Summary
Background and Objectives
Mycosis fungoides (MF) accounts for the majority of cutaneous lymphomas (CL). There is a documented delay in the diagnosis of early‐stage MF. However, its timely diagnosis is paramount to avoid potentially harmful therapies and undue patient distress. The aim of this study was to examine and compare the views held by both specialists and non‐specialists in CL regarding the diagnosis of early‐stage MF, to identify clinical needs.
Methods
Two distinct questionnaires were distributed to physicians, who either have a potential or no special interest in CL (non‐specialists), or who have a special interest in CL (specialists) and who were identified by participation in the PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study.
Results
Survey results were received from 382 participants, 86 specialists, and 296 non‐specialists. In total, 82% of respondents held the view that the diagnosis of early‐stage MF is delayed. The frequent misclassification of MF as a benign inflammatory dermatosis was identified as the most important contributing factor.
Conclusions
Non‐specialists assume that a delayed diagnosis impairs therapeutic efficacy and prognosis in MF, while specialists primarily suspect negative effects on patients’ health‐related quality of life. Our study reveals an unmet need to promote education and increase awareness among dermatologists regarding the impact of early‐stage MF on patient management.
Keywords: Cutaneous lymphoma, diagnostic delay, diagnostic challenge, early‐stage mycosis fungoides, health‐related quality of life
INTRODUCTION
Mycosis fungoides (MF) is the most common type of cutaneous T‐cell lymphoma (CTCL), accounting for almost half of all cutaneous lymphomas (CL). 1 For CL, an incidence of 0.96/100,000 per year was reported recently based on registry data from France. 2 A German analysis of insurance claims data found that the incidence of MF was higher than previously reported, at 1.79 per 100,000 per year. 3 In line with this, MF is listed as an orphan disease (ORPHA: 2584). 4 , 5 The etiology of CTCL remains largely unknown, and the clinical and molecular heterogeneity of CTCL poses a significant diagnostic and therapeutic challenge. 6 , 7 , 8
MF is believed to originate from clonal T lymphocytes that in most cases are confined to the skin at the time of diagnosis. The majority of early‐stage patients follow an indolent course without progression; however, up to 30% of cases show disease progression, leading to extracutaneous involvement of lymph nodes, peripheral blood, or visceral organs. 9 The identification of early‐stage MF patients who are at higher risk for disease progression is a major challenge. 10 , 11 MF is currently regarded as incurable and treatment options are aimed at controlling symptoms and induction and maintenance of remission. 12 However, allogeneic stem cell transplantation (alloSCT) is the only potentially curative treatment for eligible individuals. 13 Maintaining health‐related quality of life (HRQoL) is the ultimate goal of therapy in the face of common and often unbearable pruritus and the stigma of visible skin lesions. 14 , 15 Of note, the challenge of prolonging survival and preventing disease progression is unique in MF when compared to other dermatoses. 16
Patients with MF present clinically with patches and/or plaques in early‐stage disease, whereas tumors or erythroderma are characteristic of advanced‐stage disease. 1 Importantly, early‐stage MF can be clinically difficult to distinguish from benign inflammatory skin conditions, such as atopic eczema, psoriasis, and pityriasis rosea. 17 A point‐based algorithm created by the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC) incorporates clinical, histopathologic, molecular, and immunopathologic factors for establishing a diagnosis of early‐stage MF. Basic clinical and histological parameters for the diagnosis include persistent and/or progressive patches/thin plaques together with a superficial lymphoid infiltrate. Additional supporting criteria include molecular evidence of T‐cell receptor clonality and immunophenotypic loss/abnormalities such as epidermal/dermal discordance of the T‐cell markers CD2, CD3, CD5, and CD7. 6 Despite clearly defined histopathological criteria, the diagnosis of early‐stage MF usually requires careful clinicopathological correlation and often multiple biopsies. 18 , 19
Furthermore, a recent publication by the PROCLIPI investigators demonstrated that diagnostic delay in early‐stage MF is common, occurring in up to 85.6% of patients, with a median delay of 3 years. 7 With our study, we aimed to examine the personal opinions of specialists and non‐specialists in CL on making a diagnosis of early‐stage MF and to identify clinical needs.
