EPITELIAL TUMORS
Benign
Adenoma
- Tubular
- Papillary
- Tubulopapillary
Biliary cystadenoma
Papillomatosis (adenomatosis)
Intraepithelial neoplasia (dysplasia and carcinoma in situ)
We distinguish:
EPITELIAL TUMORS
Benigni
Adenoma
- Tubular
- Papillary
- Tubulopapillary
Biliary cystadenoma
Papillomatosis (adenomatosis)
Intraepithelial neoplasia (dysplasia and carcinoma in situ)
Evils
Carcinoma
- Papillary adenocarcinoma
- Intestinal type adenocarcinoma
- Gastric adenocarcinoma
- Mucinous adenocarcinoma
- Clear cell adenocarcinoma
- Signet-ring cell adenocarcinoma
- Squamous carcinoma
- Adenosquamous carcinoma
- Small cell carcinoma
- Large cell neuroendocrine carcinoma
- Undifferentiated carcinoma
- Biliary cystadenocarcinoma
Carcinoid
Carcinoid "goblet celi"
Tubular carcinoid
Carcinoid-adenocarcinoma
Others
NON-EPITHELIAL TUMORS
Granular cell tumor
Leiomyoma
Leiomyosarcoma
Rhabdomyosarcoma
Kaposi's sarcoma
Others
Malignant lymphoma
SECONDARY TUMORS, METASTASIS
We distinguish:
EPITELIAL TUMORS
Benigni
Adenoma
- Tubular
- Papillary
- Tubulopapillary
Biliary cystadenoma
Papillomatosis (adenomatosis)
Intraepithelial neoplasia (dysplasia and carcinoma in situ)
Evils
Carcinoma
- Papillary adenocarcinoma
- Intestinal type adenocarcinoma
- Gastric adenocarcinoma
- Mucinous adenocarcinoma
- Clear cell adenocarcinoma
- Signet-ring cell adenocarcinoma
- Squamous carcinoma
- Adenosquamous carcinoma
- Small cell carcinoma
- Large cell neuroendocrine carcinoma
- Undifferentiated carcinoma
- Biliary cystadenocarcinoma
Carcinoid
Carcinoid "goblet celi"
Tubular carcinoid
Carcinoid-adenocarcinoma
Others
NON-EPITHELIAL TUMORS
Granular cell tumor
Leiomyoma
Leiomyosarcoma
Rhabdomyosarcoma
Kaposi's sarcoma
Others
Malignant lymphoma
SECONDARY TUMORS, METASTASIS
The WHO classification of gallbladder tumors and extrahepatic biliary tract distinguishes epithelial tumors from non-epithelial cells and then in each of these categories benign tumors from malignant tumors. Mesenchymal tumors are without exception very rare.
Non-polypoid proliferation with
crowding and nuclear hypercromasia
with stratification and cell dysplasia
Severe dysplasia, enlarged nuclei,
round or ovoid form, hyperchromatic,
evident nucleoli
Adenomas have well-demarcated limits with respect to the surrounding wall. They are more frequent in the gallbladder than in the extrahepatic biliary tract and are found in 0.3 to 0.5% of cholecystectomies. They are generally found in the fourth to fifth decade more frequently in women, although there are no shortage of pediatric cases. The clinical picture in general is poor in symptoms or completely asymptomatic, unless it involves obstacles to the outflow of bile or that the tumor does not exceed 2 centimeters in diameter is important to remember that they may be associated with hereditary polyposis such as Peutz- Jegers and Gardner's syndrome. They are usually single and can be pedro-linked or sessile, often taking on an appearance similar to colon adenomas. The papillary type presents a velvety surface, similar to a cauliflower. ; histological point of view are distinguished adenorr: tubular, papillary and mixed tubulo-papillary, in relation to the type of growth. It is believed that gallbladder adenomas play: a minor role in carcinogens-unlike what happens in the colon. This is because it is not frequent to find remains of adenoma in cases of gallbladder carcinoma, both because adenoma and gallbladder carcinomas show different genetic alterations. However, the issue remains controversial, especially on the basis of studies conducted in the Far East.
