Eccrine Porocarcinoma (EPC), also known as malignant eccrine poroma, is a rare malignant adnexal tumor of the skin originating from the eccrine gland. This neoplasm was first recognized by Pinkus & Mehregan in 1963 as “epidermotropic eccrine carcinoma”.1 It accounts for 0.005% to 0.01% of all malignant cutaneous neoplasms.2,3 Although this neoplasm is rare, it is still the most frequently malignant tumor of eccrine gland tumor.4 Studies have shown that some EPCs are developed from their preexisting benign counterpart, Eccrine Poroma (EP).5–7 The exact etiology and pathogenesis of EPC are still unknown, and the factors that are associated with the malignant transformation of EPC have not yet been identified.8,9 Furthermore, EPC is a rare eccrine sweat gland malignancy that is often clinically misdiagnosed, and the differential diagnosis of EPC is extensive pathologically, even sometimes the differences between EP and EPC are not straightforward. To shed light on this, the authors present a series of cases and highlight the key features of the two rare diseases. Apart from cytological malignant features, the authors focus on subtle, less commonly encountered pathological features of EPC versus EP.

EPC is a relatively rare malignant cutaneous neoplasm arising from the sweat glands. As a malignant counterpart of EP, its incidence rate was about 1.866 per 100,000 according to the previous study.10 In recent years, the incidence rate of EPC has been reported to be gradually increasing. In the present study, EPC accounted for about 0.008% of all skin tumors, the incidence may be influenced by consulting cases which may increase the incidence. Local recurrences and lymph node metastasis are seen in about 17% of cases, and in 8% of patients may lead to death due to disseminated malignancy.10 According to previous studies, although EPC can be primary, most of them are derived from EP, and the associated factors for the development of EP into EPC are still unclear. The proportion of EPC cases developing from EP has varied in previous reports. In this case series, 4 patients (4/22, 18.2%) presented with sudden onset of ulceration, hemorrhage, or enlargement at the sites of pre-existing lesions, whereas 6 patients (6/22, 27.3%) had residual foci of benign eccrine lesions. These findings suggest that these EPC cases may have originated from pre-existing EP. However, some cases may have developed over a longer time, making it difficult to distinguish the transitional elements. In addition, 4 cases (4/22, 18.2%) of EPC patients in the present study developed metastases, in agreement with previous studies.

Previous studies found that chronic light exposure is a risk factor for developing EPC.5–7 This may be related to its effect on the regulation of the immune system. UVB induces and activates immunosuppressive regulatory T-cells, reduces the number and function of Langerhans cells, and increases the release of immunosuppressive mediators.8 Recent reports have debated the common location of EPCs. Some studies have shown that the most common location of EPC is the lower limb, but others have suggested that the most common location is the head neck, or trunk.5,11–13 These results showed that EPCs were predominantly located in the exposure area. This finding supports that chronic light exposure is one of the possible associated factors for malignant transformation. The difference in the mean age between the two groups suggests that elderly people are more likely to have a malignant transformation which may be due to reduced immune surveillance. While some previous case reports suggest that EPCs may be associated with larger size, actinic damage and older age, the present study provides additional evidence.

Statistically significant differences were observed in terms of disordered cell arrangement, cellular mitosis, and cytological atypia according to the diagnostic and inclusion criteria for EPC in this study. Apart from cytological malignant features, the authors focus on less commonly encountered pathological features of EPC versus EP. Infiltrative growth patterns and asymmetric tumor architecture were significantly more common in the EPC group, similar to the differences between most benign and malignant tumors. Some researchers believe that the aggressive biological behavior associated with ulceration may be the consequence of an intrinsic biological property of the tumor, which favors its dissemination and is locally manifested by the absence of epidermal integrity.14 The data supported this finding that ulceration was more common in the EPC group. Similar findings have been reported in cutaneous squamous cell carcinoma and melanoma.14–17 Central necrosis refers to the death of central cancer cells with surrounding inflammatory debris and the surrounding inflammation results in a comedo-like appearance.5 The authors observed a central necrosis pattern in 54.5% of the EPC cases, which is higher than the 32% and 45% observed by the previous researchers.5,12 This aspect may be due to localized ischemia and necrosis in the malignant tumor, leading to cell death and aggregation in the central area, forming a central necrotic zone. In the EPC group, the authors observed a significantly higher incidence of diffuse inflammatory infiltration of the dermis than in the EP group. Tumor-associated inflammation is a feature of essentially all cancers and can confer tumor-promoting function.18,19 This may be due to the highly active and invasive nature of the tumor, leading to an increased inflammatory response in the surrounding tissue.

In the EPC group, the authors identified squamous differentiation in 36.4% of patients. This is similar to the findings of Riera-Leal et al.12 The presence of squamous differentiation in EPC has been a subject of varied interpretations. Some scholars considered it a distinct pathological subtype of EPC, while others viewed it as a variant of squamous cell carcinoma.12,20 There was also a perspective that deemed it as an incidental finding with limited significance.21 In this context, the authors align with the viewpoint that regards it as a unique pathological subtype of EPC. This may represent a pattern of malignant transformation in EP, but the exact mechanisms behind it require further research and investigation. Similar to squamous differentiation, the authors also observed statistically significant differences in spindle cell change. In contrast to the 4% reported in the previous study, the authors observed spindle cell change in 18.2% of these cases.5 Robson et al. considered this type of EPC as a spindle cell variant of porocarcinoma and proposed a spectrum that may exist between a pure spindle cell porocarcinoma and tumors with more classical morphology.5 This type of EPC can express a high degree of heterogeneity and malignancy.22

The authors also suspect that tumors that differentiate into apocrine glands with more complex components, including hair, are more susceptible to malignant transformation. The authors have therefore observed decapitate secretion and sebaceous differentiation in these cases. However, we have not found significant differences in these cases to support this hypothesis. Delicate fibrovascular stroma and sharp demarcation between normal keratinocytes and poroma cells are important pathological features of poroma and were also common in the EPC group in this study, with no significant difference between the two groups.

In conclusion, the present study highlights the differences in clinicopathological features between EP and EPC patients. EPC occurs more frequently in older patients, and exposed sites, and is more likely to be ulcerated and to be larger. Histologically, the authors found infiltrative growth patterns, asymmetric tumor architecture, ulceration, central necrosis, squamous differentiation, spindle cell changes, and diffuse inflammatory infiltration significantly more frequent in the EPC group. The findings of this study may help to identify potential factors associated with the malignant transformation of EP and assist clinicians in diagnosis and management.

None declared.

Qin-Xiao Wang: Conceptualization; data curation; methodology; formal analysis; visualization; validation; writing-original draft.

Si-Yu Luo: Data Curation; investigation; visualization.

Kai-Yi Zhou: Data Curation; project administration; validation.

Xiao Shen: Resources; Supervision; writing-review & editing.

Sheng Fang: Conceptualization; Methodology; resources; supervision; writing-review & editing.