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Klaus Sellheyer - One of the best experts on this subject based on the ideXlab platform.
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follicular stem cell marker phlda1 tdag51 is superior to cytokeratin 20 in differentiating between Trichoepithelioma and basal cell carcinoma in small biopsy specimens
Journal of Cutaneous Pathology, 2011Co-Authors: Klaus Sellheyer, Paula NelsonAbstract:Background: Biopsies submitted to dermatopathologists are becoming increasingly smaller in size and thus the available diagnostic material is reduced. The distinction between Trichoepithelioma and basal cell carcinoma remains challenging, particularly if tissue is limited. Merkel cells, which can be highlighted by means of cytokeratin-20 (CK20) immunostaining, are used as a surrogate marker for the diagnosis of Trichoepithelioma, as Merkel cells commonly colonize Trichoepithelioma but are generally lacking in basal cell carcinomas. In the current study, we examined the expression of a recently characterized follicular stem cell marker, PHLDA1 (pleckstrin homology-like domain, family A, member 1), also known as TDAG51 (T-cell death-associated gene 51). Methods: Using standard immunohistochemical techniques, we examined 19 Trichoepitheliomas and 11 basal cell carcinomas for the expression of PHLDA1 and compared it with CK20 expression. Results: All 19 Trichoepitheliomas were immunoreactive for PHLDA1 and all 11 basal cell carcinomas lacked PHLDA1 expression. Two of eleven basal cell carcinomas harbored CK20-positive Merkel cells. Three Trichoepitheliomas lacked secondary CK20-positive cells. Conclusions: Our results suggest that PHLDA1 represents a practical and easily used tool that can be applied to the differentiation of Trichoepithelioma and basal cell carcinoma in small biopsy specimens. Rather than searching for CK20-positive Merkel cells, assessing PHLDA1 expression allows the differential diagnosis between Trichoepithelioma and basal cell carcinoma to be solved at scanning magnification. Sellheyer K, Nelson P. Follicular stem cell marker PHLDA1 (TDAG51) is superior to cytokeratin-20 in differentiating between Trichoepithelioma and basal cell carcinoma in small biopsy specimens.
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does the peritumoral stroma of basal cell carcinoma recapitulate the follicular connective tissue sheath
Journal of Cutaneous Pathology, 2011Co-Authors: Klaus Sellheyer, Dieter KrahlAbstract:Background: There are compelling embryologic and anatomic relationships within adnexal tumors. However, these are mostly perceived within the epithelial component while the stromal component of the tumors is frequently overlooked. In postnatal skin, nestin is almost exclusively expressed in the perifollicular mesenchyme. This study examines the expression of this neuroepithelial stem cell protein in trichoblastoma/Trichoepithelioma and in basal cell carcinoma (BCC), which is increasingly being viewed as follicular in nature. Methods: We employed standard immunohistochemical methods with three different antibodies to examine the expression of nestin in 25 BCCs and compared the staining pattern with that of 7 trichoblastomas and 11 Trichoepitheliomas. Results: Nestin is expressed in the peritumoral stroma of all tumors examined and is limited to the immediate layer of mesenchymal cells surrounding the tumor epithelium. In BCC, nestin-immunoreactive cells are found as a sheath of thin, spindled fibroblasts, while reactive cells are plump in Trichoepitheliomas/trichoblastomas. Conclusions: We postulate that the peritumoral stroma of BCC imitates the perifollicular connective tissue sheath, while in contrast that of Trichoepithelioma/trichoblastoma is similar to the papillary and immediate peripapillary follicular mesenchyme. Further functional and animal experimental studies are needed to test this hypothesis. Sellheyer K, Krahl D. Does the peritumoral stroma of basal cell carcinoma recapitulate the follicular connective tissue sheath? A comparative analysis of nestin expression in basal cell carcinoma, Trichoepithelioma, trichoblastoma and the hair follicle.
