Dermatology Online Journal

Bullous mycosis fungoides: A case report
Balighi Kamran¹, Moeineddin Fatemeh¹, Rajaee Ahmadreza¹, Nikoo Azita²
Dermatology Online Journal 14 (2): 11

1. Departement of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran. Fmoeineddin@razi.tums.ac.ir 2. Departement of Pathology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Abstract

Mycosis fungoides (MF) on extremely rare occasions is associated with vesiculobullous eruptions. We describe a 74-year-old man with previous documented histopathologic diagnosis of poikilodermic-type MF who recently developed flaccid acral bullae on erythematous MF plaques and on normal appearing skin. Histopathology and direct immunofluorescent studies revealed extensive lichenoid changes with intraepidermal bullae. Atypical lymphocyte infiltration was present at the dermoepidermal junction, in bulla fluid, and on the peripheral blood smear, but in lymph node and bone marrow tissue specimens atypical lymphocytes were absent. The plausible cause of these blister formations in cutaneous lymphoma bullosa may be from excessive epidermotropism or toxicity of the tumoral infiltrate.

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Clinical synopsis

A 74 year-old man presented with progressive development of flaccid bullae on his trunk and extremities. He had generalized scaly patches and plaques associated with poikilodermic lesions on several areas of his body.

On examination he had some purple pruritic plaques with underlying poikilodermic features (Fig. 1). Several large bullae were present on the patient's legs, forearm, and trunk (Fig. 2). Nikolsky sign was negative. Hepatosplenomegaly was not obvious but some enlarged axillary lymph nodes, approximately 1 x 1.5 cm, were detected.

Figure 1	Figure 2
Figure 1. Mycosis fungoides with generalized poikilodermic lesions Figure 2. Large bulla on a poikilodermic base on the patient's leg

The patient suffered from some other associated medical illnesses such as diabetes mellitus, hypertension, and heart failure, all partially controlled with medication.

Past medical history includes the presence of multiple scaly erythematous patches and plaques on lower extremities and gluteal region for 8 years, which have undergone treatment for eczema. In addition, there was one episode of hospitalization due to erythrodermic pattern of lesions 5 years prior.

Histopathologic evaluation of the mentioned lesions revealed nonspecific chronic dermatitis that contained the criteria neither for mycosis fungoides nor for any other specific dermatologic diagnosis. Because the patient's lesions had partially improved under treatment with topical corticosteroids during the course of admission, he was discharged with a recommendation to repeat the biopsy at a followup visit after 6 months. The patient did keep his followup appointment. Later he came to our dermatology clinic with multiple bullous and plaque type lesions.

He was admitted to our hospital and several lesional punch biopsies from bullous and non-bullous skin lesions were taken. Perilesional samples were also obtained and sent for DIF (direct immunofluorescent) study. Furosemide was omitted from the list of his medication with suspicion of bullous drug eruption, however, there was no change in the aggravating course of the disease.

Figure 3	Figure 4
Figures 3-4. Subepidermal cleft resulting from "lichenoid reaction" and multiple atypic atypical lymphocytes

Histopathologic study of the nonbullous lesions was compatible with poikilodermic mycosis fungoides (Fig. 3) while the microscopic feature of the bullous lesions revealed subepidermal cleft resulting from extensive hydropic change of the basal layer cells. This indicated lichenoid reaction. Several atypical lymphocytes were also noted (Fig. 4). The DIF and IIF studies were also negative. The atypical lymphocytes were found also in peripheral blood smear and lymph node samples. Imaging studies and flocytometeric abnormality were negative.

Ultimately, the patient underwent treatment with chlorambucil and low-dose prednisolone with the diagnosis of bullous MF because other, more common bullous disorders, were ruled out.

Despite the remarkable improvement in bullous lesions during the course of admission, the patient experienced an abrupt and generalized bulla formation and died with cardiogenic shock presentation 2 months later.

Discussion

Mycosis fungoides is the most common subtype of cutaneous lymphoma. Skin lesions are the initial presentations of this type of lymphoma [1, 2]. Mycosis fungoides has variable phenotypic and histopathologic presentations. Clinical course, prognosis, and management differ from one patient to another [3].

Vesiculobullous lesions are an extremely rare manifestation of MF. Kaposi reported the first case of bullous MF in 1887 and described it as pemphigus-like mycosis fungoides [4].

Special causes of bulla formation in MF include the following:

• Coexistence of bullous pemphigoides or pemphigus foliaceous [5].
• Treatment with topical mechlorethamine or systemic interferon, both of which can induce bullous eruption [6, 7].
• Treatment of MF with PUVA [8, 9, 10].

Bullous lesions in MF may resemble erythema multiforme because of its targetoid appearance [11]. Infection, burn, allergic contact dermatitis, and autoimmune bullous disorders can induce bullous lesions in MF cases, and the diagnosis of bullous MF can be made only after the above differential diagnoses are ruled out.

Bullous MF commonly presents in the elderly (with an average age of about 66 years) and has no gender predominance [12, 13, 14]. Bullous lesions can superimpose on typical skin lesions of classic MF and also on Sezary syndrome [15, 16]. These flaccid or tense blisters can appear either on normal skin or within MF patches and plaques in localized or generalized pattern. Trunk and limbs have been predominantly affected in bullous MF.

Bullous lesions usually appear months to years after the classic MF patches and plaques but in some cases present as the primary manifestation [17, 18, 19, 20].

MF blisters are seen in different location in skin: subcorneal, intraepithelial and subepidermal; DIF and IIF studies are also negative.

In addition to the above findings, the presence of epidermotropism and cerebriform atypical lymphocytes in microscopic studies of the bullous tissue samples, are the cardinal guide to the diagnosis of bullous MF [21].

There may be two possible mechanisms for blister formation as follows:

• Direct mechanical effect of tumoral lymphocyte accumulation between epidermal or basal layer cells leading to loss of coherence between adjacent cells
• Release of some lymphokines and their interference with normal cohesion of keratinocytes [22, 23]

Although negative immunofluorescent study and subcorneal blisters were similar to all previous reports of bullous MF, typical appearance of epidermotropism and abscess formation from tumor cell invasion was not found in this case. Yet, the main pathologic change included severe lichenoid reaction and moderate atypical lymphocyte infiltration, the appearance of which is reported in the early stages of MF. The above findings and concomitant presence of bullae suggest that the second mechanism may play a more important role in this case.

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