Classic Mycosis Fungoides Research Articles

A specific DNA methylation profile correlates with a high risk of disease progression in stage I classical (Alibert-Bazin type) mycosis fungoides

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma; in its classical presentation it evolves slowly, but it can have an aggressive course in a subset of patients. To investigate the impact of epigenetic mechanisms on the progression of early stage MF. We analysed DNA methylation at 12 different loci and long interspersed nucleotide elements-1 (LINE-1), as a surrogate marker of global methylation, on tissue samples from 41 patients with stage I MF followed up for at least 12years or until disease progression. The methylation profiles were also analysed in two T-cell lymphoma cell lines and correlated with gene expression. The selected loci were methylated in a tumour-specific manner; concomitant hypermethylation of at least four loci was more frequent in cases progressing within 1-3 and 3-6years than in late-progressive or non-progressive cases. LINE-1 methylation was significantly lower in rapidly progressive MF at 3years (61%, P<0·001) than in those at 12years (67%). PPARG, SOCS1 and NEUROG1 methylation showed remarkable differences among the prognostic groups, but only PPARG was a significant predictor of disease progression within 6years, after adjustment for patients' age or gender. Strikingly, a methylation profile similar to progressive cases was found in highly proliferative Sézary-derived HUT78 cells but not in MF-derived HUT102 cells. Exposure to a DNA demethylating agent restored sensitivity to apoptosis and cell cycle arrest. Epigenetic silencing of specific biomarkers can predict the risk of disease progression in early-stage MF, providing insights into its pathogenesis, prognosis and therapy.

Quick Consult

FigureFigureFigureA 59-year-old woman presents to the ED with a complaint of an asthma attack. Incidentally, the patient is noted to have this skin finding. What is the diagnosis and treatment for this condition? Diagnosis: Cutaneous T-cell Lymphoma: Mycosis Fungoides Non-Hodgkin's lymphoma is a relatively rare group of malignant neoplasms involving B cells, T cells, their progenitors, and, rarely, natural killer cells. A total of 4.3 percent of all new cancer cases in the United States are related to non-Hodgkin lymphoma. (Surveillance, Epidemiology, and End Results [SEER] program, National Cancer Institute; http://1.usa.gov/SaJGxa.) Cutaneous T-cell lymphoma (CTCL) represents 3.4 percent of these. CTCL is a diverse group of lymphoproliferative disorders characterized by the clonal expansion of mature T cells that infiltrate the skin. (Hematol Oncol Clin North Am 2008;22[5]:979.) Mycosis fungoides (MF) is the most common CTCL subtype, representing 44 percent of all primary cutaneous lymphomas. Primary cutaneous CD30+ lymphoproliferative disorders are the second most common subgroup of CTCLs, accounting for nearly 30 percent of these lymphomas. (Blood 2005;105[10]:3768.) Men have an increased incidence of CTCLs compared with women. The incidence of CTCL increases with age, peaking in those aged 70–84. (JAMA Dermatol 2013;149[11]:1295.) The exact cause of MF is unknown, but it is currently thought to involve chromosomal aberrations. (Cancer Res 2005;65[18]:8101), epigenetic abnormalities, and dysregulation of signaling pathways. (Semin Oncol 2006;33[1 Suppl 3]:S3.) Adhesion molecules and cytokine abnormalities have also been implicated in the pathophysiology of MF. (N Engl J Med 2004;350[19]:1978.)Figure: Various cutaneous lesions in mycosis fungoides.Patients with MF classically present with persistent, scaly patches in various shades of red and indurated, annular plaques with a central clearing. These lesions may progress to tumors or erythroderma. It should be noted that many clinical variants exist with diverse presentations that may only share diagnostic histological findings. (J Am Acad Dermatol 2002;46[3]:325.) Patients may also experience alopecia, pruritus, and dyspigmentation. (J Am Acad Dermatol 2011;64[1]:53, J Am Acad Dermatol 2011;65[2]:313.) Early diagnosis is challenging because features may overlap with known benign dermatosis, such as Acanthosis nigricans, Erythema multiforme, vitiligo, plaque-type psoriasis, and many more. (J Am Acad Dermatol 2002;47[6]:914.) Classic early patch-phase MF is characterized by lesions greater than 5 cm in diameter that vary in size, shape, and color. Most patients have multiple lesions that develop on parts of the body not often exposed to the sun, like the trunk, inner arms, thighs, and the bathing suit distribution, although this may vary. The juxtaposition of mottled pigmentation, epidermal atrophy, and telangiectasia (poikiloderma) is also relatively specific for early MF. (J Am Acad Dermatol 2005;53[6]:1053.) Patients present with patches or plaques involving less than 10 percent of the body surface area in 30 percent of MF cases while 37 percent of cases have involvement of more than 10 percent of body surface area. (Arch Dermatol 2003;139[7]:857.) The differential should include other causes of erythroderma or pruritus, such as generalized atopic dermatitis, psoriasis, drug reactions, and eczema. Also consider Sézary syndrome, the leukemic variant of MF, and other types of cutaneous lymphomas. The diagnosis of early MF involves a scoring system that considers clinical, histopathologic, molecular biological, and immunopathologic findings. The basic clinical criterion is met if a patient experiences persistent or progressive patches or thin plaques. Additional criteria include location in an area not exposed to the sun, variation in size and shape, and poikiloderma. (J Am Acad Dermatol 2005;53[6]:1053.) Treatment for MF depends on the extent of the disease, with milder cases benefiting from skin-directed therapies like topical corticosteroids (Arch Dermatol 1998;134[8]:949) or phototherapy with narrowband UVB. (J Am Acad Dermatol 2009;60[1]:39.) Combination treatments, systemic therapies, or total skin electron beam therapy may be used if escalating treatment is required. (J Am Acad Dermatol 2002;47[3]:364.) Patient prognosis varies depending primarily on staging. One cohort study of 1,263 patients with MF or Sézary syndrome found that 11.6 percent progressed to a higher stage and 8.1 percent died from the disease. The median overall survival was 24.4 years, and median progression-free survival was 16 years. Patients with stage IA limited patch and plaque MF did not experience significantly worse overall survival than matched controls. Risk factors for disease progression or death were found to be plaque stage, advanced age at diagnosis, LDH level, and tumor area. (Clin Cancer Res 2012;18[18]:5051.) This patient was diagnosed with CTCL as an outpatient and started on phototherapy treatments. Access the linksin EMN by reading this on our website or in our free iPad app, both available atwww.EM-News.com. Comments?Write to us at[email protected].

