Correspondence
2 Ota T, Clayton AC, Minot DM et al. Minichromosome maintenance protein 7 as a potential prognostic factor for progression-free survival in high-grade serous carcinomas of the ovary. Mod Pathol 2011; 24: 277–87. 3 Brown DC, Gatter KC. Ki67 protein: the immaculate deception? Histopathology 2002; 40: 2–11. 4 Ribeiro D, Narikawa S, Marques ME. Expression of apoptotic and cell proliferation regulatory proteins in keratoacanthomas and squamous cell carcinomas of the skin. Pathol Res Pract 2008; 204: 97–104. 5 Shimizu T, Muto M, Murakami T et al. Overexpression of p53 protein associated with proliferative activity as evaluated by Ki-67 immunostaining in well-differentiated squamous cell carcinoma of the skin. Dermatology 1997; 195: 224–7. Figure 2 Percentage of Ki-67 immunoreactivity in keratoacan-
thoma (KA) and squamous cell carcinoma (SCC). The range of Ki-67 positivity in SCC indicates that immunoreactivity of < 20% is more suggestive for KA.
Because the cell cycle-regulating protein Ki-67 is expressed during all phases of the cell cycle except G0, cellular expression of Ki-67 provides a measure of the growth fraction of a tumour.3 We found significant overexpression of Ki-67 in SCC compared with KA, which is in accordance with previous results.4,5 Interestingly, we did not find any SCC with a positive Ki-67 fraction of < 20% (Fig. 2); to our knowledge, this limiting value has not been reported before. The SCC in the study of Shimizu et al.5 all had a positive Ki-67 fraction of > 20% as well, although the authors did not address this point specifically. Hence, a Ki-67 fraction of < 20% could therefore be suggestive for KA. Our results provide an indication that Ki-67 could be useful for differentiating between KA and SCC, and should be validated in a larger study.
Anetodermic pilomatricoma in a patient with hypermobility syndrome doi: 10.1111/ced.12215 Pilomatricoma is a benign cutaneous neoplasm derived from matrix cells of the hair follicle.1 Anetoderma is a localized area of soft, flaccid skin caused by focal loss of dermal elastic tissue and can be seen in the skin overlying pilomatricomas in 2% cases.1 Pilomatricomas have been described in association with myotonic dystrophy, Gardner syndrome, Steinert disease, Rubinstein–Taybi syndrome, Turner syndrome, sarcoidosis and tuberous sclerosis. We report a case of anetodermic pilomatricoma in a patient with hypermobility syndrome, which to our knowledge, has not previously been described in the literature. A 23-year-old woman presented with a 1-year history of a lump on her left upper chest, where it recurrently rubbed on her bra strap. The skin overlying the lump gradually became saggy and wrinkled.
Acknowledgements We thank Sabine Richter for her excellent technical assistance. N. Scola, H. M. Segert, M. St€ ucker, P. Altmeyer, T. Gambichler,* and A. Kreuter* Department of Dermatology, Venereology and Allergology, RuhrUniversity Bochum, Gudrunstrasse 56, 44791 Bochum, Germany E-mail: [email protected] *Both authors contributed equally to this work and should be considered joint first authors. Conflict of interest: none declared. Accepted for publication 7 April 2013
References 1 Hiraiwa A, Fujita M, Adachi A et al. Specific distribution patterns of hCDC47 expression in cutaneous diseases. J Cutan Pathol 1998; 25: 285–90.
218
Clinical and Experimental Dermatology (2014) 39, pp216–234
Figure 1 Pink, scar-like area with lax skin overlying a firm
nodule on left upper chest.
ª 2013 British Association of Dermatologists
Correspondence
(a)
(b)
(c)
(d)
(e)
(f)
Figure 2 (a) Well-circumscribed nodule in the subcutis; (b) anetoderma overlying the nodule; (c) the tumour was predominantly com-
posed of keratin with visible outlines of eosinophilic shadow cells and basaloid epithelium at the periphery. Haematoxylin and eosin, original magnification (a) 920; (b) 940; (c) 9100. (d–e) Complete loss of elastic fibres in the dermis overlying the tumour with (f) surrounding skin showing normal elastic fibre. Elastic van Gieson, original magnification (d) 940; (e,f) 9100.
