Trichoepithelioma Research Articles

Expression of Early Growth Response 3 in Skin Cancers.

To assess the expression of early growth response 3 (EGR3) in normal skin and different types of skin tumors: cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), melanoma (MM), and cutaneous adnexal tumors containing sebaceous carcinoma (SC), trichoepithelioma (TE) and clear cell hidradenoma (CCH). EGR3, expressed in multiple organs, including skin, plays an important role in cell differentiation and tumor growth. Previous studies have shown that EGR3 suppresses tumor growth and is downregulated in various malignancies. However, its distribution in normal skin and its expression especially in skin tumors have not been studied. Samples of normal cases (n = 4), cSCC (n = 12), BCC (n = 12), MM (n = 12), SC (n = 4), TE (n = 4), and CCH (n = 4) were collected from patients treated in our department between 2018 and 2023. Immunohistochemistry was used to investigate the expression of EGR3. The results were analyzed with the description of the staining pattern and the histochemical score. Immunohistochemical staining showed that EGR3 was uniquely expressed in normal skin in the granular layer and upper part of the stratum spinosum, as well as in sebaceous glands and hair follicles, but not in sweat glands. In skin cancers, BCC, SC, and TE showed positive EGR3 staining, whereas cSCC, MM, and CCH were negative. EGR3 has a specific expression pattern in normal skin and in skin tumors, which is important for the differential diagnosis of skin tumors, in particular for cSCC and sebaceous gland carcinoma.

Differentiation and risk stratification of basal cell carcinoma with deep learning on histopathologic images and measuring nuclei and tumor microenvironment features.

Nuclear pleomorphism and tumor microenvironment (TME) play a critical role in cancer development and progression. Identifying most predictive nuclei and TME features of basal cell carcinoma (BCC) may provide insights into which characteristics pathologists can use to distinguish and stratify this entity. To develop an automated workflow based on nuclei and TME features from basaloid cell tumor regions to differentiate BCC from trichoepithelioma (TE) and stratify BCC into high-risk (HR) and low-risk (LR) subtypes, and to identify the nuclear and TME characteristics profile of different basaloid cell tumors. The deep learning systems were trained on 161 H&E -stained sections which contained 51 sections of HR-BCC, 50 sections of LR-BCC and 60 sections of TE from one institution (D1), and externally and independently validated on D2 (46 sections) and D3 (76 sections), from 2015 to 2022. 60%, 20% and 20% of D1 data were randomly splitted for training, validation and testing, respectively. The framework comprised four stages: tumor regions identification by multi-head self-attention (MSA) U-Net, nuclei segmentation by HoVer-Net, quantitative feature by handcrafted extraction, and differentiation and risk stratification classifier construction. Pixel accuracy, precision, recall, dice score, intersection over union (IoU) and area under the curve (AUC) were used to evaluate the performance of tumor segmentation model and classifiers. MSA-U-Net model detected tumor regions with 0.910 precision, 0.869 recall, 0.889 dice score and 0.800 IoU. The differentiation classifier achieved 0.977±0.0159, 0.955±0.0181, 0.885±0.0237 AUC in D1, D2 and D3, respectively. The most discriminative features between BCC and TE contained Homogeneity, Elongation, T-T_meanEdgeLength, T-T_Nsubgraph, S-T_HarmonicCentrality, S-S_Degrees. The risk stratification model can well predict HR-BCC and LR-BCC with 0.920±0.0579, 0.839±0.0176, 0.825±0.0153 AUC in D1, D2 and D3, respectively. The most discriminative features between HR-BCC and LR-BCC comprised IntensityMin, Solidity, T-T_minEdgeLength, T-T_Coreness, T-T_Degrees, T-T_Betweenness, S-T_Degrees. This framework hold potential for future use as a second opinion helping inform diagnosis of BCC, and identify nuclei and TME features related with malignancy and tumor risk stratification.

TRPS1: A Marker of Follicular Differentiation.

