Invasive micropapillary variant of the gallbladder adenocarcinoma and its aggressive potential for lymph node metastasis

Abstract

An invasive micropapillary variant (IMPV) has recently been described in several organs but has not been reported in the gallbladder. It has been mentioned to have aggressive behavior with a high propensity for lymphovascular invasion, lymph node metastasis and poor clinical outcome. We analyzed the clinicopathologic findings of IMPV and compared them with those of a conventional adenocarcinoma in the gallbladder to clarify the highly aggressive potential of IMPV of gallbladder carcinoma. Ninety consecutive cases of surgically resected gallbladder carcinomas were studied for age, gender, type, depth of invasion and lymph node and distant metastases. Histologically, IMPV of gallbladder carcinoma was characterized by a small cluster of tumor cells lying within clear stromal spaces. This pattern mimicked extensive lymphatic invasion, but the cluster of tumor cells showed a distinctive retraction artifact from the surrounding stroma. In total, 20 (22.2%) cases had foci of IMPV, which ranged from 5% to 10% of the primary tumor tissue. Of those 20 cases, 17 (85.0%) carcinomas with IMPV also included lymph node metastasis, which was more frequent than in conventional carcinoma (32.8%, P < 0.001). Carcinomas with IMPV had a more advanced tumor status and showed severe lymphatic invasion (P = 0.001, P < 0.001, respectively). A multivariate regression analysis demonstrated that the presence of IMPV is an independent predictor of regional nodal metastasis (Odds ratio: 9.995, 95% confidence interval: 1.996-50.052, P = 0.005). IMPV is a useful predictor of regional lymph node metastasis in gallbladder adenocarcinoma.Gallbladder cancer has geographic and ethnic variation throughout the world and is a highly fatal malignant tumor. Chile, Mexico and Bolivia have the highest incidence rates in the world. In the United States, cancer of the gallbladder accounts for 0.17% of all cancers in males and 0.49% in females (7). In Japan, cancer of the gallbladder accounts for 1.25% and 3.49% of the cancer deaths among men and women, respectively (12). The poor prognosis of this disease is due to the anatomic position of the gallbladder and the nonspecific symptoms and signs. These characteristics of gallbladder carcinomas result in advanced primary tumors and lymph node metastasis at the time of diagnosis. However, with the recent advances in preoperative imaging, early gallbladder carcinomas have currently been diagnosed more frequently and radical aggressive surgery has been performed; both of these have led to an improvement in the survival rate (16). The spread of cancer cells via the lymphatics to regional lymph nodes is an important early event during tumor progression, and lymph node metastasis is a key factor in the staging of human cancers

Submucosal Invasive Micropapillary Carcinoma of the Colon with Massive Lymph Node Metastases: A Case Report

“…IMPC has been reported in various organs, including the breast [1], lung [2], parotid gland [3], ovary [5], pancreas [6], gallbladder [7], and stomach [8]; however, reports of colorectal micropapillary carcinoma, especially in early stages, are rare.…”

Invasive micropapillary carcinoma of the extrahepatic bile duct and its malignant potential

“…The previous reports revealed that IMPC exhibited a tendency for lymphatic invasion and lymph node metastasis. In our study, IMPC component of extrahepatic bile duct ranged from 5 to 60% of the entire tumor, while with IMPC components were found in the other organs: 10–90% in salivary duct carcinoma (15), 10–90% in gastric carcinoma (21), 5–10% in gallbladder carcinoma (17), 5–95% in breast cancer (27). IMPC component, regardless of its tumor volume, has been shown to have malignant potential for lymphatic invasion and lymph node metastasis.…”

“…Recent studies have demonstrated that an invasive micropapillary carcinoma (IMPC) frequently shows aggressive tumor behaviors with marked lymph-vascular invasion, resulting in poor prognosis in several organs including the breast (3–5), urinary bladder (6–8), lung (9–13), parotid gland (14,15), pancreas (16), gallbladder (17), colorectum (18) and stomach (19–22). To the best of our knowledge, however, there has been only one case report of extrahepatic bile duct carcinoma which contains IMPC (23).…”

Histological phenotype is correlated with the wall-invasion pattern of gallbladder adenocarcinoma

“…Moreover, the majority of patients have frequent recurrences after the surgery, and pursue the chemotherapy or radiotherapy treatment when recurrences happened after the surgery (2, 15). Several previous studies have demonstrated high risks of disease progression, using surgically-resected GBC cases, and histological grade, depth of wall infiltration, and lymph node status have been determined to be clinicopathological prognostic factors (6,22). In addition, we have classified the wall-invasion pattern of GBC into two groups, i.e., infiltrative growth type (IG type) and destructive growth type (DG type) (18)(19)(20).…”