Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of extranodal non-Hodgkin lymphomas primarily involving the skin.

It is characterized by malignant proliferation of T lymphocytes exhibiting a variety of clinical presentations, ranging from indolent, patch-like lesions to aggressive tumors with systemic involvement.

Classic Presentation: Mycosis Fungoides and Sézary Syndrome

Mycosis fungoides (MF) constitutes approximately 60% of CTCL cases and often presents in stages: patch, plaque, and tumor. The patch stage typically manifests as nonspecific dermatitis-like, atrophic or erythematous patches frequently located on the trunk and buttocks, sometimes with minimal itching.

Sézary syndrome, a more aggressive variant and comparatively rare, is defined clinically by erythroderma, generalized lymphadenopathy, and atypical circulating neoplastic T-cells (Sézary cells). Patients often experience widespread edematous skin, palmar and plantar hyperkeratosis, alopecia, and nail dystrophy. The syndrome frequently includes ocular involvement such as ectropion and may present hepatosplenomegaly in advanced stages.

Primary Cutaneous Peripheral T-Cell Lymphoma-Not Otherwise Specified (pcPTCL-NOS)

This subgroup is clinically challenging due to its highly variable presentation and aggressive behavior. Lesions can manifest as solitary or multiple nodules, plaques, or tumors that tend to ulcerate. Rapid systemic progression with lymphadenopathy and extranodal involvement is common, resulting in poor prognosis despite treatment efforts.

B symptoms such as fever and weight loss may arise with disease advancement. Laboratory abnormalities often include anemia, thrombocytopenia, and elevated lactate dehydrogenase levels, underlining systemic disease.

Emerging Clinical Entities: CD8-Positive CTCL Subtypes

Distinct aggressive variants like primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma present with eruptive papules, nodules, and tumors often characterized by central ulceration. These manifest more rapidly and with deeper tissue involvement than other CTCL types.

Immunophenotypic and Histologic Correlates

Most CTCL malignant cells show a CD4-positive phenotype, often with loss of pan-T cell markers such as CD2, CD3, CD5, or CD7. The tumor microenvironment frequently exhibits a dominance of Th2 cytokines (IL-4, IL-5, IL-13), suppressing host cellular immunity. In aggressive lymphomas, high proliferation indices (Ki-67 up to 90%) correlate with poor clinical outcomes.

Diagnostic and Clinical Challenges

The clinical heterogeneity and overlapping features with benign dermatoses hinder timely diagnosis. Early-stage lesions often mimic eczema or psoriasis, while ulcerated tumors may resemble infections or other malignancies. Delayed diagnosis is frequent in aggressive subtypes that progress rapidly, impacting prognosis.

Comprehensive evaluation requires clinical suspicion, skin biopsy with immunohistochemistry, and staging studies including lymph node biopsy and PET imaging to assess extracutaneous spread.

Dr. David L. Straus, a reputable hematologic oncologist, stated, "Cutaneous T-cell lymphoma’s protean manifestations necessitate a high index of suspicion, as early intervention significantly influences survival outcomes."

Another authority, Dr. Ellen J. Kim, an expert in dermatologic oncology, emphasized, "Multidisciplinary approaches integrating dermatology and oncology optimize diagnostic precision and enable tailored therapies essential for managing this complex malignancy."

Cutaneous T-cell lymphoma encompasses a spectrum of T-cell malignancies with diverse clinical features ranging from indolent patchy dermatitis to aggressive ulcerative tumors. Mycosis fungoides and Sézary syndrome remain prototypical presentations, while newly recognized CD8+ variants add complexity to the clinical landscape.

Immunophenotypic profiling and histopathologic analysis are essential for accurate diagnosis amid clinical mimicry and staging guides treatment decisions. Recognition of disease heterogeneity and integration of multidisciplinary expertise underpin improved diagnostic accuracy and patient management in this challenging domain