DIFFERENTIAL DIAGNOSES OF ANGIOKERATOMAS


DIFFERENTIAL DIAGNOSES OF ANGIOKERATOMAS


Jesús del Pozo1*, Felipe Sacristán2, Manuel Gómez Tellado3, Servicios de Dermatología1, Anatomía Patológicay2, Cirugía Pediátrica3

1Unidad de Anomalías Vasculares Pediátricas, Instituto de Investigación Biomédica de A Coruña (INIBIC). 2Complexo Hospitalario Universitario de A Coruña (CHUAC). 3Sergas. Universidade da Coruña (UDC). As Xubias, 84. 15006, A Coruña, España.


Angiokeratomas (AK) are probably the vascular lesions that induce more confusion in the literature. The most accepted classification of AK was performed by Imperial and Helwig , and they divide these lesions into five classical types: Mibelli’s AK, Fordyce’s AK, corporis diffusum AK, circumscribed naeviforme AK and solitary or multiple acquired angiokeratomas.

Nevertheless, in the clinical practice, is not unusual to see AK type lesions associated to different types of vascular anomalies, and these lesions have difficult handling.

In ISSVA classification AKs have been included as vascular anomalies provisionally unclassified.

We perform the differential diagnoses of AKs and according to clinical picture, histopathological aspect, immunohistochemical markers and radiological findings proposed to divide AKs mainly in two groups.

Primary AKs are the classical types. The new immunohistochemical findings suggest that these lesions might be included as mixed capillary-lymphatic malformations.

Secondary AKs are related with different vascular anomalies, secondary to other process with lymphatic obstruction, related to drugs, or associated with no vascular lesions as lymphoid lesions.

Different underlying vascular anomelies might be related with AKs including deep capillary-lymphatic malformations (CLM), venous-lymphatic malformations (VLM), capillary-lymphatic-venous malformations (CLVM) (Klippel-Trenaunauy Sd), deep lymphatic malformations (LM), venous malformations (VM) as hyperkeratotic venous malformation, cavenomatous cerebral malformations, traumatic arteriovenous fistula and eccrine angiokeratomatous hamartoma.

Clinical aspect, radiological studies and histopathological examination might help to do a correct diagnosis of this heterogenous entity.


Keywords: Angiokeratomas; Vascular lesions

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How to cite this article:
Jesús del Pozo, Felipe Sacristán, Manuel Gómez Tellado, Servicios de Dermatología, Anatomía Patológicay, Cirugía Pediátrica. DIFERENTIAL DIAGNOSES OF ANGIOKERATOMAS. American Journal of Dermatological Research and Reviews, 2020; 3:34. DOI: 10.28933/ajodrr-2020-09-0205


References:

