Mycosis Fungoides: Epidemiology in Isfahan, Iran

doi:10.4236/jcdsa.2012.23043

Paper Menu >>

Journal Menu >>

Journal of Cosmetics, Dermatological Sciences and Applications, 2012, 2, 229-233

http://dx.doi.org/10.4236/jcdsa.2012.23043 Published Online September 2012 (http://www.SciRP.org/journal/jcdsa)

229

Mycosis Fungoides: Epidemiology in Isfahan, Iran

Farahnaz Fatemi Naeini1, Jamshid Najafian2, Mansoor Salehi3, Zahra Azimi4,5*, Parvin Rajabi6

1Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; 2Isfahan Cardiovascular

Research Center, Isfahan Cardiovascular Research Institue, Isfahan University of Medical Sciences, Isfahan, Iran; 3Department of

Genetics and Molecular Biology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran; 4Skin and Stem Cell Re-

search Center, Tehran University of Medical Sciences, Tehran, Iran; 5Isfahan University of Medical Sciences, Isfahan, Iran; 6Isfahan

University of Medical Sciences, Isfahan, Iran.

Email: *[email protected]

Received January 25th, 2012; revised February 28th, 2012; accepted March 13th, 2012

ABSTRACT

Background: Mycosis Fungoides (MF) is the most common and indolent form of Cutaneuse T-cell Lymphomas (CTCL),

that usually occurs in old adults. Objectives: To determine epidemiologic features and patients characteristics of MF in

Isfahan (Iran). Methods: We performed a retrospective study in MF clinic of alzahra hospital that is the main center for

treatment of MF patients in Isfahan (Iran) and evaluated clinicopathologic features. Results: In 3 years 25 patients were

referred to Alzahra MF clinic. 18 patients diagnosed as MF. Seven (38.9%) patients were male and 11 (61.1%) were

female with male to female ratio of 1:1.57. The mean age of patients was 41.06 years. 88.9% of our patients were in

stages ΙA and ΙB. Conclusion: Most of our patients presented in early stages that were similar to other studies, while

male: female ratio is different from other studies.

Keywords: Mycosis Fungoides; Epidemiology; Clinical Features; Iran

1. Introduction

Mycosis Fungoides (MF) is a disease of lymphatic tis-

sues with primary involvement of the skin and is the most

common and indolent form of Cutaneuse T-cell Lym-

phomas (CTCL), followed by Sezary Syndrome. Initially,

MF presents as a round or ovoid, flat erythematous or

eczematous patch lesion, with or without fine scales [1-

3].

MF usually occurs in old adults, with a median age

between 55 and 60 years and a 2:1 male to female ratio

[4,5].

The diagnosis of MF in its patch or early plaque phase

is often difficult, either because MF mimic other cuta-

neuse disorders such as benign dermatoses or discordance

between clinical and pathologic findings [6,7].

Etiology of MF is unknown, however some studies sug-

gested a causative role of environmental exposure to chro-

nic antigenic stimulation, but they have not been sub-

stantiated by subsequent studies [8-10].

MF is a relatively rare disease and there is no registra-

tion system for this disease in Iran and therefore there is

not enough epidemiologic information about MF in our

country. The aim of this study is to collect epidemiologic

information as well as patient characteristics and clini-

copathologic features of MF in our region, Isfahan, Iran.

2. Patients & Methods

We performed a retrospective study in Alzahra hospital

of Isfahan that is the main center for diagnosis and treat-

ment of patients suspected in MF.

Our study included 25 patients that were suspected in

MF and referred to Alzahra MF clinic in three years from

2007 to 2010.

For establishing the diagnosis each patient reexamined

clinically and the type of skin lesions (including patch,

plaque, tumor, erythroderma, …), percentage of skin in-

volvement as well as location of lesions were determined.

We used WHO classification of tumours of haemopoietic

and lymphatic tissue (2008) to classify our cases [11].

