Cutaneous Manifestations of Angioimmunoblastic T-Cell Lymphoma

Abstract

Angioimmunoblastic T-cell lymphoma (AITL), an uncommon variant of peripheral T-cell lymphoma, affects the skin in approximately 50% of cases. Its protean clinical and histopathological cutaneous manifestations pose a challenge in diagnosis, particularly when these precede the diagnosis of AITL on a lymph node biopsy. In this retrospective study, we compared 11 cases of AITL with cutaneous manifestations (mean age 67 years; male:female ratio 1:0.8; 24 skin biopsies) with 20 control cases of inflammatory and non-AITL lymphomatous diseases (mean age 52 years; male:female ratio 1:1.5; 26 skin biopsies). Clinical, histopathological, immunohistochemical, and molecular data were documented. New insights into the clinical evolution of cutaneous involvement by AITL (C-AITL), from early macular, through papular to nodular stages, were observed. Microscopically, a parallel increment in the density of the dermal infiltrate and in the detection of lymphocyte cytological atypia was noted over time. Identification and quantification of follicular T-helper cells (Tfh), the neoplastic lineage, by immunohistochemistry helped to separate cases of C-AITL from inflammatory controls, offering promise as a useful diagnostic adjunct. The presence of T-cell clonality did not have discriminatory value between the 2 groups. Our work suggests that the early maculopapular phase of C-AITL eludes identification on pathological grounds alone and that features such as cytological atypia and high endothelial venules lack diagnostic specificity. In the context of (1) a rash that simulates a drug/viral exanthem or an acute manifestation of a connective tissue disorder, but proves recalcitrant, (2) constitutional abnormalities and/or lymphadenopathy that persist, and (3) a Tfh cell-rich perivascular dermatitis, the diagnosis of early C-AITL can be suspected, but not confirmed, without the benefit of a lymph node biopsy. The later nodular phase of C-AITL occurring in a similar constitutional background, can usually be discerned as lymphomatous, clinically and pathologically. Here a Tfh cell-rich infiltrate is a clue to the specific diagnosis, but confirmation by a nodal evaluation remains mandatory. Despite the difficulty in establishing a diagnosis of C-AITL in its early stages, and speculation that the initial eruptions might be reactive in nature, our sequential data support the concept that these are lymphomatous ab initio. To address the diagnostic challenge presented by this disease, meaningful integration of clinical and pathological data is imperative.

Cutaneous lesions of angioimmunoblastic T‐cell lymphoma: Clinical, pathological, and immunophenotypic features

“…In addition to lymph node involvement, it often involves extranodal sites, such as spleen, bone marrow, lungs, and skin . Cutaneous involvement is present approximately in half of AITL patients, most commonly as a maculopapular (typically, a non‐specific morbilliform or exanthematous) eruption . Other manifestations include urticarial or purpuric eruptions, papulovesicular lesions, nodular lesions, erythematosquamous plaques, and ulcerated lesions .…”

“…5,13 Cutaneous involvement is present approximately in half of AITL patients, most commonly as a maculopapular (typically, a non-specific morbilliform or exanthematous) eruption. 5,[14][15][16][17] Other manifestations include urticarial or purpuric eruptions, papulovesicular lesions, nodular lesions, erythematosquamous plaques, and ulcerated lesions. 15 Because of such varying dermatological manifestations, cutaneous biopsy is often performed in AITL patients to differentiate true AITL involvement from inflammatory conditions.…”

Cutaneous localization of angioimmunoblastic T‐cell lymphoma may masquerade as B‐cell lymphoma or classical Hodgkin lymphoma: A histologic diagnostic pitfall

“…Nodular presentation of AITL skin lesion is unusual but may occur later in the disease course as suggested by Botros et al Interestingly, the nodular lesions arose several months after AITL diagnosis in the 3 cases. We may speculate that the EBV+ B‐cell proliferation may be responsible for such atypical clinical presentation.…”

Primary cutaneous follicular helper T‐cell lymphoma

“…Both follicular dendritic cell hyperplasia and the presence of high endothelial venules are highly characteristic of lymph node specimens infiltrated by AITL . Nevertheless, none of the authors have reported expansion of follicular dendritic cells meshwork on skin specimens infiltrated by AITL . Moreover, capillary hyperplasia is not always present on skin specimens and its presence lacks diagnostic specificity because it could be found in many other conditions .…”