Necrotizing granulomatous inflammation of the glans penis

Abstract

We describe the case of a 73-year-old man who presented with a 10-month history of an ulcerating lesion on the glans penis. Initially this was thought to be an invasive squamous cell carcinoma but a biopsy showed histological features consistent with necrotizing granulomatous inflammation. Extensive serological, immunological and microbiological tests only showed a positive antinuclear and perinuclear antineutrophil cytoplasmic antibodies indicating a possible autoimmune aetiology but an underlying systemic cause was not identified. Treatment with oral corticosteroids limited the inflammatory process but due to the gross destruction of the glans penis, he still required a glansectomy and split-skin graft reconstruction from which he recovered well. Although this patient ultimately required surgery for this rare presentation, this case highlights the differential diagnosis of penile ulceration (that transcends neoplasia) and the importance of performing and interpreting penile biopsies before undertaking potentially mutilating definitive surgery.

Background

Penile squamous cell carcinoma (SCC) is a rare cancer with reported incidence of 1 in 100 000 in most developed countries.¹ It can present as a fungating or ulcerating lesion on the foreskin or glans penis.¹ Other causes of penile ulceration include sexually acquired and non-sexually acquired infections, trauma and iatrogenic causes (eg, injectable substance reaction such as paraffin or silicone), inflammatory disorders (such as lichen sclerosus and lichen planus, bullous dermatoses, sarcoid, vasculitis, pyoderma gangrenosum (PG) and drug eruptions) and neoplasms such as lymphoma, Kaposi's sarcoma and Langerhans cell histiocytosis.^2–10 Idiopathic inflammatory ulcerative lesions affecting the penis in isolation such as necrotizing granulomatous vasculitis or PG are extremely rare and have been associated with systemic vasculitis and Crohn's disease.^11–23

Case presentation

A 73-year-old man presented with a 10-month history of a painful ulcerating lesion on the glans penis. He reported difficulty in voiding and urine was passing through a fistula formed by the ulceration of the lesion into the adjacent urethral meatus.

Eight months earlier he underwent a circumcision for presumed Zoon's balanitis as well as a biopsy of the ulcer. This biopsy only showed areas of inflammation. Although his circumcision scar healed well, there was still persistent and progressive ulceration at the site of the initial biopsy.

He had a medical history of hypertension which was well controlled with ramipril and atenolol. He did not have any relevant family history.

On examination, there was a necrotic, exudative ulcer on the ventral aspect of his glans penis with no palpable inguinal lymphadenopathy (figure 1).

Figure 1.

Ulcerative lesion on the glans penis.

Differential diagnosis

In this case, the differential diagnosis was felt to include penile SCC, PG, atypical mycobacterial infection, syphilis, sarcoid, vasculitis and Crohn's disease. But the extended differential diagnosis considered all those entities listed above.

Investigations

The case was discussed at a regional penile cancer multidisciplinary team (MDT) meeting on several occasions with input from a specialist dermatologist. CT of the chest, abdomen and pelvis and MRI of the penis following Caverjet injection did not suggest an underlying malignancy, confirming an ulcerative lesion of the glans penis with no involvement of the corpus cavernosum (figure 2).

Figure 2.

T2-weighted axial MRI image of the penis showing glans ulceration (white arrow).

A biopsy performed under general anaesthesia showed a hyperplastic epithelium with reactive changes. The lamina propria consisted predominantly of granulation tissue and prominent necrotizing granulomatous inflammation as well as subepithelial band-like Zoonoid plasma cell inflammation, but with no evidence of atypia or malignancy (figures 3 and 4).

Figure 3.

H&E staining showing granulation-like tissue and granulomata (×40 magnification).

Figure 4.

CD68 immunostaining (×20 magnification).

Additional stains for acid-fast bacilli, fungi and treponemal organisms were negative. Systemic investigations were normal, including the white cell count and C reactive protein. The erythrocyte sedimentation rate was mildly raised at 21 as well as the IgA. Autoantibody screening showed positive antinuclear antibody with a titre of 320, positive perinuclear antineutrophil cytoplasmic antibody (p-ANCA) and swabs for bacteriology as well as syphilis serology were negative. Virology was negative for herpes simplex virus (HSV), cytomegalovirus, HIV and hepatitis B and C.

Treatment

Following MDT discussion, he was treated empirically with oral prednisolone 30 mg daily, oral antibiotics and oral antifungals.

Although the ulceration was arrested by systemic corticosteroid treatment, there was no significant improvement of the glans penis (figure 5). As the glans penis had undergone ulceration and disfigurement, eventually a glansectomy followed by split-skin graft (SSG) reconstruction of the neoglans was performed to excise the diseased tissue for further tests, to provide a better cosmetic outcome and to allow voiding through a single urethral opening (figures 6 and 7).

Figure 5.

Ulcerative lesion on the glans following conservative treatment.

Figure 6.

Removal of the glans and adjacent skin during glansectomy.

Figure 7.

Neoglans formation with central urethra and split-skin graft (SSG).

Histological examination of the glansectomy specimen confirmed the previous findings. Special bacterial stains were negative as were the cultures for mycobacteria and fungi. The differential diagnosis of exclusion rested between focal granulomatous conditions such as sarcoidosis, Crohn's disease, vasculitis, for example, Wegener's and granulomatous PG, so he was treated with ongoing systemic steroids and oral antibiotics (to prevent secondary infection).

The patient recovered well from the procedure with no postoperative graft loss or wound infection, and the neoglans and donor site for the SSG had healed. Nine months following his glansectomy, the steroids were finally stopped, the neoglans appeared healthy and the patient remained well (figure 8). He did not report on any voiding difficulties such as urinary frequency, poor flow or spraying of the urinary stream and sexual function was recovered.

Figure 8.

