The Journal of Dennatology Vol. 19: 432-435, 1992
Giant Condyloma Acuminatum in a Baby Boy Noriko Matsumura, Kumiko Kumasaka, Hideo Maki*, Osamu Yoshie* and Hachiro Tagami Abstract A giant condyloma acuminatum developed on the penis of a one and a half-year-oldJapanese boy in two months. The histological features of this tumor were compatible with those of ordinary condyloma acuminatum. Although we detected the presence of human papilloma virus (HPV) type 16 by using the polymerase chain reaction system, we could not rule out the possibility that this HPV was present concurrently with other HPV types that cause condyloma acuminatum. The lesion was successfully treated with cryotherapy and topical application of 5% fluorouracil ointment under occlusion
Key words: condyloma acuminatum; human papilloma virus; Buschke-Loewenstein tumor; previous inflammation
Introduction Condyloma acuminatum is a sexually transmitted disease usually occurring in adults (1). It may occur in children, often due to sexual abuse but penile involvement is extremely rare. It is caused by an infection by the human papilloma virus (HPV), mainly types 6 and 11 (1, 2). In adults, unusually large condyloma acuminatum always suggests the possibility of malignant conversion, i.e. giant condyloma acuminatum of Buschke-Loewenstein. We report here an unusually large condyloma acuminatum affecting a one and a half-year-old boy, from which HPV-16 was detected by polymerase chain reaction method.
Case Report A one and a half-year-old Japanese boy was hospitalized because of a huge verrucous tumor on the glans and foreskin of his penis that had grown rapidly within the previous 2 months. During that Received December 16, 1991; accepted for publication May 14, 1992. Department of Dermatology, Tohoku University School of Medicine, Sendai,Japan. *Shionogi Institute for Medical Science, 2-5-1 Mishima, Settsu-shi, Osaka 566,japan. Reprint requests to: Noriko Matsumura, M.D., Department of Dermatology, Tohoku University School of Medicine, Seiryo-machi I-I, Aoba-ku, Sendai 980,japan.
period, he had been treated by a local physician with topical application of 0.12% betamethasone valerate ointment under a diagnosis of posthitis and balanitis. No other members of his family had suffered from similar genital lesions or warts on other areas. There was no evidence of cervical dysplasia or bowenoid papulosis in his mother nor any clue as to possible sexual abuse by his neighbours. On physical examination, his glans penis and the distal part of the foreskin were totally covered with a hyperkeratotic verrucous tumor measuring 4.0 x 3.0 em in size (Fig. la, b). The thick horny material covering the foreskin sloughed off 5 days after the start of daily repeated cryotherapy, exposing a soft, papillomatous lesion. Thereafter 5% fluorouracil ointment was applied under occlusion for 8 days until the surface became eroded. For the lesion on the glans penis, the topical fluorouracil application was started directly and continued intermittently until 36 days later when the papillomatous tumor totally disappeared. No verrucous tumor was found in the urethra by endoscopic examination. After six months of intermittent treatment, the entire eruption disappeared (Fig. Ie). However six months later, one verrucous papule reappeared and required topical fluorouracil application and cryotherapy for eradication.
Histology A biopsy specimen from the involved foreskin
Giant Condyloma in a Baby Boy
433
Fig. Ia. A gigantic verrucous tumor of the glans and foreskin ofthe penis.
Fig. 1b. Higher magnification. Hyperkeratotic granular appearance.
Fig. Ie. Clinical appearance 6 months after the start of treatment. showed thick parakeratotic stratum corneum covering acanthotic epidermis with numerous vacuolated cells in the upper layer (Fig. 2). HPV capsid protein antigen could not be demonstrated by immunohistological staining performed as reported in an earlier paper (3).
Detection of Human Papilloma VIrUS Frozen tumor tissue of the patient was used for DNA extraction. The details of our polymerase chain reaction (PCR) systems, including specific primers and probes for HPV-I6 and -18 synthesized from the E7 open reading frames were described elsewhere (4). By this method, an amplification product derived from HPV-I6, but not from HPV-I8, was detected in the DNA from the lesional tissue of the patient (Fig. 3). The amplified sequence of DNA was further confirmed to be similar to the corresponding region of HPV-I6 sequence after restriction endonuclease digestion as reported previously (4).
