Journal of Dermatology 2014; 41: 337–339
doi: 10.1111/1346-8138.12428
CONCISE COMMUNICATION
Pigmented condyloma acuminatum Akira SHIMIZU, Madoka KATO, Osamu ISHIKAWA Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan
ABSTRACT We herein report a case of pigmented condyloma acuminatum in the genital region. A histopathological examination revealed keratinocyte proliferation, papillomatosis and basal pigmentation. Cellular atypia was rarely observed. The patient also had ordinary skin-colored nodules on the coronal sulcus. Polymerase chain reaction amplification with consensus primers for human papillomavirus (HPV) and subsequent sequencing confirmed an infection of HPV type 6. Pigmented condyloma acuminatum is not rare; however, making the differential diagnosis between bowenoid papulosis and seborrheic keratosis is sometimes difficult. The mechanism of pigmentation in such cases remains unknown and requires further investigation. HPV typing is a useful method for diagnosing the disease.
Key words: human papillomavirus, condyloma acuminatum, bowenoid papulosis, imiquimod, human papilloma virus typing.
INTRODUCTION Condyloma acuminatum (CA) is a benign tumor caused by infection with human papillomavirus (HPV) of types 6 and 11.1,2 Bowenoid papulosis (BP) is also related to high-risk HPV types, including type 16.3 The clinical course of BP is generally benign, and the malignant potential is controversial. Typical cases of CA and BP can be easily diagnosed based on the clinical features alone. However, it is difficult to distinguish CA from BP when the CA manifests as pigmented lesions.4,5 We herein report a case of pigmented CA in the genital area. The patient also had normal skin-colored nodules on the coronal sulcus. A histopathological examination established the diagnosis of CA, and HPV typing with polymerase chain reaction (PCR) revealed an infection of HPV type 6. The clinical usefulness of HPV typing in classifying pigmented nodules in the genital area is discussed.
(a)
(b)
Figure 1. Clinical appearance. (a) Brownish nodule on the patient’s mons pubis. (b) Brownish to normal skin-colored nodules coalesced on the coronal sulcus.
CASE REPORT A 65-year-old man presented with a 2-year history of blackbrownish nodules in the genital area. He was otherwise healthy and had not received any medications. A physical examination revealed brownish-black small nodules around the genital area and perianal region. Light brown to normal skin-colored nodules coalesced on the coronal sulcus (Fig. 1). A biopsy specimen was obtained from a black perianal nodule. The histopathological examination revealed hyperkeratosis, papillomatosis and acanthosis (Fig. 2a). A high-power view demonstrated a slightly disordered arrangement of keratinocytes without atypia (Fig. 2b) and basal pigmentation (Fig. 2c). After
obtaining the patient’s informed consent, the detection of HPV DNA was performed using a PCR analysis of the tissue samples acquired from the lesions. DNA was extracted from the biopsied samples using the Maxwell 16 DNA Purification Kit (Promega, Osaka, Japan) according to the manufacturer’s instructions. HPV PCR was performed with consensus sequence primers, L1C1/L1C2, located in the L1 open reading frame of the HPV genome. The PCR conditions have been described previously.6 The PCR products were purified and subjected to direct DNA sequencing. The sequences corresponded to the L1 gene of HPV type 6. We diagnosed
Correspondence: Akira Shimizu, Ph.D., M.D., Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showamachi, Maebashi, Gunma 371-8511, Japan. Email: [email protected] Received 30 October 2013; accepted 27 December 2013.
© 2014 Japanese Dermatological Association
337
A. Shimizu et al.
(a)
the patient as having pigmented condyloma acuminatum. The lesions disappeared after treatment with topical imiquimod cream for 2 months.
