deposition or systemic oxalosis [1]. There are two principal types of the disease. Type I, which is characterized by a deficiency of the hepatic enzyme alanine-glyoxylate aminotransferase gene and type II, due to a deficiency of the D-glycerate dehydrogenase gene [2]. Skin lesions reported in PH include mostly livedo reticularis, acrocyanosis, peripheral gangrene and ulceration in rare cases [3, 4]. The prevelance of PD is approximately 10% in the dialysis population [7]. Although the pathogenesis is not clear, PD has been proposed to represent an inflammatory skin reaction to minor injuries, due to intense scratching (Koebner phenomenon), uremic toxins, microvasculopathy, metabolic changes of collagen and elastin fibers and deposition of calcium salts [5, 7]. In our patient all the above mechanisms were present; however, microvasculopathy of the right arm due to arterial necrosis seems to have played the most certain role in the development of secondary PD. In addition, other risk factors such as renal failure, peritoneal dialysis and pruritus were also associated [8]. Clinically, PD manifests as hyperkeratotic papules and nodules, while histologically it is characterized by transepidermal elimination of various dermal material (collagen or/and elastic fibers and cellular debris), whose depth possibly defines the elimination final route (transepidermal or via the follicular ostia) [5-7]. The term “acquired PD” covers three clearly distinct entities, “acquired reactive perforating collagenosis”, “elastosis perforans serpiginosa” and “per-
A
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forating folliculitis” [5]. On the contrary, secondary PD includes calcinosis cutis or calcified trichilemmal cysts and is associated with oxalate crystal deposition that usually contains calcium salts and calcifications [9, 10]. The clinical and histological findings of our patient were typical for the diagnosis of PD and were based on the fact that the eliminated material consisted of oxalate crystals; evidence of secondary PD was provided on the basis of systemic oxalosis.In conclusion, infant patients with ESRD can develop secondary PD during the first years of replacement treatment if certain risk factors are present. On particular, microvasculopathy appears to play a critical part in the pathogenesis of PD and its rapid onset. Disclosure. Financial support: none. Conflict of interest: none. 1 State Clinic, Hospital for Skin, Venereal Diseases, 124 Delfon St, 54643 Thessaloniki, Greece 2 st 1 Department of Pediatrics, Hippokratio Hospital, Thessaloniki, Greece
Ioanna LEFAKI1 Marina PAPAGEORGIOU1 Anatoli KARTERIDOU1 John DOTIS2 Christina KOTELI1 Nikoleta PRINTZA2 Fotios PAPACHRISTOU2
1. Mookadam F, El Kheir M, Alharthi M, et al. Vascular involvement in primary hyperoxalosis: an evidence based systematic overview over a fifty year spam. Inter J Nephrol Urol 2010; 2: 390-6. 2. Harambat J, Fargue S, Bacchetta J, et al. Primary hyperoxaluria. Int J Nephrol 2011: 864580. 3. Blackmon JA, Jeffy BG, Malone JC, et al. Oxalosis involving the skin : case report and literature review. Arch Dermatol 2011; 18: 1302-5. 4. Spiers EM, Sanders DY, Omura EF. Clinical and histologic features of primary oxalosis. J Am Acad Dermatol 1990; 22: 952-6. 5. Rapini R, Hebert A, Drucker C. Acquired perforating dermatosis evidence for combined transepidermal elimination of both collagen and elastic fibers. Arch Dermatol 1989; 125: 1074-8. 6. Lefaki I, Vakali G, Mourelou O, et al. Perforating necrobiosis lipoidica : 2 cases. Ann Dermatol Venereol 1996; 123: 742-4. 7. Saray Y, Sec¸kin D, Bilezikc¸i B. Acquired perforating dermatosis: clinicopathological features in twenty two cases. J Eur Acad Dermatol Venereol 2006; 20: 679-88. 8. Kurban MS, Boueiz A, Kibbi AG. Cutaneous manifestations of chronic kidney disease. Clin Dermatol 2008; 26: 255-64. 9. Walsh JS, Fairly JA. Calcifying disorders of the skin. J Am Acad Dermatol 1995; 33: 693-706. 10. Molina-Ruiz AM, Cerroni L, Kutzner H, Requena L. Cutaneous Deposits. Am J Dermatopathol 2013 [Epub ahead of print]. doi:10.1684/ejd.2014.2281
Figure 1. A) Multiple, pruritic, umbilicated papules with yellowish material plug on the dorsal side of the left hand. B) Transepidermal elimination of degenerated dermal material along with calcium oxalate crystals via epidermal perforation and giant cell foreign body reaction surrounding the oxalate crystals. Arrows show some of the oxalate crystals. C). Under polarized light the oxalate crystals in the dermis and the perforation material are strongly birefringent. EJD, vol. 24, n◦ 2, March-April 2014
