{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:15:45Z","timestamp":1788221745133,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cutan Pathol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Merkel cell carcinoma in\u00a0situ (MCCIS), especially when unaccompanied by invasive Merkel cell carcinoma, is exceptionally rare. Most reported cases of MCCIS without invasion demonstrate the typical immunophenotype of invasive MCC, including cytokeratin 20 (CK20) positivity and thyroid transcription factor\u20101 (TTF\u20101) negativity. Here we report a case of MCCIS without invasion exhibiting a phenotype not previously reported in MCCIS: CK20 negativity with diffuse nuclear TTF\u20101 positivity. Arising within a seborrheic (stucco) keratosis in a 78\u2010year\u2010old woman, the lesion demonstrated an entirely intraepidermal proliferation of atypical cells with neuroendocrine differentiation by histology (high nuclear\u2010to\u2010cytoplasmic ratio, crush artifact, and nuclear molding) and immunohistochemistry (positive synaptophysin, chromogranin, neuron\u2010specific enolase, INSM1, and SATB2). The lesion was negative for squamous markers (cytokeratin 903, cytokeratin 5\/6, p40, and p63), Merkel cell polyomavirus (MCPyV\/CM2B4), and neurofilament. A review of the literature identified no prior TTF\u20101\u2010positive MCCIS. To our knowledge, the present case represents the first reported TTF\u20101\u2010positive MCCIS and only the second reported CK20\u2010negative MCCIS. This unusual phenotype expands the recognized immunophenotypic spectrum of MCCIS and highlights a potential diagnostic pitfall.<\/jats:p>","DOI":"10.1111\/cup.70204","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:56:00Z","timestamp":1788220560000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TTF<\/scp>\n                    \u20101\u2013Positive Merkel Cell Carcinoma in Situ: Extending the Neoplasm's Immunophenotypic Spectrum Through Case Study and Literature Review"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0127-9928","authenticated-orcid":false,"given":"Daniel","family":"Wilentz","sequence":"first","affiliation":[{"name":"Platinum Dermatology Partners  Delray Beach Florida USA"},{"name":"Harvard College  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5026-1821","authenticated-orcid":false,"given":"Nikki S.","family":"Vyas","sequence":"additional","affiliation":[{"name":"Vyas Pathology  Oviedo Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Johnston","sequence":"additional","affiliation":[{"name":"Platinum Dermatology Partners  Delray Beach Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Rubenstein","sequence":"additional","affiliation":[{"name":"Platinum Dermatology Partners  Delray Beach Florida USA"},{"name":"Dermatology Residency Program Larkin Hospital  Palm Springs Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.humpath.2023.03.004","article-title":"Merkel Cell Carcinoma: An Update","volume":"140","author":"DeCoste R. C.","year":"2023","journal-title":"Human Pathology"},{"issue":"9","key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1136\/jcp.54.9.727","article-title":"Merkel Cell Carcinoma Can be Distinguished From Metastatic Small\u2010Cell Carcinoma Using Antibodies to Cytokeratin 20 and Thyroid Transcription Factor 1","volume":"54","author":"Leech S. N.","year":"2001","journal-title":"Journal of Clinical Pathology"},{"issue":"10","key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/j.1600-0560.1998.tb01744.x","article-title":"Pagetoid Merkel Cell Carcinoma: Epidermal Origin of the Tumor","volume":"25","author":"Hashimoto K.","year":"1998","journal-title":"Journal of Cutaneous Pathology"},{"issue":"1","key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1097\/00000372-200002000-00013","article-title":"Intraepidermal Merkel Cell Carcinoma With no Dermal Involvement","volume":"22","author":"Brown H. A.","year":"2000","journal-title":"American Journal of Dermatopathology"},{"issue":"3","key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1097\/00000372-200406000-00012","article-title":"A Case of Intraepidermal Merkel Cell Carcinoma Within Squamous Cell Carcinoma in Situ: Merkel Cell Carcinoma in Situ?","volume":"26","author":"Al\u2010Ahmadie