Fatal outcome of malignant transformation of hidradenitis suppurativa: A case report and literature review

Abstract Squamous cell carcinoma arising in hidradenitis suppurativa (HS) is a rare albeit the most serious complication in HS, with a reported fatality of up to 42.9%. This calls for greater clinical awareness in patients with long‐standing chronic HS.


| INTRODUCTION
We present a case of a 66-year-old woman with metastatic vulvar squamous cell carcinoma that developed within an area of chronic hidradenitis suppurativa in the groin and review the literature. The progression of SCC was so severe that she passed away only a month into her hospital stay.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder, characterized by recurrent deep-seated, inflammatory nodules in apocrine gland-bearing areas of the body, that is, the axillae, groin, and perineum. The nodules may progressively expand to abscesses and draining sinus tracts with subsequent scarring. Chronic, long-standing inflammation in HS may lead to the development of squamous cell carcinoma (SCC), a rare albeit the most serious complication of HS.
We present a case herein of a woman who developed SCC of the vulva in the setting of chronic, long-standing HS with fatal outcome and update the literature on this topic to date.
A search in the PubMed database was conducted until the 25th of September 2019 to identify articles describing patients with HS who developed SCC. All of the articles reviewed were published in English. The search terminology included the following: "Hidradenitis suppurativa AND squamous cell carcinoma."

| CASE REPORT
The patient was a 66-year-old Caucasian female with a history of HS since 2010 with Hurley stage III lesions in the groins with six nodules and six sinus tracts. She had a HSS score of 63, DLQI score of 13, and visual analogue scale (VAS) for overall disease-related distress of 5.5 and VAS for boil-associated pain from boils in the past month was 0. The patient also had hypertension, smoked 20 cigarettes per day for 54 years and had a BMI of 26.4 kg/m 2 . She had no family history of HS. The patient was first seen in our clinic in 2016, where treatment with topical clindamycin twice daily and oral tetracycline 500 mg twice daily was initiated along with topical corticosteroids for local eczema. At 3-month follow-up, the skin was characterized by | 505 NIELSEN Et aL. fibrotic and thickened cicatricial areas with purulent drainage and inflamed nodules. Topical metronidazole and oral lymecycline 300 mg twice daily were administered and the patient was referred to wide excisional plastic surgery of the groins, provided she stopped smoking 2 months prior to surgery. Surgery was canceled due to continued smoking, and no further surgery was planned. She failed to seek further help for her HS until she was admitted 3 years later after severe worsening of HS, with multiple severe fistulae and a large foul-smelling tumor with drainage in the left groin and necrosis of lymph nodes ( Figure 1). A PET-CT showed ingrowth and destruction of the left ramus inferior of the pelvis and gland metastasis under the diaphragm. Biopsy demonstrated invasive poorly differentiated SCC, transformed from several years of chronic HS. The clinical picture was compatible with ulcerating vulvar cancer, and the patient received radiation therapy as a palliative measure. However, she was shortly thereafter deemed terminal and died 1 month after the initial metastatic SCC diagnosis.   5 Including our patient, three of three of the six patients (50%) in this review passed away after their metastatic SCC diagnosis, supporting the severity of this compilation. However, fatality could be speculated to be overemphasized due to publication bias. The diagnosis of malignancy in patients with HS is less straight forward, since chronic draining wounds can mimic malignant ulceration. Biopsies are not required to diagnose HS, but should be considered in the setting of an uncertain clinical picture to rule out malignant transformation.
The Danish Board of Health recommends a 6-week smoking cessation prior to surgical removal of HS. However, our patient continued smoking and was withheld surgical excision while her HS severely worsened, to a point where surgery was not possible anymore. It is an ethical dilemma, whether surgery should be postponed until smoking cessation in every case. In a former study by Losanoff,6 surgery is the only known treatment method that provides a real chance for a cure for both HS and a complicating carcinoma. Patients that do not initially undergo surgery for severe HS can potentially develop cancerous degeneration as in the present case report. This is why complete excision in severe cases of HS is also indicated to avoid chronic progression of the disease. Retrospectively, less strict smoking policy could have allowed surgery and perhaps avoided cancer transformation and death. It is important to consider the socioeconomic situation of the patient in the treatment as well. Our patient only had one distant relative for support, lived alone and could not take care of herself, so she failed to seek medical attention even though her disease severely worsened. Support for the patients with low socioeconomic status including smoking cessation and weight loss should be considered for optimal wound healing 7 and adherence to therapy.
Biologic drugs are used for moderate to severe HS or in nonoperable patients, and have shown promising results. 8 However, they are speculated to be associated with increased risk of nonmelanoma skin cancer due to their immunosuppressive properties. Further, it is well known that chronic skin inflammation is linked to higher risk of malignant transformation as our case supports. Further research focusing on the risk of developing SCC in HS patients is needed to elucidate whether long-term treatment with biologics may lead to prevention or promotion of malignant transformation of chronic skin inflammation. Our patient did not receive biologic therapy.

| CONCLUSION
In conclusion, patients suffering from chronic inflammatory processes should be closely monitored with a high index of suspicion of malignancy, since SCC in long-standing HS is a rare, but potentially fatal complication. HS in the perianal, perineal, and sacral region should be treated early with wide and radical surgical excision due to the risk of malignant degeneration and development of aggressive SCC particularly in these regions. Dispensation from smoking policy should be considered in selected patients.