METHODS
Study Design
A survey was developed by the authors of this manuscript with a special interest in CL from Austria, the United Kingdom, and Ireland. It was designed and distributed in an online format using SurveyMonkey® (SurveyMonkey, San Mateo, CA, U.S.A.). Two versions of the survey were developed: one intended for physicians with or without a special interest in CL (non‐specialists), and another for PROCLIPI investigators with a defined expertise in CL (specialists). Both surveys contained a minimum of 20 items. Specific questions employed skip logic, allowing supplementary questions to be presented based on respondents' answers. As a result, the non‐specialist survey included up to 27 items and the specialist survey up to 25 items. Questions 1 to 6 addressed demographic characteristics, including job role, age, sex, geographical region, years of practice, and current employment status, whereas Question 7 assessed the respondent's level of experience with CL. Questions 8 to 20 were identical in content for non‐specialists and specialists and were related specifically to the individual views of physicians regarding the diagnosis of early‐stage MF. The questionnaire items, response options, and skip logic functions are presented in Table 1.
TABLE 1.
Demographics of survey respondents.
| Survey Response | Non‐Specialist (n = 296) | Specialist (n = 86) | p value | |
|---|---|---|---|---|
| Region, n (%) | UK & Ireland | 139 (46.9%) | PROCLIPI/international investigator | |
| Austria | 157 (53.1%) | |||
| Age (Years), n (%) | 18–24 | 1 (0.3%) | 0 (0%) | 0.1 |
| 25–34 | 56 (19.1%) | 7 (8.2%) | ||
| 35–44 | 85 (29.0%) | 21 (24.7%) | ||
| 45–54 | 84 (28.7%) | 28 (32.9%) | ||
| 55–64 | 53 (18.1%) | 23 (27.1%) | ||
| >65 | 14 (4.8%) | 6 (7.1%) | ||
| Sex, n (%) | Male | 118 (40.3%) | 38 (45.8%) | 0.2 |
| Female | 175 (59.7%) | 45 (54.2%) | ||
| Years practice, n (%) | <1 | 2 (0.7%) | 2 (2.4%) | 0.1 |
| 1 – 3 | 21 (7.3%) | 4 (4.9%) | ||
| 3 – 5 | 34 (11.8%) | 2 (2.4%) | ||
| 5 – 10 | 47 (16.3%) | 15 (18.3%) | ||
| 10 – 20 | 88 (30.5%) | 29 (35.4%) | ||
| >20 | 97 (33.6%) | 30 (36.6%) | ||
| Work arrangements, n (%) | Part‐time | 66 (22.9%) | 16 (19.8%) | 0.45 |
| Full‐time | 218 (75.7%) | 65 (80.2%) | ||
| 1–2 Years | 75 (26.6) | 14 (17.7%) | 0.113 | |
| 2–4 Years | 115 (40.8%) | 48 (60.8%) | ||
| >4 Years | 83 (29.4%) | 17 (21.5%) | ||
Data collection occurred between July and November in 2020. The non‐specialist survey was distributed in an online format in the United Kingdom, Ireland, and Austria. In the UK and Ireland, the survey was distributed to members of the British Association of Dermatology (BAD), the Midlands Dermatology Society (MDS), the Scottish Dermatological Society (SDS), and the Irish Association of Dermatologists (IAD). The BAD survey was included as a hyperlink in the July 2020 electronic newsletter, Communications Circular, while individual members of the MDS, SDS, and IAD were directly invited by email to complete the survey with a follow‐up reminder email two weeks later. In Austria this questionnaire was translated into German and was sent as a link in the newsletter of the Austrian Society of Dermatology and Venereology (OEGDV) to all its members on 23rd of October 2020, and as a reminder on 16th of November 2020. For specialists, an invitation containing a link to the specialist survey was sent by email to investigators of the PROCLIPI study in July–August 2020. For reasons of feasibility, non‐specialists from “only” three countries were included, namely the UK, Ireland, and Austria. However, given that CTCL is a rare disease, the authors deemed it necessary to recruit specialists globally to ensure a sufficient number of expert respondents for analysis. This recruitment approach may limit the generalizability of the results.