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Follicular stem cell marker PHLDA1 (TDAG51) is superior to cytokeratin‐20 in differentiating between Trichoepithelioma and basal cell carcinoma in small biopsy specimens
Journal of cutaneous pathology, 2011Co-Authors: Klaus Sellheyer, Paula NelsonAbstract:Background: Biopsies submitted to dermatopathologists are becoming increasingly smaller in size and thus the available diagnostic material is reduced. The distinction between Trichoepithelioma and basal cell carcinoma remains challenging, particularly if tissue is limited. Merkel cells, which can be highlighted by means of cytokeratin-20 (CK20) immunostaining, are used as a surrogate marker for the diagnosis of Trichoepithelioma, as Merkel cells commonly colonize Trichoepithelioma but are generally lacking in basal cell carcinomas. In the current study, we examined the expression of a recently characterized follicular stem cell marker, PHLDA1 (pleckstrin homology-like domain, family A, member 1), also known as TDAG51 (T-cell death-associated gene 51). Methods: Using standard immunohistochemical techniques, we examined 19 Trichoepitheliomas and 11 basal cell carcinomas for the expression of PHLDA1 and compared it with CK20 expression. Results: All 19 Trichoepitheliomas were immunoreactive for PHLDA1 and all 11 basal cell carcinomas lacked PHLDA1 expression. Two of eleven basal cell carcinomas harbored CK20-positive Merkel cells. Three Trichoepitheliomas lacked secondary CK20-positive cells. Conclusions: Our results suggest that PHLDA1 represents a practical and easily used tool that can be applied to the differentiation of Trichoepithelioma and basal cell carcinoma in small biopsy specimens. Rather than searching for CK20-positive Merkel cells, assessing PHLDA1 expression allows the differential diagnosis between Trichoepithelioma and basal cell carcinoma to be solved at scanning magnification. Sellheyer K, Nelson P. Follicular stem cell marker PHLDA1 (TDAG51) is superior to cytokeratin-20 in differentiating between Trichoepithelioma and basal cell carcinoma in small biopsy specimens.
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phlda1 tdag51 is a follicular stem cell marker and differentiates between morphoeic basal cell carcinoma and desmoplastic Trichoepithelioma
British Journal of Dermatology, 2011Co-Authors: Klaus Sellheyer, Dieter KrahlAbstract:Summary Background Morphoeic basal cell carcinoma (BCC) and desmoplastic Trichoepithelioma can often be difficult to differentiate on routine sections and few reliable immunohistochemical markers are currently available. Recent cDNA microarray studies revealed the pleckstrin homology-like domain, family A, member 1 protein (PHLDA1) as a highly reliable marker of the hair follicle stem cells. Given the differentiation of Trichoepithelioma along the follicular lineage and the proposed role of PHLDA1 as a follicular stem cell marker, we examined the staining pattern of PHLDA1 in the desmoplastic variant of Trichoepithelioma and in its differential diagnostic conundrum, morphoeic BCC. Objectives To describe the expression pattern of PHLDA1 in morphoeic BCC and desmoplastic Trichoepithelioma. Methods Evaluation of the staining pattern for PHLDA1 was performed using standard immunohistochemical techniques. For comparison reasons, we analysed staining for PHLDA1 in normal skin structures with particular reference to the hair follicle. Results With the exception of one case, all 16 desmoplastic Trichoepitheliomas were immunoreactive with more than 80% of the cells stained, whereas all 14 morphoeic BCCs were PHLDA1-negative with the exception of ulcerated tumours. In the latter, the tumour islands close to the ulcer were PHLDA1-positive whereas the deeper located tumour portions remained immunonegative. PHLDA 1 was prominently expressed in the hair follicle bulge of terminal and vellus hair follicles. Conclusions The hair follicle bulge marker PHLDA1 differentiates between desmoplastic Trichoepitheliomas and nonulcerated examples of morphoeic BCCs. We suggest incorporating PHLDA1 in the diagnostic work-up of difficult to differentiate basaloid tumours.
