Surgical treatment of perineal giant condylomata acuminata (Buschke Lowenstein tumor): Case series from a developing country

Abstract

Introduction

Giant condylomata acuminatum (GCA) also referred to as Buschke-Lowenstein tumor (BLT) is a rare tumor primarily associated with low-risk HPV 6 and 11, which is believed to be a slow growing intermediate tumor with low potential to transform into invasive cancer.

Case presentation

We presented our experience with three cases of BLT (one woman and two men).

Clinical discussion

The three patients had surgical excision and two of them had reconstruction of the surgical defect with good clinical outcome.

Conclusion

We highlighted the importance of early identification of symptoms, treatment options and risk of recurrence as well as primary preventive strategies.

Highlights

• •Giant condylomata acuminatum (GCA) also referred to as as Buschke-Lowenstein tumor (BLT) is a rare tumor primarily associated with low-risk HPV 6 and 11
• •We presented our experience of three cases of BLT
• •The three patients had surgical excision and two of them had reconstruction of the surgical defect with good clinical outcome.
• •We highlighted the importance of early identification of symptoms, treatment options, and risk of recurrence as well as primary preventive strategies.
• •Also noted is our unavailable resource for HPV testing at the time of care

1. Introduction

Giant condylomata acuminatum (GCA) is a not infrequent and indolent tumor of various especially moist epithelial surfaces like the perineal and oral mucous membranes. [1] The human papillomavirus (HPV), particularly the low-risk HPV 6 and 11, has been theorized to be responsible for the initiation and progression [2,3] of this tumor. Although usually histologically benign it can be clinically destructive showing a local, underlying-tissue invasion by a cauliflower-like fungating growth with a high degree of local recurrence [4] and malignant transformation but an extremely low metastatic potential [5]. This is all due to the presence of a deoxyribonucleic acid (DNA) genomic profile corresponding to 6 and 11 HPV subtypes in typical lesions [5,6].

Giant condyloma acuminata is also eponymously known as Buschke-Lowenstein tumor (BLT) after its first proponents Abraham Buschke who first mentioned the lesion in 1896 in the Neisser's Sterokopischer Atlas [7] and Ludwig Lowenstein, his latter assistant with whom he described another lesion in the penile in the year 1925 [7,8]. Dawson, on the other hand, is credited with reporting the first anorectal description of the disease in 1965 [9].

While some authors have suggested that BLT is preceded by the more common small lesions of simple condylomata acuminatum (CA) [7], some others consider it an intermediate lesion in the continuum of a pathological process between CA and squamous cell carcinoma (SCC) [7,10]. Other workers still classify it as an anogenital verrucous carcinoma (VC)- a well-differentiated type of SCC due to its papillomatous architecture and large size [11]. The usual absence of HPV DNA in VC and its preponderance in BLT/GCA however lend credence to their eventual recognition as different entities [12]. Bowen's disease (dyskeratotic condylomatous type) and keratotic pseudo-epitheliomatous balanitis and squamous cell carcinoma are other close differential diagnoses of GCA [13].

With a 0.1 % incidence rate, GCA is further characterized clinically by its predisposition for the male, immunocompromised young adults; predilection for the genital or anorectal region; and an indolent course which may progress from the simple CA to BLT, and further with the potential for a VC [14].

Giant CA can be dramatic when diagnosed because they represent a rare clinical entity that calls for the care of multiple clinical/surgical specialties including infectious disease, histopathology, surgical oncology, radio-oncology, reconstructive surgery, as well as immunology; the latter particularly due to the potential for the existence of a benign, malignant and infective (viral) diagnosis simultaneously [15,16].

The biological behaviour of a typical BLT, as well as its proximity to important perineal structures [17], has made it difficult to have an agreed treatment protocol for this lesion. However, surgery, radiotherapy, immunotherapy, and chemotherapy are known modalities of management [18].

We hereby report our experience with three cases of Buschke-Lowenstein tumor in otherwise healthy adults in a developing-country tertiary-hospital practice low in many ancillary supportive logistics, but rich in multidisciplinary clinical/surgical specialist physicians. This work has been reported in line with the PROCESS criteria [35].

2. Case 1

A 45-year-old HIV-negative heterosexual man presented with a perianal mass of 5 years duration which reportedly increased in size over that period, but with no change in bowel habit nor weight loss. He had a history of contact bleeding on defecation for which he had applied several herbs to the lesion without any improvement. He drank alcohol but had no history of drug abuse.

On clinical physical examination, there was a fungating, sharply demarcated fetid perianal mass, Fig. 1. It was, rough, irregular, firm, and variegated (light gray and pinkish brown) in color. It measured 15 cm by 20 cm in two dimensions, and almost occluded the anal orifice, but did not extend into the anal canal which was thus patent and had normal sphincteric tone. There was no inguinal lymphadenopathy.