Pediatric mycosis fungoides in Singapore: a series of 46 children.

Few studies have evaluated Asian children with mycosis fungoides (MF). We report a series of patients from a tertiary dermatologic institution in Singapore. A retrospective review was performed of patients younger than 16years old diagnosed with MF between 2000 and 2008 at the National Skin Centre, Singapore. Forty-six patients were identified. At initial presentation, a provisional diagnosis of MF was made in 19 patients (41.3%), pityriasis lichenoides chronica (PLC) in 11 (23.9%) and postinflammatory hypopigmentation due to eczema or other causes in 11 (23.9%). After skin biopsy, the hypopigmented variant of MF was diagnosed in 42 patients (91.3%). There was one case each of PLC-like MF, pigmented purpuric dermatosis-like MF, classic MF, and solitary MF. Pityriasis lichenoides coexisted in three cases (6.5%). All except one patient presented with the early patch-plaque stage of disease (stage IA/B). The disease did not progress in any of our patients after a mean follow-up of 71.0±52.5months. Twenty-seven patients (58.7%) had complete disease clearance after a mean duration of 27.1±28.1months; 15 (49.7%) of 32 patients who received narrowband ultraviolet B treatment had complete clearance within an average of 8.9±5.3months, but 7 patients relapsed within 14.9±14.8months. One patient with solitary MF failed multiple treatment modalities before eventually achieving disease clearance with photodynamic therapy. Hypopigmented MF is the most common MF variant in Asian children. The diagnostic difficulty is in differentiating this from PLC, which may coexist with MF. Long-term prognosis is generally favorable.

