An Update on Recent Advances of Photodynamic Therapy for Primary Cutaneous Lymphomas.
Pharmaceutics
Primary cutaneous lymphomas are rare non-Hodgkin lymphomas consisting of heterogeneous disease entities. Photodynamic therapy (PDT) utilizing photosensitizers irradiated with a specific wavelength of light in the presence of oxygen exerts promising anti-tumor effects on non-melanoma skin cancer, yet its application in primary cutaneous lymphomas remains less recognized. Despite many in vitro data showing PDT could effectively kill lymphoma cells, clinical evidence of PDT against primary cutaneous lymphomas is limited. Recently, a phase 3 "FLASH" randomized clinical trial demonstrated the efficacy of topical hypericin PDT for early-stage cutaneous T-cell lymphoma. An update on recent advances of photodynamic therapy in primary cutaneous lymphomas is provided.
10.3390/pharmaceutics15051328
Plasmacytoid dendritic cells in granulomatous variant of mycosis fungoides.
Fernandez-Flores Angel,Cassarino David S
Journal of cutaneous pathology
INTRODUCTION:Granulomatous mycosis fungoides (MF) is a rare variant in which granulomas are associated with other typical signs of MF. Its prognosis is worse than that of classical MF. Plasmacytoid dendritic cells (PDCs) are a subset of interferon-producing dendritic cells that link the innate and the adaptative immune responses. They have also been related to tolerance to certain tumors such as melanoma. MATERIALS AND METHODS:In this article, we examined for the presence of CD123+ PDC in six cases of granulomatous MF from our archives. RESULTS:We found clusters of 10 or more positive cells in three of six cases of granulomatous MF (two women and a man, in their sixth and seventh decade). Although in two of these three cases the granulomatous response was extensive, in the other, it only represented 10% of the infiltrate of the biopsy. In all three cases, the granulomas were epithelioid, sarcoidal type. CONCLUSIONS:CD123+ PDC can be identified in granulomatous MF. The pathogenic and prognostic role of this finding requires further clarification.
10.1111/cup.13438
Risk of skin cancers in mycosis fungoides patients receiving PUVA therapy: A real-life experience from a single tertiary center.
Photodermatology, photoimmunology & photomedicine
BACKGROUND:Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Skin-directed therapies, including phototherapy, are the first-line treatment modalities. Psoralen plus ultraviolet A light photochemotherapy (PUVA) is quite effective in controlling the disease; however, long-term adverse effects, particularly carcinogenesis, are the cons of this treatment. OBJECTIVE:There are various studies on the negative impact of PUVA on skin cancer in patients with autoimmune skin diseases. The data on the long-term effects of phototherapy on MF patients are scarce. METHODS:All MF cases that received PUVA alone or combined with other treatments at a single tertiary center were analyzed. This study compared the development of non-melanoma skin cancers, melanoma, and solid organ tumors in MF patients with at least 5-year follow-up data with age- and sex-matched controls. RESULTS:A total of 104 patients were included in the study. Ninety-two malignancies were detected in 16 (15.4%) patients, and six developed multiple malignancies. Skin cancers consisted of 56 basal cell carcinomas, 16 Bowen's disease, four squamous cell carcinomas, three melanomas, two basosquamous cell carcinomas, one Kaposi sarcoma, and one keratoacanthoma were found in nine (8.7%) patients. Eight patients developed three solid cancers and six lymphomas. The risk of developing skin cancer was associated with the total number of PUVA sessions (<250 vs ≥250 sessions; hazard ratio (HR) 4.44, 95% confidence interval (CI) 1.033-19.068; p = .045). 9 (13.2%) of 68 patients who had follow-ups for at least 5 years developed skin cancer. Compared to an age- and sex-matched cohort, the prevalence of new skin cancer was considerably greater (p = .009). CONCLUSIONS:Patients with MF are predisposed to develop secondary malignancies, and continual exposure to PUVA may potentiate this risk. Annual digital dermoscopic follow-up in MF patients treated with UVA is advised for early diagnosis and treatment of secondary cutaneous malignancies.
10.1111/phpp.12872
Small malignant melanoma in patients with mycosis fungoides.
Amichai B,Grunwald M H,Goldstein J,Finkelstein E,Halevy S
Journal of the European Academy of Dermatology and Venereology : JEADV
An increased risk for a second malignancy has been reported in patients with mycosis fungoides. We describe two subjects with mycosis fungoides who developed small malignant melanoma after topical application of nitrogen mustard.
