Differentiating Merkel cell carcinoma of lymph nodes without a detectable primary skin tumor from other metastatic neuroendocrine carcinomas: The ELECTHIP criteria - 19/04/18

Doi : 10.1016/j.jaad.2017.11.037

Thibault Kervarrec, MD, MSc ^a,^b, Julia Zaragoza, MD ^c, Pauline Gaboriaud ^b, Amélie Le Gouge, MSc ^d, Agnès Beby-Defaux, MD ^e,^f, Yannick Le Corre, MD ^g, Ewa Hainaut-Wierzbicka, MD ^h, Francois Aubin, MD, PhD ⁱ, Guido Bens, MD ^j, Patrick Michenet, MD ^k, Hervé Maillard, MD ^l, Antoine Touzé, PhD ^b, Mahtab Samimi, MD, PhD ^b,^c,^⁎ , Serge Guyétant, MD, PhD ^a,^b
^a Department of Pathology, Université Francois Rabelais, Centre Hospitalier Universitaire de Tours, Tours, France
^b 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
^c Dermatology Department, Université Francois Rabelais, Centre Hospitalier Universitaire de Tours, Tours, France
^d 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
^e Virology Department, Université de Poitiers, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
^f Récepteurs et Régulation des Cellules Tumorales Team, Poitiers, France
^g Dermatology Department, LUNAM (L'Université-Nantes-Angers-Le-Mans), Centre Hospitalier Universitaire d'Angers, Angers, France
^h Dermatology Department, Université de Poitiers, Centre Hospitalier Universitaire de Poitiers, Angers, France
ⁱ Dermatology Department, Université de Franche Comté, Centre Hospitalier Universitaire de Besançon, Besançon, France
^j Dermatology Department, Centre Hospitalier Régional d'Orléans, Orléans, France
^k Department of Pathology, Centre Hospitalier Régional d'Orléans, Orléans, France
^l Dermatology Department, Centre Hospitalier Régional du Mans, Le Mans, France

^∗Correspondence to: Mahtab Samimi, MD, PhD, Dermatology Department, Hospital of Tours, Avenue de la République, 37170, Chambray-les-tours, France.Dermatology DepartmentHospital of ToursAvenue de la RépubliqueChambray-les-tours37170France

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.

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Key words : CK20, differential diagnosis, lymph nodes, MCPyV, Merkel cell carcinoma, metastasis, neuroendocrine carcinoma, TTF-1

Abbreviations used : CK, CT, ELECTHIP, FFPE, LNM, LNMNEC, MANEC, MCC, MCCWOPT, MCPyV, NEC, TTF-1

Plan

Clinical and follow-up data

Histology and immunohistochemistry

Detection of MCPyV DNA

Statistical analysis

Results

Patient characteristics

Clinical data

Immunomorphologic and virologic data

Determining diagnostic features — the ELECTHIP criteria

Discussion

	Drs Samimi and Guyetant contributed to this work equally.
	Funding sources: Supported by project POCAME, Axe Immunothérapies, and Cancéropole Grand Ouest-Région Centre Val de Loire.
	Conflicts of interest: None disclosed.
	Reprints not available from the authors.

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Merkel cell carcinomas infiltrated with CD33⁺ myeloid cells and CD8⁺ T cells are associated with improved outcome
Thibault Kervarrec, Pauline Gaboriaud, Patricia Berthon, Julia Zaragoza, David Schrama, Roland Houben, Yannick Le Corre, Ewa Hainaut-Wierzbicka, Francois Aubin, Guido Bens, Jorge Domenech, Serge Guyétant, Antoine Touzé, Mahtab Samimi

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Differentiating Merkel cell carcinoma of lymph nodes without a detectable primary skin tumor from other metastatic neuroendocrine carcinomas: The ELECTHIP criteria - 19/04/18

Abstract

Background

Objective

Methods

Results

Limitations

Conclusion

Plan

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