TRPS1 expression in primary and secondary extramammary Paget diseases: An immunohistochemical analysis of 93 cases

Liu, Yi A.; Collins, Katrina; Aung, Phyu P.; Nagarajan, Priyadharsini; Curry, Jonathan L.; Prieto, Victor G.; Torres-Cabala, Carlos A.; Cho, Woo Cheal

doi:10.1016/j.humpath.2023.11.004

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…However, to our knowledge, there has been limited investigation into the TRPS1 immunoreactivity status in cutaneous mesenchymal tumors and tumors of uncertain differentiation, such as AFXs or PDSs. Our research fills this gap by demonstrating that strong and diffuse TRPS1 expression is not exclusive to certain cutaneous epithelial neoplasms, such as SCCs [ 2 , 3 ], mammary and extramammary Paget diseases [ 2 , 4 ], and EMPSGCs [ 5 ], but is also observed in a subset of non-epithelial and non-melanocytic cutaneous neoplasms. In our study, we found that TRPS1 expression was frequently observed in tumors of uncertain differentiation (AFX and PDS), tumors of fibrohistiocytic origin (DF and DFSP), and tumors of smooth muscle origin (leiomyoma and leiomyosarcoma).…”

Section: Discussionmentioning

confidence: 98%

“…Previous studies have primarily focused on examining TRPS1 expression patterns in cutaneous epithelial and melanocytic tumors [ 2 , 3 , 4 , 5 ]. However, to our knowledge, there has been limited investigation into the TRPS1 immunoreactivity status in cutaneous mesenchymal tumors and tumors of uncertain differentiation, such as AFXs or PDSs.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent studies challenge this notion, revealing that TRPS1 expression extends beyond breast neoplasms. Robust TRPS1 expression has been observed in various cutaneous epithelial neoplasms, including squamous cell carcinomas [ 2 , 3 ], mammary and extramammary Paget diseases [ 2 , 4 ], and adnexal neoplasms [ 3 , 5 , 6 , 7 ]. In dermatopathology, TRPS1 emerges as a valuable tool, particularly in distinguishing primary from secondary extramammary Paget disease, especially when arising in non-perianal cutaneous sites [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Robust TRPS1 expression has been observed in various cutaneous epithelial neoplasms, including squamous cell carcinomas [ 2 , 3 ], mammary and extramammary Paget diseases [ 2 , 4 ], and adnexal neoplasms [ 3 , 5 , 6 , 7 ]. In dermatopathology, TRPS1 emerges as a valuable tool, particularly in distinguishing primary from secondary extramammary Paget disease, especially when arising in non-perianal cutaneous sites [ 4 ]. Moreover, TRPS1 aids in confirming diagnoses of endocrine mucin-producing sweat gland carcinoma (EMPSGC) when combined with neuroendocrine markers, notably INSM1, as no other morphologic mimics of EMPSGC demonstrate strong co-expression of TRPS1 and INSM1 [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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TRPS1 Expression Is Frequently Seen in a Subset of Cutaneous Mesenchymal Neoplasms and Tumors of Uncertain Differentiation: A Potential Diagnostic Pitfall

Kim,

Liu,

Wang

et al. 2024

Dermatopathology

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Although extensively studied in cutaneous epithelial neoplasms, the TRPS1 immunoreactivity in cutaneous mesenchymal neoplasms and tumors of uncertain differentiation (CMNTUDs), such as atypical fibroxanthoma (AFX), remains largely unexplored. We assessed TRPS1 immunoreactivity in 135 CMNTUDs, comprising 46 fibrohistiocytic/fibroblastic tumors, 28 vascular tumors, 24 peripheral nerve sheath tumors (PNSTs), 21 tumors of uncertain differentiation, and 16 smooth muscle tumors. Additionally, we included selected cases of melanoma with spindled cell morphology or desmoplastic features (n = 9) and sarcomatoid squamous cell carcinoma (SSCC) (n = 5) to compare TRPS1 expression patterns with those of AFX. TRPS1 expression was prevalent in dermatofibromas (24/24), leiomyomas (8/8), AFXs/pleomorphic dermal sarcoma (PDS) (20/21), dermatofibrosarcomas protuberans (14/22), and leiomyosarcomas (6/8). It was uncommon in angiosarcomas (3/20), Kaposi sarcomas (2/8), and neurofibromas (5/17) and absent in perineuriomas (0/2). AFXs/PDS exhibited the highest median H-score of 240, contrasting with minimal TRPS1 immunoreactivity in vascular neoplasms and PNSTs, with median H-scores consistently below 10. Significant differences in H-score were observed between AFXs/PDS and angiosarcomas (p < 0.001), melanomas (p < 0.001), and leiomyosarcomas (p = 0.029). However, no significant difference was found compared to SSCCs, suggesting limited discriminatory power of TRPS1 in this context. This study sheds light on TRPS1 expression patterns in a subset of CMNTUDs, extending beyond prior studies primarily focused on epithelial tumors, while underscoring potential pitfalls associated with TRPS1 immunohistochemistry.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