The trichorhinophalangeal syndrome type 1 (TRPS1) immunohistochemical (IHC) stain has increased in use in recent years as a marker for breast carcinomas. The TRPS1 gene is involved in various tissues, including the growth and differentiation of hair follicles. This article seeks to evaluate the IHC expression of TRPS1 in cutaneous neoplasms with follicular differentiation, such as trichoblastoma (TB), trichoepithelioma (TE), and basal cell carcinoma (BCC). IHC studies were performed on 13 TBs, 15 TEs, and 15 BCCs with an antibody against TRPS1. The study found a variable staining expression of TRPS1 in the tumor nests of TB, TE, and BCC. BCCs were distinct in that none of the BCCs demonstrated intermediate or high positivity, while TBs and TEs showed intermediate-to-high positivity in 5/13 (38%) and 3/15 (20%) of cases, respectively. We observed a distinct staining pattern among the mesenchymal cells of TB and TE. We found that TRPS1 highlighted perifollicular mesenchymal cells adjacent to the nests of TB and TE tumor cells. This staining pattern was absent in BCCs, where only scattered stromal cells were positive for TRPS1. Papillary mesenchymal bodies were also highlighted by TRPS1 in TB and TE. TRPS1 stained various parts of the normal hair follicle, including the nuclei of cells in the germinal matrix, outer root sheaths, and hair papillae. TRPS1 may be a useful IHC marker for follicular differentiation.

Expression of BerEP4 and CD10 IHC Markers in Basal Cell Carcinoma, Squamous Cell Carcinoma and Adnexal Tumours of Follicular Differentiation: A Comparative Study.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy. In most cases, BCC can be diagnosed by its characteristic histopathological features. The differential diagnosis includes basaloid squamous cell carcinoma (SqCC) and adnexal tumours of follicular differentiation. Cluster of differentiation 10 (CD10) and name of an immunostain (BerEP4) are reported to be useful in differentiating between them. The primary objective was to compare the expression of BerEP4 and CD10 in BCC with that of SqCC and adnexal tumours of follicular differentiation, and the secondary objective was to evaluate the proportion of different histological subtypes of BCC. Twenty-eight cases of BCCs, 34 cases of SqCCs and 16 adnexal tumours of follicular differentiation received in the institution during the study period January 2017 to June 2018 were included in this descriptive study. Immunostaining with CD10 and BerEP4 was performed, and the staining pattern was studied in all 78 cases. A detailed histopathological evaluation including subtyping was carried out for BCC cases. All BCCs showed positivity with CD10 and BerEP4, but the intensity and pattern varied. Squamous cell carcinomas were completely negative for BerEP4 and CD10 in tumour cells, and 25 of 34 cases showed stromal CD10 positivity. Among adnexal tumours of follicular differentiation, proliferating trichilemmal tumour was completely negative for both markers; other adnexal tumours (n = 11/16) showed peritumoral stromal accentuation for CD10, and nine of 11 cases showed BerEP4 tumour cell positivity (P < 0.001). BerEP4 can reliably detect BCCs of all types and distinguish between BCC and SqCC, but it is unable to do so for adnexal tumours such as trichoepithelioma, trichilemmoma and trichoblastoma. CD10 is a useful adjunct marker in distinguishing both trichoepithelioma (TE) and SqCC from BCC. CD10-positive tumour cells favour a diagnosis of BCC and peritumoral stromal accentuation for trichoblastoma (TB) and trichilemmoma (TL). Tumour cells in SqCC are almost always negative for CD10. A combined immunohistochemistry (IHC) panel of CD10 and BerEP4 can serve as a very reliable adjunctive in the diagnosis of BCC.

Does Immunohistochemistry Add to Morphology in Differentiating Trichoepithelioma, Desmoplastic Trichoepithelioma, Morpheaform Basal Cell Carcinoma, and Microcystic Adnexal Carcinoma?

