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Staging and prognosis of mycosis fungoides and Sézary syndrome

Staging and prognosis of mycosis fungoides and Sézary syndrome
Literature review current through: Jan 2024.
This topic last updated: Dec 22, 2023.

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.

Staging of MF and SS uses the TNMB system, which is based on an evaluation of skin (T), lymph nodes (N), visceral involvement (M), and blood (B).

This topic discusses the evaluation, staging, 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".)

STAGING EVALUATION — The staging evaluation of a patient with MF or SS includes (table 1):

Physical examination – Details of clinical manifestations of MF/SS are presented separately. (See "Clinical presentation, pathologic features, and diagnosis of Sézary syndrome" and "Clinical manifestations, pathologic features, and diagnosis of mycosis fungoides".)

Skin – Careful examination of the skin for the type of lesions and estimate of involved body surface area (BSA). (See 'Skin (T)' below.)

Lymph nodes and organomegaly – Palpation of all peripheral nodal groups, liver, and spleen. (See 'Nodes (N)' below.)

Laboratory

Hematology – Complete blood count (CBC) with differential count, evaluation of blood smear for Sézary cell analysis.

Serum chemistries – Electrolytes, glucose, kidney function tests, liver function tests, and lactate dehydrogenase.

Pathology – Description of pathologic findings are presented separately. (See "Clinical manifestations, pathologic features, and diagnosis of mycosis fungoides", section on 'Pathology'.)

Skin biopsy

Lymph node biopsy, if there is clinical evidence of involvement

Imaging

Computed tomography (CT) of the chest/abdomen/pelvis or integrated positron emission tomography (PET)/CT scan is performed if lymphadenopathy is present.

Chest x-ray, if PET or CT was not performed.

Flow cytometry – Immunophenotypic findings are presented separately. (See "Clinical presentation, pathologic features, and diagnosis of Sézary syndrome", section on 'Blood assessment'.)

Our approach to staging is consistent with the approach of the Tri-Societies: the International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous Lymphoma Consortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer (EORTC) [1].

COMPONENTS OF STAGING

Skin (T) — The type and extent of skin involvement is described as T1 to T4.

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 [1]. (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), scale, and crusting 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 postinflammatory discoloration associated with inactive disease. (See "Clinical presentation, pathologic features, and diagnosis of Sézary syndrome", section on 'Skin'.)

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 the management of patients with burns. (See "Assessment and classification of burn injury", section on 'Extent of burn injury'.)

Smaller areas – Smaller areas of involvement are readily estimated using the "palm method." The palm of the patient's hand is approximately 0.5 percent of total BSA, while the palm plus palmar surface of all five fingers is slightly less than 1 percent [3].

Larger areas – Larger areas of involvement should be estimated based on one of the following methods:

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].

Skin biopsy — Skin biopsy is required to diagnose MM/SS.

Details of the pathologic features and diagnostic criteria are discussed separately. (See "Clinical presentation, pathologic features, and diagnosis of Sézary syndrome".)

The following aspects of the diagnostic skin biopsy may influence the type of skin lesion.

Both patch and plaque stage lesions, including hypopigmented MF, should meet the criteria for early MF [7].

In patients with erythroderma, where a skin biopsy is only suggestive of or suspicious for MF/SS, supportive evidence for a diagnosis of MF/SS (and exclusion of other conditions) includes findings of aberrant phenotype, dominant T cell receptor (TCR) clone in the skin, and blood or lymph node involvement (particularly if a positive clone matches that in skin).

Nodes (N) — Lymph node involvement can be documented by imaging and/or lymph node biopsy. Lymph node involvement is described as N0 to N3.

Imaging — Positron emission tomography (PET)/CT is used to define lymph node and visceral involvement in selected patients [1]. MF and SS are PET avid [1]. Lymph node assessment is based on imaging findings according to the Lugano classification (table 2) [8].

We generally perform a whole-body integrated PET/CT or diagnostic (ie, contrast-enhanced) CT of the neck, chest, abdomen, and pelvis at initial diagnosis. Imaging can be repeated if the findings might change the choice of therapy or if required by a clinical trial. Care should be taken to limit radiation exposure, particularly in younger individuals, given concerns regarding the risk for second malignancies.

