Multiple metastatic eccrine porocarcinoma with squamous differentiation in oculo-cutaneous albinism

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Patients with oculo-cutaneous albinism (OCA) are prone to skin cancers, commonly squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).¹ Eccrine porocarcinoma (EPC) is a rare malignant adnexal tumour, which originates from the intraepidermal portion of the eccrine sweat duct, i.e., acrosyringium, and accounts for about 0.005-0.01% of all cutaneous malignancies. It was first described by Pinkus and Mehregan in 1963. In 1969, Mishima and Morioka coined the term ‘eccrine porocarcinoma’. Squamous differentiation occurs in a significant proportion of EPC cases and is almost clinically and histologically indistinguishable from SCC, making the diagnosis challenging.

A 29-year-old man, known case of OCA with mental retardation, presented with painful ulcerated swelling on the left axilla for 2 months. His younger sister was also affected by OCA. His parents had a second-degree consanguineous marriage. On examination, he had a tender swelling of size 7 × 7 cm with central ulceration in the left mid-axillary region, a well-defined crusted erosive plaque of size 1 × 1 cm over the right ear pinna, two well-defined erythematous nodules of size 2 × 2 cm and 2 × 3 cm over the left supra-scapular region and a 5 × 4 cm atrophic scar over the pre-sternal area representing excisional biopsy scar over the previous site of porocarcinoma [Figures 1a-d]. Laboratory investigations revealed anaemia (haemoglobin: 9 g/dL). The viral markers were negative. Positron emission tomography with computed tomography (PET CT) scan revealed a metabolically active mass lesion in the left level 1 axillary region, of size 7x5.4x8.6cm extending to the overlying skin [Figure 2]. Dermoscopy of the skin lesions over the back showed an atypical vascular pattern with polymorphous vessels and pink-white ovoid areas [Figures 3a and b]. Excision biopsy was done for the ulcerated nodule in left axilla with 0.6 cm resection margin, and the histopathology (HPE) revealed a tumour arising from epidermis with large polygonal cells having markedly pleomorphic hyperchromatic nuclei and abundant eosinophilic cytoplasm with keratin pearls and areas of necrosis. The mitotic rate was 70/10 high-power fields (HPF). Focally, the tumour cells were forming ducts and glands. Comedo-necrosis was seen [Figures 3c-e]. Immuno-histochemistry (IHC) was strongly positive for cytokeratin 7 and 19 (CK7, CK19), p63, and epithelial membrane antigen (EMA) [Figures 4a and b]. CK 5 and 6 were focally positive. These findings were compatible with EPC with squamous differentiation. Genetic testing was not done since the facility was not available in our hospital, and the patient and his family declined to get it done elsewhere. A trucut biopsy from the skin lesion over the back revealed a malignant neoplasm composed of cells arranged in nests and sheets with nuclear pleomorphism and cellular atypia, suggestive of possible metastasis of EPC [Figure 4c]. Trucut biopsy of the crusted lesion over the right pinna also showed atypical cells [Figure 4d]. The patient had a similar history of a painful ulcerated lesion over the pre-sternal area for 6 months, for which an excision biopsy was done 2 years back and reported as porocarcinoma. The patient was discharged after 10 days of surgery and asked to review after 1 month, but did not come for follow-up.

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Figure 1:

Clinical images showing; a) swelling with ulceration in the left axilla, b) two well-defined erythematous nodules over the left supra-scapular region, c) a crusted erosive plaque over the right ear pinna, d) atrophic scar over the pre-sternal area.

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Figure 2:

PET CT scan image showing a metabolically active mass lesion in the left level 1 axillary region of size 7x5.4x8.6cm.

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Figure 3:

a) Dermoscopic picture of a lesion over the back exhibiting polymorphous vessels (white arrow) and pink-white ovoid areas (black arrow) suggestive of eccrine porocarcinoma.(Heine 30 dermatoscope, polarised 10x), b) Dermoscopic image of another lesion over the back also showing polymorphous vessels (white arrows) and pink-white areas (black arrows). (Heine 30 dermascope polarised, 10x).

