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Is the association between balanitis xerotica obliterans and penile carcinoma underestimated?

PETER PIETRZAK

Departments of Urology and Cellular Pathology, St George’s Hospital, Tooting, London, UK

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PAUL HADWAY

Departments of Urology and Cellular Pathology, St George’s Hospital, Tooting, London, UK

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CATHY M. CORBISHLEY

Departments of Urology and Cellular Pathology, St George’s Hospital, Tooting, London, UK

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NICHOLAS A. WATKIN

Departments of Urology and Cellular Pathology, St George’s Hospital, Tooting, London, UK

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First published: 08 June 2006
Cited by: 41
Nicholas Watkin, Department of Urology, St George’s Hospital, Blackshaw Road, Tooting, London SW17 0QT, UK. e‐mail: nick.watkins@stgeorges.nhs.uk

Abstract

OBJECTIVE

To determine the incidence of balanitis xerotica obliterans (BXO) in a consecutive series of penile carcinomas in one centre, as BXO is a common penile disease that usually involves the prepuce and glans, and there have been sporadic case reports of the association between BXO and penile carcinoma, although it is uncertain if there is a specific causal relationship.

PATIENTS AND METHODS

The reported incidence of penile carcinoma in patients with BXO is 2.6–5.8%, leading some to advocate circumcision in all cases, with close follow‐up in those with persistent glanular disease. We prospectively analysed all cases of penile cancer referred to the unit over a 54‐month period, to determine the prevalence of BXO.

RESULTS

In all, 155 patients with penile malignancy were reviewed, 44 of whom had BXO (28%). This group included 34 men with squamous cell carcinoma and 10 with carcinoma in situ; in 39, BXO and malignancy presented synchronously. In three other cases, cancer occurred in the background of chronic persistent BXO; in two cases penile cancer was truly metachronous. The tumours with associated BXO tended to be of lower stage and grade, and the patients presented when younger, but this was not statistically significant.

CONCLUSION

A significant proportion of patients with penile malignancy have a histological diagnosis of BXO. We think that patients presenting with long‐standing BXO and those in whom BXO has not resolved after circumcision warrant biopsies and a careful follow‐up.

Abbreviations

  • BXO
  • balanitis xerotica obliterans
  • LS
  • lichen sclerosus
  • SCC
  • squamous cell carcinoma
  • INTRODUCTION

    Balanitis xerotica obliterans (BXO) or lichen sclerosus (LS) is a chronic inflammatory skin condition of unknown cause. Stuhmer first described LS of the glans and prepuce in 1928, referring to it as BXO, based on its pathological appearance [1]. Since then several sporadic case reports have suggested an association between BXO and penile carcinoma [2-4]. Two recently published series highlighted this conspicuous relationship, reporting a 2.6–5.8% incidence of penile carcinomas in patients with BXO [5, 6]. Unfortunately the incidence of BXO in the general population is unknown, and therefore it is not possible to say whether having BXO confers a greater than normal risk of developing penile carcinoma. However, there is a well documented association between vulval LS and squamous cell carcinoma (SCC) [7]. The relative rarity of penile carcinomas, and probable long lag periods, have made establishing a link between BXO and penile carcinoma difficult. Herein we describe a contemporary series of patients with penile carcinoma in whom the incidence of BXO was higher than expected.

    PATIENTS AND METHODS

    Over a period of 54 months, 155 patients were referred to our unit for the management of penile carcinoma. A specialist uropathologist reviewed all histological specimens, including biopsy material obtained from referring centres. The diagnosis of BXO (LS) was made on the presence of the following criteria: thinning and orthokeratotic hyperkeratosis of epithelium; basal cell layer showing degeneration, sometimes with cleft formation; a band‐like infiltrate of lymphocytes and plasma cells in the dermis; and hyalinization of collagen in the upper dermis. Patient records were reviewed for previous history of BXO. The Mann–Whitney U‐test and chi‐squared tests were used to compare the grade and stage of penile carcinoma with and with no associated BXO.

    RESULTS

    Of the 155 cases referred, 121 were SCC and 34 were carcinoma in situ; 44 (28%) patients had associated BXO. In the patients who had associated BXO the mode of presentation of the tumour was: 39 synchronous, three on a background of chronic active glans LS, and two metachronously (Table 1). The mean (range) age at diagnosis was 54.5  (39–91) years in the BXO group and 61.5  (38–89) years in the non‐LS group (Figs 1 and 2). Although the stage and grade of tumours associated with BXO tended to be lower, and this relationship appeared to be clinically significant, there was no statistically significant difference (P = 0.14 and 0.28, respectively; Table 2).

    Table 1. The tumour demographics
    Group N
    Total penile carcinomas referred 155
    SCC 121
    Carcinoma in situ  34
    Mode of presentation
    Synchronous  39
    Chronic BXO   3
    Metachronous   2
    Cases associated with LS (BXO), n (%)  44 (28)
    image

    A patient with BXO and an associated superficial SCC of the penis.

    image

    A patient with chronic BXO phimosis and associated carcinoma in situ.

