Understanding YAP1::MAML2 Fusion in Complex Adnexal Tumors

Clinicians and pathologists traditionally classify poroma as a benign sweat gland tumor. Recent genomic advancements reveal that YAP1 fusion adnexal tumors represent a significant molecular category in dermatopathology. While most poromas harbor YAP1::MAML2 or YAP1::NUTM1 transcripts, researchers are uncovering a broader spectrum of these lesions. Specifically, new evidence shows that these genetic drivers can lead to tumors with mixed poroid and sebaceous features. This discovery complicates the traditional diagnostic framework but provides much-needed clarity for complex cases.

Clinical and Histological Spectrum of YAP1 Fusion Adnexal Tumors

A recent clinical report details two distinct cases involving a 55-year-old man and a 90-year-old woman. In both instances, physicians identified small neoplasms located on the back and breast. Microscopically, these lesions exhibited a fascinating biphasic appearance. They combined a superficial poroma component with well-demarcated sebaceous differentiation. Furthermore, immunohistochemical analysis showed diffuse androgen receptor positivity within the sebaceous areas. This specific finding, alongside the loss of YAP1 expression, highlights the complex nature of these neoplasms.

Molecular investigations confirmed that the YAP1::MAML2 fusion transcript acted as the primary driver in these mixed tumors. Consequently, this suggests that Hippo signaling pathway disruption can trigger multiple lines of adnexal differentiation. Therefore, pathologists should consider molecular testing when encountering atypical poroid lesions with sebaceous or follicular elements. Moreover, recognizing these molecular signatures helps in differentiating benign poroid tumors from potentially more aggressive counterparts. Ultimately, these cases confirm that YAP1 fusions define a unique subset of adnexal tumors with diverse morphological presentations.

Frequently Asked Questions

What is the significance of the YAP1::MAML2 fusion in skin tumors?

The YAP1::MAML2 fusion serves as a recurrent oncogenic driver in poromas and related adnexal tumors. It typically results in the loss of normal YAP1 protein expression, which clinicians can detect via immunohistochemistry to aid in precise diagnosis.

Can YAP1 fusion adnexal tumors show sebaceous differentiation?

Yes, recent case reports confirm that these tumors can exhibit a biphasic appearance. They combine classic poroma features with clear sebaceous differentiation, expanding the known morphological spectrum of YAP1-fused neoplasms.

How do pathologists identify these specific fusions?

Pathologists primarily use a combination of immunohistochemistry and molecular analysis. Specifically, the loss of C-terminal YAP1 expression and the presence of the YAP1::MAML2 transcript via RNA sequencing or FISH help confirm the diagnosis.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

1. Noebel C et al. YAP1::MAML2 Fusion in Adnexal Tumors Combining Poroma and Sebaceous Components: Report of Two Cases. Am J Dermatopathol. 2026 Feb 13. doi: 10.1097/DAD.0000000000003234. PMID: 41687124.


2. Sekine S, et al. Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma. J Clin Invest. 2019;129(9):3827-3832.


3. Kervarrec T, et al. YAP1::MAML2, YAP1::NUTM1, and RNF13::PAK2 rearrangements in trichoblastomas and adnexal tumors. Virchows Arch. 2025;487(2):301-310.