Hyperkeratotic cutaneous vascular malformation associated with familial cerebral cavernous malformations (FCCM) with KRIT1/CCM1 mutation We report the case of a 40-year-old male patient with a history of seizures due to multiple cerebral cavernomas since the age of 14, treated by oxycarbamazepine and
255
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GA AG A A A A C A A AC A A A A C A A C T GG E
E
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GA A G A A A A CA A AC A A A AC A A C T G G
Normal
Y GA A G A A A A CA A AY A A A AC A A C T G G
Patient c.1201C>T
Figure 1. A well-delimited verrucous plaque on the left heel (A). Histological findings: Hyperkeratosis and numerous dilated capillary and venous vessels in the upper dermis seen in the hematoxylin-eosin stain (B). The dilated vessels are highlighted by the CD31 stain (C). (D) DNA sequences of the patient compared to a healthy individual (WT) showing the c.1201C>T/p.Q401X substitution in exon 12 of KRIT1. The arrow indicates the mutated nucleotide.
lation, although penetrance is incomplete. Preimplantation genetic testing can be proposed to the affected patients in some countries. Cerebral cavernomas (CCM) are vascular malformations of the central nervous system characterized by enlarged capillary cavities without associated brain parenchyma. Its prevalence in the general population ranges from 0.10.5% [1]. Three CCM genes have been identified so far (KRIT1/CCM1, MGC4607/CCM2, PDCD10/CCM3) [2]. A mutation has been reported in >90% of familial cases, and >60% of isolated cases [3]. The association between cavernous haemangiomas of the retina and brain with vascular lesions of skin has been known since 1971 [4, 5], but the responsible mutations were first identified in 1999 [6-8]. Analysis of a series 417 CCM patients revealed cutaneous vascular malformations in 9% of cases, including 15 hyperkeratotic cutaneous capillary venous malformations (HCCVM, 39%), 13 capillary malformations (34%), 8 venous malformations (21%) and 2 unclassified lesions. All patients with HCCVM had a KRIT1/CCM1 mutation, and CCM1 was the most frequently mutated gene in cutaneous vascular malformation-FCCM patients [9], as in our case. This case illustrates the association of a hyperkeratotic cutaneous vascular malformation and familial cerebral cavernous malformations (FCCM), with a new mutation in KRIT1/CCM1. The discovery of a hyperkeratotic cutaneous vascular malformation in combination with the history of neurologic symptoms or a family history of cerebral cavernomas justifies radiological investigation (MRI) and specific genetic tests. Disclosure. Financial support: none. Conflict of interest: none. 1
lamotrigine. Familial history for cerebral cavernomas was negative. The patient was referred to the department of Dermatology by his neurologist for the evaluation of an asymptomatic dark-blue spot on the left heel, which had been present for many years. The lesion was an isolated well-delimited dark-blue hyperkeratotic plaque with an erythematous border, measuring 0.5 × 1 cm (figure 1A). Histologic examination revealed a superficial, capillaryvenous malformation with verrucous hyperorthokeratosis, discrete papillomatosis and acanthosis of the epidermis as well as multiple strongly dilated thin-walled vessels in the superficial dermis (figure 1B). The vessels stained positive for the endothelial cell marker CD31 (figure 1C) but were negative for the lymphatic endothelial cell marker D2-40 (not shown). The definitive diagnosis of the skin lesion was a hyper-keratotic angioma. Based on these findings, we suspected a familial cerebral cavernous malformation (FCCM) and performed a mutation analysis of the 16 coding exons of the KRIT1/CCM1 gene by sequencing, and detected a new mutation in exon 12 (c.1201C>T) leading to the replacement of a glutamine by a stop codon at position 401 (p.Q401X) (figure 1D). The lesion did not disturb the patient, so it was not excised. Genetic counselling was offered to the patient; indeed, the autosomal transmission mode of FCCM implies a 50% risk for the children of the patient to inherit the mutation and a higher relative risk to develop cerebral cavernomas compared to the general popu-
256
