CD30-negative bullous mycosis fungoides with large cell transformation: A case report

Dear Editor, Mycosis fungoides (MF) is the most prevalent form of cutaneous T-cell lymphoma, arising from peripheral epidermotropic memory T-cells characterized by CD45RO positivity. These neoplastic cells typically express the T-cell receptor (TCR) and display a CD4+ immunophenotype. MF exhibits a broad spectrum of clinical presentations, which has led to the classification of several distinct subtypes. Bullous MF represents one of these rare variants.[1] Herein, we present the case of MF exhibiting large cell transformation (LCT). A 42-year-old female patient presented to our clinic with recurrent tumoral lesions on her trunk and extremities. Despite prior treatment with systemic antibiotics and corticosteroids, the lesions persisted. On physical examination, widespread ulcerated violaceous plaques were observed across the body, along with a few intact bullae and remnants of bullous lesions [Figure 1]. Multiple skin biopsies were performed. Histopathological examination revealed an intraepidermal vesicle associated with diffuse lymphocytic infiltration in the dermis. The epidermis demonstrated the presence of large epidermotropic lymphocytes with prominent perinuclear halos, while smaller lymphocytes were distributed within the dermis. High-power magnification revealed the features of LCT, characterized by lymphocytes with irregular nuclear contours and marked hyperchromasia. Immunohistochemical staining showed predominant CD4 positivity in both small and large lymphocytes, while CD8 expression was limited to a small subset of cells. CD30 staining was negative [Figure 2]. Molecular studies confirmed T-cell clonality through TCR gene rearrangement analysis, supporting the diagnosis of large cell transformed MF. The diagnosis of bullous MF with LCT was confirmed based on the integration of clinical, histopathological, and molecular findings. Staging investigations revealed axillary lymphadenopathy, and excisional biopsy demonstrated dermatopathic lymphadenitis. The patient was staged as T3N1M0, corresponding to stage IIB. Despite the initiation of systemic methotrexate therapy following diagnosis and staging, the disease progressed rapidly, and the patient died several months later.Figure 1: (a) Multiple ulcerated plaques on the abdomen and trunk. An intact bulla is indicated by the blue arrow (b) ıntact bulla on the right upper arm (blue arrow) (c) widespread ulcerated plaques and nodules on the right lateral trunk and arm (d) extensive ulcerated plaques on the left lateral trunk, remnants of bullous lesions are indicated by green arrows.Figure 2: (a) Intraepidermal vesicle formation with diffuse lymphocytic infiltration in the dermis (H and E, ×40) (b) large epidermotropic lymphocytes with halo in the epidermis and small lymphocytes in the dermis (H and E, ×200) (c) large cell transformation with irregular nuclear contours and hyperchromasia (H and E, ×400) (d) predominant CD4 staining of small and large lymphocytes (immunperoxidase ×10) (e) Small percentage of CD8 staining (immunoperoxidase ×10). (f) CD30 negativity (immunperoxidase ×10).Reports of bullous MF in the literature are exceedingly rare. Since bullae can arise secondary to other causes during the course of MF, Bowman et al.[2] established the diagnostic criteria for bullous MF, emphasizing the exclusion of other potential causes of bullae formation. In accordance with the diagnostic criteria, alternative causes of blister formation were systematically excluded. The patient had no recent history of drug exposure, microbiological cultures were negative, and histopathological findings were not compatible with autoimmune blistering diseases. The presence of epidermotropic atypical lymphocytes, intraepidermal blistering, and T-cell clonality confirmed by gene rearrangement analysis supported the diagnosis of bullous MF. LCT in skin or lymph node biopsies is characterized by the presence of large cells, which are at least four times the size of small lymphocytes, and these cells can be either CD30+ or CD30− in at least 25% of the dermal infiltration. This transformation is often associated with the presence of tumors. While LCT has been reported to occur at all the stages of cutaneous T-cell lymphoma, it is more frequently observed in patients with advanced stages of the disease. In previously reported cases of bullous MF, CD30 positivity has been observed.[3,4] However, our case involved a CD30-negative bullous MF with LCT. In conclusion, LCT may occur in cases of bullous MF, and this transformation can be observed in the absence of CD30 expression. Only a few cases of bullous MF with LCT have been reported in the literature. In the case reported by Sun et al.,[3] a CD30-positive patient showed rapid deterioration despite brentuximab therapy. Another report by Porntharukcharoen et al.[4] also described CD30 positivity and an aggressive clinical course. Consistent with the literature, our patient experienced rapid progression and poor therapeutic response, underscoring the unfavorable prognosis associated with this rare MF variant.[5] The precise mechanism underlying blister formation in bullous MF is not fully understood. However, it has been proposed that marked epidermotropism and infiltration of atypical T-lymphocytes may lead to keratinocyte apoptosis and disruption of the dermoepidermal junction, resulting in intraepidermal or subepidermal clefting. This mechanism is likely responsible for bullae formation in our case. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.