Buschke-Löwenstein tumour: a rare and challenging entity

Abstract

Buschke-Löwenstein tumour (BLT) is rare and locally aggressive, and malignant transformation is a possibility. Because there is no consensus on the best treatment approach, the authors present a treatment algorithm based on several case reports. A 57-year-old male patient resorted to surgical consultation with a giant perianal cauliflower-like mass. A BLT was diagnosed. Due to the involvement of the anal sphincter, a wide local excision saving the rectum failed. Abdominoperineal resection was performed. Malignant transformation was diagnosed, and adjuvant radiotherapy was delivered. Clinical evolution was uneventful. Aggressive behaviour despite the absence of malignancy is the hallmark of BLT. The common presentation is an anal mass with a cauliflower-like appearance. Anal verrucous carcinoma and squamous cell carcinoma are the major differential diagnoses. BLT treatment is challenging. Surgery is the first-line treatment, raging from wide local excision to abdominoperineal resection. To improve outcomes, chemoradiation can be used in combination with surgery. Long-term follow-up is mandatory.

Background

The Buschke-Löwenstein tumour (BLT) was first described in 1925 by Abraham Buschke and Ludwig Löwenstein (both dermatologists), hence its name.¹ This first case report of BLT followed the description of two venereal invasive condylomas of the penis in 1896 by Abraham Buschke.² The BLT, also called giant condyloma acuminatum, is a rare entity that arises from a pre-existing warty lesion associated with human papillomavirus (HPV) infection.^2–4 Those authors described a penile lesion similar to both squamous cell carcinoma (SCC) and common condyloma acuminatum, but with different behaviour and histopathological features. Although a benign lesion, BLT is locally aggressive, and malignant transformation is a possibility.^{2 5 6} The BLT usually affects middle-aged patients below 50 years old with an incidence two to three times higher in men.^{6 7} It presents as an exophytic large tumour of the anus, perianal area, perineum, scrotum, vulva or vagina, with slow growth and with a cauliflower-like appearance.^{2 7} Pelvic pain, perianal abscess, fistula and bleeding are all possible clinical presentations.^{2 6} Less frequent presentations can be faecal incontinence, weight loss, anaemia, fatigue and abdominal distension.⁷ Although the preferred treatment option is complete excision with wide margins, chemotherapy, radiotherapy or combined approaches (neoadjuvant chemoradiotherapy followed by surgery) have also been reported. BLT has a recurrence rate of up to 67%, is locally destructive, and has no lymph node involvement nor vascular or neural invasion, and distant metastases have not been described.^{2 6–11} Malignant transformation towards an SCC has been reported in 30%–56% of cases. The reported overall mortality rate is 20%–30%.2–4 6–8 11

Case presentation

A 57-year-old male patient resorted to surgical consultation because of a giant perianal cauliflower-like lesion. He presented with local pain, pruritus, spontaneous bleeding and foul smell. Anorexia and fatigue were also present. Four years ago, the patient was diagnosed with perianal warts. Since then, he was treated with cryotherapy and local imiquimod, but recurrence was always the rule. During the last year, the disease went out of control with slow but steady growth of a giant wart. The patient had no clinically evident immunodeficiency and claimed not having homosexual activity nor multiple sexual partners. He had been a heavy smoker for 40 years (30 cigarettes a day). Besides one-medication-controlled hypertension, he had no other comorbidities. He had never been submitted to surgery.

Physical examination revealed a 20 cm exophytic sacrococcygeal lesion, with a cauliflower-like appearance and irregular surface, extensively involving the perianal region but sparing the genitalia (figure 1). There were several areas of necrosis but no evidence of infection. No inguinal lymph nodes were detected on physical examination.

Figure 1.

Buschke-Löwenstein tumour. (A) Large perianal exophytic cauliflower-like mass. (B) Foley catheter is inside the rectum for reference during wide local excision.

Investigations

The patient was in a state of evident malnutrition with a weight loss of 32% in the last year, microcytic hypochromic anaemia (100 g/L) and hypoalbuminaemia (30 g/L). Syphilis serology and HIV test were both negative.

A giant condyloma, also called Buschke-Löwenstein Tumour (BLT), was the clinical diagnosis. Total colonoscopy was performed to access local invasion of the rectum, but no rectal mucosa involvement was noted. MRI revealed an exophytic lesion with deep infiltration of the subcutaneous fat, touching the gluteus maximus fascial plane, with focal involvement of the external sphincter in the central posterior area (6 hours), without a clear involvement of the internal sphincter but raising the suspicions of a trans-sphincteric fistula (figure 2). There was an extension into the right ischioanal fossa, contacting but not invading the levator ani muscle. MRI also showed both inguinal and iliac lymph nodes without clear signs of malignancy.

