INTRODUCTION
Mycosis fungoides: Mycosis fungoides (MF) is a primary
cutaneous T-cell lymphoma. It represents the most common type of
extranodal non-Hodgkin lymphomas 12. Follicular or folliculotropic MF (F-MF, also known
as follicular T-cell lymphoma, follicular MF, MF-associated mucinosis,
or pleiotropic MF) is an under-recognized subtype of MF. It is
characterized histologically by folliculotropism (histologically
analogous to epidermotropism) with malignant T cells, with or without
associated follicular mucinosis3. In 2005, The
WHO/EORTC considered F-MF as a variant of MF in their classification4-7.
Mycosis fungoides in the Kingdom of Saudi Arabia: In the
Kingdom of Saudi Arabia, few studies are available about MF and F-MF1,8-12. AlGhamdi et al examined the clinicopathologic
features of MF in 43 cases of immunohistologically confirmed MF. The
average age was 33.5 years was reviewed. The male-to-female ratio was
2:1. Most of the cases presented in an early-stage (I and II) MF. Most
of the patients had classic MF and other subtypes included hypopigmented
MF and other variants. The patients were followed up for a duration of
27.6 months. The follow-up data indicated that few patients recovered
(9.5%) patients recovered; whereas the majority (83.3%) had persistent
MF skin lesions. A single patient had the extracutaneous disease;
whereas only two patients died of MF 8.
Al-Dawsari et al examined the surgical pathology records of Saudi
patients from 1995 to 2014 at the Johns Hopkins Aramco Healthcare Center
(Eastern Province of KSA). This medical facility is the healthcare
provider for the employees working at Saudi Aramco company and their
dependents in the Eastern Province of Saudi Arabia. The total number of
primary skin tumors was 204 and out of them 22 cases were MF10. Albasri et al examined the pattern of skin cancer
in the Madinah region of KSA. Among the 202 cancer cases examined in
their series, there were 14 (6.8%) cases of MF. The mean age of the
patients was 30.7 years with a male-to-female ratio of 11:3. The
distribution of the MF skin lesions included: 4 cases (head and neck), 3
cases (upper limb), and 7 cases (lower limb) 11.
Alsaif et al described the Leser-Trelat sign (sudden appearance of
seborrheic keratosis) in a 60-year-old Saudi male patient with MF. The
lesions appeared on the face and back 12. Alojail et
reported the clinical features and treatment regimens in 34 cases of MF
in KSA. The cases included both hyperpigmented (11 cases) and
hypopigmented (21 cases) MF, poikilodermatous MF, and pagetoid
reticulosis (a single, each). The treatment regimens included
phototherapy Narrowband UVB (NB-UVB) in combination with topical
corticosteroids, phototherapy NB-UVB in combination with the topical
corticosteroid, and phototherapy NB-UVB with topical corticosteroid and
systemic acitretin 1.
Alghubaywi et al examined all MF cases diagnosed at King Abdulaziz
Medical City in KSA (January 2016 to July 2022). A total of 73 patients
were included in their study. The incidence of MF was slightly higher in
females (male to female ratio: 1: 1.3). The average age was 44 years.
The most common MF subtypes included classic MF, followed by
hypopigmented MF. Most of the cases were presented at an early-stage MF
(IA, IB, and IIA). The treatment option was mainly in the form of
topical steroids. Immunohistological staining of CD4+/CD8+ with CD8
predominance was common and this may reason for the favorable disease
outcome 13. These authors also indicated that MF was
under-recognized with 20% of the patients with MF initially
misdiagnosed as atopic dermatitis. The correct diagnosis of MF was
rendered within a mean of 33 months from the time of presentation to the
Dermatology clinics. The authors reasoned the delay in the diagnosis of
MF the fact that chronic dermatitis and MF share several clinical
manifestations such as the presence of pruritic, erythematous, scaly
plaques 13. A summary of the previous studies is shown
in Table 1.
Follicular mucinosis: Follicular mucinosis, i.e. accumulation
of mucin in the epithelium of the hair follicles can be either a primary
idiopathic disorder or an associated event with several inflammatory
conditions (such as chronic spongiotic dermatitis), benign or malignant
neoplasms14-16. In 1957, Pinkus first described mucin
deposits in the follicular epithelium (alopecia mucinosa) that are
associated with folliculotropism, i.e., infiltration of the epithelial
cells of the outer hair sheath by atypical lymphocytes17. In 1959, the term follicular mucinosis was
introduced by Jablonska 18. There are two clinical
types of follicular mucinosis: idiopathic follicular mucinosis and
lymphoma-related follicular mucinosis, i.e., F-MF. The latter can be
separated from the classical MF on a clinical and histological basis2,19,20. Currently, there is no specific therapy for
idiopathic follicular mucinosis and the skin lesions can resolve
spontaneously within a period of 2 to 24. Some therapeutic options
include steroids (topical, intralesional, and systemic steroids),
photodynamic therapy, antimalarials, interferon, and dapson21,22.
