T-cell Lymphomas Presenting as Necrotizing Vasculitis: Histological Clues and Clinical Implications

Motew Carpenter^*
*Correspondence: Motew Carpenter, Department of Hemato-Oncology & Histopathology, National University of Singapore (NUS), 21 Lower Kent Ridge Rd, Singapore, Email:

Introduction

T-cell lymphomas are a heterogeneous group of aggressive hematologic malignancies characterized by the neoplastic transformation of mature post-thymic T-cells. Unlike their B-cell counterparts, T-cell lymphomas often present with highly variable clinical features, which can include skin involvement, systemic symptoms and autoimmune or inflammatory manifestations. One of the more elusive and diagnostically challenging presentations is when T-cell lymphomas mimic or coexist with necrotizing vasculitis. Necrotizing vasculitis is typically associated with primary autoimmune conditions, such as ANCA-associated vasculitis or systemic lupus erythematosus, but can occasionally be the initial or predominant feature of underlying T-cell lymphoma. This overlap presents significant clinical and histological diagnostic challenges, often leading to delayed or inappropriate treatment. Understanding the histopathological clues and clinical implications of this rare but important presentation is essential for accurate diagnosis and optimal patient management [1].

Description

Necrotizing vasculitis is characterized histologically by fibrinoid necrosis of vessel walls, infiltration of inflammatory cellsâ??typically neutrophils and mononuclear cellsâ??and evidence of vascular destruction such as thrombosis, hemorrhage and ischemic tissue injury. Clinically, it may present with palpable purpura, livedo reticularis, digital ischemia, renal dysfunction, neurologic deficits, or systemic features such as fever, malaise and weight loss. In the context of T-cell lymphoma, these manifestations may represent either a paraneoplastic autoimmune response or direct neoplastic involvement of blood vessels. The distinction between these possibilities is subtle and often only evident upon detailed histopathologic examination. Peripheral T-cell lymphomas, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), extranodal NK/T-cell lymphoma and adult T-cell leukemia/lymphoma (ATLL) have all been reported to present with or mimic systemic vasculitis. Among these, AITL is particularly prone to presenting with autoimmune phenomena, including vasculitis, due to its strong association with immune dysregulation and abnormal follicular helper T-cell activity. These lymphomas can produce large quantities of cytokines such as IL-6, IL-10 and TNF-α, leading to systemic inflammation, autoantibody production and vascular injury. In some cases, patients with AITL or PTCL may present with positive autoantibody screens, including rheumatoid factor, antinuclear antibodies (ANA) and even ANCAs, further confusing the clinical picture and leading to a misdiagnosis of primary vasculitis [2,3].

Histologically, the key to diagnosing T-cell lymphoma presenting as necrotizing vasculitis lies in careful examination of tissue infiltrates beyond the vasculitic lesions. In typical necrotizing vasculitis, inflammatory infiltrates consist predominantly of neutrophils and mononuclear cells without atypia. However, in lymphoma-associated cases, infiltrates may contain atypical lymphoid cells with irregular nuclei, prominent nucleoli and a high mitotic index. These neoplastic cells may exhibit angiocentric and angiodestructive patterns, particularly in extranodal NK/T-cell lymphoma, nasal type. Immunohistochemistry is essential to identify the T-cell nature of the infiltrate, with markers such as CD3, CD4, CD5, CD8, CD30 and cytotoxic markers like granzyme B and TIA-1. Epstein-Barr virus (EBV)-positive B cells are often seen in the background, reflecting the immune dysregulation associated with the disease. In extranodal NK/T-cell lymphoma, necrosis and angioinvasion are prominent features and in situ hybridization for EBV-encoded RNA (EBER) is typically positive. These histological features, when identified within a biopsy specimen initially thought to show vasculitis, can redirect the diagnosis towards lymphoma [4].

Clinically, T-cell lymphomas presenting with vasculitis may resemble systemic autoimmune vasculitides in their symptomatology. Patients may report arthralgia, skin ulcers, neuropathy, or hematuriaâ??symptoms that are not specific to either vasculitis or lymphoma. Constitutional symptoms such as fever, night sweats and weight loss, while common in lymphoma, also overlap with primary vasculitis. This clinical mimicry underscores the need for vigilance and a low threshold for performing tissue biopsies and immunophenotypic studies, especially when the disease course is atypical or refractory to standard immunosuppressive therapy. The intersection of vasculitis and lymphoma also has broader implications for our understanding of immune dysregulation and oncogenesis. T-cell lymphomas often arise in the context of chronic immune stimulation and the vasculitic presentation may reflect a paraneoplastic autoimmune phenomenon driven by the same aberrant immune pathways that underlie lymphomagenesis. The role of cytokines, regulatory T-cell dysfunction and antigenic mimicry in this process remains an area of active research. Moreover, this overlap raises important questions regarding the risk of lymphoma development in patients with longstanding autoimmune vasculitis, as well as the potential for vasculitis as a harbinger of occult malignancy [5].

Conclusion

In conclusion, T-cell lymphomas presenting as necrotizing vasculitis represent a rare but critical diagnostic entity that bridges the disciplines of oncology, pathology and immunology. Histological clues such as atypical lymphoid infiltrates, angiocentric growth and immunophenotypic abnormalities are essential for distinguishing these cases from primary autoimmune vasculitis. Clinicians must maintain a high index of suspicion, particularly in patients with atypical presentations, refractory disease, or systemic features suggestive of malignancy. Early tissue diagnosis, including immunohistochemistry and molecular studies, is vital for accurate classification and timely initiation of lymphoma-directed therapy. As understanding of the immunopathogenesis of T-cell lymphomas evolves, it may offer new insights into both cancer biology and the mechanisms of autoimmune vascular injury, ultimately improving diagnostic accuracy and therapeutic outcomes for this complex and challenging patient population.

Acknowledgement

None.

Conflict of Interest

None.

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