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Background  Pancreatic panniculitis is a rare complication of pancreas disorders occurring in 0.3–3% of patients, most often accompanied by the pancreatic acinar carcinoma.  It presents multiple, painful, deep, ill-defined, red-brown, migratory nodules and plaques of hard elastic consistency; often ulcerated and typically located on the lower proximal and distal extremities.  The pathogenesis is not fully understood, but it is thought to result from lipolysis and fat necrosis with secondary tissue inflammation induced by pancreatic enzymes. Histopathology shows subcutaneous lobular fat necrosis with anuclear adipocytes (called ghost cells) surrounded by a mixed inflammatory infiltrate. Focal calcification may also be seen. The treatment is directed to the underlying disorder, which may result in regression of skin lesions.    Case presentation  We present two cases of pancreatic panniculitis with similar clinical, laboratory, and histopathological features associated with different internal malignancy. The first case, after extensive investigations showed the presence of a pancreatic carcinoma with multiple liver metastases and a poor prognosis. The second one instead is the first case in literature where painful subcutaneous nodules of the legs were the early manifestation of a neuroendocrine carcinoma of the adrenal gland.    Conclusions  Although subcutaneous fat necrosis usually occurs late in the course of a malignancy, recognition of the association with pancreatic panniculitis may prevent a long delay in the diagnosis and management of the occult neoplasm. It should be primarily considered when panniculitis is widespread and persistent, and frequent relapses or tendency to ulcerate of the nodules are regarded as red flags.

Pancreatic panniculitis: the “bright” side of the moon in solid cancer patients