A forgotten disease reminds itself with a rare complication.

Diagnosed cases of sexually transmitted diseases (STD) represent tip of the iceberg and Donovanosis in one of them. Donovanosis, in most cases is obvious clinically, but rely for its confirmation on the demonstration of donovan bodies in histological sections and cytological preparation. In an extremely rare setting, this disease may get complicated by the development of squamous cell carcinoma. We report this occurrence in an 18-year-old girl to review the currently forgotten status of donovanosis amongst the STDs and the poor outcome of the disease if left untreated.

Introduction

Full-fledged cases of Donovanosis, characterized by genital ulcerations and buboes are not commonly seen these days. The histological characteristic of the affected tissues closely mimics, and thus, must be differentiated from the rare development of squamous cell carcinoma in the same.

Case Report

An 18-year-old girl presented with complaints of gradually increasing, painless nodule over labia for 8 months. Her main concern was a bleeding ulcer at the same site the area of which was increasing progressively over 2 weeks. She also gave history of intermittent oral ulcerations. On examination, there was diffuse enlargement of the right labia [Figure 1] which was ulcerated (3 × 3 cm). She had characteristic presence of ulcerated bubo (2 cm) formed out of the ipsilateral inguinal lymph node. The ulceration bled on touching. There were no oral ulcerations at presentation. There was a history of unprotected sexual exposure. The clinical diagnosis of donovanosis was made and the patient was referred for histopathological confirmation. A wedge biopsy was taken from the margin of the genital ulcer and impressions smears made from it and the discharging bubo. The biopsy sections were stained by hematoxylin and eosin (H and E). Impression smears were stained with both H and E and Giemsa.

Figure 1

Photograph showing large bleeding ulcer over the right labia with the arrow pointing to the bubo over the right inguinal region

Microscopic examination revealed fairly cellular smears, which in addition to mature keratinized superficial squamous epithelial cells showed numerous foamy histiocytic cells and macrophages. These cells were covered by dense sheets of inflammatory cells, chiefly neutrophils. Few small cell clusters with hyperchromatic nuclei, clumped chromatin, and occasional prominent nucleolus were present and a few bizarre cell forms with pyknotic nuclei were also seen. The inflammatory infiltrate comprised of numerous neutrophils, few plasma cells, foamy histiocytes, and vacuolated macrophages with typical basophilic bodies with bipolar condensation of chromatin (closed safety pin appearance of Donovan bodies) [Figure 2]. Microscopic examination of the sections showed tissue lined by keratinized stratified squamous epithelium. The epithelium showed pseudoepitheliomatous hyperplasia with long slender finger-like rete-pegs extending down into a heavily inflamed stroma. At places concentric keratin pearl formation was also seen.

Figure 2

Smears from ulcerated site showing bipolar Donovan bodies (H and E, ×1000)

In order to ascertain the nature of pseudoepitheliomatous hyperplasia a deeper biopsy was undertaken from the primary site as well as the pseudobubo a week later. This showed frankly invasive squamous cell carcinoma (SCC) with numerous islands of mature stratified squamous epithelium and foci of keratin pearl formation.

Meanwhile, the patient who had been started the standard treatment for donovanosis, did not show even slightest response to therapy. She had to undergo unilateral vulvectomy and ipsilateral inguinal lymph node dissection. The lymph node were however negative for metastasis.

Discussion

Here, we report a disease which has been in obscurity for long but then again came to attention following spread of HIV when it was recognized as one of the causes of its enhanced transmissibility. We have in particular brought to attention a rarer association of this disease with SCC that can complicate it.

Donovanosis (also known as “granuloma inguinale” or ‘granuloma venereum’) is caused by Calymmatobacterium granulomatosis, a gram-negative non-motile encapsulated bacillus with phylogenetic similarity to the Klebsiella species.[1] The disease, although reported from several parts of the world, is known to have certain hot spots of which India is one. Accurate epidemiological data is lacking but it is understood that the disease is on the wane. The disease is not always sexually transmitted and there have been suggestions that few cases may occur through fecal contamination and autoinoculation.[2]

Gradually increasing subcutaneous nodules which erode through the skin to form sharply defined painless ulcers which bleeds readily to touch, is how the disease usually manifests initially. It can also present as verrucous ulcer, necrotic ulcer or a cicatricial ulcer.[3] Oral Donovanosis is the commonest extra-genital manifestation (in about 6%). Dissemination to liver and bone has been rarely described. Differential diagnoses include chancre, chancroid, herpes, malignancy, and tuberculosis of the cervix. Diagnosis rests mainly upon the demonstration of intracellular Donovan bodies in mononuclear cells obtained in tissue specimens. PCR and serological methods have been also developed and are being tested for their practical utility.[45] Azithromycin is considered the drug of choice and recommended by the WHO.[6]

Untreated adequately, Donovanosis may get complicated by pseudoelephantiasis or cancer. Although known, carcinomas are fortunately very rare but a dreaded complication of this disease. In a series by Rajam and Rangiah in 1954, carcinoma developed in only 0.25% the patients;[7] but that was when the disease was much more prevalent and effective treatments were not available. Carcinomas are rarely been reported now in the context of Donovanosis. In the most recent study published in 2003, one out of the 25 patients studied developed vulval squamous cell carcinoma.[8]

To conclude, Donovanosis may be forgotten in general practice, but a forgotten disease keeps reminding itself intermittently. This report is written with an objective of not only just highlighting a very rare complication of Donovanosis but also to remind that the disease still exists.