Sections

Workup

Approach Considerations

For mycosis fungoides, clinical features, the history of the disease, and histomorphologic and cytomorphologic findings yield clues that lead to a diagnosis in most cases. However, demonstration of a dominant T-cell clone in skin biopsy specimens by a molecular assay (ie, Southern blot, polymerase chain reaction [PCR]) constitutes an additional diagnostic criterion to distinguish cutaneous T-cell lymphoma from inflammatory dermatoses.

For a diagnosis of Sézary syndrome, one or more of the following criteria should be present^[5]:

An absolute Sézary cell count of least 1000 cells/µL
Demonstration of immunophenotypic abnormalities (an expanded CD4⁺ T-cell population that results in a CD4/CD8 ratio of more than 10; loss of any or all of the T-cell antigens CD2, CD3, CD4, and CD5; or loss of both CD4 and CD5)
Demonstration of a T-cell clone in the peripheral blood by molecular or cytogenetic methods - Flow cytometry may be useful for the differential diagnosis of precursor and peripheral T-cell and NK-cell lymphomas^[6]

Following a diagnostic algorithm for the evaluation and diagnosis of erythroderma due to cutaneous T-cell lymphoma, versus erythroderma resulting from "reactive" causes, may be helpful.^[76]

Perform the following tests in the diagnostic workup of mycosis fungoides:

Conduct a complete blood count (CBC) with differential, and review the buffy coat smear for Sézary cells
Look for liver-associated enzyme abnormalities; abnormal transaminase values may indicate hepatic involvement
Obtain uric acid and lactate dehydrogenase (LDH) levels, since uric acid and LDH are markers of bulky and/or biologically aggressive disease
Conduct a flow cytometric study of the blood (include available T-cell–related antibodies) to detect a circulating malignant clone and to assess immunocompetence by quantifying the level of CD8-expressing lymphocytes
Consider human immunodeficiency virus (HIV) and HTLV-I testing

Reflectance confocal microscopy

Reflectance confocal microscopy as an investigational technique in mycosis fungoides may highlight junctional atypical lymphocytes, architectural disarray, and spongiosis.^[77]

Imaging studies

Chest radiography

Perform chest radiography to determine whether there is lung involvement.

CT scanning

Computed tomography (CT) scanning of the abdomen and pelvis may be performed in patients with advanced mycosis fungoides (stage IIB to stage IVB) or in patients with clinically suspected visceral disease.

PET scanning

Positron emission tomography (PET) scanning to determine visceral involvement can be considered in individual cases.

Polymerase Chain Reaction Assay

Consider obtaining polymerase chain reaction (PCR), Southern blot testing of the blood, or both if detecting a circulating clone of malignant cells in the blood will change medical management. Ideally, the abnormal clonal T-cell gene rearrangement detected in the blood should match that found in the skin. However, T-cell gene rearrangement by itself will not allow the physician to make a diagnosis of mycosis fungoides or Sézary syndrome. Disorders that are considered benign (eg, lymphomatoid papulosis) can have T-cell gene rearrangement.

Genetic Testing

Neoplastic mycosis fungoides cells have a mature CD3⁺, CD4⁺, CD45RO⁺, CD8^- memory T-cell phenotype. Rarely, otherwise-classic mycosis fungoides may have a CD4^-, CD8⁺ mature T-cell phenotype.^[78]An aberrant phenotype, such as a loss of pan–T cell antigens (eg, CD2, CD3, CD5), is not unusual.

An identical phenotype is seen in granulomatous slack skin syndrome and Sézary syndrome. Clonal T-cell receptor gene rearrangements are detected in most mycosis fungoides cases.^[79]

Many structural and numerical chromosomal abnormalities have been described in the advanced stages of mycosis fungoides, but recurrent, mycosis fungoides–specific chromosomal translocations have not been identified. Chromosomal loss at 10q and abnormalities in P15, P16, and TP53 tumor suppressor genes are often evident with mycosis fungoides.

