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Mycosis Fungoides


1.1 Definition

Mycosis fungoides (MF) constitutes the most frequent cutaneous T-cell lymphoma. Sézary syndrome is considered an erythrodermic leukemic variant of MF. Its postulated normal counterpart is a peripheral epidermotropic CD4+ T cell. Mycosis fungoides is included in the new WHO-EORTC classification of primary cutaneous lymphomas (Willemze 2005).

1.2 Incidence

Mycosis fungoides (MF) is an uncommon lymphoma; however, it is the most common of the primary cutaneous lymphomas. MF constitutes 50% of all primary NHL of the skin (Willemze 2005). Annual incidence is 0.29/100.000, being about 0.5% of all new cases of NHL diagnosed in the USA each year (Weinstock 1991).

1.3 Risk factors

The cause and risk factors of MF and Sézary syndrome are unclear. Although environmental and occupational exposures, such as exposure to solvents and chemical, have been implicated in the etiology of the disease, the most recent large case-controlled study failed to support this hypothesis (Whittemore 1989). A viral etiology for MF has been also suggested. There are some reports that have found human T-lymphotrophic virus-1 (HTLV-1) either in the peripheral blood or cutaneous lesions of some patients with MF or Sézary syndrome (Hall 1991). However, many studies have revealed evidence against a role of HTLV-1 (Wood 1996). At present, HTLV-1 is not considered to play any role in the etiology of MF. The role of other viruses such as cytomegalovirus is still unclear (Herne 2003). A few studies have demonstrated histocompatibility antigen associations with MF and Sézary syndrome, specifically Aw31, Aw32, B8, Bw38, and DR5 (Nisce 1981). Chromosomal abnormalities have been identified in tumor cells, mostly deletions and translocations in chromosome 1 or 6 (Johnson 1985). Recently, new molecular studies revealed alterations of NAV3 in MF and Sezary syndrome (Karenko 2005). The significance of these features is yet unclear.


2.1 Morphology

The tumor cells of mycosis fungoides are predominantly small cells with cerebriform nuclei, with a minority of larger cells with similar nuclei, which infiltrate the epidermis, circulate in the blood and involve the paracortex of lymph nodes. Atypical cells may be completely absent in early lesions (Massone 2005). The infiltrate is variable accompanied by interdigitating and Langerhans’ cells. The bone marrow is usually normal. Although MF presents usually with band-like, epidermotropic infiltrates, several clinicopathologic variants have been described (e.g., follicular MF, etc.).

2.2 Immunophenotype

The cells of mycosis fungoides express T-cell-associated antigens (CD2+, CD3+, CD5+), approximately one third are CD7+; most cases are CD4+, but rare CD8+ and/or CD56+ cases have been reported. CD25 is usually negative, but positive cases have been reported. S-100+ CD1a+ interdigitating and Langerhans’ cells are present (Ralfkiaer 1993). Flow cytometric studies of the peripheral blood may show expansion of the CD4+ CD7- population reflective of circulating atypical lymphocytes of Sézary type (Harmon 1996).

2.3 Genetic features

TCR genes are clonally rearranged, but detection of a monoclonal population of T lymphocytes may be difficult in early lesions (Massone 2005). TCR gene-rearrangement studies may show evidence of clonal expansion in peripheral blood in patients with Sézary syndrome (Muche 1997). Several chromosomal aberrations have been described using different molecular methods, but at present a repeatable pattern has not been identified.


3.1 Clinical presentations

Mycosis fungoides (MF) usually occurs in old adults, with a median age between 55 and 60 years and a 2:1 male to female ratio, presenting with multiple cutaneous plaques or nodules, or with generalized erythroderma. Cases in children have been well documented. MF presents as an indolent cutaneous eruption with erythematosus scaly patches or plaques that often resemble common skin disorders such as atopic dermatitis or psoriasis. The initial lesions are often confined to sun-protected areas, although any skin site may be affected. There may be prominent poikiloderma (skin atrophy with telangiectasia) or associated alopecia or with follicular mucinosis. In addition, several other clinical variants have been described (e.g., hypopigmented MF among others). Especially in the past, a definitive diagnosis is was often preceded by a variably long period (often referred to as the “premycotic” stage) that could range from several months to several years (Hoppe 1990). However, the identification of precise histopathologic criteria for diagnosis of early MF allows a specific diagnosis in most cases (Sanchez 1979; Massone 2005). As the disease progresses, patches may evolve into infiltrated plaques with a more generalized distribution, and patients may subsequently develop ulcerated or exophytic tumors.nt Tumors, however, develop only in a minority of the patients (Kim 1996; Willemze 2005). Another phase of skin involvement is generalized erythroderma. The erythema may be accompanied by either very atrophic or lichenified skin, and plaques or tumors may also be present. These patients are almost always affected by intense pruritus. If peripheral blood involvement is present, these patients are considered to have Sézary syndrome. It is controversial as to how many or what percentage of Sézary cells constitute a significant level to define Sézary syndrome. Although the original NCI classification used the criterion of greater than 5% lymphocytes for significant blood involvement (Bunn 1979), the current practice by many MF referral centers is to use a criterion of at least 20% lymphocytes or an absolute count of at least 1.000/mm3 to define peripheral blood involvement. Precise criteria for definition of Sezary syndrome have been proposed in the new WHO-EORT classification of cutaneous lymphomas (Willemze 2005). Sézary syndrome is considered by some authors to be an erythrodermic leukemic variant of MF, but is classified separately in the new WHO-EORT classification of cutaneous lymphomas (Willemze 2005). Patients present with generalized erythroderma, lymphadenopathy and circulating atypical T cells (Sézary cells) in the peripheral blood. Peripheral blood involvement may be subtle in MF or prominent in Sézary syndrome. Patients may present with all components of Sézary syndrome or may present initially with only one component and subsequently progress to develop other clinical features of this syndrome (Wieselthier 1990). Patients with Sézary syndrome have a worse prognosis than patients with erythrodermic MF (Kim 1995). Extracutaneous involvement is directly correlated to the extent of cutaneous disease. Cutaneous dissemination is observed in less than 10% of patients with patch or plaque disease and in 30% – 40% of patients with tumors or generalized erythrodermatous involvement (Hoppe 1990). Lymphadenopathy is usually a late occurrence, being an initial manifestation of extracutaneous dissemination. Regional lymphadenopathies especially in areas draining extensive skin involvement are the most common presentation. Visceral dissemination may develop subsequently, and the most commonly involved organs are the lungs, spleen, liver, and gastrointestinal tract (Epstein 1972). In advanced stages, transformation into a large cell lymphoma may occur, with predominance of either immunoblasts, large pleomorphic, or large anaplastic cells. Some of these cases are CD30+, thus being similar to anaplastic large cell lymphoma. An association with Hodgkin’s disease and lymphomatoid papulosis has also been reported.

3.2 Diagnostic criteria

Clinical criteria for early diagnosis of MF include presence of asymmetrical, irregular, persistent erythematous lesions on sun-protected areas, that don’t improve with or recur after conventional treatments. Histopathologic criteria for diagnosis of early MF include the following: presence of a patchy-lichenoid or band-like lymphocytic infiltrate within an expanded, partly fibrotic papillary dermis; epidermotropism of lymphocytes (arranged either as solitary units or in small collection defined as “Pautrier’s microabscesses” or aligned along the dermo-epidermal junction); presence of atypical lymphocytes (lymphocytes larger than normal and with indented – cerebriform nuclei); presence of intraepidermal lymphocytes larger than the dermal ones; intraepidermal lymphocytes surrounded by a clear halo (“haloed lymphocytes”). It should be underlined that in some cases histopathologic features alone are non-diagnostic, and only a careful clinicopathologic corelation allows a precise diagnosis. Flow cytometric studies of the peripheral blood may show expansion of the CD4+ CD7- population reflective of circulating atypical lymphocytes of Sézary type (Harmon 1996). Detection of monoclonality of the T lymphoytes by molecular techniques is a useful additional diagnostic criterion. TCR gene-rearrangement studies may show evidence of clonal expansion in peripheral blood in patients with Sézary syndrome (Muche 1997).

3.3 Additional useful tests

DNA microarray studies revealed a specific “gene signature” of MF as compared to inflammatory skin disorders (Tracey 2003). These results, if confimed by larger studies, may provide valuable additional diagnostic criteria in the near future.


4.1 Staging procedures

Complete staging work-up for mycosis fungoides (MF) includes an accurate physical examination, with a careful description of all cutaneous lesions (especially including the scalp, palms, soles and anogenital region) and complete hematological and biochemical exams with Sézary cells analysis. Even if the “blood” classification does not modify clinical stage, it usually correlates with a more advanced T-stage (usually T4) and the presence of extracutaneous disease (Hoppe 1990). Routine imaging studies in patients with early stages (I to IIA) in the absence of peripheral lymphadenopathy is unproductive (Kulin 1990). Lymph node biopsies must be obtained if lymphadenopathy is present, since the presence of lymph node involvement affects both the stage and prognosis. Appropriate imaging studies and histologic evaluation must confirm suspected sites of visceral involvement when possible. Significant bone marrow involvement with an infiltrative histologic pattern is never found as a rule in patients with limited skin disease, and can be observed in patients with advanced MF or with Sézary syndrome (Salhany 1989). Significant bone marrow disease is usually reflected by the presence of readily detectable Sézary cells in the peripheral blood. Therefore, bone marrow biopsy is not routinely used as part of the initial staging procedure for patients with MF.