Fig. 1.

a: Clinical picture showing the perianal Buschke-Lowenstein tumor mass. b: Intraoperative picture of the bed of the lesion after excision. c: Bilateral V-Y advancement flap. d: Micrograph showing.

Higher magnification (x400) of the hematoxylin and eosin section of the skin biopsy showing some keratinocytes showing koilocytic changes of perinuclear halo with irregular nucleic membranes (arrows).

A clinical diagnosis of anal giant condylomata acuminata (differential, anal carcinoma) was made and was thus further evaluated with chest X-ray, abdominopelvic ultrasound scanning, and wedge biopsy. For reasons of logistic limitations in our practice, an anoscopy was not done at the time of the visit, nor was HPV analysis. He had a diverting stoma fashioned while being worked up for surgical excision and soft tissue cover in a joint surgery with the plastic surgeons.

He was commenced on Podophyllin sitz bath while awaiting the results of the investigations.

He had surgical extirpation of the lesion with a bilateral V-Y advancement flap (Fig. 1b and c).

Biopsy results showed papillomatosis, variable hyperkeratosis, parakeratosis, and hyperplasia of the overlying keratinizing stratified squamous epithelium, an overall feature in keeping with condylomata acuminatum (Fig. 1d).

He developed a superficial surgical site infection postoperatively, and subsequently had wound dressings and antibiotics administered intravenously. Wound infection subsided and was discharged on the tenth post-operative day. He has been followed up in the surgical outpatient clinic and last follow-up was six months ago, however, he has been lost to follow-up.

3. Case 2

Another 40-year-old heterosexual HIV-negative man presented with a 2-year history of perianal and scrotal fungating mass with a putrid smell but no weight loss, or change in bowel habit. He had a history of contact bleeding on defecation. No history of drug abuse or intravenous drug use, and did not drink alcohol.

At physical examination, he was not pale, not febrile, and had no inguinal lymphadenopathy. Rectal examination revealed an exophytic cauliflower brownish mass obliterating the anal orifice and extending anteriorly in the perineum to the base of the scrotum (Fig. 2a). The anal canal was free of the mass and the anal sphincter tone was normal. A diagnosis of Condylomata acuminatum was made. Although there was no HPV analysis done, the biopsy taken confirmed condylomata acuminatum. His white cell count showed leucocytosis; the packed cell volume, abdominopelvic ultrasound scanning, and chest X-ray study were all normal.

Fig. 2.

a: Intraoperative image, positioned for surgical excision. b: Intraoperative clinical image, following mass excision and wound closure.

He had an excision of the mass with primary suture of the wound edges with no temporizing colostomy (Fig. 2b). The post-operative period was uneventful and he was subsequently discharged. He has been on follow-up evaluation as an outpatient for 8 months post-excision with no evidence of recurrence.

4. Case 3

A 24-year-old single lady presented with a year history of multiple perianal warts, perineal pruritus and weight loss, no change in bowel habits, and no contact bleeding.

She had a significant history of multiple sexual partners with a background mild intellectual disability. There are no co-morbidities, and she neither takes alcohol nor uses intravenous drugs.

Physical examination- she was not pale, not febrile, and had no lymphadenopathy. Perineal examination revealed flesh-colored papules with folded irregular surfaces extending from the labia and introitus to the anal region (Fig. 3a). The anal canal was free of the mass and the anal sphincter tone was normal.

Fig. 3.

a: Intraoperative picture showing the lesion. b: Intraoperative picture post excision. c: Picture showing excision bed 10 days post-operatively.

A clinical diagnosis of Condylomata acuminatum was made. Her white cell count showed leucocytosis; the packed cell volume, abdominopelvic ultrasound scanning, and chest X-ray study were all normal. Her retroviral status test was non-reactive.

The low socioeconomic status of this patient prevented an initial biopsy and serology testing hence she had excision of the lesion with healing by secondary intention (Fig. 3b and c).

She also had a multidisciplinary review by social workers, psychologists, and psychiatrists.

She has been regular on the follow-up clinic for 8 months.

5. Discussion

Buschke Lowenstein tumor (BLT) or Giant Condyloma Acuminatum (GCA) resulting from Human Papilloma infection (HPV) infection is a contagious and sexually transmitted disease usually occurring in the perianal, scrotal region and oral cavity [19,20]. A surrogate marker of increased sexual activity [21] and HPV infection is genital warts containing mostly HPV subtypes 6–11 and 13–15 respectively [5,6,21]. Although long-standing; our patient's disease progressed from itchy perianal papular and ‘wart-like’ skin lesions- which were seen as satellite lesions surrounding the anal region mass. Although reported to occur in less than 0.1 % of the populace [12,22]; articles on clinicopathologic characteristics, treatment, and its outcome are few, [23] and this case report seeks to highlight the importance of viral HPV-associated pathologies of surgical interest, management options and outcomes in a resource-constrained setting. The rarity of BLT in females [23,24] is epitomized by our reporting of two cases occurring in the male gender and only one female who is younger and has multiple risk factors. It tends to present more in patients in their forties [7].