1. Imperial R, Helwig E. Angiokeratoma: a clini-co-pathological study. Arch Dermatol. 1967; 95: 166-175.
2. Naranjo Sintes R, Pereda Hernández J, Delgado Florencio V, Linares Solano J. Amgioqueratoma. A propósito de 93 observaciones. Med Cutan I.L.A. 1988; 16: 255-261.
3. Requena L y cols. Cutaneous vascular anomalies. Part I. Hamartomas, malformations and dilatation of preexistent vessels. J Am Acad Dermatol. 1997; 37: 523-549.
4. Imperial R, Helwig E. Angiokeratoma: a clini-co-pathological study. Arch Dermatol. 1967; 95: 166-175.
5. Wang L, Yuan W, Geng S, Xiong Y, Zhang D, Zhao X, Li S, Bi X, Gao T, Wang G. Expression of lymphatic markers in angiokertomas. J Cutan Pathol 2014; 41: 576-81.
6. Trindade F, Torrelo A, Kutzner H, Requena L, Tellechea O, Colmenero I. An immunohisto-chemical study of angiokeratomas in children. Am J Dermatopathol 2014; 36: 796-799.
7. Couto JA, Vivers MP, Kozakewich HP, Taghinia AH, Mulliken JB, Warman ML, Greene AK. A somatic MAP3K3 mutation is associated with verrucous venous malformation. Am J Hum Gen 2015 Mar 5 96 (3): 480-6.
8. Schiller PI, Itin PH. Angiokeratomas: an up-date.Dermatology.1996; 193: 275-82.
9. Sommer S, Merchant WJ, Sheehan-Dare R. Se-vere predominantly acral variant of angioker-atoma of Mibelli: response to long-pulse Nd:YAG (1064 nm) laser treatment. J Am Acad Dermatol. 2001 Nov;45(5):764-6.
10. Dave VK, Main RA. Angiokeratoma of Mibelli with necrosis of the fingertips. Arch Dermatol. 1972 Nov;106(5):726-8.
11. Shannon PL, Ford MJ. Angiokeratomas in juve-nile dermatomyositis. Pediatr Dermatol. 1999; 16: 448-451.
12. Ca Cunha Castro EC, Galambos C. Prox-1 and VEGFR3 antibodies are superior to D2-40 in identifying endothelial cells of lymphatic mal-formations—a proposal of a new immunohisto-chemical panel to differenciate lymphatic from other vascular malformations. Pediatr Dev Pathol 2009; 12: 187-194.
13. Smith RBW, Prior IAM, Park RG. Angiokeratoma of Mibelli: a family with nodular lesions on the leg. Australas J Dermatol. 1968; 9: 329-334.
14. Su Q, Lin T, Wu Q, Wu Y, Guo L, Ge Y. Efficacy of 595nm pulsed dye laser therapy for Mibelli angiokeratoma. J Cosmet Laser Ther. 2015;17(4):209-12.
15. Zeng Y, Li XQ, Lin QZ, Zhan K. Treatment of an-giokeratoma of Mibelli alone or in combination with pulsed dye laser and long-pulsed Nd: YAG laser. Dermatol Ther. 2014 Nov-Dec;27(6):348-51.
16. Patrizi A, Neri I, Trevisi P, Landi C, Bardazzi F. Congenital angiokeratoma of Fordyce. J Eur Acad Dermatol Venereol 1998; 10: 195.
17. Sadowsky LM, Socik A, Burnes A, Rhodes AR. Genital angiokeratomas in adult men and women: prevalence and predisposing factors. J Cutan Med Surg 2019; 23: 513-518.
18. Agger P, Osmundsen PE. Angiokeratoma of the scrotum (Fordyce). A case report on response to surgical treatment of varicocele. Acta Derm Ve-nereol.1970;50(3):221-4.
19. Buehler S, Itin P. Angiokeratomas sroti associ-ated with angiokeratomas of the eyelids: coin-cidence or one entity?. A case report and review of the literature. Dermatology 2015; 231: 213-6.
20. Jansen T, Bechara FG, Stücker M, Altmeyer P. Angiokeratoma of the scrotum (Fordyce type) associated with angiokeratoma of the oral cavity. Acta Derm Venereol (Stochk). 2002; 82: 208-210.
