If cholesterol or cholesterol esters are present, they are associated with the "Maltese cross" sign under polarized light. They are pathognomonic for high urinary protein nephrotic syndrome. Formed by the adhesion of metabolic breakdown products or drug pigments, these casts are so named due to their discoloration. Pigments include those produced endogenously, such as hemoglobin in hemolytic anemia, myoglobin in rhabdomyolysis, and bilirubin in liver disease. Drug pigments, such as phenazopyridine, may also cause cast discoloration. Though crystallized urinary solutes, such as oxalates, urates, or sulfonamides, may become enmeshed within a ketanaline cast during its formation, the clinical significance of this occurrence is not felt to be great. The presence of red blood cells within the cast is always pathological, and is strongly indicative of granulomatosis with polyangiitis, systemic lupus erythematosus, post-streptococcal glomerulonephritis or Goodpasture's syndrome. They can also be associated with renal infarction and subacute bacterial endocarditis. They are a yellowish-brown color and are generally cylindrical with sometimes ragged edges; their fragility makes inspection of a fresh sample necessary. They are usually associated with nephritic syndromes or urinary tract injury. Indicative of inflammation or infection, the presence of white blood cells within or upon casts strongly suggests pyelonephritis, a direct infection of the kidney. They may also be seen in inflammatory states, such as acute allergic interstitial nephritis, nephrotic syndrome, or post-streptococcal acute glomerulonephritis. White cells sometimes can be difficult to discern from epithelial cells and may require special staining. Differentiation from simple clumps of white cells can be made by the presence of hyaline matrix. Given their appearance in pyelonephritis, these should be seen in association with loose bacteria, white blood cells, and white blood cell casts. Their discovery is likely rare, due to the infection-fighting efficiency of neutrophils, and the possibility of misidentification as a fine granular cast. This cast is formed by inclusion or adhesion of desquamated epithelial cells of the tubule lining. Cells can adhere in random order or in sheets and are distinguished by large, round nuclei and a lower amount of cytoplasm.