Atif Iqbal, MD Chief Resident Department of Surgery North Oakland Medical Centers Wayne State University Detroit, MI Faisal Aziz, MD Resident Department of Surgery North Oakland Medical Centers Wayne State University Detroit, MI Jason Winfield, MD Attending SurgeonDepartment of Surgery Brooklyn Hospital Center Brooklyn, NY
The Buschke-Lowenstein tumor (BLT) is an extremely rare, slow-growing, locally destructive, cauliflower-like mass, also known as giant condyloma acuminata. There has been considerable debate regarding the exact nature, etiology, and treatment of these lesions. Like oral florid papillomatosis and epithelioma cuniculatum, BLTs are considered to be a regional variant of verrucous carcinoma. BLTs can involve the penis, vulva, scrotum, bladder, and perianal or anorectal regions. This report focuses on the best way to manage these tumors, discussing the role of chemotherapy, radiation, and surgery.
Case report A 40-year-old black man presented with a giant perianal mass, which had afflicted him for at least 6 years. The mass was pale pink, cauliflower-like, and fungating, with surface dimensions of approximately 27 x 22 cm. It was 8 to 10 cm thick and produced purulent discharge with a foul odor (Figure 1). The mass greatly impaired his daily life, preventing him from ambulating freely and causing him to avoid social gatherings because of the foul odor it produced. His condition had been treated conservatively with podophyllin at a local hospital, but the treatment was unsuccessful.
The patient’s other symptoms included anemia, episodes of dizziness, and a 50-lb weight loss over the previous 6 months. Physical findings included bitemporal atrophy, pallor, brittle nails, and an atrophic tongue. He had no other significant medical or surgical history and reported no homosexual activity but acknowledged a 25-year history of cocaine and alcohol abuse.
Serologic tests for human immunodeficiency virus were negative. Laboratory results included a white blood cell count of 61,900 mm3 (normal, 4,300—10,800 mm3), neutrophils of 91.3% (normal, 39%–85%), a hemoglobin of 4.6 g/dL (normal, 12—18 g/dL), and a hematocrit of 13% (normal, 40.7%—50.3%). The patient’s stool was guaiac-negative. A computed tomography scan of his abdomen and pelvis was normal, and workup for anemia, including colonoscopy and upper endoscopy, was inconclusive.
The results of an elective incisional biopsy of the mass were consistent with condyloma acuminate (Figure 2). Radical surgery was attempted. The tumor was found to be very vascular and deeply infiltrating. Wide local resection of the perianal tissue was performed (Figure 3). Because there was no gross involvement of the anal sphincter, it was spared. Proximal diversion was accomplished by a loop sigmoid colostomy.
The excised tumor weighed approximately 1,600 g. Pathology confirmed it as giant condyloma of BLT, with verrucous carcinoma and severe dysplasia with positive margins. Re-excision was performed; 2-cm margins were excised circumferentially and confirmed to be free of tumor.
The patient’s postoperative course during the first 6 months after surgery was uneventful. He underwent reversal of his colostomy during that time and had no medical complaints. The patient neglected follow-up care for the next 4 months. He returned 10 months after his initial surgery, reporting weakness and swelling in the bilateral inguinal regions. The patient was found to have inguinal adenopathy and underwent an incisional biopsy, which was positive for metastatic malignant melanoma. Further workup found widespread metastasis. Treatment with dacarbazine and interferon was initiated, but the patient responded poorly. He failed to complete the course and died 5 months after his melanoma was diagnosed.
Discussion BLT is a rare clinical disease entity, first described by Buschke in 1896.1 In 1925, Buschke and Lowenstein further characterized the tumors as locally invasive, rapidly growing “carcinoma-like condylomata acuminata.”2 They can be distinguished from usual condyloma by their deep penetration of adjacent tissues. BLTs differ from carcinomas in that they do not metastasize. They are generally larger than regular condylomata acuminata and fail to respond to conservative management. Scarcely more than 35 cases of anorectal BLT have been published.3 This seems to indicate that BLT is an intermediate entity, falling between “ordinary” condyloma acuminata and squamous cell carcinoma.
Studies have shown that mutations of viral DNA may play only a minor role in tumor progression.4 Dual infections with variants of human papilloma virus (HPV)-6 are equally absent.5 Carcinogenic cofactors promote the transition to giant, locally destructive condylomata acuminata and subsequent malignant transformation.