4.2 Staging system

The standard staging classification system for mycosis fungoides (MF) is the tumor, node, metastasis, blood (TNMB) system first proposed at the NCI-sponsored Workshop on cutaneous T-cell lymphomas in 1978 (Bunn 1979), and is summarized as follows:

T (skin)
T1: limited patch/plaque (< 10% of total skin surface)
T2: generalized patch/plaque (≥10% of total body surface)
T3: tumors
T4: generalized erythroderma

N (lymph node)
N0: lymph nodes clinically uninvolved
N1: lymph nodes enlarged, histologically uninvolved
(reactive and dermatopathic nodes)
N2: lymph nodes clinically uninvolved, histologically involved
N3: lymph nodes enlarged and histologically involved

M (viscera)
M0: no visceral involvement
M1: visceral involvement

B (blood)
B0: no circulating atypical Sézary cells (< 5% of lymphocytes)
B1: circulating atypical Sézary cells (≥5% of lymphocytes)

The overall clinical stage is defined by the TNMB criteria as follows:
Stage IA: T1 N0 M0
Stage IB: T2 N0 M0
Stage IIA: T1-2 N1 M0
Stage IIB: T3 N0-1 M0
Stage IIIA: T4 N0 M0
Stage IIIB: T4 N1 M0
Stage IVA: T1-4 N2-3 M0
Stage IVB: T1-4 N0-3 M1
The “blood” classification does not modify clinical stage.

4.3 Molecular analysis of minimal residual diseaseMolecular analyses by PCR have been used for detection of minimal residual disease and of early recurrences in some study, but their reliability and repeatability are yet controversial.

4.4 Restaging proceduresRestaging should include all diagnostic procedures positive at time of diagnosis and initial staging.


 5.1 Natural history

The prognosis of mycosis fungoides (MF) is variable and strongly conditioned by the extent and type of skin involvement and presence of extracutaneous disease. Patients with stage IA-disease have an excellent prognosis with an overall long-term life expectancy that is similar to an age-, sex-, and race-matched control population (Kim 1996 ; Willemze 2005). Almost all patients with stage IA MF who die will die from causes other than MF, with a median survival longer than 33 years. Only 9% of these patients will progress to more extended disease. The latter group of patients had a lower complete remission rate to initial therapy and an older mean age than the rest of stage IA patients. Patients with stage IB or IIA have a median survival greater than 11 years (Kim 1999b). These patients with T2 disease have a likelihood of disease progression of 24% and nearly 20% die of causes related to MF. Subgroups with stage IB or IIA have similar prognosis. Patients with cutaneous tumors (stage IIB) or generalized erythroderma (stage III) have a median survival of 3 and 4.5 years, respectively. The majority of these patients will die of MF. The long-term outcome in patients with erythroderma is quite variable and is dependent on patient age at presentation (65 years), overall stage (III vs. IV), and peripheral blood involvement (B0 vs. B1) (Kim 1995). The median survival can vary widely depending on the combinations of these independent prognostic factors, and three distinct prognostic subgroups have been identified, with a median survival of 10, 3.5 and 1.5 years. Patients with extracutaneous disease at presentation involving either lymph nodes (stage IVA) or viscera (stage IVB) have a median survival of less than 1.5 years. Patients with plaque-type or erythrodermic MF may develop cutaneous tumors with large cell histology, often expressing CD30. CD30+ lymphomas arising in these patients share a common clonal origin as observed in their preexisting MF (Wood 1993). These patients usually have rapid disease progression and require more intensive local or systemic therapy. Thus, transformation of MF to a large cell lymphoma is associated with an aggressive clinical course and less favorable outcome.

5.2 Prognostic factors

The extent and type of skin involvement, that is T-stage, and presence of extracutaneous disease arethe most important indicators of survival in patients with mycosis fungoides (MF). The long-term outcome in patients with erythroderma is quite variable and is dependent on patient age at presentation (65 years), overall stage (III vs. IV), and peripheral blood involvement (B0 vs. B1) (Kim 1995). The median survival can vary widely depending on the combinations of these independent prognostic factors, and three distinct prognostic subgroups have been identified, with a median survival of 10, 3.5 and 1.5 years. The presence of a significant number of Sézary cells in the peripheral blood (B1 condition) is not factored into the overall clinical stage; however, it usually correlates with a more advanced T-stage (usually T4) and the presence of extracutaneous disease (stage IV) (Hoppe 1990). The lymph node histologic grade seems to correlate with survival. Dermatopathic changes or the presence of just a small number of atypical cells (histologic grade LN-1 or LN-2) have a 5-year survival of 80%. Patients with large clusters of paracortical atypical cells (LN-3) have a 5-yr survival of 30%, and those with effaced nodes (LN-4) have a 5-yr survival of 15% (Sausville 1988). Actual lymph node involvement with MF (N2-3, stage IVA) correlates with the histologic grade of LN-3 or -4. Some genetic features have been linked to worse prognosis, including among others the finding of an identical clone in the blood and the skin (Beylot-Barry 2001 ; Fraser-Andrews 2000).


6.1 Treatment of stage IA disease

For patients with T1 without extracutaneous involvement (stage IA), standard treatment plan is limited to topical therapeutic measures. The main therapeutic options for these patients are local or total skin topical mechlorethamine hydrochloride (HN2), phototherapy ultraviolet B (UVB), psoralen and ultraviolet A (PUVA), or localized electron-beam radiotherapy (EBRT). There is no evidence that early aggressive systemic therapy is preferable to conservative strategy in the management of limited disease (Kaye 1989). Patients treated with topical HN2 had a similar long-term survival than those treated with total-skin EBRT, with a complete remission rate of 70% – 80% and a median time to skin clearance of 6 to 8 months. When treatment is discontinued, more than half of the patients will relapse locally, but most will respond to a resumption of therapy. Twenty percent of patients treated with topic HN2 have a durable remission (>10 years). Topical HN2 with 10 to 20 mg/dL strength, either in ointment base or in water, can be applied to the entire skin once daily (Kim 1996). Treatment is continued on a daily basis until complete skin clearance, which is followed by a variable duration of maintenance therapy. By this way, HN2 seems to exert its cytotoxic activity mediated by immunostimulation. Topical BCNU produces similar outcome to those obtained with HN2 (Zackheim 1994); however, because of its systemic absorption, the potential hematologic complications are greater and the maximum duration of treatment is limited. Local EBRT is useful for the rare patients with a single lesion. EBRT is followed by a topical HN2 maintenance regimen. The total-skin EBRT should be reserved for patients with progressive skin disease. In spite of a higher remission rate, there are no difference in survival between patients treated with topical HN2 or with EBRT (Kim 1996). UVB or PUVA are also used a standard treatment in T1 disease. After 1.5 to 2 hours of oral psoralen, patients receive a timed exposure to UVA light in a phototherapy unit. Only the eyes are shielded routinely, however selected areas can be shielded to minimize undesired photodamage. Certain areas like scalp, perineum, and axillae may result shadowed and not receive adequate exposure. PUVA treatment is initiated thrice weekly until skin clearance is achieved, after which the frequency is gradually decreased to as infrequently as once every 2 weeks. Maintenance should be discontinued within one year to reduce the risk of skin carcinogenesis. With this strategy, complete remission rate is 90%, with a median time to skin clearance of 2 to 6 months (Abel 1987; Herrmann 1995; Ramsay 1992; Resnik 1993; Roenigk 1990). An alternative to PUVA is represented by narrow-band (311nm) UV-B phototherapy (Boztepe 2005; Gathers 2002 ; Diederen 2003; El-Mofty 2005;Ghodsi 2005). Erythema, pruritus, skin dryness, nausea, cataracts, and carcinogenesis are the main complications related to phototherapy (Wood 1986). Chronic complications are more common in patients treated with more topical strategies. The long-wave UVA has an advantage over UVB in its greater depth of penetration into the dermal infiltrates of MF. Other topical treatment possibilities for which experience in large, controlled studies is lacking include topical steroids, bexarotene gel, topical methotrexate, imiquimod cream, and photodynamic therapy (Breneman 2002 ; Coors 2004; de Quatrebarbes 2005; Deeths 2005; Demierre 2003 ; Heald 2003). Several aspects other than clinical stage strongly influence therapeutic decision. Among others, the assessment of prognostic factors, the accessibility of different approaches, the patient’s age, social problems, and the cost-benefit ratio should be taken into consideration. This is equally important for all other stage-disease in MF. Nonspecific symptomatic treatment is an integral component of the overall therapeutic regimen. Supportive measures such as aggressive emolliation, topical steroids, and oral antipruritics should be used as necessary. Hoppe 1991; Quiros 1997).

6.2 Treatment of stage IB – IIA disease

For patients with T2 without extracutaneous involvement (stage IB – IIA), the standard treatment plan is limited to topical therapeutic measures. The main therapeutic options for these patients are local or total skin topical mechlorethamine hydrochloride (HN2), psoralen and ultraviolet A (PUVA), or total-skin electron-beam radiotherapy (EBRT). The latter should be considered as initial therapy for patients with very thickened plaques, since the effective depth of treatment of total-skin EBRT is more substantial than with either topical HN2 or PUVA. It should also be considered for patients with rapid progression and patients who failed to respond to the other strategies. A total dose of 36 Gy administered over a 10-week period, with a 1-week split after 18 – 20 Gy is suggested .