Juvenile mycosis fungoides: Cutaneous T-cell lymphoma with frequent follicular involvement

The literature on mycosis fungoides (MF) in children/adolescents is sparse. We sought to evaluate the characteristics of juvenile MF in a large cohort. Data were collected on all patients with MF, aged 18 years or younger at the time of clinicopathologic diagnosis, who attended the Rabin Medical Center Dermatology Department, Petach Tikva, Israel, between 1994 and 2012 and were followed up prospectively. There were 50 patients (30 male; mean age 11.4 years at diagnosis); 18 (36%) had Fitzpatrick skin type IV or higher. All were given a diagnosis of early-stage disease (IA-IIA) except 1 (tumor stage, IIB). Eight had classic MF lesions only and 42 had other variants, alone or in combination; these were mainly hypopigmented MF (n = 29) and cases with subtle but clear clinicopathologic features of folliculotropic MF (FMF) (n = 18). Among the various skin-targeted therapies, psoralen plus ultraviolet A (systemic/bath) proved beneficial for FMF. During a follow-up period of 0.25 to 15 years (mean 4.5), 2 patients progressed from stage IA to IB or IIA. Relatively short follow-up is a limitation. This case series shows that FMF is not uncommon in children and adolescents. It is characterized by more superficial clinical features and less heavy perifollicular lymphocytic infiltrates than adult FMF, and responds well to psoralen plus ultraviolet A. The prognosis of childhood FMF remains unclear.

Generalized syringotropic mycosis fungoides responsive to extracorporeal photopheresis

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Syringotropic mycosis fungoides (STMF), a rare variant of mycosis fungoides (MF) and a subtype of follicular MF based on current classification,1 classically presents with punctate erythematous papules or plaques on the trunk or limbs, often with alopecia or anhidrosis, and typically follows an indolent clinical course. Because of the perieccrine localization of the dermal infiltrates, STMF is often less responsive to skin‐targeted therapies than classic MF, and given the rarity of the disease there is no accepted treatment approach, especially for those with generalized disease. A 72‐year‐old white man presented with a 10‐year history of generalized severe pruritus, scored as 10/10 on the numerical rating scale (NRS),2 with erythematous papules and plaques on his trunk and extremities, associated with generalized patchy hair loss. He reported no improvement with topical corticosteroids or emollients. Clinical examination revealed erythematous plaques, folliculotropic papules with perifollicular erythema (Fig. 1a) and large, open comedones on his upper mid‐back, flanks and thighs, amounting to a body surface area involvement of 15%. There was focal alopecia of the frontal and temporal scalp, without loss of follicular orifices, and diffuse thinning of the eyebrows and body hair. There was no evidence of organomegaly or lymphadenopathy on clinical examination. Routine laboratory testing, lactic dehydrogenase and flow‐cytometric analysis of circulating T‐cell subsets were normal.

Hypopigmented mycosis fungoides: a review of its clinical features and pathophysiology.

Several distinct clinical forms of mycosis fungoides have been described. Hypopigmented mycosis fungoides should be regarded as a subtype of mycosis fungoides, insofar as it presents some peculiar characteristics that contrast with the clinical features of the classical form. Most patients with hypopigmented mycosis fungoides are younger than patients typically diagnosed with classical mycosis fungoides. In addition to typical dark-skinned individuals impairment, hypopigmented mycosis fungoides has also been described in Asian patients. The prognosis for hypopigmented mycosis fungoides is much better than for classical mycosis fungoides: hypopigmented mycosis fungoides is diagnosed when there are only patches of affected skin, and lesions usually will not progress beyond terminal stages, although they can persist for many years. Diagnosis should involve clinicopathologic correlation: skin biopsy analysis often reveals intense epidermotropism, characterized by haloed, large, and atypical CD8+ lymphocytes with convoluted nuclei, in contrast to mild to moderate dermal lymphocytic infiltrate. These CD8+ cells, which participate in T helper 1-mediated immune responses, prevent evolution to mycosis fungoides plaques and tumors and could be considered the main cause of the inhibition of melanogenesis. Therefore, hypopigmentation could be considered a marker of good prognosis for mycosis fungoides.

