squamous epithelial-like eosinophilic cells that resemble the luminal cells lining eccrine sweat gland ducts); and in some cases c) clear cells (i.e. cells with small nuclei surrounded by pale cytoplasm). Poroma tumor tissues may appear highly vascularized and/or have areas of necrosis, i.e. dead or dying cells. Hidroacanthoma simplex variants are mainly composed of poroid cells, few cuticular cells, and no clear cells and are confined to the epidermis; dermal ductal variants are mostly confined to the superficial dermis and are composed of small solid and cystic nodular aggregates of poroid, cuticular, and clear cells; poroid hidradenoma variants have large aggregates of solid and cystic components and extend deeper into the dermis or even subcutis; and eccrine poroma variants are composed of all three cell types but are primarily located in the epidermis and superficial dermis. Poromas may have 2 or more of these variants in the same tumor tissue and the variants typically have histopathology findings that are not clearly distinguishable from each other. Immunohistochemistry
As detected by immunohistochemical analyses, the poroma tumor cells, regardless of variant type, test positive when probed with the AE1/AE3 antibody cocktail that detects various cytokeratin proteins. Tumor cells of the four variants also commonly express carcinoembryonic antigen (i.e. CEA) or MUC1 (also termed EMA) and, except for the hidroacanthoma simplex variant, the carcinoembryonic antigen and MUC1 protein. Gene abnormalities
The four poroma variants contain at least one of two YAP1 fusion genes, i.e.
Diagnosis
PSC is generally diagnosed on the basis of having at least two of three clinical criteria after secondary causes of sclerosing cholangitis have been ruled out:
serum alkaline phosphatase (ALP) > 1.5x the upper limit of normal for longer than 6 months
cholangiography demonstrating biliary strictures or irregularity consistent with PSC
liver biopsy consistent with PSC (if available)Historically, a cholangiogram would be obtained via endoscopic retrograde cholangiopancreatography (ERCP), which typically reveals "beading" (alternating strictures and dilation) of the bile ducts inside and/or outside the liver. Currently, the preferred option for diagnostic cholangiography, given its noninvasive yet highly accurate nature, is magnetic resonance cholangiopancreatography (MRCP), a magnetic resonance imaging technique. MRCP has unique strengths, including high spatial resolution, and can even be used to visualize the biliary tract of small animal models of PSC.Most people with PSC have evidence of autoantibodies and abnormal immunoglobulin levels. For example, approximately 80% of people with PSC have perinuclear antineutrophil cytoplasmic antibodies (P-ANCA); however, this and other immunoglobulin findings are not specific to those with PSC and are of unclear clinical significance/consequence. Antinuclear antibodies and anti-smooth muscle antibody are found in 20-50% of PSC patients, and likewise are not specific for the disease,but may identify a subgroup of PSC patients who also have autoimmune hepatitis (i.e. PSC-AIH overlap syndrome).The differential diagnosis can include primary biliary cholangitis (formerly referred to as primary biliary cirrhosis), drug-induced cholestasis, cholangiocarcinoma, IgG4-related disease, post-liver transplantation nonanastomotic biliary strictures,  and HIV-associated cholangiopathy.