Atypical Presentation of Pemphigus Vulgaris with Co-Existing Carcinoma Lung and Acute Onset Internal Jugular Vein Thrombosis

Sir, Pemphigus vulgaris (PV), in addition to paraneoplastic pemphigus, has been linked to neoplasms, including solid organ malignancies.[1] In PV with a prolonged disease course and treatment, uncommon complications like vascular thromboembolism have been reported.[2,3] We present a case of treatment-naïve patient with atypical PV who developed sudden-onset life-threatening right internal jugular vein (IJV) thrombosis and was detected to have co-existing lung carcinoma. A 56-year-old chronic smoker with a dry cough for 2 years and recent significant weight loss presented with blisters and erosions over the body for 1 month and painful right-sided neck swelling for 3 days. Examination showed multiple flaccid bullae, vesicles, and crusted erosions over trunk, scalp, and upper extremities [Figure 1a and b] with significant right axillary and bilateral inguinal lymphadenopathy. Direct and indirect Nikolsky signs were negative, but bulla spread was positive. Apart from a few erosions over the right angle of mouth, there were no other mucosal lesions. An ill-defined, soft-to-firm, tender, erythematous swelling with a local rise in temperature was noted on the right side of the neck. Air entry was diminished over the right side of the chest. Later, oral erosions progressed, with new erosions appearing on the hard palate [Figure 1c].Figure 1: (a and b) Flaccid bullae, vesicles, and crusted erosions on the back of trunk, chest, and abdomen (c) Erosions over the angle of mouth and hard palateTzanck smear showed mixed leucocytes without acantholytic cells. Suprabasal blister in histopathology [Figure 2] and epidermal inter-cellular IgG staining in direct immunofluorescence (DIF) confirmed PV. Neck ultrasonography revealed right IJV thrombosis. Contrast-enhanced computed tomography (CECT) thorax revealed a heterogeneously enhancing soft tissue density mass with pleural invasion, suggesting carcinoma in the right lung upper lobe (T4N3M1b; stage IVa) [Figure 3a]. The ultrasonography-guided Tru-cut biopsy of lung mass showed non-small-cell morphology, favoring squamous cell carcinoma [Figure 3b].Figure 2: Suprabasal blister diagnostic of pemphigus vulgaris (H and E, 100×)Figure 3: (a) CECT thorax: Heterogeneously enhancing soft tissue density mass in right lung upper lobe with central enhancing regions, air foci, and infiltration of adjacent pleura (b) Lung biopsy showing cell nests with eosinophilic cytoplasm, pleomorphic nuclei, and prominent nucleoli – favoring squamous cell carcinoma (H and E, 400×)Despite having poor response to systemic steroids for pemphigus, skin lesions improved slightly after initiating gemcitabine and cisplatin chemotherapy for the lung tumor. However, the patient succumbed to his malignancy after a few days. The patient failed to meet the diagnostic criteria for paraneoplastic pemphigus, which included extensive oral mucosal lesions; acantholysis, dyskeratosis, basal layer vacuolation, and lichenoid mononuclear infiltration on histology; and granular/linear IgG and complement deposition along the basement membrane zone on DIF.[4] Though histopathology and DIF were suggestive of PV, the patient had atypical features such as limited oral erosions that developed late in disease course, sparing of other mucosa, and absent acantholytic cells in Tzanck smear. PV has been significantly associated with solid malignancies of larynx, esophagus,[1] and frequently the lung.[5] Apart from malignancy, venous thrombosis has also been linked to pemphigus.[3] Elevated anti-vascular endothelial cadherin (VE-cadherin) antibodies, IgM/IgG anticardiolipin antibodies, and anti-phospholipid antibodies in pemphigus increase the risk of vascular thrombosis.[3] Unlike all previous reports, where vascular thrombosis occurred in pemphigus patients after prolonged treatment, this patient developed thrombosis before any treatment and within a few weeks of developing lesions.[2,3] Despite having persistent cough for 2 years and significant weight loss suggestive of lung malignancy, the abrupt onset of thromboembolism shortly after pemphigus lesions suggests that pemphigus may have played a role in thrombosis pathogenesis. This case emphasizes the importance of thorough evaluation for systemic associations including malignancies and regular follow-up for potential complications such as vascular thromboembolism in PV patients with atypical features. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.