For staging TNMB classification system (2007) was em-

ployed that is the newest classification system for MF

and Sezary Syndrome [12].

Haematoxylin and eosin-stained slides reviewed by

pathologist. Immunohistochemical (IHC) stains for basic

T-cell markers CD4, CD8, CD3, CD5, CD7, CD30, and

CD45RO evaluated where needed. Also fresh or paraf-

fin-embedded tissues checked for T-cell clonality, using

TCR gamma gene rearrangement assay kit (In Vivo

Scribe technologies, USA) [13].

For each patient a profile including all related infor-

mation, was collected. Among this were age, gender, ma-

rital status, address, physical examination, type of skin

*Corresponding author.

Mycosis Fungoides: Epidemiology in Isfahan, Iran

230

lesions, lesion distribution, tumor stage as well as results

of pathology and molecular biology studies.

Cases other than MF were excluded from the study

and patient’s forms were reviewed.

After data collection statistical analysis was performed

by SPSS soft ware version 19.

3. Results

During 3 years 25 patients were referred to Alzahra MF

clinic. After clinical, histological and molecular clonality

reevaluation, 18 patients diagnosed as MF. Seven (38.9%)

patients were male and 11 (61.1%) were female with

male to female ratio of 1:1.57. The mean age of patients

was 41.06 years [median, 34.5 years; range, 25 - 86;

standard deviation (SD), 17.9], and that was 41 for male

and 41.09 for female patients.

Seven (38.9%) patients presented with patch, one of

them had hypopigmented patch, 3 (16.7%) with plaque, 6

(33.3%) had combination of patch and plaque and the

disease in 2 (11.1%) patients were in tumor stage.

We performed T-cell receptor gene rearrangement

studies for all patients. In patients were diagnosed as MF,

11 (61.1%) were positive & 7 (38.9%) were negative.

Using TNM classification system, 8 patients (44.4%)

were in stage ІA, 8 patients (44.4%) were in stage ІB and

2 (11.1%) in ПB.

Exposure to radiation or chemicals, lesion distribution,

pathologic and IHC results of patients are shown in Ta-

ble 1. Twelve (66.66%) patients had no remarkable ex-

posure to sunray or chemical agents.

Fourteen (77.8%) of the cases were married. Most of

the patients (83.3%) had educational degree of diploma

or less. 81.8% of women were housekeepers and most of

men were workers (42.9%) and salesmen (28.6%).

Seven patients (38.9%) were from Flavarjan and sub-

urb, a small city close o Isfahan, and 5 (27.8%) from Is-

fahan city.

4. Discussion

The current study represents a retrospective review of

patients referred to Alzahra MF clinic in three years, in-

cluding 18 patients confirmed as MF.

There is a male predominance in almost all of studies

on CTCLs and MF with a male: female ratio of 1.30 to

Table 1. patients’ characteristics.

Patient No./sex/age Exposure to

chemicals or radiation Lesion distribution Stage Pathology IHC TCR

1/M/86 Sun ray chemical agents Trunk & lower limbs ПB Panniculitis like T-cell

lymphoma MF +

2/F/34 no Trunk & lower limbs ІB MF MF −

3/F/54 Sun ray Buttocks, right groin, lower limbs ІA MF MF −

4/F/35 no Buttocks

Lower abdomen ІA MF ND −

5/M/35 no Trunk, lower limbs ПB MF MF −

6/F/51 no Axilla, groin ІA MF MF +

7/M/26 HCL smoke Head & neck, trunk, upper & lower limbsІA MF MF +

8/M/52 Sun ray Trunk, upper & lower limbs ІB Parapsoriasis MF +

9/F/25 no Buttocks, upper & lower limbs ІA MF MF +

10/F/30 no Lower limbs ІA MF MF +

11/M/28 no Trunk, upper & lower limbs ІB MF MF +

12/F/50 no Face, back, lower limbs ІB MF ND −

13/F/80 no Buttocks, upper & lower limbs ІB MF MF +

14/F/29 no Trunk, upper & lower limbs ІA Chronic dermatitis MF +

15/F/29 no Head, trunk, upper & lower limbs ІB MF (folliculotropic) MF −

16/M/30 Oil colors Trunk, upper & lower limbs ІA MF MF +

17/M/30 Chemical colors Trunk, upper & lower limbs ІB MF MF +

18/F/35 no Upper & lower limbs ІB MF (hypopigmented) MF −

HC: Immunohistochemistry; TCR: T-cell receptor gamma gene rearrangement assay; ND: Non diagnostic.