Data Analysis
Survey results were tabulated, and all data were analyzed using Statistical Package for the Social Sciences (SPSS) software Version 27.0 (IBM SPSS Inc., Armonk, NY, USA. IBM Corp). Each option for each separate multiple‐choice question in the survey was considered a categorical variable. Histograms were created to assess distribution of continuous data. Normally distributed continuous data were expressed as mean ± standard deviation (SD), while median (range) was used to describe the non‐normally distributed continuous data. Categorical variables were presented as count and percent. Time intervals were characterized using median (range) months. Free‐text answers were grouped into categorical variables by theme. Chi‐square tests were used to analyze categorical variables. Respondents were asked to rank factors contributing to delayed diagnosis in order of perceived importance. Freidman tests were used to determine the median rank of non‐parametric ordinal variables. Post‐hoc analysis of significant differences in rank identified with the Freidman test was performed using the Wilcoxon Signed‐Rank Tests in paired combinations to determine the source of the significance.
RESULTS
Respondents
In total, 382 respondents completed the survey in 2020 encompassing 22.5% (n = 86) specialists and 77.5% (n = 296) non‐specialists (n = 157 Austria; n = 139 United Kingdom and Ireland). PROCLIPI investigators from the United Kingdom (n = 15); North America (n = 13); South America (n = 3); Australia (n = 3); Europe (n = 43); Asia (n = 4), and Africa (n = 1) responded to the survey. Among the non‐specialist cohort, 4% (n = 12; n = 4 Austria, n = 8 UK & Ireland) indicated they were PROCLIPI investigators. Participation as a PROCLIPI investigator would indicate that the respondent indeed is a specialist in CL. The aim of including this question in the non‐specialist questionnaire was to identify those participants that may have answered both the specialist and non‐specialist questionnaires and to exclude duplicates.
The majority of responses collected were from consultant dermatologists (n = 302, 79%), with dermatology trainees (n = 66, 17.8%), general practitioners (n = 1, 0.3%), and dermatology nurses (n = 2, 0.5%) also represented. Opinions from allied specialties included hematology (n = 6, 1.6%), oncology (n = 5, 1.3%), and histopathology (n = 2, 0.5%). Respondents had extensive dermatology experience, with 64% (n = 244) having worked in the field for ≥ 10 years. The majority of respondents, 74% (n = 283), reported currently working full‐time in dermatology. Geographical location varied among respondents. Among non‐specialists, 45.9% (n = 136) were from the UK and Ireland (5%, n = 15 from Ireland; 0.67%, n = 2 from Northern Ireland, 40.2%, n = 119 from the UK), and 51.4% (n = 152) were from Austria. The majority (n = 43; 52.4%) of specialists were from Europe, the United Kingdom (n = 15; 18.3%), and North America (n = 13, 15.9%). Demographic details of participants are further outlined in Table 1.
Delayed diagnosis
As outlined in Table 2, the majority (n = 301, 82%) of respondents believed that the diagnosis of early‐stage MF is delayed. However, this perception of delayed diagnosis varied significantly between specialists and non‐specialists, with specialists significantly more likely to consider diagnosis delayed in early‐stage MF (p = 0.023). When “I don't know” responses were excluded, no significant difference was observed between the groups, suggesting that the higher proportion of “I don't know” answers among non‐specialists contributed to the previously observed significant difference (p = 0.17). Significant variance in terms of the knowledge of average time to diagnosis was also observed between specialists and non‐specialists (p < 0.001). Similarly, there was a notably higher proportion of “I don't know” answers among the non‐specialist group. When these answers were excluded, no significant difference was observed between respondents (p = 0.892). The majority of specialists (60.8%, n = 48) reported an average time to diagnosis of 2–4 years in early‐stage MF, consistent with PROCLIPI data. The remaining responses varied, with 23.3% (n = 89) reporting a time interval of 1–2 years and 26.2% (n = 100) reporting > 4 years. Among non‐specialists, there was discordance regarding the average time to diagnosis with 40.8% (n = 115) reporting a delay of 2–4 years, 26.6% (n = 75) a delay of 1–2 years, and 29.4% (n = 83) a delay of > 4 years. A minority of non‐specialists (n = 9; 3.2%) attributed a delay of less than 1 year to the diagnosis of early‐stage MF.
TABLE 2.
