Advertisement

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)

Elise Olsen, Eric Vonderheid, Nicola Pimpinelli, Rein Willemze, Youn Kim, Robert Knobler, Herschel Zackheim, Madeleine Duvic, Teresa Estrach, Stanford Lamberg, Gary Wood, Reinhard Dummer, Annamari Ranki, Gunter Burg, Peter Heald, Mark Pittelkow, Maria-Grazia Bernengo, Wolfram Sterry, Liliane Laroche, Franz Trautinger and Sean Whittaker for the ISCL/EORTC
This article has an Erratum 111(9):4830

Data supplements

Article Figures & Data

Figures

Tables

  • Table 1

    Original Mycosis Fungoides Cooperative Group TNM classification of cutaneous T-cell lymphoma (CTCL)

    ClassificationDescription
    T: Skin*
        T0Clinically and/or histopathologically suspicious lesions
        T1Limited plaques, papules, or eczematous patches covering < 10% of the skin surface
        T2Generalized plaques, papules, or erythematous patches covering ≥ 10% or more of the skin surface
        T3Tumors, one or more
        T4Generalized erythroderma
    N: Lymph nodes
        N0No clinically abnormal peripheral lymph nodes; pathology negative for CTCL
        N1Clinically abnormal peripheral lymph nodes; pathology negative for CTCL
        N2No clinically abnormal peripheral lymph nodes; pathology positive for CTCL
        N3Clinically abnormal peripheral lymph nodes; pathology positive for CTCL
    B: Peripheral blood
        B0Atypical circulating cells not present (< 5%)
        B1Atypical circulating cells present (> 5%); record total white blood count and total lymphocyte counts, and number of atypical cells/100 lymphocytes
    M: Visceral organs
        M0No visceral organ involvement
        M1Visceral involvement (must have pathology confirmation and organ involved should be specified)
    • * Pathology of T1-4 is diagnostic of a CTCL. When more than 1 T exists, both are recorded and the highest is used for staging (eg, T4(3)).

    • Record number of sites of abnormal nodes (eg, cervical; left + right), axillary (left + right), inguinal (left + right), epitrochlear, and submandibular/submaxillary.

  • Table 2

    Original Mycosis Fungoides Cooperative Group staging system for cutaneous T-cell lymphoma (CTCL)

    Clinical stageTNM
    IA100
    IB200
    IIA1,210
    IIB30,10
    III40,10
    IVA1-42,30
    IVB1-40-31
    • The “B” classification does not alter clinical stage.

  • Table 3

    Algorithm for the diagnosis of early MF15

    CriteriaMajor (2 points)Minor (1 point)
    Clinical
        Persistent and/or progressive patches and plaques plusAny 2Any 1
            (1) Non–sun-exposed location
            (2) Size/shape variation
            (3) Poikiloderma
    Histopathologic
        Superficial lymphoid infiltrate plusBothEither
            (1) Epidermotropism without spongiosis
            (2) Lymphoid atypia*
    Molecular/biologic: clonal TCR gene rearrangementNAPresent
    Immunopathologic
            (1) CD2,3,5 less than 50% of T cellsNAAny 1
            (2) CD7 less than 10% of T cells
            (3) Epidermal discordance from expression of CD2,3,5 or CD7 on dermal T cells
    • — indicates not applicable.

    • * Lymphoid atypia is defined as cells with enlarged hyperchromatic nuclei and irregular or cerebriform nuclear contours.

    • Not applicable since it cannot fulfill any major criteria.

  • Table 4

    ISCL/EORTC revision to the classification of mycosis fungoides and Sézary syndrome

    TNMB stages
    Skin
        T1Limited patches,* papules, and/or plaques covering < 10% of the skin surface. May further stratify into T1a (patch only) vs T1b (plaque ± patch).
        T2Patches, papules or plaques covering ≥ 10% of the skin surface. May further stratify into T2a (patch only) vs T2b (plaque ± patch).
        T3One or more tumors (≥ 1-cm diameter)
        T4Confluence of erythema covering ≥ 80% body surface area
    Node
        N0No clinically abnormal peripheral lymph nodes§; biopsy not required
        N1Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2
            N1aClone negative#
            N1bClone positive#
        N2Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3
            N2aClone negative#
            N2bClone positive#
        N3Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3-4 or NCI LN4; clone positive or negative
        NxClinically abnormal peripheral lymph nodes; no histologic confirmation
    Visceral
        M0No visceral organ involvement
        M1Visceral involvement (must have pathology confirmation and organ involved should be specified)
    Blood
        B0Absence of significant blood involvement: ≤ 5% of peripheral blood lymphocytes are atypical (Sézary) cells
            B0aClone negative#
            B0bClone positive#
        B1Low blood tumor burden: > 5% of peripheral blood lymphocytes are atypical (Sézary) cells but does not meet the criteria of B2
            B1aClone negative#
            B1bClone positive#
        B2High blood tumor burden: ≥ 1000/μL Sézary cells with positive clone#
    • * For skin, patch indicates any size skin 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% large cells), CD30+ or CD30, and clinical features such as ulceration are important to document.