Department of Dermatology, Department of Neurology, University Hospital Zürich, Gloriastrasse 31, 8091 Zürich, Switzerland 3 Laboratoire de Cytogénétique, APHP Hôpital Lariboisière, Paris, France 2
Laurence FELDMEYER1 Heide BAUMANN-VOGEL2 Elisabeth TOURNIERLASSERVE3 Florence RIANT3 Hans H. JUNG2 Lars E. FRENCH1 Jivko KAMARASHEV1
1. Labauge P, Denier C, Bergametti F, Tournier-Lasserve E. Genetics of cavernous angiomas. Lancet Neurol 2007; 6: 237-44. 2. Labauge P, Enjolras O, Bonerandi JJ, et al. An association between autosomal dominant cerebral cavernomas and a distinctive hyperkeratotic cutaneous vascular malformation in 4 families. Ann Neurol 1999; 45: 250-4. 3. Stahl S, Gaetzner S, Voss K, et al. Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/ CCM3 protein complex. Hum Mutat 2008; 29: 709-17. 4. Ostlere L, Hart Y, Misch KJ. Cutaneous and cerebral haemangiomas associated with eruptive angiokeratomas. Br J Dermatol 1996; 135: 98-101. 5. Gass JD. Cavernous hemangioma of the retina. A neuro-oculocutaneous syndrome. Am J Ophthalmol 1971; 71: 799-814. 6. Denier C, Goutagny S, Labauge P, et al. Mutations within the MGC4607 gene cause cerebral cavernous malformations. Am J Hum Genet 2004; 74: 326-37. EJD, vol. 24, n◦ 2, March-April 2014
7. Bergametti F, Denier C, Labauge P, et al. Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am J Hum Genet 2005; 76: 42-51. 8. Laberge-le Couteulx S, Jung HH, Labauge P, et al. Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. Nature Genet 1999; 23: 189-93. 9. Sirvente J, Enjolras O, Wassef M, Tournier-Lasserve E, Labauge P. Frequency and phenotypes of cutaneous vascular malformations in a consecutive series of 417 patients with familial cerebral cavernous malformations. J Eur Acad Dermatol Venereol 2009; 23: 1066-72. doi:10.1684/ejd.2014.2280
Giant pilomatrixoma of the right arm We report a 51 year-old man with a large tumor of the right arm, showing constant progression over a period of 30 years. The patient presented to our department because of chronic bleeding of the lesion. Clinical examination revealed a large, pediculated and firm tumor, measuring 20 × 17 × 10 cm, on the lateral left upper arm. The overlying skin was smooth and partially ulcerated (figure 1A). Aside from the lesion, the skin examination was unremarkable. Blood analysis showed high grade hypochromic anaemia with haemoglobin 4.1 g/dl, erythrocyte count 2.7 T./L and iron 13 g/dl, due to lesional bleeding. A chest X-ray and an ultrasound examination of the regional lymph nodes revealed no pathology. Histological investigation showed a large, sharply demarcated tumor in the dermis, extending into the subcutis. It
was composed of basophilic cells on the periphery of the cell islands, resembling basal cell carcinoma (figure 1B). Towards the centre, eosinophilic shadow cells and focal calcification could be found (figure 1C). Thus, the diagnosis of giant-pilomatrixoma was made. The patient received several blood transfusions preoperatively, before the tumor was excised under local anaesthesia. Pilomatrixoma (calcifying epithelioma of Malherbe) is a benign adnexal tumor emanating from hair matrix-cells, accounting for almost 20% of pilar tumors. It predominantly affects children and young adults and is particularly found on the head and neck and upper extremities [1]. Etiologically, a dysregulation of beta-catenin expression as well as an upregulation of the BCL-2 oncoprotein are discussed [2, 3]. Recently, trisomy 18 has been found in some cells of calcifying epitheliomas [4]. Clinically, pilomatrixomas present as rough and firm, sharply marginated nodules. The differential diagnosis includes cysts, dermatofibromas and foreign body granulomas. In the present case, the differential diagnosis also comprised sarcoma and neurofibroma. The diagnosis is usually established histologically, as it was in this case. Two cell types are predominantly found: basophilic-basaloid cells and shadow cells. Transformation of pilomatrixoma into pilomatrix carcinoma is very rare. Usually, pilomatrix carcinoma arises de novo [5]. Surgical excision is the therapy of choice. Most reported pilomatrixomas measure approximately 0.53cm in diameter. Lesions larger than 5 cm are called “giant pilomatrixomas” [6]. In the past 10 years there have been 17 case reports of giant pilomatrixomas, the biggest reaching 18 × 12 × 8 cm. To the best of our knowledge, we report the largest giant-pilomatrixoma published to date. Disclosure. Financial support: none. Conflict of interest: none.
