Primary Cutaneous Anaplastic Large Cell Lymphoma (PC-ALCL)

Introduction

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) represents about 8% of cutaneous lymphoma cases. Unlike systemic ALCL, PC-ALCL typically follows an indolent course and although cutaneous relapses are common, an excellent prognosis is usually maintained. It is histologically characterized by diffuse, cohesive sheets of large CD30-positive (in > 75%) cells with anaplastic, pleomorphic or immunoblastic appearance. Clinical features typically include solitary or localized nodules or tumours (often ulcerated). Multifocal lesions occur in about 20% of cases. Extracutaneous disease occurs in about 10% of cases, usually involving regional lymph nodes. Patches and plaques may also be present and some degree of spontaneous remittance in lesions may also be seen [1–3].

Objective

The aim of this paper is to present the case of primary cutaneous anaplastic large cell lymphoma in an 83-year-old patient to discuss the characteristic clinical and histopathological features of this rare skin disorder.

Case report

An 83-year-old female patient was admitted to the Dermatology Department for the diagnosis of multiple, multifocal red-brown nodules with central ulcerations located on the skin of the trunk, upper limbs, and lower limbs (fig. 1). The skin lesions had been present for several months, and numerous scars from earlier eruptions were visible, raising consideration of lymphomatoid papulosis (LyP) in the differential diagnosis. In the past, the patient did not have a history of cancer and did not undergo radiotherapy or chemotherapy. Histopathological examination showed the atypical lymphocytic cells with anaplastic morphological features exhibit numerous blastoid cells with prominent and enlarged nucleoli and visible high mitotic activity, extensively infiltrating the dermis, subcutaneous tissue and epidermis (fig. 2). Immunohistochemical examination revealed the expression of CD30+ antigen in over 75% of the infiltrating cells (fig. 3). The cell proliferation marker Ki-67 was positive in approximately 70–80% of the neoplastic cells (fig. 4). ALK1 (CD246) was negative (fig. 5). In laboratory tests, only slightly elevated lactate dehydrogenase activity was found (LDH 252 U/l). Considering the appearance of the skin lesions, the results of additional tests and the histopathological findings, a diagnosis of primary cutaneous anaplastic large cell lymphoma was established. In the computed tomography (CT) scans of the head, neck and abdomen, no abnormalities were detected. The chest CT scan revealed a tumour in the left breast accompanied by enlarged axillary lymph nodes. Breast ultrasound revealed a hypoechoic focal lesion with irregular borders assessed as BI-RADS category 5. A core needle biopsy of the focal breast lesion was performed, yielding a histopathological result of invasive ductal carcinoma, not otherwise specified (NOS), grade 2. The patient was referred to an oncology centre to determine the optimal therapy.
Despite the diagnosis of pc-ALCL, no targeted therapy was implemented for this condition. During observation, the skin lesions spontaneously resolved without treatment. Photographic documentation (fig. 6) obtained 20 weeks after the initial presentation shows complete resolution of the nodules, with residual post-inflammatory changes visible on the trunk and limbs. This spontaneous regression is a notable characteristic of pc-ALCL and is an essential factor in differentiating it from other CD30+ lymphoproliferative disorders, such as LyP. Unlike LyP, no new lesions developed during the observation period, and the existing lesions did not recur. However, the possibility of coexistence of pc-ALCL and LyP cannot be entirely excluded as LyP can have variable clinical courses, and a 20-week relapse-free period does not definitively rule it out.
The patient’s clinical course underscores the importance of careful observation in cases of pc-ALCL, particularly when considering its self-regressive nature. This case highlights the necessity of differentiating pc-ALCL from LyP and other cutaneous lymphomas through a combination of clinical, histopathological, and immunohistochemical findings; as well as the necessity for imaging studies to detect a potential coexisting malignant condition. The inclusion of photographic evidence of the lesion resolution may provide additional clarity in future diagnostic and therapeutic approaches.
Additionally, this case emphasises the importance of interdisciplinary collaboration in the diagnosis and management of patients with multiple malignancies.

Discussion

PC-ALCL presents as a rapidly growing solitary nodule or localized group of nodules that may ulcerate. It typically occurs in the sixth decade of life, has a slight male predominance, and may be associated with immunosuppression. The nodules are larger than lymphomatoid papulosis, rarely multifocal (20%), and have a predilection for the head, neck, and extremities [2]. It belongs to the broad category of CD30+ T-cell lymphoproliferative disorders, the second most common form of cutaneous T-cell lymphoma (CTCL) [3]. To establish the diagnosis of PC-ALCL, the clinical and histopathological features must be correlated. Histopathological examination of the skin biopsy shows a diffuse infiltrate of CD4+ cells with loss of CD2, CD3 and/or CD5 expression. In PC-ALCL, 75% of infiltrating cells are CD30+. Atypical cells express CLA, with no EMA (epithelial membrane antigen) and ALK expression [4]. The differentiation of PC-ALCL from LyP is essential. LyP, a chronic, recurrent, and self-healing CD30+ lymphoproliferative disorder, is characterized by lesions that wax and wane over time, often leaving scars. In contrast, PC-ALCL lesions are typically more persistent and rarely regress spontaneously. While both conditions share histopathological similarities, the clinical course and treatment responses often aid in differentiation. In this case, scars from previous eruptions could suggest a coexistence of LyP or a disease entity within the spectrum of CD30+ lymphoproliferative disorders. Additional follow-up and observation of lesion dynamics over time could provide further insights. Treatment approaches for PC-ALCL include surgical excision and radiotherapy (RT) for solitary or localized lesions. For multifocal lesions or relapses, RT is recommended for those with few lesions, while low-dose methotrexate or brentuximab vedotin may be used for widespread disease or refractory cases [5]. Differential diagnosis of primary cutaneous anaplastic large cell lymphoma includes lymphomatoid papulosis, type C (diffuse large cell type), ALK+ and ALK- systemic anaplastic large cell lymphoma with skin involvement, mycosis fungoides with CD30+ large cell transformation, classic Hodgkin’s lymphoma involving skin, peripheral T lymphoma, not otherwise specified, involving skin, subcutaneous panniculitis-like T-cell lymphoma, primary cutaneous gamma-delta T-cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder. In general, primary cutaneous ALCL has a favourable prognosis with a 10-year overall survival rate of 90% [6].

Conclusions

We present the case of the rare disease PC-ALCL, emphasising that correlating the clinical presentation with histopathological features is crucial for establishing the diagnosis of primary cutaneous T-cell lymphoproliferative disorder (PCTLD). The diagnosis cannot be made based solely on histopathological findings [4]. It is also important to note that PC-ALCL may coexist with other malignancies, as demonstrated by our presented case.

Funding

No external funding.

Ethical approval

Not applicable.

Conflict of interest

The authors declare no conflict of interest.

References