Esophageal dysplasia and adenocarcinoma: a study with double immunostaining for intestinal and gastric markers.

Columnar lined esophagus is a complication of long term gastroesophageal reflux disease and the main precursor of esophageal adenocarcinoma. Incomplete intestinal metaplasia in reflux esophagitis represents one of the most important risk factors for neoplastic transformation through the metaplasia-dysplasia-adenocarcinoma sequence. However, recent studies suggest that cardiac type mucosa also shows molecular abnormalities which are similar to those of incomplete intestinal metaplasia. Immunohistochemically, three types of esophageal dysplasia and adenocarcinoma are recognized: adenomatous-intestinal, hybrid/mixed and foveolar gastric types. We are interested in the phenotypes of these dysplasias and adenocarcinomas, especially in the possible relationship between them. For this reason, we evaluated the immunohistochemical expression of intestinal and gastric markers in a series of 30 cases of esophageal high-grade dysplasia (high-grade intraepithelial neoplasia) and of 70 adenocarcinomas. For immunohistochemical classification, we used double immunohistochemical reactions CDX2/MUC5AC and CDX2/MUC6, respectively. In cases of incomplete intestinal metaplasia, hybrid/mixed high-grade dysplasia and hybrid/mixed adenocarcinoma, we found the expression of gastric mucins MUC5AC and MUC6 only in cells with intestinal differentiation (with nuclear positivity for CDX2). The double immunostaining excluded the presence of the cells with "pure" foveolar gastric phenotype in hybrid lesions. Thus, the hybrid category actually represents the intestinal type dysplasia/adenocarcinoma (which is known to have a better prognosis than the foveolar gastric type). Keywords: immunohistochemistry - double immunostaining - reflux esophagitis - Barrett esophagus - esophageal dysplasia - esophageal adenocarcinoma.

Pyloric gland adenoma: a histologic, immunohistochemical and molecular genetic study of 23 cases.

Pyloric gland adenoma is a rare neoplasm with a gastric epithelial differentiation. We report 23 cases of pyloric gland adenoma in older persons, with a mean age of 74 years (range 52 - 87 years). They occurred in the esophagus (3 cases), corporal gastric mucosa (7 cases), duodenum (10 cases), gallbladder (2 cases), and choledochus (one case). Histologically, they were characterized by closely packed pyloric gland-type tubules with a monolayer of cuboidal to low columnar epithelial cells containing basally located round nuclei, and a superficial layer of tall, columnar, foveolar-type epithelium. Immunohistochemically, most tumor glands expressed pyloric gland mucin MUC6, whereas MUC5AC was positive in superficial gastric foveolar epithelium, and in a minority of glands. In addition, scattered neuroendocrine cells positive for chromogranin A and/or synaptophysin were seen in all cases. In 3 cases (two cases in the gallbladder and one case in the esophagus), areas of intestinal metaplasia with CK20, CDX2, and MUC2 positivity were found. Focal low-grade dysplasia was found in five cases (21.7%), and diffuse high-grade dysplasia was seen in one adenoma (4.4%), i.e., 6 of 23 PGAs (26.1%) showed dysplastic features. In one esophageal case, an invasive adenocarcinoma was diagnosed. Scattered p53 positive cells were found in all cases. Their number was higher in lesions with low-grade dysplasia and it was substantially increased in adenoma with high-grade dysplasia and in adenocarcinoma. Our molecular genetic results indicate that pyloric gland adenomas neoplastic nature is associated with p53 accumulation, mutations in oncogenes GNAS, KRAS, CTTNB1 and tumor suppressor genes SMAD4, and TP53. Pyloric gland adenoma can evolve into dysplasia and adenocarcinoma.

Gastric dysplasias. A clinicopathological study of 35 cases.

Gastric epithelial dysplasia (GED) represents a recognized precursor lesion of gastric adenocarcinoma. GED types can be classified according to its morphology and patterns of mucin expression into adenomatous (intestinal), foveolar (gastric) and hybrid (mixed) types. We examined gastroscopic specimens with GED in 35 patients (21 men and 14 women, mean age 69.6 years). Adenomatous dysplasia was present in 17 patients (49 %), and was of low grade in 14 cases and high grade in 3 cases. Foveolar type dysplasia was found in 16 patients (46 %), and almost in one half of the cases it was high grade (in 7 cases, i.e. 46 %). In one woman, low grade foveolar dysplasia was found in polypoid mucosal prolapse of the gastric antrum. Hybrid dysplasia was found in only 2 cases (0.6 %), and in both of them this dysplasia was predominantly of foveolar type. One case was of low-grade and the second case was of a high-grade type. In our series GED was found mostly in the antrum. The findings in the adjacent mucosa usually included HP negative inactive chronic gastritis with intestinal metaplasia of both complete and incomplete types. In our series, foveolar type dysplasia was more frequent in comparison with previous studies. Our findings show that high grade dysplasia is more frequent in foveolar GD than in adenomatous GD, and this is in keeping with previous published findings.

Littoral cell angioma of the spleen: A case report.

Spleen tumors are an uncommon disease. Littoral cell angioma belongs to the group of vascular tumors. It is believed that this tumor originates from the tissue of the red pulp sinuses, specifically from the cells that are lining the sinuses. If this rare tumor is diagnosed, it is necessary to search for synchronous or metachronous visceral neoplasia. Littoral cell angioma can also mimic metastatic lesion of the spleen. This case report wants to draw attention on this rare tumor of the spleen which is very often associated with other visceral malignancy.

Characteristics of sentinel lymph nodes' metastatic involvement in early stage of vulvar cancer.

BACKGROUND: Nodal involvement is one of the most significant prognostic factors in early-stage vulvar cancer. AIMS: To determine the diagnostic accuracy of sentinel lymph node (SLN) detection in early-stage vulvar cancer and to describe the characteristics of metastatic lymph node involvement. METHODS: Of 23 women with early-stage squamous cell vulvar cancer included in the study, five had lateral lesions and 18 had midline lesions. SLN detection was performed by using a radioactive tracer and blue dye, followed by radical vulvectomy or radical wide excision with uni/bilateral inguinofemoral lymphadenectomy, depending on tumour size and localization. SLNs were subsequently examined with haematoxylin-eosin and immunohistochemistry. RESULTS: The SLN detection was successful in all 23 women (100%) and in 38 of 41 groins (92.3%) tested. The total number of SLNs was 67, with an average of 1.76 per groin. In total, 20 positive SLNs were detected in 14 of 23 patients. From a total of 20 positive SLNs, micrometastases were found in five SLNs and isolated tumour cells in one SLN. We experienced one case with a false negativity of SLN. Sensitivity, negative predictive value, accuracy and false negativity of SLN detection were 93.3%, 88.8%, 95.6% and 7.1% respectively. CONCLUSION: The SLN biopsy performed by an experienced team is a feasible method, with high accuracy in patients with early-stage vulvar cancer. Prognostic value of micrometastases should be confirmed in further studies.