- Email: [email protected]
Aggressive cutaneous squamous cell carcinoma in a patient with KLICK
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Mireille Priale Aujero, BS,a Sara Brooks, MD,b Ning Li, MD,c and Suraj Venna, MDd Georgetown University School of Medicine, Washington, DCa; Washington Hospital Center/ Georgetown University Combined Program in Dermatologyb; Dianon Systems, Dermatopathologyc; and Washington Cancer Institute at the Washington Hospital Centerd Funding sources: None. Conflicts of interest: None declared. Correspondence and reprint requests to: Suraj Venna, MD, Washington Cancer Institute, 110 Irving St, Suite 2149, Washington, DC 20010 E-mail: [email protected] REFERENCES 1. Darmon P, Castera V, Koeppel MC, Petitjean C, Dutour A. A type III allergy to insulin detemir. Diabetes Care 2005;28:2980.
J AM ACAD DERMATOL
JUNE 2011
2. Sola-Gazagnes A, Pecquet C, M’Bemba J, Larger E, Slama G. Type I and type IV allergy to the insulin analogue detemir. Lancet 2007;369:637-8. 3. Perez E, Gonzalez R, Martinez J, Iglesias J, Matheu V. Detemir insulin-induced anaphylaxis. Ann Allergy Asthma Immunol 2009;102:174-5. 4. Akinci B, Yener S, Bayraktar F, Yesil S. Allergic reactions to human insulin: a review of current knowledge and treatment options. Endocrine 2010;37:33-9. doi:10.1016/j.jaad.2010.11.028
Aggressive cutaneous squamous cell carcinoma in a patient with KLICK To the Editor: A 23-year-old mechanic presented to our department with ichthyosis and palmoplantar sclerotic keratoderma with constricting bands on the dorsal aspect of the hands (Fig 1, A and B). The typical clinical presentation led to the diagnosis of KLICK (keratosis linearis with ichthyosis congenita and sclerosing keratoderma); by genetic analysis, the
Fig 1. A, Dorsal aspect of foot showing sclerotic keratoderma. B, Dorsal hand showing skin erythema and thickening with typical constricting bands. C, Homozygous mutation c.-95delC in POMP gene. Upper panel: Patient. Lower panel: Control. Arrow shows site of deletion.
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Fig 2. A, Photomicrograph of skin shows compact hyperkeratosis, irregular acanthosis and dermal massive invasion by well-differentiated SCC. B, Lymph node from right axilla with SCC metastasis. (A and B, Hematoxylin-eosin stain; original magnifications: A, 3100; B, 3200.)
patient was shown to carry the recurrent c.-95 mutation in the POMP gene, shared by all patients with KLICK described to date1 (Fig 1, C ). Physical examination also revealed a 2- 3 2-cm ulcerated mass of 3 months’ duration on the right wrist and a subcutaneous mass in the right axilla. Histologic examination of the ulcerated skin tumor and the axillary mass showed a moderately differentiated squamous cell carcinoma (SCC) with axillary lymph node metastasis (Fig 2, A and B). Deep penetration into the underlying tendons and nerves prevented its complete resection, and the patient was referred for further evaluation and treatment at the oncology unit. KLICK is a rare autosomal recessive form of nonsyndromic ichthyosis, recently shown to be caused by a mutation in the gene POMP.1 The product of the POMP gene, proteasome maturation protein, is involved in the proteasome 20s subunit assembly. The main function of the proteasome, a complex of proteins in all eukaryotic cells, is to degrade unneeded or damaged proteins. Cutaneous SCCs presenting in childhood and young adulthood are rare. In most of the cases, there is an underlying predisposing condition. Immunodeficiency due to human immunodeficiency virus, chronic graft-versus-host disease, or organ transplantation is a leading cause. Among the congenital disorders, photosensitive skin disorders (eg, albinism, xeroderma pigmentosum, erythropoietic
