|Year : 2020 | Volume
| Issue : 2 | Page : 99-104
Clinical and epidemiological profile of libyan patients with mycosis fungoides: A prospective study
Nadia A El Sherif1, Abdulhamed A M. Elorfi1, Omarn O Bugrein1, Soad I Eldruki2
1 Department of Dermatology, Faculty of Medicine, Benghazi University, Benghazi, Libya
2 Department of Histopathology, Benghazi Medical Center, Benghazi, Libya
|Date of Submission||12-Jun-2020|
|Date of Acceptance||22-Jul-2020|
|Date of Web Publication||10-Nov-2020|
Dr. Nadia A El Sherif
Department of Dermatology, Faculty of Medicine, Benghazi University, Benghazi
Source of Support: None, Conflict of Interest: None
Background: Mycosis fungoides (MF) represents the most common form of primary cutaneous T-cell lymphoma (CTCL) often with an indolent course. Purpose: The objective is to determine epidemiological and clinical features of MF among Libyan patients. Methods: Clinical and histopathological evaluation was carried out in 24 patients with MF in the Department of Dermatology at El-Jumhoria Hospital in Benghazi city between 2010 and 2019. Results: Twenty-four patients with a diagnosis of MF, 11 were female and 13 were male. Age of the patients ranged between 30 and 60 year with a mean of age ± standard deviation of 47.4 ± 8 years. Clinical presentation with patches and plaques was most common, seen in 58.3% of the patients. Poikilodermatous MF was seen in 37.5% patients, hypopigmented MF seen in 12.5% of patients, follicular MF seen in 8.3% of patients, and 8.3% patients had lymphomatoid papulosis. Pruritis was the complaint of 75% of the patients. About 25% of the patients had blood eosinophilia, 33.3% had raised lactic dehydrogenase enzyme. Tumor-node-metastasis-blood (TNMB) classification of the patients revealed that 66.7% had stage IB, 20.8% of patients had stage IIA, 8.3% of patients had stage IIB, and 4.2% patients had stage IVa. About 70.8% of patients received systemic Psoralen and ultraviolet A (PUVA) therapy, 20.8% patients received narrow band ultraviolet B, 4.2% patients treated with radiotherapy, and 4.2% patients received both chemotherapy and radiotherapy. About 45.8% of patients show remission of their disease, 12.5% patients show no response, 8.3% of patients still under treatment, 25% of patients lost follow-up, and 8.3% patients died. Conclusion: MF is a low-grade primary CTCL with different clinical presentations with variable response to therapy.
Keywords: Lymphoma, mycosis fungoides, TNMB
|How to cite this article:|
El Sherif NA, Elorfi AA, Bugrein OO, Eldruki SI. Clinical and epidemiological profile of libyan patients with mycosis fungoides: A prospective study. J Dermatol Dermatol Surg 2020;24:99-104
|How to cite this URL:|
El Sherif NA, Elorfi AA, Bugrein OO, Eldruki SI. Clinical and epidemiological profile of libyan patients with mycosis fungoides: A prospective study. J Dermatol Dermatol Surg [serial online] 2020 [cited 2021 May 11];24:99-104. Available from: https://www.jddsjournal.org/text.asp?2020/24/2/99/300387
| Introduction|| |
Mycosis fungoides (MF) is a form of primary cutaneous T-cell lymphoma of T-helper cells and is clinically characterized by three stages of presentation: patches, infiltrated plaques, and tumors. Histologically, the disease demonstrated by the proliferation of small cerebriform lymphocytes showing epidermotropism. Its etiology is unknown, however, genetic, infective, and environmental causes have all been implicated. MF is a rare disease, its incidence in the USA is approximately 0.3–1.02 new cases per 100,000 inhabitants/year. The sex ratio in most series shows male predominance, with an average age of onset of 56 years.
The extent of the clinical investigations, the approach to treatment, and the prognosis of MF are related to the staging at diagnosis. Staging is based on the pattern and extension of skin involvement, lymph node involvement, extension of the disease to other organs, and finally extension to peripheral blood, and is called TNMB. Furthermore, in 2007, the ISCL and EORTC revised the TNMB staging of MF.
The current treatment of early stage MF includes topical steroids, PUVA, broadband UVB, topical nitrogen mustard, topical bexarotene, and electron beam irradiation. Narrow band ultraviolet B (NBUVB) phototherapy has only recently been described as a first-line treatment for early-stage MF.
