Differential expression of PHLDA1 (TDAG51) in basal cell carcinoma and trichoepithelioma
ABSTRACT Background A recent small series demonstrated perfect sensitivity and specificity utilizing immunostaining for PHLDA1, a marker of follicular stem cells, in the distinction of desmoplastic trichoepithelioma and morphoeiform basal cell carcinoma (BCC) in small biopsy specimens. Objectives To assess this result more broadly. Methods We performed immunoperoxidase staining of BCCs (superficial n = 16, nodular n = 15, micronodular n = 15, infiltrative n = 17, morphoeiform n = 16, infundibulocystic n = 14) and trichoepitheliomas (conventional n = 19, desmoplastic n = 16) with PHLDA1. Results Morphoeiform BCCs typically lacked PHLDA1 staining (88% demonstrated no staining and 12% of cases had staining in < 25% of the tumour), while in contrast 74% of classical and 88% of desmoplastic trichoepitheliomas demonstrated strong PHLDA1 staining in over half of the tumour. However, micronodular BCCs demonstrated focal to diffuse positive staining in a third of the cases. Conclusions Based upon our staining results, we discuss the biological significance of PHLDA1 expression and the limits in its diagnostic utility.
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ABSTRACT: Pilomatricomas are tumors that emulate the differentiation of matrix cells of the hair follicle, showing cortical differentiation, with sequential of expression of K35 and K31 keratins. Beta-catenin gene is frequently mutated in pilomatricoma, leading to beta-catenin nuclear accumulation, and to downstream expression of LEF1. Skin matrical tumors other than pilomatricoma are very rare, and comprise purely matrical tumors and focally matrical tumors. We aimed at studying cortical differentiation, beta-catenin pathway, and expression of the follicular stem-cell marker PHLDA1 in a series of matrical tumors other than pilomatricoma. In 36 prospectively collected tumors, K31, K35, CK17, LEF1, HOXC13, beta-catenin, and PHLDA1 expression was evaluated. Five pilomatricomas were used as controls. In 18 purely matrical tumors (11 matrical carcinomas, 4 melanocytic matricomas, 3 matricomas) and 18 focally matrical tumors (11 basal cell carcinomas, 3 trichoepithelioma/trichoblastomas, 4 others), sequential K35, HOXC13 and K31 expression was found, indicating cortical differentiation. Germinative matrix cells were always CK17-, and showed nuclear beta-catenin accumulation, with LEF1 and PHLDA1 expression. Nuclear beta-catenin and LEF1 expression was highly conserved in matrical tumors, and suggested a common tumorigenesis driven by Wnt pathway activation. PHLDA1 was consistently expressed in matrical tumors and in areas of matrical differentiation.Journal of Cutaneous Pathology 02/2014; 41(5). DOI:10.1111/cup.12313 · 1.56 Impact Factor
Article: TrichoblastomasAnnales de Dermatologie et de Vénéréologie 08/2014; 141(8-9). DOI:10.1016/j.annder.2014.06.001 · 0.67 Impact Factor
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ABSTRACT: Nevus sebaceus is commonly associated with the development of secondary neoplasms. Data on the frequency of malignant tumors vary considerably in published reports. We sought to analyze the distribution of secondary neoplasm in nevus sebaceus. A retrospective analysis of all cases of nevus sebaceus diagnosed at the Ackerman Academy of Dermatopathology from 1999 to 2012 was conducted. A total of 706 patients (707 specimens) were included in the study. Trichoblastoma was the most frequent benign tumor (n = 52, 7.4%) followed by syringocystadenoma papilliferum (n = 33, 5.2%). Malignant tumors were present in 2.5% of the specimens with basal cell carcinoma being the most common (n = 8, 1.1%) followed by squamous cell carcinoma (n = 4, 0.57%). The incidence of secondary neoplasms was statistically related to age and anatomic site (P < .05). Almost all malignant tumors were seen in adults. Some of our cases were referred for second opinion and there may be a bias in our data toward unusual secondary neoplasms. Our study confirms that most of the secondary neoplasms arising in association with nevus sebaceus are benign. As no malignant tumors were seen in children, we believe it is reasonable to delay surgical management until adolescence.Journal of the American Academy of Dermatology 11/2013; 70(2). DOI:10.1016/j.jaad.2013.10.004 · 5.00 Impact Factor