Fig. 2. Histopathology of the verrucous tumor. There was parakeratosis and acanthosis of the epidermis associated with numerous vacuolated cells (HE, x80).
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Matsumura et al
b
a M
2 3 N
M
2 3 N
.. Fig. 3. PCR for the detection of HPV. PCR amplifications were carried out with the primers specific for HPV-16 (a) and for HPV18 (b). Amplification products were detected by polyacrylamide gel electrophoresis and ethium bromide staining. Lanes are as follows. M: PhiX-174 DNA digested with HaeIII, 0.25 J1.g; 1: DNA from the patient, 500 ng; 2: CaSki DNA, 500 ng (a human cervical cancer cell line with integrated HPV-16); 3: HeLa DNA, 500 ng (a human cevical cancer cell line with integrated HPV-18); N: no DNA. The arrows indicate the expected position of the amplification products.
Giant condyloma of adults caused by HPV types 6 and 11 sometimes shows locally aggressive behavior and tends to recur even after apparently adequate surgery (1). In contrast, in our case, the huge verrucous tumor showed a rather good response to topical fluorouracil application, mitigating the possibility of malignancy. The causative virus types for condyloma acuminatum are most often HPV types 6 and 11, but occasionally infections by HPV type 16 or 18 are reported (2, 6). HPV-16 and 18 are closely related to maJignant diseases such as cervical cancer, Bowen's disease and anogenital cancer (7, 8). Although we could not test for HPV type 6 and 11, DNA for HPV type 16 was detected in the tumor tissue by using peR system for HPV-16 and 18 that has become recently available to us. Unfortunately we could not continue further analysis of HPV because of exhaustion of the specimen. Because the histological appearance of the present case was far from those so far reported in HPV-16 infections, which consist of bowenoid anaplastic features, we think that the possibility of a mixed HPV infection is highly likely.
Acknowledgments Discussion Because condyloma acuminatum is usually sexually transmitted, it is uncommon in children (1). Our case is unique in that a huge verrucous tumor, resembling the giant condyloma acuminatum of Buschke and Loewenstein developed on the penis of a one and a half year old baby body. In children, the penis is a more unusual site than the vulva or anus. The possibility of transmission from his family members or from sexual abuse could not be substantiated, and we were unable to trace the actual source of the infection. Although we did not find any evidence of cervical dysplasia in his mother, this does not rule out the possibility oflatent infection ofHPV type 16 on the cervix. We think, however, that the coexisting posthitis and balanitis, as well as the topical steroid treatment performed by the local physician, might at least have promoted its growth.
We thank Dr. A. Muranaka for the gynecological examination of the mother.
References I) Ive FA, Wilkinson DS: Disease of the umbilical,
2)
3)
4)
5)
peripheral and genital regions, in Rook A, Wilkinson DS, Ebling FJG, Champion RH, Burton JL (eds): Textbook of Dermatology, Vol. 3, Blackwell Scientific Publications, Oxford, 1986, pp 2163-2228. Gibson PE, Gardner SD, Best SJ: Human papilloma virus. Types in anogenital warts of children,] Med ViTol, 30: 142-145,1990. Aiba S, Rokugo M, Tagami H: Immunohistologic analysis of the phenomenon of spontaneous regression of numerous fiat warts, Cancer, 58: 1246-1251, 1986. Maki H, Saito S, Ibaraki T, et al: Use of universal and type-specific primers in the polymerase chain reaction for the detection and typing of genital human papillomavirus,jpn] Cancer &s, 82: 411-419, 1991. Fukui Y, Adachi A, Ohashi M: Giant condyloma acuminatum and analysis of human papillomavirus, Nishihihon] Dermatol, 51: 237-241, 1989. (in Japanese)
Giant Condyloma in a Baby Boy 6) Rock B, Naghashfar Z, Bernett N, et a1: Genital tract papillomavirus infection in children, Arch Dermatol, 122: 1129-1132,1986. 7) Kato T, Saijo S, Hatchome N, Tagami H: Detection of human papilloma virus type 16 in Bowenoid papulosis and invasive carcinoma occurring in the same
435
patient with a history of cervical carcinoma, Arch Dermatol, 124: 851-852, 1988. 8) Kettler AH, Rutledge M, Tschen JA, Buffone G: Detection of human papilloma virus in nongenital Bowen's disease by in situ DNA hybridization, Arch Dermatol, 126: 777-781, 1990.
