DOI: 10.4197/Med. 17-4.7
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Correspondence & reprint request to: Dr. Amal O. Al-Balbeesi
P.O. Box 2457, Riyadh 11451, Saudi Arabia Accepted for publication: 26 September 2010. Received: 15 September 2010.
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Genital Squamous Cell Carcinoma in a Congenital Ichthyosis
Amal O. Al-Balbeesi, MD Department of Dermatology
King Khalid University Hospital, King Saud University Riyadh, Saudi Arabia
Abstract. It is well known that patients with heritable cutaneous disease have an increased risk of developing tumors during their lifetime. This relationship has been proven for conditions([1] such as xeroderma pigmentosum, Basal cell nevus syndrome, and Blooms syndrome. Multiple cutaneous tumors with Lamellar Ichthyosis had been reported[2] in people with sun exposed skin. This article describes a case of genital squamous cell carcinoma in a patient with Lamellar Ichthyosis, which in our knowledge, described for the first time. During the long standing follow-up of patients with Lamellar Ichthyosis, careful attention should be paid to the occurrence of skin cancers in both, sun exposed and sun protected skin.
Keywords: Squamous cell carcinoma, Ichthyosis.
Introduction
The following case report describes a case of squamous cell carcinoma arising over the vulva in an adult patient of lamellar ichthyosis.
Such an occurrence underlines the seriousness of ichthyosis and must increase the awareness of dermatologists to thoroughly examine the sun exposed and sun protected skin during follow-up as malignant lesions could hide between the scales.
Case Presentation
A 31-years-old single Saudi lady of skin type 5 was known to have lamellar ichthyosis since childhood. The patient was presented with a painful right inguinal mass that appeared de novo and continued growing over a period of one year. Examination of the inguinal area showed 2 x 3 cm hard fungate cauliform tumor with granular surface and mobile over underlying structures (Fig. 1), regional lymph nodes were palpable. Full body examination revealed no other lesions. Skin biopsy showed moderately differentiated squamous cell carcinoma (Fig. 2-4).
Fig. 1. Fungate cauliform tumor over the vulva.
In situ hybridization for Human Papilloma Virus (HPV 6, 11, 16, 18, 33, and 51) was negative. Inguinal lymph node microscopic dissection of both sides showed follicular hyperplasia with no malignant cells.
Abdominal computed scan (CT) showed no lymph nodes enlargement.
Other laboratory tests, such as complete blood count (CBC), urea and electrolytes (U/E), creatinine, liver function test (LFT) were all within normal. Genetic tests have not been possible on our patient, although it would have been very constructive to do these tests.
The patient underwent radical wide excision of the tumor with skin grafting from the thigh. Both the donor and surgery site healed satisfactorily.
After the wound healed, a regimen of oral etretinate, such as a chemoprevention for more tumors was suggested, but was refused by the patient.
Fig. 2. Nests of squamous epithelial cells extending into the dermis (H & E).
Fig. 3. Nests of squamous epithelial cells extending into the dermis (H & E).
Fig. 4. Moderately well-differentiated squamous cell carcinoma (H & E).
Discussion
A group of heritable diseases with differing clinical features are associated with the increased incidence of neoplasia. This association occurs in conditions such as xeroderma pigmentosum, blooms syndrome, basal cell nevus syndrome and congenital ichthyosis[1-5]. The study describes a patient having lamellar ichthyosis with squamous cell carcinoma affecting the vulva. Despite a wide search, failed to find similar presentation in the literature was noted and therefore, it’s believed that this is the first report of such an association. The explanation for developing such cancers was based that lamellar ichthyosis was a contributing factor.
The limited body of knowledge to date does not explain why these patients may be at risk of cutaneous carcinogenesis. Scarring from chronic inflammation could predispose to cutaneous squamous cell carcinoma (SCC) development.
A Japanese patient described by Arita et al.[5] has been shown to have mutation in the ABCA12 gene. It remains to be seen whether this mutation has a role in promoting carcinogenesis.
