Metastatic squamous cell carcinoma complicating a chronic leprosy ulcer: Highlighting the need for long-term surveillance of ‘cured’ leprosy patients

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A 56-year-old man from Bihar, India, presented with gradually enlarging painless swellings in his right inguinal area for 4 months. He also reported weight loss of 10 kg in the last 3 months. He had a history of lepromatous leprosy treated with a 1-year course of the World Health Organization (WHO) multibacillary multi-drug treatment 20 years ago. On examination, there were multiple dusky red, firm-to-hard nodules measuring 3 cm × 4 cm on the right inguinal region, fixed to the underlying skin with surrounding induration [Figure 1a]. Further examination revealed a single large ulcer measuring 8 cm × 6 cm on the plantar aspect of the right forefoot. The ulcer margins were non-tender and hyperkeratotic with red, moist granulation tissue on the floor and an indurated base [Figure 1b]. On enquiring, the patient had noticed this plantar ulcer 1 year back.

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Figure 1a: Dusky red nodules on the right inguinal region.

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Figure 1b: Trophic ulcer on the plantar aspect of the right forefoot.

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Additional findings included distal resorption of the right great toe, flexion deformity of the right second and third toes, right ulnar claw hand, madarosis, bilateral ear lobe infiltration, and glove-and-stocking pattern of anaesthesia. A punch biopsy from the ulcer edge showed compact hyperparakeratosis, prominent irregular epidermal acanthosis, along with multiple scattered dyskeratotic keratinocytes, keratin pearl formation and focal suprabasal clefts with acantholytic cells [Figures 2a and b]. Biopsy of the inguinal nodule showed a deep dermal nodular collection of atypical cells with abundant pink cytoplasm and large hyperchromatic nuclei [Figures 2c and d]. The tumour cells were immunopositive for p40. A fine needle aspiration cytology examination of one of the enlarged inguinal lymph nodes showed sheets of dysplastic squamous epithelial cells, inflammatory cells and haemorrhage. A diagnosis of squamous cell carcinoma (SCC) complicating the trophic leprosy ulcer with lymph node metastases spreading to the overlying skin was made. A whole-body positron emission tomography-computed tomography (PET-CT) scan revealed a hypermetabolic ulcerative lesion in the right foot, causing erosion of phalanges of the 2^nd, 3^rd and 4^th toes, enlarged right inguinal and external iliac nodes and multiple skeletal lesions, including the right foot, vertebrae, pelvis and skull [Figure 3]. He developed hypercalcaemia (serum calcium 17 mg/dL, reference range: 8.6-10.2 mg/dL) and acute renal failure (serum urea 170 mg/dL, reference range: 0.7-1.2 mg/dL) during his hospital stay, which was managed with intravenous hydration, injection calcitonin (250 IU subcutaneous, twice daily for 4 days) and haemodialysis. Given the unfavourable prognosis, he was discharged on palliative care.

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Figure 2a: Biopsy from the ulcer edge shows massive hyperkeratosis (black asterisk) and irregular acanthosis (black arrows) (Haematoxylin & eosin, 20x).

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Figure 2b: Higher magnification shows keratin pearls (black arrow), dyskeratotic (green arrows) and atypical keratinocytes and focal suprabasal cleft (black asterisk) (Haematoxylin & eosin, 200x).

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Figure 2c: Biopsy from the inguinal nodule shows a deep dermal nodular collection of atypical cells (black arrow) (Haematoxylin & eosin, 20x).

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Figure 2d: Atypical cells with abundant pink cytoplasm and a large hyperchromatic nucleus (Haematoxylin & eosin, 100x).

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Figure 3: a) FDG PET/CT - Maximum intensity projection image (MIP) shows patchy increased metabolism in right foot and multiple lytic lesions in the visualised skeleton; multiple skeletal metastases foot (blue arrow) and another focal hypermetabolism in the right foot- localised to the soft tissue deposit medial to calcaneum (grey arrow). b) Sagittal fused PET/ CT images show hypermetabolism with extensive marrow metastases. Axial images fused PET/CT show c) a hypermetabolic ulcerative lesion in the right foot causing erosion of phalanges of the 2nd, 3rd and 4th toe (grey arrow), d) enlarged right external iliac nodes (grey arrow), and e) enlarged right inguinal nodes (grey arrow).

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SCC, complicating chronic wounds, including burn scars, venous ulcers, pressure sores and trophic ulcers, is well known and referred to as Marjolin ulcer.¹ Malignant transformation in chronic non-healing leprosy ulcers is well-documented in older texts, with Indian studies reporting a prevalence of 3-14%.^2-4 A Thai study reported 38 SCCs among 6,190 leprosy patients over a period of 10 years, translating to an incidence rate of 0.79 per 1,000 per year.⁵ Another study on skin biopsies of chronic leprosy ulcers found evidence of SCC in 24.5% of the specimens.⁶ SCCs arising on chronic leprosy ulcers usually affect the foot, particularly the sole.⁶ Most of the affected patients have been in the borderline-tuberculoid spectrum.^3,5 The paucity of recent reports on this subject reflects better management of disabilities and trophic ulcers and the overall success of the leprosy elimination program. However, post-release from treatment (RFT) care is often overlooked.

Our patient presented with a metastatic SCC arising from a non-healing plantar ulcer, many years after being declared ‘cured.’ Neglect of the plantar ulcer resulted in SCC, and the delay in recognising malignant transformation led to advanced disease at diagnosis, lymph node and skeletal metastases, complicated by hypercalcaemia and renal dysfunction. This case represents an extreme consequence of the systemic gaps that persons affected by leprosy continue to suffer after treatment completion in the post-elimination era.

According to the WHO, about 3-4 million ‘cured’ leprosy patients are still living with visible impairments or deformities.⁷ Further, the disability grades continue to progress even after treatment release, as evidenced by a Brazilian study that reported a 35% probability of disability worsening over 15 years.⁸ A recent nationwide Indian study found that 26% of leprosy patients seeking medical care were in the post-RFT period, with trophic ulcers and deformities accounting for 13% and 12% of complaints, respectively.⁹

Through this case, we wish to highlight a critical lacuna in the care of persons affected by leprosy. National programs should integrate surveillance for post-treatment monitoring of disabilities and other complications to ensure effective rehabilitation of persons affected by leprosy. The WHO global leprosy document for 2021-30 also emphasises “functioning post-treatment surveillance systems” as one of the key indicators of progress. However, clear operational guidelines are lacking regarding which patients should be monitored, by whom, how frequently, and for how long. Our case underscores the unmet need for long-term follow-up of leprosy patients in the post-RFT period, not just for relapse detection but also to identify and manage disabilities and resulting complications.