Survey responses for non‐specialists and specialists in cutaneous lymphoma.
| Survey Response | Non‐Specialist (n = 296) | Specialist (n = 86) | p value | ||
|---|---|---|---|---|---|
| Do you think the diagnosis of early‐stage MF is delayed? | Yes, n (%) | 228 (78.9%) | 73 (91.3%) | 0.02 * | |
| No, n (%) | 35 (12.1%) | 6 (7.5%) | |||
| Don't know, n (%) | 26 (9.0%) | 1 (1.3%) | |||
| Do you think the average time from symptom onset to diagnosis of early‐stage MF is currently known? | Yes, n (%) | 91 (31.8%) | 33 (41.8%) | < 0.001 * | |
| No, n (%) | 123 (43%) | 43 (54.4%) | |||
| Don't know, n (%) | 72 (25.2%) | 3 (3.8%) | |||
| What do you think is the average time from symptom onset to diagnosis of early‐stage MF? | < 1 Year | 9 (3.2%) | 0 (0%) | 0.01 * | |
| 1–2 Years | 75 (26.6) | 14 (17.7%) | |||
| 2–4 Years | 115 (40.8%) | 48 (60.8%) | |||
| > 4 Years | 83 (29.4%) | 17 (21.5%) | |||
| Do you think the timely diagnosis of early‐stage MF is challenging? | Yes, n (%) | 250 (87.4%) | 72 (92.3%) | 0.01 * | |
| No, n (%) | 34 (11.9%) | 3 (3.8%) | |||
| Don't know, n (%) | 2 (0.7%) | 3 (3.8%) | |||
| Factors ranked in order of importance contributing to delayed diagnosis of early‐stage MF | Misclassification of MF as a BID | Mean Rank | 1.77 | < 0.001 * | |
| Lack of reliable diagnostic techniques | 2.39 | ||||
| MF is a rare disease | 2.43 | ||||
| Lack of access to a specialist center | 3.42 | ||||
| Do you think a patient's gender is a contributing factor to a delayed diagnosis of early‐stage MF | Yes, n (%) | 68 (24.2%) | 14 (18.4%) | 0.57 | |
| No, n (%) | 159 (56.6%) | 46 (60.5%) | |||
| Don't know, n (%) | 54 (19.2%) | 16 (21.1%) | |||
| Do you think that a patient's age is a contributing factor to a delayed diagnosis of early‐stage MF? | Yes, n (%) | 127 (45.8%) | 37 (48.7%) | 0.72 | |
| No, n (%) | 103 (37.2%) | 29 (38.2%) | |||
| Don't know, n (%) | 47 (17%) | 10 (13.2%) | |||
| Do you think that a patient's prognosis is negatively affected by a delayed diagnosis of early‐stage MF? | Yes, n (%) | 93 (34.1%) | 16 (21.1%) | 0.02 * | |
| No, n (%) | 119 (43.6%) | 47 (61.8%) | |||
| Don't know, n (%) | 61 (22.3%) | 13 (17.1%) | |||
| Do you think that therapeutic success is negatively affected by a delayed diagnosis of early‐stage MF? | Yes, n (%) | 114 (41.9%) | 25 (32.9%) | < 0.001 * | |
| No, n (%) | 96 (35.3%) | 45 (59.2%) | |||
| Don't know, n (%) | 62 (22.8%) | 6 (7.9%) | |||
| Do you think that a patient's health‐related quality of life is impaired by a delayed diagnosis of early‐stage MF? | Yes, n (%) | 172 (63.2%) | 58 (76.3%) | 0.09 | |
| No, n (%) | 68 (25.0%) | 11 (14.5%) | |||
| Don't know, n (%) | 32 (11.8%) | 7 (9.2%) | |||
| Do you think that a timely diagnosis of early‐stage MF can result in cure? | Yes, n (%) | 48 (17.6%) | 12 (15.8%) | 0.05 * | |
| No, n (%) | 151 (55.5%) | 53 (69.7%) | |||
| Don't know, n (%) | 73 (26.8%) | 11 (14.5%) | |||
| Educating which of the following would be helpful in reducing the diagnostic delay in early‐ stage MF? | GPs, n (%) |
224 (85.2%) 224 (85.2%) 73 (27.8%) 52 (19.8%) |
58 (77.3%) |
0.107 0.972 0.967 0.671 |
|
| Dermatologists, n (%) | 64 (85.3%) | ||||
| Hematologists n (%) | 21 (28%) | ||||
| General Public, n (%) | 13 (17.6%) | ||||
| What educational resources would be helpful? |
National Campaign, n (%) Pamphlet for GPs, n (%) Pamphlet for consultants (%) GP Webinars, n (%) Webinars for consultants, n (%) |
20 (8.2%) 133 (54.3%) 135 (55.1%) 140 (57.1%) 174 (70.7%) |
17 (24.3%) 37 (52.9%) 41 (58.6%) 42 (60%) 55 (78.6%) |
< 0.001 * 0.833 0.606 0.670 0.195 |
|
Abbr.: MF, Mycosis fungoides; PROCLIPI, PROspective Cutaneous Lymphoma International Prognostic Index) study; MF, mycosis fungoides; BID, benign inflammatory dermatosis, GP, general practitioner
Statistically significant result
The majority (n = 322, 88.5%) of participants considered the diagnosis of early‐stage MF to be challenging, with significantly more specialists agreeing with this statement (p = 0.01).