Some areas like the top of the scalp, the perineum, the soles of the feet, underneath of the breasts or of the panniculus of obese individuals could receive relatively lower doses. Thus, these areas should be supplemented with 6 MeV electrons to a total dose of 20 Gy (Hoppe 1991). Following completion of total-skin EBRT, adjuvant topical HN2 is appropriate and may be continued for at least 6 months. Total-skin EBRT produces a complete remission rate of 80% to 90% in these patients (Jones 1994;Quiros 1997). In spite of a higher complete remission rate, patients treated with total-skin EBRT do not have an improved survival compared with those treated with topical HN2 (Kim 1999b). HN2 and PUVA are used with the same modalities as for stage IA patients . Complete remission rate with topical HN2 or with PUVA are 50% to 70% (Kim 1999b) and 50% to 80% (Abel 1987; Herrmann 1995; Ramsay 1992; Resnik 1993 ; Roenigk 1990), respectively. Patients who fail to respond to one topical therapy or who progress after an initial response may be treated with an alternative topical strategy. There is no evidence that development of resistance to one modality affects the subsequent response to an alternative topical modality (Kim 1996; Kim 1999b). Patients who failed to respond to a single-agent topical regimen can receive combined-modality therapy as appropriate for individual clinical use on a type 3 level evidence. This can be done by combining topical HN2 with total-skin EBRT or with PUVA; or adding interferon- (IFN-) or retinoids to those treatments (Duvic 1996; Jones 1992 ; Kuzel 1995).

6.3 Treatment of stage IIB disease

Standard therapeutic option for patients with stage IIB disease depends on the entity of tumors. Local electron-beam radiotherapy (EBRT) combined with topical mechlorethamine hydrochloride (HN2) or with psoralen and ultraviolet A (PUVA) are the first-choice treatments for patients with few discrete tumors. In patients with generalized tumors three effective combinations are available: total-skin EBRT plus topical HN2, PUVA plus interferon-alfa, and PUVA plus retinoids. Total-skin EBRT produces a complete remission rate of 45% to 75% in patients with stage IIB MF (Chinn 1999 ; Wilson 1995). In these patients the survival benefit of topical or systemic adjuvant treatment remains unclear (Chinn 1999 ; Wilson 1995). More aggressive combinations like PUVA plus interferon or retinoids are suitable for individual clinical use on a type 3 level evidence, in refractory disease or tumors relapsed after the above-mentioned strategies. The addition of interferon to PUVA improved survival respect to PUVA alone (Roenigk 1990), being associated with a complete remission rate of 33% (Kuzel 1995). To date, there is no evidence that a more aggressive combination using systemic chemotherapy offers superior survival outcome (Winkler 1986). Focal resistant tumors can be boosted with local EBRT or orthovoltage radiation.

6.4 Treatment of stage III disease

Standard therapeutic option for patients with stage III disease is low-dose psoralen and ultraviolet A (PUVA) with a low and caution increased of the UVA dose to avoid phototoxic reactions. Considering that erythrodermic MF usually presents very inflamed and itchy skin and that the skin in these patients is frequently irritated by prior topical therapies, electron-beam radiotherapy (EBRT) is usually associated with severe desquamation, even with very low doses. The combination between PUVA and interferon-alfa produces a complete remission rate of more than 60% and response duration longer than those obtained with PUVA or interferon alone (Kuzel 1995). In any way, there is no clear evidence that prolongation of the response duration leads to improvement in the overall survival. Photopheresis or extracorporeal photochemotherapy is suitable for individual clinical use as primary therapy for erythrodermic MF or Sézary syndrome on a type 3 level evidence (Holloway 1992). It can be effective in patients without visceral involvement or with limited lymph node disease, with a 60% of overall response rate (Wilson 1995). If the response to photopheresis is partial or slow, interferon alfa can be added, obtaining a significant improvement in response rate (Gottlieb 1996). Systemic retinoids are also suitable for individual clinical use as primary therapy for erythrodermic MF or Sézary syndrome on a type 3 level evidence. Retinoids can be used alone, or more often, in combination with PUVA or interferon alfa (Dreno 1991; Marschalko 1993). Single-agent chemotherapy is most effective in patients without extracutaneous disease. Methotrexate produces a complete remission rate of 41% with doses between 5 and 50 mg/wk (Zackheim 1996).

6.5 Treatment of stage IV disease

Standard therapeutic option for patients with stage IV disease is conventional-doses systemic chemotherapy. In MF, most chemotherapy regimens result in temporary palliative control only. Chemotherapy is used alone, or in combination with radiation or interferon alfa. In spite of a complete response rate of 80% to 100%, the median duration of response to chemotherapy is shorter than one year (Bunn 1994 ; Zackheim 1996). The most effective and commonly used combinations are CHOP and CVP regimens (Grozea 1979). Methotrexate, etoposide, bleomycin, vinblastine, fludarabine, and 2-deoxycoformycin are the most commonly used single-agent chemotherapy regimens in MF and Sézary syndrome (Bunn 1994; Rosen 1995 ; Quaglino 2004). Response rates and duration are lower than those reported for combination chemotherapy regimens. The purine analogs fludarabine and 2-deoxycoformycin are suitable for individual clinical use on a type R basis. In effect, these drugs seems to be active against MF with response rates as high as 50% (Kuchnio 1994; Mercieca 1994; Von Hoff 1990). Biologic therapy, interferon alfa an retinoids are suitable for individual clinical use on a type R basis, either when used alone, together or in combination with chemotherapy or topical treatment (Bunn 1994; Duvic 1996; Kuzel 1995). The combination fludarabine plus interferon produces a response rate of 46% with a median duration of 6 months (Foss 1992). Megavoltage photon irradiation can be used as a palliative treatment of lymph node masses. This can be associated with systemic chemotherapy or interferon alfa. High-dose chemotherapy supported by autologous bone marrow transplantation is an experimental strategy. Experience with this strategy in MF is very limited (Bigler 1991), and, thus, its efficacy has not been established. However, it seems that autologous or allogeneic bone marrow or stem cell transplantation represent a promising approach in tumor-stage patients; mini-allogeneic transplantation may provide the additional advantage of a “graf-versus-tumor” effect (Guitart 2002 ;Masood 2002; Molina 2005; Olavarria 2001; Soligo 2003).

6.6 New active drugs and therapeutic options

Anti-T-cell monoclonal antibodies are an investigational alternative on a type R basis. It was studied in small series treated with chimeric anti-helper T-cell (anti-CD4) antibody (Knox 1991). The clinical response were generally modest and short-lived. Among novel targeted therapeutic approaches to CTCL are the retinoids, all-trans retinoic acid (ATRA) (Sacchi 1997) and bexarotene (Targretin) (Duvic 2001a ; Duvic 2001b). Other targeted therapies include the anti-CD52 antibody alemtuzumab (Campath) (Lundin 1998; Lundin 2003 ; Pangalis 2001; Hagberg 2002 ; Zinzani 2005), DAB389 IL-2 (denileukin diftitox, ONTAK) (Olsen 2001; Talpur 2006), tumor vaccination (Dummer 2004; Maier 2003), unmodified or 90Y-conjugated anti-Tac Pseudomonas exotoxin conjugates, and inhibitors of intracellular signal transduction factors. Further important therapeutic modalities include Gemcitabine (Zinzani 2000 ; Marchi 2005), pegylated liposomal doxorubicin (Wollina 2003), pentostatin (Tsimberidou 2004a), etanercept (Tsimberidou 2004b), immunomodulation of pro-inflammatory cytokines such as interleukin (IL)-12 (Rook 2003), and photopheresis with or without concurrent immunoadjuvant treatment. Due to the inadequacy of standard therapy, all patients with extracutaneous disease should be considered candidates for newer investigative therapies.
An emerging class of investigational agents is represented by histone deacetylase (HDAC) inhibitors, which may restore the expression of tumor suppressor or cell cycle regulatory genes by increasing the acetylation of histones. Depsipeptide and suberoylanilide hydroxamic acid are potent histone deacetylase inhibitors and have shown in-vitro and in-vivo cytotoxic activity against various tumors (Duvic 2003 ; Wysocka 2004). Vorinostat (suberoylanilide hydroxamic acid – SAHA) is the first FDA-approved HDAC inhibitor for the treatment of cutaneous manifestations of cutaneous T-cell lymphomas. Vorinostat was active against solid tumors and hematologic malignancies as intravenous and oral preparations in phase I development. In two phase II trials, vorinostat 400 mg/day was safe and effective with an overall response rate of 24 – 30% in refractory advanced patients with cutaneous T-cell lymphomas including large cell transformation and Sézary syndrome. The common side effects of vorinostat, which are similar in all studies, include gastrointestinal symptoms, fatigue and thrombocytopenia and the most common serious event was thrombosis. Many other HDAC inhibitors, such as valproic acid (Munster 2007), MS-275 (Gojo 2007), CI-994 (Undevia 2004), and FK-228 (Robey 2006) among others, are being investigated, but clinical experience on MF patients is still limited .