Giant Condyloma Acuminatum in a Baby Boy Noriko Matsumura, Kumiko Kumasaka, Hideo Maki*, Osamu Yoshie* and Hachiro Tagami Abstract A giant condyloma acuminatum developed on the penis of a one and a half-year-oldJapanese boy in two months. The histological features of this tumor were compatible with those of ordinary condyloma acuminatum. Although we detected the presence of human papilloma virus (HPV) type 16 by using the polymerase chain reaction system, we could not rule out the possibility that this HPV was present concurrently with other HPV types that cause condyloma acuminatum. The lesion was successfully treated with cryotherapy and topical application of 5% fluorouracil ointment under occlusion
Key words: condyloma acuminatum; human papilloma virus; Buschke-Loewenstein tumor; previous inflammation
Introduction Condyloma acuminatum is a sexually transmitted disease usually occurring in adults (1). It may occur in children, often due to sexual abuse but penile involvement is extremely rare. It is caused by an infection by the human papilloma virus (HPV), mainly types 6 and 11 (1, 2). In adults, unusually large condyloma acuminatum always suggests the possibility of malignant conversion, i.e. giant condyloma acuminatum of Buschke-Loewenstein. We report here an unusually large condyloma acuminatum affecting a one and a half-year-old boy, from which HPV-16 was detected by polymerase chain reaction method.
Case Report A one and a half-year-old Japanese boy was hospitalized because of a huge verrucous tumor on the glans and foreskin of his penis that had grown rapidly within the previous 2 months. During that Received December 16, 1991; accepted for publication May 14, 1992. Department of Dermatology, Tohoku University School of Medicine, Sendai,Japan. *Shionogi Institute for Medical Science, 2-5-1 Mishima, Settsu-shi, Osaka 566,japan. Reprint requests to: Noriko Matsumura, M.D., Department of Dermatology, Tohoku University School of Medicine, Seiryo-machi I-I, Aoba-ku, Sendai 980,japan.
period, he had been treated by a local physician with topical application of 0.12% betamethasone valerate ointment under a diagnosis of posthitis and balanitis. No other members of his family had suffered from similar genital lesions or warts on other areas. There was no evidence of cervical dysplasia or bowenoid papulosis in his mother nor any clue as to possible sexual abuse by his neighbours. On physical examination, his glans penis and the distal part of the foreskin were totally covered with a hyperkeratotic verrucous tumor measuring 4.0 x 3.0 em in size (Fig. la, b). The thick horny material covering the foreskin sloughed off 5 days after the start of daily repeated cryotherapy, exposing a soft, papillomatous lesion. Thereafter 5% fluorouracil ointment was applied under occlusion for 8 days until the surface became eroded. For the lesion on the glans penis, the topical fluorouracil application was started directly and continued intermittently until 36 days later when the papillomatous tumor totally disappeared. No verrucous tumor was found in the urethra by endoscopic examination. After six months of intermittent treatment, the entire eruption disappeared (Fig. Ie). However six months later, one verrucous papule reappeared and required topical fluorouracil application and cryotherapy for eradication.
Histology A biopsy specimen from the involved foreskin
Giant Condyloma in a Baby Boy
433
Fig. Ia. A gigantic verrucous tumor of the glans and foreskin ofthe penis.
Fig. 1b. Higher magnification. Hyperkeratotic granular appearance.
Fig. Ie. Clinical appearance 6 months after the start of treatment. showed thick parakeratotic stratum corneum covering acanthotic epidermis with numerous vacuolated cells in the upper layer (Fig. 2). HPV capsid protein antigen could not be demonstrated by immunohistological staining performed as reported in an earlier paper (3).
Detection of Human Papilloma VIrUS Frozen tumor tissue of the patient was used for DNA extraction. The details of our polymerase chain reaction (PCR) systems, including specific primers and probes for HPV-I6 and -18 synthesized from the E7 open reading frames were described elsewhere (4). By this method, an amplification product derived from HPV-I6, but not from HPV-I8, was detected in the DNA from the lesional tissue of the patient (Fig. 3). The amplified sequence of DNA was further confirmed to be similar to the corresponding region of HPV-I6 sequence after restriction endonuclease digestion as reported previously (4).
Fig. 2. Histopathology of the verrucous tumor. There was parakeratosis and acanthosis of the epidermis associated with numerous vacuolated cells (HE, x80).