Ichthyosis is a benign condition. However, anaplastic and dysplastic changes has been reported by some authors, such as its association with HPV. Hence, HPV infection is now recognized as major etiological factor in anogenital cancers, including carcinoma of the vulva, cervix and penis[6,7]. Cases associated with carcinoma of the cervix were believed to be a result of direct extension of the lesion[8]. However, these occurrences were seen on rare conditions of extensive ichthyosis uteri with squamous cell carcinoma extending proximally([8].
The labia majora is the most common site of involvement and accounted for about 50% of cases. The labia minora accounts for 15- 20% of cases. The clitoris and Bartholin’s glands are less commonly involved[7].
The occurrence of squamous cell carcinoma underlines the seriousness of ichthyosis. The chemo-preventive effect of retinoids for certain cancers is well known. Clinical trials of chemo-prevention by retinoids have been performed. This showed a decreased incidence of new non-melanoma skin cancer (NMSC), particularly cutaneous SCC in high risk groups of skin cancer, such as patients with xeroderma pigmentosum, basal cell nevus syndrome, and patients who received immunosuppressive therapy after organ transplantation[9-11].
These drugs have been used in the treatment and prevention of cutaneous malignancies in patients which increases susceptibility to such complications. Doses of isotretinoin given in high dose regimen (2 mg/kg/day) for 2 years were shown to be effective in the chemo prevention of skin cancers, but with significant toxicity. Continuation on a lower dose regimen (0.5-1.5 mg/kg/day) also proved to be beneficial in some individuals[11].
In other trials, retinoids along with conventional chemotherapy have shown promise in treating cervical, breast, prostate, kidney and pancreatic cancer[10].
The ability of retinoids to have an effect on such a variety of conditions is due to their control over the growth and death of human cells, as well as cellular differentiation.
Retinoids act as hormones and interact with specific receptors in the nucleus that belong to the family of specific retinoic acid receptors
(RAR). This result in the regulation of DNA transcription through complex mechanisms[9].
Conclusion
During the long standing follow-up of patients with lamellar ichthyosis, careful attention should be paid to the occurrence of skin cancers in both sun exposed and sun protected skin.
References
[1] Kramer KH, Fitzpatrick TB. Eisen AZ, Klaus W, Irwin M, Freedberg K, Austen F.
Heritable diseases with increase sensitivity to cellular injury. In: Dermatology in General Medicine Textbook, 4th ed, New York: McGraw-Hill, 1974. 1991.
[2] Elbaum DJ, Kurz G, MacDuff M. Increased incidence of cutaneous carcinoma in patients with congenital ichthyosis. J Am Acad Dermatol 1995; 33(5 Pt 2): 884-886.
[3] Madriaga 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(10): 2026-2029.
[4] Grob JJ, Breton A, Bonafe JL, Sauvan-Ferdani M, Bonerandi JJ. Keratitis, ichthyosis, and deafness (KID) syndrome. Vertical transmission and death from multiple squamous cell carcinoma. Arch Dermatol 1987; 123(6): 777-782.
[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(2): 367-369.
[6] Toki T, Kurman RJ, Park JS, Kessis T, Daniel RW, Shah KV. Probable nonpapillomavirus etiology of squamous cell carcinoma of the vulva in older women: a clinicopathologic study using in situ hybridization and polymerase chain reaction. Int J Gynecol Pathol 1991; 10(2): 107-125.
[7] DiGiovanna JJ, Robinson-Boston L. Ichthyosis: etiology, diagnosis and management.
Am J Clin Dermatol 2003; 4(2): 81-95.
[8] Murhekar K, Majhi U, Sridevi V, Rajkumar T. Does “ichthyosis uteri” have malignant potential? Case report of squamous cell carcinoma of endometrium associated with extensive ichthyosis uteri. Diagn Pathol 2008; 3: (4).
[9] Kelly JW, Sabto J, Gurr FW, Bruce F. Retinoids to prevent skin cancer in organ transplant recipients. Lancet 1991; 338(8779): 1407.
[10] DiGiovanna JJ. Retinoid chemoprevention in the high-risk patient. J Am Acad Dermatol 1998; 39(2 Pt 3): S82-85.
[11] McKenna DB, Murphy GM. Skin cancer chemoprophylaxis in renal transplant recipient, 5 years of experience using low dose acitretin. Br J Dermatol 1999; 140(4): 656-660.
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