porphyria) and disorders of increased skin and mucosal fragility (eg, dystrophic epidermolysis bullosa) are important, as is epidermodysplasia verruciformis, a congenital syndrome of increased sensitivity to human papillomaviruseinduced malignant transformation. There are a few reports of SCCs arising at a young age in patients with congenital ichthyosis, including KID2 (keratitis, ichthyosis, deafness), Netherton syndrome,3 photosensitivityichthyosis-brittle hair-impaired intelligence-possibly decreased fertility-short stature syndrome (PIBIDS),4 and bullous and nonbullous congenital ichthyosiform erythroderma.5 Early onset and consecutive appearance of a large number of tumors in these cases make it probable that the underlying genetic disease is the cause of the cancer, as in the photosensitive and skin fragility groups of disorders. Chronic inflammation and increased proliferation rate of keratinocytes in these conditions, which may increase susceptibility to UV radiation damage, can explain the increased susceptibility to SCCs. Proteasome malfunction can lead to abnormal regulation of the cell cycle and uncontrolled cell proliferation and to cancer. Therefore it is not surprising that KLICK, characterized by increased endoplasmic reticulum stress due to dysregulated proteasome function, can be associated with increased susceptibility to cancer. We think that the early appearance of SCC in this case is due to the
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underlying skin disease and would like to add KLICK to the growing list of genodermatoses which can be complicated by skin cancer. Liran Horev, MD,a,b Sari Murad, MD,a Alexander Maly, MD,c and Abraham Zlotogorski, MDa,b Departments of Dermatologya and Pathology,c Center for Genetic Diseases of the Skin and Hair,b Hadassah - Hebrew University Medical Center, Jerusalem, Israel Funding sources: None. Conflicts of interest: None declared. Correspondence to: Dr Liran Horev, Department of Dermatology, Hadassah - Hebrew University Medical Center, Jerusalem 91120, Israel E-mail: [email protected] REFERENCES 1. Dahlqvist J, Klar J, Tiwari N, Schuster J, T€ orm€a H, Badhai J, et al. A single-nucleotide deletion in the POMP 5’ UTR causes a transcriptional switch and altered epidermal proteasome distribution in KLICK genodermatosis. Am J Hum Genet 2010;86:596-603. 2. Madariaga J, Fromowitz F, Phillips M, Hoover HC Jr. Squamous cell carcinoma in congenital ichthyosis with deafness and keratitis. A case report and review of the literature. Cancer 1986;57:2026-9. 3. Krasagakis K, Ioannidou DJ, Stephanidou M, Manios A, Panayiotides JG, Tosca AD. Early development of multiple epithelial neoplasms in Netherton syndrome. Dermatology 2003;207:182-4. 4. Dahbi-Skali H, Benamar L, Benchikhi H, Lakhdar H, Pinel N. PIBIDS syndrome (trichothiodystrophy type F) and skin cancer:
J AM ACAD DERMATOL
JUNE 2011
an exceptional association. Photodermatol Photoimmunol Photomed 2004;20:157-8. 5. Arita K, Akiyama M, Tsuji Y, Iwao F, Kodama K, Shimizu H. Squamous cell carcinoma in a patient with non-bullous congenital ichthyosiform erythroderma. Br J Dermatol 2003;148:367-9. doi:10.1016/j.jaad.2010.12.030
Condyloma accuminatum treated with recombinant quadrivalent human papillomavirus vaccine (types 6, 11, 16, 18) To the Editor: A prophylactic human papillomavirus (HPV) vaccine represents the newest approach to prevent genital HPV infection. We report a case of condyloma accuminatum, which showed dramatic improvement after a single course of HPV vaccination. A 46-year-old man was seen with exophytic masses on the perianal area that had been present for 5 weeks. He was referred to our hospital because the lesion became larger despite nightly application of imiquimod cream for 4 weeks. He had a medical history of diabetes for 5 years. On examination, we found that he had brownish cauliflower-like masses with scattered papules on the perianal area (Fig 1, A). Slightly erythematous patches around the lesion were also observed, which may have been caused by imiquimod. Laboratory studies revealed increased serum glucose levels (243 mg/dL; reference range, 70-110 mg/dL), but other tests, including
Fig 1. A, Brownish exophytic, cauliflower-like masses with scattered discrete papules and slightly erythematous patches around lesion were observed on the perianal area. B, Significant improvement was noted 4 weeks after first vaccine injection. C, Regression of lesions was noted 8 weeks after first vaccine injection. Biopsy specimens were taken from suspect papular lesions (arrows).