Skin-directed therapy and biologic response modifiers in mycosis fungoides.
Dermatology reports
The most common and widespread type of cutaneous T-cell lymphoma is mycosis fungoides (MF), and it has a multiphasic clinical and biological course, with early stages being indolent for many years and later stages being faster and more aggressive. The clinical stage has a significant impact on the management and course of treatment: in the early stages, skin-directed therapies (SDT) plus/or biologic response modifiers (BRM); in the later stages, radiotherapy and/or systemic therapies. Even though national and international societies and groups periodically update their clinical recommendations, there is still no universally accepted approach. This paper reviews and discusses the various SDT and BRM options, either separately or in combination.
10.4081/dr.2024.9926
Photochemotherapy for mycosis fungoides: current status.
Watson A
The Australasian journal of dermatology
Phototherapy for mycosis fungoides is reviewed with particular emphasis on PUVA (psoralen ultraviolet A-range) therapy and its combination with other topical and systemic treatments. PUVA therapy has the advantages of being available in all major centres, is simple to administer, relatively inexpensive and has relatively low toxicity. Medium-term results suggest that PUVA is as effective as any of the other topical therapies for stage I disease. Its combination with alpha-interferon produces significant benefit in stage II or more advanced disease. Long-term non-melanoma skin cancer is increased with PUVA and combination PUVA usage, but melanoma is not increased. Its long-term position in comparison to other therapies with regard to morbidity, mortality and quality of life needs further evaluation.
Cutaneous malignant melanoma appearing during photochemotherapy of mycosis fungoides.
Reseghetti A,Tribbia G,Locati F,Naldi L,Marchesi L
Dermatology (Basel, Switzerland)
We report a case of malignant melanoma that appeared in a 56-year-old man with mycosis fungoides (stage Ia) during treatment with PUVA. The cumulative UVA dose was 1,177 J/cm2. The pigmented lesion was removed and PUVA therapy discontinued. Histological examination revealed a superficial spreading malignant melanoma (1.77 mm thick, Clark level IV). The delayed-type cutaneous hypersensitivity was studied. The presence of a second malignancy after mycosis fungoides and PUVA therapy may have been coincidental. Nevertheless, this case suggests that the immunosuppression induced by mycosis fungoides and by PUVA therapy might be a pathogenetic factor in the development of malignant melanoma.
10.1159/000246790
The interferons.
Edwards L
Dermatologic clinics
The interferons are a group of naturally occurring biologic response modifiers that exhibit antiviral, antiproliferative, differentiating, and immune-enhancing properties. This interesting group of compounds has been found to be effective for the treatment of condylomata acuminata, skin cancers, high-risk melanoma, hepatitis C, mycosis fungoides, and keloid scars. The advantages of these agents must be weighed against their toxicities, the number of treatments, and cost.
10.1016/s0733-8635(05)70235-7
Mycosis Fungoides and Associated Malignancies in a Dutch Nationwide Retrospective Cohort Study.
Acta dermato-venereologica
The prognosis of patients with mycosis fungoides is variable. As the current literature is scarce and shows mixed results this study investigates the incidence of other primary malignancies in mycosis fungoides patients. A retrospective, nationwide, population- based cohort study was performed with patients with mycosis fungoides between 2000 and 2020 in The Netherlands. All histopathology reports were requested from the Nationwide Network and Registry of Histo- and Cytopathology and screened for other primary malignancies. Lifelong incidence rates were used to compare the incidence of malignancies in mycosis fungoides patients and the general population. In total 1,024 patients were included with a mean follow-up of 10 years (SD 6). A total of 294 cases of other primary malignancies were found with 29% of the mycosis fungoides patients developing at least 1 other primary malignancy. Only cutaneous (odds ratio [OR] 2.54; CI 2.0-3.2) and haematological malignancies (OR 2.62; CI 2.00-3.42) had a statistically significant higher incidence than the Dutch population overall. Mycosis fungoides patients have a significantly increased risk of developing melanomas (OR 2.76; CI 2.11-3.59) and cutaneous squamous cell carcinomas mycosis fungoides (OR 2.34; CI 1.58-3.45). This study shows no association between mycosis fungoides and other solid organ tumours; however, such patients are significantly at risk of developing other haematological and cutaneous malignancies. Clinicians should be aware of this increased risk.