The aim of this prospective study was to analyze the demographics data of Libyan patients with MF and their clinical presentations, comparing them with international data.
| Methods|| |
This is a prospective study. Twenty-four Libyan patients diagnosed with MF at the Dermatology Department, El-Jomharia Hospital in Benghazi city period between 2010 and 2019 were included in this study. A signed consent was obtained from all patients after explaining the nature of the study. The study was conducted in accordance with the Declaration of Helsinki standards.
All patients were subject to full history, appropriate general examination, and dermatologic examination together with routine investigations. After a skin biopsy was taken, the specimens were processed routinely and stained with H and E for light microscopic examination, immunohistochemical study had been done in 11 biopsy sample.
The diagnosis of MF was made according to clinical and histological finding. TNMB classification of the National Cancer Institute Workshop on MF was applied to all patients.
Oral 8-methoxypsoralen at a dose of 0.6 mg/kg was taken 1½ h before UVA exposure. Patients were started on a dose of 0.5 J/cm2. PUVA was administered three times a week on nonconsecutive days. Incremental increases of the previous dose were made at each visit ranging from 10 to 20%–30% depending on the response.
Narrow band ultraviolet B
NBUVB phototherapy was administered three times a week on nonconsecutive days. Phototesting was not performed and a standard initial dose of 300 mJ/cm2 was started in all patients. Depending upon response, the irradiation dose was increased by 20%.
Data were analyzed using Statistical Package for Social Sciences version 16.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics in the form of percentages, mean, and standard deviation of different parameters was used. Chi-square test was used to compare qualitative parameters, P < 0.05.
| Results|| |
Twenty-four Libyan patients with MF, 13 (54.2%) were male and 11 (45.8%) were female, with a male to female ratio of 1.2:1. The mean time from the onset of lesions to diagnosis was 10.7 ± 3.7 years, ranging from 3 to 18 years. No statistical significant difference in the mean age at diagnosis between male and female patients [Table 1].
|Table 1: The demographic data of patients with mycosis fungoides under study|
Click here to view
The clinical presentations of the patients are summarized in [Table 2]. Fourteen (58.3%) of patients presented with patches and plaques [Figure 1]a, 29.2% of patients presented with only patches [Figure 1]b, and 12.5% of patients presented with tumors [Figure 1]c. Hypopigmented MF seen in 12.5% of patients all of them presented with patches [Figure 1]d. Poikiloderma predominantly located on the breast, hips, and buttocks seen in 37.5% [Figure 1]e. Follicular MF on the scalp seen in 2 male patients with tumor presentation [Figure 1]f. Two female patients had lymphomatoid papulosis (LyP) along with their skin lesions. Scaling on the surface of the lesions seen in 54.2% of the patients.
|Table 2: Main clinical data of patients with mycosis fungoides under study|
Click here to view
|Figure 1: Plaques (a), patches (b), tumor (c), hypopigmented (d) and poikelodermatous (e) presentation of mycosis fungoides in patients under study. (f) Follicular mycosis fungoides on the scalp in patient with tumor stage mycosis fungoides|
Click here to view
Pruritus was the complaint of 75% of the patients, 41.7% were complaint of mild itching while 33.3% had severe itching interfere with their daily activities and sleeping.
Of those complaints of severe itching, 3 (12.5%) patients presented with tumors and 5 (20.8%) patients presented with patch and plaques.
The diagnosis was confirmed in all patients by skin biopsies which showed lymphocytic infiltrate in the dermis with epidermotropism of atypical lymphocytes. Pautrier's abscesses were also seen [Figure 2]a. Immunohistochemistry was done in 11 patients and showed CD4 + while CD8, CD7, CD30 were all negative [Figure 2]b. Serial biopsies were required in six cases to establish the diagnosis.
|Figure 2: (a) Dense dermal infiltrate of medium size atypical lymphocytes with Pautrier's microabscesses in the epidermis. (b) Immunohistochemistry strong immunopositivity for CD4|
Click here to view
Five (20.9%) of the patients had axillary lymphadenopathy, only one patient (4.2%) had neoplastic lymphadenopathy. Chest, abdominal, and pelvic magnetic resonance imaging were performed in two male patients with tumor presentation and revealed neither evidence of retroperitoneal lymph node enlargement nor internal organ metastasis. Six (25%) of the patients had blood eosinophilia, 8 (33.3%) had raised blood lactic dehydrogenase enzyme (LDH), all patients with eosinophilia and raised LDH had severe itching and this was statistically significant (P = 0.000).
