BJD
British Journal of Dermatology
CASE REPORT
Vismodegib induces significant clinical response in locally advanced trichoblastic carcinoma P. Lepesant,1 M. Crinquette,2 S. Alkeraye,1 X. Mirabel,3 V. Dziwniel,4 B. Cribier5 and L. Mortier1 1
Department Department 4 Department 5 Department 3
of of of of
Dermatology and 2Department of Pathology, CHRU, Lille, France Radiation Oncology, Oscar Lambret Comprehensive Cancer Center, Lille, France Modern Languages, Ecole Centrale de Lille, Lille, France Pathology, CHRU, Strasbourg, France
Summary Correspondence Pauline Lepesant. E-mail: [email protected]
Accepted for publication 29 April 2015
Funding sources None.
Conflicts of interest L.M. is an investigator of clinical trials and consultant for Roche. DOI 10.1111/bjd.13919
Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.
What’s already known about this topic?
• •
Vismodegib is a new therapeutic strategy for patients with advanced or metastatic basal cell carcinoma. Up until now, there has been no effective treatment for metastatic or unresectable trichoblastic carcinoma.
What does this study add?
• •
This observation is the first case of trichoblastic carcinoma with significant response to vismodegib. This observation tends to suggest that the patched sonic hedgehog pathway may have a relevant role in the pathogenesis of trichoblastic carcinoma.
A 43-year-old man consulted in December 2010 for a large skin tumour of the left thigh. The lesion had been present for many years and evolved gradually, according to the patient. Clinical examination revealed a preserved general condition,
left inguinal lymph node enlargement and a budding ulcerated tumour of the left thigh and the left side of the buttock, measuring 20 9 15 cm, and completely attached to deeper structures (Fig. 1). After initial diagnosis of basal cell carcinoma (BCC), two sets of skin biopsies resulted in the diagnosis of trichoblastic
© 2015 British Association of Dermatologists
British Journal of Dermatology (2015) 173, pp1059–1062
Case report
1059
1060 Vismodegib for locally advanced trichoblastic carcinoma, P. Lepesant et al.
(a)
(b)
Fig 1. A significant clinical response of trichoblastic carcinoma to vismodegib. (a) September 2011, before the treatment: a budding ulcerated tumour of the left thigh and the left side of the buttock. (b) October 2012, after 13 months of treatment: a scar without residual tumoral lesion.
carcinoma (TC) with deep invasion. Staining with PHLDA1 (pleckstrin homology-like domain, family A, member 1) was positive (Fig. 2). Deep biopsies from the sacroiliac bone and adjacent soft tissues were also in favour of this diagnosis. A positron emission tomography (PET) scan showed a first hypermetabolic cutaneous lesion of the left thigh and buttock with maximum standard uptake value (SUV) of 20. There was a second deep hypermetabolic lesion with a maximum SUV of 15 inducing iliac and sacral bone lysis (Fig. 3a). Pelvis magnetic resonance imaging (MRI) showed an important infiltration and oedematous reaction of muscles and underlying soft tissues (Fig. 4a). An abdominal and pelvic scan and bone scintigraphy revealed similar lesions. The cerebral scan was normal. In September 2011, treatment with vismodegib, a sonic hedgehog pathway inhibitor, was started at a dose of 150 mg per day. The lesion diameter was 22 9 16 cm when the treatment was started (Fig. 1a). In October 2012, after 13 months of treatment, a partial response was obtained. Complete regression of the cutaneous lesion and a decrease in the bone lesions were noted. Indeed a significant clinical response was noted, with complete disappearance of lymphadenopathies. A
16 9 10-cm scar persisted (Fig. 1b). Multiple skin biopsies confirmed the absence of residual lesions. A new staging showed partial response with a decrease in the intensity of the hypermetabolic superficial and deep lesions on the PET scan, with respective maximum SUVs of 8 and 10 (Fig. 3b). We observed reduced infiltration and oedematous reactions of the muscles and underlying soft tissues on the pelvis MRI (Fig. 4b). The patient presented with no side-effects except for some grade 1 muscular cramping. His general health condition was good, and there were no palpable lymph nodes. In December 2012, at a multidisciplinary meeting, it was proposed to stop vismodegib and to initiate a complementary radiotherapy course because of the bone involvement. Radiotherapy was carried out at a dose of 60 Gy over 30 sessions. A re-evaluation was carried out in March 2013. The MRI showed complete regression of muscle infiltration and a decrease of the contrast enhancement. Skin biopsies of the cutaneous tumour, which remained stable clinically, revealed signs of dermatitis without residual tumour. In June 2014, 33 months after the beginning of the treatment, clinical examination showed stability of the cutaneous lesions, and imaging tests highlighted persistent iliac and sacral bone lysis along with the appearance of fractures. Treatment with bisphosphonates was introduced and further radiotherapy was proposed at a multidisciplinary meeting. Radiotherapy was carried out at a dose of 20 Gy over five sessions in December 2014. In January 2015, vismodegib had been continued for 40 months.