434
Matsumura et al
b
a M
2 3 N
M
2 3 N
.. Fig. 3. PCR for the detection of HPV. PCR amplifications were carried out with the primers specific for HPV-16 (a) and for HPV18 (b). Amplification products were detected by polyacrylamide gel electrophoresis and ethium bromide staining. Lanes are as follows. M: PhiX-174 DNA digested with HaeIII, 0.25 J1.g; 1: DNA from the patient, 500 ng; 2: CaSki DNA, 500 ng (a human cervical cancer cell line with integrated HPV-16); 3: HeLa DNA, 500 ng (a human cevical cancer cell line with integrated HPV-18); N: no DNA. The arrows indicate the expected position of the amplification products.
Giant condyloma of adults caused by HPV types 6 and 11 sometimes shows locally aggressive behavior and tends to recur even after apparently adequate surgery (1). In contrast, in our case, the huge verrucous tumor showed a rather good response to topical fluorouracil application, mitigating the possibility of malignancy. The causative virus types for condyloma acuminatum are most often HPV types 6 and 11, but occasionally infections by HPV type 16 or 18 are reported (2, 6). HPV-16 and 18 are closely related to maJignant diseases such as cervical cancer, Bowen's disease and anogenital cancer (7, 8). Although we could not test for HPV type 6 and 11, DNA for HPV type 16 was detected in the tumor tissue by using peR system for HPV-16 and 18 that has become recently available to us. Unfortunately we could not continue further analysis of HPV because of exhaustion of the specimen. Because the histological appearance of the present case was far from those so far reported in HPV-16 infections, which consist of bowenoid anaplastic features, we think that the possibility of a mixed HPV infection is highly likely.
Acknowledgments Discussion Because condyloma acuminatum is usually sexually transmitted, it is uncommon in children (1). Our case is unique in that a huge verrucous tumor, resembling the giant condyloma acuminatum of Buschke and Loewenstein developed on the penis of a one and a half year old baby body. In children, the penis is a more unusual site than the vulva or anus. The possibility of transmission from his family members or from sexual abuse could not be substantiated, and we were unable to trace the actual source of the infection. Although we did not find any evidence of cervical dysplasia in his mother, this does not rule out the possibility oflatent infection ofHPV type 16 on the cervix. We think, however, that the coexisting posthitis and balanitis, as well as the topical steroid treatment performed by the local physician, might at least have promoted its growth.
We thank Dr. A. Muranaka for the gynecological examination of the mother.
References I) Ive FA, Wilkinson DS: Disease of the umbilical,
2)
3)
4)
5)
peripheral and genital regions, in Rook A, Wilkinson DS, Ebling FJG, Champion RH, Burton JL (eds): Textbook of Dermatology, Vol. 3, Blackwell Scientific Publications, Oxford, 1986, pp 2163-2228. Gibson PE, Gardner SD, Best SJ: Human papilloma virus. Types in anogenital warts of children,] Med ViTol, 30: 142-145,1990. Aiba S, Rokugo M, Tagami H: Immunohistologic analysis of the phenomenon of spontaneous regression of numerous fiat warts, Cancer, 58: 1246-1251, 1986. Maki H, Saito S, Ibaraki T, et al: Use of universal and type-specific primers in the polymerase chain reaction for the detection and typing of genital human papillomavirus,jpn] Cancer &s, 82: 411-419, 1991. Fukui Y, Adachi A, Ohashi M: Giant condyloma acuminatum and analysis of human papillomavirus, Nishihihon] Dermatol, 51: 237-241, 1989. (in Japanese)
Giant Condyloma in a Baby Boy 6) Rock B, Naghashfar Z, Bernett N, et a1: Genital tract papillomavirus infection in children, Arch Dermatol, 122: 1129-1132,1986. 7) Kato T, Saijo S, Hatchome N, Tagami H: Detection of human papilloma virus type 16 in Bowenoid papulosis and invasive carcinoma occurring in the same
435
patient with a history of cervical carcinoma, Arch Dermatol, 124: 851-852, 1988. 8) Kettler AH, Rutledge M, Tschen JA, Buffone G: Detection of human papilloma virus in nongenital Bowen's disease by in situ DNA hybridization, Arch Dermatol, 126: 777-781, 1990.
