Analysis of APC/beta-catenin genes mutations and Wnt signalling pathway in desmoid-type fibromatosis.

OBJECTIVE: The abnormalities of the Wnt signalling pathway in desmoid-type fibromatosis were analysed, with the purpose of exploring the mechanism of tumorigenesis and progression. METHODS: The clinical and histopathological features of 96 cases were analysed. Beta-catenin, cyclin-D1, c-myc, and Ki-67 proteins were detected in 69 cases using formalin-fixed, paraffin-embedded tissues. Using the same materials, apoptosis of the tumour cells was investigated by terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling (TUNEL) testing. Polymerase chain reaction (PCR), denaturing high performance liquid chromatography (DHPLC) assay, and sequencing were performed to detect abnormalities of the adenomatous polyposis coli (APC) and beta-catenin genes. RESULTS: APC gene mutations were found in 18 cases (26.1%, 18/69). Somatic mutations of codon 41 in exon 3 of beta-catenin were detected in 13 cases (18.8%, 13/69). No correlation of beta-catenin abnormal expression with the mutations of APC gene or beta-catenin gene was identified (p>0.05). The cases with abnormal beta-catenin expression showed a higher level of c-myc protein expression (69.7%, 23/33) than those without (22.2%, 8/36, p = 0.001). The apoptotic indices (AIs) were significantly lower in cyclin-D1 positive cases and c-myc positive cases (p = 0.015, p = 0.007). CONCLUSIONS: There are somatic mutations of the APC and beta-catenin gene in desmoid-type fibromatosis, and there are abnormalities in the Wnt signalling pathway. These abnormalities may result in aberrant cell proliferation and apoptosis, which are likely to be important factors in tumorigenesis and progression.

The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020) / 中华消化外科杂志

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

SMARCA4-deficient primary thoracic sarcoma:a clinicopathological analysis of five cases / 中华病理学杂志

Objective@#To investigate the clinicopathological characteristics of SMARCA4- deficient thoracic sarcomas.@*Methods@#The clinical features and CT scans of SMARCA4-deficient thoracic sarcomas (n=5) diagnosed at Fudan University Cancer Hospital from December 2016 to October 2018 were reviewed. Hematoxylin-eosin staining, immunohistochemistry and targeted next generation sequencing were performed in available cases along with a literature review.@*Results@#All 5 patients were males with age ranging from 32 to 65 years (average 54 years; median 61 years). Four patients were smokers except one with unknown smoking history. The average maximum diameter of tumor was 5.6 cm. Tumor primary sites included thoracic wall,thoracic cavity,lung and mediastinum. Histologically,tumor cells formed solid sheets or anastomosing islands with brisk mitotic figures accompanying with large areas of necrosis. Three cases focally exhibited rhabdoid morphology and vesicular chromatin. Immunohistochemically, SMARCA4, SMARCA2 and Claudin-4 were negative in all cases and all tumors demonstrated SOX2 and SMARCB1 nuclear positive staining. Among 3 cases analyzed by targeted next generation sequencing, concurrent SMARCA4 and p53 mutation was detected in all three cases. Mutations of STK11, ERBB4, NF2, GNAS, MTOR,MET and FGFR1 amplification were also detected among the three cases. The follow-up information was available in all 5 cases. Two patients died of the tumor. One relapsed multiple times after surgeries but was alive with disease. Two patients received radical excisions without relapse.@*Conclusions@#SMARCA4-deficient thoracic sarcoma is a rare but highly-aggressive tumor with dismal prognosis. The tumor is featured by rhabdoid morphology histologically and distinctive immunohistochemical and molecular phenotype.

Expression of P16 and CD44 in gastrointestinal stromal tumors and their relationship with the prognosis ;of patients / 实用医学杂志

Objective To investigate the expression of P16 and CD44 in gastrointestinal stromal tumors (GIST) and their relationship with the prognosis of patients. Methods The GIST specimens of seventy patients who received surgical excision were collected. Tissue microarray of the seventy GIST samples was constructed. The expression of P16 and CD44 were detected by the immunohistochemical staining. The patients were followed up via out-patient examination and telephone. Results All the patients were followed up for 2-212 months, and the median time for follow-up was 68 months. The differences of the expression of P16 in GISTs among NIH risk ranks were insignificant (P > 0.05). The differences of the expression of CD44 in GISTs among NIH risk ranks were statistically significant (P < 0.05). Univariate analysis showed that tumor size, mitotic count, tumor location, NIH risk rank, the expression of P16 and CD44 were related to the prognosis of GIST patients. Multivariate showed that tumor size, mitotic count, tumor location, and the expression of CD44 was independent prognosis factors of GIST patients. Conclusion CD44 could be used as a biomarker in predicting the prognosis of GIST patients.