21. Hogarth V, Dhoat S, Mehta AB, Orteu CH. Late-onset Fabry disease associated with angi-okeratoma of Fordyce and multiple cherry an-giomas. Clin Exp Dermatol. 2011; 36(5): 506-8.
22. Piqué-Durán E, Pérez-Cejudo JA, Ceme-selle-Martínez D, García-Vázquez O. Angioquer-atoma de Fordyce unilateral. Actas Dermiosifili-ogr 2013; 104: 163-4.
23. Occella C, Bleidl D, Rampini P, Schiazza L, Rampini E. Argon laser treatment of cutaneous multiple angiokeratomas. Dermatol Surg. 1995 Feb;21(2):170-2.
24. Baumgartner J, Šimaljaková M. Genital angio-keratomas of Fordyce 595-nm variable-pulse pulsed dye laser treatment. J Cosmet Laser Ther. 2017 Jun 30:1-6.
25. Zeng Y, Zhan K, Xie WL, Lin QZ. Angiokeratoma of Fordyce response to long pulsed Nd:YAG laser treatment. Dermatol Ther. 2016 Jan Feb;29(1):48-51.
26. Ozdemir M, Baysal I, Engin B, Ozdemir S. Treatment of angiokeratoma of Fordyce with long-pulse neodymium-doped yttrium aluminium garnet laser. Dermatol Surg. 2009 Jan;35 (1):92-7.
27. Lapidoth M, Ad-El D, David M, Azaria R. Treat-ment of angiokeratoma of Fordyce with pulsed dye laser. Dermatol Surg. 2006 Sep;32(9):1147 -50.
28. Seo SH, Chin HW, Sung HW. Angiokeratoma of Fordyce treated with 0.5% ethanolamine oleate or 0.25% sodium tetradecyl sulfate. Dermatol Surg. 2010 Oct;36(10):1634-7.
29. Molho-Pessach V, Bargal R, Abramowitz Y, Dovinet V, Ingber A, Raas-Rothschild A, Ne’eman Z, Zeigler M, Zlotogorski A. Angiokeratoma corporis diffisum in human beta-mannosidosis: report of a new case and a novel mutation. J Am Acad Dermatol. 2007; 57. 407-12.
30. Epinette WW, Norins AL, Zeman W, Patel V. An-giokeratoma corpòris diffusum with alpha-L fu-cosidase deficiency. Arch Dermatol. 1993; 107: 754-7.
31. Kodama K, Kobayashi H, Abe R, Ohkawara A, Yoshii N, Yotsumoto S et al. A new case of al-pha-n-acetyl-galactosaminidase deficiency with angiokeratoma corporis diffusum, with Meniere’s syndrome and without mental retardation. Br J Dermatol 2001; 144: 363-8.
32. Vargas-Díez E, Chabás A, Coll MJ, Sánchez-Pérez J, García-Díez A, Fernán-dez-Herrera JM. Angiokeratoma corporis dif-fusum in a spanish patient with aspartylglu-cosaminuria. Br J Dermatol. 2002; 147: 760-4.
33. Espinel Vázquez ML, Martín Jaramillo JA, Con-treras Steyls M, Vázquez Navarrete S. Forma cutánea de angioqueratoma corporis diffusum: descripcción de un caso. Piel. 2014; 29: 280-2.
34. Calzavara-Pinton PG, Colombi M, Carlino A, Zane C, Gardella R, Clemente M, Facchetti F, Moro L, Zoppi N, Caimi L, Barlati S, De Panfilis G. An-giokeratoma corporis diffusum and arteriovenous fistulas with dominant transmisión in the absence of metabolic disorders. Arch Dermatol. 1995; 131: 57-62.
35. Gil-Mateo MP, Miquel FJ, Velasco AM, Pitarch A, Fortea JM, Aliaga A. Widespread angiokerato-mas and tuberous sclerosis. Br J Dermatol. 1996; 135: 280-282.
36. Guinovart RM, Bielsa I, Pintos.Morell G, Fer-rández C. Enfermedad de Fabry: espectro clínico de los angioqueratomas. Actas Dermosifiliogr. 2013; 104: 261-3.
37. Martínez-Menchón T, Nagore E, Pérez-Ferriols A, Febrer I, Mahiques Santos L, Fortea-Baixauli JM. Diagnóstico y tratamiento enzimático sustitutivo de la enfermedad de Fabry. Actas Dermosifiliogr. 2004; 95: 436-9.
