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Otorhinolaryngological aspects of Xeroderma pigmentosum
Auris Nasus Larynx 26 (1999) 457 – 466 www.elsevier.com/locate/anl
Otorhinolaryngological aspects of Xeroderma pigmentosum Ahmet Kutluhan a,*, Mehmet Bekereciog˘lu b, Ercihan Gu¨ney c, Ahmet Metin d b
a Department of Otorhinolaryngology, Medical School, Yu¨zu¨ncu¨ Yil Uni6ersity, Van, Turkey Department of Plastic and Reconstructi6e Surgery, Medical School, Yu¨zu¨ncu¨ Yil Uni6ersity, Van, Turkey c Department of Otorhinolaryngology, Medical School, Erciyes Uni6ersity, Kayseri, Turkey d Department of Dermatology, Medical School, Yu¨zu¨ncu¨ Yil Uni6ersity, Van, Turkey
Received 14 July 1998; received in revised form 22 October 1998; accepted 20 November 1998
Abstract Objecti6e: to evaluate the probable presence of otorhinolaryngological pathology accompanied by head and neck region skin findings in patients with Xeroderma pigmentosum. Methods: a total of 19 patients with Xeroderma pigmentosum were investigated for otorhinolaryngological findings. The patients gave their anamnesis and underwent physical examination, audiological tests and endoscopic examination. Results: various malignancies developed in 14 patients on the sun-exposed areas of the head and neck region. Multiple malignancies were found in six of them. There was no other pathological condition secondary to this rare clinical entity. Conclusion: Xeroderma pigmentosum causes skin lesions. Some otolaryngological findings such as rhinitis, sinusitis etc. were thought to be coincidental. © 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Xeroderma pigmentosum; Ear; Nose; Larynx; Head and neck
1. Introduction Xeroderma pigmentosum (XP) is a relatively rare, autosomal recessive disorder characterized by photophobia, severe sun sensitivity, pigmentary changes and the early development of ectodermal and mesodermal tumors. The frequency is about 1 in 250 000 in the United States and Europe but is considerably higher in Japan (1 in 40 000) and Egypt [1]. In a literature survey of 830
* Corresponding author. Present address: KBB Anabilim Dali, Yu¨zu¨ncu¨ Yil U8 niversitesi Tip Faku¨ltesi, TR-65200 Van, Turkey. Tel.: + 90-432-2168348; fax: +90-432-2169519.
patients, there were almost equal numbers of males and females [2]. Xeroderma pigmentosum is a precancerous condition which begins in early childhood. Within a few years of the onset of verrucous and keratotic lesions, histologically similar to those observed in solar keratoses, malignant lesions appear and develop. More than 50% of patients with XP develop cutaneous malignancy by the age of 14 years [3]. Because most manifestations of XP are related to ultraviolet exposure, the ocular and oral structures can also be affected in XP patients. Oral abnormalities are characterized by the loss of skin elasticity and oral stenosis. Oral cavity carcinoma
0385-8146/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 8 5 - 8 1 4 6 ( 9 9 ) 0 0 0 2 7 - 9
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A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
involving the tip of the tongue, gingiva and palate have been described [3]. Another finding, interesting to an otorhinolaryngologist in XP patients is sensorineural hearing loss probably resulting from progressive neurologic degeneration. The aforementioned clinical abnormalities reported in the literature and in a rather large number of our XP patients prompted us to investigate the otorhinolaryngological findings of this rare clinical entity.
2. Patients and methods Since 1994, 19 patients with XP have been diagnosed at the hospital of Yuzuncu Yil University. A team was formed with the contributions of an otorhinolaryngologist, a plastic surgeon and a dermatologist. A special card was assigned to each patient and the patient’s age, sex, country, consanguinity between parents and patients, onset of the disease, period of skin lesions, histological diagnosis of skin lesions and follow-up data were noted. Routine physical examination was followed by complete ear, nose and throat (ENT) examination, panendoscopic examinations and audiologic investigations. Plain radiologic images of the thorax, paranasal sinuses and mastoid bones were obtained when necessary. Biopsies were taken from all subsequently developed skin lesions of the head and neck region. Panendoscopic examination included nasal endoscopy, nasopharyngoscopy, sinoscopy, laryngoscopy, bronchoscopy and oesophagoscopy. Each suspicious mucosa was investigated histopathologically. Hearing function of the patients was evaluated with pure-tone audiometry (PTO), acoustic impedancemeter (AI) and auditory-evoked brain stem response audiometry (ABSR).
