Vulval squamous cell carcinoma arising from hidradenitis suppurrativa
- 1 Department of Gynaecological Oncology, Christchurch Women's Hospital, Christchurch, New Zealand
- 2 Department of Gynaecological Oncology, Auckland City Hospital, Auckland, New Zealand
- 3 Department of Histopathology, LabPLUS, Auckland, New Zealand
- 4 Pathology North, New Lambton Heights, New South Wales, Australia
- 5 University of New South Wales, Sydney, New South Wales, Australia
- Correspondence to Dr Marilyn Boo; marilynbooma379@gmail.com
Abstract
A 47- year-old woman developed a rapidly enlarging vulvar mass. Although the clinical appearance suggested malignancy, its lack of atypia and invasion on initial superficial biopsy delayed the pathological diagnosis. It was not until a large incisional biopsy was performed that showed the diagnosis of verrucous squamous cell carcinoma (VSCC) involving pre-existing sinuses of hidradenitis suppurativa (HS). VSCC arising in HS is very rare and often leads to death in published cases. This case demonstrates the challenge in pathological diagnosis of this condition which impacted time to treatment.
Background
Hidradenitis suppurativa (HS) is a chronic inflammatory condition limited to areas of skin with terminal hair follicles and apocrine glands, characterised by follicular occlusion, chronic inflamed lesions, sinus tracts formation and progressive scarring.1–3 Squamous cell carcinoma (SCC) is a rare complication that can occur due to this disease process.1–3 Fifteen cases, including our patient, of vulval SCC arising in HS have been reported (see table 1).4–8 This is a unique case as the majority of patients described in this literature are men with SCC developing within perineal, perianal and gluteal HS.1–4
Update of published patients with vulval SCC arising in HS reported since Sevray et al in 20195
In both sexes, the usual scenario is SCC arising as a complication of known long-standing, poorly controlled HS. Its diagnosis is typically delayed and prognosis poor.1–4 These problems were magnified in our case described herein where SCC was the first presentation of HS.
This case report describes a 47-year-old woman with invasive vulval squamous cell carcinoma (VSCC) arising from vulval HS with summary of the recent literature review.
Case presentation
A 47-year-old nulliparous woman was referred with a vulval lesion of 5 months duration associated with pain and bleeding. The mass fluctuated in size, diminishing with antibiotics on at least two occasions.
She was a smoker with a history of hidradenitis of her left axilla of unknown duration. She was otherwise fit and healthy without any use of regular medications including immunosuppressive therapy.
On examination, the vulval lesion appeared exophytic, around 6 cm in size, involving the anus at the inferior-medial margin. She also had a palpable left inguinal node.
Investigations
An initial pelvic MRI showed a 61 mm×39 mm×56 mm left vulval lesion (malignant-appearing) without involvement of the urethra, anal canal or vagina with bilateral large inguinal and external iliac lymph nodes (figure 1). A positron emission tomography (PET) scan then confirmed avidity of the tumour and nodes (figure 1).
MRI showing left vulval tumour without involvement of anal canal or vagina and PET CT showing primary vulval mass is very FDG avid. Bilateral inguinal, external iliac and left obturator nodes are all avid. FDG, fluorodeoxyglucose; PET, positron emission tomography.
The clinical diagnosis was presumed to be a large vulval cancer with spread to the groin and pelvic nodes and referral for primary chemoradiation was done; however, initial biopsies were superficial and showed acanthosis without atypia or invasion and were negative for malignancy. She was subsequently referred back to the surgical team for deeper biopsy.
The incisional biopsy of the vulva showed an human papillomavirus (HPV)-independent verrucous carcinoma (VC) involving deep dermal sinus tracts in a background of HS, shown by multiple uninvolved sinus tracts and squamous cysts, marked fibrosis and inflammation (figure 2).
HPV-independent verrucous carcinoma involving deep dermal sinus tracts in a background of HS shown by multiple uninvolved sinus tracts and squamous cysts, marked fibrosis and inflammation. HPV, human papillomaviru; HS, hidradenitis suppurativa.