Folliculotropic mycosis fungoides: F-MF represents the most
common non-classic variant of MF, representing approximately 10% of the
cases of MF 23. It usually shows a male predominance
and most of the cases occur in adults 24. Its clinical
findings include follicle-based infiltrated erythematous grouped papules
resembling acne or keratosis pilaris, patches, plaques, and tumor-like
lesions with follicular accentuation 2,20,25. Other
clinical presentations include prurigo-like lesions, pseudotumors,
lichen spinulosus-like lesions, rosacea-like lesions, and lupus
tumidus-like plaques 26. Pruritis is a common
complaint and it is aggravated by superinfection by staphylococcus auras
resulting in pyoderma 25. The lesions of F-MF vary
from solitary lesions to extensive lesions giving the appearance of a
leonine face 23. The head and neck region is the most
commonly affected site. Other sites include the trunk, and the
extremities 17. The features of F-MF are seen in
nearly 10% of the patients with MF 2,20,25. The
salient histological features of F-MF include perivascular and
peri‑adnexal dermal lymphocytic infiltrates with variable infiltration
and destruction of the follicular epithelium by small, medium‑sized, or
large-sized lymphocytes with hyperconvoluted nuclei (cerebriform
nuclei). The epidermis is usually spared. Other histological findings
include follicular mucinosis, Pautrier’s Micro-abscess, follicular
plugging, tagging of the atypical lymphocytes along the follicular
epithelium, peri-eccrine infiltrate of atypical
lymphocytes23,26. Immunohistochemistry usually reveals
prominent CD3 positive infiltrate, with
a predominance of CD4 positive lymphocytes over rare CD8 positive
T-cells. CD7 expression is reduced or completely lost. Molecular
analysis (T-cell receptor-γ gene rearrangement) reveals a monoclonal
T-cell population23,26-28. The therapeutic options in
F-MF include photochemotherapy combined with interferon alpha-2a and
retinoids. Other options include local radiotherapy, topical imiquimod,
and total body electron beam irradiation 23.
Several F-MF case reports were presented in the literature. Monopoli et
al described two adult patients with F-MF. The clinical manifestations
included alopecia and follicular erythematous papules, and comedones and
cysts, respectively. The histological findings included folliculotropic
atypical T-cell infiltrate that extends to the epidermis. There was no
associated mucinosis. Clonality analyses revealed the oligo/monoclonal
nature of the T-cell lymphocytic infiltrate 27.
Rajalakshmi et al examined four cases of F-MF affecting the skin of the
face. The mean age of the patients was 17.5 years and there were no
differences in gender distribution. The lesions were in the form of
hypopigmented patches or erythematous plaques. Two patients had
associated alopecia. The salient histological finding included
folliculotropism, mucin deposition around the hair follicles, lymphocyte
tagging with haloes, atypical lymphocytes with
hyperconvoluted/cerebriform nuclei, and infiltration of the eccrine and
sebaceous glands by atypical lymphocytes. Other histological features
included the presence of epithelioid cells, parakeratosis, and a
prominent infiltrate of eosinophils 29. Magro et al
reported 6 cases of unilesional follicular MF. All the patients were
males with a mean age of 28 years. The patients were presented with a
solitary lesion on the face and scalp (five patients) and trunk (a
single patient) that persisted for a few months. There were follicular
prominence and alopecia. On histology, there was an atypical
folliculotropic lymphocytic infiltrate associated with follicular
mucinosis. Immunohistology revealed a high CD4: CD8 ratio and loss of
CD7 expression. A single untreated case developed similar lesions over
the skin of the thigh and buttock after 3-4 years 28.
F-MF usually occurs in adults with an average age at the time of
diagnosis of 60 years 30. F-MF is exceptionally rare
in children and adolescents. Mantri et al reported a case of F-MF in a
16-year-old boy who presented with 6x7 cm plaque on the forehead for a
2-month duration. Immunohistological examination revealed dense atypical
T-cell lymphocytes invading and destroying the hair follicles.
Follicular mucinosis was also seen. Most of the neoplastic cells were
CD4-positive T- T-lymphocytes with scarce CD8-positive T cells around
the hair follicles. Treatment was in the form of a spot electron beam
and the lesion completely resolved within 2 months 30.
Interestingly, Emge et al reported a case of F-MF in a 6-year-old boy.
The lymphoma was associated with idiopathic follicular
mucinosis31.
Taken collectively, these previous reports indicated that F-MF is a rare
and aggressive form of MF that has a worse prognosis compared to
conventional MF. It usually affects the head and neck region in adults.
It has distinct histological features and may or may not be associated
with follicular mucinosis. F-MF has several clinical presentations and
many histological faces. Therefore, it is often misdiagnosed, or
diagnosed with much delay at an advanced stage as compared to the
conventional MF.
Herein, we report a case of F-MF in a middle-aged male patient. To date
and to be best of our knowledge, this is the first case of F-MF to be
reported in the Southern region (Asir region) of the KSA. The
clinicopathologic features were discussed.