A
Department of Dermatology, Municipal Hospital Hietzing, Wolkersbergenstraße 1, 1130 Vienna, Austria
B
C
Figure 1. A) large tumor of the right elbow region B) basophilic cells resembling basal cell carcinoma (HE × 40) C) eosinophilic shadow cells towards the centre of the lesion (HE × 40). EJD, vol. 24, n◦ 2, March-April 2014
Dagmara E. LOADER Kerstin ORTLECHNER Friedrich BREIER Gabriele WASILEWICZSTEFANI Andreas STEINER Robert FELDMANN
1. Lan M, Lan M, Ho C, Li W, Lin C. Pilomatricoma of the head and neck: a retrospective review of 179 cases. Arch Otolaryngol Head Neck Surg. 2003; 129: 1327-30. 2. Agoston A, Liang C, Richkind K, Fletcher J, Vargas S. Trisomy 18 is a consistent cytogenetic feature in pilomatricoma. Mod Pathol. 2010; 23: 1147-50. 3. Kim Y, Shin D, Choi J, Kim K. The Immunohistochemical Patterns of the beta-Catenin Expression in Pilomatricoma. Ann Dermatol. 2010; 22: 284-9. 4. Farrier S, Morgan M. Bcl-2 Expression in pilomatricoma. Am J Dermatopathol. 1997; 19: 254-7. 5. Karaaslan O, Melih Can M, Ozlem Karatas Silistreli A, Kaan Bedir Y, Caliskan G. Malignant pilomatrixoma arising on the previously irradiated face: case report and literature review. J Cutan Med Surg. 2012; 16: 341-3. 6. Nadershah M, Alshadwi A, Salama A. Recurrent giant pilomatrixoma of the face: a case report and review of the literature. Case Rep Dent. 2012:197273. doi: 10.1155/2012/197273. Epub 2012 Oct 18. doi:10.1684/ejd.2014.2284
257
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forating folliculitis” [5]. On the contrary, secondary PD includes calcinosis cutis or calcified trichilemmal cysts and is associated with oxalate crystal deposition that usually contains calcium salts and calcifications [9, 10]. The clinical and histological findings of our patient were typical for the diagnosis of PD and were based on the fact that the eliminated material consisted of oxalate crystals; evidence of secondary PD was provided on the basis of systemic oxalosis.In conclusion, infant patients with ESRD can develop secondary PD during the first years of replacement treatment if certain risk factors are present. On particular, microvasculopathy appears to play a critical part in the pathogenesis of PD and its rapid onset. Disclosure. Financial support: none. Conflict of interest: none. 1 State Clinic, Hospital for Skin, Venereal Diseases, 124 Delfon St, 54643 Thessaloniki, Greece 2 st 1 Department of Pediatrics, Hippokratio Hospital, Thessaloniki, Greece
Ioanna LEFAKI1 Marina PAPAGEORGIOU1 Anatoli KARTERIDOU1 John DOTIS2 Christina KOTELI1 Nikoleta PRINTZA2 Fotios PAPACHRISTOU2