Grey zone lymphoma with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: clinicopathologic characterization of 16 cases showing different patterns / 中华病理学杂志

<p><b>OBJECTIVE</b>To profile the clinicopathologic features of a series of grey zone lymphoma (GZL) cases with hybrid features of diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (CHL), with a purpose to gain an in-depth understanding of the borderline B-cell neoplasm.</p><p><b>METHODS</b>The clinical, morphologic and immunophenotyical characteristics of 16 cases were retrospectively analyzed.</p><p><b>RESULTS</b>The patients were mostly male adults, with a male to female ratio of 1.7: 1.0 and a mean age of 40.2 years. Eight patients presented with peripheral nodal lesions and five cases with mediastinal involvement. Histologically and immunophenotypically, the 16 cases were classified into three sub-categories. In 4 cases, the morphologic features resembled CHL more closely, but the neoplastic cells showed uniform and intense positive staining of CD20 (pattern 1). Although the initial impression of the other 8 cases was that of DLBCL, the expression levels of CD20 and PAX5 were variable, and CD30 or CD15 was positive (pattern 2). A characteristic feature of pattern 3, observed in the remaining 4 cases, demonstrated a broad spectrum of morphology with hybrid features of both CHL and DLBCL. The neoplastic cells in pattern 3 were positive for CD20, CD30 and CD15. EBV-LMP1 was detected in 6 of the 11 tested cases. Clinically, most patients with GZL seemed insensitive to immuno-chemotherapy of the R-CHOP regimen.</p><p><b>CONCLUSIONS</b>The diagnostic criteria for GZL with features intermediate between DLBCL and CHL is proposed by the three histologic patterns commonly seen in these lesions. Cases presented with peripheral lesions might differ from those with mediastinal presentation pathologically. At current time, there is no effective treatment for these borderline B-cell lymphomas and the prognosis is poor.</p>

Immunohistochemical classification and prognosis of diffuse large B-cell lymphoma in China / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the immunohistochemical classification and prognosis of diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>A total of 148 cases of DLBCL were classified into germinal center B-cell-like (GCB) and non-GCB/activated B-cell-like (ABC) subtypes by Hans, Choi and Tally immunohistochemical stain algorithms. The clinical features and survival data of GCB and non-GCB/ABC subtypes were compared. Multivariate analysis about clinical features and results of immunohistochemical stain algorithms was carried out by using Cox regression, with overall survival as the outcome.</p><p><b>RESULTS</b>The prevalence of GCB subtype was significantly lower than that of non-GCB/ABC subtype, as classified by whichever algorithms in the 148 DLBCL cases studied. The prevalence of GCB subtype by Tally algorithm was lowest. The prevalence of GCB subtype (19 cases, 16.7%) was also significantly lower than non-GCB/ABC subtype (95 cases, 83.3%; P = 0.000 1) in the 114 (77.0%) concordant cases by the three algorithms. There was no difference between GCB and non-GCB/ABC subtypes by the three algorithms in five-year overall survival rate and survival curve of the 80 DLBCL patients with follow-up data available (P > 0.05). Primary gastric DLBCL tended to show a higher prevalence of GCB subtype, a better five-year overall survival rate and survival curve than the other groups. Multivariate analysis showed that patient age (HR = 1.036, P = 0.001) and tumor stage (HR = 1.997, P = 0) were also significantly adverse predictors of overall survival.</p><p><b>CONCLUSION</b>The Hans, Choi and Tally immunohistochemical stain algorithms cannot effectively classify Chinese DLBCL into different prognostic subtypes. Primary gastric DLBCL has different immunophenotype and outcome, as compared with DLCBL in other sites.</p>

Chondroblastoma in the long bone diaphysis: a report of two cases with literature review / 癌症

To investigate the clinical characteristics of chondroblastoma with an emphasis on lesions located in the long bone diaphysis, we reviewed the clinical data of 7 patients with histologically proven chondroblastoma treated in Tianjin Medical University Cancer Hospital and Fudan University Cancer Hospital between January 1995 and May 2009. There were two rare cases of chondroblastoma in the long bone diaphysis. One patient with a lesion in the tibial diaphysis underwent intralesional curettage and bone grafting, and the postoperative bone function was measured as excellent according to the Enneking scoring system. The patient was still alive upon follow-up at 60 months. The other patient with a lesion in the humeral diaphysis underwent resection, and the postoperative bone function was excellent at 48 months, at which there was no evidence of recurrence or metastasis. Thus, except for the distinctive site of the long bone diaphysis, which made diagnosis difficult, the patients' ages, symptoms, X-ray and CT images, treatment, and prognosis were in accordance with typical lesions in the epiphysis and metaphysis. The diagnosis of chondroblastoma in the long bone diaphysis significantly depends on histopathologic characteristics.