H. A.","year":"2004","journal-title":"American Journal of Dermatopathology"},{"issue":"2","key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/j.0303-6987.2005.00270.x","article-title":"Merkel Cell Carcinoma in Situ","volume":"32","author":"Ferringer T.","year":"2005","journal-title":"Journal of Cutaneous Pathology"},{"issue":"5","key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1097\/DAD.0b013e31817a9896","article-title":"Merkel Cell Carcinoma in Situ Arising in a Trichilemmal Cyst: A Case Report and Literature Review","volume":"30","author":"Su W.","year":"2008","journal-title":"American Journal of Dermatopathology"},{"issue":"10","key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1111\/j.1600-0560.2010.01548.x","article-title":"Merkel Cell Carcinoma in Situ Associated With Actinic Keratosis: Fortuitous or Serendipitous?","volume":"37","author":"Ferrara G.","year":"2010","journal-title":"Journal of Cutaneous Pathology"},{"issue":"1","key":"e_1_2_6_10_1","first-page":"188","article-title":"Merkel Cell Carcinoma Arising in a Seborrheic Keratosis","volume":"37","author":"Kitagawa K. P.","year":"2010","journal-title":"Journal of Cutaneous Pathology"},{"issue":"1","key":"e_1_2_6_11_1","first-page":"165","article-title":"Merkel Cell Carcinoma in Situ","volume":"37","author":"Reese J.","year":"2010","journal-title":"Journal of Cutaneous Pathology"},{"issue":"6","key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/j.1600-0560.2012.01908.x","article-title":"Combined Intraepidermal Neuroendocrine (Merkel Cell) and Squamous Cell Carcinoma in Situ With CM2B4 Negativity and p53 Overexpression","volume":"39","author":"Tan B. H.","year":"2012","journal-title":"Journal of Cutaneous Pathology"},{"issue":"2","key":"e_1_2_6_13_1","first-page":"233","article-title":"Merkel Cell Carcinoma In\u00a0Situ","volume":"41","author":"McCall M.","year":"2014","journal-title":"Journal of Cutaneous Pathology"},{"issue":"11","key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/cup.12813","article-title":"Intraepidermal Merkel Cell Carcinoma With Pagetoid Bowen Disease","volume":"43","author":"Miraflor A. P.","year":"2016","journal-title":"Journal of Cutaneous Pathology"},{"issue":"5","key":"e_1_2_6_15_1","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1111\/cup.12908","article-title":"Intraepidermal Proliferation of Merkel Cells Within a Seborrheic Keratosis: Merkel Cell Carcinoma In\u00a0Situ or Merkel Cell Hyperplasia?","volume":"44","author":"McFalls J.","year":"2017","journal-title":"Journal of Cutaneous Pathology"},{"issue":"8","key":"e_1_2_6_16_1","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1111\/cup.12966","article-title":"Intraepidermal Merkel Cell Carcinoma: A Case Series of a Rare Entity With Clinical Follow Up","volume":"44","author":"Jour G.","year":"2017","journal-title":"Journal of Cutaneous Pathology"},{"issue":"4","key":"e_1_2_6_17_1","doi-asserted-by":"crossref","first-page":"e311","DOI":"10.1111\/ajd.13068","article-title":"Merkel Cell Carcinoma In\u00a0Situ: New Insights Into the Cells of Origin","volume":"60","author":"Yang A.","year":"2019","journal-title":"Australasian Journal of Dermatology"},{"issue":"3","key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/cup.13404","article-title":"Merkel Cell Carcinoma Arising in Association With Cutaneous T\u2010Cell Lymphoma: A Potential Diagnostic Pitfall","volume":"46","author":"Zoumberos N. A.","year":"2019","journal-title":"Journal of Cutaneous Pathology"},{"issue":"12","key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1097\/DAD.0000000000001793","article-title":"Intraepidermal Merkel Cell Carcinoma Mimicking Melanoma In\u00a0Situ: A Case Report","volume":"42","author":"Song Y.","year":"2020","journal-title":"American Journal of Dermatopathology"},{"issue":"4","key":"e_1_2_6_20_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.patol.2020.04.003","article-title":"Carcinoma de Merkel intraepid\u00e9rmico. Presentaci\u00f3n de Un Caso Con expresi\u00f3n de INSM1","volume":"54","author":"Abad M. I.","year":"2021","journal-title":"Revista Espa\u00f1ola de Patolog\u00eda"},{"issue":"11","key":"e_1_2_6_21_1","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/cup.14284","article-title":"CK20\/CK7 Double\u2010Negative Merkel Cell Carcinoma