Abel EA, Sendagorta E, Hoppe RT, Hu CH. PUVA treatment of erythrodermic and plaque-type mycosis fungoides. Ten- year follow-up study. Arch Dermatol 1987; 123: 897-901 [Medline]

Andres P, Lepagney ML, Bureau B, Litoux P, Dreno B. Primary cutaneous lymphomas: a study of 37 cases. Int J Dermatol 1997; 36: 582-586 [Medline]

Antolak JA, Cundiff JH, Ha CS. Utilization of thermoluminescent dosimetry in total skin electron beam radiotherapy of mycosis fungoides. International Journal of Radiation Oncology, Biology, Physics 1998; 40: 101-108 [Medline]

Apisarnthanarax N, Talpur R, Ward S, Ni X, Kim HW, Duvic M. Tazarotene 0.1% gel for refractory mycosis fungoides lesions: an open-label pilot study. J Am Acad Dermatol 2004; 50: 600-607 [Medline]

Ardigo M, Borroni G, Muscardin L, Kerl H, Cerroni L. Hypopigmented mycosis fungoides in Caucasian patients: a clinicopathologic study of 7 cases. J Am Acad Dermatol 2003; 49: 264-270 [Medline]

Assaf C, Hummel M, Steinhoff M, Geilen CC, Orawa H, Stein H, et al. Early TCR-beta and TCR-gamma PCR detection of T-cell clonality indicates minimal tumor disease in lymph nodes of cutaneous T-cell lymphoma: diagnostic and prognostic implications. Blood 2005; 105: 503-510 [Medline]

Ben Amitai D, Michael D, Feinmesser M, Hodak E. Juvenile mycosis fungoides diagnosed before 18 years of age. Acta Derm Venereol 2003; 83: 451-456 [Medline]

Benchikhi H, Zeitoun C, Bagot M, Wechsler J, Vaillant L, Joly P, et al. [Sezary syndrome treated by cytapheresis. Short and long-term results]. [French]. Annales de Dermatologie et de Venereologie 1996; 123: 247-250 [Medline]

Berroeta L, Lewis-Jones MS, Evans AT, Ibbotson SH. Woringer-Kolopp (localized pagetoid reticulosis) treated with topical photodynamic therapy (PDT). Clin Exp Dermatol 2005; 30: 446-447 [Medline]

Beylot-Barry M, Sibaud V, Thiebaut R, Vergier B, Beylot C, Delaunay M, et al. Evidence that an identical T cell clone in skin and peripheral blood lymphocytes is an independent prognostic factor in primary cutaneous T cell lymphomas. J Invest Dermatol 2001; 117: 920-926 [Medline]

Bigler RD, Crilley P, Micaily B, Brady LW, Topolsky D, Bulova S, et al. Autologous bone marrow transplantation for advanced stage mycosis fungoides. Bone Marrow Transplant 1991; 7: 133-137 [Medline]

Boztepe G, Sahin S, Ayhan M, Erkin G, Kilemen F. Narrowband ultraviolet B phototherapy to clear and maintain clearance in patients with mycosis fungoides. J Am Acad Dermatol 2005; 53: 242-246 [Medline]

Breneman D, Duvic M, Kuzel T, Yocum R, Truglia J, Stevens VJ. Phase 1 and 2 trial of bexarotene gel for skin-directed treatment of patients with cutaneous T-cell lymphoma. Arch Dermatol 2002; 138: 325-332 [Medline]

Buhl L, Sogaard H. Immunohistochemical expression of IL-10 in mycosis fungoides. Exp Dermatol 1997; 6: 195-198 [Medline]

Bunn PAJ, Hoffman SJ, Norris D, Golitz LE, Aeling JL. Systemic therapy of cutaneous T-cell lymphomas (mycosis fungoides and the Sezary syndrome). Ann Intern Med 1994; 121: 592-602 [Medline]

Bunn PAJ, Lamberg SI. Report of the Committee on Staging and Classification of Cutaneous T- Cell Lymphomas. Cancer Treat Rep 1979; 63: 725-728 [Medline]

Cerroni L, Arzberger E, Ardigo M, Putz B, Kerl H. Monoclonality of intraepidermal T lymphocytes in early mycosis fungoides detected by molecular analysis after laser-beam-based microdissection. J Invest Dermatol 2000; 114: 1154-1157 [Medline]

Cerroni L, Fink-Puches R, Back B, Kerl H. Follicular mucinosis: a critical reappraisal of clinicopathologic features and association with mycosis fungoides and Sezary syndrome. Arch Dermatol 2002; 138: 182-189 [Medline]

Cerroni L, Rieger E, Hodl S, Kerl H. Clinicopathologic and immunologic features associated with transformation of mycosis fungoides to large-cell lymphoma. Am J Surg Pathol 1992; 16: 543-552 [Medline]

Chiarion-Sileni V, Bononi A, Fornasa CV, Soraru M, Alaibac M, Ferrazzi E, et al. Phase II trial of interferon-alpha-2a plus psolaren with ultraviolet light A in patients with cutaneous T-cell lymphoma. Cancer 2002; 95: 569-575 [Medline]

Chinn DM, Chow S, Kim YH, Hoppe RT. Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides. Int J Radiat Oncol Biol Phys 1999; 43: 951-958 [Medline]

Coors EA, von den DP. Topical photodynamic therapy for patients with therapy-resistant lesions of cutaneous T-cell lymphoma. J Am Acad Dermatol 2004; 50: 363-367 [Medline]

Crowley JJ, Nikko A, Varghese A, Hoppe RT, Kim YH. Mycosis fungoides in young patients: clinical characteristics and outcome. J Am Acad Dermatol 1998; 38: 696-701 [Medline]

Curco N, Servitje O, Llucia M, Bertran J, Limon A, Carmona M, et al. Genotypic analysis of cutaneous T-cell lymphoma: a comparative study of Southern blot analysis with polymerase chain reaction amplification of the T-cell receptor-gamma gene. Br J Dermatol 1997; 137: 673-679 [Medline]

de Quatrebarbes J, Esteve E, Bagot M, Bernard P, Beylot-Barry M, Delaunay M, et al. Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study. Arch Dermatol 2005; 141: 1117-1120 [Medline]

Deeths MJ, Chapman JT, Dellavalle RP, Zeng C, Aeling JL. Treatment of patch and plaque stage mycosis fungoides with imiquimod 5% cream. J Am Acad Dermatol 2005; 52: 275-280 [Medline]

Delfau-Larue MH, Laroche L, Wechsler J, Lepage E, Lahet C, Asso-Bonnet M, et al. Diagnostic value of dominant T-cell clones in peripheral blood in 363 patients presenting consecutively with a clinical suspicion of cutaneous lymphoma. Blood 2000; 96: 2987-2992 [Medline]

Demierre MF, Vachon L, Ho V, Sutton L, Cato A, Leyland-Jones B. Phase 1/2 pilot study of methotrexate-laurocapram topical gel for the treatment of patients with early-stage mycosis fungoides. Arch Dermatol 2003; 139: 624-628 [Medline]

Dereure O, Levi E, Vonderheid EC, Kadin ME. Infrequent Fas mutations but no Bax or p53 mutations in early mycosis fungoides: a possible mechanism for the accumulation of malignant T lymphocytes in the skin. J Invest Dermatol 2002; 118: 949-956 [Medline]

Di Lorenzo G, Di Trolio R, Delfino M, De Placido S. Pegylated liposomal doxorubicin in stage IVB mycosis fungoides. Br J Dermatol 2005; 153: 183-185 [Medline]

Diamandidou E, Colome-Grimmer M, Fayad L, Duvic M, Kurzrock R. Transformation of mycosis fungoides/Sezary syndrome: clinical characteristics and prognosis. Blood 1998; 92: 1150-1159 [Medline]

Diederen PV, Van Weelden H, Sanders CJ, Toonstra J, van Vloten WA. Narrowband UVB and psoralen-UVA in the treatment of early-stage mycosis fungoides: a retrospective study. J Am Acad Dermatol 2003; 48: 215-219 [Medline]

Dreno B, Claudy A, Meynadier J, Verret JL, Souteyrand P, Ortonne JP, et al. The treatment of 45 patients with cutaneous T-cell lymphoma with low doses of interferon-alpha 2a and etretinate. Br J Dermatol 1991; 125: 456-459 [Medline]

Dummer R, Hassel JC, Fellenberg F, Eichmuller S, Maier T, Slos P, et al. Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas. Blood 2004; 104: 1631-1638 [Medline]

Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski P, et al. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol 2001a; 19: 2456-2471 [Medline]

Duvic M, Lemak NA, Redman JR, Eifel PJ, Tucker SL, Cabanillas FF, et al. Combined modality therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol 1996; 34: 1022-1029 [Medline]

Duvic M, Martin AG, Kim Y, Olsen E, Wood GS, Crowley CA, et al. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol 2001b; 137: 581-593 [Medline]

Duvic M, Talpur R, Chiao N, Chiao J. Phase II trial of oral suberoylanilide hydroxamic acid (SAHA) for cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL) [abstract]. Blood 2003; 102: 179a [Medline]

El Mofty M, El Darouty M, Salonas M, Bosseila M, Sobeih S, Leheta T, et al. Narrow band UVB (311 nm), psoralen UVB (311 nm) and PUVA therapy in the treatment of early-stage mycosis fungoides: a right-left comparative study. Photodermatol Photoimmunol Photomed 2005; 21: 281-286 [Medline]

Epstein EHJ, Levin DL, Croft JDJ, Lutzner MA. Mycosis fungoides. Survival, prognostic features, response to therapy, and autopsy findings. Medicine (Baltimore ) 1972; 51: 61-72 [Medline]

Fierro MT, Doveil GC, Quaglino P, Savoia P, Verrone A, Bernengo MG. Combination of etoposide, idarubicin, cyclophosphamide, vincristine, prednisone and bleomycin (VICOP-B) in the treatment of advanced cutaneous T-cell lymphoma. Dermatology 1997; 194: 268-272 [Medline]

Fimiani M, Rubegni P, Pimpinelli N, Mori M, De Aloe G, Andreassi L. Extracorporeal photochemotherapy induces a significant increase in CD36+ circulating monocytes in patients with mycosis fungoides. Dermatology 1997; 194: 107-110 [Medline]

Fink-Puches R, Chott A, Ardigo M, Simonitsch I, Ferrara G, Kerl H, et al. The spectrum of cutaneous lymphomas in patients less than 20 years of age. Pediatr Dermatol 2004; 21: 525-533 [Medline]

Fink-Puches R, Zenahlik P, Back B, Smolle J, Kerl H, Cerroni L. Primary cutaneous lymphomas: applicability of current classification schemes (European Organization for Research and Treatment of Cancer, World Health Organization) based on clinicopathologic features observed in a large group of patients. Blood 2002; 99: 800-805 [Medline]

