Diagnostic accuracy of a panel of immunohistochemical and molecular markers to distinguish Merkel cell carcinoma from other neuroendocrine carcinomas

被引：80

作者：

Kervarrec, Thibault ^{[1
,2
,3
]}

Tallet, Anne ^{[4
]}

Miquelestorena-Standley, Elodie ^{[1
]}

Houben, Roland ^{[3
]}

Schrama, David ^{[3
]}

Gambichler, Thilo ^{[5
]}

Berthon, Patricia ^{[2
]}

Le Corre, Yannick ^{[6
]}

Hainaut-Wierzbicka, Ewa ^{[7
]}

Aubin, Francois ^{[8
]}

Bens, Guido ^{[9
]}

Tabareau-Delalande, Flore ^{[10
]}

Beneton, Nathalie ^{[11
]}

Fromont, Gaelle ^{[12
]}

Arbion, Flavie ^{[12
]}

Leteurtre, Emmanuelle ^{[13
]}

Touze, Antoine ^{[2
]}

Samimi, Mahtab ^{[2
,14
]}

Guyetant, Serge ^{[1
,2
]}

机构：

[1] Univ Tours, CHU Tours, Dept Pathol, Ave Republ, F-37170 Chambray Les Tours, France

[2] Univ Tours, INRA, UMR ISP 1282, Biol Infect Polyomavirus Team, 31 Ave Monge, F-37200 Tours, France

[3] Univ Hosp Wurzburg, Dept Dermatol Venereol & Allergol, Josef Schneider Str 2, D-97080 Wurzburg, Germany

[4] Univ Tours, CHU Tours, Platform Somat Tumor Mol Genet, Ave Republ, F-37170 Chambray Les Tours, France

[5] Univ Hosp Bochum, Dept Dermatol Venereol & Allergol, GudrunStr 5, D-44791 Bochum, Germany

[6] LUNAM Univ, CHU Angers, Dermatol Dept, 4 Rue Larrey, F-49933 Angers, France

[7] Univ Poitiers, CHU Poitiers, Dermatol Dept, 2 Rue Miletrie, F-86021 Poitiers, France

[8] Univ Franche Comte, CHU Besancon, Dermatol Dept, EA3181,IFR133, 2 Blvd Fleming, F-25030 Besancon, France

[9] CHR Orleans, Dermatol Dept, 14 Ave Hop, F-45100 Orleans, France

[10] CHR Orleans, Dept Pathol, 14 Ave Hop, F-45100 Orleans, France

[11] CHR Le Mans, Dermatol Dept, 194 Ave Rubillard, F-72037 Le Mans 09, France

[12] Univ Tours, CHU Tours, Dept Pathol, Blvd Tonnelle, F-37044 Tours, France

[13] Univ Lille, CHU Lille, INSERM, JPARC,UMR S 1172, F-59000 Lille, France

[14] Univ Tours, CHU Tours, Dermatol Dept, Ave Republ, F-37170 Chambray Les Tours, France

来源：

MODERN PATHOLOGY | 2019年 / 32卷 / 04期

关键词：

POLYOMAVIRUS INFECTION; UNKNOWN PRIMARY; CASE SERIES; LYMPH-NODE; EXPRESSION; DIFFERENTIATION; CYTOKERATIN; SATB2; TUMOR; ASSOCIATION;

D O I：

10.1038/s41379-018-0155-y

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Merkel cell carcinoma is a rare neuroendocrine carcinoma of the skin mostly induced by Merkel cell polyomavirus integration. Cytokeratin 20 (CK20) positivity is currently used to distinguish Merkel cell carcinomas from other neuroendocrine carcinomas. However, this distinction may be challenging in CK20-negative cases and in cases without a primary skin tumor. The objectives of this study were first to evaluate the diagnostic accuracy of previously described markers for the diagnosis of Merkel cell carcinoma and second to validate these markers in the setting of difficult-todiagnose Merkel cell carcinoma variants. In a preliminary set (n = 30), we assessed optimal immunohistochemical patterns (CK20, thyroid transcription factor 1 [TTF-1], atonal homolog 1 [ATOH1], neurofilament [NF], special AT-rich sequence-binding protein 2 [SATB2], paired box protein 5, terminal desoxynucleotidyl transferase, CD99, mucin 1, and Merkel cell polyomavirus-large T antigen) and Merkel cell polyomavirus load thresholds (real-time PCR). The diagnostic accuracy of each marker was then assessed in a validation set of 103 Merkel cell carcinomas (9 CK20-negative cases and 15 cases without a primary skin tumor) and 70 extracutaneous neuroendocrine carcinoma cases. The most discriminant markers for a diagnosis of Merkel cell carcinoma were SATB2, NF expression, and Merkel cell polyomavirus DNA detection (positive likelihood ratios: 36.6, 44.4, and 28.2, respectively). Regarding Merkel cell carcinoma variants, cases without a primary skin tumor retained a similar immunohistochemical profile and CK20-negative tumors displayed a different profile (decrease frequency of NF and SATB2 expression), but Merkel cell polyomavirus DNA remained detected (78% of cases by qPCR). Moreover, 8/9 (89%) CK20-negative Merkel cell carcinoma cases but only 3/61 (5%) CK20-negative extracutaneous neuroendocrine cases were positive for at least one of these markers. In conclusion, detection of SATB2 and NF expression and Merkel cell polyomavirus DNA helps distinguish between Merkel cell carcinoma classical and variant cases and extracutaneous neuroendocrine carcinomas.

引用

页码：499 / 510

页数：12

共 52 条

[1]

[Anonymous], AM J SURG PATHOL

[2]

[Anonymous], PATHOLOGY GENETICS S

[3] Effect of Host, Tumor, Diagnostic, and Treatment Variables on Outcomes in a Large Cohort With Merkel Cell Carcinoma [J].