Sections

Treatment

Approach Considerations

The evaluation and treatment of individuals with mycosis fungoides is usually conducted on an outpatient basis. Symptomatic treatments (eg, emollients, antipruritics) are used in combination with specific topical and systemic treatments.

Mycosis fungoides treatment selection should be based on the stage and previous treatment history. In general, topical therapies are indicated for stage I patients, and systemic therapies or combinations of topical and systemic therapies are indicated for patients with stage IIB disease or greater, or for patients with stage I mycosis fungoides who are intolerant of topical treatments or whose condition has failed to respond to such treatments.^{[9, 10, 11, 12, 13, 14, 15, 16]}

Sequential therapies that are stage appropriate are selected on the basis of convenience and availability to the patient, as well as on short- and long-term toxicity profiles. Therapies may also be selected based on the probability that a given patient's condition will respond and on the rapidity of onset of that response.

Clinicians should encourage the use of supportive treatments to decrease pruritus and to lubricate the skin in patients with mycosis fungoides. Nonspecific antipruritic treatments are useful and often necessary adjuncts to more specific therapies. Patients should avoid sun exposure and should remain in a cool environment.

Treatment of localized mycosis fungoides

Localized mycosis fungoides may benefit from a number of therapeutic modalities, including radiotherapy, intralesional steroids, or surgical excision. In early-stage cutaneous disease, complete remission rates of 80-90% have been reported with ultraviolet (UV) light therapy^[16]; narrowband UVB is recommended for patches/thin plaques, while psoralen and UVA (PUVA) is recommended for thicker plaques.^[98]PUVA may be used in conjunction with systemic treatment (eg, interferon alpha-2).^[16]

One option is to excise a patch or plaque with a 0.5-cm margin and then control subsequent disease using one of the following treatment modalities^[99]:

Irradiation
PUVA
Photodynamic therapy
Carbon dioxide laser surgery

Localized radiation or a surgical approach to localized mycosis fungoides can be used. The advantage of using surgery first is that a full dose of radiation can be delivered in the same location at a later time, thus preserving options for future therapy.

A retrospective review by Thomas et al indicated that the use of a single dose of radiation (700-800 cGy) in place of multiple-fraction radiation treatment still results in excellent palliation in patients with cutaneous T-cell lymphoma. The investigators reviewed the results of radiation treatment in 270 lesions in a total of 58 patients (most of whom had mycosis fungoides); 97% of the lesions had been treated with 700 cGy or more of radiation.^[100]

Over a mean follow-up period of 41.3 months, Thomas et al noted a complete response (CR) in 255 of the 270 lesions (94.4%) and a partial response in 10 lesions (3.7%). Four lesions (1.5%) demonstrated a partial response that, following a second treatment, became a CR. Only one lesion (0.4%) showed no response.^[100]

The investigators also found the following results:

A lower CR rate in lesions in the lower extremities than in other parts of the body
A lower CR rate in lesions treated with photons than in those treated with electrons
A lower CR rate in lesions demonstrating large-cell transformation and tumor morphology
A significantly lower overall survival rate in patients with Sézary syndrome and erythroderma than in other patients

Thomas et al also determined that the cost of multiple-fraction radiation treatment was more than 200% greater than it was for single-fraction therapy.

See also Service Guidance and Standards for Photodynamic Therapy (PDT), from the British Association of Dermatologists.

Extracorporeal photophoresis

Extracorporeal photopheresis, either alone or in combination with other treatment modalities (eg, interferon alfa), is an effective treatment for Sézary syndrome and for erythrodermic mycosis fungoides, with overall response rates of 30-80% and complete response rates of 14-25%.^[17]The alleged superiority of extracorporeal photopheresis over the traditional low-dose chemotherapy regimens has not been proven.

Combination chemotherapy

Combination chemotherapy is generally not used in mycosis fungoides, because the infectious complications of this treatment, as well as the short response duration, outweigh the modest response rates (compared with those of other non-Hodgkin lymphomas) seen in this disease. Increased survival is not demonstrated with the use of combination chemotherapy relative to sequential topical agents.

However, multiagent chemotherapy is used with unequivocal lymph node or systemic involvement or in cases with widespread tumor-stage mycosis fungoides that is refractory to skin-targeted therapies and is not early patch/plaque-stage disease.

Transplantation

In highly selected patients, allogeneic or autologous bone marrow transplantation has yielded a 5-year overall survival rate ranging from 30% to 50%, with a relapse-free survival rate of 15% to 25%.^{[101, 16]}A German study suggested that allogeneic stem cell transplantation may be an important alternative option for young patients with treatment-refractory mycosis fungoides, because "complete clinical remission can be obtained even in advanced stages."^[9]Reduced-intensity umbilical cord blood transplantation is another option for advanced mycosis fungoides.^[102]

Consultations

Consultations with a dermatologist, medical oncologist, and/or radiation oncologist may aid clinicians in the management of patients with mycosis fungoides.

