Abstract
Primary cutaneous – diffuse large B-cell lymphoma – leg type (PC-DLBCL-LT) is a less frequent but more aggressive, and potentially curable, type of cutaneous B-cell lymphoma, with intermediate prognosis, that affects elderly individuals. Our patient with indurated, pigmented foot previously treated for Filariasis, now presented with ulcers, multiple discharging sinuses, clinically suspected to have Madura Foot. Histopathological examination confirmed a diagnosis of PC-DLBCL-LT after which he underwent below-knee amputation.
Case report
An 82 year-old male presented to our hospital with complaints of swelling of the left foot for 30 years. He gave a history that this started as a reptile bite, followed by induration and pigmentation of the skin over the years. He was initially suspected to have lymphatic filariasis and was treated with diethylcarbamazine.
Three months prior to presentation, he developed multiple small nodules and yellow plaques along with discharging sinuses over the heel. On examination, two ulcers were seen on the posterior aspect of the left foot with numerous sinuses present over its medial aspect (Figure 1(a)). The discharge was yellowish, not blood-stained and non-odorous. Inguinal lymph nodes were palpable (1 × 1 cm on the left) with no evidence of tenderness and warmth. Madura Foot (Mycetoma) was suspected, and treatment with dapsone and cotrimoxazole was commenced but with no response.
(a) Indurated, pigmented foot with large ulcer and multiple discharging sinuses, mimicking Madura Foot; (b) post-debridement and amputation specimen.
A fine needle aspiration cytology specimen from an inguinal lymph node was suggestive of reactive lymphadenitis. Blood culture and peripheral blood smear did not reveal any abnormality. An MRI scan of the foot showed altered intramedullary signal intensity and an ill-defined, large, heterogeneous soft-tissue which was iso-hypointense on T1, and hyperintense on T2 and STIR imaging, with heterogeneous post-contrast enhancement seen involving all the bones forming the ankle joint, and involvement of posterior tibial neurovascular bundles and sural nerve.
An incisional biopsy was therefore performed from the non-ulcerated areas and sent for histological examination. This revealed an acanthotic epidermis overlying granulation tissue and tumour with gangrenous changes composed of diffuse sheets of large atypical malignant lymphoid cells. These had a high nucleo-cytoplasmic ratio, oval indented nuclei, irregularly dispersed chromatin and scant to moderate cytoplasm (Figure 2). On immunohistochemistry, the tumour cells showed positivity with LCA, CD20, BCL-2 and MUM1, with a Ki-67 of 75%. CD3, CD10 and CD30 were negative (Figure 3). A diagnosis of primary cutaneous diffuse large B-cell lymphoma of leg type (PC-DLBCL-LT) was established, and a left below-knee amputation under spinal anaesthesia was carried out (Figure 1(b)).
Diffuse sheets of large atypical malignant lymphoid tumour cells with irregular chromatin and scant amount of cytoplasm (original magnification ×200). Tumour cells show membrane positivity with CD20 (a), diffuse nuclear and cytoplasmic positivity with BCL-2 (b), nuclear positivity with MUM1 (c) (original magnification ×400) and negative with CD10 (original magnification ×200).
Discussion
Primary cutaneous lymphomas are defined as non-Hodgkin type with no evidence of extra-cutaneous disease at the time of diagnosis. 1 Cutaneous T-cell lymphomas account for 75–80% of these cases, whereas the remaining 20–25% are of B cell origin. 2 According to the 2018 updated WHO – EORTC classification, cutaneous B-cell lymphomas are divided into PCMZL (primary cutaneous marginal zone lymphoma), PCFCL (primary cutaneous follicular centre lymphoma), PC-DLBCL-LT, intravascular large B-cell lymphoma and EBV+ mucocutaneous ulcer. 3 PC-DLBCL-LT accounts for 4% of all primary cutaneous lymphomas and 20% of all primary cutaneous B-cell lymphomas.2,4 In around 15–20% cases, they are seen at sites other than the leg. 4 They are predominantly seen in elderly females with median range in their seventh decade, with male to female ratio of 1:2–1:4.3,4
Such patients usually present with rapidly growing red or violet tumours on one or both lower limbs, showing aggressive behaviour. A poor prognosis, owing to frequent relapses and a tendency of extending outside the skin is common,5,6 in contrast to PCFCL. WHO – EORTC reports 56% five-year disease-free survival rate. 3
The diagnosis is made on clinical, histological, immunohistochemical and molecular studies. A skin biopsy must include the reticular dermis and subcutaneous cell tissue because it may otherwise not be possible to differentiate it from an inflammatory process due to EBV infection.2,6 Microscopically, it presents as a dense diffuse infiltrate within the dermis and subcutis of a monotonous population or confluent sheets of medium-sized to large B cells with round nuclei, prominent nucleoli and coarse chromatin resembling centroblasts or immunoblasts. 7 The differential diagnosis includes epidermal cancers, melanoma, Kaposi’s sarcoma and other cutaneous B-cell and T-cell lymphomas (especially PCFCL having centrocyte-like morphology). 8
A lack of characteristic ‘sulphur’ granules, not responding to standard treatment regimen, really excluded mycetoma as a diagnosis.
Footnotes
Authors’ contribution
Manuscript has been read and approved by all the authors and the requirements for authorship have been met. The authors believe that the manuscript represents honest work.
Acknowledgements
The authors would like to acknowledge Kasturba Medical College, Manipal, India for permitting to carry out the study.
Ethical considerations
The ethical clearance was approved before the commencement of this study from the Institutional Ethics Committee (IEC) at Kasturba Medical College, Manipal, India.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Patient consent
The consent for publication of the images after proper de-identification was obtained from the patient.