Fischer TC, Gellrich S, Muche JM, Sherev T, Audring H, Neitzel H, et al. Genomic aberrations and survival in cutaneous T cell lymphomas. J Invest Dermatol 2004; 122: 579-586 [Medline]

Flaig MJ, Cerroni L, Schuhmann K, Bertsch HP, Kind P, Kaudewitz P, et al. Follicular mycosis fungoides. A histopathologic analysis of nine cases. J Cutan Pathol 2001; 28: 525-530 [Medline]

Foss F, Demierre MF, DiVenuti G. A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 2005; 106: 454-457 [Medline]

Foss FM, Ihde DC, Breneman DL, Phelps RM, Fischmann AB, Schechter GP, et al. Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sezary syndrome. J Clin Oncol 1992; 10: 1907-1913 [Medline]

Foss FM, Kuzel TM. Novel treatment approaches for cutaneous T-cell lymphoma. Cancer Treat Res 1999; 99:227-40: 227-240 [Medline]

Fouchard N, Mahe A, Huerre M, Fraitag S, Valensi F, Macintyre E, et al. Cutaneous T cell lymphomas: mycosis fungoides, Sezary syndrome and HTLV- I-associated adult T cell leukemia (ATL) in Mali, West Africa: a clinical, pathological and immunovirological study of 14 cases and a review of the African ATL cases. Leukemia 1998; 12: 578-585 [Medline]

Fraser-Andrews E, Seed P, Whittaker S, Russell-Jones R. Extracorporeal photopheresis in Sezary syndrome. No significant effect in the survival of 44 patients with a peripheral blood T-cell clone. Arch Dermatol 1998; 134: 1001-1005 [Medline]

Fraser-Andrews EA, Woolford AJ, Russell-Jones R, Seed PT, Whittaker SJ. Detection of a peripheral blood T cell clone is an independent prognostic marker in mycosis fungoides. J Invest Dermatol 2000; 114: 117-121 [Medline]

Gathers RC, Scherschun L, Malick F, Fivenson DP, Lim HW. Narrowband UVB phototherapy for early-stage mycosis fungoides. J Am Acad Dermatol 2002; 47: 191-197 [Medline]

Ghodsi SZ, Hallaji Z, Balighi K, Safar F, Chams-Davatchi C. Narrow-band UVB in the treatment of early stage mycosis fungoides: report of 16 patients. Clin Exp Dermatol 2005; 30: 376-378 [Medline]

Girardi M, Heald PW, Wilson LD. The pathogenesis of mycosis fungoides. N Engl J Med 2004; 350: 1978-1988 [Medline]

Gojo I, Jiemjit A, Trepel JB, Sparreboom A, Figg WD, Rollins S, et al. Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias. Blood 2007; 109: 2781-2790 [Medline]

Goldberg DJ, Stampien TM, Schwartz RA. Mycosis fungoides palmaris et plantaris: successful treatment with the carbon dioxide laser. British Journal of Dermatology 1997; 136: 617-619 [Medline]

Gottlieb SL, Wolfe JT, Fox FE, DeNardo BJ, Macey WH, Bromley PG, et al. Treatment of cutaneous T-cell lymphoma with extracorporeal photopheresis monotherapy and in combination with recombinant interferon alfa: a 10-year experience at a single institution. J Am Acad Dermatol 1996; 35: 946-957 [Medline]

Grozea PN, Jones SE, McKelvey EM, Coltman CAJ, Fisher R, Haskins CL. Combination chemotherapy for mycosis fungoides: a Southwest Oncology Group study. Cancer Treat Rep 1979; 63: 647-653 [Medline]

Guitart J, Kaul K. A new polymerase chain reaction-based method for the detection of T- cell clonality in patients with possible cutaneous T-cell lymphoma. Arch Dermatol 1999; 135: 158-162 [Medline]

Guitart J, Peduto M, Caro WA, Roenigk HH. Lichenoid changes in mycosis fungoides. J Am Acad Dermatol 1997; 36: 417-422 [Medline]

Guitart J, Wickless SC, Oyama Y, Kuzel TM, Rosen ST, Traynor A, et al. Long-term remission after allogeneic hematopoietic stem cell transplantation for refractory cutaneous T-cell lymphoma. Arch Dermatol 2002; 138: 1359-1365 [Medline]

Hagberg H, Lundin J, Cavallin-Stahl E, Freden S, Juliusson G, et al. Phase 2 study of alemtuzumab (Campath-1H) in patients with advanced mycosis fungoides/Sèzary syndrome. Ann Oncol 2002; 13 (Suppl 2): 85 [Medline]

Hall WW, Liu CR, Schneewind O, Takahashi H, Kaplan MH, Roupe G, et al. Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides. Science 1991; 253: 317-320 [Medline]

Harmon CB, Witzig TE, Katzmann JA, Pittelkow MR. Detection of circulating T cells with CD4+CD7- immunophenotype in patients with benign and malignant lymphoproliferative dermatoses. J Am Acad Dermatol 1996; 35: 404-410 [Medline]

Heald P, Mehlmauer M, Martin AG, Crowley CA, Yocum RC, Reich SD. Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol 2003; 49: 801-815 [Medline]

Herne KL, Talpur R, Breuer-McHam J, Champlin R, Duvic M. Cytomegalovirus seropositivity is significantly associated with mycosis fungoides and Sezary syndrome. Blood 2003; 101: 2132-2136 [Medline]

Herrmann JJ, Roenigk HHJ, Hurria A, Kuzel TM, Samuelson E, Rademaker AW, et al. Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol 1995; 33: 234-242 [Medline]

Hodak E, Klein T, Gabay B, Ben Amitai D, Bergman R, Gdalevich M, et al. Familial mycosis fungoides: report of 6 kindreds and a study of the HLA system. J Am Acad Dermatol 2005; 52: 393-402 [Medline]

Holloway KB, Flowers FP, Ramos-Caro FA. Therapeutic alternatives in cutaneous T-cell lymphoma [see comments]. J Am Acad Dermatol 1992; 27: 367-378 [Medline]

Hoppe RT, Wood GS, Abel EA. Mycosis fungoides and the Sezary syndrome: pathology, staging, and treatment. Current Problems in Cancer 1990; 14: 293-371 [Medline]

Hoppe RT. Total skin electron beam therapy in the management of mycosis fungoides. Frontiers of Radiation Therapy & Oncology 1991; 25: 80-89 [Medline]

Huber MA, Kunzi-Rapp K, Staib G, Scharffetter-Kochanek K. Management of refractory early-stage cutaneous T-cell lymphoma (mycosis fungoides) with a combination of oral bexarotene and psoralen plus ultraviolet bath therapy. J Am Acad Dermatol 2004; 50: 475-476 [Medline]

Izban KF, Hsi ED, Alkan S. Immunohistochemical analysis of mycosis fungoides on paraffin-embedded tissue sections. Mod Pathol 1998; 11: 978-982 [Medline]

Johnson GA, Dewald GW, Strand WR, Winkelmann RK. Chromosome studies in 17 patients with the Sezary syndrome. Cancer 1985; 55: 2426-2433 [Medline]

Jones G, McLean J, Rosenthal D, Roberts J, Sauder DN. Combined treatment with oral etretinate and electron beam therapy in patients with cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome). J Am Acad Dermatol 1992; 26: 960-967 [Medline]

Jones GW, Kacinski BM, Wilson LD, Willemze R, Spittle M, Hohenberg G, et al. Total skin electron radiation in the management of mycosis fungoides: Consensus of the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group. J Am Acad Dermatol 2002; 47: 364-370 [Medline]

Jones GW, Tadros A, Hodson DI, Rosenthal D, Roberts J, Thorson B. Prognosis with newly diagnosed mycosis fungoides after total skin electron radiation of 30 or 35 GY. International Journal of Radiation Oncology, Biology, Physics 1994; 28: 839-845. [Medline]

Jones GW, Wilson LD. Mycosis fungoides and total skin electron beam radiation. Blood 1997; 89: 3062-3064 [Medline]

Juarez T, Isenhath SN, Polissar NL, Sabath DE, Wood B, Hanke D, et al. Analysis of T-cell receptor gene rearrangement for predicting clinical outcome in patients with cutaneous T-cell lymphoma: a comparison of Southern blot and polymerase chain reaction methods. Arch Dermatol 2005; 141: 1107-1113 [Medline]

Kamarashev J, Burg G, Kempf W, Hess SM, Dummer R. Comparative analysis of histological and immunohistological features in mycosis fungoides and Sezary syndrome. J Cutan Pathol 1998; 25: 407-412 [Medline]

Karenko L, Hahtola S, Paivinen S, Karhu R, Syrja S, Kahkonen M, et al. Primary cutaneous T-cell lymphomas show a deletion or translocation affecting NAV3, the human UNC-53 homologue. Cancer Res 2005; 65: 8101-8110 [Medline]

Karenko L, Kahkonen M, Hyytinen ER, Lindlof M, Ranki A. Notable losses at specific regions of chromosomes 10q and 13q in the Sezary syndrome detected by comparative genomic hybridization. J Invest Dermatol 1999; 112: 392-395 [Medline]

Karenko L, Sarna S, Kahkonen M, Ranki A. Chromosomal abnormalities in relation to clinical disease in patients with cutaneous T-cell lymphoma: a 5-year follow-up study. Br J Dermatol 2003; 148: 55-64 [Medline]

Kaye FJ, Bunn PAJ, Steinberg SM, Stocker JL, Ihde DC, Fischmann AB, et al. A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. N Engl J Med 1989; 321: 1784-1790 [Medline]