Discussion
Fig 2. Histology of trichoblastic carcinoma with PHLDA1 staining: brown staining of the tumour. British Journal of Dermatology (2015) 173, pp1059–1062
Vismodegib is a new drug for locally advanced or metastatic BCC, which induces tumour regression. It is already on the market in the U.S.A. and Europe, after having received authorization from the US Food and Drug Administration and the European Medicines Agency, respectively. Vismodegib is the first molecule classified as an inhibitor of the patched sonic hedgehog pathway in the treatment of skin tumours. However, vismodegib can induce significant side-effects that may lead practitioners to stop treatment. These side-effects are muscle spasm (71%), alopecia (65%), dysgeusia (57%), © 2015 British Association of Dermatologists
Vismodegib for locally advanced trichoblastic carcinoma, P. Lepesant et al. 1061
(a1)
(b1)
(a2)
(b2)
Fig 3. Positron emission tomography scan of trichoblastic carcinoma: a decrease in the intensity of hypermetabolic cutaneous and bone lesions with vismodegib. (a) December 2010, before the treatment, maximum standard uptake value of 20 and 15. (b) October 2012, after 13 months of treatment, maximum standard uptake value of 8 and 10.
(a1)
(b1)
(a2)
(b2)
Fig 4. Pelvis magnetic resonance imaging of trichoblastic carcinoma: reduced infiltration and oedematous reaction of muscles and underlying soft tissues. (a) December 2010, before the treatment. (b) October 2012, after 13 months of treatment.
weight loss (54%), fatigue (45%), nausea (34%), decrease in appetite and diarrhoea.1 Although we observed a recurrence of BCC after drug withdrawal and some acquired resistance to treatment, vismodegib represents a new therapeutic strategy presenting real clinical benefits to patients. This may provide an improvement over sunitinib, which has shown efficacy in a small number of patients, but its efficacy is partial and the tolerance not always good.2 © 2015 British Association of Dermatologists
Data in the literature differ regarding the role of the patched sonic hedgehog pathway in the pathogenesis of adnexal tumours. Indeed, some studies suggest that this pathway is involved in the formation of adnexal tumours such as trichoepithelioma, trichoblastoma and cylindroma, as in BCC. There are several lines of evidence that support this involvement. Firstly, there is the spontaneous appearance of numerous BCCs, trichoepitheliomas, trichoblastomas and cylindromas in mice with constitutive activation of the sonic hedgehog British Journal of Dermatology (2015) 173, pp1059–1062