ª 2013 British Association of Dermatologists
Clinical and Experimental Dermatology (2014) 39, pp216–234
219
Correspondence
On physical examination, an oval, pink, scar-like area 30 9 18 mm in size was seen. The skin over the area was lax, while beneath it, a firm, mobile subcutaneous nodule could be palpated (Fig. 1). Wide scars were also visible on the patient’s arms resulting from surgery for previous injuries. Her joints were hypermobile, with a Beighton score of 6 out of 9. Although her skin was not hyperextensible, she had increased scarring over her elbows. These characteristics fitted with the phenotype of hypermobility syndrome, which overlaps with hypermobile Ehlers–Danlos Syndrome (EDS). There was no family history of hypermobility. On histological examination of the lesion, a wellcircumscribed nodule was seen in the subcutis (Fig. 2a), predominantly composed of keratin with eosinophilic shadow cells and basaloid epithelium at the periphery (Fig. 2b). This was associated with marked foreign bodytype granulomatous inflammation (Fig. 2c). There was complete loss of elastic tissue in the dermis overlying the tumour (Fig. 2d). The features were of secondary anetoderma overlying pilomatricoma. Pilomatricoma has two peak ages of presentation, in the first and sixth decades of life. It usually presents in the head and neck region and has a slight female preponderance.1 First described in 1943, anetodermic pilomatricoma has a later age of onset, usually in the third decade of life. It also has a different site of predilection and occurs in areas prone to mechanical trauma, such as the trunk or arms. Anetodermic pilomatricoma presents as a firm, subcutaneous nodule and the skin overlying the nodule is atrophic, wrinkled or keloid-like.2 There are two hypotheses to explain the pathogenesis of the anetoderma. It could either be due to elastic-tissue destruction caused by catabolic enzymes released by the tumour or the inflammatory infiltrate,3 or to lymphatic compression by the tumour, resulting in vasodilatation and subsequent dermal oedema.4 Abnormalities of collagen and elastic fibres have been proposed as causes behind perforating disorders and anetoderma could be a preceding step to perforation, giving rise to perforating pilomatricoma.3 Although haploinsufficiency of the TNXB gene is found in a small percentage of female patients with hypermobile EDS and COL3A1 mutation has been implicated in one family, the cause is not yet known in the majority of hypermobility syndrome/hypermobile EDS.5,6 Although the association of anetoderma in pilomatricoma in our patient with hypermobility syndrome may be a coincidence, it seems likely that the development of anetoderma in our patient was a result of combined mechanical challenge due to her bra strap, disrupted dermal integrity due to hypermobility syndrome and skin stretching due to the presence of underlying tumour. Ultrastructural and clinical abnormalities of elastic tissues, such as elastosis perforans serpiginosa, have previously been described in inherited diseases of connective-tissue disorders including EDS.5
220
Clinical and Experimental Dermatology (2014) 39, pp216–234
This is the first report of anetodermic pilomatricoma in hypermobility syndrome and extends the spectrum of elastic abnormalities seen in this condition. M. Chattopadhyay,1 E. Rytina,2 J. C. Sterling,1 and N. P. Burrows1 Departments of 1Dermatology and 2Histopathology, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK E-mail: [email protected] Conflict of interest: none declared. Accepted for publication 3 May 2013
References 1 Julian CG, Bowers PW. A clinical review of 209 pilomatricomas. J Am Acad Dermatol 1998; 39: 191–5. 2 Fern andez-Flores A, Gonzalez-Montero JM. Anetodermic variant of pilomatricoma. Int J Dermatol 2005; 44: 876–7. 3 Jones CC, Tschen JA. Anetodermic cutaneous changes overlying pilomatricomas. J Am Acad Dermatol 1991; 25: 1072–6. 4 Weichert GE, Bush KL, Crawford RI. Bullous pilomatricoma: a report of clinical and pathologic findings and review of dermal bullous disorders. J Cutan Med Surg 2001; 5: 394–6. 5 Mehta RK, Burrows NP, Payne CM et al. Elastosis perforans Serpiginosa and associated disorders. Clin Exp Dermatol 2001; 26: 521–4. 6 Zweers MC, Bristow J, Steijlen PM et al. Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers–Danlos syndrome. Am J Hum Genet 2003; 73: 214–17.
Acute generalized exanthematous pustulosis due to acetazolamide: negative on patch testing and confirmed by delayed-reading intradermal testing doi: 10.1111/ced.12214 Acute generalized exanthematous pustulosis (AGEP) is usually secondary to drug intake. Certain drugs (pristinamycin, diltiazem, penicillin, hydroxychloroquine and antiinfective sulfonamides) have been implicated more often,1 whereas other drugs, including paracetamol, have been implicated more rarely.2 As the rash may be severe, oral challenging is usually contraindicated. Patch testing is one way to rechallenge the patient when several drugs are suspected. However, in a recent series of 45 patients with AGEP, 26 had a positive drug patch test (PT) and 5 with negative PT results had a positive result after delayed intradermal testing.3 We report a case of AGEP negative to PTs with suspected drugs. Intradermal testing with delayed reading allowed identification of acetazolamide as the culprit drug.