DISCUSSION
(b)
(c)
The existence of pigmented papules of CA has been rarely described. In 1980, Kimura reported five cases of CA with pigmented papular lesions.4 We also previously reported a case of pigmented plaque-like CA.7 CA usually presents as soft, pink, velvety and protuberant lesions. In a few cases, these lesions grow to form a cauliflower-like large tumor. Some of the lesions may be deeply pigmented, resembling those of seborrheic keratosis or BP. It has been reported that HPVinfected anogenital seborrheic keratosis actually may be CA.8 Why the lesion in the present case was pigmented is unclear. Histopathologically, focal and basal pigmentation were noted. As some HPV types, including HPV type 56, cause longitudinal melanonychia, various HPV strains may stimulate melanogenesis.9 The capacity of HPV for transformation has been investigated; however, the mechanism underlying HPVinduced melanogenesis remains largely unknown. Because HPV type 16-immortalized keratinocytes are related to the endothelin-1 autocrine loop,10 keratinocytes infected with HPV may stimulate melanocytes via a cytokine pathway. Human papilloma virus type 6 or 11 is usually detected in cases of CA, while oncogenic HPV type 16 is detected in cases of BP. Sturegard et al.11 performed HPV typing of 621 subjects with CA and found that 94% of the CA samples contained genital HPV types, with HPV type 6 (62%), 16 (13%) and 11 (10%) being the most common. Although physicians should pay attention to the fact that some individuals with CA are positive for oncogenic HPV, the majority of CA patients are positive for HPV types 6 and 11. PCR HPV typing is helpful for distinguishing black lesions of CA from those of BP. Recently, Kazlouskaya et al.12 reported that p16 staining is a powerful tool for differentiating CA from BP. The authors clearly showed that diffuse p16 staining is observed in the lesions of BP, while only sporadic or focal p16 staining is noted in the lesions of CA. Therefore, both HPV typing and p16 staining are useful methods for distinguishing CA from BP. Because making the clinical diagnosis between pigmented CA, BP and seborrheic keratosis is sometimes difficult in certain cases, HPV typing is worth performing in order to understand the relationship between the clinical phenotypes and HPV genotypes.
CONFLICT OF INTEREST: Figure 2. Histopathological findings of the perianal brownishblack nodule. (a) Low-power view showing hyperkeratosis, acanthosis and papillomatosis (hematoxylin–eosin stain [HE], original magnification 920). (b) High-power view of the same section showing a slightly disorderly arrangement of keratinocytes without atypia in addition to koilocytes (black arrow) (HE, 9100). (c) High-power view of the same section showing a slightly disorderly arrangement of keratinocytes with basal pigmentation (white arrow) (HE, 9100).
338
None.
REFERENCES 1 Gissmann L, Zur Hausen H. Partial characterization of viral DNA from human genital warts (Condylomata acuminata). Int J Cancer 1980; 25: 605–609. 2 Greer CE, Wheeler CM, Ladner MB et al. Human papillomavirus (HPV) type distribution and serological response to HPV type 6 virus-like particles in patients with genital warts. J Clin Microbiol 1995; 33: 2058–2063.
© 2014 Japanese Dermatological Association
Pigmented condyloma acuminatum
3 Ikenberg H, Gissmann L, Gross G et al. Human papillomavirus type-16-related DNA in genital Bowen’s disease and in Bowenoid papulosis. Int J Cancer 1983; 32: 563–565. 4 Kimura S. Condylomata acuminata with pigmented papular lesions. Dermatologica 1980; 160: 390–397. 5 Sanderson KV. Multicentric pigmented Bowen’s disease. Proc R Soc Med 1974; 67: 23–24. 6 Yoshikawa H, Kawana T, Kitagawa K et al. Detection and typing of multiple genital human papillomaviruses by DNA amplification with consensus primers. Jpn J Cancer Res 1991; 82: 524–531. 7 Shimizu A, Tamura A, Nakatani Y et al. Pigmented plaque-type condyloma acuminatum associated with human papillomavirus type 6. J Dermatol 2012; 39: 860–861. 8 Li J, Ackerman AB. “Seborrheic keratoses” that contain human papillomavirus are condylomata acuminata. Am J Dermatopathol 1994; 16: 398–405.
© 2014 Japanese Dermatological Association
9 Shimizu A, Tamura A, Abe M et al. Detection of human papillomavirus type 56 in Bowen’s disease involving the nail matrix. Br J Dermatol 2008; 158: 1273–1279. 10 Venuti A, Marcante ML, Flamini S et al. The autonomous growth of human papillomavirus type 16-immortalized keratinocytes is related to the endothelin-1 autocrine loop. J Virol 1997; 71: 6898– 6904. 11 Sturegard E, Johansson H, Ekstrom J et al. Human papillomavirus typing in reporting of condyloma. Sex Transm Dis 2013; 40: 123– 129. 12 Kazlouskaya V, Shustef E, Allam SH et al. Expression of p16 protein in lesional and perilesional condyloma acuminata and bowenoid papulosis: clinical significance and diagnostic implications. J Am Acad Dermatol 2013; 69: 444–449.
