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Acantholytic squamous cell carcinoma arising in actinic keratoacanthoma: Two cases with E-cadherin expression supporting a potentially different prognosis
Rev Esp Patol. 2016;49(1):23---26
Patología R E V I S TA
E S PA Ñ O L A
D E
www.elsevier.es/patologia
BRIEF REPORT
Acantholytic squamous cell carcinoma arising in actinic keratoacanthoma: Two cases with E-cadherin expression supporting a potentially different prognosis Vicente Sabater Marco a,∗ , Ana García Rabasco b , Miguel Martorell Cebollada a , Rafael Botella Estrada c a
Department of Pathology, University General Hospital, Valencia, Spain Department of Dermatology, Clínica Dermatológica RBE, Valencia, Spain c Department of Dermatology, University Hospital La Fe, Valencia, Spain b
Received 20 June 2015; accepted 7 August 2015 Available online 1 December 2015
KEYWORDS Keratoacanthoma; Acantholytic squamous cell carcinoma; Malignant transformation; E-cadherin; p63; Prognosis
PALABRAS CLAVE Queratoacantoma; Carcinoma de células escamosas acantolítico; Transformación maligna; E-cadherina;
∗
Abstract Among crateriform squamous proliferation, keratoacanthoma is considered as a squamous cell carcinoma or as a non-malignant, self-healing lesion that frequently becomes malignant. To date, published cases of neoplasms originating from keratoacanthoma are always conventional squamous cell carcinomas. Acantholytic squamous cell carcinoma arising in keratoacanthomas has not been previously reported. We present two crater-shaped nodular lesions on the face of elderly patients with clinical and histopathological features of keratoacanthoma with transformation areas to acantholytic squamous cell carcinoma. In the immunohistochemical study, Ki-67 and p63 immunostaining supports the diagnosis of acantholytic squamous cell carcinoma ex-keratoacanthoma. We suggest that E-cadherin expression and vimentin negativity could probably be related with less aggressive behaviour and a better prognosis. © 2015 SEAP y SEC. Published by Elsevier España, S.L.U. All rights reserved.
Carcinoma de células escamosas acantolítico originado en queratoacantoma actínico: dos casos con expresión de E-cadherina indicando un pronóstico diferente Resumen Dentro de las proliferaciones escamosas crateriformes, el queratoacantoma se considera como un carcinoma escamoso o como una lesión benigna autocurativa que frecuentemente se vuelve maligna. Las neoplasias descritas que se originan del queratoacantoma son siempre carcinomas escamosos convencionales. Carcinomas escamosos acantolíticos originados en queratoacantomas no se han descrito en la literatura. Presentamos 2 nódulos crateriformes en la cara de ancianos con características clínicas e histopatológicas de
Corresponding author. E-mail address: [email protected] (V. Sabater Marco).
http://dx.doi.org/10.1016/j.patol.2015.08.001 1699-8855/© 2015 SEAP y SEC. Published by Elsevier España, S.L.U. All rights reserved.
24
V. Sabater Marco et al.
p63; Pronóstico
queratoacantoma con áreas de transformación a carcinoma escamoso acantolítico. En el estudio inmunohistoquímico, la expresión de Ki-67 y p63 apoya el diagnóstico de carcinoma escamoso acantolítico ex-queratoacantoma. Nosotros hipotetizamos que la expresión de E-cadherina y la negatividad de vimentina están probablemente relacionadas con menor agresividad y excelente pronóstico en estos pacientes. © 2015 SEAP y SEC. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.
Introduction Keratoacanthomas (KAs) are epidermal tumours of unknown aetiology occurring in patients with a history of sun damage and/or skin trauma1 ; their evolution is unpredictable2 as some KAs regress while others develop into squamous cell carcinoma (SCC). We present two actinic KAs with malignant transformation into acantholytic SCC.
