Discussion
Indeterminate cell histiocytosis owns both Langerhans cell and non-Langerhans cell immunophenotypic features with CD1a, S-100 and CD68 positive as well as CD207 negative. Our study showed that the histiocytes in epidermis and dermis co-expressed CD1a, S-100 and CD68 marker, but were negative for CD207/Langerin in dermis. The CD207/Langerin was involved in formation of Birbeck and its expression could be a sign of Langerhans cells. Therefore, a diagnosis was made for ICH and not for Langerhans cell histiocytosis (LCH).
Indeterminate cell histiocytosis is morphologically similar to Langerhans cell histiocytosis (LCH). Previous studies have found that there are two relationship models between LCH and tumor[3]. Bubolz et al.[4] reported that the average of BRAFV600E oncogene was 48.5% in LCH. Elsewhere, Badalian-Very G et al.[5] found a recurrent mutation of the BRAFV600E gene in LCH. The BRAF V600E mutation has been detected in two out of seven ICH cases [6]. Generally, BRAF gene has been verified as an oncogene in many studies, which was involved in colorectal cancer, liver cancer, pancreatic cancer, malignant melanoma and papillary thyroid carcinoma. It played a crucial role in the process of tumorigenesis, development and transfer [7-9]. Therefore, mutation of BRAF V600E could be the reason for our case with ICH following esophageal cancer. Apart from BRAF V600E mutation, ETV3-NCOA2 translocation has been found in some ICH cases[10].
Bullous pemphigoid (BP) is an autoimmune blistering disorder that primarily occurs in elderly men. However, the relationship between BP and cancer is still controversial. Although it has been reported that the malignancy can occur before, during and after the appearance of typical bullous skin lesions, the detailed pathogenetic mechanism of the correlation remains unclear [11]. However, different studies have convincingly revealed that there is no relativity between BP and tumor [12, 13]. In our case, the patient received the radiation therapy (RT) for esophageal carcinoma. So the occurrence of BP may be in association with RT. Tegan et al.[14] summarized the literature about RT-associated BP and proposed different theories on the possible mechanism about the occurrence of RT-associated BP. In addition, we found no case reported on the association of ICH with BP. But Akdogan et al.[15] presented a case of multi-lesional cutaneous ICH in a 27-year-old male patient with SLE together with antiphospholipid antibody syndrome (APS), which were autoimmune disorders.
In this case, the point of attention was that esophageal carcinoma, ICH and BP were found in a single patient and to determine whether there was any association among them. This provided important information towards establishing the possible mechanism between cancer and the development of ICH and BP.