The preferred method of assessment of lymph nodes selected as a target lesion is the product of the perpendicular diameters (PPD) of up to six of the largest target nodes >1.5 cm in longest diameter, preferentially from different body regions that are representative of the patient's overall disease burden.

Asymptomatic, early-stage disease – Decisions regarding imaging for asymptomatic, otherwise healthy patients should be individualized, but imaging is not required for early-stage MF without diffuse plaque disease (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].

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].

Lymph node biopsy — Lymph node biopsy is generally reserved for patients in whom clinical examination or imaging suggests lymphadenopathy.

Selection of a node – Biopsy should involve a lymph node ≥1.5 cm in long diameter; a firm, irregular, clustered, or fixed lymph node; or a node with significant metabolic activity by fluorodeoxyglucose (FDG) PET/CT [12].

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 (SUV) on PET/CT. 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 – An excisional biopsy is the gold standard for assessing lymph node involvement [1]. Core needle biopsies (eg, three or four cores) are acceptable if this provides adequate pathologic material for light microscopy, immunophenotyping (including immunohistochemistry), flow cytometry, and molecular methods (eg, clonality, pathogenic genetic variants) [13].

Fine needle aspirate is not adequate to document lymph node involvement by MF/SS.

Node involvement – Lymph node classification reflects the extent of lymph node replacement by atypical cells [1]. 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 TCR gene rearrangement.

The amount and/or size of the abnormal lymphocytes and the degree of effacement of the normal lymph node architecture are used to give a grade of involvement, using either the National Cancer Institute (NCI) or the Dutch scoring system [1]. A clinically abnormal lymph node that is not biopsied (eg, due to skin ulcerations or concerns for poor healing) should be characterized as Nx.

Viscera (M) — Visceral involvement (M1) is usually suspected based on PET/CT and/or diagnostic CT. No visceral involvement is M0.

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 performed for initial staging in patients with MF, but it may be useful in selected cases for an unexplained hematologic abnormality [12].

A bone marrow core biopsy that demonstrates >5 percent nodular, diffuse, or interstitial involvement by MF/SS is considered stage M1. A bone marrow aspirate alone is not sufficient for documenting marrow involvement.

Other organs – Suspected involvement of other viscera should be confirmed histologically, when possible.

Blood (B) — Evaluation should assess the burden of blood involvement (ie, by flow cytometry) and clonality (eg, by TCR rearrangement). Blood involvement is described as B0 to B2.

Flow cytometry is the preferred method for establishing the phenotype of the population of aberrant lymphocytes and classifying the blood tumor burden [1]. Flow cytometry has largely supplanted microscopic examination of the buffy coat of peripheral blood (ie, Sézary cell preparation). (See 'Flow cytometry' below.)

Morphologic findings from a bone marrow biopsy that constitute stage M1 are described above. (See 'Viscera (M)' above.)

Findings associated with SS in peripheral blood are described separately. (See "Clinical presentation, pathologic features, and diagnosis of Sézary syndrome", section on 'Blood assessment'.)

Flow cytometry — Flow cytometry is a standardized, objective method for defining subsets of lymphocytes and for quantification of circulating cells. Flow cytometry has largely replaced Sézary cell preparations for evaluation of blood involvement.

For staging SS by flow cytometry, cells that are CD4+, CD7- or CD4+, and CD26- are considered to be Sézary cells [1]. (See "Clinical presentation, pathologic features, and diagnosis of Sézary syndrome", section on 'Diagnostic criteria'.)

B classification is based on the absolute number of immunophenotypically abnormal lymphocytes. The absolute value is determined by the percentage of aberrant lymphocytes multiplied by the total lymphocyte count from the complete blood count (CBC); it may also be calculated by determining the percentage of aberrant CD45+ white blood cells (WBCs) on flow cytometry multiplied by the WBC count.

B0 (Absence of significant blood involvement) – <250/microL of CD41+/CD26- or CD41+/CD72- cells.