The neoplastic T cells in pagetoid reticulosis may have either a CD3⁺, CD4⁺, CD8^- phenotype or a CD3⁺, CD4^-, CD8⁺ phenotype, with CD30 often being expressed.^[80]

Genetic features show T-cell receptor genes to be clonally rearranged in persons with mycosis fungoides, granulomatous slack skin syndrome, or Sézary syndrome. Demonstration of clonal T cells in the peripheral blood is an important diagnostic criterion that allows differentiation between Sézary syndrome and benign forms of erythroderma.^[5]

Recurrent chromosomal translocations are not detected in persons with Sézary syndrome, but complex karyotypes are common, as is a consistent pattern of identical chromosomal abnormalities in Sézary syndrome as seen in mycosis fungoides.^[81]

The neoplastic T cells in adult T-cell leukemia/lymphoma express a CD3⁺, CD4⁺, CD8^- phenotype, with CD25 being highly expressed.^[44]T-cell receptor genes are clonally rearranged; clonally integrated HTLV-1 genes are present and are useful in differentiating between chronic or smoldering variants of adult T-cell leukemia/lymphoma and classic mycosis fungoides or Sézary syndrome.

Panniculitis-like T-cell lymphoma shows an alpha/beta⁺, CD3⁺, CD4^-, CD8⁺ T-cell phenotype, with expression of cytotoxic proteins.^[28]CD30 and CD56 are not expressed. Neoplastic T cells do show clonal T-cell receptor gene rearrangements, although neither specific genetic abnormalities nor EBV has been identified.

Nasal-type extranodal NK/T-cell lymphoma has neoplastic cells that express CD2, CD56, and cytoplasmic CD3.

Biopsy

Perform a skin punch biopsy, which is submitted on sodium chloride–soaked gauze to allow for fixation and snap freezing.

Perform a bone marrow examination only if the patient has proven blood or nodal involvement.

Perform a lymph node biopsy if the nodes are palpable. In a study by Pai et al, the investigators determined that fine-needle aspiration (FNA) biopsy combined with immunophenotyping and T-cell receptor gamma chain PCR (TCR-gamma PCR) assay was “significantly useful” in evaluating lymphadenopathy in patients with mycosis fungoides or, specifically, Sézary syndrome, “especially for triaging lymph nodes that would otherwise not be sampled or for evaluating multiple lymph nodes."^[82]

In the study, the investigators assessed a series of 11 FNA biopsy specimens from 10 patients with mycosis fungoides or Sézary syndrome and performed flow cytometric immunophenotyping and TCR-gamma PCR assay on the FNA biopsy material. These were correlated with cytologic findings.^[82]

Seven of 10 patients in the study demonstrated "lymph node involvement by cutaneous T-cell lymphoma, with 3 cases exhibiting large-cell transformation and 4 cases exhibiting a small-cell pattern."

Another 6 patients in the study were identified, using flow cytometric immunophenotyping, as having an abnormal T-cell population. In 2 cases—one in which insufficient events were present for evaluation by flow cytometry and one in which flow cytometry was not diagnostic of T-cell lymphoma—TCR-gamma PCR assay demonstrated a clonal T-cell rearrangement. Immunohistochemistry on cell block material revealed classic Hodgkin lymphoma in 2 cases.

Histology

In the early stages of mycosis fungoides, the histopathology is nonspecific,^{[83, 84, 85, 86]}and the condition is often misdiagnosed as an inflammatory disorder. Early patch mycosis fungoides shows superficial bandlike or lichenoid infiltrates, mainly consisting of lymphocytes and histiocytes.

A few atypical cells with small to medium, highly indented (cerebriform), and sometimes hyperchromatic nuclei are present and are mostly confined to the epidermis (epidermotropism). They tend to colonize the basal layer of the epidermis either as single, often haloed cells or in a linear configuration,^[79]especially at the tips of the rete ridges. (See the image below.)

Mycosis fungoides with large, atypical T lymphocytes in the epidermis and dermis.

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When a clear halo surrounds an intraepidermal mononuclear cell singly or in clumps, it is called a Pautrier microabscess. Its presence is suggestive of mycosis fungoides, but it is not necessary for the diagnosis. (See the image below.)

