Screening of differentially expressed microRNAs in borderline and malignant gastrointestinal stromal tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>Gastrointestinal stromal tumors (GISTs) have a broad spectrum of biological behaviors ranging from benign, borderline and malignant. This study aimed to screen differentially expressed microRNAs (miRNAs) between malignant and borderline GISTs and to investigate the potential role of miRNAs in the malignant transformation of GISTs.</p><p><b>METHODS</b>Six GIST samples including borderline tumors (n = 3) and malignant tumors (n = 3) were collected based on the clinical and pathological characteristics. Total RNA was extracted, followed by miRNA microarray analysis to screen the differentially expressed miRNAs. The most significantly expressed 4 miRNAs were then chosen for further validation by real-time PCR in 22 additional GIST samples.</p><p><b>RESULTS</b>Direct comparison of malignant group versus borderline group revealed 14 significantly and differentially expressed miRNAs (P < 0.05, with a fold change of < 0.5 or > 2). Five miRNAs were up-regulated and nine were down-regulated in the malignant group. Four miRNAs (miR-221, miR-135b, miR-675(*) and miR-218) were most significantly and differentially expressed between the two groups. The differential expression of 2 miRNAs (miR-221 and miR-675(*)) were subsequently confirmed with good concordance by real-time PCR.</p><p><b>CONCLUSIONS</b>The differential miRNA expression profiles between two groups are revealed by miRNA microarray assay, and confirmed by real-time PCR. Among differentially expressed miRNAs, miR-221 and miR-675(*) might be related to the malignant transformation of GISTs, and have a potential value in predicting biological behavior of GISTs.</p>

Study on clinicopathologic grading system and prognosis of primary hepatic neuroendocrine neoplasms / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, criteria for grading and prognostic factors of primary hepatic neuroendocrine neoplasms.</p><p><b>METHODS</b>Thirty-five cases of primary hepatic neuroendocrine neoplasm were retrieved from the archival files over a period of 11 years (with 32 cases having integrated data). According to the 2010 WHO classification of tumors of the digestive system, the cases were categorized into three groups: neuroendocrine tumor grade 1 (NET G1), neuroendocrine tumor grade 2 (NET G2) and neuroendocrine carcinoma (NEC). Statistical correlation between various histologic parameters and survival data was analyzed.</p><p><b>RESULTS</b>Statistical analysis showed significant difference between NET [G1 (1 case)/G2 (14 cases)] and NEC (17 cases) groups in terms of tumor differentiation, necrosis, nuclear atypia, mitotic count and Ki-67 proliferative index (P < 0.05). There was no statistically significant difference in tumor size, growth pattern and presence of vascular tumor emboli (P > 0.05). The survival rate of patients correlated with tumor differentiation, growth pattern, necrosis, nuclear atypia, mitotic count and proliferative index (P < 0.05). There was no statistically significant difference between patient survival and tumor size or presence of vascular tumor emboli (P > 0.05).</p><p><b>CONCLUSIONS</b>The subdivision of primary hepatic neuroendocrine neoplasm according to the 2010 WHO classification of tumors of the digestive system helps to evaluate the malignant potential and prognosis of the tumors. Prognostically useful histologic parameters include tumor differentiation, growth pattern, necrosis, nuclear atypia, mitotic count and proliferative index.</p>

Focal nodular hyperplasia of liver: a clinicopathologic study of 238 patients / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of focal nodular hyperplasia (FNH) of liver.</p><p><b>METHODS</b>The clinical, radiologic, pathologic findings and follow-up data of 238 cases of FNH were retrospectively analyzed.</p><p><b>RESULTS</b>The patients included 93 females and 145 males. The age of the patients ranged from 11 to 77 years (median = 39.1 years). Amongst the 233 patients who had clinical information available, 188 were asymptomatic, 216 had no history of hepatitis B and/or C infection and 232 had negative serum alpha-fetoprotein level. Amongst the 185 patients who had undergone radiologic examination, 123 (66.5%) were accurately diagnosed as such. Macroscopically, of the 284 lesions from 238 patients, the average diameter was 3.7 cm. Two hundred and fifteen cases (90.3%) were solitary, 172 cases were located in the right lobe and 115(40.5%) had central stellate fibrotic scars or lobulated cut surface. Histologically, 229 lesions belonged to classic type and 9 lesions were of non-classic type. The latter was further classified as the telangiectatic form (6 lesions) and the mixed hyperplastic and adenomatous form (3 lesions). There was no evidence of significant cytologic atypia. Follow-up data were available in 173 patients (72.7%). None of them died of the disease and 2 patients suffered from relapses after 2 and 4 years, respectively.</p><p><b>CONCLUSIONS</b>FNH is a hyperplastic response of normal liver cells to local blood flow anomalies. It has no obvious sex predilection and more than 66% can be diagnosed accurately with radiologic examination. The lesions in the current study show no cytologic atypia.</p>