1. Mookadam F, El Kheir M, Alharthi M, et al. Vascular involvement in primary hyperoxalosis: an evidence based systematic overview over a fifty year spam. Inter J Nephrol Urol 2010; 2: 390-6. 2. Harambat J, Fargue S, Bacchetta J, et al. Primary hyperoxaluria. Int J Nephrol 2011: 864580. 3. Blackmon JA, Jeffy BG, Malone JC, et al. Oxalosis involving the skin : case report and literature review. Arch Dermatol 2011; 18: 1302-5. 4. Spiers EM, Sanders DY, Omura EF. Clinical and histologic features of primary oxalosis. J Am Acad Dermatol 1990; 22: 952-6. 5. Rapini R, Hebert A, Drucker C. Acquired perforating dermatosis evidence for combined transepidermal elimination of both collagen and elastic fibers. Arch Dermatol 1989; 125: 1074-8. 6. Lefaki I, Vakali G, Mourelou O, et al. Perforating necrobiosis lipoidica : 2 cases. Ann Dermatol Venereol 1996; 123: 742-4. 7. Saray Y, Sec¸kin D, Bilezikc¸i B. Acquired perforating dermatosis: clinicopathological features in twenty two cases. J Eur Acad Dermatol Venereol 2006; 20: 679-88. 8. Kurban MS, Boueiz A, Kibbi AG. Cutaneous manifestations of chronic kidney disease. Clin Dermatol 2008; 26: 255-64. 9. Walsh JS, Fairly JA. Calcifying disorders of the skin. J Am Acad Dermatol 1995; 33: 693-706. 10. Molina-Ruiz AM, Cerroni L, Kutzner H, Requena L. Cutaneous Deposits. Am J Dermatopathol 2013 [Epub ahead of print]. doi:10.1684/ejd.2014.2281
Figure 1. A) Multiple, pruritic, umbilicated papules with yellowish material plug on the dorsal side of the left hand. B) Transepidermal elimination of degenerated dermal material along with calcium oxalate crystals via epidermal perforation and giant cell foreign body reaction surrounding the oxalate crystals. Arrows show some of the oxalate crystals. C). Under polarized light the oxalate crystals in the dermis and the perforation material are strongly birefringent. EJD, vol. 24, n◦ 2, March-April 2014
Hyperkeratotic cutaneous vascular malformation associated with familial cerebral cavernous malformations (FCCM) with KRIT1/CCM1 mutation We report the case of a 40-year-old male patient with a history of seizures due to multiple cerebral cavernomas since the age of 14, treated by oxycarbamazepine and
255
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GA AG A A A A C A A AC A A A A C A A C T GG E
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N
W
GA A G A A A A CA A AC A A A AC A A C T G G
Normal
Y GA A G A A A A CA A AY A A A AC A A C T G G
Patient c.1201C>T
Figure 1. A well-delimited verrucous plaque on the left heel (A). Histological findings: Hyperkeratosis and numerous dilated capillary and venous vessels in the upper dermis seen in the hematoxylin-eosin stain (B). The dilated vessels are highlighted by the CD31 stain (C). (D) DNA sequences of the patient compared to a healthy individual (WT) showing the c.1201C>T/p.Q401X substitution in exon 12 of KRIT1. The arrow indicates the mutated nucleotide.