Rare condition, characterized by multiple papillary tumors with a tendency to relapse. It mainly involves extrahepatic biliary tract, but it can also be observed in the gallbladder (WHO, 2000). The prognosis is negative, partly because complete excision is difficult to obtain. The 5-year survival is 38%. While some authors consider this to be a precancerous lesion, others are of the opinion that this is a form of multifocal, mucosecretory papillary carcinoma, similar to papillary intraductal mucinous carcinoma of the pancreas (AFIP, 1998).
Intraepithelial neoplasia is the primary precancerous lesion of the gallbladder (WHO 2000, Wistuba, 2004). The prevalence of biliary intraepithelial neoplasia corresponds to that of adenocarcinoma of the gallbladder and biliary tract. The prevalence varies therefore from 0.5% to 3% of the cholecystectomies in the different cases. The average age of diagnosis is 45 years (Roa 1996). Neoplastic changes usually originate in a "background" of chronic cholecystitis or in familial adenomatous polyposis (FAP). From the macroscopic point of view the gallbladder does not show significant alterations, also because it is almost invariably home to chronic cholecystitis and therefore has thickened and fibrotic walls. From a microscopic point of view, intraepithelial neoplasia is defined as the presence of columnar or cuboidal cells with variable degree of pseudostratification, nuclear atypia, loss of polarity, mitotic figures and presence of atypical goblet cells. Minor, moderate or severe changes are distinguished. In situ carcinoma presents the morphological aspects of carcinoma, but without infiltration of the stroma.
The typical alterations in biliary intraepithelial neoplasia are the same that are found in adenocarcinoma of the biliary tract, ie LOH in the loci corresponding to the genes for FHIT (3pl2), p53 (17ql3), pl6 (9p21) and 18q21 (DCC). These results correspond to the immunohistochemical positivity for p53 described in dysplasia and in situ carcinoma. It is therefore considered probable that the progressive accumulation of these alterations corresponds to the genesis of gallbladder adenocarcinoma.
Adenocarcinoma of the gallbladder.
Malignant epithelial tumor with glandular differentiation, which occurs in the
gallbladder. It occupies the fifth position for frequency among malignant tumors
of the digestive tract. It is two to six times more common in women than men and
the incidence increases with age. The frequency with which it is diagnosed
varies in different geographical areas and between different ethnic groups,
reaching the maximum (23/100000) among the American Indians. The same
variability is observed within a single state: for example, it is much higher in
the North than in the South of Japan or among the white Americans compared to
the blacks. In Italy the annual incidence is about 5/100000 (Lazcano-Ponce,
2001). These epidemiological differences indicate that genetic and environmental
factors probably occur in the etiopathogenesis of this tumor. Risk factors are
pathological events associated with the development of gallbladder carcinoma. In
particular, the concomitant presence of cholecystitis and / or lithiasis,
exposure to mutagenic substances (possibly present in the working environment),
genetic factors, the presence of an abnormal pancreatic duct hepatic duct should
be noted.
Gallbladder carcinoma is closely associated with the presence of gallbladder inflammation combined with cholelithiasis. Calculations are found in 85% of cases of gallbladder carcinoma and the risk increases with increasing size of the calculations. However, about 15% of cases of carcinoma occur in non-calculous gallbladder. Probably the mechanism through which the calculations act is based on the mechanical irritation cycle - biliary stasis - chronic inflammation - necrosis - regeneration - neoplastic transformation. An additional role can be attributed to Salmonella and
Gallbladder cancer, liver incision to detach the neoplastic cholecyst |
Escherichia infections.
Numerous mutagens have been associated with the development of gallbladder
carcinoma. In particular, an increase in frequency was observed among paper
workers, tanners, workers in synthetic fiber factories and even miners exposed
to radon. A possible carcinogenic role has also been hypothesized for some bile
constituents.
Genetic predisposition. A role for genetic predisposition is suggested, as well
as by the observation of gallbladder adenocarcinoma in some family polyposes
such as Gardner's syndrome and Peutz-Jeghers syndrome, by studies on some ethnic
groups such as the Mapuche in Chile and the Maori in New Zeland.
