Radiation-Induced Vasculopathy Precipitating Penile Gangrene

Sir,

Anal carcinoma is a rare tumor with age-standardized incidence rates mostly between 1 and 2 per 100,000 per year [1]. Abdominoperineal resection of the rectum remained the mainstay of treatment until mid-1970s; however, with the introduction of Nigro protocol, definitive chemoradiotherapy became a popular modality and led to a paradigm shift in the management of anal carcinoma [2, 3]. However, radiotherapy has its own complications—both acute effects and long-term sequelae. Besides being tumoricidal, therapeutic radiation also damages normal tissues and has the potential to induce second malignancies.

Known complications of anorectal irradiation were decreased sphincter competency, lumbosacral plexus toxicities, and radiodermatitis [4]. Meatal stenosis of penile urethra is a common late effect, but a tissue gangrene secondary to obliterative changes and radiation-induced vasculopathy is rarely reported.

A 46-year-old gentleman presented with a 3-day history of painful swelling of scrotum and penis. He was a non-diabetic and non-hypertensive and denied any history of trauma or immunosuppressive therapy. He was an anal carcinoma survivor who had undergone definitive chemoradiation 10 years ago at a center with a cobalt-60 teletherapy unit. Though the exact details of the chemoradiotherapy could not be retrieved, he was treated with 30 fractions over a period of 6 weeks (likely 54 to 60 Gy) and weekly intravenous chemotherapy. The patient had erectile dysfunction subsequent to the radiation therapy. His physical examination revealed swelling of the penis and scrotum. The distal third of penis was dry, shriveled, and black in color (Fig. 1a).

Fig. 1.

a Clinical picture of the penile gangrene with shriveled up distal one third of the shaft. b Cut section of the partial penectomy specimen with fibrosis and unidentifiable urethra and meatus. c Inhomogenous fibrosis (hematoxylin and eosin stain, × 100). d Hyalinized vessels (hematoxylin and eosin stain, × 400)

The patient was initially managed with broad-spectrum antibiotics and urinary diversion with percutaneous suprapubic cystostomy. Subsequently, color Doppler ultrasonography of the penis confirmed the absence of flow in the dorsal penile artery. Subsequently, he underwent partial penectomy and perineal urethrostomy in view of complete obliteration of anterior urethra.

Gross examination of the partial penectomy specimen showed partly ulcerated, shriveled, and discolored skin. Cut surface showed fibrosed cavernosae with no identifiable meatus or urethra (Fig. 1b).

On microscopy, areas of geographic, inhomogenous fibrosis were seen (Fig. 1 c and d). Fibrinous exudate was observed as a delicate network of acidophilic fibrils. Atypical fibroblasts were identified (hyperchromatic and smudged), but no mitotic figures were seen. Small-sized arteries showed subendothelial fibrosis, “hyalinization” of the media, and accumulation of lipid-laden macrophages in the intima. Lipid-containing macrophages (foam cells) were observed in the intima, causing narrowing of lumen. Few medium-sized arteries showed inflammatory infiltrate around the wall (Fig. 2a–f).

Fig. 2.

a Hyalinized blood vessels with proliferating myofibroblasts and foam cells (hematoxylin and eosin stain, × 100). b Prominent myofibroblasts in vessel wall (hematoxylin and eosin stain, × 400). c Foam cells within the media of blood vessels (hematoxylin and eosin stain, × 400). d Interspersed fibrinous exudate between fibroblasts and fibrosis (hematoxylin and eosin stain, × 400). e Atypical fibroblasts with “smudgy” nuclear chromatin along with sparse inflammatory infiltrate comprising of lymphocytes and eosinophils (hematoxylin and eosin stain, × 400). Neutrophils are conspicuously absent. f Inflammation involving the external and outer part of media of the blood vessels (hematoxylin and eosin stain, × 400)

The infiltrate was predominantly lymphocytic, moderate to heavy, and localized in the adventitia. Large-sized arteries and veins were spared. No thrombi were identified. Thus, a diagnosis of penile gangrene secondary to radiation-induced vasculopathy with obliterative changes was made.

Radiation-induced gangrene of the penis is a rare complication following pelvic irradiation, and most of the case reports are limited to periods ranging from weeks to months. Majority of cases are secondary to dermatologic toxicities [4, 5].

Zyczkowski reported a case of a58-year-old man presenting with gangrene of penis and scrotum immediately following radiotherapy for rectal cancer. Patient was managed with debridement of necrotic tissue and antibiotics [5].

In another case reported by Kohjimoto, a 77-year-old man presented with painful purulent discharge and erythema of penile skin 16 months following irradiation for pelvic cancer. Biopsy of the necrotic tissue showed non-specific inflammation without vasculitis and dysplasia. In view of sterile culture reports, patient was managed with prednisolone [6].

Ghosh et al. reported an unusual case of radiation arteritis manifesting more than two decades after radiotherapy for Wilms’ tumor. Angiogram revealed occlusion of aorta and inferior mesenteric and celiac artery. Histopathology of aortic tissue revealed fibrocalcific thickening and other changes consistent with radiation-induced arteritis [7].

In the present case, the patient had remote history of radiotherapy. Considering the age and absence of risk factors for atherosclerosis, atherosclerotic occlusion was unlikely. Additionally, peripheral pulses were normal and this was confirmed by Doppler studies. The other cause of penile gangrene after chemoradiation is Fournier’s gangrene [8]. However, there were no clinical features of sepsis, and the penis was dry and shriveled and did not have erythema or crepitus. The histopathology of the specimen also did not show neutrophilic exudate or extensive necrosis.

The histopathologic changes of radiation-induced vasculopathy are subtle. Fibrosis is the hallmark of radiation-induced vascular changes and is the commonest delayed manifestation, with extent varying with site, time, and dose. The typical inhomogenous fibrosis with admixed fibrinous exudate and paucicellular inflammation are features helpful in identifying radiation-induced fibrosis [9].

Vascular lesions are important in the pathogenesis of delayed radiation injury. Foam cell plaques in medium and small arteries are highly suggestive of delayed radiation injury [9, 10].

To conclude delayed radiation-induced vasculopathy being subtle and bereft of systemic association is likely to be missed unless carefully searched for in cases of penile gangrene.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Informed Consent

Informed written consent was taken from the patient for publication of case details.