# Secondary Primary Carcinoma Arising on the Flap Skin in the Oral Cavity--Case Series
## 5 Discussion  
While the occurrence of secondary primary OSCC is not uncommon, especially in the oral region, because of the previous prolonged effect of tobacco and alcohol consumption in the majority of these patients, a secondary primary carcinoma on the flap used in a previous surgical management is particularly rare. A recent systematic review reported that there were only 27 cases described in the literature [12]. All of the cases were in the oral cavity, and all of the secondary primary OSCC were located in the center of the flap skin with clear margins. Furthermore, there was a recent cohort study that included 21 patients with potentially malignant disorders or skin cancer on the intraoral flap skin [15]. They conducted an immunohistochemical study with a focus on p53 and p16. Their results showed that these second primary tumors had a relatively low altered p53 and a relatively high p16 positivity. The pathophysiology underlying cancer development on skin flaps in the oral cavity is a subject of controversy and ongoing discussion [12; 15]. One theory posits that neoplastic  
Figure 1: Microscopic image of the tumor where overlying skin and adnexal structures are visible. The enlarged circle is showing the apocrine and accrine glands (HE 200\(\times\)). cells migrate from altered mucosa to the skin flap, a phenomenon known as the \"Borst-Jadasson phenomenon\", subsequently progressing into cancer [16; 17]. This process is further elucidated by the field cancerization theory [13; 18; 19]. Moreover, [PERSON] et al. discovered that neoplastic lesions originating on skin flaps in the oral cavity share the same clone and genetics as the primary oral squamous cell carcinoma (OSCC) [20]. Hence, a possible explanation is that the cancer cells migrate from the surrounding mucosa to the flap. Conversely, in a retrospective study, [PERSON] et al. argue that cancers on the skin of flaps exhibit low TP53 mutations and higher p16 positivity compared to OSCC, suggesting they should be considered a distinct entity [21]. They propose that exposure of the skin to a new environment induces carcinogenesis through chronic irritation and inflammatory reactions, resulting in the formation of skin cancer within the oral cavity [22]. Furthermore, [PERSON] et al. assert that skin exposure to new stressors, such as saliva, altered pH, and oral flora, may contribute to carcinogenesis. They draw parallels with the development of adenocarcinoma in [PERSON]'s esophagus [12]. Additionally, [PERSON] et al. compare the mechanism of carcinogenesis on skin flaps due to chronic irritation with the carcinogenesis commonly observed in burn scar tissue [15; 23; 24]. Therefore, another possibility is that the skin, due to new and \"alien\" environmental factors in the oral cavity, undergoes inflammatory reactions that could trigger an emergence of a new primary cancer. Nevertheless, determining the correctness of either theory, or if both theories exert some influence, requires further research. Another possible explanation of the secondary primary cancer emergence on the flap skin is the process called mucozalization [11]. Macroscopically, the skin of the flaps after a prolonged time in the oral cavity starts to appear similar to the surrounding mucosa [25]. Moreover, several histological articles have suggested that there is an alteration of the skin histology after several years in the oral cavity [11; 26]. These histological changes are characterized by inflammatory infiltration, reduction of the stratum corneum thickness, and loss of skin appendages. However, this theory is severely challenged, and some authors have proposed that actually the chronic candida infection due to the \"alien\" environment is the reason behind the histological changes of the flap skin [27]. Nevertheless, it seems that the skin gradually undergoes some changes.