Mycosis fungoides with an epidermal nest of large, atypical T cells displaying bizarre, convoluted nuclei surrounded by a clear space (Pautrier microabscess).

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To summarize, the histologic criteria for the diagnosis of mycosis fungoides include the following^[87]:

A bandlike upper dermal infiltrate of lymphocytes and other inflammatory cells, with no grenz zone, is present
Epidermotropism of mononuclear cells occurs
Little spongiosis of the epidermis is found.
Lymphocytes have nuclei that are hyperchromatic and convoluted or cerebriform

Plaque and tumor stages

In mycosis fungoides plaques, the histologic changes are diagnostic; epidermotropism is generally more pronounced than in mycosis fungoides patches. The presence of intraepidermal collections of atypical cells (Pautrier microabscesses) is a highly characteristic feature observed in only a minority of cases (10%).

In the tumor stage, the dermal infiltrates become more diffuse and epidermotropism may be lost. The tumor cells increase in number and size, demonstrating variable proportions of small, medium, and large cerebriform blast cells with prominent nuclei and intermediate forms. Transformation to a diffuse large cell lymphoma of either CD30^- or CD30⁺ phenotype may occur, portending a poor prognosis. Eosinophils, plasma cells, and histiocytes are frequent companions.

Folliculotropic mycosis fungoides

Folliculotropic mycosis fungoides shows a primarily perivascular and periadnexal localization of the dermal infiltrate, with variable involvement of the follicular epithelium by small, medium, or sometimes large hyperchromatic cells with cerebriform nuclei and sparing of the epidermis (folliculotropism instead of epidermotropism).^[29]

Most patients have mucinous degeneration of the follicular epithelium (follicular mucinosis)—which is best demonstrated with Alcian blue staining—and an admixture of eosinophils and sometimes plasma cells. Prominent infiltration of both follicular epithelium and eccrine sweat glands is often observed. Similar cases with prominent infiltration of eccrine sweat glands, often seen with alopecia, have been called syringotropic mycosis fungoides.^[88]Basaloid folliculolymphoid hyperplasia is a distinctive finding in follicular mycosis fungoides.^[89]

Granulomatous mycosis fungoides

Granulomatous mycosis fungoides shows sarcoidal, granuloma annulare–like, or giant cell–rich reactions. Granulomatous slack skin syndrome shows a dermal infiltrate composed of atypical T cells with a dissemination of many multinucleated giant cells containing fragments of elastic fibers.

Pagetoid reticulosis

Pagetoid reticulosis shows a hyperplastic epidermis with marked pagetoid infiltration by atypical, haloed lymphoid cells, singly or arranged in nests. The upper dermis has a mixed infiltrate of lymphocytes or histiocytes.

Sézary syndrome

The histology of Sézary syndrome may be nonspecific, but it is often similar to mycosis fungoides, although the cellular infiltrates in Sézary syndrome are more often monotonous,^{[90, 91]}and epidermotropism may sometimes be absent. Involved lymph nodes have a dense, monotonous infiltrate of Sézary cells with effacement of the normal lymph node architecture, whereas bone marrow infiltrates, when present, are often sparse and mainly interstitial. (See the image below.)^[92]

Electron micrograph of a Sézary cell.

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Adult T-cell leukemia/lymphoma

In adult T-cell leukemia/lymphoma, the cutaneous nodules show a superficial or more diffuse infiltration of medium to large T cells with pleomorphic or multilobated nuclei, often with marked epidermotropism. The histologic picture may be the same as that seen with mycosis fungoides. In the smoldering type of adult T-cell leukemia/lymphoma, dermal infiltrates may be sparse, with only slightly atypical cells.

Subcutaneous panniculitis-like T-cell lymphoma

In subcutaneous panniculitis-like T-cell lymphoma, subcutaneous infiltrates simulate a panniculitis and show small, medium, or sometimes large pleomorphic T cells with hyperchromatic nuclei and often many macrophages.^[30]The overlying epidermis and dermis are typically not involved.^[93]Rimming of individual fat cells by neoplastic T cells is a helpful, although not completely specific, diagnostic feature.^[28]Necrosis, karyorrhexis, and cytophagocytosis are common.