Topical Therapy

Topical mycosis fungoides treatments, such as topical steroids, topical retinoids, topical chemotherapy, and light treatment that may be enhanced by the ingestion of psoralen, are used to induce remissions, which may be lengthy in patients whose disease is largely confined to the skin. In the patch or plaque stage of the disease, the following topical treatments are generally used:

Topical steroids
Topical retinoids
Topical chemotherapy - Eg, nitrogen mustard or bischloroethylnitrosourea (BCNU)
Phototherapy with ultraviolet (UV) light - UV-B light treatment or UV-A light treatment enhanced with psoralen (PUVA)
Total-body electron beam radiation

These modalities are also used in combination with systemic modalities (eg, PUVA plus interferon) for higher-stage disease.

A majority of patients in the patch stage will have a response, usually to class I (highest potency) steroids; steroids lyse T lymphocytes and block cytokine secretion. Most cases of patch- or plaque-stage disease will respond to PUVA (76-90% complete responses); psoralens inhibit DNA synthesis in tissues exposed to psoralen and UV-A. In addition, most cases of patch- or plaque-stage disease will respond to topical chemotherapy agents, which inhibit cell growth and proliferation (complete response rate, 60%).

Retinoids are vitamin A analogues involved in the modulation of cell growth, division, reproduction, and differentiation.^[103]Their biologic effects result from alterations in gene expressions that are mediated through 2 major types of nuclear receptors, the retinoic acid receptor and the retinoic X receptor. Each receptor subtype likely controls the expression of unique and common genes. Subclass-specific retinoids are available.

Mechlorethamine topical (Valchlor) is approved for mycosis fungoides–type cutaneous T-cell lymphoma (MF-type CTCL). Approval was based on a trial in patients with refractory stage IA-IIA MF-type CTCL, in which 60% of patients treated with mechlorethamine had a confirmed response at 12 months, compared with 48% of those treated with a pharmacy-compounded mechlorethamine preparation.^{[104, 105, 106]}

Systemic Therapy

Systemic treatment, such as oral retinoids, recombinant interferon alfa, fusion toxins, monoclonal antibodies, and single-agent chemotherapy, can be used sequentially to palliate symptoms from more advanced mycosis fungoides. Many active agents exist, including antimetabolites, alkylating agents, topoisomerase II inhibitors, anthracyclines, and purine analogues. The most extensive data exist for the use of methotrexate.^[107]

Other examples of systemic treatment for mycosis fungoides include the following:

Extracorporeal photopheresis - Leukapheresis with UV-A light treatment enhanced with psoralen (PUVA) for the collected white blood cells, with reinfusion of treated cells
Oral retinoids
Histone deacetylase inhibitor treatment (eg, romidepsin) - These agents may inhibit gene transcription
CC chemokine receptor type 4 (CCR4)–directed monoclonal antibody

Biologic response modifiers may inhibit the proliferative capacity of malignant T cells by modulating cytokine production. These agents may also enhance the antitumor immune response by augmenting cell-mediated cytotoxicity.

Brentuximab vedotin (Adcetris), an antibody-drug conjugate, was first approved by the FDA in 2011 for treatment of relapsed or refractory Hodgkin lymphoma and relapsed or refractory systemic anaplastic large cell lymphoma (ALCL). In 2018, approval was extended to previously untreated CD30-expressing peripheral T-cell lymphomas, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP). Approval was based on results of the phase III ECHELON-2 clinical trial, in which brentuximab vedotin plus CHP provided clinically meaningful improvement in progression-free and overall survival versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).^[108]

Mogamulizumab, a CCR4-directed monoclonal antibody, was approved by the FDA in 2018 for adults with mycosis fungoides or Sézary syndrome who have received at least 1 prior systemic therapy. Approval was based on the MAVORIC (Mogamulizumab anti-CCR4 Antibody Versus ComparatOR In CTCL) phase III clinical trial that compared mogamulizumab with vorinostat. Significantly superior progression-free survival (PFS) was observed with mogamulizumab (7.7 months) compared with vorinostat (3.1 months) (P < 0.0001).^[109]

Specific Therapies

When mycosis fungoides is confined to the skin (cutaneous T-cell lymphoma [CTCL]), skin-targeted therapies, such as the following, are often effective in controlling manifestations^[110]:

Topical corticosteroids
Heliotherapy
Photochemotherapy - Eg, psoralen plus ultraviolet-A light (PUVA)
Topical application of nitrogen mustard (mechlorethamine) or carmustine (BCNU)
Radiotherapy - Including total skin electron beam irradiation

Bexarotene is also sometimes used for disease confined to the skin. Beneficial effects of bexarotene and of alemtuzumab (anti-CD52) have been noted, but the long-term effects of these therapies remain to be established.^[111]

Psoriatic doses of methotrexate have been used, but some concern exists relating to large cell transformation that is occasionally observed in these patients. Narrow-band UV-B therapy is another option.^[112]

Treatment of stages T1 and T2 mycosis fungoides with total skin electron beam therapy is highly effective without adjuvant therapy. Management of relapses with local radiotherapy or a second round of total skin electron beam irradiation is feasible, timesaving, and cost-effective.^[113]In patients with limited patch-stage mycosis fungoides, topical steroids or bexarotene gel can be used.