Mireille Priale Aujero, BS,a Sara Brooks, MD,b Ning Li, MD,c and Suraj Venna, MDd Georgetown University School of Medicine, Washington, DCa; Washington Hospital Center/ Georgetown University Combined Program in Dermatologyb; Dianon Systems, Dermatopathologyc; and Washington Cancer Institute at the Washington Hospital Centerd Funding sources: None. Conflicts of interest: None declared. Correspondence and reprint requests to: Suraj Venna, MD, Washington Cancer Institute, 110 Irving St, Suite 2149, Washington, DC 20010 E-mail: [email protected] REFERENCES 1. Darmon P, Castera V, Koeppel MC, Petitjean C, Dutour A. A type III allergy to insulin detemir. Diabetes Care 2005;28:2980.
J AM ACAD DERMATOL
JUNE 2011
2. Sola-Gazagnes A, Pecquet C, M’Bemba J, Larger E, Slama G. Type I and type IV allergy to the insulin analogue detemir. Lancet 2007;369:637-8. 3. Perez E, Gonzalez R, Martinez J, Iglesias J, Matheu V. Detemir insulin-induced anaphylaxis. Ann Allergy Asthma Immunol 2009;102:174-5. 4. Akinci B, Yener S, Bayraktar F, Yesil S. Allergic reactions to human insulin: a review of current knowledge and treatment options. Endocrine 2010;37:33-9. doi:10.1016/j.jaad.2010.11.028
Aggressive cutaneous squamous cell carcinoma in a patient with KLICK To the Editor: A 23-year-old mechanic presented to our department with ichthyosis and palmoplantar sclerotic keratoderma with constricting bands on the dorsal aspect of the hands (Fig 1, A and B). The typical clinical presentation led to the diagnosis of KLICK (keratosis linearis with ichthyosis congenita and sclerosing keratoderma); by genetic analysis, the
Fig 1. A, Dorsal aspect of foot showing sclerotic keratoderma. B, Dorsal hand showing skin erythema and thickening with typical constricting bands. C, Homozygous mutation c.-95delC in POMP gene. Upper panel: Patient. Lower panel: Control. Arrow shows site of deletion.
J AM ACAD DERMATOL VOLUME 64, NUMBER 6
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Fig 2. A, Photomicrograph of skin shows compact hyperkeratosis, irregular acanthosis and dermal massive invasion by well-differentiated SCC. B, Lymph node from right axilla with SCC metastasis. (A and B, Hematoxylin-eosin stain; original magnifications: A, 3100; B, 3200.)
patient was shown to carry the recurrent c.-95 mutation in the POMP gene, shared by all patients with KLICK described to date1 (Fig 1, C ). Physical examination also revealed a 2- 3 2-cm ulcerated mass of 3 months’ duration on the right wrist and a subcutaneous mass in the right axilla. Histologic examination of the ulcerated skin tumor and the axillary mass showed a moderately differentiated squamous cell carcinoma (SCC) with axillary lymph node metastasis (Fig 2, A and B). Deep penetration into the underlying tendons and nerves prevented its complete resection, and the patient was referred for further evaluation and treatment at the oncology unit. KLICK is a rare autosomal recessive form of nonsyndromic ichthyosis, recently shown to be caused by a mutation in the gene POMP.1 The product of the POMP gene, proteasome maturation protein, is involved in the proteasome 20s subunit assembly. The main function of the proteasome, a complex of proteins in all eukaryotic cells, is to degrade unneeded or damaged proteins. Cutaneous SCCs presenting in childhood and young adulthood are rare. In most of the cases, there is an underlying predisposing condition. Immunodeficiency due to human immunodeficiency virus, chronic graft-versus-host disease, or organ transplantation is a leading cause. Among the congenital disorders, photosensitive skin disorders (eg, albinism, xeroderma pigmentosum, erythropoietic