    Table 2.
    The tumour grade and stage
    Grade/stage Cancers, n
    associated with LS not associated with LS
    Tumour grade
     G1 10 22
     G2 18 37
     G3  6 28
    Tumour stage
     TIS 10 24
     TA  2
     T1 21 33
     T2  9 43
     T3  3  4
     T4  1  5

    DISCUSSION

    BXO is a regional genital manifestation of LS; the cause remains unknown but genetic factors, autoimmune disease, infective processes and local trauma have been suggested [8]. Patients commonly present with itching, soreness and phimosis. On clinical examination there are ivory‐white plaques involving the glans and prepuce. Complications include fusion of the prepuce to the glans, meatal stenosis and urethral strictures. The incidence of BXO is uncertain but it is not a rare condition. Chalmers et al.[9] reported that 14 of 100 boys who were referred for a medical circumcision had BXO. Estimates of the true incidence are difficult to calculate. Although BXO is a histological diagnosis, in reality the diagnosis is often made on clinical findings alone. Hospital‐based studies reported the incidence to be 1 in 300–1000 patients referred to dermatological clinics [10], but these values are likely to underestimate the true incidence, as patients present not only to dermatologists but also to urologists, GPs and genitourinary medicine clinics. Furthermore, surgery is often curative, and as BXO is commonly thought to have no malignant potential, some surgeons do not send specimens for histological examination. There is also some evidence that BXO is clinically under‐diagnosed. In a prospective study of 43 adult men referred for medical circumcision, 21% had a clinical diagnosis of BXO. A review of the histology showed the presence of BXO in 32% of the specimens [11]. Another prospective study by Liatsikos et al.[4] showed a similar discrepancy between the clinical and histopathological diagnosis of BXO.

    The premalignant potential of BXO is a contentious issue. The European Association of Urology classified BXO as a premalignant lesion, sporadically associated with SCC of the penis [12]. There are numerous reports documenting this association. Wallace [10] reported that in his series of 44 patients with BXO, two developed SCC. Bingham [2] described a 39‐year‐old man who had a previous circumcision for phimosis and 6 years later developed primary penile SCC. Bart and Kopf [13] reported simultaneously presenting penile LS and SCC. More recently Nasca et al.[5] reported on 86 patients with penile LS; in their series, five had histologically confirmed SCC (5.8%). The mean (range) interval from the onset of LS to development of SCC was 17 (10–23) years. However, most significantly they also found evidence of histological progression from LS to neoplasia. Epithelial dysplasia and LS were found adjacent to tumour foci in all cases of SCC. Depasquale et al.[6] published the largest series of BXO cases to date; of the 522 patients who had been diagnosed with BXO, 12 had developed SCC. Seven patients had been circumcised before the diagnosis of SCC, whilst the remaining five had BXO in uncircumcised penises. Reviewing the histology and case notes of 20 patients with penile SCC, Powell et al.[14] reported that in half the patients BXO was as an associated finding.

    In the present report we show that BXO is an associated finding in 28% of patients presenting with penile carcinoma. Whilst this is less then the reported 50% incidence by Powell et al.[14], we only included patients who had histologically confirmed BXO. The nature of this relationship is not clear. It is possible that this is merely a phenomenon that occurs when a rare condition, penile carcinoma, arises on the background of a common disease process, BXO. As the true incidence of BXO in the community is unknown it is not possible to quantitatively prove or refute the above statement. It is unlikely that the association between BXO and penile carcinoma is merely coincidental, and thus might reflect a common aetiology. This conspicuous relationship cannot be ignored and it would be prudent to send all pathological circumcision specimens, where the procedure is for clinical indications, for histological examination.

    Three modes of presentation of BXO and penile tumours have been described; the most common is synchronous, when BXO and penile SCC are diagnosed at the same time [13, 14]. Carcinomas are also not infrequently diagnosed on the background of long‐standing BXO [13, 15]. A less frequent but nevertheless well documented mode is metachronous presentation. This refers to the development of penile SCC several years after the diagnosis and curative treatment of BXO. Although this pattern of presentation is evident in the present series, we found it difficult to prove this histologically. In most of the present patients the histological diagnosis of SCC and BXO was made on the same biopsy. Although at least three patients had been treated for BXO for some time, no biopsies were taken at the time of diagnosis and the existence of SCC at the time of presentation cannot be excluded. Similarly, in patients who had curative circumcisions for BXO phimosis, 12 and 15 years before presenting to us with penile SCC, we were unable to review the original histological specimens.

    No clear guidelines for the follow‐up of patients with BXO exist. With most clinicians regarding the risk of malignancy on the background of BXO negligible, very few will follow these cases. By contrast to this, the premalignant potential of LS involving the vulva is well recognized and women with vulval LS are followed routinely, and biopsies are taken frequently [7]. Some authors, e.g. Depasquale et al.[4], Liatsikos et al.[6] and Powell et al.[14], not only recommend routine histological examination of all circumcision specimens, but also a regular follow‐up. By limiting the follow‐up to patients in whom the disease remains chronically active, the numbers of those requiring follow‐up become manageable. Close monitoring of the diseased areas will allow early biopsy and prompt diagnosis of a possible carcinoma. Patients in whom BXO regresses after treatment probably only need to be made aware of the slight risk of developing associated carcinoma, and the need for regular self‐examination should be encouraged. To our knowledge there are no data for a link between neoplasia and paediatric cases of BXO.

    There should be a low threshold for biopsy in uncircumcised patients presenting with chronic disease and in patients in whom glans BXO persists despite having been circumcised. All circumcision specimens, where the procedure is for clinical indications, should be sent for histological examination. In conclusion the pre‐cancerous nature of BXO remains unconfirmed, but the close association with penile carcinoma at least suggests a common aetiology.

    CONFLICT OF INTEREST

    None declared.

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