38. Dammert By K. Angiokaratosis naeviformis—a form of naevus telangiectaticus lateralis (nevus flammeus). Dermatologica. 1965; 130: 17-39.
39. Somasundaram V, Premalatha S, Rao NR, Ra-zack EMA, Zabra A. Hemangiectatic hyperthropy with angiokeratoma circumscriptum. Int J Der-matol. 1988; 27: 45-46.
40. Vijaikumar M, Thappa DM, Karthikeyan K, Jayanthi S. Angiokeratoma circumscriptum of the tongue. Pediatr Dermatol 2003; 20: 180-2.
41. Jessen RT, Thompson S, Smith SB. Cobb sín-drome. Arch Dermatol 1977; 113: 1587-90.
42. Lynch PJ, Kosanovich M. Angiokeratoma cir-cumscriptum. Arch Dermatol 1967; 96: 665-8.
43. Foucar E, Mason WV. Angiokeratoma circum-scriptim following damage to underlying vascu-lature. Arch Dermatol 1986; 122: 245-6.
44. Mittal R, Aggarwal A, Srivastava G. Angioker-atoma circumscriptum: a case report and review of the literature. Int J Dermatol. 2005; 44: 1031-1034.
45. Bechara FG, Happle R, Altmeyer P, Grabbe S, Jansen T. Angiokeratoma circumscriptum arra- nged in a systematied band-like pattern sug-gesting mosaicism. J Dermatol 2006; 33: 489-491.
46. Rossi A, Bozzi M, Barra E. Verrucous heman-gioma and angiokeratoma circumscriptum: clin-ical and histologic differential characteristics. J Dermatol Surg Oncol. 1989; 15: 88-91.
47. Yang CH, Ohara K. Successful surgical treatment of verrucous hemangioma: a combined ap-proach. Dermatol Surg. 2002; 28: 913-920.
48. Del Pozo J, Fonseca E. Angiokeratoma circum-scriptum naeviforme: successful treatment with carbon-dioxide laser vaporization. Dermatol Surg 2005; 31: 232-6.
49. Ranjan N, Mahajan VK. Oral angiokeratomas: proposed clinical classification. Int J Dermatol 2009; 48: 778-781.
50. Carlson JA, Daulat S, Goodheart HP. Targetoid hemosiderotic hemangioma—a dynamic vascular tumor: report of 3 cases with episodic and cyclic changes and comparison with solitary angioker-atomas. J Am Acad Dermatol 1999; 41. 215-24.
51. Siponen M, Penna T, Apaja-Sarkkinen M, et al. Solitary angiokeratoma of the tongue. J Oral Pathol Med 2006; 35: 252–253.
52. Ergun S, Mete Ö, Yesil S, Tanyeri H. Solitaty angiokeratoma of the tongue treated with diode laser. Lasers Med Sci 2009; 24: 123-125.
53. Leung CS, Jordan RC. Solitary angiokeratoma of the oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997; 84: 51–53.
54. Wang L, Gao T, Wang G. Solitary angiokeratoma on palms and soles: a clinicopathological analy-sis of 21 cases. J Dermatol 2013; 40: 653-6.
55. Barhuah J, Roy KK, Rahman SM, Kumar S, Pushparaj M, Mirdha AR. Angiokeratoma of vulva with coexisting human papilloma virus infection: a case report. Arch Gynecol Obstet 2008; 278: 165-167.
56. Hasegawa M, Tamura A. Subungual angioker-atoma presenting as a longirudina pigmented band in the nail. Acta Derm Venereol 2015; 95: 1001-1002.
57. Varshney S. Angiokeratoma circumscriptum of the tongue. Int J Dermatol 2005; 44: 886–888.
58. Prindaville B, Lawrence H, Singh V, Nopper AJ, Horii KA. Immunohistochemical staining of pedi-atric solitary angiokeratomas. Pediatr Dermatol 2017; 34: 211-213.
59. Vijaikumar M, Tapa DM, Karthikeyan K, Jayanthi S. Angiokeratoma circumscriptum of the tongue. Pediatr Dermatol. 2003; 20: 180-182.