Case reports The first patient was a 91-year-old man who had undergone surgery 7 years previously for Bowen’s disease on the left temple. He was being treated with cryotherapy for multiple actinic keratoses on the face and scalp. In February 2013 he presented with a fast-growing, ulcerated, exophytic nodule on the lower lip. The clinical diagnosis was SCC or KA (Fig. 1a). The second patient was a 78-year-old woman with a past medical history of actinic skin damage. In October 2011 she presented with a fast-growing nodule on her right cheek, clinically suspicious of KA. Both patients underwent complete surgical excision of the lesion with tumour-free margins. Histopathological
examination revealed two exoendophytic epidermal nodules, both 1 cm in size, one of which was ulcerated. In each case, the lesion was composed of a keratin-filled crater surrounded by overhanging lips of epithelium and an acantholytic neoplasia. In the first case, the acantholytic neoplasia was on top of the KA, laterally displacing the keratin-filled crater and infiltrating the papillary dermis (Fig. 1b). In the second case, the infiltration pattern was through the KA, reaching the reticular dermis (Fig. 2a). KAs were composed of squamous cell lobes with abundant palestaining cytoplasm and central keratinization. Neutrophilic micro-abscesses were also observed. A neoplastic proliferation of polygonal cells with nuclear pleomorphism and dyskeratosis, arranged in an acantholytic pattern, was seen arising from the squamous cell lobes. Tumour cells were loose or floating within pseudoglandular spaces (Fig. 2b). In acantholytic areas, mitotic activity was 5---10 mitoses (10HPF) in the first case and 15---20 mitoses (10HPF) in the second. In both patients, the reticular dermis showed fibrosis, solar elastosis, lymphocytes, plasma cells and eosinophils. No lymphovascular or perineural invasion was present. Immunohistochemical study revealed, in KA and acantholytic neoplasia, cytoplasmic staining with CKAE1/3, CK5/6 and CK34E12 and strong membrane staining with
Figure 1 Case 1: (a) ulcerated exophytic nodule in the lower lip, clinically suspected of SCC or KA; (b) exo-endophytic nodule composed of a lateralized keratin-filled crater surrounded by overhanging lips of epithelium and acantholytic SCC on the surface (haematoxylin and eosin, original magnification 2×).
Acantholytic squamous cell carcinoma ex-keratoacanthoma
25
Figure 2 Case 2: (a) typical KA with acantholytic SCC (haematoxylin and eosin, original magnification 2×); (b) acantholytic cells floating within pseudoglandular spaces showing nuclear pleomorphism and dyskeratosis (haematoxylin and eosin, original magnification 400×).
Figure 3 (a) Membrane immunostaining for E-cadherin in KA and acantholytic SCC (original magnification 100×); (b) nuclear staining for p63 in basal cells of KA and acantholytic squamous cells (original magnification 100×).
E-cadherin (Fig. 3a); whereas vimentin, CK7, carcinoembryonic antigen (CEAm), CD31, CD34 and CD117 were negative. Ki-67 and p63 (Fig. 3b) were positive preferentially in the KA basal cells and in all squamous acantholytic tumour cells. According to the morphological and immunohistochemical findings, the diagnosis was acantholytic SCC arising in KA. In both cases, cervical ultrasound ruled out lymphadenopathy and after follow-ups of 21 and 37 months respectively there is neither recurrence nor metastasis.
Discussion KAs are part of the spectrum of invasive keratinocytic hyperplasias of unpredictable evolution, which includes regression, expansion and neoplastic progression.2 Thus, to establish a diagnosis of malignant transformation of KA, one must recognize typical morphological features of KA and, besides, a SCC in the same lesion. There are major clinicopathological criteria to help us recognize a KA and distinguish it from SCC. Clinically, KA is a fast growing and volcano-like nodular lesion. Histopathologically, it is a wellcircumscribed, exo-endophytic nodular lesion of symmetric
architecture composed of a keratin-filled crater surrounded by overhanging lips of epithelium. An important feature is the extensive degree of keratinization within the nodule with abundant pale-staining cytoplasm cells and intraepithelial abscesses.3---5 We describe two crater-shaped nodular facial lesions with clinical findings and histological criteria of KA; at the same time an acantholytic SCC arising from KA was observed. Acantholytic SCCs are distinguished from typical KA by the marked cellular pleomorphism and mitotic activity as well as by tumour cell acantholysis. In one case, the presence of ulceration, which is not typical of KA, suggested malignant transformation of KA. In both cases, Ki-67 and p63 immunostaining distinguishes KA from acantholytic SCC, since only the latter showed strong nuclear staining. Both KAs with malignant transformation may have a differential diagnosis with the early/proliferative stage KA and crateriform infundibular SCC.6,7 Histopathologically, our two lesions were characterized by a combination of two components with a clear border, namely the typical KA and the acantholytic SCC. However, an early/proliferative stage KA principally shows the features of KA, the atypical findings being confined to the base of the lesion.6 The infundibular SCC with keratin-filled crater generally has no clear