Sclerosing angiomatoid nodular transformation of spleen: a clinicopathologic study of 10 cases with review of literature / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, differential diagnosis and pathogenesis of sclerosing angiomatoid nodular transformation of spleen.</p><p><b>METHODS</b>Ten cases of sclerosing angiomatoid nodular transformation of spleen were retrieved from the archival file. Histochemical and immunohistochemical (EnVision method) studies were performed. Ultrastructural findings were also available in one of them.</p><p><b>RESULTS</b>Sclerosing angiomatoid nodular transformation was characterized by micronodular appearance of vascular spaces lined by plump endothelial cells with interspersed ovoid spindle cells. Immunohistochemical study showed that the endothelial cells of vessels in the angiomatoid nodules had various expressions of immunologic phenotypes and could be mainly classified into 3 types: CD34(+)/CD31(+)/CD8⁻ endothelial cells of the capillaries, CD8(+)/CD31(+)/CD34⁻ lining cells of the sinusoids and CD31(+)/CD8⁻/CD34⁻ endothelial cells of the small veins. Collagen network and dilated lymphatic sinuses were evident under transmission electron microscope.</p><p><b>CONCLUSIONS</b>Sclerosing angiomatoid nodular transformation of spleen is a rare benign entity. It may represent a reactive condition and bears some relationship with splenic angioma. It needs to be distinguished from borderline or malignant vascular tumors of spleen.</p>

Study on clinicopathologic features and metastasizing potential of solid pseudopapillary tumor of pancreas / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and metastasizing potential of solid pseudopapillary tumor of the pancreas (SPT).</p><p><b>METHODS</b>Forty-five cases of SPT were retrieved from the archival file and subdivided into metastasizing group (MG, n = 4), and non-metastasizing group (NMG, n = 41), according to the follow-up clinical information. The histological features were reviewed and immunohistochemical study for vimentin, alpha 1-antitrypsin, alpha 1-antichymotrypsin, CD10, neuron-specific enolase, progesterone receptor, chromogranin A, synaptophysin, AE1/AE3, beta-catenin, p53, cyclin D1, CD34 and Ki-67 was carried out. The results were correlated with follow-up data.</p><p><b>RESULTS</b>There was no statistically significant difference between MG and NMG, in terms of age and gender of the patients, site, size and capsular status of the tumor. No single morphologic parameter could distinguish MG from NMG. In general, increased mitotic activity, tumor emboli in vessels and necrotic foci were more conspicuous in MG than in NMG. According to a morphologic scoring system, all cases of MG had score ≥ 5, in contrast to < 5 in 95.1% (39 cases) of NMG. Immunohistochemically, there was no statistically significant difference between MG and NMG for beta-catenin, p53, cyclin D1 and CD34 staining. Ki-67 positivity however was significantly higher in MG. Amongst the 37 cases with follow-up information available, the average duration of follow up was 37.4 months. Thirty-three patients were alive and disease-free.Four suffered from liver metastases; and none of them died of the tumor.</p><p><b>CONCLUSIONS</b>Mitotic activity, presence of tumor emboli and necrotic foci represent as the useful parameters in predicting metastasizing potential of SPT, especially with application of morphologic scoring system. Immunostaining for Ki-67 can also serve as an additional prognostic indicator.</p>

Clinical and histopathological alterations of lymphangioleiomyomatosis in 14 Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lymphangioleiomyomatosis (LAM) is a rare disease that predominantly affects young females. It is considered as an "orphan" life-threatening disease of unknown etiology, with uncertain clinical prognosis, and no effective treatment. LAM can arise sporadically or in association with tuberous sclerosis complex (TSC), an autosomal inherited syndrome characterized by hamartoma-like tumor growth and pathologic features that are distinct from manifestations of pulmonary LAM. The clinical course of LAM is characterized by progressive dyspnea on exertion, recurrent pneumothorax, and chylous fluid collections.</p><p><b>METHODS</b>Fourteen cases of LAM from Zhongshan Hospital, Fudan University are reviewed, twelve were confirmed by lung biopsy, one by retroperitoneal lymphangioleiomyoma resection, and one by autopsy.</p><p><b>RESULTS</b>All 14 patients were women, aged 18 to 69 years (mean 43.3 years, median 46.5 years). Haemoptysis (57.1%) and chylothorax (35.7%) were more frequent than those described in previous case series. Extrapulmonary findings such as renal angiomyolipoma (AML), enlarged abdominal lymph nodes, liver AML and retroperitoneal lymphangioleiomyoma were seen in 21.4%, 14.3%, 7.14% and 7.14% in 14 cases respectively, which is remarkably lower than in the previously reported. Abnormal smooth muscle cells (LAM cells) were found to line the airways, bronchioles, lymphatics and blood vessels leading to airflow obstruction and replacement of the lung parenchyma by cysts. There were some surprises in the autopsy case as several LAM cell emboli were found in the veins of mediastinum lymph nodes; LAM cells were found to be disseminated in soft tissues adjacent to the ilium.</p><p><b>CONCLUSIONS</b>Women with unexplained recurrent pneumothorax, tuberous sclerosis, or a diagnosis of primary spontaneous pneumothorax or emphysema in the setting of limited or absent tobacco use should undergo high-resolution computed tomography (HRCT) scan screening for LAM. Routine abdominal and pelvic imaging examinations should be performed to detect extrapulmonary involvement. The autopsy studies histologically suggested that LAM could be a multisystemic disease and LAM cells might possess metastatic potential.</p>