B1 (Low blood tumor burden) – Does not meet criteria for B0 or B2.

B2 (High blood tumor involvement) – ≥1000/microL of CD41+/CD26- or CD41+/CD72- cells (or other aberrant population of lymphocytes identified by flow cytometry).

Bx – Unable to quantify blood involvement according to agreed-upon guidelines.

Clonality — Molecular methods are used to assess clonality of circulating cells.

BIOMED-2 or other polymerase chain reaction (PCR)-based method is used to evaluate TCR-gamma and TCR-beta gene rearrangement. Next-generation sequencing can also be used to establish clonality.

For each category of blood involvement (see 'Flow cytometry' above), a subscript is added to describe clonality.

Subscript A (A) – Clone positive and identical to skin

Subscript B (B) – Clone negative or equivocal

As an example, stage B2 disease should be categorized as B2A (negative for TCR clonality) or B2B (TCR clonality present).

Nonidentical T cell clones are often detected in peripheral blood with increasing age and are of unknown clinical significance [1].

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 3) [12], as described above. (See 'Components of staging' above.)

DISEASE SEVERITY — Scoring systems can be used to document disease burden and 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 (mSWAT) — The modified Severity Weight Assessment Tool (mSWAT) score provides 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 4) [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.

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.

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 the 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 5).

PROGNOSIS — The course of MF and SS is variable. Some patients have limited skin-only disease that waxes and wanes over decades. Others have more generalized thick skin involvement, true folliculotropic disease, or multiple tumors that are prone to disease progression or development of extracutaneous involvement. Features that are associated with poor 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)

These factors can be used to define three distinct risk groups across stages that are associated with significantly different outcomes, as discussed below. (See 'Prognostic indices' below.)

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 3), as described above. (See 'TNMB staging' above.)

The extent and type of skin involvement (T classification) 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 blood involvement [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 a >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). The 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, the median OS was 18 years, disease progression occurred in 34 percent of patients, 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 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 an increased risk of disease progression. N, M, and B classifications, age, and male sex were predictors of poor survival, but they were not associated with the risk of disease progression. By 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, the median OS was not reached after >32 years [19].

The extent of blood involvement (ie, B1 or B2) 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 significant blood involvement had inferior OS and DSS [20]. 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.)

Folliculotropic variant — Folliculotropic MF is an uncommon variant of MF characterized by infiltration of follicles [21,22]. Folliculotropic MF presenting with thick plaques and tumors ("advanced" folliculotropic MF) is generally associated with a greater risk for disease progression and worse prognosis compared with other MF variants [22], but this is a heterogeneous category with variable natural history.

Details of diagnosis, management, and outcomes of folliculotropic MF are presented separately. (See "Variants of mycosis fungoides", section on 'Folliculotropic mycosis fungoides'.)

Transformation to large-cell histology — LCT is reported in 10 to 25 percent of patients with MF [23-25]. Patients with LCT have heterogeneous outcomes with some experiencing rapid deterioration and others having a more indolent clinical course [26,27]. 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 [28]. 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 transformation to large-cell histology – 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 [29]. In a 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 [30]. A retrospective study of 100 patients with transformed MF reported a median survival after transformation of 24 months [26]. 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 [31,32].

A retrospective study of two cancer registries evaluated the outcomes of 399 patients who were diagnosed before age 30 [33]. 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 [34]. Rates of OS at 5 and 10 years were 97 and 96 percent, respectively; all deaths were due to progressive lymphoma. With a 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 [35-37]. (See "Clinical presentation, pathologic features, and diagnosis of Sézary syndrome", section on 'Skin pathology'.)

Ribonucleic acid (RNA) sequencing from lesional cutaneous T cell lymphoma (CTCL) skin of 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 (which encodes a glycosylphosphatidylinositol-anchored glycoprotein with potential roles in T cell migration and costimulation of the immune response) were associated with disease progression and decreased DSS [38]. 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, noncoding, regulatory molecules that may be associated with the progression of MF [39]. 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 [40]. 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.