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p75 neurotrophin receptor differentiates between morphoeic basal cell carcinoma and desmoplastic Trichoepithelioma insights into the histogenesis of adnexal tumours based on embryology and hair follicle biology
British Journal of Dermatology, 2010Co-Authors: Dieter Krahl, Klaus SellheyerAbstract:Summary Background Tumour development is frequently described in the basic pathology literature as a recapitulation of embryogenesis. However, a link between the embryology of the skin and the histogenesis of adnexal tumours has been largely overlooked. The low-affinity p75 neurotrophin receptor (p75NTR) has a profound role in hair follicle biology. We therefore speculated that it is involved in the histogenesis of follicular adnexal tumours. One of the most challenging diagnoses in dermatopathology is differentiating morphoeic basal cell carcinoma from desmoplastic Trichoepithelioma. Objectives To describe the expression pattern of p75NTR during cutaneous embryogenesis, in the adult hair follicle and in morphoeic basal cell carcinoma and desmoplastic Trichoepithelioma. Methods Evaluation of the staining pattern for p75NTR was performed using standard immunohistochemical techniques. For comparison, we examined staining for cytokeratin 20 which highlights Merkel cells. Results All 17 desmoplastic Trichoepitheliomas were immunoreactive with > 80% of the cells stained, whereas 12 of the 14 (86%) morphoeic basal cell carcinomas were p75NTR negative. In the two positive cases of morphoeic basal cell carcinoma < 30% of cells were labelled. In the late bulbous hair peg stage and in the postnatal anagen hair follicle p75NTR highlights the outer root sheath. Conclusions Our results support the classification of desmoplastic Trichoepithelioma as a follicular hamartoma mimicking the outer root sheath. In contrast, the lack of p75NTR expression in morphoeic basal cell carcinoma favours a concept of this tumour as a more primitive follicular lesion with the characteristics of a carcinoma and not a hamartoma. We suggest including p75NTR as a tool in the differential diagnosis between morphoeic basal cell carcinoma and desmoplastic Trichoepithelioma.
Dieter Krahl - One of the best experts on this subject based on the ideXlab platform.
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does the peritumoral stroma of basal cell carcinoma recapitulate the follicular connective tissue sheath
Journal of Cutaneous Pathology, 2011Co-Authors: Klaus Sellheyer, Dieter KrahlAbstract:Background: There are compelling embryologic and anatomic relationships within adnexal tumors. However, these are mostly perceived within the epithelial component while the stromal component of the tumors is frequently overlooked. In postnatal skin, nestin is almost exclusively expressed in the perifollicular mesenchyme. This study examines the expression of this neuroepithelial stem cell protein in trichoblastoma/Trichoepithelioma and in basal cell carcinoma (BCC), which is increasingly being viewed as follicular in nature. Methods: We employed standard immunohistochemical methods with three different antibodies to examine the expression of nestin in 25 BCCs and compared the staining pattern with that of 7 trichoblastomas and 11 Trichoepitheliomas. Results: Nestin is expressed in the peritumoral stroma of all tumors examined and is limited to the immediate layer of mesenchymal cells surrounding the tumor epithelium. In BCC, nestin-immunoreactive cells are found as a sheath of thin, spindled fibroblasts, while reactive cells are plump in Trichoepitheliomas/trichoblastomas. Conclusions: We postulate that the peritumoral stroma of BCC imitates the perifollicular connective tissue sheath, while in contrast that of Trichoepithelioma/trichoblastoma is similar to the papillary and immediate peripapillary follicular mesenchyme. Further functional and animal experimental studies are needed to test this hypothesis. Sellheyer K, Krahl D. Does the peritumoral stroma of basal cell carcinoma recapitulate the follicular connective tissue sheath? A comparative analysis of nestin expression in basal cell carcinoma, Trichoepithelioma, trichoblastoma and the hair follicle.