3. Results Of the patients, 12 were male and seven were female. Their age ranged between 3 and 27 years (mean, 13.5 years). The minimum and maximum ages at onset of the XP were 5 months and 8
years, respectively (median, 3.6 years). The patients are seen in as a group in Fig. 1. Consanguinity between parents was present in all patients except one. Various malignancies developed in 14 patients. Of these, 11 developed their first skin malignancy before the age of 14 (% 78). Multiple malignant lesions were found in six of them. Squamous cell carcinoma (SCC) was the most frequent type (12 lesions) followed by basal cell carcinoma (BCC) (7 lesions). Malignant melanoma (MM) was encountered in only one patient. The duration of these lesions was less than a year in eight patients and ranged between 1 and 25 years (median, 9.3 years) in others (Table 1). A total of three patients had lip malignancies, of which two had SCC and one had MM. Other skin lesions determined on histopathological studies were actinic keratosis (16), skin atrophy (15), hipo-hyperpigmentation (19), telangiectasia (14), angioma (1), lentigo maligna (1) and atypic fibroxanthoma (2). The findings of ENT examinations are given on Table 2. All patients had normal external ears and tympanic membranes except one that could not be examined because of auricular lesion (case 3). There are minimal sclerotic and calcer plaques in some cases. Sinusitis was diagnosed in three patients and chronic rhinitis in one patient. Other regions of oral cavity out of lips, oropharynx, nasopharynx, hypopharynx, larynx, oesophagus and main bronchial tubes were assessed as normal. Any internal malignancy could not be established in these regions. Audiologic investigations were carried out on 18 patients. Audiologic investigations could not be performed on patient number three because he died of disease soon after. It was also impossible to perform these investigations on case six because of auricular lesion. Hearing test results are given on Table 3. PTO performed on the 29 ears of 15 patients with XP showed normal hearing levels, except in one where slightly conductive type hearing loss was determined. A small group of four patients were noncooperative to PTO (cases 1, 2, 6 and 7). Stapedial reflexes were positive in all of these ears and none of the ears tested showed a sensorineural hearing loss.
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
Fig. 1. Facial appearance of the patients.
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A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
Fig. 1. (Continued)
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
Fig. 1. (Continued)
461
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A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
Fig. 1. (Continued)
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
4. Discussion The exact genetic defect in XP appears to be related to the DNA repair system which is responsible for detecting and excising segments of DNA that have been damaged. Ultraviolet radiation seems to be the most prominent among a variety of environmental causes leading to DNA damage. The initial manifestation of XP is an abnormal response to sunlight exposure. Usually, there is a delayed onset of erythema and prolonged response. Other early signs are freckling and pigment abnormalities of sun-exposed areas. More
463
than 50% of patients with XP develop cutaneous malignancy by the age of 14 and the median age for development of the skin malignancy is 8 years [3]. The most common types are SCC and BCC with a predominance of SCC and 97% of these cancers occur on the face, head, or neck. Melanoma was reported in 5% of the cases and was estimated at a rate of 2000 times greater than that expected for the general population. Moreover most XP patients develop two or more skin malignancies [2]. Ultraviolet induced head and neck malignancies were found in 14 out of 19 XP patients in our
Fig. 1. (Continued)
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
464
Table 1 Patient characteristics and their skin lesionsa Cases
Name
Age
Sex
Age at onset of XP (years)
Age at first skin malignancy noted
Types of malignancy
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
RG HG FG YA AA As¸ IS KS AS VS FB VD BD MD FD ND MA SS EE
7 3 16 8 16 15 7 12 20 22 27 6 12 14 6 16 17 9 23
M F M M F M M M M M F F M F F F M M M
1 0.5 4 3 4 3 3 5 6 7 1 4 7 5 4 3 1 1 8
6,5 3 13 7.5 16 6 – 1 – – 2 6 11 13 – – 16.5 9 21
SCC, BCC SCC SCC, BCC SCC, BBC SCC, BCC SCC –– BCC –– –– SCC SCC BCC, MM SCC ––– ––– SCC SCC SCC, BCC
a
M, male; F, female; SCC, squamous cell carcinoma; BCC, basal cell carcinoma; MM, malignant melanoma.