Mycosis Fungoides: Epidemiology in Isfahan, Iran 231

4.00:1 [14-20]. Male to Female ratio was about 1.00 -

1.4:1 in studies performed in some cities of Iran (Mash-

had, Tabriz and Tehran) [21-23]. In present study this

ratio is 1:1.57 that is similar to our previous study on

incidence rate of MF in Isfahan with male: Female ratio

of 3:4 (1:1.33) [24]. These ratios are completely in con-

trast to other studies. This difference might be due to

ethnic group diversity, however to identify the causes of

this difference, studies with more patients should be done.

Although MF usually affect older adults with median

age of more than 50 years [1,25,26], it was lower in

study in Singapore (33 years) [27]. The mean age of pa-

tients in a study in Kuwait was 35.2 years [28]. Their

results are similar to our study with median of 34.5 years.

It seems the age of disease presentation in Asian coun-

tries is lower, in contrast to western studies.

Approximately 80% of MF patients present in early

stages (ΙA, ΙB and ΠA) [15,20,29]. In agreement to other

studies, 88.9% of our patients were in stages ΙA and ΙB.

T-cell clonality was present in about 70% (50% - 100%)

of the biopsies diagnosed as MF [30-33]; this was 28.5%

in a study in Hong Kong [20]. In current study 61.1% of

cases showed clonality.

In present study high percentages of patients (38.9%)

were from an agricultural area near to Isfahan (Flavarjan).

A reason for this could be closeness of this city to Isfa-

han, so they can come to Isfahan easily; another might be

environmental pollution due to huge industries near that

area because according to previous studies environmental

exposure to chronic antigenic stimulation (e.g., industrial

chemicals, metals, and herbicides/pesticides) may have a

causative role [8,10,34].

Occupations involving sun exposure increases the risk

of MF [35]; but in this study 66.66% of patients hadn’t

had remarkable exposure to sun, radiations or chemicals,

although we hadn’t detail history of the patients’ expo-

sures.

In a study in the United States, CTCL incidence rate

correlated with high physician density, family income

and higher education that were related to more access to

health care. They also found higher incidence rate of MF

in blacks and concluded that immunogenetics or interac-

tion of genetic susceptibility and the environment in

CTCL, may have a role in MF incidence [18]. In our

study majority of the patients were educated up to the

high school degree and commonly were housekeepers

(women) and workers or salesmen (men).

In conclusion most of our patients presented in early

stages that were similar to other studies, while male: fe-

male ratio is different from other studies.

5. Acknowledgements

We thank Research Department of Isfahan University of

Medical Sciences for their, financial support and Mrs

hassankhani and other Alzahra dermatology clinic staff,

for their contribution in this study.

REFERENCES

[1] S. R. Parker and J. V. Bethaney, “Cutaneous T Cell Lym-

phoma-Mycosis Fungoides and Sezary Syndrome: An

Update,” G Ital Dermatol Venereol, Vol. 144, No. 4,

2009, pp. 467-485.