porphyria) and disorders of increased skin and mucosal fragility (eg, dystrophic epidermolysis bullosa) are important, as is epidermodysplasia verruciformis, a congenital syndrome of increased sensitivity to human papillomaviruseinduced malignant transformation. There are a few reports of SCCs arising at a young age in patients with congenital ichthyosis, including KID2 (keratitis, ichthyosis, deafness), Netherton syndrome,3 photosensitivityichthyosis-brittle hair-impaired intelligence-possibly decreased fertility-short stature syndrome (PIBIDS),4 and bullous and nonbullous congenital ichthyosiform erythroderma.5 Early onset and consecutive appearance of a large number of tumors in these cases make it probable that the underlying genetic disease is the cause of the cancer, as in the photosensitive and skin fragility groups of disorders. Chronic inflammation and increased proliferation rate of keratinocytes in these conditions, which may increase susceptibility to UV radiation damage, can explain the increased susceptibility to SCCs. Proteasome malfunction can lead to abnormal regulation of the cell cycle and uncontrolled cell proliferation and to cancer. Therefore it is not surprising that KLICK, characterized by increased endoplasmic reticulum stress due to dysregulated proteasome function, can be associated with increased susceptibility to cancer. We think that the early appearance of SCC in this case is due to the
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underlying skin disease and would like to add KLICK to the growing list of genodermatoses which can be complicated by skin cancer. Liran Horev, MD,a,b Sari Murad, MD,a Alexander Maly, MD,c and Abraham Zlotogorski, MDa,b Departments of Dermatologya and Pathology,c Center for Genetic Diseases of the Skin and Hair,b Hadassah - Hebrew University Medical Center, Jerusalem, Israel Funding sources: None. Conflicts of interest: None declared. Correspondence to: Dr Liran Horev, Department of Dermatology, Hadassah - Hebrew University Medical Center, Jerusalem 91120, Israel E-mail: [email protected] REFERENCES 1. Dahlqvist J, Klar J, Tiwari N, Schuster J, T€ orm€a H, Badhai J, et al. A single-nucleotide deletion in the POMP 5’ UTR causes a transcriptional switch and altered epidermal proteasome distribution in KLICK genodermatosis. Am J Hum Genet 2010;86:596-603. 2. Madariaga J, Fromowitz F, Phillips M, Hoover HC Jr. Squamous cell carcinoma in congenital ichthyosis with deafness and keratitis. A case report and review of the literature. Cancer 1986;57:2026-9. 3. Krasagakis K, Ioannidou DJ, Stephanidou M, Manios A, Panayiotides JG, Tosca AD. Early development of multiple epithelial neoplasms in Netherton syndrome. Dermatology 2003;207:182-4. 4. Dahbi-Skali H, Benamar L, Benchikhi H, Lakhdar H, Pinel N. PIBIDS syndrome (trichothiodystrophy type F) and skin cancer:
J AM ACAD DERMATOL
JUNE 2011
an exceptional association. Photodermatol Photoimmunol Photomed 2004;20:157-8. 5. Arita K, Akiyama M, Tsuji Y, Iwao F, Kodama K, Shimizu H. Squamous cell carcinoma in a patient with non-bullous congenital ichthyosiform erythroderma. Br J Dermatol 2003;148:367-9. doi:10.1016/j.jaad.2010.12.030
Condyloma accuminatum treated with recombinant quadrivalent human papillomavirus vaccine (types 6, 11, 16, 18) To the Editor: A prophylactic human papillomavirus (HPV) vaccine represents the newest approach to prevent genital HPV infection. We report a case of condyloma accuminatum, which showed dramatic improvement after a single course of HPV vaccination. A 46-year-old man was seen with exophytic masses on the perianal area that had been present for 5 weeks. He was referred to our hospital because the lesion became larger despite nightly application of imiquimod cream for 4 weeks. He had a medical history of diabetes for 5 years. On examination, we found that he had brownish cauliflower-like masses with scattered papules on the perianal area (Fig 1, A). Slightly erythematous patches around the lesion were also observed, which may have been caused by imiquimod. Laboratory studies revealed increased serum glucose levels (243 mg/dL; reference range, 70-110 mg/dL), but other tests, including
Fig 1. A, Brownish exophytic, cauliflower-like masses with scattered discrete papules and slightly erythematous patches around lesion were observed on the perianal area. B, Significant improvement was noted 4 weeks after first vaccine injection. C, Regression of lesions was noted 8 weeks after first vaccine injection. Biopsy specimens were taken from suspect papular lesions (arrows).