Percutaneous biopsy of the external iliac nodes was not considered, as the inguinofemoral nodes were accessible. As our pathological diagnosis was initially inconclusive despite multiple biopsies of the lesion and the patient’s groin nodes were clinically enlarged as well as PET avid, a decision was made to debulk her left groin nodes and perform a larger incisional biopsy at the same time to achieve a clearer pathological diagnosis.
These investigations over multiple departments took 11 months.
Differential diagnosis
A subsequent incisional biopsy showed acanthosis with minimal atypia in the epidermis and lining large tracts, consistent with VC of the cuniculatum type. Pre-existing HS was inferred as some sinus tracts were partly lined by normal squamous epithelium and because marked dermal fibrosis and chronic inflammation were seen well away from the VC. A differential diagnosis of differentiated vulval intraepithelial neoplasia (VIN) involving sinus tracts of HS was considered instead of VC. A focus where close-packed small nests of mildly atypical squamous epithelium budded off a verrucous tract and extended 4 mm into the adjacent dermis was favoured to be conventional SCC arising from VC on architectural grounds. This remained an uncertainty as no atypia of the degree expected in conventional SCC was seen.
Clinical correlation supported the pathological diagnoses of HS and VC. Supporting HS, the vulval mass partially reduced in size with antibiotics on two occasions and left axillary HS was observed. The diagnosis of VC over dVIN was preferred due to rapid growth of the lesion while under medical care.
Treatment
Owing to the delay in diagnosis, the tumour had enlarged to 15 cm×12 cm. A radical left hemivulvectomy and gracilis flap reconstruction was performed (figure 3).
Image showing preoperative finding of a left exophytic vulval lesion 150 mm×120 mm, intraoperative myocutaneous left gracilis flap raised from inner thigh and vulva at completion of surgery.
The radical left hemivulvectomy was performed down to deep fascia and pubic bone. The lesion was peeled off fibres of external anal sphincter and perineum down to rectum, although rectum was intact. Primary closure was performed at the superior and inferior aspects. Myocutaneous left gracilis flap raised from the patient’s inner thigh and swung medially to cover the defect.
Bilateral inguinofemoral lymphadenectomy was not performed at the same time as vulval surgery, as the preliminary diagnosis was VC. Risk of nodal involvement in VC is thought to be negligible, therefore, inguinal lymphadenectomy was not recommended.
Her recovery was complicated by dehiscence of the posterior medial aspect of the perineal wound and a complex collection 11 cm×5 cm×3 cm under her left thigh wound. This was drained and treated with antibiotics.
The final pathologic specimen showed within the VC a focus of conventionally invasive SCC 11 mm in size and 4 mm deep, margins were clear. A CT showed bilateral groin and external iliac lymphadenopathy without evidence of metastatic disease elsewhere.
Bilateral inguinofemoral lymphadenectomy was performed 6 weeks after her vulval excision. All nodes were negative.
There were 11 months between the initial development of the tumour to definitive treatment.
Outcome and follow-up
She was reviewed 4 months postradical vulval excision. Her donor leg wound had healed well and no longer required dressing changes. She was noted to have some lymphocyst formation in the right groin.
Two years later, there was no evidence of recurrence and her vulval and left thigh flap had softened and healed with a good cosmetic result.
Follow-up imaging was not performed, as the inguinofemoral nodes were negative and it was assumed that the iliac nodes were not involved. Follow-up protocols in New Zealand for vulval cancers do not include regular imaging, and as she has remained asymptomatic and clinically recurrence-free for 2 years, further imaging has not been indicated.
