# Tumor Microenvironment and Dermatological Conditions in Prostate Cancer
## 2 The Cutaneous Manifestations Associated with PCa
### Potential Nonmalignant Cutaneous Manifestations Associated with PCa  
Paraneoplastic syndromes are conditions linked to cancer that are not caused by direct tumor invasion. These syndromes are considered indirect systemic manifestations related to the tumor. PCa in advanced stages is the second most frequent urological neoplasm connected to paraneoplastic syndromes, following renal cell carcinoma [13; 55]. SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is an uncommon autoimmune disorder exceptionally associated with cutaneous metastasis of PCa. In general, paraneoplastic arthritides represent immune-mediated inflammatory diseases that can occur in conjunction with occult or manifest malignancy [56]. The coexistence of malignant acanthosis nigricans and PCa is rare, and few cases have been reported. Acanthosis nigricans most probably appears due to substances produced by tumors that stimulate keratinocytes, melanocytes, and fibroblasts. Hyperpigmentation and hyperkeratosis are clinical features found in patients with acanthosis nigricans; sometimes, the lesions may also involve the mucous membranes [49]. PCa has been linked to simultaneous paraneoplastic manifestations of the skin in the same patient, such as Bazex syndrome, acquired ichthyosis, or the Leser-Trelat sign [57]. Paraneoplastic acrokeratosis (Bazex syndrome) is defined by the symmetrical occurrence of of erythemat-squamous plaques with undefined margins in the acral areas and nail damage (hyperkeratosis, onycholysis, growth and thickening, and yellow pigmentation) [57]. In addition to the connection with paraneoplastic lesions, Bazex syndrome has been detected in association with multiple simultaneous genitourinary tumors (multifocal basal cell carcinoma, squamous cell carcinoma of the lung, PCa, and possibly undifferentiated bladder carcinoma) [58]. Occasionally, Bazex syndrome has developed simultaneously with PCa, undifferentiated carcinoma of the submandibular gland, or psoriasisform acral dermatitis [52]. Adult-onset ichthyosis should be seen as a marker of systemic disease, including malignancy [57]. A case of PCa associated with cutaneous lymphangitis and paraneoplastic ichthyosis was reported. A large angiomatous skin lesion, axillary nodule, and paraneoplastic ichthyosis demonstrated prostatic origin with carcinomas metastases to lymphatic vessels [59]. The Leser-Trelat sign is a rare paraneoplastic manifestation that indicates an internal malignancy. The Leser-Trelat sign has been described as the sudden appearance of numerous seborrheic keratoses of different sizes; in some cases, the lesions are pruriginous [57]. It has been most commonly reported in association with colon or breast cancer, but it has also been described among patients with prostate cancer. The mechanism of occurrence is not fully understood, but it seems that cytokines and growth factors have an important role in the sudden onset of numerous seborrheic keratoses. In most cases, the diagnosis is easy, but histopathological examination may sometimes be necessary [60]. Hematological neoplasms are the most frequently associated with Sweet. The association of Sweet syndrome with solid tumors is unusual. The simultaneous presence of Sweet syndrome with PCa and transitional cell carcinoma of the urinary bladder, occurring in the same patient, has been reported. Sweet syndrome, also known as acute febrile neutrophil dermatosis, is defined as an eruption consisting of painful plaques or nodules, predominantly located on the head, neck, and upper extremities. In some cases, the mucous membranes are involved [61]. Occasionally, metastatic PCa has been associated with immune-mediated cytopenias such as [PERSON] syndrome. Evans syndrome can cause petechiae, ecchymosis, spontaneous bleeding, or autoimmune thrombocytoprotein pur pur purura [55]. [PERSON] disease, an autosomal dominant hereditary acantholytic dermatosis associated with metastatic PCa, is an unusual presentation [62].