series (74%). Secondary malignant lesions developed in six of these patients. In total, 20 malignant lesions were determined in 14 XP patients. Of these, 17 malignant lesions were on the head and neck skin and three were located on the lips. The malignant lesions were 12 SCC, seven BCC and one MM. Most of the patients (78%) developed their first carcinoma before the age of 14. On the other hand, several skin disorders affecting the sun-exposed skin of the head and neck areas, such as actinic keratosis and lentigo maligna encountered in our patients, exhibit a natural history for the development of invasive carcinoma and malignant melanoma. Although most skin cancers are amenable to cure with early diagnosis and appropriate treatment, skin cancers associated with XP represent the most relentless, deforming and ultimately lethal skin cancers. Management of these cancers is more complex than dealing with standard skin tumors. The clinician must realise that all skin of the face and the entire body has the potential to develop cancer. Therefore, both conservative resection or ideally Mohs technique and conservative reconstruction should be considered. Primary
healing or skin grafting appears to be more useful and best satisfies the patient’s needs. Early recognition of the disease, ultraviolet shielding and life-long periodic control of skin for development of malignancies are essential. Color photos of the patient’s cutaneous surface are helpful in following changes of the skin lesions [3]. In XP patients the incidence of cancer of the internal organs was higher than in normal individuals [4]. In a study of Kraemer et al [5] oral cavity carcinomas including the tip of the tongue, the gingiva and the palate have been documented. The frequency of nonskin neoplasms has been reported to be 10- to 20-fold higher in XP patients than in normal subjects by the authors. This incidence was found to be 24 times greater for XP patients over the age of 40 [6]. In our series malignant lip lesions were determined in three patients as oral cavity tumors. Of the three, two were SCC and one was MM (Table 2). All of these lesions were considered as ultraviolet-induced malignancies. Other regions of the oral cavity and upper aerodigestive system were assesed as normal. Any internal malignancy could not be determined in our study.
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
A subgroup of patients with XP exhibit neurological abnormalities. Impaired hearing has become recognised as being associated with this disease. Longridge [7] studied a pair of siblings and came to the conclusion that the disorder was central instead of cochlear in origin. He based his opinion on the absence of stapedial reflexes and tone decay. Kenyon et al. [8] reported three cases on whom detailed neuro-otological investigations had been carried out. These patients had widely differing ages (16, 46 and 57 years) and all of them showed recruiting hearing loss. ABSR was completely normal in one patient and only mildly deranged in another, strongly suggesting that the origin of the deafness would be more peripheral in origin than central. Hearing loss was documented in 28 of 830 XP cases collected by Kraemer et al. [2]. We determined only a slightly conductive hearing loss in one case (case 15). However, this hearing loss appeared as an otitis sequelae, rather than as a result of XP. Normal ABSR results
showed that any pathology of the acoustic nerve and brain stem hearing ways secondary to the XP had not developed. Rhinologic findings of our XP patients were also similar to those of the normal population. The incidence of sinusitis varies widely in the general population, however, it is estimated that 0.5% of all common colds progress to sinusitis. On the other hand, 8% of people who are asymptomatic and 34% of people with acute rhinitis have abnormal X-rays [9]. In our study, sinusitis was diagnosed in three, acute rhinitis in two and chronic rhinitis in one patient (Table 2). In conclusion, otorhinolaryngological screening of the patients with XP did not demonstrate any abnormalities other than skin malignancies and premalignant skin lesions. The lack of the other pathological conditions described in the literature, such as internal malignancies and hearing loss, may be related to the lower ages of our patients. Considering the risk that both development of
Table 2 Evaluation of ENT findingsa n
Ear
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 a
R
L
N N * N N N N N N N N N N N N N N N N
N N N N N N N N N N N N N N N N N N N
Nose
Throat
Otorhinolaryngological diagnosis
Seropurulent discharge Serous discharge * Purulent discharge N * Purulent discharge N N Septal deviation N N Serous discharge Septal deviation N N N Serous discharge Septal deviation
N N Upper lip lesion Tonsillar hypertrophy N * N N N N N N Lower lip lesion Tonsillar hypertrophy N N Lower lip lesion N N
Sinusitis Chronic rhinitis Epidermoid carcinoma (upper lip) Sinusitis, chronic tonsillitis N Invasive epidermoid carcinoma (right check) Sinopharyngitis N N Septal deviation N N Rhinitis, malignant melanoma (lower lip) Chronic tonsillitis N N Epidermoid carsinoma (lower lip) Rhinitis Septal deviation
R, Right; L, Left; N, Normal. * These patients could not be examined.