In\u00a0Situ: A Case Report","volume":"49","author":"Richardson W. M.","year":"2022","journal-title":"Journal of Cutaneous Pathology"},{"key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1097\/DAD.0000000000002097","article-title":"Merkel Cell Carcinoma In\u00a0Situ: No More Serendipity?","volume":"44","author":"Brem C. E.","year":"2022","journal-title":"American Journal of Dermatopathology"},{"issue":"8","key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"e58","DOI":"10.1097\/DAD.0000000000002489","article-title":"Merkel Cell Carcinoma In\u00a0Situ Arising in Association With an Infundibular Cyst With Unusual Reticulated Infundibulocystic Proliferation","volume":"45","author":"Peralta I.","year":"2023","journal-title":"American Journal of Dermatopathology"},{"issue":"4","key":"e_1_2_6_24_1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/DAD.0000000000002372","article-title":"MCPyV\u2010Negative Merkel Cell Carcinoma In\u00a0Situ Associated With Immunosuppression","volume":"45","author":"Mazumder A.","year":"2023","journal-title":"American Journal of Dermatopathology"},{"issue":"6","key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/cup.70073","article-title":"Lack of RB and p53 Expression in a Case of CM2B4\u2010Negative Merkel Cell Carcinoma In\u00a0Situ Associated With Squamous Dysplasia","volume":"53","author":"Miller A. C.","year":"2026","journal-title":"Journal of Cutaneous Pathology"},{"issue":"8","key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/cup.14428","article-title":"Pigmented Intraepithelial Merkel Cell Carcinoma Mimicking Melanoma In\u00a0Situ","volume":"50","author":"Holliday D.","year":"2023","journal-title":"Journal of Cutaneous Pathology"},{"issue":"11","key":"e_1_2_6_27_1","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1097\/DAD.0000000000000124","article-title":"Loss of Cytokeratin 20 and Acquisition of Thyroid Transcription Factor\u20101 Expression in a Merkel Cell Carcinoma Metastasis to the Brain","volume":"36","author":"Shalin S. C.","year":"2014","journal-title":"American Journal of Dermatopathology"},{"issue":"4","key":"e_1_2_6_28_1","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/modpathol.2014.148","article-title":"Cytokeratin 20\u2010Negative Merkel Cell Carcinoma Is Infrequently Associated With the Merkel Cell Polyomavirus","volume":"28","author":"Miner A. 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M.","year":"2013","journal-title":"Journal of Cutaneous Pathology"},{"issue":"11","key":"e_1_2_6_34_1","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1038\/s41379-019-0288-7","article-title":"Morphologic and Immunophenotypical Features Distinguishing Merkel Cell Polyomavirus\u2010Positive and Negative Merkel Cell Carcinoma","volume":"32","author":"Kervarrec T.","year":"2019","journal-title":"Modern Pathology"},{"issue":"6","key":"e_1_2_6_35_1","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1097\/00000372-199312000-00002","article-title":"Neuroendocrine (Merkel Cell) Carcinoma With an Intraepidermal Component","volume":"15","author":"Smith K. J.","year":"1993","journal-title":"American Journal of Dermatopathology"},{"issue":"5","key":"e_1_2_6_36_1","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/DAD.0000000000001536","article-title":"TTF\u20101 Positivity in Merkel Cell Carcinoma: The Chosen Clone Matters","volume":"42","author":"Creytens D.","year":"2020","journal-title":"American Journal of Dermatopathology"}],"container-title":["Journal of Cutaneous Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cup.70204","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cup.70204","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cup.70204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:56:05Z","timestamp":1788220565000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cup.70204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":35,"alternative-id":["10.1111\/cup.70204"],"URL":"https:\/\/doi.org\/10.1111\/cup.70204","archive":["Portico"],"relation":{},"ISSN":["0303-6987","1600-0560"],"issn-type":[{"value":"0303-6987","type":"print"},{"value":"1600-0560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"assertion":[{"value":"2026-07-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cup.70204"}}