Discussion
Malignant transformation is well recognised in association with chronic wounds from burns, ulcers and pressure sores. In a chronic inflammatory condition like HS it is rarely seen.1–3 These cases can be fatal where diagnosis is delayed.1–4
The prevalence of SCC in HS is 4.6%.2 9 10 104 cases have been published in the literature so far, Jourabchi et al described 80 cases, 5 additional cases was reported by Chapman et al, Kohorst et al published 12 additional cases of SCC arising in HS, Nielsen et al reported an additional 5 cases including an axillary case and we found 1 most recent case.4 7 10–13 Although the prevalence of HS is greater in women, malignant transformation of HS is predominantly in men. A possible explanation for this is that HS in men occurs more frequently in high-risk locations such as perineal, perianal and buttock areas. These areas have an inordinate exposure to microbes which tends to promote chronic inflammation thereby causing poor healing and ulcerations predisposing to the development of SCC.5 11 14 This has been described as the Majorlin’s ulcer phenomenon.15
We have identified 15 cases in the literature, including our patient, of HS associated with vulval SCC. In addition to the seven cases reported by Sevray et al, we found an additional six cases, although reporting of patient information for three cases were suboptimal (table 1).4–8 The average age of diagnosis is 55 years; however, the mean history of HS prior to SCC diagnosis is 25 years. SCC typically develops 20–30 years after the initial HS diagnosis within the affected area.2–6 Of interest, apart from having had left axillary HS, our patient had no prior groin or vulval history of HS. VC is a type of SCC with a warty gross appearance.16 There are two cases in the literature, including our patient describing VC inwomen arising from HS. The other case is a 63-year-old woman with an inguinal, left gluteal and perianal tumour.9 It has previously only been reported in men.
‘High-risk’ human papillomavirus (HrHPV) can be found in a third of vulval SCC.6 It has been identified as a contributory factor in the malignant transformation of HS.11 15 17 HrHPV 16 was found in seven of eight cases of SCC in HS in a study by Lavogiez et al.1 Our case was HPV-independent, which fits the presumed pathogenesis of the scar-cancer model for SCC arising in HS. HPV vaccination should be strongly recommended to patients with HS if not to reduce malignant transformation of HS but to reduce the risk of cervical and anogenital neoplasia.
Early recognition and management are recommended to optimise patient outcomes; however, this can be somewhat challenging given the limited clinical, pathological and prognostic data available. Delay in diagnosis of SCC in HS is frequently described in the literature.1 4 5 11 This diagnostic conundrum is because HS itself may cause a clinical appearance confusing with cancer, and histologically, SCC may arise in deep sinus tracts and not be discovered on superficial biopsy.1 18 Multiple biopsies is frequently described before the pathologist diagnose SCC.14 15 Similar to that of our patient, who had multiple vulval biopsies, all of which were superficial and reported benign. Given our clinical and radiological concerns for malignancy, a wider and deeper resection of the lesion was performed. International pathological second opinion was sought, and the diagnosis of SCC within HS was made.
42%–58% of patients with SCC arising in HS die within 2 years of diagnosis.1 2 4 A review by Losanoff et al 18 found that this poor prognosis is related to late cancer diagnosis and inadequately treated disease.
MRI or PET scans can be used prior to surgery to assess extent of disease and also useful for surveillance after.10 11 Another problem we encountered was that our patient’s PET scan prior to surgery could not separate inflammation from neoplasia as both were avid. This further added to our diagnostic challenge.
‘Aggressive’ surgical excision is the primary treatment for SCC in HS with recommendations of at least a 2 cm margin.1 4 18 In a study by Losanoff et al 18, surgical excision appears to provide patients with the best prognosis compared with radiotherapy or chemotherapy. Additionally, sentinel node assessment is also recommended since there is a high prevalence of lymph node metastasis associated with SCC in HS. Huang et al 19 recommend that radiation therapy only be used in those patients not suitable for surgical excision while chemotherapy is not effective in this context. Makris et al 20 described that cases treated with palliative radiotherapy or chemotherapy had poorer survival of 2–6 months compared with patients who had radical excision who on average were recurrence free after 1 year. There is minimal data in the literature about the effectiveness of adjuvant treatment.
We expect our patient to have a better prognosis than the literature suggests as she has a predominantly VC and has been treated adequately. At 12 months follow-up, there has been no evidence of recurrence and the vulval is asymptomatic and functional.
Learning points
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Squamous cell carcinoma (SCC) may be the first presentation of vulval hidradenitis suppurativa (HS).
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The rarity of this condition, especially in the female population, makes the diagnosis of SCC arising in HS challenging.
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Correct diagnosis is achieved when clinicopathological correlation accounts for all observations.
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Positron emission tomography and clinical assessment of nodes in patients with HS and cancer may be falsely positive.
Ethics statements
Footnotes
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Contributors MB: author of case report; LE: supervisor; MK: pathologist and advisor; JS: overseas pathologist and advisor.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
References
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