26 components of KA but is composed of conventional SCC components or neoplastic infundibular canals associated with a SCC focus involving the follicular infundibulum at the periphery.7 The possibility of a KA developing into an SCC is well established. Sánchez Yus et al.4 published the first formal study on the transformation of a subset of KAs into SCCs. They found that at least 25% of KAs underwent malignant transformation. However, in another series,5 malignant transformation incidence was 5.7%, increasing to 13.9% in patients over 90. Neoplasms originating from KA are almost always conventional SCCs; only one verrucous SCC arising from an underlying giant KA8 has been described. However, to the best of our knowledge, the development of an acantholytic SCC in a KA has not been reported to date. Most KAs with malignant transformation, including our cases, have presented in the head and neck region of elderly patients with history of actinic skin damage5,9 ; it therefore seems appropriate to call such lesions actinic KAs. In this context, it is reasonable to deduce that additional mutations in these KAs, due to prolonged solar exposure, can result in the development of an SCC within the lesion. The occurrence of an acantholytic SCC in actinic KA may have prognostic implications. In some cases, there is evidence that SCC developing in a KA or an actinic keratosis behaves more benignly than the de novo SCC5 , perhaps a SCC arising in KA still has the ability to regress spontaneously.6 Acantholytic SCC of the skin is an aggressive neoplasm with frequent metastases and a mortality rate of 19%10 ; when invading the dermis, it shows loss of, or decreased, expression of two cell adhesion molecules, E-cadherin and syndecan-1.11 In both cases we have observed strong expression of E-cadherin, and absence of vimentin expression, possibly indicating lower aggressivity.
Ethical disclosures Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this study. Confidentiality of data. The authors declare that they have followed the protocols of their work centre on the publication of patient data Right to privacy and informed consent. The authors declare that no patient data appear in this article.
V. Sabater Marco et al.
Funding There has been no funding source for this work.
Conflicts of interest The authors have no conflicts of interest to declare.
References 1. Savage JA, Maize JC. Keratoacanthoma clinical behavior: a systematic review. Am J Dermatopathol. 2014;36: 422---9. 2. Lawrence N, Reed RJ. Actinic keratoacanthoma speculations on the nature of the lesion and the role of cellular immunity in its evolution. Am J Dermatopathol. 1990;12:517---33. 3. Ackerman AB, Niven J, Grant-Kels JM. Keratoacanthoma vs squamous-cell carcinoma. In: Differential diagnosis in dermatopathology. Philadelphia: Lea & Febiger; 1982. p. 122---5. 4. Sánchez Yus E, Simón P, Requena L, Ambrojo P, de Eusebio E. Solitary keratoacanthoma: a self-healing proliferation that frequently becomes malignant. Am J Dermatopathol. 2000;22:305---10. 5. Weedon DD, Malo J, Brooks D, Williamson R. Squamous cell carcinoma arising in keratoacanthoma: a neglected phenomenon in the elderly. Am J Dermatopathol. 2010;32:423---6. 6. Misago N, Takai T, Murata Y, Nagase K, Narisawa Y. Cases with a spontaneous regression of an infiltrating noncrateriform keratoacanthoma and squamous cell carcinoma with a keratoacanthoma-like component. J Dermatol. 2014;41: 430---4. 7. Misago N, Inoue T, Toda S, Narisawa Y. Infundibular (follicular) and infundibulocystic squamous cell carcinoma: a clinicopathological and immunohistochemical study. Am J Dermatopathol. 2011;33:687---94. 8. Bansal M, Manchanda K, Pandey SS. Verrucous cell carcinoma arising from an underlying giant keratoacanthoma. Int J Low Extrem Wounds. 2012;11:85---7. 9. Godbolt AM, Sullivan JJ, Weedon D. Keratoacanthoma with perineural invasion: a report of 40 cases. Aust J Dermatol. 2001;42:168---71. 10. Nappi O, Pettinato G, Wick MR. Adenoid (acantholytic) squamous cell carcinoma of the skin. J Cutan Pathol. 1989;16:114---21. 11. Bayer-Garner IB, Smoller BR. The expression of syndecan-1 is preferentially reduced compared with that of E-cadherin in acantholytic squamous cell carcinoma. J Cutan Pathol. 2001;28:83---9.