Implications of a delayed diagnosis
Both specialists and non‐specialists ranked the frequent misclassification of MF as a benign inflammatory dermatosis as the most important of four possible factors contributing to delayed diagnosis (specialists: mean rank 1.9 [SD ± 0.964; p < 0.001]; non‐specialists: mean rank 1.73 [SD ± 0.93; p < 0.001]). The rarity of MF and a lack of reliable diagnostic techniques were reported as the next most important influences contributing to a delayed diagnosis. There was no significant difference in the perceived rank between these answers, with the rarity of MF receiving a mean rank of 2.43 and lack of diagnostic techniques a mean rank of 2.39 (Z = 0.437, p = 0.662). Lack of specialists was the least important factor identified, with a mean rank of 3.42 (SD ± 0.883).
Sex was thought to contribute to a delayed diagnosis in early‐stage MF by 23% (n = 82) of respondents. Upon categorizing respondents’ comments to this question, three suspected causes emerged: a general tendency for male patients to be less vigilant about skin complaints; a greater likelihood of males seeking medical attention at a later stage; and the higher prevalence of MF in males. The majority of respondents (57.4%, n = 205) felt that patient age did not affect timely diagnosis in early‐stage MF.
Significantly more non‐specialists believed that a delayed diagnosis negatively impacted a patient's prognosis (Table 3). When “I don't know” was excluded, this difference remained (21.1% vs 25.4%, p = 0.008). A larger proportion of non‐specialists reported “I don't know” regarding the impact of delayed diagnosis on therapeutic efficacy (22.8% vs 7.9%; p < 0.001). When “I don't know” responses were excluded, significantly more specialists stated that delayed diagnosis did not affect therapeutic efficacy in early‐stage MF (64.3% vs 45.7%; p = 0.007).
TABLE 3.
Survey responses for non‐specialists in the United Kingdom and Ireland vs Austria.
| Survey Response | UK & Ireland (n = 139) | Austria (n = 157) | p value | |
|---|---|---|---|---|
| Do you think the diagnosis of early‐stage MF is delayed? | Yes, n (%) | 112 (83.6%) | 116 (74.8%) | 0.076 |
| No, n (%) | 10 (7.5%) | 25 (16.1%) | ||
| Don't know, n (%) | 12 (9.0%) | 14 (9%) | ||
| Do you think the average time from symptom onset to diagnosis of early‐stage MF is currently known? | Yes, n (%) | 26 (19.7%) | 65 (42.2%) | < 0.001 |
| No, n (%) | 81 (61.4%) | 42 (27.3%) | ||
| Don't know, n (%) | 25 (18.9%) | 47 (30.5%) | ||
| What do you think is the average time from symptom onset to diagnosis of early‐stage MF? | < 1 Year | 2 (1.5%) | 7 (4.6%) | < 0.001 |
| 1‐2 Years | 23 (17.7%) | 52 (34.2%) | ||
| 2‐4 Years | 51 (39.2%) | 64 (42.1%) | ||
| >4 Years | 54 (41.5%) | 29 (19.1%) | ||
| Do you think the timely diagnosis of early‐stage MF is challenging? | Yes, n (%) | 125 (95.4%) | 125 (80.6%) | < 0.001 |
| No, n (%) | 4 (3.1%) | 30 (19.4%) | ||
| Don't know, n (%) | 2 (1.5%) | 0 (0%) | ||
