Werner Kempf1,2, Tony Petrella3, Rein Willemze4, Patty Jansen5, Emilio Berti6, Marco Santucci7, Eva Geissinger8, Lorenzo Cerroni9, Eve Maubec10, Maxime Battistella11, John Goodlad12, Emmanuella Guenova2,13, Katariina Lappalainen14, Annamari Ranki14, Paul Craig15, Eduardo Calonje16, Blanca Martin16, Sean Whittaker17, Ilske Oschlies18, Ulrike Wehkamp19, Jan P Nicolay20, Marion Wobser21, Julia Scarisbruck22, Nicola Pimpinelli23, Rudi Stadler24, Katrin Kerl French25, Pietro Quaglino26, Jinran Lin27, Lianjun Chen27, Michaela Beer1, Patrick Emanuel28,29, Stephane Dalle30, Alistair Robson31,32. 1. Kempf und Pfaltz Histologische Diagnostik, Zurich, Switzerland. 2. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. 3. Department of Pathology, Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada. 4. Department of Dermatology. 5. Department of Clinical Pathology, Leiden University Medical Center, Leiden, the Netherlands. 6. University of Milan, Director U.O.C. of Dermatology Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico of Milan, Milan, Italy. 7. Department of Health Sciences, University of Florence School of Human Health Sciences and Division of Histopathology and Molecular Diagnostics, Careggi University Hospital, Florence, Italy. 8. Institute of Pathology, University of Würzburg, Würzburg, Germany. 9. Department of Dermatology, Medical University of Graz, Graz, Austria. 10. Service de Dermatologie du Pr F. Caux, Hôpital Avicenne, Bobigny, CEDEX, France. 11. Department of Pathology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris University, INSERM U976, Paris, France. 12. NHS Greater Glasgow and Clyde, Glasgow, UK. 13. Department of Dermatology, University Hospital Lausanne, Faculty of Biology and Medicine, University of Lausanne, CH-1011, Lausanne, Switzerland. 14. Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland. 15. Gloucestershire Hospitals NHS Foundation Trust, Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham, UK. 16. Department of Dermatopathology, St John's Institute of Dermatology, St Thomas' Hospital, London, UK. 17. St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK. 18. Department of Pathology, Section Hematopathology and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. 19. Department of Dermatology and Allergology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. 20. Department of Dermatology, University Medical Center Mannheim, Mannheim, Germany. 21. Department of Dermatology, Venereology and Allergology and Skin Cancer Center, University Hospital Würzburg, Würzburg, Germany. 22. Department of Dermatology, University Hospital Birmingham, Birmingham, UK. 23. Dermatology Unit, Department of Health Sciences, University of Florence Medical School, Florence, Italy. 24. Department of Dermatology, Venerology, Allergology and Phlebology, Johannes Wesling Klinikum Minden, University Clinic Ruhr-Universität Bochum, Minden, Germany. 25. Department of Dermatology, Ludwig-Maximilian University Hospital of Munich, Munich, Germany. 26. Dermatologic Clinic, Department of Medical Sciences, University of Turin Medical School, Torino, Italy. 27. Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China. 28. Clinica Ricarda Palma, Lima, Peru. 29. University of Auckland, Auckland, New Zealand. 30. Unit of Dermatology, Cancer Research Centre of Lyon, Hôpital Lyon Sud, Hospices Civils de Lyon, Université Claude Bernard, Lyon 1, France. 31. Institute of Oncology, Lisbon, Portugal. 32. LDPath, London, UK.