10.2340/actadv.v104.40065
Screening for second malignancies in mycosis fungoides: non-Hodgkin lymphoma, Hodgkin lymphoma, lung cancer, bladder cancer and melanoma.
Goyal A,O'Leary D,Goyal K,Rubin N,Janakiram M
Journal of the European Academy of Dermatology and Venereology : JEADV
BACKGROUND:Patients with mycosis fungoides (MF) are at increased risk of developing non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), lung cancer, bladder cancer and melanoma. The characteristics of patients developing these malignancies have not been specifically delineated. In addition, there are no established guidelines for screening MF patients for second malignancies. MATERIALS/METHODS:We identified 742 patients with MF who developed second malignancies in the Surveillance Epidemiology and End Result-18 database. RESULTS:The majority of second malignancy patients were white and male, mean age 55-67 years at diagnosis of MF, and mean age 61-72 years at diagnosis of second malignancy. The majority of patients diagnosed with second malignancies had early stage MF. MF patients with NHL, lung cancer, and bladder cancer tended to be diagnosed at earlier stages of the second malignancy than patients without MF and demonstrated better 5-year overall survival. There was no improvement in stage at diagnosis or survival for MF patients who were diagnosed with melanoma compared to patients without MF. CONCLUSIONS:Improvements in survival in MF/NHL, MF/lung cancer and MF/bladder cancer patients may reflect differences in disease biology secondary to having MF or the importance of increased contact with the healthcare system. MF/melanoma data suggest that patients require regular pigmented-lesion-focused skin examinations. Tools for screening include regular lymph node examinations, pigmented-lesion-focused examinations and detailed review of systems questions. Smoking cessation counseling is key intervention in this population, as is ensuring that all age- and sex-specific cancer screenings are up-to-date (e.g. lung cancer screening, mammography, and colonoscopy). The utility of regular imaging for second malignancy screening and lab testing such as routine urinalysis requires additional study and expert consensus.
10.1111/jdv.17384
Mycosis fungoides associated with malignant melanoma and dysplastic nevus syndrome.
Pielop J A,Brownell I,Duvic M
International journal of dermatology
BACKGROUND:The increased risk of second malignancies, including nonmelanoma skin cancers, in cutaneous T-cell lymphoma (CTCL) patients has been well documented. However, relatively few studies of malignant melanoma in CTCL patients have been reported. METHODS:A database of 250 CTCL patients registered over a 3-year period was searched to identify patients with diagnoses of both mycosis fungoides (MF) and malignant melanoma. RESULTS:We identified six cases of MF associated with malignant melanoma and one associated with dysplastic nevus syndrome, which is a marker of increased risk of melanoma. In four patients, melanoma was diagnosed along with or before MF. In the remaining two patients, MF was diagnosed prior to melanoma, although dysplastic nevi were noted at the time MF was diagnosed. These two patients received treatment for their MF (one with topical nitrogen mustard and another with radiation therapy and nitrogen mustard) prior to the histologic confirmation of melanoma. Six patients had early stages of MF (IA or IB), while one patient presented with simultaneous erythrodermic mycosis fungoides involving the lymph nodes as well as melanoma metastatic to the lymph nodes from an unknown primary. CONCLUSION:There is an elevated prevalence of malignant melanoma in MF patients compared to the general US population (P < 0.00001) with a relative risk of 15.3 for observing malignant melanoma in MF patients (95% confidence interval 7.0-33.8). Possible pathologic links between the two diagnoses include effects of mycosis fungoides therapies, immunosuppression secondary to mycosis fungoides, and genetic alterations in the p16 tumor suppressor protein.
10.1046/j.1365-4362.2003.01697.x
Cutaneous malignant melanoma in association with mycosis fungoides.
Evans Alun V,Scarisbrick Julia J,Child F J,Acland Katharine M,Whittaker Sean J,Russell-Jones Robin
Journal of the American Academy of Dermatology
We retrospectively analyzed the first 461 cases entered into our cutaneous lymphoma database and found 285 cases of mycosis fungoides. We also identified 6 cases of malignant melanoma, all of which were found in patients with mycosis fungoides. The crude rate of melanoma in the general population in England, United Kingdom, in 1998 was 8.8/100,000 in men and 11.4/100,000 in women. The incidence of melanoma found in our cohort of patients with mycosis fungoides was far higher, and in 4 of the 6 patients cannot be explained on the basis of prior therapy. The reason for this association is unclear, but this report emphasizes the risk of second malignancies for patients with cutaneous T-cell lymphoma and melanoma.