According to the clinical findings, results of investigations, and peripheral blood smear for atypical lymphocytes, TNMB classification were done for the patients [Table 3].
According to the clinical presentations, different treatment modalities have been used [Table 4]. All patients received topical clobetasol propionate 0.05% cream. During follow-up, 11 (45.8%) patients show remission of their disease, most of them 33.3% had stage IB, 8.3% of patients are still under treatment and 2 (8.3%) patients died.
|Table 4: Types of treatment used for patients with mycosis fungoides and it's out come|
Click here to view
| Discussion|| |
This paper describes 24 Libyan patients with MF. Half of the patients in the study were more than 50 years of age with slight male predominance, which is consistent with the previous studies, in which MF is reported to occur predominantly in older adults., However, one patient aged at the time of diagnosis was 20 years. MF is unusual in this age group; over 75% of MF cases occur in those over 50 years of age, moreover, a review of MF in those under 30 years of age has suggested that these patients do well in the long term and rarely progress.
An initial diagnosis of nonspecific dermatitis and parapsoriasis were reported in our patients, in agreement with previous studies,, which have suggested an association between chronic inflammation in the skin and subsequent development of cutaneous T-cell lymphomas (CTCLs). Moreover, it is well known that 7.5%–35% of patients with parapsoriasis will be diagnosed with MF over time., This supports hypotheses on the pathogenesis of MF, that constantly activated T-lymphocytes might eventually give rise to an atypical T-cell clone. A wide range of atypical presentations has been described including erythrodermic, poikilodermatous, verrucous, hyperkeratotic, hypopigmented, vesicular, bullous, and pustular MF. Although the most common presentation among our patients were patches and plaques, nine patients present with poikilodermatous MF. Poikiloderma atrophicans vasculare, as described by Jacobi in 1906, represents a poikilodermatous variant of CTCL. However, in the past, it was classified in the large-plaque parapsoriasis group, but there is now an increasing tendency to consider it as an early form of CTCL. Follicular MF on the scalp seen in two patients with tumor presentation, both patients shown progressive disease and both of them died. Follicular MF usually localizes in the head and neck area presented with papules, alopecia, frequent secondary bacterial infection, and less commonly mucinorrhea; moreover, patients with follicular MF proved generally more refractory to standard MF therapies, more disease progression, and had a less favorable prognosis.
Hypopigmented MF, seen in 12.5% of our patients, was lower than the reported prevalence from previous studies. The younger age of patients in the previous studies may explained this difference. It is well known that hypopigmented MF occurs commonly in children and younger age. The pathogenesis of hypopigmented MF is still unclear, however, hypomelanosis may be due to the cytotoxic effect of T suppressor lymphocytes in melanocytes.
LyP is CD30+ lymphoproliferative disorder that typically presents as recurrent crops of red-brown papulonodules with necrotic centers on the trunk or extremities. While LyP is a benign disease that does not require treatment, it can be associated with different types of lymphoma, requiring close follow-up. LyP patients have a 10% to 20% increased risk of developing lymphoma, most commonly MF, primary cutaneous anaplastic large-cell lymphoma, and Hodgkin's disease.
About 25% of the patients under study had blood eosinophilia. Blood eosinophilia has been reported in 20% of patients with MF in previous study. In CTCL blood eosinophilia may be due to the predominant secretion of T helper cell type 2 (TH2) cytokines by neoplastic cells. It has been hypothesized that eosinophilia in patients with CTCL would correlate with the increased tumor burden and worse prognosis.
In the present study, 33.3% of patients had raised LDH level, which was comparable to previous study. LDH has been demonstrated to correlate with progression of malignancy specially lymphoma and leukemia. Saif suggest that high LDH level may be used as an independent prognostic factor to measure the progression of MF.