[2] E. Samuelson, “Cutaneous T-Cell Lymphomas,” Semi-

nars in Oncology Nursing, Vol. 14, No. 4, 1998, pp. 293-

301. doi:10.1016/S0749-2081(98)80007-7

[3] M. A. Weinstock and B. Gardstein, “Twenty-Year Trends

in the Reported Incidence of Mycosis Fungoides and As-

sociated Mortality,” American Journal of Public Health,

Vol. 89, No. 8, 1999, pp. 1240-1244.

doi:10.2105/AJPH.89.8.1240

[4] S. P. Patel and O. A. Holtermann, “Mycosis Fungoides:

An Overview,” Journal of Surgical Oncology, Vol. 22,

No. 4, 1983, pp. 221-227. doi:10.1002/jso.2930220403

[5] S. M. Worobec-Victor, “Cutaneous T Cell Lymphoma,”

New Jersey Medicine, Vol. 86, No. 5, 1989, pp. 395-400.

[6] N. Pimpinelli, E. A. Olsen, M. Santucci, E. Vonderheid,

A. C. Haeffner, S. Stevens, et al., “Defining Early Myco-

sis Fungoides,” Journal of the American Academy of

Dermatology, Vol. 53, No. 6, 2005, pp. 1053-1063.

doi:10.1016/j.jaad.2005.08.057

[7] H. S. Zackheim and T. H. McCalmont, “Mycosis Fun-

goides: The Great Imitator,” Journal of the American

Academy of Dermatology, Vol. 47, No. 6, 2002, pp. 914-

918. doi:10.1067/mjd.2002.124696

[8] M. M. Morales-Suarez-Varela, J. Olsen, P. Johansen, L.

Kaerlev, P. Guenel, P. Arveux, et al., “Occupational Risk

Factors for Mycosis Fungoides: A European Multicenter

Case-Control Study,” Journal of Occupational and Envi-

ronmental Medicine, Vol. 46, No. 3, 2004, pp. 205-211.

doi:10.1097/01.jom.0000116819.01813.8c

[9] A. S. Whittemore, E. A. Holly, I. M. Lee, E. A. Abel, R.

M. Adams, B. J. Nickoloff, et al., “Mycosis Fungoides in

Relation to Environmental Exposures and Immune Re-

sponse: A Case-Control Study,” Journal of the National

Cancer Institute, Vol. 81, No. 20, 1989, pp. 1560-1567.

doi:10.1093/jnci/81.20.1560

[10] Y. Wohl and E. Tur, “Environmental Risk Factors for

Mycosis Fungoides,” Current Problems in Dermatology,

Vol. 35, 2007, pp. 52-64. doi:10.1159/000106410

[11] S. H. Swerdlow, E. Campo, N. L. Harris, E. S. Jaffe, A. S.

Pileri, H. Stein, et al., “WHO Classification of Tumours

of Haemopoietic and Lymphatic Tissue,” IARC Press,

Lyon, 2008.

[12] E. Olsen, E. Vonderheid, N. Pimpinelli, R. Willemze, Y.

Kim, R. Knobler, et al., “Revisions to the Staging and

Classification of Mycosis Fungoides and Sezary Syn-

drome: A Proposal of the International Society for Cuta-

neous Lymphomas (ISCL) and the Cutaneous Lymphoma

Task Force of the European Organization of Research and

Treatment of Cancer (EORTC),” Blood, Vol. 110, No. 6,

Mycosis Fungoides: Epidemiology in Isfahan, Iran

232

2007, pp. 1713-1722. doi:10.1182/blood-2007-03-055749

[13] J. J. van Dongen, A. W. Langerak, M. Bruggemann, P. A.

Evans, M. Hummel, F. L. Lavender, et al., “Design and

Standardization of PCR Primers and Protocols for Detec-

tion of Clonal Immunoglobulin and T-Cell Receptor Gene

Recombinations in Suspect Lymphoproliferations: Report

of the BIOMED-2 Concerted Action BMH4-CT98-

3936,” Leukemia, Vol. 17, No. 12, 2003, pp. 2257-2317.

doi:10.1038/sj.leu.2403202

[14] M. W. Lee, “Characteristics of Cutaneous Lymphomas in

Korea,” Clinical and Experimental Dermatology, Vol. 28,

No. 6, 2003, pp. 639-646.