ª 2013 British Association of Dermatologists
2 Ota T, Clayton AC, Minot DM et al. Minichromosome maintenance protein 7 as a potential prognostic factor for progression-free survival in high-grade serous carcinomas of the ovary. Mod Pathol 2011; 24: 277–87. 3 Brown DC, Gatter KC. Ki67 protein: the immaculate deception? Histopathology 2002; 40: 2–11. 4 Ribeiro D, Narikawa S, Marques ME. Expression of apoptotic and cell proliferation regulatory proteins in keratoacanthomas and squamous cell carcinomas of the skin. Pathol Res Pract 2008; 204: 97–104. 5 Shimizu T, Muto M, Murakami T et al. Overexpression of p53 protein associated with proliferative activity as evaluated by Ki-67 immunostaining in well-differentiated squamous cell carcinoma of the skin. Dermatology 1997; 195: 224–7. Figure 2 Percentage of Ki-67 immunoreactivity in keratoacan-
thoma (KA) and squamous cell carcinoma (SCC). The range of Ki-67 positivity in SCC indicates that immunoreactivity of < 20% is more suggestive for KA.
Because the cell cycle-regulating protein Ki-67 is expressed during all phases of the cell cycle except G0, cellular expression of Ki-67 provides a measure of the growth fraction of a tumour.3 We found significant overexpression of Ki-67 in SCC compared with KA, which is in accordance with previous results.4,5 Interestingly, we did not find any SCC with a positive Ki-67 fraction of < 20% (Fig. 2); to our knowledge, this limiting value has not been reported before. The SCC in the study of Shimizu et al.5 all had a positive Ki-67 fraction of > 20% as well, although the authors did not address this point specifically. Hence, a Ki-67 fraction of < 20% could therefore be suggestive for KA. Our results provide an indication that Ki-67 could be useful for differentiating between KA and SCC, and should be validated in a larger study.
Anetodermic pilomatricoma in a patient with hypermobility syndrome doi: 10.1111/ced.12215 Pilomatricoma is a benign cutaneous neoplasm derived from matrix cells of the hair follicle.1 Anetoderma is a localized area of soft, flaccid skin caused by focal loss of dermal elastic tissue and can be seen in the skin overlying pilomatricomas in 2% cases.1 Pilomatricomas have been described in association with myotonic dystrophy, Gardner syndrome, Steinert disease, Rubinstein–Taybi syndrome, Turner syndrome, sarcoidosis and tuberous sclerosis. We report a case of anetodermic pilomatricoma in a patient with hypermobility syndrome, which to our knowledge, has not previously been described in the literature. A 23-year-old woman presented with a 1-year history of a lump on her left upper chest, where it recurrently rubbed on her bra strap. The skin overlying the lump gradually became saggy and wrinkled.
Acknowledgements We thank Sabine Richter for her excellent technical assistance. N. Scola, H. M. Segert, M. St€ ucker, P. Altmeyer, T. Gambichler,* and A. Kreuter* Department of Dermatology, Venereology and Allergology, RuhrUniversity Bochum, Gudrunstrasse 56, 44791 Bochum, Germany E-mail: [email protected] *Both authors contributed equally to this work and should be considered joint first authors. Conflict of interest: none declared. Accepted for publication 7 April 2013
References 1 Hiraiwa A, Fujita M, Adachi A et al. Specific distribution patterns of hCDC47 expression in cutaneous diseases. J Cutan Pathol 1998; 25: 285–90.
218
Clinical and Experimental Dermatology (2014) 39, pp216–234
Figure 1 Pink, scar-like area with lax skin overlying a firm
nodule on left upper chest.
ª 2013 British Association of Dermatologists
Correspondence
(a)
(b)
(c)
(d)
(e)
(f)
Figure 2 (a) Well-circumscribed nodule in the subcutis; (b) anetoderma overlying the nodule; (c) the tumour was predominantly com-
posed of keratin with visible outlines of eosinophilic shadow cells and basaloid epithelium at the periphery. Haematoxylin and eosin, original magnification (a) 920; (b) 940; (c) 9100. (d–e) Complete loss of elastic fibres in the dermis overlying the tumour with (f) surrounding skin showing normal elastic fibre. Elastic van Gieson, original magnification (d) 940; (e,f) 9100.