Patología R E V I S TA
E S PA Ñ O L A
D E
www.elsevier.es/patologia
BRIEF REPORT
Acantholytic squamous cell carcinoma arising in actinic keratoacanthoma: Two cases with E-cadherin expression supporting a potentially different prognosis Vicente Sabater Marco a,∗ , Ana García Rabasco b , Miguel Martorell Cebollada a , Rafael Botella Estrada c a
Department of Pathology, University General Hospital, Valencia, Spain Department of Dermatology, Clínica Dermatológica RBE, Valencia, Spain c Department of Dermatology, University Hospital La Fe, Valencia, Spain b
Received 20 June 2015; accepted 7 August 2015 Available online 1 December 2015
KEYWORDS Keratoacanthoma; Acantholytic squamous cell carcinoma; Malignant transformation; E-cadherin; p63; Prognosis
PALABRAS CLAVE Queratoacantoma; Carcinoma de células escamosas acantolítico; Transformación maligna; E-cadherina;
∗
Abstract Among crateriform squamous proliferation, keratoacanthoma is considered as a squamous cell carcinoma or as a non-malignant, self-healing lesion that frequently becomes malignant. To date, published cases of neoplasms originating from keratoacanthoma are always conventional squamous cell carcinomas. Acantholytic squamous cell carcinoma arising in keratoacanthomas has not been previously reported. We present two crater-shaped nodular lesions on the face of elderly patients with clinical and histopathological features of keratoacanthoma with transformation areas to acantholytic squamous cell carcinoma. In the immunohistochemical study, Ki-67 and p63 immunostaining supports the diagnosis of acantholytic squamous cell carcinoma ex-keratoacanthoma. We suggest that E-cadherin expression and vimentin negativity could probably be related with less aggressive behaviour and a better prognosis. © 2015 SEAP y SEC. Published by Elsevier España, S.L.U. All rights reserved.
Carcinoma de células escamosas acantolítico originado en queratoacantoma actínico: dos casos con expresión de E-cadherina indicando un pronóstico diferente Resumen Dentro de las proliferaciones escamosas crateriformes, el queratoacantoma se considera como un carcinoma escamoso o como una lesión benigna autocurativa que frecuentemente se vuelve maligna. Las neoplasias descritas que se originan del queratoacantoma son siempre carcinomas escamosos convencionales. Carcinomas escamosos acantolíticos originados en queratoacantomas no se han descrito en la literatura. Presentamos 2 nódulos crateriformes en la cara de ancianos con características clínicas e histopatológicas de
Corresponding author. E-mail address: [email protected] (V. Sabater Marco).
http://dx.doi.org/10.1016/j.patol.2015.08.001 1699-8855/© 2015 SEAP y SEC. Published by Elsevier España, S.L.U. All rights reserved.
24
V. Sabater Marco et al.
p63; Pronóstico
queratoacantoma con áreas de transformación a carcinoma escamoso acantolítico. En el estudio inmunohistoquímico, la expresión de Ki-67 y p63 apoya el diagnóstico de carcinoma escamoso acantolítico ex-queratoacantoma. Nosotros hipotetizamos que la expresión de E-cadherina y la negatividad de vimentina están probablemente relacionadas con menor agresividad y excelente pronóstico en estos pacientes. © 2015 SEAP y SEC. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.
Introduction Keratoacanthomas (KAs) are epidermal tumours of unknown aetiology occurring in patients with a history of sun damage and/or skin trauma1 ; their evolution is unpredictable2 as some KAs regress while others develop into squamous cell carcinoma (SCC). We present two actinic KAs with malignant transformation into acantholytic SCC.