| Do you think a patient's gender is a contributing factor to a delayed diagnosis of early‐stage MF | Yes, n (%) | 21 (16.7%) | 47 (30.3%) | 0.004 |
| No, n (%) | 72 (57.1%) | 87 (56.1%) | ||
| Don't know, n (%) | 33 (26.2%) | 21 (13.5%) | ||
| Do you think that a patient's age is a contributing factor to a delayed diagnosis of early‐stage MF? | Yes, n (%) | 57 (45.2%) | 70 (46.4%) | 0.873 |
| No, n (%) | 46 (36.5%) | 57 (37.7%) | ||
| Don't know, n (%) | 23 (18.3%) | 24 (15.9%) | ||
| Do you think that a patient's prognosis is negatively affected by a delayed diagnosis of early‐stage MF? | Yes, n (%) | 25 (19.8%) | 68 (46.3%) | < 0.001 |
| No, n (%) | 64 (50.8%) | 55 (37.4%) | ||
| Don't know, n (%) | 37 (29.4%) | 24 (16.3%) | ||
| Do you think that therapeutic success is negatively affected by a delayed diagnosis of early‐stage MF? | Yes, n (%) | 35 (28%) | 79 (53.7%) | < 0.001 |
| No, n (%) | 51 (40.8%) | 45 (30.6%) | ||
| Don't know, n (%) | 39 (31.2%) | 23 (15.6%) | ||
| Do you think that a patient's health‐related quality of life is impaired by a delayed diagnosis of early‐stage MF? | Yes, n (%) | 78 (62.4%) | 94 (63.9%) | 0.887 |
| No, n (%) | 31 (24.8%) | 37 (25.2%) | ||
| Don't know, n (%) | 16 (12.8%) | 16 (10.9%) | ||
| Do you think that a timely diagnosis of early‐stage MF can result in cure? | Yes, n (%) | 8 (6.4%) | 40 (27.2%) | < 0.001 |
| No, n (%) | 74 (59.2%) | 77 (52.4%) | ||
| Don't know, n (%) | 43 (34.4%) | 30 (20.4%) | ||
| Educating which of the following would be helpful in reducing the diagnostic delay in early‐stage MF? | GPs, n (%) |
106 (90.6%) 99 (84.6%) 40 (34.2%) 32 (27.4%) |
118 (80.8%) |
0.027 0.958 0.037 0.006 |
| Dermatologists, n (%) | 125 (85.6%) | |||
| Hematologists n (%) | 33 (22.6%) | |||
| General Public, n (%) | 20 (13.7%) | |||
| What educational resources would be helpful? |
National Campaign, n (%) Pamphlet for GPs, n (%) Pamphlet for consultants (%) GP Webinars, n (%) Webinars for consultants, n (%) |
0 (0%) 51 (47.2%) 50 (46.3%) 77 (71.3%) 81 (74.3%) |
20 (14.6%) 82 (59.9%) 85 (62%) 63 (46%) 93 (67.9%) |
< 0.001 0.049 0.014 < 0.001 0.271 |
Abbr.: MF, Mycosis fungoides; GP, general practitioner
Significantly more specialists reported that delayed diagnosis had a negative impact on a patient's HRQoL when “I don't know” was excluded (84% vs 72%, p = 0.038) (Table 3). When asked about any relationship between timely diagnosis and cure in early‐ stage MF there was no significant difference between groups. However, there was a trend towards a higher proportion of specialists reporting that timely diagnosis did not impact cure rates (70% vs 55.5%; p = 0.052) and a higher proportion of non‐specialists reporting they did not know (27% vs 14.5%).
Differences among non‐specialists
A number of key differences were noted between non‐specialists from UK/Ireland and Austria, as further elaborated in Table 3. While significantly more UK/Irish dermatologists felt that early diagnosis of MF was delayed (92% vs 82%, p = 0.023), Austrian dermatologists were more likely to identify a delay as harmful to patients (73% vs 43%, p < 0.001).
