Engrailed Homeobox 1 and Cytokeratin 19 Are Independent Diagnostic Markers of Eccrine Porocarcinoma and Distinguish It From Squamous Cell Carcinoma

Miura, Keiko; Akashi, Takumi; Namiki, Takeshi; Hishima, Tsunekazu; Bae, Yun‐Jung; Sakurai, Urara; Murano, Keimei; Shiraishi, Junichi; Warabi, Masahiro; Tanizawa, Toru; Tanaka, Michio; Bhunchet, Ekapot; Kumagai, Jun; Ayabe, Shinya; Sekiya, Takahiro; Ando, Noboru; Shintaku, Hiroshi; Kinowaki, Yuko; Tomii, Shohei; Kirimura, Susumu; Kayamori, Kou; Yamamoto, Kurara; Ito, Takashi; Eishi, Yoshinobu

doi:10.1093/ajcp/aqaa066

Cited by 6 publications

(10 citation statements)

References 29 publications

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“…Among the adult organs, En1 is expressed only in the eccrine gland, 12 contrary to its expression in the embryonic brain 29 and epidermis of the ventral limb 10 . In tumor tissues, En1 is occasionally expressed in cutaneous squamous cell carcinoma 12,30 and triple‐negative breast carcinoma 31 occurs in the organs other than the salivary glands and eccrine glands. According to the open database resource of Human Protein Atlas, 32 En1 expression was found in 15 of 207 tumor cases occurring in 20 organs, and only four of them were En1‐positive based on our criteria, which showed En1 expression in more than 25% of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Homeobox transcription factor engrailed homeobox 1 is a possible diagnostic marker for adenoid cystic carcinoma and polymorphous adenocarcinoma

Baba

Akashi

Kayamori

et al. 2020

Pathology International

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Diagnostic utility of a homeobox transcription factor, engrailed homeobox 1 (En1) in the histopathology of salivary gland neoplasms was studied. The expression of En1 was immunohistochemically examined in 51 cases of adenoid cystic carcinoma (AdCC) and 143 cases of other salivary gland neoplasms. In all 51 AdCCs, En1 was expressed in 30–100% of tumor cells. In eight of nine polymorphous adenocarcinomas (PACs), En1 was expressed in 40–100% of tumor cells. Less than 5% of tumor cells expressed En1 in three of 12 epithelial–myoepithelial carcinomas, one of 17 basal cell adenomas (BCAs), and one of 34 pleomorphic adenomas (PAs). Among 55 other carcinoma cases, 1–30% of tumor cells expressed En1 in three salivary duct carcinomas (SDCs) ex PA. None of the myoepitheliomas and Warthin tumors expressed En1. When the cut‐off value of the percentage of En1‐expressing cells was set to 25%, all 51 AdCCs, eight of nine PACs and one SDC ex PA were En1‐positive and the others were En1‐negative. En1 is expressed consistently in AdCCs, frequently in PACs, but rarely in other salivary gland neoplasms. En1 is a possible diagnostic marker for AdCC and PAC in the histopathology of salivary gland neoplasms.

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Section: Discussionmentioning

confidence: 99%

Homeobox transcription factor engrailed homeobox 1 is a possible diagnostic marker for adenoid cystic carcinoma and polymorphous adenocarcinoma

Baba

Akashi

Kayamori

et al. 2020

Pathology International

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“…Moreover, the distinction between porocarcinoma, the malignant counterpart of poroma, and poorly differentiated squamous cell carcinoma can be a diagnostic challenge in current practice. 7 In this context, several immunohistochemical markers have been proposed to distinguish benign and malignant poroid tumors from their differential diagnoses. Indeed, epithelial membrane antigen is expressed in poroma cells, and carcinoembryonic antigen highlights the ductal structures.…”

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confidence: 99%

“…Accordingly, a wide range of epidermal and adnexal neoplasms have to be considered in the differential diagnoses. Moreover, the distinction between porocarcinoma, the malignant counterpart of poroma, and poorly differentiated squamous cell carcinoma can be a diagnostic challenge in current practice 7…”

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confidence: 99%

NUT Is a Specific Immunohistochemical Marker for the Diagnosis of YAP1-NUTM1-rearranged Cutaneous Poroid Neoplasms