Primary cutaneous aggressive epidermotropic CD8

Primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T-cell lymphoma, characterized by a proliferation of epidermotropic CD8⁺ cytotoxic T cells, has an acanthotic or atrophic epidermis, necrotic keratinocytes, ulceration, and variable spongiosis, sometimes with blister formation.^{[38, 71]}Epidermotropism tends to be marked, ranging from a linear distribution to a pagetoid pattern throughout the epidermis.

This disorder has a beta-F1⁺, CD3⁺, CD8⁺, granzymes-B⁺, perforin⁺, TIA-1⁺, CD45RA⁺, CD45RO, CD2^-, CD4^-, CD5^-, CD7^+/- phenotype.^{[55, 71]}It is usually associated with EBV seronegativity. The lymphoma cells show clonal TCR gene rearrangements, although specific genetic abnormalities have not been described.

Cutaneous gamma/delta-positive T-cell lymphoma

Cutaneous gamma/delta-positive T-cell lymphoma has 3 major histologic patterns of involvement that can be present in the skin; specifically, epidermotropic, dermal, and subcutaneous.^[30]More than 1 is often present in the same patient in different biopsy specimens or within a single biopsy specimen.^[59]The lymphoma cells are generally medium to large, with coarsely clumped chromatin; large blastic cells with vesicular nuclei and prominent nucleoli are infrequent and apoptosis and necrosis are common, often with angioinvasion. The subcutaneous involvement may demonstrate rimming of fat cells.

Cutaneous gamma/delta-positive T-cell lymphoma cells are generally of beta-F1^-, CD3⁺, CD2⁺, CD5^-, CD7^+/-, CD56⁺ phenotype with strong expression of cytotoxic proteins.^[30]Most lack both CD4 and CD8, although CD8 may be expressed in some cases.^{[59, 94]}In frozen-section specimens, the lymphoma cells are strongly positive for TCR -delta. If only paraffin sections are available, the absence of beta-F1 may be used to infer a gamma/delta origin.^[95]

The lymphoma cells show clonal rearrangement of the TCR -gamma gene, while TCR -beta may be rearranged or deleted but is not expressed. EBV test results are usually negative.^[59]

Primary cutaneous CD4

Histologically, this disorder shows dense, diffuse, or nodular infiltrates within the dermis that have a tendency to infiltrate the subcutis. Epidermotropism is often present focally. A predominance of small/medium-sized pleomorphic T cells may be seen, with a smaller proportion of large pleomorphic cells present.^[96]

Primary cutaneous CD4⁺ small/medium T-cell lymphoproliferative disorder is a CD3⁺, CD4⁺, CD8^-, CD30^- phenotypic lymphoma. Cytotoxic proteins are generally not expressed, and sometimes there is a loss of pan–T-cell markers.^[55]The TCR genes are clonally rearranged.^[72]

Nasal-type extranodal NK/T-cell lymphoma

Nasal-type extranodal NK/T-cell lymphoma has dense dermal and often subcutaneous infiltrates with prominent angiocentricity and angiodestruction, often accompanied by extensive necrosis.^{[56, 97]}

Primary cutaneous peripheral T-cell lymphoma, unspecified

Primary cutaneous peripheral T-cell lymphoma, unspecified, shows an aberrant CD4⁺ T-cell phenotype with variable loss of pan–T-cell antigens. CD30 staining is negative or restricted to a few scattered tumor cells. Rare cases may show coexpression of CD56. Expression of cytotoxic proteins is uncommon.^[55]

Staging of Mycosis Fungoides

Despite the fact that mycosis fungoides and Sézary syndrome are types of non-Hodgkin lymphoma, an entirely different staging system is used for these disorders. The system is based on the particular skin findings and findings of extracutaneous disease that are observed in affected patients, with the stages defined as follows:

Stage IA disease (as defined by the tumor, node, metastases, blood [TNMB] system) - Patchy or plaquelike skin disease involving less than 10% of the skin surface area (T1 skin disease)
Stage IB - Patchy or plaquelike skin disease involving 10% or more of the skin surface area (T2 skin disease)
Stage IIB disease - Tumors are present (T3 skin lesions)
Stage III disease - Generalized erythroderma is present
Stage IVA1 disease - Erythroderma and significant blood involvement occur^[7]
Stage IVA2 disease - Lymph node biopsy result shows total effacement by atypical cells (LN4 node)^[7]
Stage IVB disease - Visceral involvement (eg, liver, lung, bone marrow) occurs

These definitions are denoted in Table 3. Table 4 lists the TNMB stage definitions. Table 5 is a comparison of the 2 systems.

Table 3. Staging of Cutaneous T-Cell Lymphoma (Open Table in a new window)

Stage	Skin Lesions			Lymphadenopathy	Erythroderma	Histology
Stage	Patches/ plaques (less than10%)	Plaques/ plaques (10% or more)	Tumors	Lymphadenopathy	Erythroderma	Lymph Nodes	Viscera
IA	+	-	-	-	-	-	-
IB	+ or -	+	-	-	-	-	-
IIA	+ or -	+ or -	+ or -	+	-	-	-
IIB	+ or -	+ or -	+	+ or -	-	-	-
III	+ or -	+ or -	+ or -	+ or -	+	-	-
IVA	+ or -	+ or -	+ or -	+ or -	+ or -	+	-
IVB	+ or -	+ or -	+ or -	+ or -	+ or -	+ or -	+

Table 4. TNMB Staging of Cutaneous T-Cell Lymphoma (Open Table in a new window)

Stage Class	Stage	Definition
T (tumor)	T₁	Patches/plaques involving less than 10% of body surface
	T₂	Patches/plaques involving 10% or more of body surface
	T₃	Tumor(s) present on skin
	T₄	Erythroderma
N (nodes)	N₀	No enlarged lymph node present
	N₁	Enlarged lymph nodes, histologically uninvolved
	N₂	No enlarged lymph node; 1 or more nodes histologically involved*
	N₃	Enlarged lymph nodes, histologically involved
M (metastasis to viscera)	M₀	No visceral lesion present
M (metastasis to viscera)	M₁	Visceral involvement
B (blood involvement)	B₀	Circulating atypical lymphocytes (Sézary cells) less than 5% of lymphocytes
B (blood involvement)	B₁	Circulating atypical lymphocytes 5% or more of lymphocytes (Sézary syndrome)
*Uncommon finding, usually not considered/investigated.

Table 5. Comparison of Staging Systems for CTCL (Open Table in a new window)

Clinical Stage	TNM (B) Stage
IA	T₁ N₀ M₀
IIB	T₂ N₀ M₀
IIA	T₁ N₁ M₀	T₂ N₁ M₀
IIB	T₃ N₀ M₀	T₃ N₁ M₀
III	T₄ N₀ M₀	T₄ N₁ M₀
IVA	T₁ N₂ M₀	T₂ N₂ M₀	T₃ N₂ M₀	T₄ N₂ M₀
IVA	T₁ N₃ M₀	T₂ N₃ M₀	T₃ N₃ M₀	T₄ N₃ M₀
IVB	T₁ N₀ M₁	T₂ N₀ M₁	T₃ N₀ M₁	T₄ N₀ M₁
	T₁ N₁ M₁	T₂ N₁ M₁	T₃ N₁ M₁	T₄ N₁ M₁
	T₁ N₂ M₁	T₂ N₂ M₁	T₃ N₂ M₁	T₄ N₂ M₁
	T₁ N₃ M₁	T₂ N₃ M₁	T₃ N₃ M₁	T₄ N₃ M₁

