
chronic lymphocytic leukemia: Revised guidelines for diagnosis and treatment. Blood 1996; 87:4990.
2. Sacks H, Chalmers TC, Smith H Jr. Randomized versus historical controls for clinical trials. Am J Med 1982;
72:233.
Research and Treatment of Cancer. J Clin Oncol 2011; 29:2598-607. Reprinted with permission. Copyright © 2011
American Society of Clinical Oncology. All rights reserved.
Contributor Disclosures
Richard T Hoppe, MD No relevant financial relationship(s) with ineligible companies to disclose. Youn
H Kim, MD Grant/Research/Clinical Trial Support: Corvus [Cutaneous T cell lymphoma/peripheral T cell
lymphoma]; CRISPR Therapeutics [Cutaneous T cell lymphoma]; Eisai [Cutaneous T cell lymphoma];
Elorac [Cutaneous T cell lymphoma]; Innate [Cutaneous T cell lymphoma]; Kyowa Hakko Kirin
[Cutaneous T cell lymphoma]; Soligenix [Cutaneous T cell lymphoma]; Trillium [Cutaneous T cell
lymphoma/peripheral T cell lymphoma]. Consultant/Advisory Boards: Galderma [Cutaneous T cell
lymphoma]; Innate [Cutaneous T cell lymphoma/peripheral T cell lymphoma]; Kyowa Hakko Kirin
[Cutaneous T cell lymphoma]; Mundipharma [Cutaneous T cell lymphoma]; Regeneron [Cutaneous T
cell lymphoma]; Sanofi [Cutaneous T cell lymphoma]; Secura Bio [Cutaneous T cell lymphoma]; Takeda
[CTCL]. All of the relevant financial relationships listed have been mitigated. Timothy M Kuzel, MD,
FACP Grant/Research/Clinical Trial Support: Elocon [CTCL ointment];Esai [CTCL];Soligenix [CTCL
ointment]. Speaker's Bureau: Kyowa Kirin[Biology of cutaneous lymphoma]. All of the relevant financial
relationships listed have been mitigated. John A Zic, MD No relevant financial relationship(s) with
ineligible companies to disclose. Alan G Rosmarin, MD No relevant financial relationship(s) with
ineligible companies to disclose. Rosamaria Corona, MD, DSc No relevant financial relationship(s) with
ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
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Staging and prognosis of mycosis fungoides and

● SS is a distinctive erythrodermic CTCL with a leukemic involvement of malignant T

Diagnosis and management of MF and SS are discussed separately.

● (See "Clinical manifestations, pathologic features, and diagnosis of mycosis

● (See "Clinical presentation, pathologic features, and diagnosis of Sézary syndrome".)

● (See "Treatment of early stage (IA to IIA) mycosis fungoides".)

● (See "Treatment of advanced stage (IIB to IV) mycosis fungoides".)

● Plaque – Any size lesion that is elevated or indurated; crusting, ulceration, or

● Tumor – Any solid or nodular lesions ≥1 cm in diameter with evidence of deep

infiltration in the skin and/or vertical growth.

Clinicians should make special note of signs of follicular/folliculotropic disease (eg,

● Larger areas of involvement should be estimated based on the "rule of nines" or

● Selection of a node – Biopsy should involve a lymph node ≥1.5 cm in diameter; a

● Type of biopsy – Excisional biopsy is generally preferred. However, in selected cases

● Node involvement – The International Society for Cutaneous Lymphomas/European

• Extent of involvement – Lymph node involvement is scored from N0 (no atypical

• Clonality – Lymph node involvement is further subclassified by the absence (a) or

Imaging — Imaging should be performed to define lymph node and visceral

● Asymptomatic, early stage disease – Decisions regarding imaging for

● Symptomatic or more advanced disease – Imaging is usually reserved for patients

We generally perform diagnostic (ie, contrast-enhanced) CT of the neck, chest,

● Liver or spleen – For suspected liver or spleen involvement, imaging is usually

A bone marrow core biopsy that demonstrates nodular, diffuse, or interstitial

● Other organs – Suspected involvement of other viscera should be confirmed

Flow cytometry — Flow cytometry is a standardized, objective method for defining

● B0 – Normal peripheral blood counts and either:

• <250 Sézary cells/microL

• <15 percent of total CD4+ lymphocytes are Sézary cells

● B1 – Not meeting criteria for B0 or B2

● B2 – TCR clonal rearrangement in blood and one of the following:

• ≥1000 Sézary cells/microL

• Increased CD4+ or CD3+ cells with CD4/CD8 ≥10

Blood involvement is categorized as:

● B2 – Sézary count ≥1000/microL and TCR rearrangement is detected

Proposed cutaneous lymphoma prognostic indices require further validation in

● Extracutaneous disease (stage IV)

● Age >60 years

● Transformation to large-cell histology (LCT)

● Increased lactate dehydrogenase (LDH)

● Low-risk – 68 percent five-year OS

● Intermediate – 44 percent five-year OS

● High-risk – 28 percent five-year OS

● A multicenter retrospective analysis of 1412 patients with MF and SS described the

Folliculotropic variant — Folliculotropic MF is an uncommon variant of MF

Transformation to large-cell histology (LCT) — LCT is reported in 10 to 25 percent of

● Stage-dependence – The rate of LCT varies with disease stage. A retrospective

Biomarkers — No biomarkers have been validated as having prognostic value in

● The Cutaneous Lymphoma International Prognostic Index (CLIPi) was developed

● The Cutaneous Lymphoma International Consortium (CLIC) was developed from a

• Intermediate risk (2 risk factors) – Median survival 46 months; estimated survival

• High risk (3 to 4 risk factors) – Median survival 34 months; estimated survival

Evaluation — Outside of a clinical research protocol, response to treatment should

● Survey of the lymph nodes and assessment for organomegaly

● Complete blood count with differential count

● Flow cytometry (for assessment for Sézary cells and/or clonality)

● Repeat imaging studies that were previously abnormal

Response criteria — A consensus statement regarding response criteria was published

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

● Mycosis fungoides (MF) is an extranodal non-Hodgkin lymphoma of T cell origin

Sézary syndrome (SS) is a more aggressive leukemic variant of cutaneous T cell