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phlda1 tdag51 is a follicular stem cell marker and differentiates between morphoeic basal cell carcinoma and desmoplastic Trichoepithelioma
British Journal of Dermatology, 2011Co-Authors: Klaus Sellheyer, Dieter KrahlAbstract:Summary Background Morphoeic basal cell carcinoma (BCC) and desmoplastic Trichoepithelioma can often be difficult to differentiate on routine sections and few reliable immunohistochemical markers are currently available. Recent cDNA microarray studies revealed the pleckstrin homology-like domain, family A, member 1 protein (PHLDA1) as a highly reliable marker of the hair follicle stem cells. Given the differentiation of Trichoepithelioma along the follicular lineage and the proposed role of PHLDA1 as a follicular stem cell marker, we examined the staining pattern of PHLDA1 in the desmoplastic variant of Trichoepithelioma and in its differential diagnostic conundrum, morphoeic BCC. Objectives To describe the expression pattern of PHLDA1 in morphoeic BCC and desmoplastic Trichoepithelioma. Methods Evaluation of the staining pattern for PHLDA1 was performed using standard immunohistochemical techniques. For comparison reasons, we analysed staining for PHLDA1 in normal skin structures with particular reference to the hair follicle. Results With the exception of one case, all 16 desmoplastic Trichoepitheliomas were immunoreactive with more than 80% of the cells stained, whereas all 14 morphoeic BCCs were PHLDA1-negative with the exception of ulcerated tumours. In the latter, the tumour islands close to the ulcer were PHLDA1-positive whereas the deeper located tumour portions remained immunonegative. PHLDA 1 was prominently expressed in the hair follicle bulge of terminal and vellus hair follicles. Conclusions The hair follicle bulge marker PHLDA1 differentiates between desmoplastic Trichoepitheliomas and nonulcerated examples of morphoeic BCCs. We suggest incorporating PHLDA1 in the diagnostic work-up of difficult to differentiate basaloid tumours.
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p75 neurotrophin receptor differentiates between morphoeic basal cell carcinoma and desmoplastic Trichoepithelioma insights into the histogenesis of adnexal tumours based on embryology and hair follicle biology
British Journal of Dermatology, 2010Co-Authors: Dieter Krahl, Klaus SellheyerAbstract:Summary Background Tumour development is frequently described in the basic pathology literature as a recapitulation of embryogenesis. However, a link between the embryology of the skin and the histogenesis of adnexal tumours has been largely overlooked. The low-affinity p75 neurotrophin receptor (p75NTR) has a profound role in hair follicle biology. We therefore speculated that it is involved in the histogenesis of follicular adnexal tumours. One of the most challenging diagnoses in dermatopathology is differentiating morphoeic basal cell carcinoma from desmoplastic Trichoepithelioma. Objectives To describe the expression pattern of p75NTR during cutaneous embryogenesis, in the adult hair follicle and in morphoeic basal cell carcinoma and desmoplastic Trichoepithelioma. Methods Evaluation of the staining pattern for p75NTR was performed using standard immunohistochemical techniques. For comparison, we examined staining for cytokeratin 20 which highlights Merkel cells. Results All 17 desmoplastic Trichoepitheliomas were immunoreactive with > 80% of the cells stained, whereas 12 of the 14 (86%) morphoeic basal cell carcinomas were p75NTR negative. In the two positive cases of morphoeic basal cell carcinoma < 30% of cells were labelled. In the late bulbous hair peg stage and in the postnatal anagen hair follicle p75NTR highlights the outer root sheath. Conclusions Our results support the classification of desmoplastic Trichoepithelioma as a follicular hamartoma mimicking the outer root sheath. In contrast, the lack of p75NTR expression in morphoeic basal cell carcinoma favours a concept of this tumour as a more primitive follicular lesion with the characteristics of a carcinoma and not a hamartoma. We suggest including p75NTR as a tool in the differential diagnosis between morphoeic basal cell carcinoma and desmoplastic Trichoepithelioma.
Julide Tok Celebi - One of the best experts on this subject based on the ideXlab platform.
