Dermatology: Practical and Conceptual DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Observation | Dermatol Pract Concept 2013;3(4):14 55 Introduction The desmogleins are a family of cadherins cell-cell adhesion molecules consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes, which form the major types of intercellular adhesive junctions. DSGs are currently thought to be involved in autoimmune diseases, infectious diseases, and inherited diseases. Patients with pemphigus, an autoimmune blistering disease of the skin and mucous membranes, carry IgG autoantibodies directed against DSG1 and DSG3 [1]. Pemphigus vulgaris antigen is also considered a tissue-specific type of desmoglein [1]. Case presentation A 67-year-old Japanese woman noted an erosive lesion on the median side of the soft palate four months earlier and was referred to the Department of Oral Surgery for suspected pemphigus vulgaris. Physical examination showed slightly elevated erosive lesion measuring approximately 3 cm in diameter on the central soft palate, with a clear demarcated border (Figure 1). No enanthema were seen in other areas of Squamous cell carcinoma of the soft palate associated with autoantibodies to desmoglein 1 and 3 Yoshifumi Maumi1, Reiko Suzaki1, Naoko Ito1, Mizuki Sawada1, Sumiko Ishizaki1, Mariko Fujibayashi2, Motohiko Aiba2, Hiroyuki Kaneko3, Masaru Tanaka1 1 Department of Dermatology, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan 2 Department of Pathology, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan ¶ 3 Department of Oral Surgery, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan Key words: desmoglein, squamous cell carcinoma, mucous membrane, soft palate, autoantibody Citation: Maumi Y, Suzaki R, Ito N, Sawada M, Ishizaki S, Fujibayashi M, Aiba M, Kaneko H, Tanaka M. Squamous cell carcinoma of the soft palate associated with autoantibodies to desmoglein 1 and 3. Dermatol Pract Conc. 2013;3(4):14. http://dx.doi.org/10.5826/ dpc.0304a14. Received: June 4, 2013; Accepted: July 1, 2013; Published: October 31, 2013 Copyright: ©2013 Maumi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: Masaru Tanaka, M.D., Department of Dermatology, Tokyo Women’s Medical University, Medical Center East, 2-1- 10 Nishi-Ogu, Arakawa-ku, Tokyo 116-8567, Japan. Tel: +81 3 3810 1111. Fax: +81 3 3894 1441. E-mail: tanaka.twmu@gmail.com. Figure 1. Clinical finding: Erosive lesion measuring approximately 3 cm in diameter on the central part of the soft palate. [Copyright: ©2013 Maumi et al.] 56 Observation | Dermatol Pract Concept 2013;3(4):14 fluorouracil (5-FU)] combined with tegafur, gimeracil, and oteracil potassium (TGO). The treatment resulted in a sig- nificant fall in anti-DSG antibody titer (DSG1: 10, DSG3: 5) by ELISA. Discussion To our knowledge, there are no reports of primary squamous cell carcinoma associated with anti-DSG antibody, although there is a case of pemphigus foliaceus developing after metas- tasis of cutaneous squamous cell carcinoma to regional lymph nodes [2]. Recently, a possible role of DSG3 in the process of squamous cell carcinogenesis has been hypothesized [3]. There are several recent studies reporting the overexpression of DSG3 in head and neck squamous cell carcinoma [4] or conversely decrease in expression of desmocollin 3 and DSG3 in oral squamous cell carcinoma [5] especially when the tumor is poorly differentiated. There is also a study describing decrease of desmoplakin, plakophillin and DSG1 in dysplasia and oral squamous cell carcinoma [6]. Furthermore, DSG3 is reported as a biomarker for occult lymph node metastasis in oral cancer [7]. It was assumed in the present case that the increase in anti-DSG antibody titer was secondary in response to tumor cells, which might be overexpressing DSG1 and DSG3, although no evidence of autoimmune disease was available. Interestingly, surgical treatment followed by CDDP/5-FU and TGO resulted in normalization of autoantibody titer by ELISA. The findings suggest that anti-DSG antibodies could be potentially used to screen for tumor relapse or metastasis in this patient. the oral cavity. Anti-DSG antibodies were positive (DSG1: 42, DSG3: 25) by ELISA, and a biopsy was taken from the soft palate. Histopathological examination of the biopsy showed proliferation of atypical epithelial cells and invasion into the lamina propria mucosa by tumor cells (Figure 2). These cells showed wide variation in size and mitoses of the nucleus in the mucous membrane. The lamina propria mucosa showed prominent cell infiltration mainly composed of lymphocytes and plasma cells (Figure 3). Immunostaining for MIB1 (Ki67) showed positive staining in approximately 80% of tumor cells (Figure 4). There were no features of acantholysis, sug- gesting the histopathological diagnosis of pemphigus. Direct immunofluorescence staining demonstrated no deposition of IgG or C3 on the epithelial cell surface or basement mem- brane zone. The final diagnosis of squamous cell carcinoma was established. Treatment included complete excision of the tumor on June 6, 2007, followed by chemotherapy [cisplatin (CDDP)/5- Figure 2. Histopathological examination of hematoxylin-eosin stained tissue biopsy showed invasion of the lamina propria mucosa by tumor cells. Magnification, 20x. [Copyright: ©2013 Maumi et al.] Figure 3. Histopathological examination of hematoxylin-eosin stained tissue biopsy under high magnification confirmed the diag- nosis of undifferentiated squamous cell carcinoma. The subepithelial tissue shows marked inflammatory reaction with a mixture of lym- phocytes and plasma cells. Magnification, 200x. [Copyright: ©2013 Maumi et al.] Figure 4. Immunohistochemical staining for MIB1 (Ki67) showed nuclear staining in approximately 80% of tumor cells. Magnifica- tion, 200x. [Copyright: ©2013 Maumi et al.] Observation | Dermatol Pract Concept 2013;3(4):14 57 5. Wang L, Liu T, Wang Y, et al. Altered expression of desmocollin 3, desmoglein 3, and beta-catenin in oral squamous cell carcinoma: correlation with lymph node metastasis and cell proliferation. Virchows Arch. 2007;451(5);959-66. 6. Narayana N, Gist J, Smith T, et al. Desmosomal component ex- pression in normal, dysplastic, and oral squamous cell carcinoma. Dermatol Res Pract. 2010:649731. 7. Patel V, Martin D, Malhotra R, et al. DSG3 as a biomarker for the ultrasensitive detection of occult lymph node metastasis in oral cancer using nanostructured immunoarrays. Oral Oncol. 2013;49(2);93-101. References 1. Amagai M, Klaus-Kovtun V, Stanley JR. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell. 1991;67(5);869-77. 2. Inaoki M, Kaji K, Furuse S, et al. Pemphigus foliaceus developing after metastasis of cutaneous squamous cell carcinoma to regional lymph nodes. J Am Acad Dermatol. 2001;45(5);767-70. 3. Alaibac M. Targeting DSG3: from pemphigus to squamous cell carcinoma. Expert Opin Ther Targets. 2013;17(5);477-9. 4. Chen YJ, Chang JT, Lee L, et al. DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis. Oncogene. 2007;26(3);467-76.