lation, although penetrance is incomplete. Preimplantation genetic testing can be proposed to the affected patients in some countries. Cerebral cavernomas (CCM) are vascular malformations of the central nervous system characterized by enlarged capillary cavities without associated brain parenchyma. Its prevalence in the general population ranges from 0.10.5% [1]. Three CCM genes have been identified so far (KRIT1/CCM1, MGC4607/CCM2, PDCD10/CCM3) [2]. A mutation has been reported in >90% of familial cases, and >60% of isolated cases [3]. The association between cavernous haemangiomas of the retina and brain with vascular lesions of skin has been known since 1971 [4, 5], but the responsible mutations were first identified in 1999 [6-8]. Analysis of a series 417 CCM patients revealed cutaneous vascular malformations in 9% of cases, including 15 hyperkeratotic cutaneous capillary venous malformations (HCCVM, 39%), 13 capillary malformations (34%), 8 venous malformations (21%) and 2 unclassified lesions. All patients with HCCVM had a KRIT1/CCM1 mutation, and CCM1 was the most frequently mutated gene in cutaneous vascular malformation-FCCM patients [9], as in our case. This case illustrates the association of a hyperkeratotic cutaneous vascular malformation and familial cerebral cavernous malformations (FCCM), with a new mutation in KRIT1/CCM1. The discovery of a hyperkeratotic cutaneous vascular malformation in combination with the history of neurologic symptoms or a family history of cerebral cavernomas justifies radiological investigation (MRI) and specific genetic tests. Disclosure. Financial support: none. Conflict of interest: none. 1
lamotrigine. Familial history for cerebral cavernomas was negative. The patient was referred to the department of Dermatology by his neurologist for the evaluation of an asymptomatic dark-blue spot on the left heel, which had been present for many years. The lesion was an isolated well-delimited dark-blue hyperkeratotic plaque with an erythematous border, measuring 0.5 × 1 cm (figure 1A). Histologic examination revealed a superficial, capillaryvenous malformation with verrucous hyperorthokeratosis, discrete papillomatosis and acanthosis of the epidermis as well as multiple strongly dilated thin-walled vessels in the superficial dermis (figure 1B). The vessels stained positive for the endothelial cell marker CD31 (figure 1C) but were negative for the lymphatic endothelial cell marker D2-40 (not shown). The definitive diagnosis of the skin lesion was a hyper-keratotic angioma. Based on these findings, we suspected a familial cerebral cavernous malformation (FCCM) and performed a mutation analysis of the 16 coding exons of the KRIT1/CCM1 gene by sequencing, and detected a new mutation in exon 12 (c.1201C>T) leading to the replacement of a glutamine by a stop codon at position 401 (p.Q401X) (figure 1D). The lesion did not disturb the patient, so it was not excised. Genetic counselling was offered to the patient; indeed, the autosomal transmission mode of FCCM implies a 50% risk for the children of the patient to inherit the mutation and a higher relative risk to develop cerebral cavernomas compared to the general popu-
256
Department of Dermatology, Department of Neurology, University Hospital Zürich, Gloriastrasse 31, 8091 Zürich, Switzerland 3 Laboratoire de Cytogénétique, APHP Hôpital Lariboisière, Paris, France 2
Laurence FELDMEYER1 Heide BAUMANN-VOGEL2 Elisabeth TOURNIERLASSERVE3 Florence RIANT3 Hans H. JUNG2 Lars E. FRENCH1 Jivko KAMARASHEV1
1. Labauge P, Denier C, Bergametti F, Tournier-Lasserve E. Genetics of cavernous angiomas. Lancet Neurol 2007; 6: 237-44. 2. Labauge P, Enjolras O, Bonerandi JJ, et al. An association between autosomal dominant cerebral cavernomas and a distinctive hyperkeratotic cutaneous vascular malformation in 4 families. Ann Neurol 1999; 45: 250-4. 3. Stahl S, Gaetzner S, Voss K, et al. Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/ CCM3 protein complex. Hum Mutat 2008; 29: 709-17. 4. Ostlere L, Hart Y, Misch KJ. Cutaneous and cerebral haemangiomas associated with eruptive angiokeratomas. Br J Dermatol 1996; 135: 98-101. 5. Gass JD. Cavernous hemangioma of the retina. A neuro-oculocutaneous syndrome. Am J Ophthalmol 1971; 71: 799-814. 6. Denier C, Goutagny S, Labauge P, et al. Mutations within the MGC4607 gene cause cerebral cavernous malformations. Am J Hum Genet 2004; 74: 326-37. EJD, vol. 24, n◦ 2, March-April 2014