CD20+ Mycosis Fungoides

Mycosis fungoides (MF) is the most common of the family of cutaneous T-cell lymphomas, accounting for 65% of all cases of cutaneous T-cell lymphomas. The classic phenotypic profile is one defined by CD4+ T cells showing a reduction in the expression of CD7 and CD62L. There are 3 previous reports describing CD20 expression in MF. The cell surface antigen CD20 is a transmembrane glycosylated phosphoprotein expressed in the early stages of B-cell development before differentiation into plasma cells. Two male patients, aged 14 and 44 years, presented with persistent truncal plaques up to 8 cm of 1 and 4 years duration, respectively. A third patient, an 80-year-old female, presented with a 1-year history of progressive nodules involving the head and neck area. Cases 1 and 2 both responded to topical treatment modalities. The biopsies in cases 1 and 2 showed features typical of plaque stage MF, whereas case 3 was compatible with follicular MF with tumor stage transformation. Phenotypically, the aberrant cell populace demonstrated a CD4+, CD7-, and CD62L- phenotype; at variance with classic MF was the expression of CD20. Although there were a few PAX5-positive staining cells, definitive colocalization studies were negative. Other B-cell markers and heavy chain immunoglobulin rearrangement were not detected. There are a growing number of reports describing T-cell lymphomas and leukemias with CD20 expression. Of the 6 CD20+ MF cases reported in the literature to date, 3 have been associated with a more aggressive clinical course; all but one case have occurred in males.

Response Of Rare Variants Of Cutaneous T Cell Lymphoma (CTCL) To Treatment With Bexarotene. A Prospective German DeCOG Trial

▪The Retinoid-X-Receptor specific retinoid bexarotene is approved for treatment of cutaneous T-cell lymphoma (CTCL) in the United States and Europe. CTCL is a heterogeneous group of peripheral non-Hodgkin lymphomas with different prognosis and different response to treatment and the current WHO classification contains nine different entities with Mycosis fungoides (MF) as the most common subtype. Since most data on efficacy and tolerability are available from studies with MF, this Dermatologic Cooperative Oncology Group (DeCOG) trial (ADO-CTCL-3) evaluates treatment response to bexarotene in patients with non-MF CTCL, encompassing CD30+ primary cutaneous ALCL and severe lymphomatoid papulosis (LyP), CD-30 negative pleomorphic TCL, Sezary's syndrome (SS), subcutaneous panniculitis-like TCL, and other defined variants. Additionally, patients with different rare variants of MF, including folliculotropic (fMF), granulomatous, erythrodermic, and CD30+ transformed MF were included.200 patients with CTCL stage IB or higher and at least one prior treatment failure were registered in this trial with bexarotene at an initial daily dose of 150mg/m² orally und prophylactic fenofibrate medication. Bexatrotene was increased to a target dosage of 300 mg/m² in patients with tolarable serum lipids under these conditions. Patients were evaluated according to a standardized evaluation tool (tumor burden index; TBI) up to 24 weeks of of treatment or until progression occured. In responding patients, treatment could be continued until progression.After a central pathology board review process 2 patients needed to be excluded from evaluation because of misdiagnoses. Additional 11 patients could not be evaluated for response due to early withdrawal. Among the remaining patients there were 18 patients with SS, 8 cutaneous CD30+ ALCL, 10 Lyp, 9 other rare entities. In addition MF cases with folliculotropic subtype (18), CD30+ transformation (11), CD30- transformation (4), and a variety of other MF subtypes could be compared to the response in classical MF.Response to bexarotene could be confirmed in classical MF with an objective response (OR) rate of 37 percent (5% CR; 32% PR). Response rates for the other entities were as follows: CD30+ ALCL 50% OR, LyP 60% OR, SS 33% OR, other forms of CTCL together 33% OR. In MF with CD30+ transformation 46% responded, in contrast to only 11% of cases with folliculotropic MF.Tolerability was as expected with most grade III/IV toxicities limited to hyperlipidemia. Side effect management anf the incidence of serious adverse events could be substantially improved using standard algorithms for lipid control.In conclusion, this is one of the largest CTCL cohorts with exact pathological review worldwide evaluated for treatment response with bexarotene. Bexarotene appears to be a safe and effective treatment option also in non-classical MF and CTCL variants. Folliculotropic MF proved to be a difficult-to-treat entity and CD30 expression seems to be a favourable prognostic marker for treatment response. Disclosures:Weichenthal:Cephalon GmbH: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; TEVA GmbH: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Goldinger:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Wehkamp:TEVA GmbH: Travel costs Other. Beyer:TEVA GmbH: Honoraria, Research Funding; Cephalon GmbH: Honoraria, Research Funding. Stein:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Tsianakas:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Koch:Cephalon: Travel costs Other. Yazdi:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Wobser:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Frambach:Cephalon: Travel costs Other; TEVA: Travel costs, Travel costs Other. Dippel:Cephalon GmbH: Honoraria, Travel costs Other; TEVA GmbH: Honoraria, Travel costs, Travel costs Other. Geißler:Cephalon GmbH: Travel costs Other; TEVA GmbH: Travel costs, Travel costs Other. Loquai:TEVA GmbH: Travel costs Other. Kurschat:Cephalon: Travel costs Other; TEVA GmbH: Honoraria, Travel costs, Travel costs Other. Pföhler:Cephalon: Travel costs Other. Hartmann:Cephalon GmbH: Travel costs Other; TEVA GmbH: Travel costs, Travel costs Other. Coors:Cephalon GmbH: Travel costs Other; TEVA GmbH: Honoraria, Travel costs, Travel costs Other. Hallermann:TEVA GmbH: Travel costs Other. Mohr:TEVA: Honoraria, Travel costs Other. Hillen:TEVA: Travel costs Other. Belloni:Cephalon GmbH: Travel costs Other. Mitteldorf:Cephalon: Travel costs Other. Assaf:TEVA: Honoraria, Research Funding, Travel costs Other. Klemke:TEVA GmbH: Consultancy, Honoraria; Cephalon GmbH: Honoraria. Becker:Cephalon GmbH: Honoraria, Research Funding; TEVA GmbH: Honoraria. Dummer:Cephalon GmbH: Honoraria, Research Funding; TEVA GmbH: Honoraria. Nicolay:TEVA: Travel costs Other.