Kern DE, Kidd PG, Moe R, Hanke D, Olerud JE. Analysis of T-cell receptor gene rearrangement in lymph nodes of patients with mycosis fungoides. Prognostic implications. Arch Dermatol 1998; 134: 158-164 [Medline]

Kim ST, Jeon YS, Sim HJ, Kim SH, Kim YK, Suh KS, et al. Clinicopathologic features and T-cell receptor gene rearrangement findings of mycosis fungoides palmaris et plantaris. J Am Acad Dermatol 2006; 54: 466-471 [Medline]

Kim YH, Bishop K, Varghese A, Hoppe RT. Prognostic factors in erythrodermic mycosis fungoides and the Sezary syndrome. Arch Dermatol 1995; 131: 1003-1008 [Medline]

Kim YH, Chow S, Varghese A, Hoppe RT. Clinical characteristics and long-term outcome of patients with generalized patch and/or plaque (T2) mycosis fungoides. Arch Dermatol 1999b; 135: 26-32 [Medline]

Kim YH, Hoppe RT. Mycosis fungoides and the Sezary syndrome. Semin Oncol 1999a; 26: 276-289 [Medline]

Kim YH, Jensen RA, Watanabe GL, Varghese A, Hoppe RT. Clinical stage IA (limited patch and plaque) mycosis fungoides. A long- term outcome analysis. Arch Dermatol 1996; 132: 1309-1313 [Medline]

Kim YH, Liu HL, Mraz-Gernhard S, Varghese A, Hoppe RT. Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Arch Dermatol 2003; 139: 857-866 [Medline]

Kim YH, Martinez G, Varghese A, Hoppe RT. Topical nitrogen mustard in the management of mycosis fungoides: update of the Stanford experience. Arch Dermatol 2003; 139: 165-173 [Medline]

Klemke CD, Mansmann U, Poenitz N, Dippel E, Goerdt S. Prognostic factors and prediction of prognosis by the CTCL Severity Index in mycosis fungoides and Sezary syndrome. Br J Dermatol 2005; 153: 118-124 [Medline]

Knox SJ, Levy R, Hodgkinson S, Bell R, Brown S, Wood GS, et al. Observations on the effect of chimeric anti-CD4 monoclonal antibody in patients with mycosis fungoides. Blood 1991; 77: 20-30 [Medline]

Ko JW, Seong JY, Suh KS, Kim ST. Pityriasis lichenoides-like mycosis fungoides in children. Br J Dermatol 2000; 142: 347-352 [Medline]

Kodama K, Fink-Puches R, Massone C, Kerl H, Cerroni L. Papular mycosis fungoides: a new clinical variant of early mycosis fungoides. J Am Acad Dermatol 2005; 52: 694-698 [Medline]

Kong LR, Samuelson E, Rosen ST, Roenigk HHJ, Tallman MS, Rademaker AW, et al. 2-Chlorodeoxyadenosine in cutaneous T-cell lymphoproliferative disorders. Leuk Lymphoma 1997; 26: 89-97 [Medline]

Kuchnio M, Sausville EA, Jaffe ES, Greiner T, Foss FM, McClanahan J, et al. Flow cytometric detection of neoplastic T cells in patients with mycosis fungoides based on levels of T-cell receptor expression. Am J Clin Pathol 1994; 102: 856-860 [Medline]

Kulin PA, Marglin SI, Shuman WP, Chew DE, Olerud JE. Diagnostic imaging in the initial staging of mycosis fungoides and Sezary syndrome. Arch Dermatol 1990; 126: 914-918 [Medline]

Kuzel TM, Roenigk HHJ, Samuelson E, Herrmann JJ, Hurria A, Rademaker AW, et al. Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sezary syndrome. Journal of Clinical Oncology 1995; 13: 257-263 [Medline]

Kuzel TM. Systemic chemotherapy for the treatment of mycosis fungoides and Sezary syndrome. Dermatol Ther 2003; 16: 355-361 [Medline]

Lambert WC, Cohen PJ, Schwartz RA. Surgical management of mycosis fungoides. Journal of Medicine 1997; 28: 211-222 [Medline]

Liebmann RD, Anderson B, McCarthy KP, Chow JW. The polymerase chain reaction in the diagnosis of early mycosis fungoides. J Pathol 1997; 182: 282-287 [Medline]

Lundin J, Hagberg H, Repp R, Cavallin-Stahl E, Freden S, Juliusson G, et al. Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood 2003; 101: 4267-4272 [Medline]

Lundin J, Osterborg A, Brittinger G, Crowther D, Dombret H, Engert A, et al. CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin’s lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low-Grade Non-Hodgkin’s Lymphoma. J Clin Oncol 1998; 16: 3257-3263 [Medline]

Maier T, Tun-Kyi A, Tassis A, Jungius KP, Burg G, Dummer R, et al. Vaccination of patients with cutaneous T-cell lymphoma using intranodal injection of autologous tumor-lysate-pulsed dendritic cells. Blood 2003; 102: 2338-2344 [Medline]

Mao X, Lillington D, Scarisbrick JJ, Mitchell T, Czepulkowski B, Russell-Jones R, et al. Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in Sezary syndrome and mycosis fungoides. Br J Dermatol 2002; 147: 464-475 [Medline]

Mao X, Orchard G, Lillington DM, Russell-Jones R, Young BD, Whittaker SJ. Amplification and overexpression of JUNB is associated with primary cutaneous T-cell lymphomas. Blood 2003; 101: 1513-1519 [Medline]

Marchi E, Alinari L, Tani M, Stefoni V, Pimpinelli N, Berti E, et al. Gemcitabine as frontline treatment for cutaneous T-cell lymphoma: phase II study of 32 patients. Cancer 2005; 104: 2437-2441 [Medline]

Marschalko M, Knobler R, Soos G, Berecz M, Paloczy K, Racz I. [Extracorporeal photopheresis in the therapy of Sezary syndrome]. [Hungarian]. Orvosi Hetilap 1993; 134: 1253-1257 [Medline]

Masood N, Russell KJ, Olerud JE, Sabath DE, Sale GE, Doney KC, et al. Induction of complete remission of advanced stage mycosis fungoides by allogeneic hematopoietic stem cell transplantation. J Am Acad Dermatol 2002; 47: 140-145 [Medline]

Massone C, Kodama K, Kerl H, Cerroni L. Histopathologic features of early (patch) lesions of mycosis fungoides: a morphologic study on 745 biopsy specimens from 427 patients. Am J Surg Pathol 2005; 29: 550-560 [Medline]

McBride SR, Dahl MG, Slater DN, Sviland L. Vesicular mycosis fungoides. Br J Dermatol 1998; 138: 141-144 [Medline]

McNiff JM, Schechner JS, Crotty PL, Glusac EJ. Mycosis fungoides palmaris et plantaris or acral pagetoid reticulosis? Am J Dermatopathol 1998; 20: 271-275 [Medline]

Mehrany K, El Azhary RA, Bouwhuis SA, Pittelkow MR. Cutaneous T-cell lymphoma and atopy: is there an association? Br J Dermatol 2003; 149: 1013-1017 [Medline]

Mercieca J, Matutes E, Dearden C, MacLennan K, Catovsky D. The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype. J Clin Oncol 1994; 12: 2588-2593 [Medline]

Miracco C, Rubegni P, De Aloe G, D’Ascenzo G, Mazzatenta C, De Santi MM, et al. Extracorporeal photochemotherapy induces apoptosis of infiltrating lymphoid cells in patients with mycosis fungoides in early stages. A quantitative histological study. Br J Dermatol 1997; 137: 549-557 [Medline]

Molina A, Zain J, Arber DA, Angelopolou M, O’Donnell M, Murata-Collins J, et al. Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and mycosis fungoides. J Clin Oncol 2005; 23: 6163-6171 [Medline]

Muche JM, Lukowsky A, Asadullah K, Gellrich S, Sterry W. Demonstration of frequent occurrence of clonal T cells in the peripheral blood of patients with primary cutaneous T-cell lymphoma. Blood 1997; 90: 1636-1642 [Medline]

Muche MJ, Karenko L, Gellrich S, Karhu R, Kytola S, Kahkonen M, et al. Cellular coincidence of clonal T cell receptor rearrangements and complex clonal chromosomal aberrations-a hallmark of malignancy in cutaneous T cell lymphoma. J Invest Dermatol 2004; 122: 574-578 [Medline]

Munster P, Marchion D, Bicaku E, Schmitt M, Lee JH, DeConti R, et al. Phase I trial of histone deacetylase inhibition by valproic acid followed by the topoisomerase II inhibitor epirubicin in advanced solid tumors: a clinical and translational study. J Clin Oncol 2007; 25: 1979-1985 [Medline]

Navas IC, Ortiz-Romero PL, Villuendas R, Martinez P, Garcia C, Gomez E, et al. p16(INK4a) gene alterations are frequent in lesions of mycosis fungoides. Am J Pathol 2000; 156: 1565-1572 [Medline]

Nisce LZ, Safai B, Kim JH. Effectiveness of once weekly total skin electron beam therapy in mycosis fungoides and Sezary syndrome. Cancer 1981; 47: 870-876 [Medline]

Olavarria E, Child F, Woolford A, Whittaker SJ, Davis JG, McDonald C, et al. T-cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement. Br J Haematol 2001; 114: 624-631 [Medline]

Olsen E, Duvic M, Frankel A, Kim Y, Martin A, Vonderheid E, et al. Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J Clin Oncol 2001; 19: 376-388 [Medline]

Pangalis GA, Dimopoulou MN, Angelopoulou MK, Tsekouras C, Vassilakopoulos TP, Vaiopoulos G, et al. Campath-1H (anti-CD52) monoclonal antibody therapy in lymphoproliferative disorders. Med Oncol 2001; 18: 99-107 [Medline]