The distinction among cutaneous basaloid neoplasms such as trichoepithelioma (TE), desmoplastic trichoepithelioma (DTE), morpheaform basal cell carcinoma (MBCC), and microcystic adnexal carcinoma (MAC) can be difficult, especially in superficial biopsies. As the treatment plan of each entity is different, accurate characterization is important for appropriate management. While TE and DTE are benign neoplasms with indolent behavior, MBCC and MAC are typically locally aggressive. The expression of several recently described immunohistochemical (IHC) markers, including p40, IMP3, and ProEx C, has not been adequately established in cutaneous neoplasms. We explored the potential utility of a broad IHC panel, including previously reported and novel markers to differentiate TE, DTE, MBCC, and MAC. A total of 35 archival cases [TE (n=14), DTE (n=9), MBCC (n=6), and MAC (n=6)] were stained with 9 IHC markers: p40, IMP3, ProEx C, p16, CK20, Ki-67, androgen receptor, D2-40, and beta-catenin. Tumors with >5% immunoreactivity were scored as positive. The intensity was scored on a scale from 1+ to 3+. The pattern of positivity- nuclear, cytoplasmic, membranous, or in combination; peripheral or central distribution with lesion was also recorded. CK20 (in contrast to prior studies) and IMP3 were negative in all cases. Likewise, with the exception of one case of TE, androgen receptor showed no immunoreactivity in all categories. No significant difference was observed in the expression of beta-catenin, p16, ProEx C, and p40 among the four groups of cutaneous neoplasms. The mean Ki-67 labeling index for MBCC (8%) was slightly higher than DTE (3%). Interestingly, the proliferation index for TE (15%) was significantly higher than that of MBCC. All six cases of MAC and 36% of TEs expressed D2-40; neither the MBCC nor DE cases showed D2-40immunoreactivity. Also, we confirmed the previously published observation of scattered CK20 positive Merkel cells in the epidermis of all cases of DTE; whereas, no Merkel cells were identified in MBCC and MAC cases. Except Ki-67, our IHC panel showed no significant added diagnostic utility of IHC in discriminating among TE, DTE, MBCC, and MAC. Among the four cutaneous neoplasms, DTE and MBCC show a small but discernible difference in Ki-67.

Difficulties Differentiating Between Basal Cell Carcinoma and Trichoepithelioma: A Case Report

Background. Basal cell carcinoma (BCC) is the most common type of malignant skin tumor with basal cell differentiation. Trichoepithelioma (TE), however, is a rare benign skin tumor with follicular differentiation. Both types of tumor have commonalities in terms of clinical and histopathological features. Some cases, in fact, require ancillary studies to distinguish between the two. Confusing the two tumors may result in different future outcomes for the patient, due to their vastly different prognoses and treatments. This case report outlines two different cases, and discusses how to distinguish between the two types of tumor without the use of an ancillary study.Method. We examined the cases of one patient with basal cell carcinoma and one patient with trichoepithelioma, comparing their clinical manifestations and characteristic histological features.Results. Trichoepithelioma and BCC share several overlapping histopathological features. Trichoepithelioma and BCC share several overlapping histopathological features. The TE in this case report also exhibited a nodular pattern, connection to the epidermis, stromal cleft, and prominent nuclear palisading, which are more commonly found in BCC. However, scanty mitotic activity, the presence of non-atypia cells, and symmetry of the lesion, are favor TE.Conclusion. Differentiation between BCC and TE is only possible using cytomorphological assessment with a high-power field of view.

Immunohistochemical Expression of CK19, AR, PHLDA1, CD10 and Ki67 in the Differentiation between Trichoepithelioma and Basal Cell Carcinoma: A Systematic Review