Tazarotene, long-term and low-dose oral etoposide, and imiquimod may be of value in the treatment of early CTCL.^{[114, 115]}One small pilot study showed tazarotene 0.1% gel to be a well-tolerated and effective adjuvant topical therapy for the treatment of refractory mycosis fungoides.^[116]

Biologic agents such as interferon alfa and other cytokines (eg, IL-2) and traditional and newer retinoids such as bexarotene are increasingly being used.

Combination therapy with bexarotene and PUVA should be considered for patients with treatment-resistant CTCL that is refractory to monotherapy.^[117]However, the precise use of these newer treatments, either as single-agent therapy or in combination with other therapies (eg, PUVA) in the treatment of mycosis fungoides, remains to be established.

Fujimura et al evaluated the treatment efficacy of low-dose bexarotene (150-300 mg/m²) with narrow-band ultraviolet B light (NBUVB) versus bexarotene alone at a conventional dose (300 mg/m²) in a series of 23 CTCL cases. Mean event-free survival was 6.7 months for the bexarotene conventional-dose cohort and 19.1 months for the low-dose bexarotene with NBUVB cohort. Severe adverse events occurred in 23.8% of the patients taking conventional-dose bexarotene and 12.5% of those receiving the low-dose bexarotene with NBUVB. These authors suggested that low-dose bexarotene with NBUVB "could be one of the optimal therapies for advanced CTCL".^[118]

Beneficial results have been described with interferon alfa, alone or in combination with PUVA, prolonged treatment with a combination of low-dose chlorambucil (2-4 mg/day) and prednisone (10-20 mg/day), or methotrexate (MTX) (5-25 mg/wk). Complete responses are uncommon, however.^{[119, 120]}

As previously mentioned, multiagent chemotherapy is used in cases with unequivocal lymph node or systemic involvement or in cases with widespread tumor-stage mycosis fungoides that is refractory to skin-targeted therapies and is not early patch/plaque-stage disease.

Subcutaneous panniculitis-like T-cell lymphoma usually responds poorly to chemotherapy. Cyclosporine has shown some efficacy for cases that relapse after chemotherapy, and a case report of a long-term complete remission with cyclosporine as a first-line therapy has been published.^[121]Systemic corticosteroids have also been found effective for first-line single-agent therapy, inducing complete remission in four of five patients in one study.^[122]

Treatment of Sézary Syndrome

The treatment of Sézary syndrome should be predicated on disease burden and rapidity of progression.^[19]Because infection is the major cause of death in patients with mycosis Sézary syndrome, one should attempt to preserve immune response, use immunomodulatory therapy before chemotherapy unless the disease burden or therapeutic failure requires otherwise, and consider combination therapy, particularly systemic immunomodulatory therapy plus skin-directed treatments, as a better option than monotherapy.

Because Staphylococcus infection may be associated with a disease flare, systemic antibiotics should be administered when in doubt to prevent life-threatening sepsis. Pruritus treatment is an important quality-of-life consideration and should not be neglected.^[123]It can be so severe that special itch-targeted therapies may need to be devised.

Mogamulizumab, a CCR4-directed monoclonal antibody, was approved by the FDA in 2018 for adults with Sézary syndrome or mycosis fungoides who have received at least 1 prior systemic therapy.^[109] For more information, see Systemic Therapy.

Treatment of Folliculotropic Mycosis Fungoides

Perifollicular localization of the dermal infiltrates in folliculotropic mycosis fungoides is often less responsive to skin-targeted therapies (eg, PUVA, topical nitrogen mustard) than is classic plaque-stage mycosis fungoides; total skin electron beam irradiation is superior.^[124]However, because sustained complete remissions are rarely achieved with electron beam therapy, PUVA combined with retinoids or interferon alfa should be considered, although persistent tumors can be effectively treated with local radiotherapy.

Follicular mycosis fungoides may benefit from isotretinoin for persistent cysts and comedones.^[125]Many patients benefit from PUVA therapy, although they may not respond as well as patients with classic mycosis fungoides do.^[65]Early syringotropic cutaneous T-cell lymphoma may be treated with local radiotherapy, with excellent local control.^[126]

A pilot study in 6 patients with refractory folliculotropic mycosis fungoides unresponsive to both topical and systemic therapies reported successful treatment with a combination of interferon gamma, topical carmustine, and low0-dose isotretinoin. In some cases, other skin-directed therapies including phototherapy and local radiation were included in the treatment. Four patients experienced complete responses while the other two had nearly complete responses with this novel regimen.^[127]

Guidelines

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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