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A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
466
Table 3 Evaluation of hearing function testsa Odiometer (dB) n 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 a
R –––– ––––– ––––– 15/10 20/13 ––––– –––– 12/7 13/13 18/15 20/14 16/8 18/10 12/8 30/10 15/10 18/12 14/8 18/4
Tympanogram (dapa) L ––––– ––––––– ––––– 18/8 18/10 22/14 ––––– 15/6 15/12 15/15 18/16 10/0 18/12 18/18 22/10 18/15 15/13 18/14 16/3
R −200 N ––– −15 0 ––– 0 0 −5 0 0 0 0 0 −50 0 0 0 0
ABSR L −200 N ––– −15 0 0 0 0 −35 0 0 0 0 0 −20 0 0 0 0
R N N –––– N N ––––– N N N N N N N N N N N N N
L N N ––––– N N N N N N N N N N N N N N N N
ABSR, auditory-evoked brain stem response; R, right; L, left; N, normal.
new skin malignancies and multiplication of these malignancies will also increase with age, we suggest that life-long regular follow-up of the XP patients is mandatory.
References [1] Cleaver EJ, Kraemer KH. Xeroderma pigmentosum. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic Basis of Inherited Disease, 6th Edition. New York: Mcgraw-Hill, 1989:2949–71. [2] Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum: cutaneous, ocular and neurologic abnormalities in 830 published cases. Arch Dermatol 1987;123:241–50. [3] Shumrick KA, Coldiron B. Genetic syndromes associated with skin cancer. Otolaryngol Clin North Am 1993;26:117 – 38.
.
[4] Kondo S, Fukuro S, Nishioka K, Satoh Y. Xeroderma pigmentosum: recent clinical and photobiological aspects. J Dermatol 1992;19:690 – 5. [5] Kraemer KH, Lee MM, Scotto J. DNA repair protects against cutaneous and internal neoplasia: evidence from Xeroderma pigmentosum. Carcinogenesis 1984;5:511 – 4. [6] Mamada A, Miura K, Tsunoda K, Hirose I, Furuya M, Kondo S. A Xeroderma pigmentosum variant associated with multiple skin cancers and a lung cancer. Dermatology 1992;184:177 – 81. [7] Longridge NS. Audiological assessment of deafness associated Xeroderma pigmentosa. J Laryngol Otol 1976;90:539 – 51. [8] Kenyon GS, Booth JB, Prasher DK, Rudge P. Neuro-otological abnormalities in Xeroderma pigmentosum with particular reference to deafness. Brain 1985;108:771 – 84. [9] White JA. Paranasal sinus infections. In: Ballenger JJ, editor. Diseases of The Nose, Throat, Ear, Head and Neck, 14th Edition. Philadelphia: Lea and Febiger, 1991:184 – 202.
Otorhinolaryngological aspects of Xeroderma pigmentosum Ahmet Kutluhan a,*, Mehmet Bekereciog˘lu b, Ercihan Gu¨ney c, Ahmet Metin d b
a Department of Otorhinolaryngology, Medical School, Yu¨zu¨ncu¨ Yil Uni6ersity, Van, Turkey Department of Plastic and Reconstructi6e Surgery, Medical School, Yu¨zu¨ncu¨ Yil Uni6ersity, Van, Turkey c Department of Otorhinolaryngology, Medical School, Erciyes Uni6ersity, Kayseri, Turkey d Department of Dermatology, Medical School, Yu¨zu¨ncu¨ Yil Uni6ersity, Van, Turkey
Received 14 July 1998; received in revised form 22 October 1998; accepted 20 November 1998
Abstract Objecti6e: to evaluate the probable presence of otorhinolaryngological pathology accompanied by head and neck region skin findings in patients with Xeroderma pigmentosum. Methods: a total of 19 patients with Xeroderma pigmentosum were investigated for otorhinolaryngological findings. The patients gave their anamnesis and underwent physical examination, audiological tests and endoscopic examination. Results: various malignancies developed in 14 patients on the sun-exposed areas of the head and neck region. Multiple malignancies were found in six of them. There was no other pathological condition secondary to this rare clinical entity. Conclusion: Xeroderma pigmentosum causes skin lesions. Some otolaryngological findings such as rhinitis, sinusitis etc. were thought to be coincidental. © 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Xeroderma pigmentosum; Ear; Nose; Larynx; Head and neck
1. Introduction Xeroderma pigmentosum (XP) is a relatively rare, autosomal recessive disorder characterized by photophobia, severe sun sensitivity, pigmentary changes and the early development of ectodermal and mesodermal tumors. The frequency is about 1 in 250 000 in the United States and Europe but is considerably higher in Japan (1 in 40 000) and Egypt [1]. In a literature survey of 830
* Corresponding author. Present address: KBB Anabilim Dali, Yu¨zu¨ncu¨ Yil U8 niversitesi Tip Faku¨ltesi, TR-65200 Van, Turkey. Tel.: + 90-432-2168348; fax: +90-432-2169519.