Background. Basal cell carcinoma (BCC) and trichoepithelioma (TE) are follicular adnexal neoplasms that arise from the follicular germ but with divergent biological behavior. The gold standard in the differentiation is through histopathological examination using hematoxylin and eosin (H and E) stain. There are cases, however, when the distinction is not straightforward.&#x0D; Objective. To assess the association and diagnostic accuracy of the immunohistochemical (IHC) expressions of CD10, Ki67, CK19, androgen receptor (AR), and PHLDA1 in distinguishing between basal cell carcinoma and trichoepithelioma.&#x0D; Methods. We conducted a comprehensive search on cross-sectional studies on human tissue from 2000 to 2020 in MEDLINE (PubMed), CENTRAL and EMBASE for comparative studies and reference lists. The data were summarized and analyzed using Microsoft Excel and RevMan. We used Chi-square test for independence, summary receiver operator curves (sROC), and diagnostic odds ratio (OR).&#x0D; Results. We included 15 articles containing 686 BCC and 367 TE in the systematic review. The pooled staining of biomarkers showed a significant difference in the staining of CK19 (p&lt;0.05) and AR (p&lt;0.0001), and PHLDA1 (p&lt;0.0001). Diagnostic odds ratio was used to confirm these associations. AR was found to have the highest odds in the diagnosis of BCC (OR 27.92, 95% CI 10.69, 72.86). The pattern of staining of CD10 is significant (p&lt;0.001) with staining of both tumor and stroma (OR 8.09, 95% CI 4.57, 13.53) and staining of tumor alone (OR 8.15, 95% CI 4.56, 14.35) (p&lt;0.001) in the diagnosis of BCC. CD10 stromal staining, on the other hand, is significantly associated with the diagnosis of TE (OR 7.26, 95% CI 5.06, 10.44) (p&lt;0.0001). There is no significant association between Ki67 staining (OR 1.22, 95% CI 0.48, 3.09) (p=0.67) and the diagnosis of BCC. The forest plot and sROC showed that AR had high specificity across all included studies in the diagnosis of basal cell carcinoma, while PHLDA1 demonstrated high specificity and high sensitivity in diagnosing trichoepithelioma.&#x0D; Conclusion. The biomarkers AR and PHLDA1 are useful as an initial panel to distinguish between BCC and TE, given that both showed high sensitivity as well as significant association with BCC and TE respectively. CD10 and CK19 may also be used with AR and PHLDA1 for further confirmation.

Effectiveness of (Ki-67) a Cell Proliferative Marker for Distinguishing Overlapping Skin Lesions

Background: it has been always a challenge to differentiate keratoacanthoma (KA) from squamous cellcarcinoma (SCC) and trichoepithelioma (TE) from Basal Cell Carcinoma (BCC). K-i67, a nuclear marker, isa protein whose expression is strictly related to cell proliferation. Therefore, this can be used as an excellentproliferative marker to differentiate between benign and malignant skin lesions.Aim of the Current Study: this study was conducted to investigate the quantitative differences in nuclearexpression of the proliferative index (Ki-67) in SCC, KA, BCC and TE.Materials and Methods: A cross-sectional study enrolling 65 patients selected from private dermatologicaloutpatients clinics at Ibn-Sina Teaching Hospital, Mosul, Iraq diagnosed clinically by dermatologists asBCC, SCC, KA, and TE during the period from Jan 2019- Jan 2020. Their biopsies were sent for routinehistopathological study and additional Immunohistochemical staining using a Ki-67 marker.Results: Ki- 67 expression was seen in all cases ranging in intensity between 3-70%. Moderate expressionwas noticed in (79%) of BCC cases whereas (43%) of well-differentiated SCC cases had mild expression.Quite the reverse, the intensity of Ki-67 immunostaining ranged from 1-20% and 1-5% in KA and TErespectively.Conclusion: Ki-67 can be used as a significant biological marker to differentiate between benignity andmalignancy of overlapping

Expression of Hedgehog signalling molecules inmicrocystic adnexal carcinoma.

Microcystic adnexal carcinoma (MAC) is a rare skin neoplasm that has not been characterized on a molecular basis. To assess expression profiles of Hedgehog (HH) signalling molecules in MAC and control tumours. Immunohistochemistry was performed for Sonic Hedgehog (SHH), Indian Hedgehog (IHH), Patched 1 (PTCH1) and Smoothened (SMO) on patient MAC tissue (n=26) and control tumour tissue, including syringoma (SyG; n=11), trichoepithelioma (TE; n=11) and basal cell carcinoma (BCC; n=12) tissues. Patched 1 and SMO immunoreactivity was significantly higher in BCC than in SyG, TE or MAC (P<0.001 and P<0.03, respectively). The highest IHH expression was observed in BCC and TE compared with SyG and MAC (P<0.04). Notably, the highest SHH protein expression was observed in SyG compared with MAC, TE and even BCC (P<0.001). In patients with MAC, SMO immunoreactivity significantly (r=0.51; P<0.01) correlated with PTCH1 expression. Further correlation studies did not show significant associations between the HH expression markers assessed (P>0.05). Our results indicate that alterations of the HH signalling are unlikely to play a major role in the pathogenesis of MAC, which is in contrast to the morphologically similar BCC and TE. Our observation provides additional information to the limited molecular pathology knowledge on this rare tumour.