Case reports The first patient was a 91-year-old man who had undergone surgery 7 years previously for Bowen’s disease on the left temple. He was being treated with cryotherapy for multiple actinic keratoses on the face and scalp. In February 2013 he presented with a fast-growing, ulcerated, exophytic nodule on the lower lip. The clinical diagnosis was SCC or KA (Fig. 1a). The second patient was a 78-year-old woman with a past medical history of actinic skin damage. In October 2011 she presented with a fast-growing nodule on her right cheek, clinically suspicious of KA. Both patients underwent complete surgical excision of the lesion with tumour-free margins. Histopathological
examination revealed two exoendophytic epidermal nodules, both 1 cm in size, one of which was ulcerated. In each case, the lesion was composed of a keratin-filled crater surrounded by overhanging lips of epithelium and an acantholytic neoplasia. In the first case, the acantholytic neoplasia was on top of the KA, laterally displacing the keratin-filled crater and infiltrating the papillary dermis (Fig. 1b). In the second case, the infiltration pattern was through the KA, reaching the reticular dermis (Fig. 2a). KAs were composed of squamous cell lobes with abundant palestaining cytoplasm and central keratinization. Neutrophilic micro-abscesses were also observed. A neoplastic proliferation of polygonal cells with nuclear pleomorphism and dyskeratosis, arranged in an acantholytic pattern, was seen arising from the squamous cell lobes. Tumour cells were loose or floating within pseudoglandular spaces (Fig. 2b). In acantholytic areas, mitotic activity was 5---10 mitoses (10HPF) in the first case and 15---20 mitoses (10HPF) in the second. In both patients, the reticular dermis showed fibrosis, solar elastosis, lymphocytes, plasma cells and eosinophils. No lymphovascular or perineural invasion was present. Immunohistochemical study revealed, in KA and acantholytic neoplasia, cytoplasmic staining with CKAE1/3, CK5/6 and CK34E12 and strong membrane staining with
Figure 1 Case 1: (a) ulcerated exophytic nodule in the lower lip, clinically suspected of SCC or KA; (b) exo-endophytic nodule composed of a lateralized keratin-filled crater surrounded by overhanging lips of epithelium and acantholytic SCC on the surface (haematoxylin and eosin, original magnification 2×).
Acantholytic squamous cell carcinoma ex-keratoacanthoma
25
Figure 2 Case 2: (a) typical KA with acantholytic SCC (haematoxylin and eosin, original magnification 2×); (b) acantholytic cells floating within pseudoglandular spaces showing nuclear pleomorphism and dyskeratosis (haematoxylin and eosin, original magnification 400×).
Figure 3 (a) Membrane immunostaining for E-cadherin in KA and acantholytic SCC (original magnification 100×); (b) nuclear staining for p63 in basal cells of KA and acantholytic squamous cells (original magnification 100×).
E-cadherin (Fig. 3a); whereas vimentin, CK7, carcinoembryonic antigen (CEAm), CD31, CD34 and CD117 were negative. Ki-67 and p63 (Fig. 3b) were positive preferentially in the KA basal cells and in all squamous acantholytic tumour cells. According to the morphological and immunohistochemical findings, the diagnosis was acantholytic SCC arising in KA. In both cases, cervical ultrasound ruled out lymphadenopathy and after follow-ups of 21 and 37 months respectively there is neither recurrence nor metastasis.
Discussion KAs are part of the spectrum of invasive keratinocytic hyperplasias of unpredictable evolution, which includes regression, expansion and neoplastic progression.2 Thus, to establish a diagnosis of malignant transformation of KA, one must recognize typical morphological features of KA and, besides, a SCC in the same lesion. There are major clinicopathological criteria to help us recognize a KA and distinguish it from SCC. Clinically, KA is a fast growing and volcano-like nodular lesion. Histopathologically, it is a wellcircumscribed, exo-endophytic nodular lesion of symmetric
architecture composed of a keratin-filled crater surrounded by overhanging lips of epithelium. An important feature is the extensive degree of keratinization within the nodule with abundant pale-staining cytoplasm cells and intraepithelial abscesses.3---5 We describe two crater-shaped nodular facial lesions with clinical findings and histological criteria of KA; at the same time an acantholytic SCC arising from KA was observed. Acantholytic SCCs are distinguished from typical KA by the marked cellular pleomorphism and mitotic activity as well as by tumour cell acantholysis. In one case, the presence of ulceration, which is not typical of KA, suggested malignant transformation of KA. In both cases, Ki-67 and p63 immunostaining distinguishes KA from acantholytic SCC, since only the latter showed strong nuclear staining. Both KAs with malignant transformation may have a differential diagnosis with the early/proliferative stage KA and crateriform infundibular SCC.6,7 Histopathologically, our two lesions were characterized by a combination of two components with a clear border, namely the typical KA and the acantholytic SCC. However, an early/proliferative stage KA principally shows the features of KA, the atypical findings being confined to the base of the lesion.6 The infundibular SCC with keratin-filled crater generally has no clear
