A Primary Pulmonary Carcinoma With Combined Neuroendocrine and Squamous Cell Features in a Patient With Long-standing Tripe Palms and Digital Clubbing

Abstract

INTRODUCTION: Cutaneous paraneoplastic syndromes are rare, but frequently herald the presence of an occult internal malignancy. Often documented after a diagnosis of cancer is made, skin manifestations are postulated to be of concurrent onset with the neoplastic process (1). We report a case of a primary pulmonary carcinoma in a patient with cutaneous abnormalities noted on physical examination for several years prior to diagnosis. CASE PRESENTATION: A 64-year-old male smoker with long-standing digital clubbing was referred to a dermatologist for evaluation of actinic keratoses. Comprehensive skin examination revealed an incidental finding of ridged palmar keratoderma, or "tripe palms, " often a paraneoplastic entity associated with bronchogenic or gastrointestinal carcinoma. Computed tomography of the thorax was obtained, which was notable for severe emphysematous changes and basilar reticular interstitial thickening peripherally. Colonoscopy and esophagogastroduodenoscopy were unremarkable. No further work-up was performed. Three years later, the patient was referred for pulmonary consultation with chief complaint of mild dyspnea on exertion in the setting of a ten pound unintentional weight loss. Medications at the time of evaluation included ranitidine and aspirin. Pulmonary function testing revealed a mildly decreased FEV1 (80% predicted) with a normal FEV1/FVC ratio and a diminished diffusing capacity (52% predicted). Total lung capacity was normal, with decreased residual volume (76% predicted). Physical examination demonstrated fine basilar inspiratory crackles. Tripe palms and digital clubbing were again noted. Repeat computed tomography of the chest and abdomen was obtained. Imaging revealed a four centimeter spiculated pulmonary mass in the left lower lobe with bulky subcarinal, left hilar, and left paratracheal lymphadenopathy. Several hypodense liver lesions were additionally noted. Bronchoscopy revealed tumor studding of the left lower lobe basilar segmental bronchi. Scant tumor material from both fine needle aspiration of the subcarinal node and brushing of the left lower lobe basilar segments demonstrated a poorly-differentiated carcinoma. Immunohistochemistry staining was positive for neural cell adhesion molecule (CD56), suggestive of neuroendocrine tumor origin. Other neuroendocrine markers, including leukocyte common antigen (LCA) and synaptophysin, returned negative. Small cell carcinoma was suspected. Given the prolonged duration of paraneoplastic skin changes temporally inconsistent with a traditionally aggressive malignancy, additional tissue was requested for clarification of diagnosis. Repeat bronchoscopy with brushings from the left lower lobe again demonstrated CD56 positivity, but also focal positivity to p63 and CK5/6, suggestive of non-small cell carcinoma with squamous differentiation. Forceps biopsy of the left lower lobe segmental wall demonstrated similar staining features to the initial cytology specimen, with additional negative staining to p63 and CK5/6, consistent with the original diagnosis of a neuroendocrine carcinoma. Chemotherapy was ultimately initiated with cisplatin and etoposide for presumed small cell lung cancer. DISCUSSION: Acanthosis palmaris, or "tripe palms, " was first described in the 1970s, likening the condition to tripe, the edible lining of the bovine foregut. It is a rare, often paraneoplastic, cutaneous syndrome thought to be associated with an excess of circulating epidermal growth factor (1). Malignancy is reported in greater than 90% of patients with tripe palms, about one-quarter of which manifest lung cancer. Clubbing in association with tripe palms appears to be more specific for lung carcinoma. The appearance of tripe palms precedes the diagnosis of malignancy in about half of reported cases (2). Tripe palms are rarely associated with neuroendocrine carcinomas (3), and we can find no published reports of tripe palms associated with a biopsy-confirmed morphologically mosaic primary lung carcinoma. CONCLUSION(S): There are no widely-accepted recommendations regarding cancer screening in patients with documented cutaneous findings indicative of paraneoplastic syndromes. Our case importantly underscores the need for careful physical examination of all patients, with continued close surveillance for neoplastic disease in patients who manifest dermatologic findings associated with malignancies.