Clinicopathological study of pseudomyogenic hemangioendothelioma.

OBJECTIVES: Pseudomyogenic hemangioendothelioma (PHE) is a rare intermediate hemangioendothelioma. This article aims to study the clinicopathological features of PHE. METHODS: We collected the clinicopathological features of 10 new PHE, and examined their molecular pathological features by fluorescence in situ hybridization. In addition, we summarized and analyzed the pathological data of 189 reported cases. RESULTS: The case group consisted of six men and four women aged 12-83 years (median: 41 years). Five instances occurred in the limbs, three in the head and neck, and two in the trunk. Tumor tissues were composed of spindle cells and round or polygonal epithelioid cells, which were either arranged in sheets or interwoven, along with areas of transitional morphology. Scattered or patchy stromal neutrophil infiltration was observed. Tumor cells had abundant cytoplasm, and some contained vacuoles. The nuclei had mild to moderate atypia, with visible nucleoli, and mitosis was rare. PHE tissues diffusely expressed CD31 and ERG, but not CD34, Desmin, SOX-10, HHV8 or S100, while some samples expressed CKpan, FLI-1 and EMA. INI-1 stain is retained. The proliferation index of Ki-67 is 10-35%. Seven samples were detected by fluorescence in situ hybridization, six of which had breakages in FosB proto-oncogene (AP-1 transcription factor subunit). Two patients experienced recurrence; however, no metastasis or death occurred. CONCLUSIONS: PHE is a rare soft tissue vascular tumor, which has biologically borderline malignant potential, local recurrence, little metastasis, and good overall survival and prognosis. Immunomarkers and molecular detection are valuable for diagnosis.

Hepatic perivascular epithelioid cell tumor: Clinicopathological analysis of 26 cases with emphasis on disease management and prognosis.

BACKGROUND: Perivascular epithelioid cell tumor (PEComa) is an uncommon tumor of mesenchymal origin. Cases of PEComa in the liver are extremely rare. AIM: To analyze the clinicopathological features and treatment of hepatic PEComa and to evaluate the prognosis after different treatments. METHODS: Clinical and pathological data of 26 patients with hepatic PEComa were collected. All cases were analyzed by immunohistochemistry and clinical follow-up. RESULTS: This study included 17 females and 9 males, with a median age of 50 years. Lesions were located in the left hepatic lobe in 13 cases, in the right lobe in 11, and in the caudate lobe in 2. The median tumor diameter was 6.5 cm. Light microscopy revealed that the tumor cells were mainly composed of epithelioid cells. The cytoplasm contained heterogeneous eosinophilic granules. There were thick-walled blood vessels, around which tumor cells were radially arranged. Immunohistochemical analysis of pigment-derived and myogenic markers in PEComas revealed that 25 cases were HMB45 (+), 23 were Melan-A (+), and 22 SMA (+). TFE3 and Desmin were negative in all cases. All the fluorescence in situ hybridization samples were negative for TFE3 gene break-apart probe. Tumor tissues were collected by extended hepatic lobe resection or simple hepatic tumor resection as the main treatments. Median follow-up was 62.5 mo. None of the patients had metastasis or recurrence, and there were no deaths due to the disease. CONCLUSION: Hepatic PEComa highly expresses melanin and smooth muscle markers, and generally exhibits an inert biological behavior. The prognosis after extended hepatic lobe resection and simple hepatic tumor resection is semblable.

The Role and Significance of Wnt5a in Regulating Epithelial-Mesenchymal Transition in Endometrioid Adenocarcinoma.

PURPOSE: As a non-classical ligand of Wnt, the abnormal regulation of Wnt5a contributes to the progression of malignant tumors; however, its effects differ depending on tumor type. Here, we evaluated the expression and significance of Wnt5a in endometrioid adenocarcinoma and its relationship with epithelial-mesenchymal transition (EMT)-related proteins. PATIENTS AND METHODS: Immunohistochemical streptavidin-peroxidase method and reverse transcription polymerase chain reaction (RT-PCR) method were used to analyze the expression and correlation of Wnt5a, and EMT-related protein ß-catenin, E-cadherin and enhancer of zeste homolog 2 (EZH2) in endometrial cancer tissues and cell samples of each group. RESULTS: The expression of Wnt5a and E-cadherin decreased in the following order, normal endometrium > atypical hyperplasia endometrium > endometrioid adenocarcinoma. In contrast, the expression of ß-catenin and EZH2 increased gradually. Moreover, Wnt5a expression was associated with the degree of tissue differentiation, International Federation of Gynecology and Obstetrics (FIGO) stage, and lymph node metastasis (all P<0.05). Wnt5a expression was also negatively correlated with ß-catenin and EZH2 expression and positively correlated with E-cadherin expression. RT-PCR results further indicated that E-cadherin mRNA expression was upregulated in a Wnt5a-overexpressing Ishikawa cell line compared to cells transfected with an empty vector or negative control cells (P<0.01). Furthermore, the expression of EZH2 and ß-catenin mRNA was downregulated in overexpressing cells compared to empty vector and negative control cells (P<0.01). CONCLUSION: Wnt5a may elicit a suppressive effect on endometrioid adenocarcinoma by inhibiting EMT. This study provides a theoretical basis for the pathological diagnosis and targeted therapy of endometrioid adenocarcinoma and extends our understanding of the Wnt5a signaling pathway.