Mycosis fongoïde papuleux

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. A new form of incipient MF has recently been described: papular MF. Herein, we report a case and propose a literature review. A 63-year-old man presented with erythematous and non-pruritic papular lesions of the trunk. The general examination was unremarkable. A skin biopsy showed moderately dense epidermotropic lymphocytic infiltration consistent with MF. Screening for CD30 was negative. Treatment with an extremely potent corticosteroid (clobetasol, one application per day) seemed effective, with almost complete disappearance of the lesions. Many clinical variants of the initial stages of MF have been described, one of the most recent of which is papular mycosis fungoides (PMF), of which 10 cases are reported in the literature. PMF begins clinically with an erythematous, non-pruritic and chronic papular rash that is not associated with the classic erythematous-squamous lesions of incipient MF. There appears to be no predominance of gender, and the age of onset ranges from 31 to 63 years. Histological examination of the PMF lesions revealed an epidermotropic subepidermal infiltrate composed predominantly of CD4+T-cells. The prognosis appeared good with the treatments conventionally used for incipient MF. PMF is likened to a form of incipient MF with a good prognosis. Associated classic MF lesions comprising erythematous-squamous plaques have been described as the condition progresses. Differential diagnoses include pilotropic MF, pityriasis lichenoides chronica, pityriasis lichenoides varioliformis acuta, and especially type B lymphomatoid papulosis, the histopathological findings of which may be close to PMF. Papular MF would appear to be a papular variant of incipient MF with a good prognosis. However, it is necessary to obtain clinical and disease progression data for a greater number of patients in order to better characterize this entity.