    • 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 peripheral lymph node(s) indicates any palpable peripheral node that on physical examination is firm, irregular, clustered, fixed or 1.5 cm or larger in diameter. Node groups examined on physical examination include cervical, supraclavicular, epitrochlear, axillary, and inguinal. Central nodes, which are not generally amenable to pathologic assessment, are not currently considered in the nodal classification unless used to establish N3 histopathologically.

    • For viscera, spleen and liver may be diagnosed by imaging criteria.

    • For blood, Sézary cells are defined as lymphocytes with hyperconvoluted cerebriform nuclei. If Sézary cells are not able to be used to determine tumor burden for B2, then one of the following modified ISCL criteria along with a positive clonal rearrangement of the TCR may be used instead: (1) expanded CD4+ or CD3+ cells with CD4/CD8 ratio of 10 or more, (2) expanded CD4+ cells with abnormal immunophenotype including loss of CD7 or CD26.

    • # A T-cell clone is defined by PCR or Southern blot analysis of the T-cell receptor gene.

  • Table 5

    Histopathologic staging of lymph nodes in mycosis fungoides and Sézary syndrome

    Updated ISCL/EORTC classificationDutch system58NCI-VA classification13,57,59
    N1Grade 1: dermatopathic lymphadenopathy (DL)LN0: no atypical lymphocytes
    LN1: occasional and isolated atypical lymphocytes (not arranged in clusters)
    LN2: many atypical lymphocytes or in 3-6 cell clusters
    N2Grade 2: DL; early involvement by MF (presence of cerebriform nuclei > 7.5 μm)LN3: aggregates of atypical lymphocytes; nodal architecture preserved
    N3Grade 3: partial effacement of LN architecture; many atypical cerebriform mononuclear cells (CMCs) Grade 4: complete effacementLN4: partial/complete effacement of nodal architecture by atypical lymphocytes or frankly neoplastic cells
  • Table 6

    Recommended evaluation/initial staging of the patient with mycosis fungoides/Sézary syndrome

    Complete physical examination including
        Determination of type(s) of skin lesions
            If only patch/plaque disease or erythroderma, then estimate percentage of body surface area involved and note any ulceration of lesions
            If tumors are present, determine total number of lesions, aggregate volume, largest size lesion, and regions of the body involved
        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
        Most indurated area if only one biopsy
        Immunophenotyping to include at least the following markers: CD2, CD3, CD4, CD5, CD7, CD8, 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.
        Evaluation for clonality of TCR gene rearrangement
    Blood tests
        CBC with manual differential, liver function tests, LDH, comprehensive chemistries
        TCR gene rearrangement and relatedness to any clone in skin
        Analysis for abnormal lymphocytes by either Sézary cell count with determination absolute number of Sézary cells and/or flow cytometry (including CD4+/CD7 or CD4+/CD26)
    Radiologic tests
        In patients with T1N0B0 stage disease who are otherwise healthy and without complaints directed to a specific organ system, and in selected patients with T2N0B0 disease with limited skin involvement, radiologic studies may be limited to a chest X-ray or ultrasound of the peripheral nodal groups to corroborate absence of adenopathy
        In all patients with other than presumed stage IA disease, or selected patients with limited T2 disease and the absence of adenopathy or blood involvement, CT scans of chest, abdomen, and pelvis alone ± FDG-PET scan are 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 either ≥ 1.5 cm in diameter and/or is firm, irregular, clustered, or fixed
        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 (SUV).
            If there is no additional imaging information and multiple nodes are enlarged and otherwise equal in size or consistency, the order of preference is cervical, axillary, and inguinal areas.
        Analysis: pathologic assessment by light microscopy, flow cytometry, and TCR gene rearrangement.
  • Table 7

    ISCL/EORTC revision to the staging of mycosis fungoides and Sézary syndrome

    TNMB
    IA1000,1
    IB2000,1
    II1,21,200,1
    IIB30-200,1
    III40-200,1
    IIIA40-200
    IIIB40-201
    IVA11-40-202
    IVA21-4300-2
    IVB1-40-310-2