title: Cutaneous clear cell/signet-ring cell squamous cell carcinoma arising in the right thigh of a patient with type 2 diabetes: combined morphologic, immunohistochemical, and etiologic analysis.
abstract: BACKGROUND
  The clear cell/signet-ring cell variant of cutaneous squamous cell carcinoma (cSCC) is extremely rare. Its carcinogenesis has consistently been linked to ultraviolet radiation and HPV in the literature. However, there is little definite information about the contribution of diabetes mellitus (DM) to cSCC.
  
  
  METHODS
  A 78-year-old Chinese woman with type 2 DM presented with a mushroom-like lump in her right thigh. Histological findings revealed that the lesion was mainly composed of clear cells and signet-ring cells. The septa of vacuoles in cytoplasm displayed positivity for periodic acid schiff (PAS) and cytokeratins such as AE1/AE3, CK5/6, CK14, and CK19. Malignant cells did not express CK7, CK8, CK18, CK20, p16, p53, or c-erbB-2, and the Ki-67 index was less than 5 %. We further explored the etiology of clear cell/signet-ring cell cSCC using human papillomavirus (HPV) type-specific PCR and genotyping and confirmed that the patient was not infected with HPV. Nucleus positivity for p63 indicated the involvement of the p53 family in the lesion. Meanwhile, the expression of fibroblast growth factor receptor-2 (FGFR2), a downstream effector of p63, was upregulated in tumor cells.
  
  
  CONCLUSIONS
  This study provides the first report on the clear cell/signet-ring cell variant of cSCC found in the right thigh of a patient with type 2 DM. Metabolic imbalance in addition to conventional pathogens such as UV and HPV may contribute to the development of the lesion via p63/FGFR2 axis.
authors.affiliation: Molecular Medicine and Genetics Center, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Nong-Rong
authors.initials: NR
authors.lastname: Wang
authors.affiliation: Molecular Medicine and Genetics Center, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Wang
authors.affiliation: Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, 133 South Guangchang Road, Nanchang, 330003, China.
authors.forename: Lv
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Molecular Medicine and Genetics Center, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China.|Department of Endocrinology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Ze-Lin
authors.initials: ZL
authors.lastname: Liu
authors.affiliation: Molecular Medicine and Genetics Center, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Nan-Ping
authors.initials: NP
authors.lastname: Chen
authors.affiliation: Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, 133 South Guangchang Road, Nanchang, 330003, China.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Hu
authors.affiliation: Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, 133 South Guangchang Road, Nanchang, 330003, China.
authors.forename: Yan-Juan
authors.initials: YJ
authors.lastname: Deng
authors.affiliation: Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, 133 South Guangchang Road, Nanchang, 330003, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Qi
authors.affiliation: Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, 133 South Guangchang Road, Nanchang, 330003, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Huang
authors.affiliation: Medical College, Nanchang University, Nanchang, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Su
authors.affiliation: Medical College, Nanchang University, Nanchang, China.
authors.forename: Si-Yao
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: Medical College, Nanchang University, Nanchang, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Tong
authors.affiliation: Medical College, Nanchang University, Nanchang, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Medical College, Nanchang University, Nanchang, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Medical College, Nanchang University, Nanchang, China.
authors.forename: Zi-Yu
authors.initials: ZY
authors.lastname: Zhu
authors.affiliation: Molecular Medicine and Genetics Center, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China. beandeng@hotmail.com.|Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, 133 South Guangchang Road, Nanchang, 330003, China. beandeng@hotmail.com.|Renmin Institute of Forensic Medicine, Nanchang, China. beandeng@hotmail.com.
authors.forename: Huan
authors.initials: H
authors.lastname: Deng
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D018279:Carcinoma, Signet Ring Cell / Q000737:chemistry / Q000209:etiology* / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000209:etiology* / Q000473:pathology / Q000601:surgery; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000175:diagnosis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011237:Predictive Value of Tests; D012307:Risk Factors; D012878:Skin Neoplasms / Q000737:chemistry / Q000150:complications* / Q000473:pathology / Q000601:surgery; D013848:Thigh
chemical_list: D014408:Biomarkers, Tumor
keywords: Clear cell; Diabetes mellitus; HPV; Signet-ring cell; Squamous cell carcinoma