Clinicopathologic analysis of 92 cases of pancreatic cystic neoplasm / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic and immunohistochemical features of cystic neoplasms of the pancreas.</p><p><b>METHODS</b>Ninety-two cases of cystic neoplasm of pancreas were retrieved from the Department archival file during the period from 1999 to 2005. Histologic features were studied and the tumors were typed according to WHO classification. Immunohistochemistry was also carried out using paraffin-embedded tissues.</p><p><b>RESULTS</b>The age of patients ranged from 16 to 80 years. The patients included 33 males and 59 females. The tumors varied from 2 cm to 21 cm in diameter. They consisted of intraductal papillary mucinous neoplasm (36/92), serous cystic neoplasm (18/92), solid pseudopapillary tumor (18/92), mucinous cystic neoplasm (14/92), cystic pancreatic ductal adenocarcinoma (4/92) and cystic pancreatic endocrine neoplasm (2/92). Immunohistochemical study revealed variable staining patterns, with frequent overlaps between different tumor types. In general, serous cystic neoplasm expressed MUC1, while mucinous cystic neoplasm was positive for MUC-5AC, intraductal papillary mucinous neoplasm for MUC-2 and cystic pancreatic ductal adenocarcinoma for MUC-1. On the other hand, solid pseudopapillary tumor expressed alpha-antitrypsin, alpha-antichymotrypsin, vimentin and progesterone receptor.</p><p><b>CONCLUSIONS</b>Accurate diagnosis of pancreatic cystic neoplasms requires correlation of clinical findings, radiologic examination, histologic features and immunostaining results. Pathologic distinction is important because of different prognostic significance. Two-thirds of pancreatic cystic neoplasms are premalignant or malignant and warrant surgical resection, whereas the remaining one-third (including pseudocyst and serous cystadenoma) are benign and can be treated conservatively.</p>

Diagnosis and differential diagnosis of intraductal papillary mucinous neoplasm of pancreas / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of intraductal papillary mucinous neoplasm (IPMN) and its distinction from mucinous cystic neoplasm of pancreas.</p><p><b>METHODS</b>The clinical, radiologic and histologic features of 17 cases of IPMN and 13 cases of mucinous cystic neoplasm (MCN) were reviewed. Mucin profiles (MUC1, MUC2 and MUC5AC) were studied by histology (HE) and immunohistochemistry (EnVision).</p><p><b>RESULTS</b>10 of the 17 cases of IPMN were males. 13 cases of the IPMN were located in head of pancreas. Communication with the main pancreatic duct was demonstrated in 15 cases. Histologically, there were mild to severe papillary ingrowths of dysplastic epithelial cells, associated with intervening normal or atrophic pancreatic parenchyma. Ovarian-like stroma was not seen. Ancillary investigations showed that MUC2 and MUC5AC were detected in tumor cells of 9 and 4 cases respectively. The 4 cases with invasive component showed MUC1 positivity. On the other hand, 11 of the 13 cases of MCN occurred in middle-aged to elderly females and were located in the body and tail of pancreas. Ovarian-like stroma was commonly seen and there was no connection with the main pancreatic duct. All non-invasive MCN, regardless of the degree of cytologic atypia, were positive for MUC5AC (but not MUC2). In the 2 cases with invasive component, MUC1 expression was observed, as in IPMN.</p><p><b>CONCLUSIONS</b>The age and sex of patients, tumor location, absence of ovarian-like stroma, communication with main pancreatic duct and characteristic mucin profiles represent useful parameters in distinguishing IPMN from MCN of pancreas. The tumor cells of IPMN express mainly MUC2, while those of MCN express MUC5AC. MUC1 may also be a useful marker in demonstration of stromal invasion in these tumors.</p>