Collision Tumor in the Lower Eyelid: Basal Cell Carcinoma Adjacent to Trichoepithelioma.

The coexistence of 2 neoplasms in a single cutaneous specimen is unusual. We describe a lower eyelid lesion in which the biopsy revealed a trichoepithelioma (TE) and an adjacent basal cell carcinoma (BCC). A 57-year-old female patient reported a 5-year history of lower eyelid pruritus and had been treated for blepharitis elsewhere. She was referred for eyelid evaluation due to the presence of a plaque, loss of eyelashes, and areas of inflammation in the right lower eyelid. She underwent tumor excision, and the eyelid was reconstructed using an orbicularis muscle advancement flap combined with a free tarsoconjunctival graft and a skin graft. Preoperative photographs show an extensive lesion, with madarosis in the right lower eyelid (Fig. A and B). Biopsy specimen from the right lower eyelid revealed 2 different tumor types: a TE and an adjacent BCC (Fig. C and D). A focus of TE is seen (left) juxtaposed with a focus of BCC (right). The area containing the TE was composed of basaloid cell nests and horn cysts, embedded within an organized stroma. Areas of cicatricial fibrosis and foreign body-type reaction were also observed. These histopathology features were consistent with that of a desmoplastic TE (DTE). The adjacent BCC area showed proliferation of atypical basaloid cells with peripheral palisading. Cytoplasm was basophilic and relatively scant, nuclei were large and mildly irregular, and contained grumous chromatin and mitotic figures. Trichoepithelioma is a benign tumor of follicular origin with 3 distinctive variants: multiple familial, solitary, and DTE. DTE is a rare benign adnexal tumor, derived from basal cells in the outer root sheath of the hair follicle, histologically characterized by narrow strands of basaloid tumor cells, keratinous cysts, and a desmoplastic stroma. TEs and BCCs both present with nests of basaloid cells. Histologic features that favor TE include the following: architectural symmetry, horn cysts, and associated giant cell reaction (rare in BCC), papillary mesenchymal bodies, no high-grade atypia, no or very low mitotic activity, monomorphic nuclei, no tumor necrosis, no peripheral clefting. The presence of peripheral palisading of basaloid cells, clefting between the epithelial and stromal components, necrosis, and high mitotic activity are associated with BCC. When histologic examination does not permit to differentiate a TE from a BCC, immunohistochemical stains, such as BCL2, CD10, CD34, AR, may be useful. Transformation of TE to BCC is rare and usually occurs in the setting of multiple TEs. A possible way to investigate transformation would be to compare the DNA of both tumors to find a common mutation. In our patient, it is more likely that this is a collision tumor (coexistence of 2 different tumors in the same lesion). Concomitant presence of a TE and a BCC is rare, and, to the best of our knowledge, this is the only case showing a DTE adjacent to a BCC, involving the eyelid. This case highlights that benign and malignant pathology can coexist within the same lesion. Special attention should be addressed to collision tumors since, in these cases, a small incisional biopsy might not be sufficient for accurate diagnosis.Fig.: Basal cell carcinoma adjacent to trichoepithelioma. A and B, A 57-year-old female patient presented an extensive lesion, with madarosis in the right lower eyelid. C and D, Hematoxylin and eosin stain of the biopsy specimen (100× and 200×) revealed 2 different tumor types: a focus of trichoepithelioma is seen (left) juxtaposed with a focus of basal cell carcinoma (right).

Differentiation of Basal Cell Carcinoma and Trichoepithelioma: An Immunohistochemical Study.