Pruritus is frequent complaint in patients with CTCL, it is severe, and unrelieved by emollients, topical steroids, or oral antihistamines., Pruritus was the complaint of 75% of the patients under study, however, the prevalence of pruritus in patients with MF varies in different studies and ranging from 68% to 93%.,,
Pruritus may be a presenting feature in patients with CTCL and can occur in without skin lesions, making the diagnosis of CTCL difficult. Folliculotropic form of CTCL, Sézary syndrome, and advanced stage of MF are extremely itchy as compared to patch stages of MF.
Pathophysiology of pruritus in CTCL still unknown, it has been reported that mast cells and histamine may play a role in MF particularly in advanced stages of the disease. However, the itch of patients with CTCL often fails to or only partially responds to antihistamines. Several data are supporting the fact that CTCL produce high amounts of Th2 cytokine including interleukin (IL)-2 and IL-6 which proposed as histamine-independent itch mediators.,
The treatment should be considered in all patients with MF, moreover, the choice of treatment varies depending on the staging of the diseases and the presence of distance metastasis.
A nonaggressive approach is suggested as first-line treatment in early MF, such as, PUVA, topical nitrogen mustard, and topical corticosteroids. A combination of aggressive chemotherapy and radiotherapy has shown no added benefit for survival in this group. Phototherapy is by far the most successful therapy, and is the first-line therapy for early MF stage.
PUVA is generally well tolerated by patients and is often used as initial treatment, moreover, the response to PUVA varies according to the stage of the disease and patients with early stage disease showed excellent clearance. However, as the disease progresses, or a lack of response to initial treatment occurs, advanced treatment may be considered.
Our study shows that PUVA and NB-UVB were effective treatments for patients with MF. The patients who responded to both treatments were stage IB. All patients with stage IIA received PUVA and none of them received NB-UVB. It is well known that UVB has a limited ability to penetrate thicker lesions.
Patients with later stages of MF (stage IIB or higher) will require some form of systemic therapy. El-Mofty et al. and Diederen et al. compared the efficacy of PUVA and NB-UVB in patients with stage IA and IB MF. These two studies showed favorable and equal responses of early stage MF to NB-UVB and PUVA.
NB-UVB is a safe and easily administered therapy for early-stage MF. Side effects are limited to erythema and pruritus. NB-UVB phototherapy has advantages compared with PUVA because patients do not have to take psoralen or wear ultraviolet (UV) protective glasses.
The mechanisms of action of NB-UVB therapy in MF are still unknown. Ultraviolet B (UVB) has been shown to decrease the antigen-presenting capacity of Langerhans cells, and increase IL-2 and IL-6 production by human keratinocytes, and also increase tumor necrosis factor-α. As a result, UVB could suppress the function of the neoplastic population of clonal T cells in the skin and serve as an up-regulator of the immune system.
PUVA is an accepted method of treatment for patients with more advanced plaque stage MF, but has a higher rate of carcinogenicity and side effects than NB-UVB.
The effect of PUVA in MF may be a result of killing of neoplastic T cells, psoralen-adduct damage to cell organelles and alterations in the immune system. Other effects are achieved by inducing apoptosis, as it can trigger apoptotic cascade through p53-independent programmed cell death as well as protein-synthesis-independent preprogrammed cell death mechanisms.
Fortunately, the majority of patients with early stage MF, when treated appropriately, do well, and their survival is similar to that of a matched population., Early stage disease (IA–IB) does not require expensive or invasive investigations, as shown in our study and in the recent literature.
| Conclusion|| |
The present study is the first prospective study reported from Benghazi city on demographic data and clinical presentation of patients with MF. MF is a rare disease that needs a high index of suspicion with repeated skin biopsies to be diagnosed. Poikilodermatous MF and hypopigmented MF are also seen among our patients.
It is not possible to comment on patients with disease more advanced than stage IB because of insufficient numbers of patients. Disease progression clinically is a good guide to the need for further investigations or the need for further treatment.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): Part I. Diagnosis: Clinical and histopathologic features and new molecular and biologic markers. J Am Acad Dermatol 2014;70:205.e1-16.
Kazakov DV, Burg G, Kempf W. Clinicopathological spectrum of mycosis fungoides. J Eur Acad Dermatol Venereol 2004;18:397-415.
Willemze R. Cutaneous T-cell lymphoma: Epidemiology, etiology, and classification. Leuk Lymphoma 2003;44 Suppl 3:S49-54.
Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, et al
. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: A proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 2007;110:1713-22.