1062 Vismodegib for locally advanced trichoblastic carcinoma, P. Lepesant et al.
patched pathway.3 Secondly, in trichoepitheliomas, there have been positive results in molecular research into PTCH1, a tumour suppressor gene, mutations of which cause constitutive activation of the sonic hedgehog patched pathway.4 Thirdly, GLI15 and SOX9,6 transcription factors involved in the signalling pathway of patched sonic hedgehog, seem to have increased levels in adnexal carcinomas. BCC and TC are two very close entities, both clinically and histologically, and differential diagnosis is often problematic. TC typically develops from a trichoblastoma at the expense of the epithelium of the hair shaft, after a long period of evolution. From a histological point of view, TC, unlike BCC, is a proliferation of lobules of basaloid cells not connected with the epidermis, devoid of a clear palisading arrangement in the periphery and with less stromal retraction. Most TCs show deeper extension and higher metastatic risks than BCCs. Several attempts have been made to differentiate these two entities using different markers.7–10 Currently, the most widely used marker to differentiate these two diagnoses is PHLDA1.11–13 Indeed, this is a reliable marker of hair follicle stem cells, the expression of which is reported in trichoepitheliomas and TCs but not in BCCs. This marker is also known as TDAG51 (for T-cell death-associated gene 51). It is present in normal skin in hair follicles at the bulb and the lower portion of the inner root sheath, and also in eccrine glands, scattered dendritic cells and melanocytes. Differentiating these two entities remains difficult and error prone, and the use of these markers is limited to reference centres and research settings. In conclusion, we report the first case of TC that showed response to vismodegib. Vismodegib could represent a new therapeutic tool in the treatment of TC. Further studies are needed to confirm the role of vismodegib in the management of advanced TC.
References 1 Dessinioti C, Plaka M, Stratigos AJ. Vismodegib for the treatment of basal cell carcinoma: results and implications of the ERIVANCE BCC trial. Future Oncol 2014; 10:927–36.
British Journal of Dermatology (2015) 173, pp1059–1062
2 Battistella M, Mateus C, Lassau N et al. Sunitinib efficacy in the treatment of metastatic skin adnexal carcinomas: report of two patients with hidradenocarcinoma and trichoblastic carcinoma. J Eur Acad Dermatol Venereol 2010; 24:199–203. 3 Nilsson M, Unden AB, Krause D et al. Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1. Proc Natl Acad Sci U S A 2000; 97:3438–43. 4 Vorechovsky I, Unden AB, Sandstedt B et al. Trichoepitheliomas contain somatic mutations in the overexpressed PTCH gene: support for a gatekeeper mechanism in skin tumorigenesis. Cancer Res 1997; 57:4677–81. 5 Hatta N, Hirano T, Kimura T et al. Molecular diagnosis of basal cell carcinoma and other basaloid cell neoplasms of the skin by the quantification of Gli1 transcript levels. J Cutan Pathol 2005; 32:131–6. 6 Vidal VP, Ortonne N, Schedl A. SOX9 expression is a general marker of basal cell carcinoma and adnexal-related neoplasms. J Cutan Pathol 2008; 35:373–9. 7 Arits AHMM, Van Marion AMW, Lohman BGPM et al. Differentiation between basal cell carcinoma and trichoepithelioma by immunohistochemical staining of the androgen receptor: an overview. Eur J Dermatol 2011; 21:870–3. 8 Heidarpour M, Rajabi P, Sajadi F. CD10 expression helps to differentiate basal cell carcinoma from trichoepithelioma. J Res Med Sci 2011; 16:938–44. 9 Sengul D, Sengul I, Astarci MH et al. CD10 for the distinct differential diagnosis of basal cell carcinoma and benign tumours of cutaneous appendages originating from hair follicle. Pol J Pathol 2010; 61:140–6. 10 Sellheyer K, Nelson P, Kutzner H, Patel RM. The immunohistochemical differential diagnosis of microcystic adnexal carcinoma, desmoplastic trichoepithelioma and morpheaform basal cell carcinoma using BerEP4 and stem cell markers. J Cutan Pathol 2013; 40:363–70. 11 Sellheyer K, Krahl D. PHLDA1 (TDAG51) is a follicular stem cell marker and differentiates between morphoeic basal cell carcinoma and desmoplastic trichoepithelioma. Br J Dermatol 2011; 164:141–7. 12 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. J Cutan Pathol 2011; 38:542–50. 13 Yeh I, McCalmont TH, LeBoit PE. Differential expression of PHLDA1 (TDAG51) in basal cell carcinoma and trichoepithelioma. Br J Dermatol 2012; 167:1106–10.
