Bullous pemphigoid (BP) is an acquired, autoimmune, subepidermal blistering disease that is more common in elderly patients.1 An association with internal neoplasms and BP has been established; however, there is debate regarding the precise nature of the relationship.2 Several gastrointestinal tract tumors have been associated with BP, including adenocarcinoma of the colon, adenosquamous cell carcinoma and adenocarcinoma of the stomach, adenocarcinoma of the rectum, and liver and bile duct malignancies.3-5 Association with pancreatic neoplasms (eg, carcinoma of the pancreas) rarely has been reported.5-7 We present an unusual case of a lymphoepithelial cyst of the pancreas in a patient with BP.
Case Report
A 67-year-old man presented with erythematous crusted plaques and pink scars over the chest, back, arms, and legs (Figure 1). A 1.5-cm tense bullous lesion was observed on the right knee. The patient’s medical history was notable for biopsy-proven BP of 8 months’ duration as well as diabetes mellitus and hypothyroidism. The patient was being followed by his surgeon for a 1.9-cm soft-tissue lesion in the pancreatic tail and was awaiting surgical excision at the time of the current presentation. The pancreatic lesion was discovered incidentally on magnetic resonance imaging performed following urologic concerns. At the current presentation, the patient’s medications included nifedipine, hydralazine, metoprolol, torsemide, aspirin, levothyroxine, atorvastatin, insulin lispro, and insulin glargine. He had previously been treated for BP with prednisone at a maximum dosage of 60 mg daily, clobetasol propionate cream 0.05%, and mupirocin ointment 2% without improvement. Because of substantial weight gain and poorly controlled diabetes, prednisone was discontinued.
Figure 1. Erythematous crusted plaques on the chest and arms in a patient with bullous pemphigoid.
Bullous pemphigoid had been diagnosed histopathologically by a prior dermatologist. Hematoxylin and eosin staining demonstrated a subepidermal separation with eosinophils within the perivascular infiltrate (Figure 2). Direct immunofluorescence was noted in a linear pattern at the dermoepidermal junction with IgG and C3. Bullous pemphigoid antigen antibodies 1 and 2 were obtained via enzyme-linked immunosorbent assay with a positive BP-1 antigen antibody of 19 U/mL (positive, >15 U/mL) and a normal BP-2 antigen antibody of less than 9 U/mL (reference range, <9 U/mL). The glucagon level was elevated at 245 pg/mL (reference range, ≤134 pg/mL).
Figure 2. Subepidermal separation of the dermis and epidermis associated with eosinophils with a mild perivascular lymphocytic infiltrate consistent with bullous pemphigoid (H&E, magnification approximately ×100 by digital system).
The patient was prescribed minocycline 100 mg twice daily and niacinamide 500 mg 3 times daily. Topical treatment with clobetasol and mupirocin was continued. One month later, the patient returned with an increase in disease activity. Changes to his therapeutic regimen were deferred until after excision of the pancreatic lesion based on the decision not to start immunosuppressive therapy until the precise nature of the pancreatic lesion was determined.
The patient underwent excision of the pancreatic lesion approximately 3 months later, which proved to be a benign lymphoepithelial cyst of the pancreas. Histology of the cyst consisted of dense fibrous tissue with a squamous epithelial lining focally infiltrated by lymphocytes (Figure 3A). Immunoperoxidase staining of the cyst revealed focal linear areas of C3d staining along the basement membrane of the stratified squamous epithelium (Figure 3B).
Figure 3. Histopathology of the lymphoepithelial cyst of the pancreas revealed squamous epithelial lining with no malignant features. A prominent lymphocytic component abutting the squamous epithelial lining was observed, which is characteristic of lymphoepithelial cysts of the pancreas (A)(H&E, magnification approximately ×100 by digital system). Immunoperoxidase staining of the cyst revealing focal linear areas of C3d staining along the basement membrane of the stratified squamous epithelium (B)(magnification approximately ×400 by digital system).
The patient stated that his skin started to improve virtually immediately following the excision without systemic treatment for BP. On follow-up examination 3 weeks postoperatively, no bullae were observed and there was a notable decrease in erythematous crusted plaques (Figure 4).
Figure 4. Three weeks following the surgical removal of the pancreatic lymphoepithelial cyst, pink and hypopigmented scars were noted in the same distribution as the previously active bullous pemphigoid lesions.
Comment
Paraneoplastic BP has been documented; however, lymphoepithelial cysts of the pancreas in association with BP are rare. We propose that the lymphoepithelial cyst of the pancreas provided the immunologic stimulus for the development of cutaneous BP based on the observation that our patient’s condition remarkably improved with resection of the tumor.
There are fewer than 100 cases of lymphoepithelial cysts of the pancreas reported in the literature.8 The histologic appearance is consistent with a true cyst exhibiting a well-differentiated stratified squamous epithelium, often with keratinization, surrounded by lymphoid tissue. These tumors are most commonly seen in middle-aged men and are frequently found incidentally,8-10 as was the case with our patient. Although histologically similar, lymphoepithelial cysts of the pancreas are considered distinct from lymphoepithelial cysts of the parotid gland or head and neck region.10 Lymphoepithelial cysts of the pancreas are unrelated to elevated glucagon levels; it is likely that our patient’s glucagon levels were associated with his history of diabetes.11