7. Bergametti F, Denier C, Labauge P, et al. Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am J Hum Genet 2005; 76: 42-51. 8. Laberge-le Couteulx S, Jung HH, Labauge P, et al. Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. Nature Genet 1999; 23: 189-93. 9. Sirvente J, Enjolras O, Wassef M, Tournier-Lasserve E, Labauge P. Frequency and phenotypes of cutaneous vascular malformations in a consecutive series of 417 patients with familial cerebral cavernous malformations. J Eur Acad Dermatol Venereol 2009; 23: 1066-72. doi:10.1684/ejd.2014.2280
Giant pilomatrixoma of the right arm We report a 51 year-old man with a large tumor of the right arm, showing constant progression over a period of 30 years. The patient presented to our department because of chronic bleeding of the lesion. Clinical examination revealed a large, pediculated and firm tumor, measuring 20 × 17 × 10 cm, on the lateral left upper arm. The overlying skin was smooth and partially ulcerated (figure 1A). Aside from the lesion, the skin examination was unremarkable. Blood analysis showed high grade hypochromic anaemia with haemoglobin 4.1 g/dl, erythrocyte count 2.7 T./L and iron 13 g/dl, due to lesional bleeding. A chest X-ray and an ultrasound examination of the regional lymph nodes revealed no pathology. Histological investigation showed a large, sharply demarcated tumor in the dermis, extending into the subcutis. It
was composed of basophilic cells on the periphery of the cell islands, resembling basal cell carcinoma (figure 1B). Towards the centre, eosinophilic shadow cells and focal calcification could be found (figure 1C). Thus, the diagnosis of giant-pilomatrixoma was made. The patient received several blood transfusions preoperatively, before the tumor was excised under local anaesthesia. Pilomatrixoma (calcifying epithelioma of Malherbe) is a benign adnexal tumor emanating from hair matrix-cells, accounting for almost 20% of pilar tumors. It predominantly affects children and young adults and is particularly found on the head and neck and upper extremities [1]. Etiologically, a dysregulation of beta-catenin expression as well as an upregulation of the BCL-2 oncoprotein are discussed [2, 3]. Recently, trisomy 18 has been found in some cells of calcifying epitheliomas [4]. Clinically, pilomatrixomas present as rough and firm, sharply marginated nodules. The differential diagnosis includes cysts, dermatofibromas and foreign body granulomas. In the present case, the differential diagnosis also comprised sarcoma and neurofibroma. The diagnosis is usually established histologically, as it was in this case. Two cell types are predominantly found: basophilic-basaloid cells and shadow cells. Transformation of pilomatrixoma into pilomatrix carcinoma is very rare. Usually, pilomatrix carcinoma arises de novo [5]. Surgical excision is the therapy of choice. Most reported pilomatrixomas measure approximately 0.53cm in diameter. Lesions larger than 5 cm are called “giant pilomatrixomas” [6]. In the past 10 years there have been 17 case reports of giant pilomatrixomas, the biggest reaching 18 × 12 × 8 cm. To the best of our knowledge, we report the largest giant-pilomatrixoma published to date. Disclosure. Financial support: none. Conflict of interest: none.
A
Department of Dermatology, Municipal Hospital Hietzing, Wolkersbergenstraße 1, 1130 Vienna, Austria
B
C
Figure 1. A) large tumor of the right elbow region B) basophilic cells resembling basal cell carcinoma (HE × 40) C) eosinophilic shadow cells towards the centre of the lesion (HE × 40). EJD, vol. 24, n◦ 2, March-April 2014
Dagmara E. LOADER Kerstin ORTLECHNER Friedrich BREIER Gabriele WASILEWICZSTEFANI Andreas STEINER Robert FELDMANN
1. Lan M, Lan M, Ho C, Li W, Lin C. Pilomatricoma of the head and neck: a retrospective review of 179 cases. Arch Otolaryngol Head Neck Surg. 2003; 129: 1327-30. 2. Agoston A, Liang C, Richkind K, Fletcher J, Vargas S. Trisomy 18 is a consistent cytogenetic feature in pilomatricoma. Mod Pathol. 2010; 23: 1147-50. 3. Kim Y, Shin D, Choi J, Kim K. The Immunohistochemical Patterns of the beta-Catenin Expression in Pilomatricoma. Ann Dermatol. 2010; 22: 284-9. 4. Farrier S, Morgan M. Bcl-2 Expression in pilomatricoma. Am J Dermatopathol. 1997; 19: 254-7. 5. Karaaslan O, Melih Can M, Ozlem Karatas Silistreli A, Kaan Bedir Y, Caliskan G. Malignant pilomatrixoma arising on the previously irradiated face: case report and literature review. J Cutan Med Surg. 2012; 16: 341-3. 6. Nadershah M, Alshadwi A, Salama A. Recurrent giant pilomatrixoma of the face: a case report and review of the literature. Case Rep Dent. 2012:197273. doi: 10.1155/2012/197273. Epub 2012 Oct 18. doi:10.1684/ejd.2014.2284
257