Treatment & Management

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Media Gallery

Patch-stage mycosis fungoides.
Plaque-stage mycosis fungoides.
A 40-year-old woman complained of a recurrent skin rash, which she described as "bug bites." Skin biopsy results demonstrated an atypical lymphoid infiltrate that was CD30 positive. The clinical picture and pathologic findings were consistent with lymphomatoid papulosis. This condition has a benign natural history, despite clonal gene rearrangement in some cases. Skin eruptions occur in self-limited crops, which do not require treatment.
Erythroderma of Sézary syndrome.
Nail changes of Sézary syndrome.
Electron micrograph of a Sézary cell.
Tumor-stage mycosis fungoides.
Tumor-stage cutaneous T-cell lymphoma.
Patch-stage cutaneous T-cell lymphoma. Courtesy of Jeffrey Meffert, MD.
Plaque-stage parapsoriasis.
Patch-stage mycosis fungoides progressing to plaque stage, with cutaneous cigarette-paper appearance evident.
Partially confluent, erythematous plaques in advancing mycosis fungoides.
Close-up view of advancing plaque-stage mycosis fungoides with partially confluent, erythematous plaques.
Early patch-stage cutaneous T-cell lymphoma.
Hypopigmented cutaneous T-cell lymphoma. Courtesy of Jeffrey Meffert, MD.
Hypopigmented cutaneous T-cell lymphoma. Courtesy of Jeffrey Meffert, MD.
Nodular mycosis fungoides.
Middle-aged woman with mycosis fungoides showing ulceration and marked depigmentation of advanced disease.
Middle-aged woman with mycosis fungoides showing ulceration and marked depigmentation of advanced disease.
Middle-aged woman with mycosis fungoides showing ulceration and marked depigmentation of advanced disease.
Middle-aged woman with mycosis fungoides showing ulceration and marked depigmentation of advanced disease.
Mycosis fungoides with large, atypical T lymphocytes in the epidermis and dermis.
Mycosis fungoides with an epidermal nest of large, atypical T cells displaying bizarre, convoluted nuclei surrounded by a clear space (Pautrier microabscess).
A 42-year-old woman who had moved to the United States from Peru several year ago presented with an ulcerative lesion on her face near her nose, and destruction of her hard palate. Tissue biopsy revealed NK/T-cell lymphoma. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.

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Table 1. WHO-EORTC Classification of Cutaneous T-Cell Lymphoma

WHO-EORTC Classification	Frequency (%)	5-Year Survival Rate (%)
Indolent Clinical Behavior
Mycosis fungoides	39	88
Mycosis fungoides variants and subtypes
Folliculotropic mycosis fungoides	5	75
Pagetoid reticulosis	< 1	100
Granulomatous slack skin	< 1	100
Primary cutaneous CD30⁺ lymphoproliferative disorder
Primary cutaneous anaplastic large cell lymphoma	8	95
Lymphomatoid papulosis	12	100
Subcutaneous panniculitis-like T-cell lymphoma (provisional)	1	82
Primary cutaneous CD4⁺ small/medium-sized pleomorphic T-cell lymphoma (provisional)	2	75
Aggressive Clinical Behavior
Sézary syndrome	2%	36%
Adult T-cell leukemia/lymphoma	< 1	NDA
Extranodal NK/T-cell lymphoma, nasal type	< 1	16
Primary cutaneous peripheral T-cell lymphoma, unspecified	2	15
Primary cutaneous peripheral T-cell lymphoma, rare subtypes
Primary cutaneous acral CD8⁺ T-cell lymphoma (provisional)	< 1	100
Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (provisional)	< 1	31
Primary cutaneous gamma/delta-positive T-cell lymphoma	< 1	11
Source: Adapted from Willemze et al. Blood. 2019;133(16):1703-14.^[3] EORTC = European Organization of Research and Treatment of Cancer; NDA = no data available; NK = natural killer; WHO = World Health Organization.

Table 2. Cluster Designations

CD Type	Representative Cells	Also Known As
CD2	T, NK	Sheep RBC
CD3	T
CD4	T subset	Helper
CD5	T
CD7	T, NK	Prothymocyte
CD8	T subset, NK	Suppressor
CD25	Active T, B, M	IL-2R (Tac)
CD30	Active T, B	Ki-1
CD45	T subset	CLA
CD56	NK	NCAM
B = B cell; CD = cluster designation; CLA = common leukocyte antigen; IL-2R = interleukin-2 receptor; M = M cell; NCAM = neural cell adhesion molecule; NK = natural killer; RBC = red blood cell; T = T cell; Tac = Tac antigen.

