{'fraction_non_alphanumeric': 0.03650396328744264, 'fraction_numerical': 0.01376720901126408, 'mean_word_length': 5.497289972899729, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 1, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Painful Oral Ulcers With Lymphadenopathy and Respiratory Symptoms.

DISCUSSION Paraneoplastic pemphigus (PNP) was initially described in 1990 as an autoimmune mucocutaneous disease associated with an underlying neoplasia. Both cellular and humoral immunity are thought to play a role in the pathogenesis of PNP, ultimately resulting in painful blisters and erosions involving the mucosa and the skin as well as potential injury to other types of epithelia such as the gastrointestinal and respiratory tract. Clinically, the mucosal lesions are seen in .95% of cases, and a small subset of patients only has mucosal disease (,10%). The oral mucosal lesions are severe and, oftentimes mimic those findings seen in erythema multiforme (EM) and Stevens–Johnson syndrome (SJS). The patients can also develop blisters, lichen planus–like, bullous pemphigoid–like, or linear IgA–like lesions. Less common psoriasiform and pustular variants have been described. The flaccid blisters are identical to those seen in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Lesions in acral sites are a good clue that distinguishes them from PV. The histologic features of acantholysis or lichenoid or interface dermatitis and mucositis are classic for PNP. The suprabasilar acantholysis is more typical of the noninflammatory blisters, whereas the interface and lichenoid patterns are more common in erythematous inflammatory maculopapular lesions. Some cases may not reveal acantholysis or interface changes. Less common histologic features include transepidermal necrosis and eosinophilic spongiosis. Other features that are characteristic of PNP include the presence of IgG autoantibodies, including periplakin (66%, 190 kd), envoplakin/desmoplakin (64%, 210 kd), desmoglein 3 (23%, 130 kd), BPAG1 (13%, 230 kd), desmoplakin 1 (13%, 250 kd), and desmoglein 1 (13%, 160 kd); an underlying neoplasm; and frequent respiratory involvement in the form of bronchiolitis obliterans. The prevalence of autoantibodies in these patients, by indirect immunofluorescence using serum samples on monkey esophagus, is approximately 75% and 80% using rat bladder. It is presumed that the mechanism for the interface reaction is secondary to the anti–desmoglein 3 antibodies. The most common PNP-associated tumors are hematologic, including non-Hodgkin lymphomas (such as chronic lymphocytic leukemia) and Castleman disease (CD), but nonhematologic tumors, including carcinomas, sarcomas, and melanoma have been reported. The differential diagnosis of PNP includes PV, PF, pemphigus erythematosus (PE), lichen planus, major aphthous stomatitis, drug eruptions, subepidermal blistering disorders (such as epidermolysis bullosa), EM, and SJS/toxic epidermal necrolysis. As opposed to PNP, PV only shows the suprabasilar acantholysis without the interface changes, or the immunoglobulin deposits in the basement membrane zone (BMZ). It also lacks the association with an underlying neoplasia. PF typically has a more superficial acantholysis, and the degree of eosinophilia is more prominent. PF typically lacks the associated oral lesions. When the clinical blisters are present in the distal extremity, the disease can mimic BP. Histologically, BP shows eosinophilic spongiosis in its urticarial phase and a subepidermal inflammatory blister with eosinophils in the more classic phase. As opposed to PNP, BP shows a linear pattern of IgG and C3 in the BMZ. PNP typically has a mixed, epidermal fishnet intercellular pattern of IgG and C3, with the associated granular pattern in the BMZ. The difference of PNP and PE can be more challenging, because both can present with acantholysis and interface changes. However, in PE, acantholysis is higher (as seen in PF), and there is mucin deposition in the dermis, with follicular plugging, features typical of lupus erythematosus. Both PE and PNP can show similar findings on direct immunofluorescence (DIF). The more useful clue to distinguish them is the presence of oral lesions in the latter, because mucosal surfaces are spared in PE. It is important to From the *Division of Hematopathology, Department of Pathology, The Ohio State University Wexner Medical Center; †Department of Radiation Oncology, The Ohio State University Wexner Medical Center; ‡Division of Oral and Maxillofacial Pathology, The Ohio State University College of Dentistry; and §Divisions of Dermatology and Dermatopathology, Department of Pathology and Internal Medicine, The Ohio State University Wexner Medical Center. The authors declare no conflicts of interest. Reprints: Alejandro A. Gru, MD, The Ohio State University Wexner Medical Center, N337A Doan Hall 410 W. 10th Ave, Columbus OH 43210 (e-mail: alejandro.gru@osumc.edu). Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.