10.1016/j.jaad.2003.11.054
Is Cutaneous T-Cell Lymphoma Caused by Ultraviolet Radiation? A Comparison of UV Mutational Signatures in Malignant Melanoma and Mycosis Fungoides.
Cells
Ultraviolet (UV) radiation is a strong environmental carcinogen responsible for the pathogenesis of most skin cancers, including malignant melanoma (MM) and non-melanoma (keratinocyte) skin cancers. The carcinogenic role of UV was firmly established based on epidemiological evidence and molecular findings of the characteristic mutation signatures which occur during the excision repair of cyclobutane pyrimidine dimers and 6,4-photoproducts. The role of UV in the pathogenesis of mycosis fungoides (MF), the most common type of primary cutaneous T-cell lymphoma, remains controversial. Here, we performed whole-exome sequencing of 61 samples of MF cells microdissected from cutaneous lesions, and compared their mutational signatures to 340 MMs. The vast majority of MM mutations had a typical UV mutational signature (SBS 7, SBS 38, or DSB 1), underscoring the key role of ultraviolet as a mutagen. In contrast, the SBS 7 signature in MF comprised < 5% of all mutations. SBS 7 was higher in the intraepidermal MF cells (when compared to the dermal cells) and in the cells from tumors as compared to that in early-stage plaques. In conclusion, our data do not support the pathogenic role of UV in the pathogenesis of MF and suggest that the UV mutations are the result of the cumulative environmental ultraviolet exposure of cutaneous lesions rather than an early mutagenic event.
10.3390/cells12121616
Melanoma Risk is Increased in Patients with Mycosis Fungoides Compared with Patients with Psoriasis and the General Population.
Acta dermato-venereologica
Patients with mycosis fungoides (MF) are thought to be at increased risk of melanoma. However, studies addressing surveillance-bias and treatments as a possible confounder are lacking. This retrospective study compared the prevalence and risk of melanoma between 982 patients with MF, and 3,165 patients with psoriasis attending tertiary cutaneous-lymphoma/psoriasis clinics during 2009 to 2018. Melanoma was diagnosed in 47 patients with MF (4.8%; 43 early-stage) and in 23 patients with psoriasis (0.7%) (odds ratio 6.6, p < 0.0001). In 60% of patients, MF/psoriasis preceded melanoma diagnosis. Hazard ratio (HR) for a subsequent melanoma in MF vs psoriasis was 6.3 (95% confidence interval (95% CI) 3.4-11.7, p < 0.0001). Compared with the general population, melanoma standardized incidence ratios were 17.5 in patients with MF (95% CI 11.0-23.9, p < 0.0001), and 2.2 (95% CI 0.6-3.8, p = 0.148) in patients with psoriasis. Narrow-band ultraviolet B was not a contributory factor (HR 1.15, 95% CI 0.62-2.14, p = 0.66). These findings add evidence that patients with MF have a significantly higher risk of melanoma, not only compared with the general population, but also compared with patients with psoriasis. This comorbidity may be inherent to MF.
10.2340/00015555-3704
Vitamin D and the Skin: An Update for Dermatologists.
Kechichian Elio,Ezzedine Khaled
American journal of clinical dermatology
Vitamin D plays a key role in skeletal and cardiovascular disorders, cancers, central nervous system diseases, reproductive diseases, infections, and autoimmune and dermatological disorders. The two main sources of vitamin D are sun exposure and oral intake, including vitamin D supplementation and dietary intake. Multiple factors are linked to vitamin D status, such as Fitzpatrick skin type, sex, body mass index, physical activity, alcohol intake, and vitamin D receptor polymorphisms. Patients with photosensitive disorders tend to avoid sun exposure, and this practice, along with photoprotection, can put this category of patients at risk for vitamin D deficiency. Maintaining a vitamin D serum concentration within normal levels is warranted in atopic dermatitis, psoriasis, vitiligo, polymorphous light eruption, mycosis fungoides, alopecia areata, systemic lupus erythematosus, and melanoma patients. The potential determinants of vitamin D status, as well as the benefits and risks of vitamin D (with a special focus on the skin), will be discussed in this article.
10.1007/s40257-017-0323-8