Table 3. Staging of Cutaneous T-Cell Lymphoma

Stage	Skin Lesions			Lymphadenopathy	Erythroderma	Histology
Stage	Patches/ plaques (less than10%)	Plaques/ plaques (10% or more)	Tumors	Lymphadenopathy	Erythroderma	Lymph Nodes	Viscera
IA	+	-	-	-	-	-	-
IB	+ or -	+	-	-	-	-	-
IIA	+ or -	+ or -	+ or -	+	-	-	-
IIB	+ or -	+ or -	+	+ or -	-	-	-
III	+ or -	+ or -	+ or -	+ or -	+	-	-
IVA	+ or -	+ or -	+ or -	+ or -	+ or -	+	-
IVB	+ or -	+ or -	+ or -	+ or -	+ or -	+ or -	+

Table 4. TNMB Staging of Cutaneous T-Cell Lymphoma

Stage Class	Stage	Definition
T (tumor)	T₁	Patches/plaques involving less than 10% of body surface
	T₂	Patches/plaques involving 10% or more of body surface
	T₃	Tumor(s) present on skin
	T₄	Erythroderma
N (nodes)	N₀	No enlarged lymph node present
	N₁	Enlarged lymph nodes, histologically uninvolved
	N₂	No enlarged lymph node; 1 or more nodes histologically involved*
	N₃	Enlarged lymph nodes, histologically involved
M (metastasis to viscera)	M₀	No visceral lesion present
M (metastasis to viscera)	M₁	Visceral involvement
B (blood involvement)	B₀	Circulating atypical lymphocytes (Sézary cells) less than 5% of lymphocytes
B (blood involvement)	B₁	Circulating atypical lymphocytes 5% or more of lymphocytes (Sézary syndrome)
*Uncommon finding, usually not considered/investigated.

Table 5. Comparison of Staging Systems for CTCL

Clinical Stage	TNM (B) Stage
IA	T₁ N₀ M₀
IIB	T₂ N₀ M₀
IIA	T₁ N₁ M₀	T₂ N₁ M₀
IIB	T₃ N₀ M₀	T₃ N₁ M₀
III	T₄ N₀ M₀	T₄ N₁ M₀
IVA	T₁ N₂ M₀	T₂ N₂ M₀	T₃ N₂ M₀	T₄ N₂ M₀
IVA	T₁ N₃ M₀	T₂ N₃ M₀	T₃ N₃ M₀	T₄ N₃ M₀
IVB	T₁ N₀ M₁	T₂ N₀ M₁	T₃ N₀ M₁	T₄ N₀ M₁
	T₁ N₁ M₁	T₂ N₁ M₁	T₃ N₁ M₁	T₄ N₁ M₁
	T₁ N₂ M₁	T₂ N₂ M₁	T₃ N₂ M₁	T₄ N₂ M₁
	T₁ N₃ M₁	T₂ N₃ M₁	T₃ N₃ M₁	T₄ N₃ M₁

Table 4. International Society for Cutaneous Lymphoma/European Organization for Research and Treatment of Cancer tumor-node-metastasis-blood revised classification for mycosis fungoides and Sezary syndrome

Skin	Involvement	Node	Involvement	Viscera	Involvement
T1	Patchy or plaquelike skin disease involving ≤10% of the skin surface area	N0	No abnormal lymph nodes	M0	No visceral organ involvement
T2	Patchy or plaquelike skin disease involving ≥10% of the skin surface area	N1	Histopathology Dutch Gr 1 or NCI LN 0-2	M1	Visceral organ involvement
T3	Tumors are present ≥1 cm in diameter	N2	Histopathology Dutch Gr 2 or NCI LN 3	MX	Abnormal visceral site; no histologic confirmation
T4	Erythroderma ≥80% of body area	N3	Histopathology Dutch Gr 3-4 or NCI LN 4	Blood	Involvement
		Nx	Abnormal lymph nodes; no histologic confirmation	B0	≤5% of peripheral blood lymphocytes are Sezary cells
				B1	>5% of peripheral blood lymphocytes are Sezary cells but do met B2 criteria
				B2	≥1000/mcL Sezary cells or CD4/CD8 ≥10 or ≥40% CD4+/CD7- or ≥30% CD4+/CD26- cells