A case-control study of clinicopathologic features, prognosis, and therapeutic responses in patients with granulomatous mycosis fungoides

Granulomatous mycosis fungoides (GMF) is an uncommon variant of mycosis fungoides (MF). We sought to analyze the relative frequency, clinicopathologic characteristics, prognosis, and therapeutic responses of GMF. We conducted a retrospective case-control study of patients with GMF and age- and stage-matched patients with classic MF between 1981 and 2012. A total of 27 patients with GMF were identified, representing 6.3% of all patients with MF at our center. Skin manifestations were similar to classic MF having an atypical lichenoid CD4(+) CD8(-) lymphocytic infiltrate with interstitial histiocytes and/or perivascular granulomas with giant cells. Fewer patients with GMF achieved a partial response or complete response with topical (57% vs 83%; P = .002) or ultraviolet light (62% vs 90%; P = .006) therapy. The 5- and 10-year progression-free survival rates were significantly lower in patients with GMF (59% and 33%) compared with patients with classic MF (84% and 56%; P = .02), but overall survival was similar between groups (86% and 72% vs 85% and 85%; P = .54). The retrospective methodology may underestimate the frequency of GMF. The median follow-up time may be too short to detect possible differences in overall survival. More frequent disease progression and poorer response to skin-directed therapies were observed in patients with GMF. Our findings may be helpful in selecting the most appropriate treatment for these patients.

Hyperpigmented mycosis fungoides: a rare variant

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. The diagnosis of classic MF is based on a combination of clinical presentation, histopathology, immunohistochemistry, and T-cell monoclonality detected by molecular studies. However, the diagnosis can be difficult in some cases. We report a case of hyperpigmented mycosis fungoides. A 60-year-old woman, phototype IV, presented for more than 4 years a history of asymptomatic hyperpigmented non- infiltrated plaques on the face. Cutaneous lupus was diagnosed based on a skin biopsy. Hydroxychloroquine and photoprotection was started. Considering non improvement, another biopsy was done, in favor of a mycosis fungoides CD3+, CD4+, CD8-. The diagnostic of hyper pigmented mycosis fungoides stage I was retained and topical steroid was introduced. Mycosis fungoides can appear in various clinical forms, the hyperpigmented form is rare but this diagnosis should be evoked.

Poikilodermatous mycosis fungoides

Poikilodermatous mycosis fungoides (MF) is a variant of MF, formerly referred to as poikiloderma vasculare atrophicans. The lesions are classically characterized by large plaques of hypopigmentation and hyperpigmentation with atrophy and telangiectases. The plaques may be asymptomatic or mildly pruritic and typically involve the major flexural areas and trunk. Poikilodermatous MF has an early stage (IA-IIA) at diagnosis and a male predominance. Poikilodermatous MF shows an atypical T-cell infiltrate in the papillary dermis with evidence of epidermotropism, epidermal atrophy, dilated blood vessels in the dermis, melanophages, and melanin incontinence. Recent studies suggest a predominance of a CD8+, CD4- immunophenotype. Treatment modalities are similar to classic MF with phototherapy being the most common first-line therapy. Poikilodermatous MF has an excellent prognosis.

Management of the Cutaneous Peripheral T-Cell Lymphomas

The cutaneous T-cell lymphomas are a heterogeneous collection of many biologically and clinically distinct cancers. The World Health Organization 2008 reclassification of cutaneous lymphomas delineated provisional entities that were previously classified simply as primary cutaneous peripheral T-cell lymphoma not otherwise specified. Because of the relative rarity of cases, standard treatment recommendations and algorithms are lacking. However, identification of these subtypes is important as they can have vastly different clinical outcomes. Furthermore, cytokine treatments effective in classic mycosis fungoides or Sezary syndrome not only are ineffective, but also may exacerbate certain subtypes. The aim of this review was to summarize the biological bases of the recently defined entities, reinforce the importance of acute clinical/pathologic diagnosis, and propose treatment strategies based on the available data.

Unilesional follicular mycosis fungoides: report of two cases with progression to tumor stage and review of the literature

Mycosis fungoides (MF) is the most common type of cutaneous lymphoma and has protean clinicopathological manifestations. Follicular or folliculotropic MF (FMF) is a rare variant, which histopathologically is characterized by pronounced folliculotropism of neoplastic T cells, with or without follicular mucinosis, and clinically by an impaired prognosis compared to classic MF. In contrast, unilesional MF is a very rare variant with an excellent prognosis, with a single case of large-cell transformation reported to date. The combination of folliculotropic and unilesional MF is very unusual, with only two cases reported to date. Here we report two patients with unilesional folliculotropic MF with progression to tumor stage in both patients. To the best of our knowledge, this is the first report on the disease evolution with large-cell transformation and progression of unilesional FMF. Complete remission was achieved by local radiation therapy in both patients. The differential diagnoses, classification and implications for the treatment of unilesional FMF as well as the pertinent literature are discussed.