Macagno

Kervarrec

Sohier

et al. 2021

American Journal of Surgical Pathology

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YAP1-NUTM1 fusion transcripts have been recently reported in poroma and porocarcinoma. NUTM1 translocation can be screened by nuclear protein in testis (NUT) immunohistochemistry in various malignancies, but its diagnostic performance has not been thoroughly validated on a large cohort of cutaneous epithelial neoplasms. We have evaluated NUT immunohistochemical expression in a large cohort encompassing 835 cases of various cutaneous epidermal or adnexal epithelial neoplasms. NUT expression was specific to eccrine poromas and porocarcinoma, with 32% of cases showing NUT expression. All other cutaneous tumors tested lacked NUT expression, including mimickers such as seborrheic keratosis, Bowen disease, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, nodular hidradenoma, and all other adnexal tumors tested. Remarkably, NUT expression was more frequent in a distinct morphologic subgroup. Indeed, 93% of poroid hidradenoma (dermal/subcutaneous nodular poroma, 13/14) and 80% of poroid hidradenocarcinoma cases (malignant poroid hidradenoma, 4/5) showed NUT expression, in contrast to 17% and 11% of classic poroma (4/23) and porocarcinoma cases (4/35), respectively. RNA sequencing of 12 NUT-positive neoplasms further confirmed the presence of a YAP1-NUTM1 fusion transcript in all cases, and also an EMC7-NUTM1 gene fusion in a single case. In the setting of a cutaneous adnexal neoplasm, nuclear expression of NUT accurately and specifically diagnosed a specific subgroup of benign and malignant poroid tumors, all associated with a NUTM1 fusion, which frequently harbored a poroid hidradenoma morphology.

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“…The morphology of porocarcinomas can be variable, with the squamoid variant posing a particular challenge to differentiate from invasive squamous cell carcinoma, as reflected in our case. [7][8][9][10] However, it is imperative to make this histologic distinction because porocarcinomas have been shown to have a higher risk of local recurrence, lymph node metastasis, systemic metastasis, and overall mortality compared with squamous cell carcinoma. 7 Helpful histologic clues that distinguish this tumor from squamous cell carcinoma include the prominent anastomosing cords and the identification of a coexisting poroma component.…”

Section: Discussionmentioning

confidence: 99%

“…For example, 94% of porocarcinomas in 1 study were found to express both engrailed homeobox 1 (En1) and CK19, compared with the lack of combined expression in any of the squamous cell carcinomas examined. 9 CD117 (C-kit) has also been shown to be useful in separating squamous cell carcinoma from porocarcinoma because most porocarcinomas should express CD117, at least focally, while only a minority of squamous cell carcinomas express CD117 (∼20%). 11…”

Section: Discussionmentioning

confidence: 99%

An Unusual Case of a Scrotal Porocarcinoma and Review of the Literature

Hartsough¹,

Moran²,

Devins³

et al. 2022

The American Journal of Dermatopathology

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:Porocarcinomas are rare tumors derived from the acrosyringium and eccrine ducts, which most commonly occur on the lower extremities or head and neck region in older adults. Microscopically, they invariably demonstrate continuity with the epithelium, showing downgrowth of broad anastomosing bands with more infiltrative intradermal cords and nests of pleomorphic tumor cells with ductal lumina; an associated poroma may also be seen. We report an unusual case of a porocarcinoma arising on the scrotum of a 55-year-old man. Because of the extraordinary location and the presence of keratinizing squamous differentiation, distinction from a squamous cell carcinoma was particularly challenging. Close examination revealed the presence of a co-existing poroma, and immunohistochemistry revealed loss of YAP1 with diffuse nuclear expression of NUT in both the porocarcinoma and poroma components. This finding is particularly suggestive of a YAP1::NUTM1 fusion which has been reported to be highly specific for poroid neoplasms. Distinction of porocarcinoma from its mimics is important due to the frequent aggressive behavior of this neoplasm.

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Engrailed Homeobox 1 and Cytokeratin 19 Are Independent Diagnostic Markers of Eccrine Porocarcinoma and Distinguish It From Squamous Cell Carcinoma

Cited by 6 publications

References 29 publications

Homeobox transcription factor engrailed homeobox 1 is a possible diagnostic marker for adenoid cystic carcinoma and polymorphous adenocarcinoma

Homeobox transcription factor engrailed homeobox 1 is a possible diagnostic marker for adenoid cystic carcinoma and polymorphous adenocarcinoma

NUT Is a Specific Immunohistochemical Marker for the Diagnosis of YAP1-NUTM1-rearranged Cutaneous Poroid Neoplasms

An Unusual Case of a Scrotal Porocarcinoma and Review of the Literature

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