TRPS1 Expression Is Frequently Seen in a Subset of Cutaneous Mesenchymal Neoplasms and Tumors of Uncertain Differentiation: A Potential Diagnostic Pitfall

Kim,

Liu,

Wang

et al. 2024

Dermatopathology

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“…It is also important to distinguish EMPD from mammary Paget disease, which is an epidermal extension from breast cancer, and secondary EMPD, which is an extension from visceral cancers 1 , 2 . A panel of immunohistochemical staining such as CK7, CK20, GCDFP15, CDX2, and TRPS1 can be helpful in making this distinction 1 , 2 , 15 , 16 . EMPD lesions often have an unclear tumor border and may have hidden skip lesions 17 .…”

Section: Introductionmentioning

confidence: 99%

FOXM1: a new therapeutic target of extramammary Paget disease

Ito,

Tanaka,

Kaku-Ito

et al. 2024

Sci Rep

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Extramammary Paget disease (EMPD) is a rare skin cancer that primarily affects older individuals predominantly in areas with apocrine sweat glands. Although most early EMPD lesions are indolent, patients with metastatic EMPD have a poor prognosis due to the lack of effective systemic treatment. In this study, we investigated the role of forkhead box M1 (FOXM1), a potent transcription factor, in EMPD and assessed the potential of FOXM1 as a therapeutic target. Immunohistochemistry of 112 primary and 17 metastatic EMPD samples revealed that FOXM1 expression increased with tumor progression. Patients in whom FOXM1 was expressed in more than 10% of tumor cells had significantly shorter disease-specific survival than the other patients (p = 0.0397). In in vitro studies using our newly established EMPD cell line, KS-EMPD-1, we found high expression of FOXM1. Knockdown of FOXM1 impaired tumor cell viability, migration, and invasion. Inhibition of FOXM1 using thiostrepton also reduced tumor cell viability in a dose-dependent manner. These findings suggest that FOXM1 is a promising therapeutic target for patients with EMPD.

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Syringocystadenoma Papilliferum-Like Features in Poroma: An Unusual Morphologic Pattern of Poroma or True Synchronous Occurrence of 2 Distinct Neoplasms?

Alsawas,

Muhaj,

Aung

et al. 2024

The American Journal of Dermatopathology

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Poromas are benign adnexal neoplasms of eccrine origin, believed to arise from the outer layer of acrosyringia and upper dermal eccrine ducts, with a predilection for glabrous skin. They typically present as a pink or red papule with a surrounding thin moat on the palms and soles. We report a case of poroma with histopathologic features reminiscent of syringocystadenoma papilliferum (SCAP). A 70-year-old woman presented with a 2.0 cm pedunculated nodule on the left suprapubic abdomen. Histopathologically, the lesion predominantly displayed features of a conventional poroma but also included areas with endophytic invaginations lined by large, plump epithelioid cells with abundant eosinophilic cytoplasm and occasional decapitation secretion, alongside a stroma rich in plasma cells—characteristics suggestive of SCAP. However, definitive bilayers with myoepithelial cells were not observed. Immunohistochemical studies revealed that the tumor cells were positive for TRPS1 (particularly around SCAP-like areas) and CEA (indicating ductal differentiation), but negative for BRAF V600E and NUT. The diagnosis of poroma with apocrine differentiation mimicking SCAP was favored. This unusual morphologic variation in poromas is rare, with fewer than 5 cases documented in the literature. These SCAP-like features likely represent a variation within the morphologic spectrum of poromas rather than the presence of 2 synchronous tumors. Our case highlights the importance of recognizing such variations in poroid neoplasms to ensure accurate diagnosis.

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TRPS1 expression in primary and secondary extramammary Paget diseases: An immunohistochemical analysis of 93 cases

Cited by 7 publications

References 11 publications

TRPS1 Expression Is Frequently Seen in a Subset of Cutaneous Mesenchymal Neoplasms and Tumors of Uncertain Differentiation: A Potential Diagnostic Pitfall

TRPS1 Expression Is Frequently Seen in a Subset of Cutaneous Mesenchymal Neoplasms and Tumors of Uncertain Differentiation: A Potential Diagnostic Pitfall

FOXM1: a new therapeutic target of extramammary Paget disease

Syringocystadenoma Papilliferum-Like Features in Poroma: An Unusual Morphologic Pattern of Poroma or True Synchronous Occurrence of 2 Distinct Neoplasms?

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