Time course, clinical pathways, and long‐term hazards risk trends of disease progression in patients with classic mycosis fungoides

Mycosis fungoides (MF) is an indolent primary cutaneous T-cell lymphoma. To the authors' knowledge, no data currently are available regarding the evolution over time of the risk of developing specific pathways of disease progression. This retrospective study analyzed 1422 patients with MF who were diagnosed and followed from 1975 through 2010 in 27 Italian Study Group for Cutaneous Lymphoma centers. The primary objectives were to ascertain the time course, pathways, and hazards risk trends of cutaneous/extracutaneous disease progression; to evaluate whether different tumor-lymph node-metastasis-blood (TNMB) stages have different pathways of disease progression; and to analyze differences between tumor-stage and erythrodermic MF with regard to clinical onset, disease evolution, and prognosis. The secondary objective was to provide a further validation for the revised International Society for Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (ISCL/EORTC) classification. The median follow-up was 14.5 years; stage progression occurred in 29.7% of patients and blood involvement was the most frequent extracutaneous site of disease progression. Patients with stage IA to stage IB disease demonstrated a steady low annual incidence of disease progression to tumor-stage (1%-2%); patients with stage IIA disease had a higher risk within the first years (up to 9.4%). Erythroderma evolved with a significantly higher frequency from patches/plaques (13.9%/28.2%) than tumors (P = .028 and P = .013, respectively). Hazards rates of extracutaneous involvement were low (< 1%). The T-score was found to be associated with extracutaneous involvement site, tumor-stage disease with lymph node/visceral lesions, and erythroderma with blood involvement. TNMB classification and stage progression resulted as independent prognostic variables being detected on multivariate analysis; the type of extracutaneous involvement was found to affect survival . The data from the current study support the need for a stage-tailored follow-up, suggest that the classification of tumor-stage disease at a stage below erythroderma could be modified, and offer a further validation for the revised TNMB classification.

Profile of mycosis fungoides in 43 Saudi patients

BACKGROUND AND OBJECTIVESMycosis fungoides (MF) is a rare disease; and to our knowledge, there are no reports on its profile in Arabs. The objective of this study was to preliminarily analyze the clinical characteristics of MF patients seen in our institution.DESIGN AND SETTINGRetrospective review of 140 patients with pathologic or clinical diagnosis or differential diagnosis of MF for the period 2000–2006.PATIENTS AND METHODSPathology reports with diagnosis or differential diagnosis of MF were retrieved and suspected cases were identified and reviewed. For pathologically confirmed cases, sociodemographic, clinical, laboratory, and radiological details were collected. Details of staging, treatment modalities, and disease status at the last follow-up were retrieved.RESULTSA total of 43 pathologically confirmed MF patients (skin phototypes IV and V) with a mean age at diagnosis of 33.5 years were reviewed. This comprised 29 males (M:F ratio, 2:1), and the majority (86%) of patients had early-stage (I and II) MF. Twenty-one (48.8%) patients had classic MF; 18 (41.8%), hypopigmented MF; and 4 (9.3%), other variants. The male-to-female ratio was higher in the hypopigmented (3.5:1) than in the classic variant (1.6:1). The mean age at diagnosis was lower in the hypopigmented compared to the classic variant (25 versus 38.8 years, P=.019). The mean duration of follow-up was 27.6 months (range, 1–98 months). At the final assessment, 4 (9.5%) patients recovered; whereas 35 (83.3%) had MF skin disease; 1 had (2.4%) extracutaneous disease; and 2 (4.8%) died of MF.CONCLUSIONSMF tends to affect younger Saudi patients. The hypopigmented variant constitutes a significant proportion of MF cases, especially in younger patients.