339
doi: 10.1111/1346-8138.12428
CONCISE COMMUNICATION
Pigmented condyloma acuminatum Akira SHIMIZU, Madoka KATO, Osamu ISHIKAWA Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan
ABSTRACT We herein report a case of pigmented condyloma acuminatum in the genital region. A histopathological examination revealed keratinocyte proliferation, papillomatosis and basal pigmentation. Cellular atypia was rarely observed. The patient also had ordinary skin-colored nodules on the coronal sulcus. Polymerase chain reaction amplification with consensus primers for human papillomavirus (HPV) and subsequent sequencing confirmed an infection of HPV type 6. Pigmented condyloma acuminatum is not rare; however, making the differential diagnosis between bowenoid papulosis and seborrheic keratosis is sometimes difficult. The mechanism of pigmentation in such cases remains unknown and requires further investigation. HPV typing is a useful method for diagnosing the disease.
Key words: human papillomavirus, condyloma acuminatum, bowenoid papulosis, imiquimod, human papilloma virus typing.
INTRODUCTION Condyloma acuminatum (CA) is a benign tumor caused by infection with human papillomavirus (HPV) of types 6 and 11.1,2 Bowenoid papulosis (BP) is also related to high-risk HPV types, including type 16.3 The clinical course of BP is generally benign, and the malignant potential is controversial. Typical cases of CA and BP can be easily diagnosed based on the clinical features alone. However, it is difficult to distinguish CA from BP when the CA manifests as pigmented lesions.4,5 We herein report a case of pigmented CA in the genital area. The patient also had normal skin-colored nodules on the coronal sulcus. A histopathological examination established the diagnosis of CA, and HPV typing with polymerase chain reaction (PCR) revealed an infection of HPV type 6. The clinical usefulness of HPV typing in classifying pigmented nodules in the genital area is discussed.
(a)
(b)
Figure 1. Clinical appearance. (a) Brownish nodule on the patient’s mons pubis. (b) Brownish to normal skin-colored nodules coalesced on the coronal sulcus.
CASE REPORT A 65-year-old man presented with a 2-year history of blackbrownish nodules in the genital area. He was otherwise healthy and had not received any medications. A physical examination revealed brownish-black small nodules around the genital area and perianal region. Light brown to normal skin-colored nodules coalesced on the coronal sulcus (Fig. 1). A biopsy specimen was obtained from a black perianal nodule. The histopathological examination revealed hyperkeratosis, papillomatosis and acanthosis (Fig. 2a). A high-power view demonstrated a slightly disordered arrangement of keratinocytes without atypia (Fig. 2b) and basal pigmentation (Fig. 2c). After
obtaining the patient’s informed consent, the detection of HPV DNA was performed using a PCR analysis of the tissue samples acquired from the lesions. DNA was extracted from the biopsied samples using the Maxwell 16 DNA Purification Kit (Promega, Osaka, Japan) according to the manufacturer’s instructions. HPV PCR was performed with consensus sequence primers, L1C1/L1C2, located in the L1 open reading frame of the HPV genome. The PCR conditions have been described previously.6 The PCR products were purified and subjected to direct DNA sequencing. The sequences corresponded to the L1 gene of HPV type 6. We diagnosed
Correspondence: Akira Shimizu, Ph.D., M.D., Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showamachi, Maebashi, Gunma 371-8511, Japan. Email: [email protected] Received 30 October 2013; accepted 27 December 2013.
© 2014 Japanese Dermatological Association
337
A. Shimizu et al.
(a)
the patient as having pigmented condyloma acuminatum. The lesions disappeared after treatment with topical imiquimod cream for 2 months.
