CDX2 expression in primary skin tumors—case series and review of the literature

Tekin, Burak; Kundert, Peter; Yang, Hongyu Henry; Guo, Ruifeng

doi:10.1016/j.humpath.2022.07.013

Cited by 3 publications

(3 citation statements)

References 31 publications

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“…The present case provides 2 novel findings in comparison with the previously reported cases of CDX2-positive primary cutaneous tumors other than those of pilomatrical tumors. 2,7,8 The present lesion expressed the adnexal marker SOX9, and both bowenoid and basaloid components were positive for multiple Wnt signaling pathway molecules.…”

Section: Discussionmentioning

confidence: 73%

“…In addition, the “adenocarcinoma” component was also positive for CDX2 and cytokeratin 20. Tekin et al 2 reported 5 cases of CDX2-positive basaloid cutaneous carcinoma with a primitive cytomorphology. Of these, 3 cases had lesions with a focal squamoid morphology and 1 of them was positive for LEF1.…”

Section: Discussionmentioning

confidence: 99%

“…The Wnt signaling pathway, which involves caudal type homeobox 2 (CDX2), beta-catenin, and lymphoid enhancer-binding factor 1 (LEF1), plays an essential role in hair follicle morphogenesis, stem cell proliferation, and hair cycle in the skin. 1 Tekin et al 2 classified CDX2-positive cutaneous tumors into 4 types: those with metastases, those with involvement of anorectal or urethral extramammary Paget disease, pilomatrical tumors, and primary cutaneous carcinomas with an intestinal phenotype. They then proposed an additional tumor category of basaloid cutaneous carcinoma with primitive cytomorphology.…”

Section: Introductionmentioning

confidence: 99%

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A Case of Biphenotypic Adnexal Carcinoma With Bowenoid and Basaloid Features: Focus on the Expression of SOX9 and Wnt Signaling Pathway Molecules, Including CDX2

Sugimoto,

Fujimoto,

Masuo

et al. 2023

The American Journal of Dermatopathology

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An 87-year-old woman presented with a pedunculated nodule of 1.2 × 1.2 × 0.6 cm on her left cheek. Microscopic examination of the lesion revealed bowenoid and rosette-like basaloid components, resembling Bowen disease and neuroendocrine carcinoma, respectively. Immunohistochemically, both components were positive for Wnt signaling pathway molecules—nuclear/cytoplasmic beta-catenin, lymphoid enhancer binding factor 1 (LEF1), and caudal type homeobox 2 (CDX2)—and the adnexal marker SRY-box transcription factor 9 (SOX9). Unlike neuroendocrine tumors and basal cell carcinomas, the basaloid component in the present case was negative for chromogranin A, INSM1, synaptophysin, and p40. Previously reported cases of similar CDX2-positive lesions were diagnosed as squamous cell carcinoma with enteric adenocarcinomatous differentiation and basaloid cutaneous carcinoma with a primitive cytomorphology. However, the lesion in the present case was simultaneously positive for SOX9, indicating adnexal differentiation. In particular, the expression of multiple Wnt signaling pathway molecules indicates follicular differentiation despite the absence of morphological follicular features, such as shadow cells. Moreover, shared immunopositivity for SOX9, CDX2, nuclear/cytoplasmic beta-catenin, and LEF1 by both bowenoid and basaloid components indicated that the bowenoid component did not represent Bowen disease but a part of the adnexal tumor, and that the basaloid component was not a tumor-to-tumor metastasis. After complete excision, no recurrence has been observed for 5 months. The findings of the present case expand the histological spectrum of cutaneous adnexal tumors with follicular immunophenotypic differentiation.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Case of Biphenotypic Adnexal Carcinoma With Bowenoid and Basaloid Features: Focus on the Expression of SOX9 and Wnt Signaling Pathway Molecules, Including CDX2

Sugimoto,

Fujimoto,

Masuo

et al. 2023

The American Journal of Dermatopathology

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Wnt/β-Catenin–Activated Nonpilomatrical Carcinoma of the Skin: A Case Series

Kervarrec,

Cheok Lei,

Sohier

et al. 2024

Modern Pathology

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Role of Immunohistochemistry in the Diagnosis of Pilomatrical Tumors

Alnaqshanbandi,

McAfee,

et al. 2024

American Journal of Surgical Pathology

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Pilomatrical skin tumors harbor mutations in CTNNB1, which encodes for β-catenin, a downstream effector of the Wnt signaling pathway responsible for the differentiation, proliferation, and adhesion of epithelial stem cells. Therefore, downstream molecules, such as CDX2, LEF-1, and SATB2, in the Wnt signaling pathway could be useful diagnostic markers. Here, we sought to investigate the potential of immunohistochemistry (IHC) to differentiate between pilomatricoma and pilomatrical carcinoma, as well as from other cutaneous adnexal tumors. We studied 88 cases of cutaneous tumors (14 pilomatrical carcinomas, 18 pilomatricomas, 13 basal cell carcinomas, 12 squamous cell carcinomas, 12 sebaceous carcinomas, 10 Merkel cell carcinomas, 7 trichoblastomas, and 2 hidradenocarcinomas) using a broad panel of IHC markers: β-catenin, SATB2, CDX2, LEF1, Ber-EP4, and PRAME. Pilomatricoma and pilomatrical carcinoma displayed >75% nuclear staining for β-catenin. CDX2 also strongly stained pilomatrical tumors; however, the staining distribution was limited in pilomatricoma and more widespread in pilomatrical carcinoma. But, overall, it was less than β-catenin. SATB2 and Ber-EP4 expressions were noted only in a subset of both pilomatrical carcinoma and pilomatricoma, whereas LEF-1 showed strong, diffuse nuclear positivity in both pilomatricoma and pilomatrical carcinoma. Among the IHC markers evaluated, none could distinguish between pilomatricoma and pilomatrical carcinoma. However, the combined use of β-catenin with CDX2 markers may assist in not only confirming the pilomatrical nature of the proliferation but also in differentiating benign from malignant cases when there is a significant presence of CDX2 staining. Despite these findings, the diagnosis should continue to primarily depend on a thorough histopathologic examination.

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CDX2 expression in primary skin tumors—case series and review of the literature

Cited by 3 publications

References 31 publications

A Case of Biphenotypic Adnexal Carcinoma With Bowenoid and Basaloid Features: Focus on the Expression of SOX9 and Wnt Signaling Pathway Molecules, Including CDX2

A Case of Biphenotypic Adnexal Carcinoma With Bowenoid and Basaloid Features: Focus on the Expression of SOX9 and Wnt Signaling Pathway Molecules, Including CDX2

Wnt/β-Catenin–Activated Nonpilomatrical Carcinoma of the Skin: A Case Series

Role of Immunohistochemistry in the Diagnosis of Pilomatrical Tumors

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