26 components of KA but is composed of conventional SCC components or neoplastic infundibular canals associated with a SCC focus involving the follicular infundibulum at the periphery.7 The possibility of a KA developing into an SCC is well established. Sánchez Yus et al.4 published the first formal study on the transformation of a subset of KAs into SCCs. They found that at least 25% of KAs underwent malignant transformation. However, in another series,5 malignant transformation incidence was 5.7%, increasing to 13.9% in patients over 90. Neoplasms originating from KA are almost always conventional SCCs; only one verrucous SCC arising from an underlying giant KA8 has been described. However, to the best of our knowledge, the development of an acantholytic SCC in a KA has not been reported to date. Most KAs with malignant transformation, including our cases, have presented in the head and neck region of elderly patients with history of actinic skin damage5,9 ; it therefore seems appropriate to call such lesions actinic KAs. In this context, it is reasonable to deduce that additional mutations in these KAs, due to prolonged solar exposure, can result in the development of an SCC within the lesion. The occurrence of an acantholytic SCC in actinic KA may have prognostic implications. In some cases, there is evidence that SCC developing in a KA or an actinic keratosis behaves more benignly than the de novo SCC5 , perhaps a SCC arising in KA still has the ability to regress spontaneously.6 Acantholytic SCC of the skin is an aggressive neoplasm with frequent metastases and a mortality rate of 19%10 ; when invading the dermis, it shows loss of, or decreased, expression of two cell adhesion molecules, E-cadherin and syndecan-1.11 In both cases we have observed strong expression of E-cadherin, and absence of vimentin expression, possibly indicating lower aggressivity.
Ethical disclosures Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this study. Confidentiality of data. The authors declare that they have followed the protocols of their work centre on the publication of patient data Right to privacy and informed consent. The authors declare that no patient data appear in this article.
V. Sabater Marco et al.
Funding There has been no funding source for this work.
Conflicts of interest The authors have no conflicts of interest to declare.
References 1. Savage JA, Maize JC. Keratoacanthoma clinical behavior: a systematic review. Am J Dermatopathol. 2014;36: 422---9. 2. Lawrence N, Reed RJ. Actinic keratoacanthoma speculations on the nature of the lesion and the role of cellular immunity in its evolution. Am J Dermatopathol. 1990;12:517---33. 3. Ackerman AB, Niven J, Grant-Kels JM. Keratoacanthoma vs squamous-cell carcinoma. In: Differential diagnosis in dermatopathology. Philadelphia: Lea & Febiger; 1982. p. 122---5. 4. Sánchez Yus E, Simón P, Requena L, Ambrojo P, de Eusebio E. Solitary keratoacanthoma: a self-healing proliferation that frequently becomes malignant. Am J Dermatopathol. 2000;22:305---10. 5. Weedon DD, Malo J, Brooks D, Williamson R. Squamous cell carcinoma arising in keratoacanthoma: a neglected phenomenon in the elderly. Am J Dermatopathol. 2010;32:423---6. 6. Misago N, Takai T, Murata Y, Nagase K, Narisawa Y. Cases with a spontaneous regression of an infiltrating noncrateriform keratoacanthoma and squamous cell carcinoma with a keratoacanthoma-like component. J Dermatol. 2014;41: 430---4. 7. Misago N, Inoue T, Toda S, Narisawa Y. Infundibular (follicular) and infundibulocystic squamous cell carcinoma: a clinicopathological and immunohistochemical study. Am J Dermatopathol. 2011;33:687---94. 8. Bansal M, Manchanda K, Pandey SS. Verrucous cell carcinoma arising from an underlying giant keratoacanthoma. Int J Low Extrem Wounds. 2012;11:85---7. 9. Godbolt AM, Sullivan JJ, Weedon D. Keratoacanthoma with perineural invasion: a report of 40 cases. Aust J Dermatol. 2001;42:168---71. 10. Nappi O, Pettinato G, Wick MR. Adenoid (acantholytic) squamous cell carcinoma of the skin. J Cutan Pathol. 1989;16:114---21. 11. Bayer-Garner IB, Smoller BR. The expression of syndecan-1 is preferentially reduced compared with that of E-cadherin in acantholytic squamous cell carcinoma. J Cutan Pathol. 2001;28:83---9.