Pawson R, Matutes E, Brito-Babapulle V, Maljaie H, Hedges M, Mercieca J, et al. Sezary cell leukaemia: a distinct T cell disorder or a variant form of T prolymphocytic leukaemia? Leukemia 1997; 11: 1009-1013 [Medline]

Pereyo NG, Requena L, Galloway J, Sangueza OP. Follicular mycosis fungoides: a clinicohistopathologic study. J Am Acad Dermatol 1997; 36: 563-568 [Medline]

Pimpinelli N, Olsen EA, Santucci M, Vonderheid E, Haeffner AC, Stevens S, et al. Defining early mycosis fungoides. J Am Acad Dermatol 2005; 53: 1053-1063 [Medline]

Poszepczynska-Guigne E, Bagot M, Wechsler J, Revuz J, Farcet JP, Delfau-Larue MH. Minimal residual disease in mycosis fungoides follow-up can be assessed by polymerase chain reaction. Br J Dermatol 2003; 148: 265-271 [Medline]

Quaglino P, Fierro MT, Rossotto GL, Savoia P, Bernengo MG. Treatment of advanced mycosis fungoides/Sezary syndrome with fludarabine and potential adjunctive benefit to subsequent extracorporeal photochemotherapy. Br J Dermatol 2004; 150: 327-336 [Medline]

Quiros PA, Jones GW, Kacinski BM, Braverman IM, Heald PW, Edelson RL, et al. Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides). Int J Radiat Oncol Biol Phys 1997; 38: 1027-1035 [Medline]

Ralfkiaer E, Wollf-Sneedorff A, Thomsen K, Vejlsgaard GL. Immunophenotypic studies in cutaneous T-cell lymphomas: clinical implications. Br J Dermatol 1993; 129: 655-659 [Medline]

Ramsay DL, Lish KM, Yalowitz CB, Soter NA. Ultraviolet-B phototherapy for early-stage cutaneous T-cell lymphoma. Arch Dermatol 1992; 128: 931-933 [Medline]

Resnik KS, Vonderheid EC. Home UV phototherapy of early mycosis fungoides: long-term follow-up observations in thirty-one patients. J Am Acad Dermatol 1993; 29: 73-77 [Medline]

Robey RW, Zhan Z, Piekarz RL, Kayastha GL, Fojo T, Bates SE. Increased MDR1 expression in normal and malignant peripheral blood mononuclear cells obtained from patients receiving depsipeptide (FR901228, FK228, NSC630176). Clin Cancer Res 2006; 12: 1547-1555 [Medline]

Roenigk HHJ, Kuzel TM, Skoutelis AP, Springer E, Yu G, Caro W, et al. Photochemotherapy alone or combined with interferon alpha-2a in the treatment of cutaneous T-cell lymphoma. J Invest Dermatol 1990; 95: 198S-205S [Medline]

Rook AH, Kuzel TM, Olsen EA. Cytokine therapy of cutaneous T-cell lymphoma: interferons, interleukin-12, and interleukin-2. Hematol Oncol Clin North Am 2003; 17: 1435-48, ix [Medline]

Rosen ST, Foss FM. Chemotherapy for mycosis fungoides and the Sezary syndrome. Hematology – Oncology Clinics of North America 1995; 9: 1109-1116 [Medline]

Rosenblatt E, Kuten A, Leviov M, Cederbaum M. Total skin electron irradiation in mycosis fungoides dose and fractionation considerations. Leuk Lymphoma 1998; 30: 143-151 [Medline]

Sacchi S, Russo D, Avvisati G, Dastoli G, Lazzarino M, Pelicci PG, et al. All-trans retinoic acid in hematological malignancies, an update. GER (Gruppo Ematologico Retinoidi). Haematologica 1997; 82: 106-121 [Medline]

Salhany KE, Greer JP, Cousar JB, Collins RD. Marrow involvement in cutaneous T-cell lymphoma. A clinicopathologic study of 60 cases. Am J Clin Pathol 1989; 92: 747-754 [Medline]

Sanchez JL, Ackerman AB. The patch stage of mycosis fungoides. Criteria for histologic diagnosis. Am J Dermatopathol 1979; 1: 5-26 [Medline]

Santucci M, Biggeri A, Feller AC, Burg G. Accuracy, concordance, and reproducibility of histologic diagnosis in cutaneous T-cell lymphoma: an EORTC Cutaneous Lymphoma Project Group Study. European Organization for Research and Treatment of Cancer. Arch Dermatol 2000a; 136: 497-502 [Medline]

Santucci M, Biggeri A, Feller AC, Massi D, Burg G. Efficacy of histologic criteria for diagnosing early mycosis fungoides: an EORTC cutaneous lymphoma study group investigation. European Organization for Research and Treatment of Cancer. Am J Surg Pathol 2000b; 24: 40-50 [Medline]

Sausville EA, Eddy JL, Makuch RW, Fischmann AB, Schechter GP, Matthews M, et al. Histopathologic staging at initial diagnosis of mycosis fungoides and the Sezary syndrome. Definition of three distinctive prognostic groups. Ann Intern Med 1988; 109: 372-382 [Medline]

Scarabello A, Leinweber B, Ardigo M, Rutten A, Feller AC, Kerl H, et al. Cutaneous lymphomas with prominent granulomatous reaction: a potential pitfall in the histopathologic diagnosis of cutaneous T- and B-cell lymphomas. Am J Surg Pathol 2002; 26: 1259-1268 [Medline]

Scarisbrick JJ, Mitchell TJ, Calonje E, Orchard G, Russell-Jones R, Whittaker SJ. Microsatellite instability is associated with hypermethylation of the hMLH1 gene and reduced gene expression in mycosis fungoides. J Invest Dermatol 2003; 121: 894-901 [Medline]

Scarisbrick JJ, Woolford AJ, Calonje E, Photiou A, Ferreira S, Orchard G, et al. Frequent abnormalities of the p15 and p16 genes in mycosis fungoides and sezary syndrome. J Invest Dermatol 2002; 118: 493-499 [Medline]

Scarisbrick JJ, Woolford AJ, Russell-Jones R, Whittaker SJ. Allelotyping in mycosis fungoides and Sezary syndrome: common regions of allelic loss identified on 9p, 10q, and 17p. J Invest Dermatol 2001; 117: 663-670 [Medline]

Seo N, Tokura Y, Matsumoto K, Furukawa F, Takigawa M. Tumour-specific cytotoxic T lymphocyte activity in Th2-type Sezary syndrome: its enhancement by interferon-gamma (IFN-gamma) and IL-12 and fluctuations in association with disease activity. Clin Exp Immunol 1998; 112: 403-409 [Medline]

Sibaud V, Beylot-Barry M, Thiebaut R, Parrens M, Vergier B, Delaunay M, et al. Bone marrow histopathologic and molecular staging in epidermotropic T-cell lymphomas. Am J Clin Pathol 2003; 119: 414-423 [Medline]

Soligo D, Ibatici A, Berti E, Morandi P, Longhi E, Venegoni L, et al. Treatment of advanced mycosis fungoides by allogeneic stem-cell transplantation with a nonmyeloablative regimen. Bone Marrow Transplant 2003; 31: 663-666 [Medline]

Stadler R, Otte HG, Luger T, Henz BM, Kuhl P, Zwingers T, et al. Prospective randomized multicenter clinical trial on the use of interferon -2a plus acitretin versus interferon -2a plus PUVA in patients with cutaneous T-cell lymphoma stages I and II. Blood 1998; 92: 3578-3581 [Medline]

Stefanato CM, Tallini G, Crotty PL. Histologic and immunophenotypic features prior to transformation in patients with transformed cutaneous T-cell lymphoma: is CD25 expression in skin biopsy samples predictive of large cell transformation in cutaneous T-cell lymphoma? Am J Dermatopathol 1998; 20: 1-6 [Medline]

Talpur R, Jones DM, Alencar AJ, Apisarnthanarax N, Herne KL, Yang Y, et al. CD25 expression is correlated with histological grade and response to denileukin diftitox in cutaneous T-cell lymphoma. J Invest Dermatol 2006; 126: 575-583 [Medline]

Telle H, Koeppel MC, Jreissati M, Andrac L, Horschowski N, Sayag J. Granulomatous mycosis fungoides. Eur J Dermatol 1998; 8: 506-510 [Medline]

Thangavelu M, Finn WG, Yelavarthi KK, Roenigk HHJ, Samuelson E, Peterson L, et al. Recurring structural chromosome abnormalities in peripheral blood lymphocytes of patients with mycosis fungoides/Sezary syndrome. Blood 1997; 89: 3371-3377 [Medline]

Thomas M, Chandi SM, George S, Pulimood S, Sitaram U. Sezary syndrome – unmasked by cyclosporine. Int J Dermatol 1998; 37: 957-958 [Medline]

Tomasini C, Aloi F, Solaroli C, Pippione M. Psoriatic erythroderma: a histopathologic study of forty-five patients. Dermatology 1997; 194: 102-106 [Medline]

Tracey L, Villuendas R, Dotor AM, Spiteri I, Ortiz P, Garcia JF, et al. Mycosis fungoides shows concurrent deregulation of multiple genes involved in the TNF signaling pathway: an expression profile study. Blood 2003; 102: 1042-1050 [Medline]

Trotter MJ, Whittaker SJ, Orchard GE, Smith NP. Cutaneous histopathology of Sezary syndrome: a study of 41 cases with a proven circulating T-cell clone. J Cutan Pathol 1997; 24: 286-291 [Medline]

