Giant condyloma acuminatum was first described by Buschke and Löwenstein as a lesion of the penis in 1925 [
7]. Subsequently, it has been observed in the anorectal and perianal regions [
8]. It is a large, exophytic lesion, slow growing and with a tendency to relapse. A high incidence of GCA has been reported in the homo and bisexual populations and recurrent aggressive GCA has been reported in HIV positive patients [
9]. All our cases were homosexual and HIV positive and treated with antiretroviral drugs. As regards its etiology, the HPV-6 and HPV-11 are the most common types identified but HPV-16 and HPV-18 are also detected especially in cases with foci of SCC [
8,
10]. In our patients, we identified HPV-6 in two patients and HPV-18 in one patient. Especially in HIV patients, the transformation in SCC should be suspected even in the presence of a strain not considered carcinogenic. The histological features are similar to those of condyloma acuminatum but remarkable thickening of the stratum corneum, marked papillary proliferation and the tendency to invade deeply are present [
5]. In the past, BLT was not considered a malignant lesion but a transformation in squamous cell carcinoma can occur after an average of five years [
3]. Careful histological examination is necessary to rule out the presence of SCC [
5]. In a 2001 systematic review of the literature, Trombetta
et al. found the presence of neoplastic foci in 23 of 52 patients undergoing surgery for GCA [
11]. GCA differs from SCC in that it demonstrates an intact basement membrane, infrequent mitosis, absence of metastases and the tendency to displace deep tissues rather than to infiltrate. When malignant transformation is not detected early, it is no longer distinguishable from an invasive carcinoma. Topical applications such as podophyllin and immunotherapy have been used in the treatment of CGA but without success [
6]. Wide local excision or abdomino-perineal resection (APR) are considered the treatment of choice of GCA depending on local extension of the lesion and the involvement of the anal canal, but Chu reported a recurrence rate of 50% after radical surgery alone [
3]. In cases of GCA, an accurate preoperative study is indispensable as malignant transformation, not always diagnosed before surgery, was found in a high percentage. In 42 cases of anorectal GCA reported in the literature, malignant transformation was observed in 52% of the patients [
3]. Creasman, in another review, observed malignant transformation in 30% of cases [
12]. Thus, we perform EUS and CT to assess the exact extent of the disease and multiple biopsies to detect neoplastic transformation. In the presence of foci of SCC, we believe it advisable to refer patients to radio-chemotherapy, using the same protocols adopted in epidermoid cancer of the anus [
13‐
15]. Two months after the end of treatment, we reevaluate the patients with endoanal ultrasound, total body CT scan, endoscopy and HRA. In our patients, the histological examination performed on a wide local excision has allowed us to exclude the presence of GCA and neoplastic foci which would indicate a need for APR. Butler
et al. reported a case of anal GCA invading the perineum and pelvis, with foci of SCC treated by fecal diversion and chemo-radiation. APR was then performed with no evidence of disease in the resected specimen [
16]. We believe that APR is indicated only in non-responding patients or in the presence of a large residual tumor; in all other cases we consider adequate local excision. In all our patients with extensive involvement of the perianal region and the anal canal, neo-adjuvant radio-chemotherapy has allowed the preservation of the anal sphincters and complete cure of the local disease. The patient who died two years after surgical treatment from distant metastases had more advanced disease at diagnosis, with involvement of the inguinal lymph nodes. Despite this, neo-adjuvant therapy allowed a loco-regional control of the disease, thus avoiding colostomy. We believe that the patients treated with this multimodal therapy should undergo careful clinical and instrumental follow-up to identify local recurrence in the early stages when it can still be susceptible to further surgical treatment. Prolonged follow-up is also indicated because the majority of patients with GCA are homosexual and HIV positive and, therefore, may undergo reinfection with HPV and development of new cancer of the anus [
17].