doi:10.1046/j.1365-2230.2003.01374.x

[15] C. Assaf, S. Gellrich, M. Steinhoff, D. Nashan, F. Weisse,

E. Dippel, et al., “Cutaneous Lymphomas in Germany:

An Analysis of the Central Cutaneous Lymphoma Regis-

try of the German Society of Dermatology (DDG),” Jour-

nal der Deutschen Dermatologischen Gesellschaft, Vol. 5,

No. 8, 2007, pp. 662-668.

doi:10.1111/j.1610-0387.2007.06337.x

[16] T. Ishiji, Y. Takagi and M. Niimura, “Cutaneous Lym-

phomas in Tokyo: Analysis of 62 Cases in A Dermatol-

ogy Clinic,” International Journal of Dermatology, Vol.

40, No. 1, 2001, pp. 37-40.

[17] N. McFadden, A. Nyfors, G. Tanum, A. Granholt, P.

Helme and G. Kavli, “Mycosis Fungoides in Norway

1960-1980. A Retrospective Study,” Acta Derm Venereol

Suppl (Stockh), Vol. 109, 1983, pp. 1-13.

[18] V. D. Criscione and M. A. Weinstock, “Incidence of Cu-

taneous T-Cell Lymphoma in the United States, 1973-

2002,” Archives of Dermatology, Vol. 143, No. 7, 2007,

pp. 854-859. doi:10.1001/archderm.143.7.854

[19] K. A. Gurney and R. A. Cartwright, “Increasing Inci-

dence and Descriptive Epidemiology of Extranodal Non-

Hodgkin lymphoma in Parts of England and Wales,” The

Hematology Journal, Vol. 3, No. 2, 2002, pp. 95-104.

doi:10.1038/sj.thj.6200154

[20] L. S. Ku and K. K. Lo, “Mycosis Fungoides—A Retro-

spective Study of 40 Cases in Hong Kong,” International

Journal of Dermatology, Vol. 44, No. 3, 2005, pp. 215-

220. doi:10.1111/j.1365-4632.2004.02362.x

[21] H. Hamideh, A. Hamideh, G. Farideh and Y. Neda,

“Demographic and Clinical Features of Mycosis Fun-

goides in Tabriz, Iran,” Iranian Journal of Medical Sci-

ences, Vol. 34, No. 2, 2009, p. 152.

[22] A. R. Khooei and M. R. Keramat, “Cutaneous Lympho-

mas and Pseudolymphomas: A Ten-Year Study at Emam

Reza and Omid Hospitals in Mashhad, Using Immuno-

histochemical and New Classification Methods,” Iranian

Journal of Dermatology, Vol. 31, No. 8, 2005, pp. 201-

210.

[23] H. M. Manuchehri and M. Rakhshan, “Characteristics of

Primary Cutaneous Lymphomas in Tehran, Iran (1998-

2004),” Journal of the European Academy of Dermatol-

ogy and Venereology, Vol. 20, No. 6, 2006, pp. 758-760.

doi:10.1111/j.1468-3083.2006.01536.x

[24] M. Salehi, Z. Azimi, F. Fatemi, P. Rajabi, M. Kazemi and

G. Amini, “Incidence Rate of Mycosis Fungoides in Isfa-

han (Iran),” The Journal of Dermatology, Vol. 37, No. 8,

2010, pp. 703-707.

doi:10.1111/j.1346-8138.2010.00899.x

[25] E. J. Kim, J. Lin, J. M. Junkins-Hopkins, C. C. Vittorio

and A. H. Rook, “Mycosis Fungoides and Sezary Syn-

drome: An Update,” Current Oncology Reports, Vol. 8,

No. 5, 2006, pp. 376-386.

doi:10.1007/s11912-006-0061-1

[26] P. L. Zinzani, A. J. Ferreri and L. Cerroni, “Mycosis Fun-

goides,” Critical Reviews in Oncology/Hematology, Vol.

