Thibault Kervarrec1, Julia Zaragoza2, Pauline Gaboriaud3, Amélie Le Gouge4, Agnès Beby-Defaux5, Yannick Le Corre6, Ewa Hainaut-Wierzbicka7, Francois Aubin8, Guido Bens9, Patrick Michenet10, Hervé Maillard11, Antoine Touzé3, Mahtab Samimi12, Serge Guyétant1. 1. Department of Pathology, Université Francois Rabelais, Centre Hospitalier Universitaire de Tours, Tours, France; Biologie des Infections à Polyomavirus Team Unite Mixte de Recherche 1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique (INRA), Université Francois Rabelais, Tours, France. 2. Dermatology Department, Université Francois Rabelais, Centre Hospitalier Universitaire de Tours, Tours, France. 3. Biologie des Infections à Polyomavirus Team Unite Mixte de Recherche 1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique (INRA), Université Francois Rabelais, Tours, France. 4. Centre Hospitalier Universitaire de Tours, Biometrical Department, Centre d'Investigation Clinique - Institut National de la Santé et de la Recherche Médicale Centres d'Investigation Clinique 1415, Tours, France. 5. Virology Department, Université de Poitiers, Centre Hospitalier Universitaire de Poitiers, Poitiers, France; Récepteurs et Régulation des Cellules Tumorales Team, Poitiers, France. 6. Dermatology Department, LUNAM (L'Université-Nantes-Angers-Le-Mans), Centre Hospitalier Universitaire d'Angers, Angers, France. 7. Dermatology Department, Université de Poitiers, Centre Hospitalier Universitaire de Poitiers, Angers, France. 8. Dermatology Department, Université de Franche Comté, Centre Hospitalier Universitaire de Besançon, Besançon, France. 9. Dermatology Department, Centre Hospitalier Régional d'Orléans, Orléans, France. 10. Department of Pathology, Centre Hospitalier Régional d'Orléans, Orléans, France. 11. Dermatology Department, Centre Hospitalier Régional du Mans, Le Mans, France. 12. Biologie des Infections à Polyomavirus Team Unite Mixte de Recherche 1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique (INRA), Université Francois Rabelais, Tours, France; Dermatology Department, Université Francois Rabelais, Centre Hospitalier Universitaire de Tours, Tours, France. Electronic address: mahtab.samimi@univ-tours.fr.
Abstract
BACKGROUND: Merkel cell carcinoma (MCC) can present as a cutaneous tumor or a lymph node metastasis without a primary tumor. MCC presenting without a primary tumor (MCCWOPT) can be misinterpreted on histologic examination as lymph node metastasis (LNM) from another neuroendocrine carcinoma (LNMNEC). However, this distinction is crucial for therapeutic management. OBJECTIVE: To determine the discriminative criteria for the differential diagnosis of MCCWOPT, LNM from cutaneous MCC, and LNMNECs. METHODS: Clinical, morphologic, and immunohistochemical data (expression of cytokeratins AE1, AE3, 7, 19, and 20; chromogranin A, synaptophysin, thyroid transcription factor-1 [TTF-1]), as well as the presence of Merkel cell polyomavirus (by immunohistochemistry and PCR) were compared in patients with MCCWOPT (n = 17), LNM from a cutaneous MCC (n = 11), and LNMNEC (n = 20; 8 lung, 7 thyroid, 3 digestive tract, 2 other). RESULTS: MCC (including MCCWOPT and LNM from a cutaneous MCC) differed from LNMNEC by 7 discriminative criteria: 1) elderly age, 2) location of the tumor, 3) extent of the disease, 4) cytokeratin expression, 5) TTF-1 expression, 6) histologic type, and 7) Merkel cell polyomavirus detection, summarized under the acronym ELECTHIP. All MCC patients had ≥5 of the ELECTHIP criteria, whereas all patients with LNMNEC (except 1) had <3 criteria. LIMITATIONS: The discriminant ability of the ELECTHIP criteria should be validated in a second independent set. CONCLUSION: MCCWOPT can be distinguished from other LNMNEC by the ELECTHIP criteria.
BACKGROUND:Merkel cell carcinoma (MCC) can present as a cutaneous tumor or a lymph node metastasis without a primary tumor. MCC presenting without a primary tumor (MCCWOPT) can be misinterpreted on histologic examination as lymph node metastasis (LNM) from another neuroendocrine carcinoma (LNMNEC). However, this distinction is crucial for therapeutic management. OBJECTIVE: To determine the discriminative criteria for the differential diagnosis of MCCWOPT, LNM from cutaneous MCC, and LNMNECs. METHODS: Clinical, morphologic, and immunohistochemical data (expression of cytokeratins AE1, AE3, 7, 19, and 20; chromogranin A, synaptophysin, thyroid transcription factor-1 [TTF-1]), as well as the presence of Merkel cell polyomavirus (by immunohistochemistry and PCR) were compared in patients with MCCWOPT (n = 17), LNM from a cutaneous MCC (n = 11), and LNMNEC (n = 20; 8 lung, 7 thyroid, 3 digestive tract, 2 other). RESULTS: MCC (including MCCWOPT and LNM from a cutaneous MCC) differed from LNMNEC by 7 discriminative criteria: 1) elderly age, 2) location of the tumor, 3) extent of the disease, 4) cytokeratin expression, 5) TTF-1 expression, 6) histologic type, and 7) Merkel cell polyomavirus detection, summarized under the acronym ELECTHIP. All MCC patients had ≥5 of the ELECTHIP criteria, whereas all patients with LNMNEC (except 1) had <3 criteria. LIMITATIONS: The discriminant ability of the ELECTHIP criteria should be validated in a second independent set. CONCLUSION: MCCWOPT can be distinguished from other LNMNEC by the ELECTHIP criteria.