Folliculotropic Mycosis Fungoides in an Adolescent: A Rare Case.

Folliculotropic mycosis fungoides (FMF) is an uncommon and aggressive form of mycoses fungoides with preferential involvement of head and neck region. Lesions of FMF present as erythematous plaques or papules with follicular prominences, acneiform lesions, cysts, nodules, patches of scarring alopecia, and prurigo-like lesions. The mean age of diagnosis is at 60 years and it is extremely rare in childhood and adolescence. We report a case of a 16-year-old male patient who presented with a 2-month history of an asymptomatic erythematous infiltrated plaque over the forehead. Histological examination was consistent with diagnosis of FMF. He was successfully treated with local electron beam therapy.

What was known?

Folliculotropic mycosis fungoides (MF) is very rare and aggressive variant of MF, which usually occurs in old age and has a worse prognosis than classical MF.

Introduction

Folliculotropic mycosis fungoides (FMF), also termed as pilotropic or follicular MF, is a rare and aggressive form of MF, which usually involves head and neck region and accounting for <10% cases of MF.[1] It is characterized histopathologically by the presence of atypical lymphocytic infiltrates in the hair follicles and follicular mucinosis. The disease is commonly underrecognized by both dermatologist and pathologist, especially in early stages. Most relevant feature of FMF is the deep, follicular, and perifollicular localization of neoplastic cells which make them less accessible to skin targeted therapies.[2] Mean age of presentation is around 60 years and it is extremely rare in childhood and adolescent with very few cases reported in the literature. We report a case of a 16-year-old male patient with FMF, who was treated successfully with local electron beam therapy.

Case Report

A 16-year-old male patient presented with a single painless red raised lesion over the forehead of 2 months duration slowly increasing in size. There was a history of trauma over the same site 2 months ago. There was no history of itching, pain, or loss of sensation over the lesion. Past medical history was not significant.

On clinical examination, a single firm well-circumscribed erythematous infiltrated plaque of size 6 cm × 7 cm was seen over the forehead [Figure 1]. Sensations over the plaque were intact. There were no thickened nerves or feeding nerve palpated in/around the lesion. Lymphadenopathy was not appreciated. No Significant skin lesions were appreciated on other body areas. A differential diagnosis of tuberculoid leprosy, alopecia mucinosa, deep fungal infection, leishmaniasis, and sarcoidosis were considered.

Figure 1

A single firm well-circumscribed erythematous infiltrated plaque of size 6 cm × 7 cm was seen over the forehead

All hematological, biochemical, radiological investigations and peripheral blood smear were within normal limits. Fine-needle aspiration cytology of the lesion showed hemorrhagic background with few lymphocytes, occasional macrophages, and occasional cluster of giant cells. Ziehl–Neelsen stain was negative for acid fast bacilli and Gomori methenamine silver stain was negative for fungi.

Histopathological examination of a 4 mm skin biopsy showed multiple dilated and distorted hair follicles in the dermis with inflammatory infiltrate on low power magnification [Figure 2]. On higher magnification, distortion and destruction of hair follicular structures with moderately dense infiltrate of atypical lymphocytes (larger with more cytoplasm and irregular nuclear contour) and mucin deposition was seen. Mild epidermotropism was present with haloed lymphocytes in epidermis [Figure 3]. No Pautrier microabscess was seen. No eccrine gland infiltration was seen. Stains for mycobacteria and fungi were negative.

Figure 2

Multiple dilated and distorted hair follicles in the dermis with inflammatory infiltrate (H and E, ×40)

Figure 3

(a) Moderately dense infiltrate of atypical lymphocytes and mild epidermotropism. Haloed lymphocytes are seen in epidermis (H and E, ×400). (b) Destruction of hair follicle and mucin deposition (H and E, ×400)

Immunohistochemistry (IHC) showed predominance of CD4 lymphocytes around hair follicles and paucity of CD8 cells. CD4:CD8 ratio was 8:1 [Figure 4].

Figure 4

Predominance of CD4+ cells and paucity of CD8+ cells around follicles with CD4:CD8 ratio of 8:1 (immunohistochemistry, ×400)

Based on characteristic histopathological findings of follicular mucinosis with folliculotropism of predominantly CD4 lymphocytes, a final diagnosis of FMF was made. Whole body computed tomography scan and bone marrow biopsy of the patient did not show any systemic involvement. Hence, the patient was staged as Stage 1a (tumor-node-metastasis) and started on spot electron beam therapy under supervision of radiation oncologist (12 Gy in three fraction delivered on alternate days). Patient tolerated the treatment well with minimal side effects in the form of mild erythema and itching. There was complete resolution of the lesion within 2 months. There was no recurrence on monthly follow-up till 2 years.

Discussion

MF is the most common form of cutaneous T-cell lymphoma. FMF is an uncommon and aggressive subtype of MF accounting for <10% cases of MF.[1] It is characterized by the presence of folliculotropic infiltrates with preferential involvement of head and neck.[2] Gender distribution shows male:female ratio of 3:1.[3] The mean age of presentation is 55 years in Western literature. However, one Indian cases series of four cases of FMF reported a mean age of 17.5 years with less aggressive disease course and better treatment outcomes.[4] To the best of our knowledge, MF is extremely rare in adolescent and children with very few cases reported worldwide.

Lesions are erythematous plaques or papules with follicular prominences, acneiform lesions, cysts, nodules, patches of scarring alopecia, and prurigo-like lesions. Lesions may be associated with severe pruritus.[5] Several patients may have concurrent lymph node involvement or other hematological malignancy. Circulating Sezary cells may be seen on peripheral blood smear even in the absence of erythroderma. Differential diagnosis or plaque lesions are leprosy, sarcoidosis, leishmaniasis, alopecia mucinosa, and deep fungal infections. For acneiform lesions, acne and milia are considered as differentials.

The morphological spectrum of FMF is broad and differ from the patches and plaques of classical MF. Hence, a high index of clinical suspicion is required for diagnosis. Histopathological examination and IHC are essential for confirmation. Flow cytometric immunotyping and T-cell receptor gene rearrangement analysis of involved skin or peripheral blood demonstrate monoclonality of T-lymphocytes.[6]

Histopathology of FMF is characterized by atypical lymphocytic infiltration of hair follicles with or without follicular mucinosis and epidermotropism. Presence of eosinophils and granuloma may be seen and necessitates exclusion of infectious etiology.[4] In some cases of FMF, infiltration of eccrine glands also occurs along with hair follicles when the term “syringotropic MF” is used.[3] Mechanism of folliculotropism is unknown and may be due to specific cell surface antigens of T cells or abnormal follicular epithelium. IHC shows predominance of CD4 lymphocytes. Increased CD1a+ Langerhans cell density has also been reported.[7]

Prognosis of FMF is poor compared to classical MF. Early disease has 10 year survival of 82% and 42% by 15 years. Late disease has similar prognosis as classical MF (91% at both 5 and 10 years).[5]

Treatment modalities for early disease include narrowband ultraviolet B, local plus ultraviolet A therapy with interferon alpha or retinoids, local radiotherapy, local electron beam therapy, and topical nitrogen mustard. For advanced disease chemotherapy (CHOP), alemtuzumab, irradiation, and allogeneic bone marrow transplant are used.[89]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

The case is being reported for its rarity in India. Furthermore, folliculotropic mycosis fungoides usually occurs in old age and is known to have aggressive course, but our patient was a teenage boy with less aggressive course and excellent prognosis.