65, No. 2, 2008, pp. 172-182.

doi:10.1016/j.critrevonc.2007.08.004

[27] E. S. Tan, M. B. Tang and S. H. Tan, “Retrospective

5-Year Review of 131 Patients with Mycosis Fungoides

and Sezary Syndrome Seen at the National Skin Centre,

Singapore,” Australasian Journal of Dermatology, Vol.

47, No. 4, 2006, pp. 248-252.

doi:10.1111/j.1440-0960.2006.00290.x

[28] Q. A. Alsaleh, A. Nanda, H. Al-Ajmi, H. Al-Sabah, M.

Elkashlan, S. Al-Shemmari, et al., “Clinicoepidemiologi-

cal Features of Mycosis Fungoides in Kuwait, 1991-

2006,” International Journal of Dermatology, Vol. 49,

No. 12, 2010, pp. 1393-1398.

[29] R. van Doom, C. W. Van Haselen, et al., “Mycosis Fun-

goides: Disease Evolution and Prognosis of 309 Dutch

Patients,” Archives of Dermatology, Vol. 136, No. 4,

2000, pp. 504-510. doi:10.1001/archderm.136.4.504

[30] S. E. Thurber, B. Zhang, Y. H. Kim, I. Schrijver, J.

Zehnder and S. Kohler, “T-Cell Clonality Analysis in

Biopsy Specimens from Two Different Skin Sites Shows

High Specificity in the Diagnosis of Patients with Sug-

gested Mycosis Fungoides,” Journal of the American

Academy of Dermatology, Vol. 57, No. 5, 2007, pp. 782-

790. doi:10.1016/j.jaad.2007.06.004

[31] C. Xu, C. Wan, L. Wang, H. J. Yang, Y. Tang and W. P.

Liu, “Diagnostic Significance of TCR Gene Clonal Rear-

rangement Analysis in Early Mycosis Fungoides,” Chi-

nese Journal of Cancer, Vol. 30, No. 4, 2011, pp. 264-

272. doi:10.5732/cjc.010.10344

[32] P. F. Hsiao, C. H. Hsiao, Y. C. Lin, M. P. Tseng, T. F.

Tsai and S. H. Jee, “Histopathologic-Molecular Correla-

tion in Early Mycosis Fungoides Using T-Cell Receptor

Gamma Gene Rearrangement by Polymerase Chain Re-

action with Laser Capture Microdissection,” Journal of

the Formosan Medical Association, Vol. 106, No. 4, 2007,

pp. 265-272. doi:10.1016/S0929-6646(09)60251-5

[33] S. L. Kandolf, B. Cikota, O. Stojadinovic, J. Basanovic,

D. Skiljevic, L. Medenica, et al., “TCRgamma Gene Re-

arrangement Analysis in Skin Samples and Peripheral

Blood of Mycosis Fungoides Patients,” Acta Derma-

tovenerol Alp Panonica Adriat, Vol. 16, No. 4, 2007, pp.

149-155.

[34] M. M. Morales-Suarez-Varela, J. Olsen, P. Johansen, L.

Kaerlev, P. Guenel, P. Arveux, et al., “Occupational Ex-

posures and Mycosis Fungoides. A European Multicentre

Case-Control Study (Europe),” Cancer Causes Control,

Vol. 16, No. 10, 2005, pp. 1253-1259.

doi:10.1007/s10552-005-0456-6

[35] M. M. Morales-Suarez-Varela, J. Olsen, P. Johansen, L.

Mycosis Fungoides: Epidemiology in Isfahan, Iran

233

Kaerlev, P. Guenel, P. Arveux, et al., “Occupational Sun

Exposure and Mycosis Fungoides: A European Multicen-

ter Case-Control Study,” Journal of Occupational and

Environmental Medicine, Vol. 48, No. 4, 2006, pp. 390-

393. doi:10.1097/01.jom.0000194160.95468.20