Cutaneous CD8+ Cytotoxic T-Cell Lymphoma Infiltrates: Clinicopathological Correlation and Outcome of 35 Cases

Abstract

Introduction: Cytotoxic CD8+ T-cell lymphomas are only rarely encountered and thus remain only poorly characterized. Our aim was to collect and correlate clinical and histological data of CD8+ skin lymphoma infiltrates to obtain a proper subtype assignment of CD8+ skin lymphoma infiltrates and to derive putative prognostic markers thereof.

Methods: Formalin-fixed and paraffin-embedded (FFPE) tissue of 35 patients with CD8+ cytotoxic cutaneous T-cell lymphoma infiltrates was retrieved from the archives of the Institute of Pathology and the Department of Dermatology, University Hospital Wuerzburg, dating back from 1998 until 2015. Cytological, histological, immunohistochemical and molecular genetic features were assessed and correlated with respective clinical data.

Results: The identified cases of CD8+ cytotoxic atypical lymphoproliferative infiltrates of the skin (n = 35) comprised 13 cases of mycosis fungoides (MF)/Sézary syndrome (SS), 4 cases of subcutaneous panniculitis-like T-cell lymphoma (SPTCL), 5 cases of primary cutaneous acral CD8+ lymphoma [formerly indolent CD8+ lymphoid proliferation (ILP)] and 1 case of aggressive epidermotropic primary cutaneous T-cell lymphoma (AECTCL). Moreover, nine cases were classified as primary cutaneous peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and three cases as systemic PTCL-NOS. Multiple skin lesions, a high proliferative index and especially a final subtype attribution to AECTCL or systemic PTCL-NOS were associated with a worse survival. Coexpression of CD68 by tumor cells was exclusively observed in indolent acral CD8+ T-cell lymphoma and thus indicated an invariably benign clinical course. No further distinctive markers could be derived from our analysis.

Conclusion: Cutaneous infiltrates of CD8+ cytotoxic T-cell lymphoma comprise clinically and histologically heterogeneous entities of either primary cutaneous T-cell lymphomas or secondary infiltrates of otherwise systemic peripheral T-cell lymphomas. A thorough clinicopathological correlation with respective staging examinations remains the mainstay for correct subtype assignment and proper prognostication as long as no better markers have been defined.

Keywords: Cutaneous lymphomas; Cytotoxic; Histology; Prognosis.

Fig. 1

Overall survival of all analyzed CD8+ lymphoma subtypes and overall survival according to extent of skin lesions. a Overall survival of the different subtypes of CD8+ cytotoxic cutaneous lymphomas shows large heterogeneity with unrestricted survival in ILP up to highly limited survival in AECTL and systemic PTCL-NOS. b Overall survival of patients presenting with solitary/localized skin lesions is significantly higher than the overall survival of patients with multiple lesions (74 ± 63 vs. 31 ± 30 months for patients; P = 0.01), albeit showing wide variation. AECTCL aggressive epidermotropic primary cutaneous T-cell lymphoma, ILPacral CD8+ T-cell lymphoma, formerly indolent CD8+ lymphoid proliferation, NOS not otherwise specified, PTCL peripheral T-cell lymphoma, SPTCL subcutaneous panniculitis-like T-cell lymphoma

Fig. 2

Selected clinical and histological examples of atypical presentation of CD8+ MF cases. CD8+ cytotoxic MF frequently exhibits atypical clinical presentation mimicking mastocytosis (urticaria pigmentosa) a in the case of hyperpigmented and purpuric MF or pityriasis alba/vitiligo and b in hypopigmented juvenile MF. c Histology of case (a) shows an atypical band-like infiltrate of pleomorphic small-/medium-sized lymphocytes with frank epidermotropism in a pagetoid pattern together with interface dermatitis, dermal erythrocytes, melanophages and hemosiderophages. Dermal and epidermal lymphoma cells of case (a) strongly express CD8 (d) and cytotoxic molecules. MF mycosis fungoides

Fig. 3

Representative clinical and histological examples of cutaneous PTCL-NOS. Localized skin lesions at time of diagnosis of primary cutaneous PTCL-NOS a exhibiting a highly epidermotropic lymphoma infiltrate of highly proliferating pleomorphic small-/medium-sized lymphoma cells (b). c Multiple disseminated non-ulcerated patches, plaques and flat tumors at the trunk and extremities are present in this patient with cutaneous PTCL-NOS. d Histology shows blast-like large dermal tumor cells with multiple mitotic figures. PTCL-NOS peripheral T-cell lymphoma, not otherwise specified

Fig. 4

Overall survival with respect to proliferation rate and cytotoxic phenotype. a Overall survival for patients showing a high proliferation rate as assessed by >60% ki67-positive lymphoma cells is significantly lower than low-proliferating tumors (P < 0.05). b Presence of an activated cytotoxic phenotype [positivity of GrB together with perforin and/or T-cell intracellular antigen (TIA)] does not affect overall survival