Table 5. Staging classifications for mycosis fungoides and Sezary syndrome

Clinical Stage	5-Year Survival ^[131]	TNM (B) Stage
IA	98%	T₁N₀M₀B₀	T₁N₀M₀B₁
IB	89%	T₂N₀M₀B₀	T₂N₀M₀B₁
IIA	89%	T₁N₁M₀B₀	T₁N₁M₀B₁	T₁N₂M₀B₀	T₁N₂M₀B₁
IIA		T₂N₁M₀B₀	T₂N₁M₀B₁	T₂N₂M₀B₀	T₂N₂M₀B₁
IIB	56%	T₃N₀M₀B₀	T₃N₀M₀B₁	T₃N₁M₀B₀	T₃N₁M₀B₁
IIB		T₃N₂M₀B₀	T₃N₂M₀B₁
IIIA	54%	T₄N₀M₀B₀	T₄N₁M₀B₀	T₄N₂M₀B₀
IIIB	48%	T₄N₀M₀B₁	T₄N₁M₀B₁	T₄N₂M₀B₁
IVA1	41%	T₁N₀M₀B₂	T₂N₀M₀B₂	T₃N₀M₀B₂	T₄N₀M₀B₂
		T₁N₁M₀B₂	T₂N₁M₀B₂	T₃N₁M₀B₂	T₄N₁M₀B₂
		T₁N₂M₀B₂	T₂N₂M₀B₂	T₃N₂M₀B₂	T₄N₂M₀B₂
IVA2	23%	T₁N₃M₀B₀	T₂N₃M₀B₀	T₃N₃M₀B₀	T₄N₃M₀B₀
		T₁N₃M₀B₁	T₂N₃M₀B₁	T₃N₃M₀B₁	T₄N₃M₀B₁
		T₁N₃M₀B₂	T₂N₃M₀B₂	T₃N₃M₀B₂	T₄N₃M₀B₂
IVB	18%	T₁N₀M₁B₀	T₂N₀M₁B₀	T₃N₀M₁B₀	T₄N₀M₁B₀
		T₁N₁M₁B₁	T₂N₁M₁B₁	T₃N₁M₁B₁	T₄N₁M₁B₁
		T₁N₂M₁B₂	T₂N₂M₁B₂	T₃N₂M₁B₂	T₄N₂M₁B₂
		T₁N₃M₁B₃	T₂N₃M₁B₃	T₃N₃M₁B₃	T₄N₃M₁B₃

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Author

Lauren C Pinter-Brown, MD Director of Lymphoma Program, Clinical Professor of Medicine, Department of Internal Medicine, Division of Hematology and Oncology, University of California, Los Angeles, Medical Center

Lauren C Pinter-Brown, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Hematology, SWOG

Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Francisco J Hernandez-Ilizaliturri, MD Professor of Medicine, Department of Medical Oncology, Associate Professor of Immunology, Department of Immunology, Chief, Lymphoma and Myeloma Section, Director, The Lymphoma Translational Research Program, Roswell Park Cancer Institute, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Francisco J Hernandez-Ilizaliturri, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Priyank P Patel, MD Hematology/Oncology Fellow, Roswell Park Cancer Institute, University

Priyank P Patel, MD is a member of the following medical societies: American Society of Hematology, American Society of Clinical Oncology, European Society for Medical Oncology, American College of Physicians

Disclosure: Nothing to disclose.

Acknowledgements

Günter Burg, MD Professor and Chairman Emeritus, Department of Dermatology, University of Zürich School of Medicine; Delegate of The Foundation for Modern Teaching and Learning in Medicine Faculty of Medicine, University of Zürich, Switzerland

Günter Burg, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, International Society for Dermatologic Surgery, North American Clinical Dermatologic Society, and Pacific Dermatologic Association

Disclosure: Nothing to disclose

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa