Discussion
PC is a rare, aggressive, and chemoresistant skin cancer arising from one of the four primary adnexal structures of the skin: the hair follicle and sebaceous, eccrine, and apocrine glands; more exactly, it derives from terminal cells of the intraepithelial part of the eccrine duct called the acrosyringium [4].
This aggressive tumor can metastasize to local lymph nodes or distant organs. Skin metastases may be found near the primary tumor. Other less usual metastatic sites include lung, liver, breast, ovaries, bone, bladder, and retroperitoneum. The most common locations affected by PC are the lower extremities, head and neck, trunk, genitalia/buttocks, and upper extremities [5].
PCs located on the genitalia and buttocks have a higher propensity for distant metastases compared to those arising in the head and neck area. Metastatic disease is already present at diagnosis in up to 31% of cases, where the most common sites involved are regional lymph nodes (60%) and lungs (13%). The related prognosis is poor, with 50%– 80% mortality and 9% of overall survival rates of 10-years.
To date, only 15 cases occurring on the arms (including the current case) have been documented in the literature [7-31]. Clinically, PC presents as a slow-growing, red, dome-shaped skin nodule with a shiny surface or as a wart-like plaque, papule, or polyp that is sometimes painful and ulcerative. The lesion size can range from less than 1 cm to up to 10 cm.
Due to its rarity, PC can mimic other skin conditions and could be misdiagnosed as other cutaneous neoplasms, particularly as squamous cell carcinoma. Differential diagnosis is mandatory in the presence of other skin lesions, such as amelanotic melanoma, seborrheic keratosis, pyogenic granuloma, Bowen’s disease, verruca vulgaris, fibroma, or even metastatic adenocarcinoma. Thus, diagnosis is often delayed, and optimal management is lacking. Due to its aggressive nature, the prognosis for local recurrence after standard-wide local excision is poor, with a recurrence rate of 20% [10].
Histologically, PC can be recognized by lobules and cords of pleomorphic basaloid cells with enlarged hyperchromatic nuclei and mitotic activity. Two histopathological variants of PC exist: trabecular and epidermotropic. The second one is more aggressive than the first and is frequently associated with local recurrences and metastatic lesions [6].
The survival for patients with distant metastases is reported to be 5 to 24 months. Mortality is high, reaching 80% in distant diseases and 65%–67% when lymph nodes are involved. Given its rare occurrence, most of the literature has reported single clinical cases and a few case series, and there are currently no uniform international guidelines for these patients [7-31].
There is no standard treatment for metastatic disease. Undoubtedly, the treatment of choice is wide excision, which results in cure rates of 70% to 80%. Although good results have been reported with 3- to 5-mm resection margins, surgical margins should range from 1 to 2 cm. When the disease is inoperable or advanced, systemic treatment represents a challenge. Mohs micrographic surgery may be a valid effective treatment option for PC. The role of sentinel lymph node biopsy is not yet well defined, although it could be useful for high-risk PC in cases with signs of histological aggression or intralymphatic involvement [10].
Treatment of distant metastatic PC is not yet well defined. Neither chemotherapy nor radiotherapy has been clinically advantageous in metastatic disease. In this regard, various therapeutic schemes have been evaluated with many uncertain results. Among these, taxane-based regimes have proven to be effective, with a response in 50% of cases. Paclitaxel plus cetuximab have been observed to provide an almost complete morphological response and a complete metabolic response at all locations of metastatic PC with strong epidermal growth factor receptor (EGF-R) expression, except for persistent bone metastases, where, however, metabolic activity was low due to the radiation therapy [32].
In the literature, we found other interesting case reports. Complete remission was also seen with polychemotherapy with doxorubicin, mitomycin C, vincristine, and 5-fluorouracil (5-FU), alternating with cisplatin and bleomycin or hyperthermic perfusion with 5-FU and melphalan. Other agents have been administered in combination, including cisplatin and docetaxel, carboplatin and paclitaxel; doxorubicin, mitomycin, vincristine, and 5-fluorouracil; anthracycline, cyclophosphamide, vincristine, and bleomycin; isotretinoin and interferon-alpha [33-35]. Other case series described using topical 5-FU and intraarterial docetaxel and docetaxel as a single agent. Furthermore, long-term outcomes have been recently achieved with pembrolizumab [36].
Radiosensitivity of PC is suggested by some case reports. Adjuvant radiotherapy is not yet standard of care, but it would be recommended in high-risk situations, such as cases with positive surgical margins, tumors larger than 5 cm, lymphovascular involvement, and tumors with moderate to poorly differentiated grading [37]. Metastatic cervical lymph nodes successfully treated with cyberknife radiosurgery have also been mentioned [38].
In conclusion, the best chance for cure is early diagnosis and surgery because neither chemotherapy nor radiotherapy has shown some clinical benefit in metastatic PC.