記住我
Abstract
Background: 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. Objectives: 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. Materials and Methods: 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. Results: 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). Conclusion: 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.
Keywords: Basal cell carcinoma, BerEP4, CD10, trichoblastoma, trichoepithelioma
Introduction 
Basal cell carcinomas (BCCs) are the most common cutaneous tumours (70%). It develops predominantly over sun-exposed skin in fair-skinned individuals as a slow-growing, locally invasive lesion that rarely metastasizes.
They are derived from immature pluripotent cells of interfollicular epidermis and those present in the outer sheath of the hair follicle.[1] In most cases, BCC can be diagnosed by its characteristic histopathological features. The differential diagnosis includes basaloid SqCC, trichoepithelioma and other adnexal tumours of follicular differentiation.
A cluster of differentiation 10 (CD10) is a 100 kDa transmembrane glycoprotein. Within normal adult skin, CD10 immunopositivity has been noted in the inner sheath of hair follicles, hair matrix and perifollicular fibrous sheath.[2] Studies have shown that BCC shows positivity for CD10 in tumour cells, SqCC shows stromal diffuse positivity and trichoepithelioma shows peritumoral stromal positivity.[3],[4]
Epithelial cell adhesion molecule (EpCAM) is a 40 kDa transmembrane glycoprotein epithelial adhesion molecule, present in all nonsquamous epithelial cells. It is often overexpressed in breast, colon carcinomas and BCC. BerEP4 is an anti-EpCAM antibody clone and a sensitive marker for BCC but fails to stain areas of squamous differentiation. The diagnostic utility of panel of markers CD10 and BerEP4 in differentiating between these tumours is evaluated in this study.
Materials and Methods Inclusion criteria: It includes all biopsy specimens of histopathologically proven cases of BCC, SqCC of the skin and adnexal tumours of follicular differentiation.
Exclusion criteria: It includes unlabelled and inadequate specimens.
Data collection tool
A structured performa is made using patient details, name, age, sex, IP no., HPR no., site and clinical appearance of lesionDetailed histopathological evaluation including subtypingIHC marker—CD10 and BerEP4.All specimens of BCC, SCC and adnexal tumours of follicular differentiation received during the study period were fixed in formalin. After cutting, bits were taken, and 4- to 5-μ-thick sections were taken from paraffin-embedded blocks. H and E staining and immunohistochemical staining with CD10 and BerEP4 were performed in unstained slides. The results were compared. A detailed histopathological evaluation including subtyping was performed for BCC cases. The H and E slides were viewed by two observers.
Data analysis
All collected data were entered in Microsoft Excel and analysed using the statistical software SPSS version 16. A P value (by Pearson's Chi-square test) less than 0.05 is considered significant for all the tests.
Results The study included 78 cases, of which there were 28 cases of BCCs and 34 cases of SqCCs. The different adnexal tumours of follicular differentiation included in the study were trichoblastoma (n = 2), trichoepithelioma (n = 8), trichilemmoma (n = 1) and proliferating trichilemmal tumour (n = 5).
BCC cases were more common in female patients (18/28), and SCCs showed male predilection (30/34). Adnexal tumours of follicular differentiation predominated in females (10/16).
The subjects included in this study ranged from 29 to 94 years. The major proportion of affected individuals was in the age range of 61–70 yrs. The mean age of occurrence of BCC in our study is 62.1 years; SqCC, 58.53 years; and adnexal tumors of follicular differentiation (ATOFD), 57.38 years. BCC patients were more than 50 years in about 70% of cases.
Site-wise distribution of lesion
For almost all types of BCC and for both genders, the relative tumour density was highest in the face except for superficial BCC. The BCCs on the face were mostly found on the nose, followed by the cheeks.The most common site for adnexal tumours was scalp/forehead (10/16, 62.5%) followed by cheeks (2/16, 12.5%), orbital region (2/16, 12.5%) and nose and upper lip (1/16, 6.2%).Site distribution for cutaneous SqCC
Squamous cell carcinomas were predominantly located over extremities (15/34, 44.1%) followed by cheeks (8/34, 23.5%).
Subtypes of BCC
Of the 28 cases of BCCs, 11 (39.3%) cases showed a prominent nodular pattern, and the next most frequent pattern was superficial BCC (n = 6 (21.4%)) [Figure 2]. Four (14.3%) cases of infiltrative BCC and three (10.7%) keratotic BCCs were constituted in the study. The nodular subtype was the predominant type in both males and females. The superficial types represented 20% of BCCs in men and 22.2% in women. The male/female ratio was 0.67 in nodular BCC, 0.90 in superficial BCC and 0.90 in keratotic BCC.