patients, there were almost equal numbers of males and females [2]. Xeroderma pigmentosum is a precancerous condition which begins in early childhood. Within a few years of the onset of verrucous and keratotic lesions, histologically similar to those observed in solar keratoses, malignant lesions appear and develop. More than 50% of patients with XP develop cutaneous malignancy by the age of 14 years [3]. Because most manifestations of XP are related to ultraviolet exposure, the ocular and oral structures can also be affected in XP patients. Oral abnormalities are characterized by the loss of skin elasticity and oral stenosis. Oral cavity carcinoma
0385-8146/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 8 5 - 8 1 4 6 ( 9 9 ) 0 0 0 2 7 - 9
458
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
involving the tip of the tongue, gingiva and palate have been described [3]. Another finding, interesting to an otorhinolaryngologist in XP patients is sensorineural hearing loss probably resulting from progressive neurologic degeneration. The aforementioned clinical abnormalities reported in the literature and in a rather large number of our XP patients prompted us to investigate the otorhinolaryngological findings of this rare clinical entity.
2. Patients and methods Since 1994, 19 patients with XP have been diagnosed at the hospital of Yuzuncu Yil University. A team was formed with the contributions of an otorhinolaryngologist, a plastic surgeon and a dermatologist. A special card was assigned to each patient and the patient’s age, sex, country, consanguinity between parents and patients, onset of the disease, period of skin lesions, histological diagnosis of skin lesions and follow-up data were noted. Routine physical examination was followed by complete ear, nose and throat (ENT) examination, panendoscopic examinations and audiologic investigations. Plain radiologic images of the thorax, paranasal sinuses and mastoid bones were obtained when necessary. Biopsies were taken from all subsequently developed skin lesions of the head and neck region. Panendoscopic examination included nasal endoscopy, nasopharyngoscopy, sinoscopy, laryngoscopy, bronchoscopy and oesophagoscopy. Each suspicious mucosa was investigated histopathologically. Hearing function of the patients was evaluated with pure-tone audiometry (PTO), acoustic impedancemeter (AI) and auditory-evoked brain stem response audiometry (ABSR).
3. Results Of the patients, 12 were male and seven were female. Their age ranged between 3 and 27 years (mean, 13.5 years). The minimum and maximum ages at onset of the XP were 5 months and 8
years, respectively (median, 3.6 years). The patients are seen in as a group in Fig. 1. Consanguinity between parents was present in all patients except one. Various malignancies developed in 14 patients. Of these, 11 developed their first skin malignancy before the age of 14 (% 78). Multiple malignant lesions were found in six of them. Squamous cell carcinoma (SCC) was the most frequent type (12 lesions) followed by basal cell carcinoma (BCC) (7 lesions). Malignant melanoma (MM) was encountered in only one patient. The duration of these lesions was less than a year in eight patients and ranged between 1 and 25 years (median, 9.3 years) in others (Table 1). A total of three patients had lip malignancies, of which two had SCC and one had MM. Other skin lesions determined on histopathological studies were actinic keratosis (16), skin atrophy (15), hipo-hyperpigmentation (19), telangiectasia (14), angioma (1), lentigo maligna (1) and atypic fibroxanthoma (2). The findings of ENT examinations are given on Table 2. All patients had normal external ears and tympanic membranes except one that could not be examined because of auricular lesion (case 3). There are minimal sclerotic and calcer plaques in some cases. Sinusitis was diagnosed in three patients and chronic rhinitis in one patient. Other regions of oral cavity out of lips, oropharynx, nasopharynx, hypopharynx, larynx, oesophagus and main bronchial tubes were assessed as normal. Any internal malignancy could not be established in these regions. Audiologic investigations were carried out on 18 patients. Audiologic investigations could not be performed on patient number three because he died of disease soon after. It was also impossible to perform these investigations on case six because of auricular lesion. Hearing test results are given on Table 3. PTO performed on the 29 ears of 15 patients with XP showed normal hearing levels, except in one where slightly conductive type hearing loss was determined. A small group of four patients were noncooperative to PTO (cases 1, 2, 6 and 7). Stapedial reflexes were positive in all of these ears and none of the ears tested showed a sensorineural hearing loss.
