Pemphigus vulgaris with squamous cell carcinoma of the tongue : An uncommon association

Pemphigus Vulgaris (PV) is an autoimmune blistering disease with circulating anti desmoglein 3 (DSG3) and desmoglein 1 (DSG1) antibodies, targetting intercellular adhesion molecules, desmosomes. PVwith cancers of oral cavity and tongue is uncommon and rarely reported [1-4]. The link between PV and malignancy still needs to be elucidated.We describe a patient with pemphigus vulgaris in whom Squamous Cell Carcinoma (SCC) of the tongue subsequently developed.


INTRODUCTION
Pemphigus Vulgaris (PV) is an autoimmune blistering disease with circulating anti desmoglein 3 (DSG3) and desmoglein 1 (DSG1) antibodies, targetting intercellular adhesion molecules, desmosomes.PVwith cancers of oral cavity and tongue is uncommon and rarely reported [1][2][3][4].The link between PV and malignancy still needs to be elucidated.We describe a patient with pemphigus vulgaris in whom Squamous Cell Carcinoma (SCC) of the tongue subsequently developed.

CASE REPORT
A 35-year-old non-diabeticman, with pemphigus vulgaris of 2 years duration on systemic steroids, was referred to us for Dexamethasone-Cyclophosphamide Pulse (DCP) therapy.He had multiple flaccid blisters over the face, axillae, and the body with extensive ulcerations and erosions of oral mucosa and tongue.In addition, there was a large vegetative, cauliflowerlike growth over the right lateral margin of the tongue (Fig. 1a and b).Clinical history revealed that the patient initially developed oral lesions, followed by cutaneous blisters two years ago and consulted a dermatologist.A diagnosis of pemphigus vulgaris was made and has been on systemic steroids since then.He observed a small growth on the right lateral margin of the tongue six months ago.The growth gradually increased in size and attained the present form.There was no regional lymphadenopathy and systemic examination was normal.Patient was non-smoker, non-alcoholic and was not in the habit of chewing tobacco or betel nut.We suspected ABSTRACT Pemphigus Vulgaris (PV) is an autoimmune blistering disease wherein, many keratinocyte adhesion molecules (desmogleins) are targets of circulating autoantibodies like anti desmoglein 3 (DSG3) and desmoglein 1 (DSG1) antibodies.DSG3 appears to be of primary importance in maintaining the integrity of oral epithelium.It is targeted in pemphigus vulgaris and paraneoplastic pemphigus with severe oral involvement.DSG1, on the other hand is essential for the integrity of non-mucosal skin surface.Recent studies have shown that desmosomes are not merely static structures but may also play an important role in the regulation of cell-proliferation, apoptosis and migration.Thus, desmosomes have a potential role in cancer development can be hypothesized.Cases of PV with systemic malignancies have been reported frequently but PV with cancers of oral cavity and tongue are rarely reported.The link between PV and malignancy still needs to be elucidated.We report a 35-year-old man with PV in whom Squamous Cell Carcinoma of the tongue developed subsequently.We tried to explore the role of antidesmosomal antibodies for association of these two conditions with the help of the available literature.
squamous cell carcinoma of the tongue and took biopsies from the growth and also from the cutaneous lesions.Histopathological and immunofluorescence studies of cutaneous lesions were consistent with pemphigus vulgaris (Fig. 2a and b).Biopsy from the tongue growth revealed well-differentiated squamous cell carcinoma (Fig. 3).Enzyme-linked immunosorbent assay (ELISA) detectedserum anti DSG3 and DSG1 antibodies.All relevant hematological and biochemical tests were within normal limits.Ultrasound abdomen and radiograph of chest were normal.He was referred to a surgical oncologist for further management.He did not report to us subsequently.

DISCUSSION
This rare case has prompted us to study and ascertain if these two conditions are just coincidental or related.Do antidesmosomal antibodies play a role in carcinogenesis?Recent studies [5,6] have shown that the desmosomes are not merely static structural entities.They may play an important role in the regulation of cell proliferation, apoptosis and migration.Consequently, a potential role of desmosomes in cancer development can be hypothesized.Although an understanding of the role of desmosomes in cancer is still evolving, human cancer expression data and functional studies on cultured cells suggest that desmosomes normally function as tumor suppressive complexes and that loss of desmosome proteins and desmosome-mediated adhesins is associated with cancer development and progression [6].But there are divergent hypotheses concerning the role of DSG3 in tumor aggressiveness.There are several studies reporting the increased expression of DSG1 and DSG 3 in squamous cell carcinoma of the soft palate [7], and DSG3 in head and neck squamous cell carcinoma [8] or conversely decreased expression of desmocollin3 and DSG3 in oral squamous cell carcinoma [9].There is one study describing decrease of desmoplakin and plakophilin-1 in dysplastic and oral squamous cell carcinoma [10].In another recent study, the authors were of the opinion that antibodies against desmocollins and subsequent loss of keratinocytes adhesion might be the linking facts for squamous cell carcinoma and pemphigus [3].Furthermore, DSG3 was reported as a biomarker of occult lymph node metastasis in oral cancer [11].All the data suggest that the mechanism by which desmosomes induced carcinogenesis is unclear, but altered expression of desmosome proteins might promote cancer development in certain contexts.
In the present case, the rare association between SCC and PV could be coincidental.But, it is possible to speculate that multiple factors like chronic mucosal damage, circulating anti DSG3 and DSG1 antibodies and subsequent loss of desmosomes, auto immunity, genetic factors might have contributed to carcinogenesis in the background of PV.However, large scale studies are warranted to establish the role of desmosomes and anti desmosomal antibodies in the pathogenesis of oral cancers and SCC of tongue.

Consent
The examination of the patient was conducted according to the Declaration of Helsinki principles.

Figure 1 :Figure 2 :
Figure 1: (a) Pemphigus vulgaris lesions in the axilla.(b) A growth on the right lateral margin of the tongue.ba