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".)

●(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", section on 'Skin lesions'.)

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", section on 'Flow cytometry'.)

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", section on 'Peripheral blood'.)

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 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", section on 'Diagnosis'.)

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.)