Almost 30% of UK/ Irish respondents did not know whether delayed diagnosis affects therapeutic success. This may reflect demographic differences between the two groups, with a higher proportion of trainees in the UK/Ireland group (28% vs 16%, p = 0.045) and a greater number of consultants with more than 20 years of experience in the Austrian group (39% vs 27%, p = 0.018). Significantly more dermatologists in UK/Ireland reported working part time which may also be a factor in clinical exposure to a rare disease (36.4% vs 12%, p < 0.001).
Non‐specialists were asked how many cases of CTCL they encounter per month. A large discrepancy in response rates was noted between groups (UK/Ireland 10% vs 99% Austria). This limited the ability to make an accurate comparison between the two groups. However, both groups reported very limited clinical exposure, with 71.4% of UK/Ireland respondents and 95% of Austrian respondents seeing fewer than 10 CTCL patients per month.
Future Directions
In an effort to improve early diagnosis in MF, participants acknowledged the importance of education. Respondents from both groups suggested training for dermatologists (n = 288, 85.2%) to be most important. Significantly more specialists suggested that a public campaign or advertisement to increase public awareness of MF would be helpful (24% vs 8%; p < 0.001). Respondents thought pamphlets would be somewhat helpful in the education of general practitioners (n = 170, 54%), dermatologists, hematologists, and oncologists (n = 176, 55.9%). However, educational webinars for dermatologists, hematologists, and oncologists (n = 229; 72.5%) were deemed to be more useful.
DISCUSSION
This is the first multi‐stakeholder, international study to explore the views held by specialists and non‐specialists regarding the challenges facing the diagnosis of early‐stage MF. We recruited 382 participants from eight geographical locations, including UK, Ireland, Europe, Australia, North America, South America, Asia, and Africa. We sought to identify factors that were considered most important to specialists and non‐specialists in contributing to a delayed diagnosis of early‐stage MF. The majority of respondents had extensive experience of greater than 10 years working in dermatology.
Reaching a diagnosis of early‐stage MF is often challenging as clinical presentation and histological findings can be subtle and often mimic inflammatory dermatoses. 20 For many patients, a diagnosis of MF is preceded by years of repeated biopsies, incorrect diagnoses, and often inappropriate treatments. 21 There was agreement between specialists and non‐specialists surveyed that the diagnosis of early‐stage MF is delayed. However, when we excluded respondents who answered, “I don't know”, specialists were significantly more likely to agree with this statement. This may potentially reflect the common perception among specialists that early‐stage MF often lacks clearly diagnostic features for a prolonged period due to uncharacteristic clinical and/or histological findings and is therefore more difficult to diagnose. It may also reflect an unmet need among general dermatologists and allied specialists regarding the complexities of diagnosing early‐stage MF.
MF is considered an indolent disease in most patients, with progression over decades observed in a subset. 11 As a result, early‐stage patients are treated and maintained with skin‐directed therapies, unless their disease worsens. 12 Greater percentage body surface area involvement is associated with a somewhat higher risk of progression, and up to 25% of patients may develop a more aggressive, advanced disease that can be fatal. However, predicting prognosis and outcomes remains challenging. 22 , 23 PROCLIPI data has shown no difference in diagnostic delay among patients of different stages of MF, suggesting that there is no relationship between time to diagnosis and disease progression. 7 Among our survey cohort, non‐specialists were more likely to consider that delayed diagnosis affects disease progression and prognosis, while they were less likely to recognize its impact on HRQoL.
Previous evidence has shown that early‐stage MF has at least a mild to moderate impact on HRQoL scores, comparable to that observed in patients with atopic dermatitis or psoriasis. 10 A correlation has also been shown between the degree of cutaneous involvement, as measured by the modified Severity‐Weighted Assessment Tool (mSWAT), and overall HRQoL, indicating a possible relationship between symptom burden and morbidity in patients. 10 Key symptoms of concern for patients include pruritus, pain, and cosmetic disfigurement. 21 It has been well documented that the impact on HRQoL worsens with disease progression in MF patients. 24 , 25 Of note, patients’ perception of their illness–known to be predictive of coping in cancer – are clearly related to HRQoL in MF, further underscoring the importance of maintaining and improving patients’ quality of life.