© 2015 British Association of Dermatologists
British Journal of Dermatology
CASE REPORT
Vismodegib induces significant clinical response in locally advanced trichoblastic carcinoma P. Lepesant,1 M. Crinquette,2 S. Alkeraye,1 X. Mirabel,3 V. Dziwniel,4 B. Cribier5 and L. Mortier1 1
Department Department 4 Department 5 Department 3
of of of of
Dermatology and 2Department of Pathology, CHRU, Lille, France Radiation Oncology, Oscar Lambret Comprehensive Cancer Center, Lille, France Modern Languages, Ecole Centrale de Lille, Lille, France Pathology, CHRU, Strasbourg, France
Summary Correspondence Pauline Lepesant. E-mail: [email protected]
Accepted for publication 29 April 2015
Funding sources None.
Conflicts of interest L.M. is an investigator of clinical trials and consultant for Roche. DOI 10.1111/bjd.13919
Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.
What’s already known about this topic?
• •
Vismodegib is a new therapeutic strategy for patients with advanced or metastatic basal cell carcinoma. Up until now, there has been no effective treatment for metastatic or unresectable trichoblastic carcinoma.
What does this study add?
• •
This observation is the first case of trichoblastic carcinoma with significant response to vismodegib. This observation tends to suggest that the patched sonic hedgehog pathway may have a relevant role in the pathogenesis of trichoblastic carcinoma.
A 43-year-old man consulted in December 2010 for a large skin tumour of the left thigh. The lesion had been present for many years and evolved gradually, according to the patient. Clinical examination revealed a preserved general condition,
left inguinal lymph node enlargement and a budding ulcerated tumour of the left thigh and the left side of the buttock, measuring 20 9 15 cm, and completely attached to deeper structures (Fig. 1). After initial diagnosis of basal cell carcinoma (BCC), two sets of skin biopsies resulted in the diagnosis of trichoblastic
© 2015 British Association of Dermatologists
British Journal of Dermatology (2015) 173, pp1059–1062
Case report
1059
1060 Vismodegib for locally advanced trichoblastic carcinoma, P. Lepesant et al.
(a)
(b)
Fig 1. A significant clinical response of trichoblastic carcinoma to vismodegib. (a) September 2011, before the treatment: a budding ulcerated tumour of the left thigh and the left side of the buttock. (b) October 2012, after 13 months of treatment: a scar without residual tumoral lesion.
carcinoma (TC) with deep invasion. Staining with PHLDA1 (pleckstrin homology-like domain, family A, member 1) was positive (Fig. 2). Deep biopsies from the sacroiliac bone and adjacent soft tissues were also in favour of this diagnosis. A positron emission tomography (PET) scan showed a first hypermetabolic cutaneous lesion of the left thigh and buttock with maximum standard uptake value (SUV) of 20. There was a second deep hypermetabolic lesion with a maximum SUV of 15 inducing iliac and sacral bone lysis (Fig. 3a). Pelvis magnetic resonance imaging (MRI) showed an important infiltration and oedematous reaction of muscles and underlying soft tissues (Fig. 4a). An abdominal and pelvic scan and bone scintigraphy revealed similar lesions. The cerebral scan was normal. In September 2011, treatment with vismodegib, a sonic hedgehog pathway inhibitor, was started at a dose of 150 mg per day. The lesion diameter was 22 9 16 cm when the treatment was started (Fig. 1a). In October 2012, after 13 months of treatment, a partial response was obtained. Complete regression of the cutaneous lesion and a decrease in the bone lesions were noted. Indeed a significant clinical response was noted, with complete disappearance of lymphadenopathies. A
16 9 10-cm scar persisted (Fig. 1b). Multiple skin biopsies confirmed the absence of residual lesions. A new staging showed partial response with a decrease in the intensity of the hypermetabolic superficial and deep lesions on the PET scan, with respective maximum SUVs of 8 and 10 (Fig. 3b). We observed reduced infiltration and oedematous reactions of the muscles and underlying soft tissues on the pelvis MRI (Fig. 4b). The patient presented with no side-effects except for some grade 1 muscular cramping. His general health condition was good, and there were no palpable lymph nodes. In December 2012, at a multidisciplinary meeting, it was proposed to stop vismodegib and to initiate a complementary radiotherapy course because of the bone involvement. Radiotherapy was carried out at a dose of 60 Gy over 30 sessions. A re-evaluation was carried out in March 2013. The MRI showed complete regression of muscle infiltration and a decrease of the contrast enhancement. Skin biopsies of the cutaneous tumour, which remained stable clinically, revealed signs of dermatitis without residual tumour. In June 2014, 33 months after the beginning of the treatment, clinical examination showed stability of the cutaneous lesions, and imaging tests highlighted persistent iliac and sacral bone lysis along with the appearance of fractures. Treatment with bisphosphonates was introduced and further radiotherapy was proposed at a multidisciplinary meeting. Radiotherapy was carried out at a dose of 20 Gy over five sessions in December 2014. In January 2015, vismodegib had been continued for 40 months.
