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Fig. 9.05 Intestinal type adenocarcinoma. A Tubular glands similar to colonic adenocarcinoma. B Goblet cell type of adenocarcinoma. C Numerous serotonin containing cells in a neoplastic gland.

Fig. 9.06 Well differentiated adenocarcinoma infiltrating gallbladder wall.
Fig. 9.07 Mucinous adenocarcinoma of gallbladder.
Fig. 9.08 Signet-ring cell carcinoma of gallbladder.

become calcified {1465, 1606}. About one-third of the well differentiated tumours show focal intestinal differentiation and contain goblet and endocrine cells {36, 2152, 2158}. The endocrine cells may be numerous and show immunoreactivity for serotonin and peptide hormones, but a diagnosis of neuroendocrine neoplasm is not warranted. Paneth cells may rarely be seen. An extremely well differentiated adenocarcinoma with gastric foveolar phenotype that simulates adenoma has been described in the extrahepatic bile ducts {39}. Adenocarcinomas may show cribriform or angiosarcomatous patterns. They may also contain cyto- and synctio-trophoblast cells.

Extrahepatic bile duct adenocarcinomas tend to be better differentiated than their gallbladder counterparts. Many gallbladder carcinomas are immunoreactive for TP53 {1907, 2125}

Histological variants of adenocarcinoma Papillary adenocarcinoma. This malignant tumour is composed predominantly of papillary structures lined by cuboidal or columnar epithelial cells often containing variable amounts of mucin. Some tumours show intestinal differentiation with collections of goblet, endocrine, and Paneth cells. Papillary adenocarcinomas may fill the lumen before invading the wall. Papillary adenocarcinomas appear to be more frequent in the gallbladder than in the extrahepatic biliary tree {2150}. In addition, skip lesions may be observed in approximately 10% of cases {1989}.

Adenocarcinoma, intestinal type. This unusual variant of adenocarcinoma is composed of tubular glands or papillary structures lined predominantly by cells with an intestinal phenotype, namely goblet cells or colonic-type epithelium or both, with or without a variable number of endocrine and Paneth cells {41}.

Mucinous adenocarcinoma. Mucinous adenocarcinomas of the biliary tree are similar to those that arise in other anatomic sites. By definition, more than 50% of the tumour contains extracellular mucin {1774}. There are two histological variants of mucinous adenocarcinomas of the gallbladder and extrahepatic bile ducts: one variant is characterized by neoplastic glands distended with mucin and lined by columnar cells with mild to moderate nuclear atypia, and the second variant is characterized by small groups or clusters of cells surrounded by abundant mucin. Some tumours show both growth patterns. The abundant mucin makes the tumour appear hypocellular.

Cystadenocarcinoma refers to a unilocu-lar or multilocular glandular tumour that may be the result of malignant transformation of a cystadenoma.

Clear cell adenocarcinoma. This rare malignant tumour is composed predominantly of glycogen-rich clear cells having well-defined cytoplasmic borders and hyperchromatic nuclei. In addition to clear cells, a variable number of cells contain eosinophilic granular cytoplasm. The clear cells line glands or are arranged in nests, sheets, cords, trabec-ulae or papillary structures {40, 145, 1856}. Foci of conventional adenocarci noma with focal mucin production are usually found and are useful in separating primary from metastatic clear cell carcinomas. In some clear cell adenocarcinomas of the biliary tree the columnar cells contain subnuclear and supranuclear vacuoles similar to those seen in secretory endometrium. Focal hepatoid differentiation with production of alpha-fetopro-tein has been documented in clear cell carcinomas of the gallbladder {2000}.

Signet-ring cell carcinoma. Cells containing intracytoplasmic mucin displacing the nuclei toward the periphery predominate in this variant of adenocarcinoma. A variable amount of extracellular mucin is usually present. Lateral spread through the lamina propria is a common feature.

Fig. 9.09 Adenosquamous carcinoma of gallbladder.
Fig. 9.10 Squamous cell carcinoma of gallbladder.
Fig. 9.11 Undifferentiated carcinoma of gallbladder, spindle and giant cell type. No glandular differentiation.

A diffusely infiltrating linear pattern resembling linitis plastica of the stomach is observed in some cases.

Adenosquamous carcinoma

This tumour consists of two malignant components, one glandular and the other squamous. The extent of differentiation of the two components varies, but in general they tend to be moderately differentiated {1357, 1867}. Keratin pearls are often present in the squamous component, and mucin is usually demonstrable in the neoplastic glands.

Squamous cell carcinoma

This malignant epithelial tumour is composed entirely of squamous cells. The extent of differentiation varies considerably. Keratinizing and non-keratinizing types exist. Spindle cells predominate in some poorly differentiated tumours, which may be confused with sarcomas. Immunostains for cytokeratin may clarify the diagnosis in these spindle cell cases. The tumour may arise from areas of squamous metaplasia. Intraepithelial neoplasia can be found in the metaplas-tic squamous mucosa {35}.

Small cell carcinoma

This lesion is covered in the chapter on endocrine tumours of the gallbladder and extrahepatic bile ducts.

Undifferentiated carcinoma Undifferentiated carcinomas are more common in the gallbladder than in the extrahepatic bile ducts. Characteristically, glandular structures are absent in undifferentiated carcinomas. There are four histological variants {40, 411, 643, 1360}. Undifferentiated carcinoma, spindle and giant cell type. The spindle and giant cell type is the most common and resem-

Fig. 9.12 Carcinosarcoma of gallbladder. The tumour shows malignant glandular elements and a sarcomatous component with osteoid formation.

Fig. 9.13 Adenocarcinoma (CA) of the distal common bile duct, infiltrating the duodenal wall.

Fig. 9.12 Carcinosarcoma of gallbladder. The tumour shows malignant glandular elements and a sarcomatous component with osteoid formation.

bles a sarcoma. These tumours have been referred to as pleomorphic spindle and giant cell adenocarcinomas or sar-comatoid carcinomas. They consist of variable proportions of spindle, giant and polygonal cells, but foci of well-differentiated neoplastic glands are usually found in some of these tumours after extensive sampling. Areas of squamoid differentiation may also be seen. Rarely, foci of osteoclast-like multinucleated giant cells are present. The presence of cytokeratin in the spindle cells may help to distinguish this tumour from carcinosarcoma. Undifferentiated carcinoma with osteo-clast-like giant cells. This variant contains mononuclear cells and numerous evenly spaced osteoclast-like giant cells resembling giant cell tumour of bone. The mononuclear cells show immunore-activity for cytokeratin and epithelial membrane antigen while the osteoclast-like giant cells are positive for histiocytic markers such as CD68. Undifferentiated carcinoma, small cell type. The tumour is composed of sheets of round cells with vesicular nuclei and prominent nucleoli that occasionally contain cytoplasmic mucin. Undifferentiated carcinoma, nodular or lobular type. The fourth variant consists of well defined nodules or lobules of neo-plastic cells superficially resembling breast carcinoma.

Carcinosarcoma

This malignant tumour consists of a mixture of two components: carcinomatous and sarcomatous. The epithelial elements usually predominate in the form of glands but may be arranged in cords or sheets. Foci of malignant squamous cells are occasionally seen. The mesenchymal component includes foci of heterologous elements such as chondrosarcoma, osteosarcoma, and rhabdomyosarcoma. Cytokeratin and carcinoembryonic antigen are absent from the mesenchymal

Fig. 9.14 Clear cell carcinoma of extrahepatic bile duct. The overlying biliary epithelium is nonneoplastic.

component, which helps to distinguish carcinosarcomas from spindle and giant cell carcinomas.

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