Cutaneous Lymphoma International Prognostic Index (CLIPi) – The 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 [41]. Adverse prognostic factors identified in early (IA to IIA) stage MF and SS were male sex, age >60, plaques, folliculotropic disease, and N1/Nx classification, while adverse factors those in advanced stage (IIB to IVB) disease included male sex, age >60, B1/B2, N2/3, and visceral involvement. Male sex, age >60, plaques, folliculotropic disease, and N1/Nx classification 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.

Cutaneous Lymphoma International Consortium (CLIC) – The CLIC was developed from a retrospective analysis of 1275 patients at 29 international centers with advanced-stage (IIB to IVB) 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 (zero to one risk factor) – Median survival not reached; estimated survival rates at one, two, and five years were 94, 87, and 68 percent, respectively.

Intermediate risk (two risk factors) – Median survival 46 months; estimated survival rates at one, two, and five years were 84, 72, and 43 percent, respectively.

High risk (three to four 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 — The assessment of the response to treatment should include the following [1]:

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 peripheral lymph nodes and assessment for organomegaly.

Complete blood count with differential count, routine chemistry panels, and lactate dehydrogenase.

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

Repeat imaging studies that were previously abnormal if they are likely to provide additional management information, acknowledging costs of such imaging can be significant, and radiation exposure carries risks.

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 — Standardized response criteria, as described by the Tri-society consensus, consider responses in skin and other involved disease categories (ie, lymph nodes, viscera, and blood) that have been sustained for ≥4 weeks [1]:

Complete response – Complete disappearance of all clinical evidence of disease.

Complete response (CR) in skin plus CR in all categories that were involved at baseline or other categories were not involved (NI).

Partial response – Partial regression of measurable disease.

Partial response (PR) may include either of the following:

CR in skin plus all other involved categories do not have a CR/NI, and no category has progressive disease (PD).

PR in skin plus no other category has PD, and at least one involved category has a PR or CR.

Stable disease – Failure to attain CR, PR, or PD representative of all disease.

Stable disease (SD) may include either of the following:

PR in skin plus no other disease category has PD, and there is no CR or PR in any category of involvement at baseline.

SD in skin plus no other disease category has PD, and there is CR/NI, PR, or SD in any category of involvement.

Progressive disease – PD in any category.

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

Description – The most common types of cutaneous T cell lymphoma (CTCL; ie, non-Hodgkin lymphomas of T cell origin that involve the skin) are:

Mycosis fungoides (MF) – An extranodal CTCL that may also involve lymph nodes, blood, and viscera. The clinical course of MF varies from indolent to aggressive behavior.

Sézary syndrome (SS) – A more aggressive leukemic variant of CTCL with increased levels of circulating malignant (Sézary) cells.

Evaluation – Evaluation for staging of MF/SS (table 1) includes (see 'Staging evaluation' above):

Clinical examination of skin, lymph nodes, and viscera

Complete blood count with differential

Serum chemistries, including lactate dehydrogenase

Skin biopsy

Flow cytometry

Imaging - Chest x-ray; other imaging is performed if visceral involvement is suspected

Components of staging

Skin – Total body skin examination and estimation of body surface area involvement by patches, papules, plaques, and tumors. The type and extent of skin involvement is described as T1 to T4. (See 'Skin (T)' above.)

Lymph nodes – If lymphadenopathy is present, CT of chest/abdomen/pelvis or integrated positron emission tomography (PET)/CT. An excisional biopsy is needed for staging and diagnosis if there are involved lymph nodes. Lymph node involvement is described as N0 to N3. (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, but suspected involvement of other viscera (eg, bone marrow) should be confirmed histologically, when possible. Visceral involvement is described as M1. (See 'Viscera (M)' above.)

Blood – Blood involvement is determined by flow cytometry of peripheral blood and assessment of clonality. Blood involvement is described as B0 to B2. (See 'Blood (B)' above.)

TNMB Staging – The standard method for staging MF and SS is TNMB classification, which is based on evaluation of skin (T), lymph nodes (N), viscera (M), and blood (B) (table 3). (See 'TNMB staging' above.)

Prognosis – Prognosis of MF and SS varies with disease stage. 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. 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 24.0

References

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