Ahmad K, Rogers S, McNicholas PD, Collins P. Narrowband UVB and PUVA in the treatment of mycosis fungoides: A retrospective study. Acta Derm Venereol 2007;87:413-7.
AlGhamdi KM, Arafah MM, Al-Mubarak LA, Khachemoune A, Al-Saif FM. Profile of mycosis fungoides in 43 Saudi patients. Ann Saudi Med 2012;32:283-7.
Burns MK, Ellis CN, Cooper KD. Mycosis fungoides--type cutaneous T-cell lymphoma arising before 30 years of age. Immunophenotypic, immunogenotypic and clinicopathologic analysis of nine cases. J Am Acad Dermatol 1992;27:974-8.
Eklund Y, Aronsson A, Schmidtchen A, Relander T. Mycosis fungoides: A retrospective study of 44 Swedish cases. Acta Derm Venereol 2016;96:669-73.
Mataix J, Bañuls J, Lucas A, Belinchón I, Betlloch I. Poikilodermatous mycosis fungoides. Int J Dermatol 2007;46:950-1.
Simon M, Flaig MJ, Kind P, Sander CA, Kaudewitz P. Large plaque parapsoriasis: Clinical and genotypic correlations. J Cutan Pathol 2000;27:57-60.
van Doorn R, Scheffer E, Willemze R. Follicular mycosis fungoides, a distinct disease entity with or without associated follicular mucinosis: A clinicopathologic and follow-up study of 51 patients. Arch Dermatol 2002;138:191-8.
Jang MS, Kang DY, Park JB, Kim ST, Suh KS. Cutaneous T-cell lymphoma in asians. ISRN Dermatol 2012;2012:575120.
Zackheim HS, Jones C, Leboit PE, Kashani-Sabet M, McCalmont TH, Zehnder J. Lymphomatoid papulosis associated with mycosis fungoides: A study of 21 patients including analyses for clonality. J Am Acad Dermatol 2003;49:620-3.
Tancrède-Bohin E, Ionescu MA, de La Salmonière P, Dupuy A, Rivet J, Rybojad M, et al
. Prognostic value of blood eosinophilia in primary cutaneous T-cell lymphomas. Arch Dermatol 2004;140:1057-61.
Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): Part II. Prognosis, management, and future directions. J Am Acad Dermatol 2014;70:223.e1-17.
Al Saif F. Prognostic significance of serum lactate dehydrogenase in saudi patients with mycosis fungoides: A retrospective study of 47 patients. J Clin Exp Dermatol Res 2016;7:2.
Meyer N, Paul C, Misery L. Pruritus in cutaneous T-cell lymphomas: Frequent, often severe and difficult to treat. Acta Derm Venereol 2010;90:12-7.
Bradford PT, Devesa SS, Anderson WF, Toro JR. Cutaneous lymphoma incidence patterns in the United States: A population-based study of 3884 cases. Blood 2009;113:5064-73.
Görge T, Schiller M. Pruritus in cutaneous T-cell lymphoma. In: Misery L, Ständer S, editors. Pruritus. London: Springer-Verlag; 2010. p. 121-4.
Ahern K, Gilmore E. S, Poligone B. Pruritus in cutaneous T-cell lymphoma: A review. J Am Acad Dermatol. 2012;67:760-68.
Lenane P, Powell FC, O'Keane C, Dervan P, O'Sullivan D, Bourke E, et al
. Mycosis fungoides – A review of the management of 28 patients and of the recent literature. Int J Dermatol 2007;46:19-26.
Whittaker SJ, Marsden JR, Spittle M, Russell Jones R; British Association of Dermatologists, U.K. Cutaneous Lymphoma Group. 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;149:1095-107.
Clark C, Dawe RS, Evans AT, Lowe G, Ferguson J. Narrowband TL-01 phototherapy for patch-stage mycosis fungoides. Arch Dermatol 2000;136:748-52.
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;21:281-6.
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 Aead Dermatol 2003;48:215-9.
Duthie MS, Kimber I, Norval M. The effects of ultraviolet radiation on the human immune system. Br J Dermatol 1999;140:995-1009.
Toro JR, Stoll HL Jr., Stomper PC, Oseroff AR. Prognostic factors and evaluation of mycosis fungoides and Sézary syndrome. J Am Acad Dermatol 1997;37:58-67.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]