Appearance of the neoglans 9 months following surgery.

Discussion

This case illustrates a rare presentation. The first issue is that of diagnosis; not all penile ulcers are cancers and screening tests for sexually transmitted diseases and a diagnostic biopsy are necessary in all suspicious penile lesions to exclude inflammatory and other benign conditions prior to radical treatment.

Benign isolated ulcerating lesions of the glans penis are rare and can be mistaken for a malignant condition such as SCC.¹ Here once a malignant lesion was excluded, the differential diagnoses of the necrotizing granulomatous inflammation were an infective or autoimmune cause or PG.

The prior diagnosis of Zoon's plasma cell balanitis cannot be sustained by the history, signs and subsequent clinical events and histology.^{2 24 25} Plasma cell balanitis was first described by Zoon in 1952.^{2 24 25} It presents clinically with asymptomatic, well-circumscribed symmetrical orange-red glazed patches and histologically shows a dense plasmocyte-rich subepidermal infiltrate.^{2 24 25} In practice, Zoonoid inflammation is commonly seen in penile biopsies and can distract clinicians and histopathologists from the true underlying diagnosis, as is often the case with lichen sclerosus.^{2 24–26}

Necrotizing granulomatous inflammation of the glans has been associated with non-sexually transmitted infection with mycobacterium following Bacillus Calmette-Guérin installation for bladder cancer.^5–7 Tuberculosis of the penis is a rare pathology and diagnosis is established by the finding of granulomas histologically and mycobacteria following culture.^5–7 Lepromatous leprosy skin lesions of the penis are also related to acid-fast bacilli but are rarely isolated and usually present as multiple and widespread skin lesions.⁸ Sexually acquired infections such as syphilis and HSV have been associated with ulcerative lesions of the glans penis and are more prevalent in patients with HIV or haematological malignancies.^2–4 However, extensive serological and tissue culturing for bacteria, fungi, mycobacteria, syphilis and sexually transmitted viruses did not identify an infective agent and no haematological malignancy was identified in our case.

Penile granulomata secondary to foreign body reaction following injection of paraffin oil and silicone are not uncommon in the literature.^{2 9 10} These are used to augment the penis; however, patients are rarely warned of adverse effects such as skin necrosis, penile deformity, granulomatous lymphoedema and the need for skin excision and grafting.^{2 9 10} Nicorandil-induced skin ulceration, including of the penis, are well recognised complications; however, there was no such history in our case.²⁷

Extensive review of the literature revealed two cases similar to ours where autoimmune vasculitis was proposed as the underlying cause.^11–13 Congregado et al¹² reported the case of a 68-year-old man with localised granulomatous arteritis causing necrotizing granulomatous inflammation. However, granulomatous arteritis usually affects the upper and lower respiratory tracts, the renal glomerulus and presents with ocular and skin lesions.¹² Another similar case is that of a 62-year-old patient with Wegener's granulomatosis of the penis.¹³ The histopathology revealed necrotizing granulomatous inflammation and vasculitis with c-ANCA levels of 320. This patient later presented with leg lesions that also showed granulomatous vasculitis.¹³

PG is an uncommon ulcerative skin disease of unknown cause. Fewer than 20 cases have been reported affecting the penis.^11–22 PG can be associated with systemic diseases such as Crohn's disease, rheumatoid arthritis and haematological malignancies, but it also complicates trauma and surgical procedures.^{11–15 22} Crohn's disease is a chronic relapsing, granulomatous and inflammatory bowel disorder.^{11 23} Variable extraintestinal manifestations may occur, which include erythema nodosum, erythema multiforme and PG.²⁴ However, penile ulcerative lesions associated with Crohn's are not usually necrotizing and steroid treatment or other immunosuppressive therapies are usually curative.²³

Genital PG tends to occur without systemic complications and can mimic SCC.^11–22 The diagnosis of PG rests on clinical features and there are no pathognomonic histopathological characteristics. Histopathological features include oedema, neutrophil infiltration, engorgement and thrombosis of small-sized and medium-sized vessels and necrosis but this depends on the type of lesion, the stage of evolution and the site of the biopsy.^{11 15} Granulomatous inflammation is not a widely accepted associated finding in PG.^{11 15} However, two cases reported by Park et al¹⁵ have been characterised as PG and they appear similar to our own case clinically without evidence of systemic disease and histologically with granulomatous inflammation. PG, as stated above, can complicate surgery. In our case, the ulcerating lesion was initially biopsied at the time of the patients' circumcision. The area failed to heal and evolved into a complex deep ulcer over a period of 8 months. The clinical presentation and the lack of an infective or neoplastic cause for this patients' ulceration lead us to favour a diagnosis of postsurgical granulomatous PG in this case; however, we are monitoring the patient long term for recurrence and systemic disease.

Benign causes of glans ulceration are rarely reported in the literature and once malignancy is excluded with a diagnostic biopsy, serological, autoimmune and infective screening should be performed prior to corticosteroid treatment. However, the outcomes following surgical reconstruction have been promising in this case, with the neoglans allowing better cosmesis and normal voiding.

The second issue of interest in this case relates to the clinical management. The importance of performing a biopsy or biopsies has been highlighted. However, surgical techniques used in the management of premalignant or malignant diseases of the penis such as wide local excision, glans resurfacing or glansectomy followed by reconstruction are also useful in cases where medical treatment fails to restore the normal architecture of the penis.

Learning points.

• Ulcerative lesions on the glans penis should be biopsied prior to surgical treatment to exclude squamous cell carcinoma.

• In cases of cryptic ulcerative lesions of the penis, a multidisciplinary approach to diagnosis and treatment is advisable given the broad differential diagnosis.

• Where medical treatment fails to improve penile structure and function, surgical excision and reconstruction are legitimate and successful interventions.