Tsimberidou AM, Giles F, Duvic M, Fayad L, Kurzrock R. Phase II study of pentostatin in advanced T-cell lymphoid malignancies: update of an M.D. Anderson Cancer Center series. Cancer 2004a; 100: 342-349 [Medline]

Tsimberidou AM, Giles FJ, Duvic M, Kurzrock R. Pilot study of etanercept in patients with relapsed cutaneous T-cell lymphomas. J Am Acad Dermatol 2004b; 51: 200-204 [Medline]

Undevia SD, Kindler HL, Janisch L, Olson SC, Schilsky RL, Vogelzang NJ, et al. A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabine. Ann Oncol 2004; 15: 1705-1711 [Medline]

Vacca A, Moretti S, Ribatti D, Pellegrino A, Pimpinelli N, Bianchi B, et al. Progression of mycosis fungoides is associated with changes in angiogenesis and expression of the matrix metalloproteinases 2 and 9. Eur J Cancer 1997; 33: 1685-1692 [Medline]

Valencak J, Becherer A, Der-Petrossian M, Trautinger F, Raderer M, Hoffmann M. Positron emission tomography with [18F] 2-fluoro-D-2- deoxyglucose in primary cutaneous T-cell lymphomas. Haematologica 2004; 89: 115-116 [Medline]

van Doorn R, van Haselen CW, Voorst Vader PC, Geerts ML, Heule F, de Rie M, et al. Mycosis fungoides: disease evolution and prognosis of 309 Dutch patients. Arch Dermatol 2000; 136: 504-510 [Medline]

van Haselen CW, Diederen PV, Toonstra J, van der Putte SC, Rademakers LH, Faber JA, et al. The small-cell variant of mycosis fungoides. A clinicopathological and quantitative electron microscopic study on 14 patients. Arch Dermatol Res 1998; 290: 583-590 [Medline]

Von Hoff DD, Dahlberg S, Hartstock RJ, Eyre HJ. Activity of fludarabine monophosphate in patients with advanced mycosis fungoides: a Southwest Oncology Group study. J Natl Cancer Inst 1990; 82: 1353-1355 [Medline]

Vonderheid EC, Ekbote SK, Kerrigan K, Kalmanson JD, Van Scott EJ, Rook AH, et al. The prognostic significance of delayed hypersensitivity to dinitrochlorobenzene and mechlorethamine hydrochloride in cutaneous T cell lymphoma. J Invest Dermatol 1998; 110: 946-950 [Medline]

Wain EM, Mitchell TJ, Russell-Jones R, Whittaker SJ. Fine mapping of chromosome 10q deletions in mycosis fungoides and sezary syndrome: identification of two discrete regions of deletion at 10q23.33-24.1 and 10q24.33-25.1. Genes Chromosomes Cancer 2005; 42: 184-192 [Medline]

Watson A. Photochemotherapy for mycosis fungoides: current status. [Review]. Australasian Journal of Dermatology 1997; 38: 9-11 [Medline]

Weinstock MA, Reynes JF. The changing survival of patients with mycosis fungoides: a population- based assessment of trends in the United States. Cancer 1999; 85: 208-212 [Medline]

Weinstock MA. A registry-based case-control study of mycosis fungoides. Ann Epidemiol 1991; 1: 533-539 [Medline]

Whittaker SJ, Marsden JR, Spittle M, Russell JR. Joint British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous T-cell lymphomas. Br J Dermatol 2003; 149: 1095-1107 [Medline]

Whittemore AS, Holly EA, Lee IM, Abel EA, Adams RM, Nickoloff BJ, et al. Mycosis fungoides in relation to environmental exposures and immune response: a case-control study. J Natl Cancer Inst 1989; 81: 1560-1567 [Medline]

Wieselthier JS, Koh HK. Sezary syndrome: diagnosis, prognosis, and critical review of treatment options. Journal of the American Academy of Dermatology 1990; 22: 381-401 [Medline]

Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al. WHO-EORTC classification for cutaneous lymphomas. Blood 2005; 105: 3768-3785 [Medline]

Wilson LD, Jones GW, Kim D, Rosenthal D, Christensen IR, Edelson RL, et al. Experience with total skin electron beam therapy in combination with extracorporeal photopheresis in the management of patients with erythrodermic (T4) mycosis fungoides. J Am Acad Dermatol 2000; 43: 54-60 [Medline]

Wilson LD, Kacinski BM, Jones GW. Local superficial radiotherapy in the management of minimal stage IA cutaneous T-cell lymphoma (Mycosis Fungoides). Int J Radiat Oncol Biol Phys 1998; 40: 109-115 [Medline]

Wilson LD, Licata AL, Braverman IM, Edelson RL, Heald PW, Feldman AM, et al. Systemic chemotherapy and extracorporeal photochemotherapy for T3 and T4 cutaneous T-cell lymphoma patients who have achieved a complete response to total skin electron beam therapy. International Journal of Radiation Oncology, Biology, Physics 1995; 32: 987-995 [Medline]

Winkler CF, Sausville EA, Ihde DC, Fischmann AB, Schechter GP, Kumar PP, et al. Combined modality treatment of cutaneous T cell lymphoma: results of a 6-year follow-up. J Clin Oncol 1986; 4: 1094-1100 [Medline]

Wollina U, Dummer R, Brockmeyer NH, Konrad H, Busch JO, Kaatz M, et al. Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 2003; 98: 993-1001 [Medline]

Wollina U. Partial regrowth of scalp hair in a patient treated with extracorporeal photochemotherapy and interferon alpha 2a. J Eur Acad Dermatol Venereol 1998; 11: 261-262 [Medline]

Wood GS, Abel EA, Hoppe RT, Warnke RA. Leu-8 and Leu-9 antigen phenotypes: immunologic criteria for the distinction of mycosis fungoides from cutaneous inflammation. J Am Acad Dermatol 1986; 14: 1006-1013 [Medline]

Wood GS, Bahler DW, Hoppe RT, Warnke RA, Sklar JL, Levy R. Transformation of mycosis fungoides: T-cell receptor beta gene analysis demonstrates a common clonal origin for plaque-type mycosis fungoides and CD30+ large-cell lymphoma. J Invest Dermatol 1993; 101: 296-300 [Medline]

Wood GS, Salvekar A, Schaffer J, Crooks CF, Henghold W, Fivenson DP, et al. Evidence against a role for human T-cell lymphotrophic virus type I (HTLV-I) in the pathogenesis of American cutaneous T-cell lymphoma. J Invest Dermatol 1996; 107: 301-307 [Medline]

Wysocka M, Benoit BM, Newton S, Azzoni L, Montaner LJ, Rook AH. Enhancement of the host immune responses in cutaneous T-cell lymphoma by CpG oligodeoxynucleotides and IL-15. Blood 2004; 104: 4142-4149 [Medline]

Yamamoto T, Takahashi Y, Katayama I, Nishioka K. Alteration of cytokine genes and bcl-2 expression following immunotherapy with intralesional IFN-gamma in a patient with tumor- stage mycosis fungoides. Dermatology 1998; 196: 283-287 [Medline]

Zackheim H. Ultraviolet radiation and cutaneous lymphoma. Br J Cancer 1998a; 78: 1397-1398 [Medline]

Zackheim HS, Amin S, Kashani-Sabet M, McMillan A. Prognosis in cutaneous T-cell lymphoma by skin stage: long-term survival in 489 patients. J Am Acad Dermatol 1999; 40: 418-425 [Medline]

Zackheim HS, Kashani-Sabet M, Amin S. Topical corticosteroids for mycosis fungoides. Experience in 79 patients. Arch Dermatol 1998b; 134: 949-954 [Medline]

Zackheim HS, Kashani-Sabet M, Hwang ST. Low-dose methotrexate to treat erythrodermic cutaneous T-cell lymphoma: results in twenty-nine patients. J Am Acad Dermatol 1996; 34: 626-631 [Medline]

Zackheim HS, Kashani-Sabet M, McMillan A. Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 2003a; 49: 873-878 [Medline]

Zackheim HS. Topical carmustine (BCNU) for patch/plaque mycosis fungoides. Seminars in Dermatology 1994; 13: 202-206 [Medline]

Zackheim HS. Topical carmustine (BCNU) in the treatment of mycosis fungoides. Dermatol Ther 2003b; 16: 299-302 [Medline]

Zaucha JM, Lewandowski K, Hellmann A, Pawlik H, Siedlewicz A. 2-Chlorodeoxyadenosine treatment in the Sezary syndrome. Blood 1997; 89: 1462-1464 [Medline]

Zic JA, Miller JL, Stricklin GP, King LEJ. The North American experience with photopheresis. Ther Apher 1999; 3: 50-62 [Medline]

Zinzani PL, Alinari L, Tani M, Fina M, Pileri S, Baccarani M. Preliminary observations of a phase II study of reduced-dose alemtuzumab treatment in patients with pretreated T-cell lymphoma. Haematologica 2005; 90: 702-703 [Medline]

Zinzani PL, Baliva G, Magagnoli M, Bendandi M, Modugno G, Gherlinzoni F, et al. Gemcitabine treatment in pretreated cutaneous T-cell lymphoma: experience in 44 patients. J Clin Oncol 2000; 18: 2603-2606 [Medline]

Prof. Lorenzo Cerroni (Reviewer)
Medical University of Graz, Austria

Dr. Andrés Ferreri (Associate Editor)
San Raffaele Scientific Institute – Milan, Italy

Dr. Carlo Tondini (Editor)
START Clinical Editor – Ospedali Riuniti – Bergamo, Italy

Prof. Pier Luigi Zinzani (Author)
Institute of Hematology and Oncology Seragnoli, University of Bologna, Italy