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
Fig. 1. Facial appearance of the patients.
459
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A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
Fig. 1. (Continued)
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
Fig. 1. (Continued)
461
462
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
Fig. 1. (Continued)
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
4. Discussion The exact genetic defect in XP appears to be related to the DNA repair system which is responsible for detecting and excising segments of DNA that have been damaged. Ultraviolet radiation seems to be the most prominent among a variety of environmental causes leading to DNA damage. The initial manifestation of XP is an abnormal response to sunlight exposure. Usually, there is a delayed onset of erythema and prolonged response. Other early signs are freckling and pigment abnormalities of sun-exposed areas. More
463
than 50% of patients with XP develop cutaneous malignancy by the age of 14 and the median age for development of the skin malignancy is 8 years [3]. The most common types are SCC and BCC with a predominance of SCC and 97% of these cancers occur on the face, head, or neck. Melanoma was reported in 5% of the cases and was estimated at a rate of 2000 times greater than that expected for the general population. Moreover most XP patients develop two or more skin malignancies [2]. Ultraviolet induced head and neck malignancies were found in 14 out of 19 XP patients in our
Fig. 1. (Continued)
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
464
Table 1 Patient characteristics and their skin lesionsa Cases
Name
Age
Sex
Age at onset of XP (years)
Age at first skin malignancy noted
Types of malignancy
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
RG HG FG YA AA As¸ IS KS AS VS FB VD BD MD FD ND MA SS EE
7 3 16 8 16 15 7 12 20 22 27 6 12 14 6 16 17 9 23
M F M M F M M M M M F F M F F F M M M
1 0.5 4 3 4 3 3 5 6 7 1 4 7 5 4 3 1 1 8
6,5 3 13 7.5 16 6 – 1 – – 2 6 11 13 – – 16.5 9 21
SCC, BCC SCC SCC, BCC SCC, BBC SCC, BCC SCC –– BCC –– –– SCC SCC BCC, MM SCC ––– ––– SCC SCC SCC, BCC
a
M, male; F, female; SCC, squamous cell carcinoma; BCC, basal cell carcinoma; MM, malignant melanoma.
series (74%). Secondary malignant lesions developed in six of these patients. In total, 20 malignant lesions were determined in 14 XP patients. Of these, 17 malignant lesions were on the head and neck skin and three were located on the lips. The malignant lesions were 12 SCC, seven BCC and one MM. Most of the patients (78%) developed their first carcinoma before the age of 14. On the other hand, several skin disorders affecting the sun-exposed skin of the head and neck areas, such as actinic keratosis and lentigo maligna encountered in our patients, exhibit a natural history for the development of invasive carcinoma and malignant melanoma. Although most skin cancers are amenable to cure with early diagnosis and appropriate treatment, skin cancers associated with XP represent the most relentless, deforming and ultimately lethal skin cancers. Management of these cancers is more complex than dealing with standard skin tumors. The clinician must realise that all skin of the face and the entire body has the potential to develop cancer. Therefore, both conservative resection or ideally Mohs technique and conservative reconstruction should be considered. Primary
healing or skin grafting appears to be more useful and best satisfies the patient’s needs. Early recognition of the disease, ultraviolet shielding and life-long periodic control of skin for development of malignancies are essential. Color photos of the patient’s cutaneous surface are helpful in following changes of the skin lesions [3]. In XP patients the incidence of cancer of the internal organs was higher than in normal individuals [4]. In a study of Kraemer et al [5] oral cavity carcinomas including the tip of the tongue, the gingiva and the palate have been documented. The frequency of nonskin neoplasms has been reported to be 10- to 20-fold higher in XP patients than in normal subjects by the authors. This incidence was found to be 24 times greater for XP patients over the age of 40 [6]. In our series malignant lip lesions were determined in three patients as oral cavity tumors. Of the three, two were SCC and one was MM (Table 2). All of these lesions were considered as ultraviolet-induced malignancies. Other regions of the oral cavity and upper aerodigestive system were assesed as normal. Any internal malignancy could not be determined in our study.