Basal cell carcinoma (BCC) is the most common malignancy of the skin. It is an epithelial neoplasm with origin in the precursor cells of the interfollicular epidermis. Even though it has low metastatic potential, delay in management may lead to local destruction and morbidity. In contrast, trichoepithelioma (TE) is a benign tumor originating from the outer root sheath of the hair follicle. Similar to BCC, TE tends to affect the head and neck region. Both neoplasms may exhibit clinical and histopathological similarities, making them prone to misdiagnosis. Multiple immunomarkers have been used to distinguish among these entities, but so far, no single agent or combination of agents appear to be neither sensitive nor specific enough to differentiate between them. This study was divided into 2 parts. First, 17 cases of BCC and 14 cases of TE were stained with androgen receptor and bcl-2. Then, 27 cases of borderline/equivocal of BCC and 13 cases of borderline/equivocal TE were stained with the same protocol. Sensitivity and specificity were calculated for each individual immunomarker and for the combination of them. Androgen receptor positivity was 100% specific for BCC and borderline/equivocal BCC, whereas bcl-2 diffuse staining pattern demonstrated a sensitivity of 82.4% for BCC and 88.9% borderline/equivocal BCC. When both immunomarkers were combined, the sensitivity for BCC decreased (70.6%) but the specificity remained high (100%). Similarly, the sensitivity for borderline/equivocal BCC was 55.6%, whereas the specificity was 100%. Although moderately sensitive, combining both immunomarkers showed an excellent specificity to discriminate between BCC and TE.

Basal Cell Carcinoma Arising within a Trichoepithelioma: An Immunohistochemical Study

Abstract Background: Trichoepithelioma (TE) and basal cell carcinoma (BCC) of skin represent distinct tumor entities but they have a close histogenetic and phenotypic relationship. Objective: A unique case of a BCC arising within a TE is described with an emphasis on the analysis of different and for each tumor type typical immunophenotype. Material and Methods: A 71-year-old man presented with a subcutaneous solid tumor in the lumbar region. The resected tumor specimen was studied by immunohistochemistry. Results: Histology revealed a coexistence of classic TE and nodular BCC. Both tumors were strongly positive for BerEP4 and negative for EMA. Neoplastic epithelium of the BCC showed a diffuse staining for Bcl-2, while the TE expressed Bcl-2 almost exclusively in the peripheral cells of tumor islands. In the BCC, neoplastic nodules exhibited a focal staining for CD10, while the peritumorous stroma did not. In contrast, the TE showed a focal immunoreactivity for CD10 in the stromal cells around the neoplastic islands which were completely negative. The TE contained intratumorous CK20-labeled Merkel cells but they were not detected in the BCC. A stromal immunore-activity for CD34 was found in both tumors. Proliferative activity (Ki-67) was slightly higher in the BCC than in the TE. Conclusion: Although a concomitant presence of TE and BCC in the same skin lesion is a unique finding, it may be sometimes encountered in a biopsy practice. Pathologists should provide a careful histologic examination of the whole TE lesion with precise section sampling to unveil such possible association.

Diagnostic accuracy of immunohistochemical markers in differentiation between basal cell carcinoma and trichoepithelioma in small biopsy specimens.

The distinction of trichoepithelioma from basal cell carcinoma in small superficial biopsies is important but often challenging. This has inspired many scientists to test the validity of immunohistochemical markers in the differential diagnosis. To develop an immunohistochemical protocol that helps in differentiation between both trichoepithelioma (TE) and basal cell carcinoma (BCC) with higher sensitivity and specificity. Using standard immunohistochemical techniques, we examined 10 TEs and 19 BCCs for the expression of CK19, Ki-67, androgen receptors (AR), CD10, and PHLDA1. Immunoreactivity of AR, Ki-67, and CD10 in tumor cells was significantly higher in BCC than TE with a diagnostic accuracy in BCC of 75.5%, 75.8%, and 79.3% respectively, whereas immunoreactivity of PHLDA1 in tumor cells and stromal CD10 was significantly higher in TE than BCC with a diagnostic accuracy in TE of 100% and 82.8%, respectively. In contrast, immunoreactivity for CK19 showed no statistically significant differences between both tumors. The analysis of CD10, Ki-67, and PHLDA1 can be used as a helpful immunohistochemical panel in the distinction between TE and BCC especially in small and superficial biopsies.

Distinct expression profile of stem cell markers, LGR5 and LGR6, in basaloid skin tumors.