BLTs appear as small warts on or around the prepuce and gradually become nodular, penetrating underlying tissue. They may grow in the anal canal, where they can give rise to fistulas with putrid-smelling, purulent discharge. Eventually, the genitalia may become overgrown with condylomatous masses. Secondary infections are common and may result in regional lymph node enlargement. Buschke and Lowenstein thought that BLT was restricted to men, but these lesions have been reported in women.6 The mean age of patients who present with perianal giant condyloma acuminata is 43 years, with a male to female ratio of 2.2 to 1.3,7,8
BLT is associated with HPV-6 and HPV-115. Risk factors include immunosuppression, chronic irritation, and poor personal hygiene.3,9,10 Chronic irritation from perianal fistulas and ulcerative colitis have been implicated in anal occurrences of this tumor.7,8 The risk of recurrence after excision is 60% to 66%, with an overall mortality rate of 20% to 30%, and the transformation of BLTs into malignant tumors has been reported in 30% to 56% of cases.2,7,8
The histopathological basis of this tumor shows a pattern of unrestrained local growth but no evidence of malignant changes. Microscopically, the tumor forms a luxuriant mass comprised of broad, rounded rete pegs, which often extend deeply into underlying tissues. The pegs are composed of well-differentiated squamous cells, which show no cellular anaplasia. These epithelial pegs typically are surrounded by a dense band of acute and chronic inflammatory cells.
Treatment options Medical management—A variety of chemotherapeutic modalities have been used with mixed success as adjuvants to surgery or to treat recurrences. The postulated viral origin of these tumors led to the use of interferon with moderate success. One case of vaginal BLT responded to 6 months of interferon-2 alpha with what appeared to be complete resolution.11 Traditional systemic antitumor agents also have been used. In one case, the patient was treated with bleomycin, cisplatin, methotrexate, and leucovorin after multiple surgeries for BLT.8 An autopsy 1 year later found no evidence of active disease. In a separate case, tumor shrinkage was noted after using mitomycin-C and 5-fluorouracil combined with fractionated radiotherapy; unfortunately the patient manifested pulmonary metastases.8 Etretinate and photodynamic therapy with intravenous porphyrins have been used with some success in treating vaginal BLT.12 Topical therapy with either podophyllin or 5-fluorouracil has been attempted around the world but, as in our patient’s case, is often unsuccessful.
Radiation therapy remains controversial. A Brazilian paper reported total regression of a highly recurrent BLT following radiation therapy.13 The patient initially was treated with multiple excisions, but continuous recurrences led surgeons to try telecobalt therapy, which resulted in complete resolution of the patient’s BLT. Extensive evidence supports the conclusion that tumors behave aggressively after radiation-like anaplastic transformation in oral and plantar verrucous carcinoma. One review recommended avoiding radiation but suggested that, if necessary, administering a large dose of radiation to minimize chances of further mutation may be effective for patients who are poor surgical candidates.13 We conclude that radiation therapy is a valid treatment modality for managing giant perianal condylomata in selected cases.
Surgical management—The standard approach for managing perianal giant condyloma acuminata is radical surgical excision. Patients with multiple fistulous tracts and purulent discharge may require a temporary loop colostomy. Any compromise regarding radicality is reported to predispose the patient to local recurrence.9,10,14 Some have advocated abdominoperineal resection in cases involving infiltration of the sphincter muscles or rectum.10,15,16 For patients who have BLT with malignant transformation, optimal treatment has not been well-defined.
In a review of 11 patients treated with radical surgery, only 5 remained disease free.2 This has prompted some authors to recommend preoperative chemoradiotherapy to downstage extensive tumors before performing radical surgery.9 For classical anal canal cancers, the role of chemotherapy and radiotherapy is now well established, and the combined modality approach is superior to abdominoperineal resection in terms of colostomy-free survival, with many patients maintaining good anal function.17
Several case reports describe squamous cell cancers arising from giant condyloma acuminata in patients who respond well to radiotherapy alone or chemoradiotherapy.6 Butler and colleagues reported on a patient with unresectable disease who received combined modality therapy.18 A pathological complete response was demonstrated following abdominoperineal resection 32 weeks later. Chu and associates treated one patient’s unresectable disease using preoperative chemoradiotherapy followed by abdominoperineal resection and reconstructive surgery.8 The patient remained disease free 22 months postoperatively. Marsh and colleagues discussed a patient with extensive locoregional disease who was successfully palliated with chemoradiotherapy.19 Bertram and associates described two patients with inoperable disease whose conditions were successfully downstaged using moderate-dose radiotherapy before they proceeded to surgery.3
Conclusion Wide, radical excision of BLT is the preferred treatment for achieving local control, but excision alone often is ineffective in treating the melanoma variant of BLT. Neoadjuvant chemotherapy may alleviate pain and decrease the tumor burden, but it does not prevent recurrence of the disease. Interferons have been used intralesionally and systemically and have been proven effective in selected cases; however, their adverse effects cannot be ignored.
Troublesome recurrences of BLT occur frequently, and a propensity for infection and fistula formation is common. Adjuvant therapies hold promise, but remain uninvestigated. Regardless of the size and origin of BLTs, gaining early control of the disease using wide, radical surgical excision provides the best overall rate of survival.
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