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
A subgroup of patients with XP exhibit neurological abnormalities. Impaired hearing has become recognised as being associated with this disease. Longridge [7] studied a pair of siblings and came to the conclusion that the disorder was central instead of cochlear in origin. He based his opinion on the absence of stapedial reflexes and tone decay. Kenyon et al. [8] reported three cases on whom detailed neuro-otological investigations had been carried out. These patients had widely differing ages (16, 46 and 57 years) and all of them showed recruiting hearing loss. ABSR was completely normal in one patient and only mildly deranged in another, strongly suggesting that the origin of the deafness would be more peripheral in origin than central. Hearing loss was documented in 28 of 830 XP cases collected by Kraemer et al. [2]. We determined only a slightly conductive hearing loss in one case (case 15). However, this hearing loss appeared as an otitis sequelae, rather than as a result of XP. Normal ABSR results
showed that any pathology of the acoustic nerve and brain stem hearing ways secondary to the XP had not developed. Rhinologic findings of our XP patients were also similar to those of the normal population. The incidence of sinusitis varies widely in the general population, however, it is estimated that 0.5% of all common colds progress to sinusitis. On the other hand, 8% of people who are asymptomatic and 34% of people with acute rhinitis have abnormal X-rays [9]. In our study, sinusitis was diagnosed in three, acute rhinitis in two and chronic rhinitis in one patient (Table 2). In conclusion, otorhinolaryngological screening of the patients with XP did not demonstrate any abnormalities other than skin malignancies and premalignant skin lesions. The lack of the other pathological conditions described in the literature, such as internal malignancies and hearing loss, may be related to the lower ages of our patients. Considering the risk that both development of
Table 2 Evaluation of ENT findingsa n
Ear
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 a
R
L
N N * N N N N N N N N N N N N N N N N
N N N N N N N N N N N N N N N N N N N
Nose
Throat
Otorhinolaryngological diagnosis
Seropurulent discharge Serous discharge * Purulent discharge N * Purulent discharge N N Septal deviation N N Serous discharge Septal deviation N N N Serous discharge Septal deviation
N N Upper lip lesion Tonsillar hypertrophy N * N N N N N N Lower lip lesion Tonsillar hypertrophy N N Lower lip lesion N N
Sinusitis Chronic rhinitis Epidermoid carcinoma (upper lip) Sinusitis, chronic tonsillitis N Invasive epidermoid carcinoma (right check) Sinopharyngitis N N Septal deviation N N Rhinitis, malignant melanoma (lower lip) Chronic tonsillitis N N Epidermoid carsinoma (lower lip) Rhinitis Septal deviation
R, Right; L, Left; N, Normal. * These patients could not be examined.
465
A. Kutluhan et al. / Auris Nasus Larynx 26 (1999) 457–466
466
Table 3 Evaluation of hearing function testsa Odiometer (dB) n 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 a
R –––– ––––– ––––– 15/10 20/13 ––––– –––– 12/7 13/13 18/15 20/14 16/8 18/10 12/8 30/10 15/10 18/12 14/8 18/4
Tympanogram (dapa) L ––––– ––––––– ––––– 18/8 18/10 22/14 ––––– 15/6 15/12 15/15 18/16 10/0 18/12 18/18 22/10 18/15 15/13 18/14 16/3
R −200 N ––– −15 0 ––– 0 0 −5 0 0 0 0 0 −50 0 0 0 0
ABSR L −200 N ––– −15 0 0 0 0 −35 0 0 0 0 0 −20 0 0 0 0
R N N –––– N N ––––– N N N N N N N N N N N N N
L N N ––––– N N N N N N N N N N N N N N N N
ABSR, auditory-evoked brain stem response; R, right; L, left; N, normal.
new skin malignancies and multiplication of these malignancies will also increase with age, we suggest that life-long regular follow-up of the XP patients is mandatory.
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