Figure 2.

Pelvic MRI showing deep infiltration of the subcutaneous fat by the Buschke-Löwenstein, with focal involvement of the external sphincter without clear invasion of the internal sphincter, with suspicions of a trans-sphincteric fistula. (A) Axial plane. (B) Sagittal plane.

Differential diagnosis

Anal verrucous carcinoma (VC) and SCC are the major differential diagnosis of BLT.²

Treatment

In a multidisciplinary cancer meeting, a wide local excision aiming at an R0 resection was decided. During local resection, the surgical team found that the tumour was more extensive and was invading both internal and external sphincters, probably causing the described trans-sphincteric fistula, with extension into the levator ani muscle and the rectum. In that setting, the surgical team decided that a radical resection saving the rectum was not going to be possible. A laparoscopic terminal colostomy was performed at the same time for complete bowel diverting since a future abdominoperineal resection was highly probable. The defect was left open. Neither bowel resection nor fistula mucosa was performed (figure 3). Pathology confirmed a BLT with features of malignant transformation into a well-differentiated SCC. One week later, a standard abdominoperineal resection under laparoscopic assistance was performed, along with a proper wide local excision enlarging the previous resection margins (figure 4). A substantial loss of tissue at the surgical site was managed with a V-Y myocutaneous advancement gluteal flap. An R0 resection was achieved in the rectum, skin and soft tissue. Final pathology concluded for a BLT with malignant transformation into a well-differentiated SCC of the anus, invading the rectal wall, pT4N0-stage IIIB, with free surgical margins (figure 5).

Figure 3.

Wide local excision. (A) Final aspect after local excision. (B) Terminal colostomy was performed by laparoscopy.

Figure 4.

Abdominoperineal resection with negative margins. (A) The large perineal defect following surgery. It was closed with a V-Y miocutaneous advancement flap. (B) Specimen with macroscopic negative margins. (C) Final aspect at 18 months of follow-up.

Figure 5.

Pathology findings. (A) Area of the superficial tumour with dyskeratosis. (B) High magnification image with intense mitotic activity and abnormal mitotic figures. (C) Deep rectal invasion and neutrophilic microabscesses. (D) Positive p16 immunohistochemistry (staining in more than 70% of tumour cells).

Since we were now treating an anal SCC extending into the rectum, National Comprehensive Cancer Network (NCCN) guidelines for anal SCC and rectum treatment were followed.^{12 13} Adjuvant external radiotherapy of 45 Gy in 25 fractions of 1.8 Gy each (5 weeks) was conducted. Similar to rectal cancer, a long course radiotherapy scheme was used, although a wider window to include pelvic and inguinal lymph nodes was performed as indicated for anal SCC. The irradiation field was influenced by the tumour size, underlying invasive SCC, deep invasion, existence of enlarged lymph nodes and high recurrence rate.

Outcome and follow-up

Clinical evolution was uneventful with full recovery. At 18 months of follow-up, the patient was asymptomatic and with no signs of recurrence, neither in clinical evaluation nor in the pelvic MRI. His general condition improved significantly, with normal blood tests and normal weight.

Discussion

BLT is a rare entity resulting from a sexually transmitted disease (HPV), with a few case reports and case series published in worldwide literature.2 3 5 9 10 14 The aggressive behaviour (locally destructive and extreme invasive capacity) despite the absence of histological features of malignancy is the hallmark of BLT.^{2 4 5} It usually presents as an exophytic cauliflower-like mass with slow growth in the anogenital region (anus, perianal area, perineum, scrotum, vulva and vagina), but it can also affect the bladder.2 6 7 10

BLT is associated with low-risk HPV types 6 and 11 and less frequently with high-risk HPV 16 and 18.2 3 6–10 14 According to Zhang et al, high-risk HPV infection (type 16) is correlated with invasive BLT.² A higher incidence of BLT has been reported in homosexual and bisexual populations.⁵ Risk factors include homosexuality, bad genital hygiene, chronic genital infection and multiple sexual partners.¹⁴ A strong association with smoking, HIV status and other malignancies has also been described.^{2 5 7}

