Metastatic eccrine carcinoma with stomach and pericardial involvement

Eccrine carcinoma is the most aggressive among skin adnexal tumors. They can arise on the lower limbs, trunk, head and neck, scalp and ears, upper extremities, abdomen, and genital sites.⁷

The cells of eccrine sweat glands express low molecular weight keratin, epithelial membrane antigen, carcinoembryonic antigen, as well as S100 protein, smooth muscle actin, p63, calponin, cytokeratin 14, and bcl-2.⁸ Skin tumors with eccrine differentiation may stain for estrogen and progesterone, which has important clinical implications because those patients can be treated with hormonal therapy.⁹ Positivity for estrogen receptors does not differentiate cutaneous eccrine tumors from cutaneous metastases of breast cancers.^8,9 Androgen receptor evaluation in these cases can help distinguish between the two.¹⁰ Human epidermal growth factor receptor 2 (HER-2) is expressed in 3.5% of skin adnexal tumors.¹¹

The molecular pathogenesis of malignant adnexal tumors is not clear, but overexpression of tumor suppressor protein p16 has been described as a common feature in eccrine carcinomas.¹²

Prognostic factors for sweat gland carcinoma are difficult to identify, because of the small number of reported cases. The likely prognostic factors include size, histological type, lymph node involvement, and presence of distant metastasis. Absent of lymph node involvement correlates with 10-year disease-free survival rate of 56%, which falls to 9% if nodes are involved.¹³

There are no uniform guidelines for the treatment sweat gland carcinomas, and the clinical experience described in the literature is the only source of available information.

The treatment of choice of all subtypes of localized sweat gland carcinomas is wide surgical excision with broad tumor margins, given the propensity for local recurrences along with regional lymph node dissection in the presence of clinically positive nodes. Prophylactic lymph node resection does not seem to improve survival or decrease recurrence rates.⁷ The use of adjuvant radiotherapy to prevent local recurrence also is not well established. One report suggested radiosensitivity of these tumors, and adjuvant radiation was therefore recommended in high-risk cases (ie, large tumors of 5 cm and positive surgical margins of 1 cm) and moderate to poorly differentiated tumors with lymphovascular invasion.¹⁴ Adjuvant radiation to the involved lymph node basin is suggested in the setting of extranodal extension or extensive involvement, that is, 4 lymph nodes.¹⁵ The role of lymphadenectomy has not been adequately addressed in the literature.

The role of chemotherapy in metastatic disease is not clear, but sweat gland carcinomas are considered chemoresistant (Table). Several combinations have been used with short-term responses. In one case treated with doxorubicin, mitomycin, vincristine, and 5-FU followed by maintenance therapy, the patient achieved a complete response that lasted for 16 months.¹⁶ In another report, the treatment response was 2 years with treatment consisted of anthracyclin, cyclophosphamide, vincristine, and bloemycin.¹⁷ Other combinations used in the literature include carboplatin and paclitaxel, which led to prolonged remission.¹⁴ Cisplatin and 5-FU, or cisplatin plus cetuximab have been reported but with discouraging results.¹⁸ Results to taxanes showed conflicting results.^19,20

Hormonal therapy can be effective in cases in which estrogen and progesterone receptors are expressed, which can range from 19%-30% of eccrine sweat gland carcinomas.^21,22 Two cases have reported complete regression of lymph nodes in patients with metastatic disease, and in 1 patient relief from pain caused by bone metastases with durable response of around 3 years.^23,24 a

Experience with targeted therapy is very limited. Sunitinib has been reported to have some activity in metastatic adnexal tumors as a second-line therapy in 2 patients, with disease control for 8 and 10 months respectively.²⁵ Trastuzumab has been reported as having activity in 1 patient with strong HER2 expression (IHC score of 3+, denoting HER2 positivity), with complete regression of metastatic tumor. Upon progression in the same patient, a combination of lapatinib and capecitabine also showed positive response.²⁶

In conclusion, metastatic sweat gland tumors treatment has not been standardized because of a dearth of reports in the literatures. Its early identification and complete excision gives the best chance of a cure. Neither chemotherapy nor radiation therapy has been proven to be of clinical benefit in treating metastatic disease.