Solid-Pseudopapillary Neoplasm of the Pancreas: A 63-Case Analysis of Clinicopathologic and Immunohistochemical Features and Risk Factors of Malignancy.

PURPOSE: Solid-pseudopapillary neoplasm (SPN) of the pancreas, a rare tumor, has low malignant potential. However, some patients develop metastasis and recurrence after resection, with aggressive biological behaviors. This study aimed to explore the features and risk factors associated with the aggressive biological behaviors of SPNs. PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological and long-term follow-up data of 63 patients diagnosed with SPN at the First Affiliated Hospital of Bengbu Medical College between January 2007 and February 2019. RESULTS: Sixty-three patients presented atypical clinical symptoms. The median tumor size was 7.0 cm (range, 2.4-17 cm), and imaging features were solid and cystic or solid tumors with uneven density. Frequent and diffuse nuclear LEF1 protein expression (94.2%) was observed with LEF1 having a higher sensitivity and specificity. Overall survival significantly correlated with tumor size, Ki-67 index, and lymph node metastasis (P < 0.05). CONCLUSION: SPN is a rare low-grade malignancy with a specific pseudopapillary structure. LEF1 is an effective biomarker of SPNs. Although SPNs generally display indolent biological behavior, a large tumor size, high proliferation index, and lymph node metastasis may be risk factors for the aggressive behavior and poor prognosis of SPN.

Clinicopathological features and prognostic factors associated with gastroenteropancreatic mixed neuroendocrine non-neuroendocrine neoplasms in Chinese patients.

BACKGROUND: The incidence of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) is low. To improve our understanding of this rare tumor type and optimally guide clinical treatment, associated risk factors, clinical manifestations, and prognosis must be explored. AIM: To identify risk factors that influence the prognosis of patients with gastroenteropancreatic MiNEN (GEP-MiNEN). METHODS: We retrospectively analyzed the clinical data of 46 patients who were diagnosed with GEP-MiNEN at the First Affiliated Hospital of Bengbu Medical College (Anhui, China) between January 2013 and December 2017. Risk factors influencing the prognosis of the patients were assessed using Kaplan-Meier curves and cox regression models. We compared the results with 55 randomly selected patients with gastroenteropancreatic GEP neuroendocrine tumors, 47 with neuroendocrine carcinomas (NEC), and 58 with poorly differentiated adenocarcinoma. RESULTS: Among the 46 patients with GEP-MiNEN, thirty-five had gastric tumors, nine had intestinal tumors (four in the small intestine and five in the colon and rectum), and two had pancreatic tumors. The median age of the patients was 66 (41-84) years, and the male-to-female ratio was 2.83. Thirty-three (71.7%) patients had clinical stage III and IV cancers. Distant metastasis occurred in 14 patients, of which 13 had metastasis to the liver. The follow-up period was 11-72 mo, and the median overall survival was 30 mo. Ki-67 index ≥ 50%, high proportion of NEC, lymph node involvement, distant metastasis, and higher clinical stage were independent risk factors affecting the prognosis of patients with GEP-MiNEN. The median overall survival was shorter for patients with NEC than for those with MiNEN (14 mo vs 30 mo, P = 0.001), but did not significantly differ from those with poorly differentiated adenocarcinoma and MiNEN (30 mo vs 18 mo, P = 0.453). CONCLUSION: A poor prognosis is associated with rare, aggressive GEP-MiNEN. Ki-67 index, tumor composition, lymph node involvement, distant metastasis, and clinical stage are important factors for patient prognosis.

Fluorescence in situ hybridization for WWTR1-CAMTA1 has higher sensitivity and specificity for epithelioid hemangioendothelioma diagnosis.

Epithelioid hemangioendothelioma (EHE) is a rare medium-to-low-grade malignant vascular tumor characterized by vascular differentiation along with specific morphological and genetic alterations. Approximately 90% and 5% of EHE cases are associated with the WWTR1-CAMTA1 and YAP1/TFE3 fusion gene, respectively. Therefore, nuclear CAMTA1 protein expression is considered to be an effective marker for EHE diagnosis. However, the specificity and reliability of this approach have recently been put into question. The purpose of this study was to compare the detection of CAMTA1 expression in cases of EHE and histologic mimics using fluorescence in situ hybridization (FISH) and conventional protein immunohistochemistry via hematoxylin and eosin staining. Fifteen EHE and 37 histologic mimic samples were immunohistochemically stained with polyclonal anti-CAMTA1 antibody to evaluate the nuclear protein expression level of CAMTA1. In addition, 15 EHE samples and 10 vascular tumor samples were subjected to FISH to detect the WWTR1-CAMTA1 fusion gene. Histologically, EHE typically showed a mucous hyaline or cartilaginous stroma, often forming a primitive vascular lumen, and expressed vascular endothelial markers. Twelve of the 15 EHE samples showed positive nuclear CAMTA1 expression with immunohistochemistry, whereas six of the 37 histologic mimics showed positive nuclear expression. FISH detected a red-green signal fusion in 14 of the 15 cases of EHE, but in none of the 10 vascular tumors. These results indicate that CAMTA1 is an effective and useful EHE marker, but that FISH fusion gene detection has better diagnostic value and clinical significance.