Discussion
Fig 2. Histology of trichoblastic carcinoma with PHLDA1 staining: brown staining of the tumour. British Journal of Dermatology (2015) 173, pp1059–1062
Vismodegib is a new drug for locally advanced or metastatic BCC, which induces tumour regression. It is already on the market in the U.S.A. and Europe, after having received authorization from the US Food and Drug Administration and the European Medicines Agency, respectively. Vismodegib is the first molecule classified as an inhibitor of the patched sonic hedgehog pathway in the treatment of skin tumours. However, vismodegib can induce significant side-effects that may lead practitioners to stop treatment. These side-effects are muscle spasm (71%), alopecia (65%), dysgeusia (57%), © 2015 British Association of Dermatologists
Vismodegib for locally advanced trichoblastic carcinoma, P. Lepesant et al. 1061
(a1)
(b1)
(a2)
(b2)
Fig 3. Positron emission tomography scan of trichoblastic carcinoma: a decrease in the intensity of hypermetabolic cutaneous and bone lesions with vismodegib. (a) December 2010, before the treatment, maximum standard uptake value of 20 and 15. (b) October 2012, after 13 months of treatment, maximum standard uptake value of 8 and 10.
(a1)
(b1)
(a2)
(b2)
Fig 4. Pelvis magnetic resonance imaging of trichoblastic carcinoma: reduced infiltration and oedematous reaction of muscles and underlying soft tissues. (a) December 2010, before the treatment. (b) October 2012, after 13 months of treatment.
weight loss (54%), fatigue (45%), nausea (34%), decrease in appetite and diarrhoea.1 Although we observed a recurrence of BCC after drug withdrawal and some acquired resistance to treatment, vismodegib represents a new therapeutic strategy presenting real clinical benefits to patients. This may provide an improvement over sunitinib, which has shown efficacy in a small number of patients, but its efficacy is partial and the tolerance not always good.2 © 2015 British Association of Dermatologists
Data in the literature differ regarding the role of the patched sonic hedgehog pathway in the pathogenesis of adnexal tumours. Indeed, some studies suggest that this pathway is involved in the formation of adnexal tumours such as trichoepithelioma, trichoblastoma and cylindroma, as in BCC. There are several lines of evidence that support this involvement. Firstly, there is the spontaneous appearance of numerous BCCs, trichoepitheliomas, trichoblastomas and cylindromas in mice with constitutive activation of the sonic hedgehog British Journal of Dermatology (2015) 173, pp1059–1062
