A rapidly growing breast tumour in a young woman

Abstract

A 31-year-old, otherwise healthy Caucasian woman presented with an 8-year history of a generalised pruritic rash only partially responding to topical steroids. Initial skin biopsies showed chronic inflammation with microabscesses, suggesting psoriasiform dermatitis along with epidermal hyperplasia, spongiosis, and chronic infiltrate with neutrophils indicating eczema. In February 2022, the rash on her right breast thickened, and by summertime, it began to ulcerate. By September 2022, the rapid progression of ulcerative lesions raised suspicion of advanced mammary Paget's disease (MPD) or soft tissue sarcoma. However, coarse needle biopsies revealed only granulomatous inflammatory changes, while MR mammography showed thickened tumorous skin tissue with oedema, and pathologically changed lymph nodes in the right axilla. Neither contrast-enhanced CT nor skeletal scintigraphy showed any sign of metastases. Dermatological examination in October 2022 revealed around 50% skin involvement, mainly annular patches, plaques and erosive tumours (Figure 1a). The right breast presented as an extensive ulcerating tumour with exudate (Figure 1b). Skin biopsies from the breast (Figure 2) and other lesions were performed in late September and mid-October 2022, respectively.

Skin biopsies confirmed folliculotropic and epidermotropic MF with Pautrier microabscesses (Figure 2) and numerous CD3 staining intraepidermal lymphocytes. Flow cytometry of peripheral blood and a bone marrow biopsy were unremarkable. The enlarged lymph node in the right axilla exhibited conserved architecture. However, the same monoclonal T-cell receptor gene rearrangement was found in both skin lesions and in the lymph node. Hence, her MF was classified as T3N1aM0B0/stage IIB.¹

Initial treatment entailed topical 0.05% clobetasol, radiotherapy with electron beams (8 Gy) to selected skin lesions, photon beams (24 Gy) to the involved breast, and bexarotene 450 mg once daily. The irradiated breast tumour tissue underwent necrosis, precipitating systemic Pseudomonas infection, which was treated with meropenem, gradual surgical debridement, and daily dressings containing 10% povidone iodine for 10 days (Figure 3). Urinary iodine concentration on day 10 exceeded the corresponding tolerable upper intake level (UL) by 47-fold, yet typical symptoms of high iodine uptake were absent. Iodine levels fell below UL within 5 weeks after cessation, and subsequent thyroid ultrasound demonstrated normal morphology. Observed transient secondary hypothyroidism was attributed to bexarotene treatment.

Bexarotene exhibited limited response and was replaced by interferon alpha 2-a therapy (180 µg/10 days) after 4 weeks, resulting in significant improvement. Six months after diagnosis, the patient's skin was almost clear of MF lesions (Figure 4). Subsequently, a matched related allogeneic stem cell transplantation (allo-SCT) was pursued for a potential cure.² However, MF lesions recurred by day +58 post allo-SCT. Around day +71 of allo-SCT, she experienced diarrhoea and epigastric pain, but endoscopy with biopsies excluded graft-versus-host disease (GvHD). Cyclosporine was tapered rapidly and stopped by day +111 without evidence of GvHD. Radiation therapy targeting tumours was initiated to achieve an abscopal effect on other lesions. Due to further progression of MF lesions, interferon alpha 2-a (135 µg/week) was reintroduced, leading to disease regression. Consolidation with donor lymphocyte infusion from her sibling donor is imminently planned.

MF represents the predominant form of cutaneous T-cell lymphoma. Typically diagnosed in the fifth decade, with a male-to-female ratio of 2:1. MF exhibits diverse clinical, histological, and immunophenotypical characteristics. Most patients experience persistent, slowly progressive skin lesions and pruritus.³ Solid tumours ≥1 cm in diameter develop in 20% of patients,⁴ but extensive tumorous changes are infrequently reported, usually occurring in older individuals as a progression from earlier-stage MF.⁵ Breast involvement in MF is uncommon, often described as mild to moderate changes^{6, 7} or large masses in older individuals,⁸ underscoring the unusual nature of this case.

MPD is a noninvasive breast malignancy affecting the nipple-areolar complex, usually in females over 50, accounting for 1%–3% of all primary breast cancers and is often associated with underlying carcinoma. Advanced MPD often presents with ulcerating breast tissue.⁹ MPD and MF share similar initial presentations, mimicking benign dermatological conditions like eczema or dermatitis, leading to potential misdiagnosis and delayed treatment. Both may initially respond to corticosteroids, further obscuring the underlying malignancy.

In this case, the patient's pruritic rash, partially responsive to topical steroids mimicked dermatitis, delaying suspicion of MF. Chronic inflammation and eczematous changes in prior biopsies, further complicated early recognition. As the disease progressed and began to resemble advanced MPD, the diagnostic process intensified, ultimately confirming MF.

This case also highlighted complications, such as radiotherapy-induced necrosis leading to a severe Pseudomonas infection of the breast tissue. The infection was managed with iodine dressings due to severe pain from acetic acid use, but elevated iodine levels required careful monitoring. Although locally applied iodine is considered safe for wound treatment, some reports suggest potential post-application toxicity.¹⁰ We advocate considering the vascularity of treated areas, as highly perfused wounds may exhibit elevated iodine uptake, which we believe was the case for our patient.

In summary, this case emphasises the challenges in the diagnosis of advanced-stage MF, particularly when it mimics other malignancies like MPD. A multidisciplinary approach is critical in managing such complex cases, with ongoing monitoring and adaptive therapies essential for optimising outcomes. Based on the reviewed literature, this is the first report of aggressive tumour-stage MF resembling advanced MPD in a young woman.

K. A. Zub Carlsson: Writing—original draft; writing—review and editing, methodology; investigation; visualisation; project administration; corresponding author. S. Spetalen: Review and editing; visualisation. K. M. A. S. Endre: Review and editing. T. O. A. Hegna: Review and editing. G. E. Tjønnfjord: Review and editing. G. Lehne: Review and editing. Ø. Sandangerndanger: Writing—original draft; writing—review and editing; methodology; investigation; visualisation; project administration; supervision.

S. Spetalen received an honorarium from EUSA Pharma for delivering a lecture. K. M. A. S. Endre received honoraria from Sanofi, Perrigo, and AbbVie for presentations and served as a member of the Advisory Boards for Sanofi, Almirall and Incyte. The remaining authors declare no conflicts of interest.

The patient in this manuscript has given written informed consent for the use deidentified, anonymized, aggregated data and case details (including photographs) for publication. Ethical Approval: not applicable.