BerEP4 expression in tumour cells
The expression of BerEP4 in various lesions studied is depicted in [Table 4]. All 28 cases of BCC showed positivity at least focally when stained with BerEP4. Proliferating trichiemmal tumor (PTT) and SqCC completely lacked BerEP4 expression. One case of TL showed positivity. Two of two cases of trichoblastoma showed positivity with BerEP4. Of the eight TE cases, two cases completely lacked BerEP4 expression [Table 2].
All cases of BCC showed positivity for CD10 in the tumour cells. This was statistically significant (P = 0.001). The intensity of staining differed. Twelve of 28 cases showed weak positivity in the periphery of tumour nests. Thirteen of 28 cases showed strong positivity of cells in the periphery. Three of 28 cases showed diffuse strong positivity. Among the subtypes of BCC, superficial BCCs were the ones that showed diffuse strong positive staining pattern (3/6) for CD10.
Among ATOFD, trichoblastoma, trichoepithelioma and trichilemmoma showed peculiar peritumoral stromal accentuation, but the tumour cells were negative for CD10. All five cases of PTT were negative for CD10 in both stroma and tumour cells. Squamous cell carcinomas showed stromal positivity in 25 of 34 cases. CD10 immunostaining pattern in the stroma is depicted in [Table 3].
Discussion The most common location for BCC in this study was the face followed by the trunk, neck and extremities [Table 1] and [Figure 1]. This was found to be broadly consistent with that in previous studies from many countries across the world.[5],[6]
Although in most literature, males have a higher incidence of BCC, in our study we found female predominance. Another study from South India also showed similar results.[7]
The most frequent histological subtype of BCC from our data was nodular followed by superficial type (90.9%) of nodular BCC in the study being located on the face, whereas only 33.3% of superficial BCCs were present on the face. Four of six (66.6%) cases of superficial BCC were distributed between the neck, trunk and extremities. These results were in line with other studies that report the same.[5],[8],[9],[10]
In addition to histological criteria, immunohistochemical markers such as CD10 and BerEP4 can be useful in differentiating between BCC, cutaneous SqCC and ATOFD like trichoepithelioma, trichoblastoma and trichilemmoma. This is particularly important because of the differences in management and prognosis for these lesions.
Immunohistochemical study
The findings for BerEP4 immunostaining were similar to previous studies. Two of two (100%) cases of TB in this study showed BerEP4 positivity. This was in concordance with previous studies.[11],[12] PTT and SCC completely lacked BerEP4 expression. Basosquamous carcinoma (1/28) also showed a similar immunostaining pattern for BerEP4 like other subtypes of BCC.
After an extensive literature search, it is seen that almost all previous studies have obtained 100% BerEP4 positivity in the case of BCC and 100% BerEP4 negativity in SqCC. It can be confirmed that BerEP4 is a useful marker for differentiating between BCC and SqCC. ATOFD (TE, TB and TL) also showed positivity for BerEP4, and even though more variable, this might be due to the common follicular germinative differentiation of these tumours with BCC.
The pattern of CD10 expression in BCC is cytoplasmic and membranous and is most remarkable in the outermost layers, whereas in TE/TB, it is a peculiar peritumoral stromal accentuation, and the tumour cells are negative for CD10. These findings were confirmed by our study such that all 28 of 28 cases of BCC showed positivity for CD10 in the tumour cells, but the intensity and pattern of staining differed. Another important observation made in the study was that among all subtypes, superficial BCCs were the ones showing diffuse strong CD10 positivity. Wagoner et al. describe this strong expression in the superficial subtype as probably due to the indolent nature of these subtypes.[18] Squamous cell carcinomas showed stromal positivity in 25 of 34 cases, but no tumour cells were positive. Our findings were on par with the studies of Pham et al.[19] (2006), Córdoba et al.[20] (2008), Tebcherani et al.[21] (2012) and Aslani et al.[22] (2013).
Conclusion To conclude the panel of markers, CD10 and BerEP4 have good diagnostic utility in differentiating between skin tumours.BerEP4 is useful in distinguishing between BCC and SqCC, and CD10 is a useful adjunct marker in distinguishing TE/TB/TL and SqCC from BCC. CD10-positive tumour cells favour a diagnosis of BCC and peritumoral stromal accentuation for TB and TL. Tumour cells in SqCC are almost always negative for CD10.Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References 
留言 (0)