Squamous cell carcinoma complicating donovanosis not a thing of the past!

Introduction

Donovanosis is a chronic, slowly progressive, mildly contagious bacterial infection that usually involves the genital region. It is caused by a Gram-negative bacillus, Klebsiella granulomatis and characterised by granulomatous ulceration of genitalia and neighbouring sites with little tendency to heal spontaneously.^1,2 Nowadays, it is an infrequent diagnosis in sexually transmitted infection (STI) clinics of northern India.^3,4 Hence, the case is reported because of its scarcity and association with an even rarer complication of carcinoma.

Case report

A 47-year-old married man, presented with a single large non-healing ulcer on the scrotum of one year's duration. The lesion initially started as a pea-sized, raised, painless, skin coloured nodule over the scrotum. It gradually increased in size over a period of four months and subsequently broke down to leave behind a raw painless area. As the ulcer was asymptomatic, he did not seek any medical advice and used an over-the-counter topical application. He had a history of multiple, unprotected, extramarital contacts but denied having any genital complaints in the past.

Examination of genitalia revealed a single, foul smelling, 5 × 4 cm well-defined ulcer involving the left side of the scrotum. The lesion was bright-red in colour with a wavy outline and exuberant growth of moist granulation tissue. The granulation tissue was projecting from the surface and spilling over the edges. It was firm, non-tender, extremely friable and bled on palpation (Figure 1). The inguinal lymph nodes were not enlarged. Rest of the cutaneous and systemic examination revealed no abnormality. Genital examination of the spouse was normal. A clinical diagnosis of squamous cell carcinoma was made with donovanosis as a close differential. OPEN IN VIEWER

A tissue smear was prepared from the edge of the ulcer and stained with Giemsa. It revealed the presence of numerous histiocytes, neutrophils and plasma cells. Vacuolated macrophages in the smear exhibited the presence of basophilic bipolar Donovan bodies inside them, thus confirming the diagnosis of donovanosis (Figure 2). VDRL and HIV serologies were non-reactive. OPEN IN VIEWER

He was started on antibiotic therapy, oral doxycycline 100 mg twice a day. The patient came back in 10 days with no improvement. Failure of the lesion to respond to medical therapy made us suspect malignant transformation. A biopsy taken from the edge of the ulcer showed islands of atypical squamous cells infiltrating the dermis with evidence of keratin pearl formation. There was desmoplastic stromal response to the tumour and evidence of granulation tissue formation in the ulcer bed. Features were those of a well-differentiated squamous cell carcinoma. The biopsy section was stained with overnight slow Giemsa technique and it revealed the presence of Donovan bodies inside macrophages (Figure 3). OPEN IN VIEWER

The patient was counselled regarding the disease and prognosis. He was started on oral azithromycin 1 g/week along with gentamicin 1 mg/kg every 8 h and was referred to the department of surgery in our hospital. He underwent an excision of the lesion along with bilateral modified inguinal lymph node dissection. The lymph nodes were later found to be negative for metastasis. Histopathology of the resected specimen confirmed carcinoma (Figure 4). OPEN IN VIEWER

Discussion

Donovanosis had a fairly wide geographical distribution in the pre-antibiotic era.^1,2 The main foci of donovanosis were in Papua New Guinea, southern Africa, Zimbabwe, parts of India, French Guyana and aboriginal communities in Australia. In India the disease was mainly reported from southern parts, especially Tamil Nadu, Pondicherry, Andhra Pradesh and Orissa. However, the disease is rarely reported nowadays, especially in north India.^3–5 Donovanosis has been on the wane and its incidence has declined considerably over the last 10 years.^3–5 This may be due to rising literacy, increased awareness of HIV, syndromic management of STIs and availability of broad spectrum antibiotics.^3–5

Development of carcinoma in cases of donovanosis has been reported by various authors from India in the past.^1,6,7 Sardana et al. ⁸ reported carcinoma in an immunosuppressed HIV-positive case of donovanosis. In a series of 2000 patients of donovanosis in the 1950s, carcinoma was reported to be a rare occurrence (0.025%), either as a complication or a sequel to long-standing donovanosis. ¹

Long-standing donovanosis may closely mimic squamous carcinoma in the exuberant fleshy growth or in an ulcer with a nodular base and everted edge.^1,2 Even the histological distinction between the two entities may sometimes be difficult.^1,9 Carcinoma has been reported alongside active donovanosis or supervening on long-standing cases and even developing at sites of healed lesions.^1,10 Donovanosis has rarely occurred as a superimposed infection in histologically proven cases of carcinoma. ¹ Both the conditions are associated with poor genital hygiene and tend to develop in populations that are marginalised, impoverished and with limited access to health facilities. ¹

The diagnosis of donovanosis is often missed in non-endemic areas because it is not suspected. ⁹ The index of clinical suspicion for donovanosis is low, even in endemic areas; and it was not uncommon in earlier times for mutilating operations to be performed on patients, misdiagnosing the lesion as cancer. ¹ However, failure of a case donovanosis to respond to antibiotics must cast a serious doubt on the diagnosis and a biopsy must then be undertaken.^1,9 Donovanosis has often been ignored in the past due to its low incidence and occurrence at few specific geographic locations. The low incidence has been explained by long incubation period, low infective nature of the disease and easy availability of antibiotics. However, the scarcity of donovanosis in the STI clinics of north India makes this case worthy of mention. Clinicians still need to be vigilant for this uncommon disease along with its rare complication, so that the diagnosis is not missed.