Worldwide literature on BLT resumes to small case series and case reports; thus, detailed histopathological features are not well known. Abbass et al present papillomatosis, acanthosis and increased mitotic activity as microscopic features of the BLT.⁶ In a case series of 38 patients with BLT, Zhang et al pointed out dyskeratosis, keratin cyst and intraepithelial neutrophilic inflammation as features that can help to differentiate BLT from conventional condyloma.² From the same analysis, the authors also found that dyskeratosis, neutrophilic microabscess and abnormal mitotic figures can potentially predict underlying invasive carcinoma.²

Anal VC and SCC are the major differential diagnoses of BLT.² Although there is an ongoing debate whether VC and BLT are different entities or part of the spectrum from condyloma to SCC, VC is nowadays considered a different entity without HPV aetiology.^{2 6 7} In that setting, Zhang et al consider that HPV testing can help differentiate BLT from a VC.¹ According to Jorgaqi and Jafferany, the thicker stratum corneum, the papillary proliferation, infrequent mitosis, the deep invasion and destruction of adjacent tissues are histological hallmarks that differentiate BLT from SCC.^{6 8} Rather than the ‘infiltrating’ effect of common condyloma and SCC, BLT has a ‘pushing’ effect that compresses and displaces the underlying tissues.^{4 8}

Clinical presentation can vary. The most common presentation is an anal mass with a cauliflower-like appearance.^{6 7} Other signs and symptoms associated with the mass can include local pain or discomfort, pruritus, bleeding, foul smell, change in bowel habits, faecal incontinence, weight loss, anaemia and fatigue. Draining abscess of the perianal area, fistula and necrosis can also be present.2 3 6 7 14 Although BLT usually arises from the perianal skin, both the distal rectum and the anal canal are also possible locations.⁶ BLT has no potential to metastasise.^{2 10} Distant metastases have only been described following malignant transformation into SCC.^{2 8} Although BLT does not have lymph node involvement, lymphadenopathies can be found secondary to inflammation or infection of the tumour.^{2 6 9} To exclude rectal mucosa involvement, colonoscopy has been advised.¹⁰ CT scan has been used to demonstrate the location and extent of this highly destructive lesion.^{5 9} Pelvic MRI can help to evaluate the depth of invasion and exclude/confirm anal sphincter involvement.^{7 11} As reported by Indinnimeo et al, the use of endoscopic ultrasonography can accurately evaluate anal canal invasion.⁸

In the presence of a BLT, multiple preoperative biopsies have been reported to be of good help in the treatment decision.^{5 8} Malignant transformation can occur in up to 56% of cases, but it is not always diagnosed before surgery.2–4 6–8 If foci of SCC are found in the preoperative biopsy, Indinnimeo et al believe it is advisable to offer the patient the same radiochemotherapy protocols used in SCC of the anus.⁸

In the case reported, the patient presented with the classical cauliflower-like perianal mass, painful and foul-smelling. HIV was negative and there was no medical history of malignancies. No risky sexual behaviour was reported, and being a heavy smoker for 40 years was the only identified predisposing factor. A colonoscopy to evaluate rectum invasion was performed, and no signs of mucosa invasion were apparent. MRI showed focal involvement of the external sphincter without invasion of the internal sphincter, with suspicion of trans-sphincteric fistula. These data were crucial for treatment decisions in performing a terminal colostomy ad initium, along with a wide local excision. However, during operation, the tumour was found invading the internal sphincter and the rectum, precluding a radical resection preserving the rectum. The trans-sphincteric fistula was probably due to anal sphincter invasion by the tumour.

BLT approach is challenging because of its size, degree of invasion and recurrence rate.⁶ Although the optimal treatment strategy has not been defined, surgery is the first-line treatment for BLT aiming at radical resection with negative margins.2–9 14 15 Following a wide local excision, skin grafts or flaps can be necessary to close the defect.^{5 6} Staged surgical excision has been described in cases of a great number of lesions, aiming at decreasing operation time and blood loss. To prevent faecal wound contamination after wide local excision, a colostomy has been performed by some authors.⁷ The decision to perform a colostomy must be individualised, considering the severity of perineal involvement with anal sphincter invasion, faecal incontinence or continuous faecal contamination of the surgical wound.¹⁶ Abdominoperineal resection is indicated in cases of invasion into the anal sphincters, involvement of the anal canal or rectum, deep penetration and multiple fistulae.^{6–8 15} Recurrence after radical surgery alone has been reported to be 50%–67%.^{6–8 10} In that setting, chemoradiation has been used as an adjuvant but rarely as first option.² However, like SCC, chemoradiation or radiation alone can also be used as neoadjuvant therapy aiming at downsizing to allow a complete excision with negative margins.^{6 7} Indinnimeo et al reported three cases of BLT with foci of SCC in whom a significant downsizing was achieved with neoadjuvant chemoradiation, allowing for a wide local excision.⁸ In patients not suitable for surgery, chemoradiation alone should be offered.^{6 7} Topical chemotherapy (5-fluorouracil, bleomycin and interferon), immunotherapy (imiquimod) and laser are still controversial treatment options.^2–4 Although being solely a case report, Coelho et al reported a BLT invading the anal sphincters in which the topical treatment with imiquimod allowed for a wide local excision preserving the anal sphincters.¹⁰ Topical podophyllin has proven to be useless in BLT despite being extensively used in conventional condyloma acuminata.⁵