A larger proportion of non‐specialists reported they did not know whether a delayed diagnosis impacted therapeutic efficacy. Available evidence suggests that early initiation of systemic therapy is not associated with improved outcomes compared to local topical treatment alone. 26 Delayed diagnosis may, however, expose patients to inappropriate or unnecessary treatment that has the potential to accelerate disease progression. 11 , 27 We also observed a potential misconception among non‐specialists that timely diagnosis influences cure rates. However, specialists were aware that alloSCT remains the only potential curative treatment for eligible patients. 13
Factors thought to impact the timely diagnosis of early‐stage MF include heterogeneity in clinical presentation, clinical features that mimic benign inflammatory dermatoses, and the absence of a unifying, reliable diagnostic test. Diagnosis often requires multiple biopsies for histopathologic confirmation. 7 , 28 , 29 Specialists and non‐specialists agreed that the most important factor contributing to delayed diagnosis was the misdiagnosis of MF as a benign inflammatory dermatosis. The clinical presentation of early‐stage MF is highly variable and often mimics eczema, psoriasis, tinea corporis, alopecia, or vitiligo, among other conditions. A diagnosis of MF is often not established until after treatment failure or following exposure to systemic or biologic therapies, which may cause apparent disease progression and/or unmask previously undiagnosed MF. 30 , 31 In addition to being misdiagnosed as atopic dermatitis or psoriasis, MF may also be overlooked in cases of subtle cutaneous findings and/or when a full skin examination is not performed, as it typically affects sun‐protected areas. 20
The lack of access to a reliable diagnostic test was also considered by respondents to be an important factor contributing to delayed diagnosis. Typically, repeated biopsies are required to confirm a diagnosis of MF. As with clinical presentation, histopathological findings can be subtle and non‐diagnostic. Classic histological patterns include superficial lymphoid aggregates with epidermotropism and dermoepidermal tagging by lymphocytes. 19 , 32 However, several clinical and histopathological variants have been described, further complicating diagnosis. 32 Furthermore, patients may have been exposed to topical or systemic treatment that has the possibility of further masking histopathological findings. 32 Ultimately, a stepwise approach with clinicopathological correlation, immunophenotyping, and TCR gene rearrangement is required to confirm diagnosis.
This survey highlights the unmet need for education and greater awareness among dermatologists regarding the challenges of diagnosing early‐stage MF and the impact of delayed diagnosis on patients' HRQoL. It also underscores the need for further research into reliable and validated diagnostic tools for early‐stage MF. Online seminars were considered the most useful platform for future educational interventions by both specialists and non‐specialists.
CONCLUSIONS
Specialists and non‐specialists have highlighted challenges associated with the diagnosis of early‐stage MF. Misdiagnosis as a benign inflammatory dermatosis is deemed the most important factor contributing to such a delay. Non‐specialists were more likely to incorrectly believe that a delayed diagnosis has a negative impact on prognosis and therapeutic success, whereas specialists emphasized the burden of delayed diagnosis on patients’ HRQoL. This study unveils an unmet need for education and increasing awareness in the (timely) diagnosis of early‐ stage MF, which may have implications for patient care.
FUNDING
This work was funded by a charitable grant donation by Antony Otofsky.
CONFLICT OF INTEREST STATEMENT
C.J. has received speaker honoraria and consultant fees from Kyowa Kirin, Recordati Rare Diseases, Takeda, and Stemline Therapeutics (related to the content of this manuscript).
F.T. has received speaker honoraria and consultant fees from Kyowa Kirin, Recordati Rare Diseases, and Takeda (related to the content of this manuscript).
K.M. has received honoraria from Kyowa Kirin, Takeda, Recordati Rare Diseases, Almirall, and LEO Pharma; served as a consultant/advisor for Kyowa Kirin; received research funding from Kyowa Kirin; and received travel funding from Almirall and Mallinckrodt.
J.S. has no conflicts of interest to declare.
ACKNOWLEDGEMENT
The authors thank the dermatology societies in the participating countries and all respondents of the PROCLIPI study for their contribution to this work, and especially Antony Otofsky for funding this project.
Beatty P, Molloy K, Porkert S, et al. The diagnosis of early‐stage mycosis fungoides: Views held by experts and non‐experts in cutaneous lymphoma. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2025;23:1094–1102. 10.1111/ddg.15799
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