1062 Vismodegib for locally advanced trichoblastic carcinoma, P. Lepesant et al.
patched pathway.3 Secondly, in trichoepitheliomas, there have been positive results in molecular research into PTCH1, a tumour suppressor gene, mutations of which cause constitutive activation of the sonic hedgehog patched pathway.4 Thirdly, GLI15 and SOX9,6 transcription factors involved in the signalling pathway of patched sonic hedgehog, seem to have increased levels in adnexal carcinomas. BCC and TC are two very close entities, both clinically and histologically, and differential diagnosis is often problematic. TC typically develops from a trichoblastoma at the expense of the epithelium of the hair shaft, after a long period of evolution. From a histological point of view, TC, unlike BCC, is a proliferation of lobules of basaloid cells not connected with the epidermis, devoid of a clear palisading arrangement in the periphery and with less stromal retraction. Most TCs show deeper extension and higher metastatic risks than BCCs. Several attempts have been made to differentiate these two entities using different markers.7–10 Currently, the most widely used marker to differentiate these two diagnoses is PHLDA1.11–13 Indeed, this is a reliable marker of hair follicle stem cells, the expression of which is reported in trichoepitheliomas and TCs but not in BCCs. This marker is also known as TDAG51 (for T-cell death-associated gene 51). It is present in normal skin in hair follicles at the bulb and the lower portion of the inner root sheath, and also in eccrine glands, scattered dendritic cells and melanocytes. Differentiating these two entities remains difficult and error prone, and the use of these markers is limited to reference centres and research settings. In conclusion, we report the first case of TC that showed response to vismodegib. Vismodegib could represent a new therapeutic tool in the treatment of TC. Further studies are needed to confirm the role of vismodegib in the management of advanced TC.
References 1 Dessinioti C, Plaka M, Stratigos AJ. Vismodegib for the treatment of basal cell carcinoma: results and implications of the ERIVANCE BCC trial. Future Oncol 2014; 10:927–36.
British Journal of Dermatology (2015) 173, pp1059–1062
2 Battistella M, Mateus C, Lassau N et al. Sunitinib efficacy in the treatment of metastatic skin adnexal carcinomas: report of two patients with hidradenocarcinoma and trichoblastic carcinoma. J Eur Acad Dermatol Venereol 2010; 24:199–203. 3 Nilsson M, Unden AB, Krause D et al. Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1. Proc Natl Acad Sci U S A 2000; 97:3438–43. 4 Vorechovsky I, Unden AB, Sandstedt B et al. Trichoepitheliomas contain somatic mutations in the overexpressed PTCH gene: support for a gatekeeper mechanism in skin tumorigenesis. Cancer Res 1997; 57:4677–81. 5 Hatta N, Hirano T, Kimura T et al. Molecular diagnosis of basal cell carcinoma and other basaloid cell neoplasms of the skin by the quantification of Gli1 transcript levels. J Cutan Pathol 2005; 32:131–6. 6 Vidal VP, Ortonne N, Schedl A. SOX9 expression is a general marker of basal cell carcinoma and adnexal-related neoplasms. J Cutan Pathol 2008; 35:373–9. 7 Arits AHMM, Van Marion AMW, Lohman BGPM et al. Differentiation between basal cell carcinoma and trichoepithelioma by immunohistochemical staining of the androgen receptor: an overview. Eur J Dermatol 2011; 21:870–3. 8 Heidarpour M, Rajabi P, Sajadi F. CD10 expression helps to differentiate basal cell carcinoma from trichoepithelioma. J Res Med Sci 2011; 16:938–44. 9 Sengul D, Sengul I, Astarci MH et al. CD10 for the distinct differential diagnosis of basal cell carcinoma and benign tumours of cutaneous appendages originating from hair follicle. Pol J Pathol 2010; 61:140–6. 10 Sellheyer K, Nelson P, Kutzner H, Patel RM. The immunohistochemical differential diagnosis of microcystic adnexal carcinoma, desmoplastic trichoepithelioma and morpheaform basal cell carcinoma using BerEP4 and stem cell markers. J Cutan Pathol 2013; 40:363–70. 11 Sellheyer K, Krahl D. PHLDA1 (TDAG51) is a follicular stem cell marker and differentiates between morphoeic basal cell carcinoma and desmoplastic trichoepithelioma. Br J Dermatol 2011; 164:141–7. 12 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. J Cutan Pathol 2011; 38:542–50. 13 Yeh I, McCalmont TH, LeBoit PE. Differential expression of PHLDA1 (TDAG51) in basal cell carcinoma and trichoepithelioma. Br J Dermatol 2012; 167:1106–10.
© 2015 British Association of Dermatologists