DISCUSSION
(b)
(c)
The existence of pigmented papules of CA has been rarely described. In 1980, Kimura reported five cases of CA with pigmented papular lesions.4 We also previously reported a case of pigmented plaque-like CA.7 CA usually presents as soft, pink, velvety and protuberant lesions. In a few cases, these lesions grow to form a cauliflower-like large tumor. Some of the lesions may be deeply pigmented, resembling those of seborrheic keratosis or BP. It has been reported that HPVinfected anogenital seborrheic keratosis actually may be CA.8 Why the lesion in the present case was pigmented is unclear. Histopathologically, focal and basal pigmentation were noted. As some HPV types, including HPV type 56, cause longitudinal melanonychia, various HPV strains may stimulate melanogenesis.9 The capacity of HPV for transformation has been investigated; however, the mechanism underlying HPVinduced melanogenesis remains largely unknown. Because HPV type 16-immortalized keratinocytes are related to the endothelin-1 autocrine loop,10 keratinocytes infected with HPV may stimulate melanocytes via a cytokine pathway. Human papilloma virus type 6 or 11 is usually detected in cases of CA, while oncogenic HPV type 16 is detected in cases of BP. Sturegard et al.11 performed HPV typing of 621 subjects with CA and found that 94% of the CA samples contained genital HPV types, with HPV type 6 (62%), 16 (13%) and 11 (10%) being the most common. Although physicians should pay attention to the fact that some individuals with CA are positive for oncogenic HPV, the majority of CA patients are positive for HPV types 6 and 11. PCR HPV typing is helpful for distinguishing black lesions of CA from those of BP. Recently, Kazlouskaya et al.12 reported that p16 staining is a powerful tool for differentiating CA from BP. The authors clearly showed that diffuse p16 staining is observed in the lesions of BP, while only sporadic or focal p16 staining is noted in the lesions of CA. Therefore, both HPV typing and p16 staining are useful methods for distinguishing CA from BP. Because making the clinical diagnosis between pigmented CA, BP and seborrheic keratosis is sometimes difficult in certain cases, HPV typing is worth performing in order to understand the relationship between the clinical phenotypes and HPV genotypes.
CONFLICT OF INTEREST: Figure 2. Histopathological findings of the perianal brownishblack nodule. (a) Low-power view showing hyperkeratosis, acanthosis and papillomatosis (hematoxylin–eosin stain [HE], original magnification 920). (b) High-power view of the same section showing a slightly disorderly arrangement of keratinocytes without atypia in addition to koilocytes (black arrow) (HE, 9100). (c) High-power view of the same section showing a slightly disorderly arrangement of keratinocytes with basal pigmentation (white arrow) (HE, 9100).
338
None.
REFERENCES 1 Gissmann L, Zur Hausen H. Partial characterization of viral DNA from human genital warts (Condylomata acuminata). Int J Cancer 1980; 25: 605–609. 2 Greer CE, Wheeler CM, Ladner MB et al. Human papillomavirus (HPV) type distribution and serological response to HPV type 6 virus-like particles in patients with genital warts. J Clin Microbiol 1995; 33: 2058–2063.
© 2014 Japanese Dermatological Association
Pigmented condyloma acuminatum
3 Ikenberg H, Gissmann L, Gross G et al. Human papillomavirus type-16-related DNA in genital Bowen’s disease and in Bowenoid papulosis. Int J Cancer 1983; 32: 563–565. 4 Kimura S. Condylomata acuminata with pigmented papular lesions. Dermatologica 1980; 160: 390–397. 5 Sanderson KV. Multicentric pigmented Bowen’s disease. Proc R Soc Med 1974; 67: 23–24. 6 Yoshikawa H, Kawana T, Kitagawa K et al. Detection and typing of multiple genital human papillomaviruses by DNA amplification with consensus primers. Jpn J Cancer Res 1991; 82: 524–531. 7 Shimizu A, Tamura A, Nakatani Y et al. Pigmented plaque-type condyloma acuminatum associated with human papillomavirus type 6. J Dermatol 2012; 39: 860–861. 8 Li J, Ackerman AB. “Seborrheic keratoses” that contain human papillomavirus are condylomata acuminata. Am J Dermatopathol 1994; 16: 398–405.
© 2014 Japanese Dermatological Association
9 Shimizu A, Tamura A, Abe M et al. Detection of human papillomavirus type 56 in Bowen’s disease involving the nail matrix. Br J Dermatol 2008; 158: 1273–1279. 10 Venuti A, Marcante ML, Flamini S et al. The autonomous growth of human papillomavirus type 16-immortalized keratinocytes is related to the endothelin-1 autocrine loop. J Virol 1997; 71: 6898– 6904. 11 Sturegard E, Johansson H, Ekstrom J et al. Human papillomavirus typing in reporting of condyloma. Sex Transm Dis 2013; 40: 123– 129. 12 Kazlouskaya V, Shustef E, Allam SH et al. Expression of p16 protein in lesional and perilesional condyloma acuminata and bowenoid papulosis: clinical significance and diagnostic implications. J Am Acad Dermatol 2013; 69: 444–449.
339