After a multidisciplinary meeting and matching other case reports of BLT treatment, our patient was submitted in the first stage to a wide local excision aiming at negative margins. Terminal colostomy was performed at the same time to completely derive bowel and prevent faecal wound contamination. The terminal colostomy also worked as a bridge to a second surgery since radical resection was not possible due to invasion of both the anal sphincter and the rectum. In a second stage, an abdominoperineal resection was necessary to achieve complete excision of the tumour after obtaining patient consent for definitive loss of anorectal function. Following the NCCN Guidelines, adjuvant radiotherapy was delivered because of malignant transformation into an SCC aiming at a recurrence rate reduction.^{12 13} The case presented highlights the challenging management of this entity from diagnosis to radical resection and adjuvant therapy, passing through the local invasion and malignant transformation diagnosis. So far, success was achieved due to the aggressive strategy.

The variability of approaches reported in the literature reveals that the best management is still a matter of debate. From the scarce published literature (essentially case reports), radical resection is the cornerstone of the treatment of BLT.2–9 14 15 After reviewing several cases reports, the authors propose an algorithm for the management of these patients (figure 6). The surgical treatment with R0 resection is stressed as the first-line aim. Chemoradiation therapy alone is reserved for patients unfit for surgery. Under exceptional circumstances (multiple fistulae, invasion into anal sphincter, anal canal or rectum, and deep penetration), the combination of neoadjuvant chemoradiation and surgery can improve complete resection. Based on a multidisciplinary decision, adjuvant therapy should be considered for all patients with malignant transformation. One of the main characteristics of the BLT is the high recurrence rate, which increases with the duration of the disease.2–4 6 9 11 According to Chu et al, the median time before the first recurrence was 10 months, and the average duration of disease was 9.6 years in patients with recurrences and 2.8 years without recurrence. Additionally, these authors state that mortality only affects patients with recurrences.¹¹ In that setting and matching other authors’ suggestions, we advise for a close and prolonged follow-up for an undefined period.^{4 8 10} As a follow-up, we suggest clinical evaluation every 3 months and pelvic MRI every 6 months for the first 2 years. If the patient is free of disease after 24 months, we suggest clinical evaluation every 6 months and an annual pelvic MRI for the following years.

Figure 6.

Proposed algorithm for BLT treatment. R0 resection is the first-line treatment. Although a wide local excision should be preferable, sometimes abdominoperineal resection is necessary. If a negative-margin resection is not possible, neoadjuvant chemoradiation should be offered to aim at downsizing. Chemoradiation alone is indicated for patients unfit for surgery or in cases of downsizing failure. When malignant transformation towards an SCC is present, adjuvant radiotherapy should be considered. A long-time follow-up is mandatory. ¹Multiple fistulae; invasion into the anal sphincter, anal canal or rectum; deep penetration. BLT, Buschke-Löwenstein tumour; SCC, squamous cell carcinoma.

In conclusion, BLT is a rare entity resulting from a sexually transmitted disease. Although benign, it is locally aggressive, has a high recurrence rate, and malignant transformation towards an SCC is a possibility. The suspected diagnosis must arise in condylomas that recur several times after local treatment. Due to the lack of studies, treatment is still a matter of debate. Wide local excision seems to be the first-line treatment, but sometimes an abdominoperineal resection is mandatory to achieve an R0 resection. Probably, the treatment success of large BLTs can only be achieved with radical approaches.

Learning points.

• Buschke-Löwenstein tumour (BLT) has an aggressive behaviour despite the absence of malignancy.

• BLT has no metastatic potential, but malignant transformation towards SCC is a possibility.

• Surgery (wide local excision or abdominoperineal resection) is the first-line treatment aiming at an R0 resection.

• Chemoradiation can be used alone or in combination with surgery.

• Prolonged follow-up is advised due to the high rate of recurrence.

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