Mammalian epidermis, which is composed of hair follicles, sebaceous glands, and interfollicular epidermis, is maintained by discrete stem cells. In vivo lineage tracing demonstrated that murine LGR5 cells are mainly responsible for hair follicle regeneration whereas LGR6 cells generate sebaceous glands and interfollicular epidermis. However, little is known about their expression in the human skin tumors. In this study, we investigated the expression profile of LGR5 and LGR6 in a variety of human skin tumors including basaloid tumors with follicular differentiation (94 basal cell carcinomas, 18 trichoepitheliomas, 3 basaloid follicular hamartomas, and 12 pilomatricomas) and tumors with ductal differentiation (7 eccrine poromas, 8 hidradenomas, and 5 spiradenomas). LGR5 expression was highest in basal cell carcinomas (BCCs) followed by trichoepitheliomas (TEs) and basaloid follicular hamartomas. LGR6 had the same expression pattern as LGR5, even though its expression was lower. Interestingly, LGR6 expression was detected in stromal cells around the tumor and papillary mesenchymal bodies of TEs but not in stromal cells of BCCs, suggesting different characteristics of tumor-associated fibroblasts between TEs and BCCs. It was unexpected to find that pilomatricomas exclusively expressed LGR6, and its expression was limited to the basaloid cells. Notably, LGR6-positive cells were observed in sweat gland ductal cells in normal skin. This might explain, in part, the finding that LGR6 expression was relatively higher in basaloid tumors with ductal differentiation than in those with follicular differentiation. In particular, spiradenomas displayed the same distribution pattern of LGR6 as normal sweat glands, suggesting the possibility of LGR6-positive cells as tumor stem cells. In conclusion, we documented the different expression patterns of stem cell markers, LGR5 and LGR6 in various skin tumors. These data may provide important insights to understand the origin and development of basaloid skin tumors.

P40 in Conjunction With CK20 and E-Cadherin Distinguishes Primary Adnexal Neoplasms of the Skin.

Although basal cell carcinomas (BCC) show typical histomorphologic features, they sometimes remain difficult in distinction from benign adnexal skin tumors of follicular origin like trichoepithelioma (TE) or trichoblastoma (TB). Consequently, an immunohistochemical marker panel separating described entities would be helpful in clinical routine. Thus, we stained 22 skin lesions (BCC, TE, and TB) against β-catenin, CK20, E-cadherin, p40, and p63. The staining pattern was described and quantified using an immunohistochemical score. Although p40 and p63 revealed a strong staining intensity of all skin lesions without distinction between BCC and benign lesions (P=1.000), established Merkel cell marker CK20 illustrated a loss of staining in BCC compared with TE and TB (P=0.007). In contrast, BCC exhibited an increased expression of E-cadherin in relation to TE and TB (P=0.009). Single application of CK20 or E-cadherin could predict diagnosis of BCC in 81.8% or 72.7%, respectively. Combining consecutive staining of E-cadherin and CK20 could even enhance specificity toward diagnosis of TE or TB. Hence, findings of our study imply that sequential staining of CK20 and E-cadherin prevents false-positive classification of BCC. Furthermore, our study demonstrated that p40 exhibits the same staining pattern in BCC, TE, and TB. Therefore, p40 might replace p63 equivalently establishing diagnosis of primary adnexal neoplasms of the skin in the form of BCC as well as benign adnexal tumors. As a result, the depicted immunohistochemical marker panel may be applied for adnexal skin neoplasms as a diagnostic adjunct especially in surgically challenging body regions.

Significance of androgen receptor and CD10 expression in cutaneous basal cell carcinoma and trichoepithelioma.

Differential diagnosis of trichoepithelioma (TE) and basal cell carcinoma (BCC) on the basis of clinical symptoms and laboratory investigations may be difficult in certain patients. The aim of the present study was to compare cluster of differentiation 10 (CD10) and androgen receptor (AR) expression patterns in BCC and TE, to investigate the predictive power of these proteins as markers of the two conditions. A total of 39 cases of BCC and 15 cases of TE were retrieved from the pathology department archives. AR and CD10 immunohistochemistry was performed on all of the specimens; 23 BCC cases displayed focal nuclear AR staining, however, none of the cases demonstrated diffuse nuclear staining and 16 BCC cases were negative for AR staining. Stromal CD10 staining was more common in TE cases than in BCC cases, and peripheral CD10 staining was more common in BCC cases than in TE cases. AR immunostaining of the BCC samples typically appeared as scattered clusters and individual cells. In addition, AR and CD10 staining exhibited varying staining intensities within each samples. Incisional punch biopsy specimens have the potential to present false-negative results. Therefore, AR and CD10 staining of total excision biopsies provides a more accurate differential diagnosis of BCC and TE for cases with difficulties in the histopathological analysis.