ª 2013 British Association of Dermatologists
Clinical and Experimental Dermatology (2014) 39, pp216–234
219
Correspondence
On physical examination, an oval, pink, scar-like area 30 9 18 mm in size was seen. The skin over the area was lax, while beneath it, a firm, mobile subcutaneous nodule could be palpated (Fig. 1). Wide scars were also visible on the patient’s arms resulting from surgery for previous injuries. Her joints were hypermobile, with a Beighton score of 6 out of 9. Although her skin was not hyperextensible, she had increased scarring over her elbows. These characteristics fitted with the phenotype of hypermobility syndrome, which overlaps with hypermobile Ehlers–Danlos Syndrome (EDS). There was no family history of hypermobility. On histological examination of the lesion, a wellcircumscribed nodule was seen in the subcutis (Fig. 2a), predominantly composed of keratin with eosinophilic shadow cells and basaloid epithelium at the periphery (Fig. 2b). This was associated with marked foreign bodytype granulomatous inflammation (Fig. 2c). There was complete loss of elastic tissue in the dermis overlying the tumour (Fig. 2d). The features were of secondary anetoderma overlying pilomatricoma. Pilomatricoma has two peak ages of presentation, in the first and sixth decades of life. It usually presents in the head and neck region and has a slight female preponderance.1 First described in 1943, anetodermic pilomatricoma has a later age of onset, usually in the third decade of life. It also has a different site of predilection and occurs in areas prone to mechanical trauma, such as the trunk or arms. Anetodermic pilomatricoma presents as a firm, subcutaneous nodule and the skin overlying the nodule is atrophic, wrinkled or keloid-like.2 There are two hypotheses to explain the pathogenesis of the anetoderma. It could either be due to elastic-tissue destruction caused by catabolic enzymes released by the tumour or the inflammatory infiltrate,3 or to lymphatic compression by the tumour, resulting in vasodilatation and subsequent dermal oedema.4 Abnormalities of collagen and elastic fibres have been proposed as causes behind perforating disorders and anetoderma could be a preceding step to perforation, giving rise to perforating pilomatricoma.3 Although haploinsufficiency of the TNXB gene is found in a small percentage of female patients with hypermobile EDS and COL3A1 mutation has been implicated in one family, the cause is not yet known in the majority of hypermobility syndrome/hypermobile EDS.5,6 Although the association of anetoderma in pilomatricoma in our patient with hypermobility syndrome may be a coincidence, it seems likely that the development of anetoderma in our patient was a result of combined mechanical challenge due to her bra strap, disrupted dermal integrity due to hypermobility syndrome and skin stretching due to the presence of underlying tumour. Ultrastructural and clinical abnormalities of elastic tissues, such as elastosis perforans serpiginosa, have previously been described in inherited diseases of connective-tissue disorders including EDS.5
220
Clinical and Experimental Dermatology (2014) 39, pp216–234
This is the first report of anetodermic pilomatricoma in hypermobility syndrome and extends the spectrum of elastic abnormalities seen in this condition. M. Chattopadhyay,1 E. Rytina,2 J. C. Sterling,1 and N. P. Burrows1 Departments of 1Dermatology and 2Histopathology, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK E-mail: [email protected] Conflict of interest: none declared. Accepted for publication 3 May 2013
References 1 Julian CG, Bowers PW. A clinical review of 209 pilomatricomas. J Am Acad Dermatol 1998; 39: 191–5. 2 Fern andez-Flores A, Gonzalez-Montero JM. Anetodermic variant of pilomatricoma. Int J Dermatol 2005; 44: 876–7. 3 Jones CC, Tschen JA. Anetodermic cutaneous changes overlying pilomatricomas. J Am Acad Dermatol 1991; 25: 1072–6. 4 Weichert GE, Bush KL, Crawford RI. Bullous pilomatricoma: a report of clinical and pathologic findings and review of dermal bullous disorders. J Cutan Med Surg 2001; 5: 394–6. 5 Mehta RK, Burrows NP, Payne CM et al. Elastosis perforans Serpiginosa and associated disorders. Clin Exp Dermatol 2001; 26: 521–4. 6 Zweers MC, Bristow J, Steijlen PM et al. Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers–Danlos syndrome. Am J Hum Genet 2003; 73: 214–17.
Acute generalized exanthematous pustulosis due to acetazolamide: negative on patch testing and confirmed by delayed-reading intradermal testing doi: 10.1111/ced.12214 Acute generalized exanthematous pustulosis (AGEP) is usually secondary to drug intake. Certain drugs (pristinamycin, diltiazem, penicillin, hydroxychloroquine and antiinfective sulfonamides) have been implicated more often,1 whereas other drugs, including paracetamol, have been implicated more rarely.2 As the rash may be severe, oral challenging is usually contraindicated. Patch testing is one way to rechallenge the patient when several drugs are suspected. However, in a recent series of 45 patients with AGEP, 26 had a positive drug patch test (PT) and 5 with negative PT results had a positive result after delayed intradermal testing.3 We report a case of AGEP negative to PTs with suspected drugs. Intradermal testing with delayed reading allowed identification of acetazolamide as the culprit drug.
ª 2013 British Association of Dermatologists
![[Anetodermic pilomatricoma. Uncommon variant of a common childhood adnexal tumor].](/assets/img/hold.png)