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Figure 3c-e:

Histopathological examination (HPE) of excised lesion from left axilla showing c) tumour cells with pleomorphic nuclei and cellular atypia forming ducts and glands, d) atypical cells and comedo necrosis (red arrows). (Haematoxylin & eosin, 40x), e) large polygonal tumour cells with increased mitoses (Haematoxylin & eosin, 100x).

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Figure 4a:

Immuno-histochemistry (IHC) of tumour excised from left axilla showing positivity for cytokeratin 7 highlighting the ducts (CK7, 40x).

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Figure 4b:

Immuno-histochemistry (IHC) of tumour excised from left axilla, positive for cytokeratin 19 highlighting the tumour cells, (CK 19, 40x).

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Figure 4c:

Histopathological examination of the trucut biospy specimen taken from the lesion over upper back showing atypical cells with nuclear pleomorphism (Haematoxylin & eosin, 40x).

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Figure 4d:

Histopathology of trucut biopsy specimen taken from the right ear pinna showing pleomorphic cells (Haematoxylin & eosin, 10x).

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EPC is a rare malignant skin appendageal tumour, which usually manifests as an erythematous to violaceous nodule; either asymptomatic or presenting with pain, ulceration, and spontaneous bleeding, with a mean diameter of 2.4 cm.² The most common dermoscopic features are an atypical vascular pattern with diffuse arrangement of polymorphous vessels and pinkish-white ovoid areas. Fine scaling, erosions, and structureless pink-white areas have also been described. The dermoscopic features of our case aligned with those of classical EPC.

The histopathological characteristics are diverse and may pose difficulties in the diagnosis; mainly it can be confused with SCC. Histopathological findings of large basaloid poroid cells exhibiting ductal differentiation, cytologic atypia, increased mitoses, tumour necrosis, and infiltrative growth pattern enable the diagnosis of EPC. Comedo-necrosis, i.e., tumour cells containing central necrosis with an inflammatory reaction, is a unique finding. On immunohistochemistry (IHC), cells stain positive for cytokeratin 7 and 19 (CK7,CK19), epithelial membrane antigen (EMA), carcino-embryogenic antigen (CEA), and tumour protein (p63).³ In SCC, CK 5 and 6 are strongly positive.

In our case, IHC was strongly positive for CK7, CK19, and EMA, while CK 5 and 6 were only focally positive, which is in favour of porocarcinoma with squamous differentiation and hence, rules out SCC. Studies report an approximately 20% risk of local recurrence and 10% risk of distant metastasis. The standard treatment is wide local excision with at least a 2-mm margin.

EPC arising in a patient with OCA is very rare. Only three cases have been reported in the literature so far.^4,5 Out of these three cases, two had squamous differentiation. In a meta-analysis of 120 EPCs, 25% of cases showed squamous differentiation.⁶ In a study of 21 cases of EPC with squamous differentiation, the average tumour size was 46.5 mm, almost twice that of the average EPC, and one patient had OCA.⁷ The important differential diagnosis of EPC with squamous differentiation is SCC. Table 1 compares and contrasts SCC and porocarcinoma with squamous differentiation. EPC has a poorer prognosis compared to SCC.

In our case, large tumour size, rapid progression, and high mitotic index were poor prognostic factors. The presence of multiple lesions having features of EPC on clinical, dermoscopic, and HPE examination indicate that the tumour had progressed to an advanced stage with multiple metastases. The case required a multi-disciplinary approach. The tumour was surgically removed and no adjuvant therapies were given.⁸

We conclude that EPC arising in a patient of OCA is extremely rare. Squamous differentiation in a subset of patients may be attributed to UV radiation and immunosuppression. EPC can also present as multiple metastatic variant.