In most cases, diagnosis is clinical [25] and familiarity with the clinical presentation of GCA ensures the ability to make a diagnosis based upon a full clinical interaction with the patients as was done in the cases presented. The tricky part is ensuring a proper histologic diagnosis to offer the best possible sequence of treatment. Germaine to this is the acquisition of a proper biopsy, which must be wide and deep-seated enough to accurately [24,25] determine the presence or not of basement membrane infiltration, lymphatic or angioinvasion, and indeed distant metastases [25]. The foregoing is important because GCA and VC share clinical and histologic homogeneity [7].

Histologically, there are well-formed papillae, with hyperkeratosis and parakeratosis. Koilocytes may be seen in the upper third of the epithelium and a chronic inflammatory infiltrate is often present. Local invasion of surrounding tissue is not uncommon however there is no dysplasia. About a third of patients may develop an invasive component, particularly those who harbor high-risk HPV [26,27].

The viable options of treatment for BLT in our environment are Surgery- radical or wide local excision with or without reconstruction; option of cytoreduction with immune-chemoradiotherapy may be used pre or post-operatively depending on the extent of disease/ local invasion and proximity to important structures, thus promoting tumor shrinkage and/or reducing the need for extensive surgery [26,28]. The recurrence risk has been reported to be as high as 60–70 %; with a direct impact of needing to seek margins free of tumor [18,26]. Moreso because responses to topical, immunotherapy, and chemotherapy are temporary and lack an adequate series of patients for the same procedure [26,29]. The use of immunotherapy which has shown promising results in a small group of patients is contingent on demonstrating a viral etiology [29], and the ability to perform DNA sequencing, immunohistochemistry, hybridization, or other molecular techniques is not readily available and in cases where facilities exist, the cost may be the issue- as it was with the cases reported above. The literature evidence suggests that subtypes 6 and 11 are mostly implicated. [6,21]

External beam radiotherapy is controversial because available evidence suggests that there is an increased risk of anaplastic transformation along with the worsening of already existing condylomata acuminatum (CA) [26,30]. The use of topical chemotherapy like 5-FU or systemic chemotherapy is not well defined due to the paucity of patients and limited data [18]. We state that conservative surgical options like Moh's microsurgery, cryosurgery, or laser are best suited for managing small or early recurrences picked up by a vigilant follow-up protocol, because the initial large tumor size, verrucous surface, exophytic and endophytic growth are mostly responsive to radical excision options with reconstruction [26]. Other circumstances that guide the extent of radical surgery include the occurrence of a fistula or involvement of the anal sphincters or mucosa above the dentate line, with a resultant need for colostomy and abdominoperineal resection considerations [31]. We did not need fecal diversion for the resulting wounds in the perineal region for two of the patients as reported by Giorgio De Toma et al. in Italy [31] and the lesions were peri anal with no extension above the dentate line.

A close follow-up is recommended to detect recurrence early but thus far no recommendation has been found agreeable to all on the duration of follow-up [32], although recurrences have mostly been found to occur in the immediate month's post excision [32]. One of the three patients presented had a surgical intervention with no complication and has been followed up for 8 months with no recurrence presently.

With the guarded outcome and prognosis of active BLT disease and management outcome, we will rather attention shift to the use of HPV quadrivalent and nonvalent vaccines (Gardasil vaccines), which significantly decrease the incidence of genital warts (precursor lesions) as pre-emptive care [33]. Vaccines also have HPV-6 and HPV-11 implicated in BLT etiology, which means that the risk/incidence of BLT will reduce as vaccination improves [33]. Indeed, reports of their therapeutic efficacy have been published whereby regression in the size of giant BLT has been recorded after HPV vaccination in the setting of active disease [34].

6. Conclusion

BLT is a rare tumor of increasing importance, and we report our experience in managing this multispecialty demanding diagnosis surgically while highlighting key points in its mode of presentation and management approach to it from an LMIC perspective.

7. Limitations

There was limitation to getting readily available HPV testing at the time of care of these patients.

After initial relief of symptoms, follow-up is an issue.

Ethical approval

University of Ibadan/University College Hospital ethical committee. UI/EC/23/0779.

Funding

No source of funding.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Guarantor

O.O Ayandipo.

CRediT authorship contribution statement

O.A Ajagbe - study concept, data collection, analysis, writing paper.

O.O Ayandipo - study concept, data collection, analysis, writing paper.

O.O Afuwape - study concept, data collection, analysis, writing paper, review.

O.K Idowu - study concept, data collection, analysis, writing paper.

A.O Adeleye - study concept, data collection, analysis, writing paper, review.

T.O Ogundiran - study concept, data collection, analysis, writing paper, review.

Declaration of competing interest

There was no conflict of interest and there was no funding for this work.