Normally the pancreatic duct and the common bile duct are united within the duodenum wall. If the junction occurs outside, it is called an abnormal junction. In this condition there is reflux of pancreatic juice in the biliary tree and in the gallbladder with consequent irritation and biliary stasis and hyperplastic, metaplastic and finally frankly neoplastic changes of the epithelium. In this condition the molecular alterations are different from what happens in the other types of gallbladder carcinoma.
On the basis of epidemiological, clinical, pathological and molecular data, two different pathogenic mechanisms can be considered. The main mechanism involves the calculosis and the consequent cholecystitis and in it plays a fundamental role the mutation of the gene coding for the p53, with consequent loss of the control of the cell proliferation and acquisition of the transformed phenotype. Further observed molecular changes relate to pl6, DCC, APC. The second mechanism is mainly observed in cases associated with abnormal pancreatic-biliary junction and involves the K-Ras oncogene, while alterations of p53, which are also observed, occur later.
From the macroscopic point of view there are two types of gallbladder carcinoma:
a diffuse infiltrating form and an exophytic, polypoid form.
Infiltrator type: this is the most frequent form and manifests itself as a more
or less widespread thickening of the gallbladder wall, sometimes ulcerated or
even with perforation and fistula formation. In the localized forms the
differential diagnosis with chronic cholecystitis can be difficult.
Exophytic type polypoid: more rare, usually sessile (see ultrasound image). It
occupies almost completely the lumen of the organ, sometimes with a cauliflower
appearance. If it occurs in the neck of the gallbladder it can cause empyema.
Often necrotic, it can be ulcerated.
From the microscopic point of view most of the carcinomas are adenocarcinomas,
sometimes of papillary appearance. The rarer varieties are the mucinous
adenocar-cinoma, the adenosquamous, the undifferentiated and rare forms of
endocrine differentiation. In general, at the time of diagnosis the tumor has
already infiltrated the liver. Other possible diffusion sites by contiguity are
the biliary tract, the pancreas, the peritoneum, the abdominal wall, the colon
and the duodenum. The main metastatic pathway is the lymphatic one, while
distant metastases are observed with the greatest frequency in the lung, the
bones, the kidneys and the heart; very rare brain metastases.
In most cases the symptoms are those of chronic cholecystitis, so much so that a
preoperative diagnosis is made in less than 20% of cases. The prognosis is
therefore largely dependent on the stage at the time of diagnosis that is
generally advanced, so the median survival is around 10-12 months. The
extrahepatic biliary cell carcinoma is rather rare (the incidence is 0.54 /
100.000 / year) and has some epidemiological differences compared to gallbladder
carcinoma. In fact, it is more frequent in male sex with an average age of about
seventy years onset and does not show significant variations between different
ethnic groups.
A certain association has been described with ulcerative colitis and sclerosing
cholangitis (relative risk 31.2); probably through chronic inflammation, the
biliary epithelium becomes more susceptible to the process of neoplastic
transformation. The same is true of Clonorchis sinensis infestation and
Salmonella infection (WHO, 2000). Another predisposing condition is the bile
duct cyst, probably as a consequence of the biliary stasis. The calculations, on
the other hand, do not seem to play an important role.
In the carcinoma of extrahepatic bile ducts, a fundamental role seems to be played by mutation in the KRAS protooncogene, while the alterations of p53 appear to be more rare and later.
From the macroscopic point of view we can distinguish a polypoid form (nodular or papillary) and a diffuse infiltrating form. A particular type of extrahepatic biliary cell carcinoma is the so-called "Klatskin tumor", which occurs between the junction of the cystic and the confluence of the right and left hepatic ducts in the common hepatic duct. This tumor represents a particular clinicopathological entity because it grows rather slowly, is strongly sclerosing and rarely gives distant metastases. From the microscopic point of view, most of the extrahepatic biliary tract carcinomas are represented by adenocarcinomas, similar to what is observed in the gallbladder. Metastasization usually occurs lymphatically towards the hepatis port. In general, at the time of diagnosis, most tumors "are already metastatic.
The main symptom is jaundice, often associated with vomiting, nausea and hepatomegaly. The differential diagnosis arises with respect to other forms of surgical jaundice. The prognosis is very poor (median survival 2 years).
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