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mutations in the cyld gene in brooke spiegler syndrome familial cylindromatosis and multiple familial Trichoepithelioma lack of genotype phenotype correlation
Journal of Investigative Dermatology, 2005Co-Authors: Sarah Bowen, Melissa Gill, David A Lee, Galen H Fisher, Roy G Geronemus, Marialuisa Espinel Vazquez, Julide Tok CelebiAbstract:Brooke-Spiegler syndrome (BSS), familial cylindromatosis (FC), and multiple familial Trichoepithelioma (MFT), originally described as distinct entities, share overlapping clinical findings. Patients with BSS are predisposed to multiple skin appendage tumors such as cylindroma, Trichoepithelioma, and spiradenoma. FC, however, is characterized by cylindromas and MFT by Trichoepitheliomas as the only tumor type. These disorders have recently been associated with mutations in the CYLD gene. In this report, we describe three families with BSS, one with FC, and two with MFT phenotypes associated with novel and recurrent mutations in CYLD. We provide evidence that these disorders represent phenotypic variation of a single entity and lack genotype-phenotype correlation.
A. Riyaz - One of the best experts on this subject based on the ideXlab platform.
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Epithelioma Adenoides Cysticum: A Report of Two Cases in a Family.
International Journal of Trichology, 2016Co-Authors: Najeeba Riyaz, Bindurani Sudhamani, A. RiyazAbstract:: Epithelioma adenoides cysticum or multiple Trichoepitheliomas are rare benign hamartomas arising from the hair germ. A 35-year-old female presented with multiple skin-colored firm papules and nodules mainly affecting the central face, scalp, and external ear canal since the age of 9 years. The lesions gradually increased with age. Her 13-year-old son also had similar but smaller lesions on the central face. Histopathology was consistent with Trichoepithelioma.
Meera Mahalingam - One of the best experts on this subject based on the ideXlab platform.
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Microcystic adnexal carcinoma: an immunohistochemical reappraisal
Modern Pathology, 2008Co-Authors: Mai P Hoang, Karen A Dresser, Payal Kapur, Whitney A High, Meera MahalingamAbstract:Even though immunohistochemical comparisons of microcystic adnexal carcinoma vs infiltrative basal cell carcinoma and desmoplastic Trichoepithelioma exist, they are mostly restricted to the use of a single stain. In addition, a comparison with squamous cell carcinoma has not been reported previously. In this study, we compare the expression of cytokeratin (CK) 15, CK7, CK20, CK903, carcinoembryonic antigen (CEA), CD10, CD15 and BerEP4 in 13 microcystic adnexal carcinoma, eight desmoplastic Trichoepithelioma, 10 infiltrative basal cell carcinoma, and eight squamous cell carcinoma of which five exhibited ductal differentiation. We found that the majority of microcystic adnexal carcinoma (92%) and desmoplastic Trichoepithelioma (100%) cases expressed CK15 while the infiltrative basal cell carcinoma and squamous cell carcinoma cases were all negative. Forty percent of infiltrative basal cell carcinoma expressed CK7; while only two microcystic adnexal carcinoma cases (15%) and one squamous cell carcinoma with ductal differentiation (12%) expressed CK7 in the remaining three tumor categories. None of the desmoplastic Trichoepithelioma expressed CK7. All tumors were strongly positive for CK903. While the neoplastic cells were negative, luminal staining of ductal structures was noted for CK7, CD15 and CEA in some of the microcystic adnexal carcinoma, desmoplastic Trichoepithelioma and squamous cell carcinoma with ductal differentiation cases. Sixty percent of infiltrative basal cell carcinoma, 31% of microcystic adnexal carcinoma, and 25% of squamous cell carcinoma express CD10. BerEP4 expression was noted in 38% of microcystic adnexal carcinoma, 57% of desmoplastic Trichoepithelioma, 100% of infiltrative basal cell carcinoma, and 38% of squamous cell carcinoma. In conclusion, we found CK15 to be a useful marker in distinguishing microcystic adnexal carcinoma from infiltrative basal cell carcinoma and squamous cell carcinoma with ductal differentiation. Our experience indicates that microcystic adnexal carcinoma and desmoplastic Trichoepithelioma have a similar immunohistochemical profile that is, CK15+ and BerEP4+/−; thus, additional studies are needed to separate these two entities.