60. Ostlere L, Hart Y, Misch KJ. Cutaneous and cerebral haemangiomas associated with eruptive angiokeratomas. Br J Dermatol. 1996; 135: 98-101.
61. Labauge P, Enjolras O, Bonerandi JJ, Laberge S, Dandurand M, Joujoux JM, Tournier-Lasserve E. An association between autosomal dominant cerebral cavernomas and a distinctive hyperker-atotic cutaneous vascular malfomation in 4 fami-lies. Ann Neurol. 1999; 45: 250-4.
62. Toll A, Parera E, Jiménez-Arnau AM, Pou A, Lloreta J, Limaye N, Vikkula M, Pujol RM. Cuta-neous venous malformations in familial cerebral cavernomatosis caused by KRIt1 gene mutations. Dermatology. 2009; 218: 307-313.
63. Sirvente J, Enjolras O, Wassef M, Tour-nier-Lasserve E, Labauge P. Frequency and phenotypes of cutaneous vascular malformations in a consecutive series of 417 patients with fa-milial cerebral cavernous malformations. J Eur Acad Dermatol Venereol. 2009; 23: 1066-72.
64. Foucar E, Masson WV. Angiokeratoma circum-scriptum following damaging to underlying vas-culature. Arch Dermatol. 1986; 122: 245-246.
65. Kanitakis J, Ly A, Claudy A. Eccrine angioker-atomatous hamartoma: a new variant of eccrine hamartoma with angiokeratoma. J Am Acad Dermatol. 2006 Nov;55(5 Suppl):S104-6.
66. Maeda M. Solitary angiokeratoma seen in a pa-tient with pretibial epidermolysis bullosa. J Der-matol. 1987; 14: 89-91.
67. Marks E, Dorokhova O, Amin B, Jacobson M. Eruptive angiokeratomas and porokeratosis in the setting of sclerodermatous graft-vs-host disease. J Cutan Pathol 2016; 43: 516-519.
68. Luzan B, Neil SM, Calonje E. Angiokeratoma-like changes in extragenital and genital lichen scle-rosus. J Cutan Pathol. 2009; 36: 540-542.
69. Bathelier E, Gunera-Saad N, Bérard F, Nicolas FJ. Angiokeratoma induced by injection of etaner-cept for psoriasis J Am Acad Dermatol. 2008; 59; s124-125.
70. Schliep S, Kiesewetter F, Simon M, Grupp C, Heinzerling L. Drug-induced dilema: angioker-atomas and decreased renal function. Am J Med 2014; 127: 598-600.
71. Kim Y, Dawes-Higgs E, Mann S, Cook DK. Acral pseudolymphomatous angiokeratoma of children (APACHE). Australas J Dermatol. 2005; 46: 177-80.
72. Brown A, Warren S, Losken W, Morrell DS. Ver-rucous lymphovascular malformation versus verrucous hemangioma: controversial nomen-clature. Cutis. 2008; 81: 390-396.
73. Calduch L, Ortega C, Navarro V, Martínez E, Mo-lina I, Jordá E. Verrucous hemangioma: report of two cases and review of the literatura. Pediatr Dermatol. 2000; 17: 213-217.
74. Cruces MJ, De la Torre C. Multiple eruptive ver-rucous hemangiomas as variant of multiple he-mangiomatosis. Dermatologica. 1985; 171: 106-111.
75. Wentscher U, Happle R. Linear verrucous he-mangioma. J Am Acad Dermatol. 2000; 42:516-518.
76. Tennant LB, Mulliken JB, Pérez-Atayde AR, kozakewitz HPW. Verrucous hemangioma revis-ited. Pediatr Dermatol. 2006; 23: 208-215.
77. Trindade F, Torrelo A, Requena L, Tellechea O, Del Pozo J, Sacristán F, Esteve-Martínez A, de Unamuno B, de Miquel VA, Colmenero I. An immunohistochemical study of verrucous he-mangiomas. J Cutan Pathol. 2013; 40: 472-6.
78. Wang L, Gao T, Wang G. Verrucous hemangioma: a clinicopathological and immunohistochemical analysis of 74 cases. J Cutan Pathol 2014; 41: 823-30.