Abstract
BACKGROUND: The differential diagnosis of atypical dermal nonepidermotropic CD8+ lymphocytic infiltrates includes a heterogeneous spectrum of lymphoproliferations with overlapping histological and phenotypic features, but divergent clinical manifestations and prognoses. As these neoplasms are rare, more data on their clinicopathological presentation and course are needed. OBJECTIVES: To assess the clinical, histological and immunophenotypic features; outcomes of; and differences between dermal CD8+ lymphoproliferations. METHODS: Retrospective analysis of a series of 46 patients and biopsies by the international EORTC Cutaneous Lymphoma Group. RESULTS: The dermal CD8+ lymphoproliferations (n = 46) could be assigned to one of three groups: (i) cutaneous acral CD8+ T-cell lymphoma (n = 31), characterized mostly by a solitary nodule arising at acral sites, a monotonous dermal infiltrate of small-to-medium-sized CD8+ lymphocytes with a characteristic dot-like pattern of CD68, a low proliferation rate and an excellent prognosis; (ii) primary cutaneous CD8+ peripheral T-cell lymphoma, unspecified/NOS (n = 11), presenting with one or multiple rapidly evolving tumours, mostly medium-sized pleomorphic CD8+ tumour cells with expression of several cytotoxic markers, and high proliferative activity; and (iii) cutaneous CD8+ lymphoproliferations (n = 4), associated with congenital immunodeficiency syndromes in two patients with persisting localized or disseminated violaceous to brownish plaques on the extremities, a histiocyte-rich infiltrate of mostly small CD8+ lymphocytes with subtle atypia and a protracted course; and papular CD8+ eruptions in two patients with acquired immunosuppression. CONCLUSIONS: A constellation of distinct clinical, histopathological and phenotypic features allows discrimination and assignment of dermal CD8+ infiltrates into distinct disease entities. Primary cutaneous acral CD8+ lymphoma, assigned a provisional category in current lymphoma classifications, is a distinct and reproducible entity. A correct diagnosis is essential to avoid unnecessarily aggressive treatment for indolent CD8+ lymphoproliferations and to identify cases with underlying immuno-deficiency or potential for dismal outcome.
BACKGROUND: The differential diagnosis of atypical dermal nonepidermotropic CD8+ lymphocytic infiltrates includes a heterogeneous spectrum of lymphoproliferations with overlapping histological and phenotypic features, but divergent clinical manifestations and prognoses. As these neoplasms are rare, more data on their clinicopathological presentation and course are needed. OBJECTIVES: To assess the clinical, histological and immunophenotypic features; outcomes of; and differences between dermal CD8+ lymphoproliferations. METHODS: Retrospective analysis of a series of 46 patients and biopsies by the international EORTC Cutaneous Lymphoma Group. RESULTS: The dermal CD8+ lymphoproliferations (n = 46) could be assigned to one of three groups: (i) cutaneous acral CD8+ T-cell lymphoma (n = 31), characterized mostly by a solitary nodule arising at acral sites, a monotonous dermal infiltrate of small-to-medium-sized CD8+ lymphocytes with a characteristic dot-like pattern of CD68, a low proliferation rate and an excellent prognosis; (ii) primary cutaneous CD8+ peripheral T-cell lymphoma, unspecified/NOS (n = 11), presenting with one or multiple rapidly evolving tumours, mostly medium-sized pleomorphic CD8+ tumour cells with expression of several cytotoxic markers, and high proliferative activity; and (iii) cutaneous CD8+ lymphoproliferations (n = 4), associated with congenital immunodeficiency syndromes in two patients with persisting localized or disseminated violaceous to brownish plaques on the extremities, a histiocyte-rich infiltrate of mostly small CD8+ lymphocytes with subtle atypia and a protracted course; and papular CD8+ eruptions in two patients with acquired immunosuppression. CONCLUSIONS: A constellation of distinct clinical, histopathological and phenotypic features allows discrimination and assignment of dermal CD8+ infiltrates into distinct disease entities. Primary cutaneous acral CD8+ lymphoma, assigned a provisional category in current lymphoma classifications, is a distinct and reproducible entity. A correct diagnosis is essential to avoid unnecessarily aggressive treatment for indolent CD8+ lymphoproliferations and to identify cases with underlying immuno-deficiency or potential for dismal outcome.