The clinicopathological spectrum of trichoepitheliomas: a retrospective descriptive study.

Trichoepithelioma (TE) is a benign adnexal neoplasm derived from basal cells in the hair follicle. Solitary TE occurs sporadically as opposed to the multiple familial variant that presents as an autosomal dominant genodermatosis. The solitary variant can be confused with basal cell carcinoma both clinically and histologically. Multiple familial TEs are a cosmetically disfiguring condition with limited satisfactory treatment options. Skin biopsies diagnosed as TE from January 1, 2001, to December 31, 2011, were retrieved from the archives of the Division of Anatomical Pathology (University of Stellenbosch and National Health Laboratory Service, Cape Town, South Africa). Clinical and demographic data were retrieved from the patient records at Tygerberg Academic Hospital. Data of patients with solitary TE and multiple TE were compared. Thirty-three biopsy specimens were collected from 30 patients. Twenty patients had solitary TE, nine patients had multiple TEs, and one patient had multiple linear TEs. Multiple TEs started to develop in patients at an average age of 17.3years. Three patients in the study had tumoral TE with a diameter greater than 20mm. One patient had TE associated with a basal cell carcinoma. Multiple TEs were commonly misdiagnosed clinically as tuberous sclerosis and showed a cribriform histopathological tumor pattern in 80% of cases as compared to only 10% of solitary TEs. The current study was confined to a cohort of patients, in the Western Cape Province of South Africa, whose ethnic and geographic origins were not available. The extrapolation of findings from this study to the rest of the South African population may not be valid. A cribriform growth pattern occurs in the majority of cases of multiple TEs.

Basaloid follicular hamartoma on the upper eyelid.

Basaloid follicular hamartoma on the upper eyelid.

Trichoepithelioma and Basal Cell Carcinoma with Squamous Differentiation: Is it Causal or Coincidental?

Trichoepitheliomas (TEs) are benign cutaneous tumors that occur either as solitary non-familial or multiple familial. We report a case of multiple familial trichoepithelioma (MFT) in a 55-year-old female patient and her son who came with complaints of single ulcerated mass involving the left nasolabial fold and cheek. She had multiple papules and nodules all over the face and neck since 25 years. Histopathological examination of an ulcerated lesion revealed features of basal cell carcinoma (BCC) with squamous differentiation, which was confirmed by immunohistochemistry. A skin biopsy obtained from the papule on neck showed features of TE. However, whether BCC developed independently or by transformation from TE was uncertain. Her 36-year-old son presented with similar lesions on the face and a skin biopsy showed features of TE. Though malignant transformation of TE is quite rare, awareness of the potential for evolution of carcinoma in patients with MFT is important for management of these patients.

The importance of cytokeratin 19 expression in the differentiation of Basal cell carcinoma and trichoepithelioma.

Basal cell carcinoma (BCC) is the most common skin neoplasm reported in human. On the other hand, trichoepithelioma (TE) is a rare, benign tumour of skin adnexa. The differentiation of BCC and TE may be difficult since their morphological findings are similar. In a few studies, it has been determined that undifferentiated basaloid cells are highly positively stained with cytokeratin 19. The aim of this study was the comparison of cytokeratin 19 expression in cases of BCC and TE. Sections of skin tissues of 17 TE, 25 BCC and 12 non-neoplastic cases were used for cytokeratin 19 (CK19) immunohistochemical staining. Staining with CK19 of the BCC cases gave 15(60%) diffuse, 7 (28%) focal and 3 (12%) negative staining. On the other hand, among TE cases, 2 (12%) gave diffuse, 5 (29%) focal and 10 (59%) negative staining with CK19. In the non-neoplastic skin tissue samples, while positive staining with cytokeratin 19 in the outer root sheath of hair follicles and sweat glands were observed, there was no staining in basal layers. CK19 expression may be helpful in the differential diagnosis of BCC and TE especially in small skin biopsy samples in which morphologic differentiation is difficult.