Solitary mycosis fungoides: A distinct clinicopathologic entity with a good prognosis

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL), accounting for almost 50% of all primary cutaneous lymphomas. The occurrence of solitary lesions, which are clinically and histopathologically indistinguishable from classic MF has been described. We describe 15 cases of solitary MF and discuss the relationship to classic MF, "reactive" processes and to other, rarer forms of CTCL that may present with solitary lesions. We conducted a retrospective chart review and a PubMed search to identify all reported cases of solitary MF to date, as well as information about other CTCLs presenting as a solitary lesion. Fifteen patients were identified. Follow-up data were available on 10 patients with a median follow-up of 10 months (range, 1 to 48 months). Clinical, pathological, immunocytochemical, and molecular-genetic features were analyzed. Five cases were diagnosed as folliculotropic MF (FMF). Of the 10 cases with follow-up, 2 were treated with topical steroids, 2 were completely excised, 5 received radiotherapy, and 1 received tacrolimus. One hundred twenty-eight cases of solitary MF were identified in the literature and reviewed for commonalities to and differences with our cases and other CTCLs. This study was retrospective; follow-up data were not available in some cases and were only short term in others. Solitary MF appears to have a good prognosis. In lesions that are not completely excised, curative radiotherapy can be used. Long-term follow up is advised.

Recognizing large-cell transformation of mycosis fungoides

Although patients with mycosis fungoides (MF) typically experience an indolent disease course, a minority undergo a process of large-cell transformation (LCT), which often heralds more aggressive disease and shortened survival. Regrettably, most dermatologists are unfamiliar with LCT, and even fewer understand how to recognize it clinically. Because a diagnosis of LCT typically triggers more aggressive therapy and/or referral to cutaneous T-cell lymphoma (CTCL) centers, it is paramount for clinicians to be able to recognize suspect lesions visually. LCT is diagnosed histologically; however, diagnostic biopsy is performed only if transformed lesions are suspected clinically. Because the literature provides little information on what clinical features should lead to suspicion of LCT, we sought to identify and categorize the presentations of LCT to aid in its recognition. We identified 14 patients with biopsy-proven LCT confirmed by a board-certified dermatopathologist experienced with this diagnosis. The clinical presentations of LCT, timing of its evolution, and treatment regimens were evaluated by chart and photograph review. We devised 3 categories that clinically represent LCT: (1) LCT occurring as a new, solitary nodule within a classic MF patch or plaque, (2) LCT occurring as abrupt onset of multiple scattered papules and/or nodules without spontaneous resolution, and (3) LCT occurring within new or enlarging tumors. A larger number of reviewed cases might reveal additional clinical presentations of LCT. Dermatologists may use our categories of clinical indicators to recognize and diagnose LCT earlier, allowing implementation of more aggressive treatment regimens when appropriate.

Various skin manifestations of mycosis fungoides: histopathological features and prognosis.

Mycosis fungoides (MF) is a type of T cell lymphoma, and comprises more than one-half of primary cutaneous T cell lymphomas (CTCL). Many variants of MF have been reported to date, although there are only three descriptions of MF variants in the WHO-EORTC classification published in 2005. Herein, we present four cases of MF, namely classical MF, Woringer-Kolopp disease, bullous MF, and folliculotropic MF. These variants of MF were all typical, although they are quite rare. Their unique clinical manifestations arise from characteristic histolopathological changes in the lesions. The location and amount of infiltrating tumor cells in the epidermis seem to be profoundly correlated with the prognosis.

Early-stage mycosis fungoides variants: case-based review

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. The diagnosis of classic MF is based on a combination of clinical presentation, histopathology, and T-cell monoclonality detected by molecular studies. However, the diagnosis can be difficult in cases of early MF because of the subtle nature of histologic findings and, in cases of variants of MF, because of the unusual clinical and/or pathologic features. In this review, we presented the most frequent variants of MF at early stage including hypopigmented, folliculotropic, pagetoid reticulosis, unilesional, granulomatous, and ichthyosis forms. This case-based clinicopathologic review provides the notion that a comprehensive clinicopathologic correlation is of substantial importance to render the diagnosis of MF. In addition, we discuss the role of molecular studies, which are highly sensitive and recently more applicable to routinely processed skin biopsy specimens in the diagnosis of MF.