Primary and metastatic hepatic neuroendocrine carcinoma: a clinicopathological study / 中华肝胆外科杂志

Objective To study the clinicopathological features of primary and metastatic hepatic neuroendocrine carcinoma.Methods The records of 35 patients with primary hepatic neuroendocrine carcinoma and 35 patients with metastatic hepatic neuroendocrine carcinoma were retrospectively reviewed.These patients served as the primary group(priNET,n=35)and the metastasis group (metNET,n=35),respectively.Results There were significant differences between the two groups of patients in gender,site,size and number of tumor(P＜0.05).Although there was no significant difference between the two groups in the distribution of the tumors in the two lobes of liver (P＞0.05),priNET had more tumors localized to one lobe of liver while metNET had more tumors involving both lobes of liver(P＜0.05).Conclusions Gender,size,site and number of tumor may play an important role in the differentiation of primary or metastatic hepatic neuroendocrine tumor.

Primary Hodgkin disease of the supermaxilla: a case report and review of the literatures / 白血病·淋巴瘤

Objective To intensify the diagnosis and treatment of primary osseous Hodgkin disease (HD) and reinforce the impression of its features of pathology and imaging. Methods The clinical manifestation, laboratory examination, treatment and outcome of a patient with primary Hodgkin disease of the supermaxilla were first reported and the pertinent literatures were reviewed. Results Pain of the right supermaxilla was the first clinicM symptom. Plain X-rays showed mixed osteolytic and partially osteosclerotie lesions in the right supermaxiUa. The tumor was removed and the pathohistology was HD lymphocyte-depletion. The clinical diagnosis was primary HD of the supermaxilla (Stage Ⅰ ). The case was treated with ABVD regimen and no obviously adverse reaction appeared. Conclusion Primary osseous HD rarely presents as a malignant bone lymphoma and is easily misdiagnoed. Pathological and immunohistologic studies can be useful to confirm the diagnosis of primary osseous HD. Early diagnosis and the differentiation from other disease should be performed and the prognosis of the present-day chemotherapy regimen appears good.

Study on the clinical pathology of gastrointestinal stromal tumors / 肿瘤研究与临床

The content of gastrointestinal stromal tumors had changed many times since the appearance of this idea. Along with the progress of molecular and biological study in recent years, it was a kind of tumor with specific clinical, pathological and molecular genetic characteristics, and was different from other specific tumors originated from the smooth muscle or nerves. Along with the success of targeted therapy of GIST, the disease was paid more attention. Therefore, a review of the clinical pathological study of GIST was needed.

Molecular and biologic study of gastrointestinal stromal tumors / 肿瘤研究与临床

Gastrointestinal stromal tumors is a new kind of tumor known recently, especially the important progress in the molecular and biologic study of GIST were used quickly in the clinical diagnosis and treatment, and made a close combination of basic research and clinical applications. The study and application of target therapy of new molecules on the mechanism of molecular genetics of GIST was another successful example. Therefore, GIST was paid extensive attention by the scholars. The progress on the molecular and biological study was summarized.

Advances in research on extranodal NK/T cell lymphoma(nasal type) / 中国癌症杂志

Extranodal NK/T cell lymphoma(nasal type) is a common,high malignant degree and poor prognosis entity of the nasal lymphoma.It is the most important to understand its genesis,development,clinical manifestation,pathologic diagnosis,therapy and prognosis.

New series of WHO classification of tumors / 中国癌症杂志

Since 2000,the new series WHO classification of tumors has been greatly changed. The name of the volumes altered from 《Histological Typing of Tumors》 to 《Pathology and Genetics of Tumors》.The series regards the type of tumor as a disease entity. A new approach to classification has been adopted. In this approach,all available information--morphology,immunophentype,genetic features, clinical features, and imaging features--is used to define a disease entity. Pathologist,oncologists and geneticists should be familiar to the new series WHO classification of tumors. The series provides an international standard. It will serve as an indispensable guide for the design of trials monitoring response to therpy and clinical outcome.

Clinicopathological features and management of gastrointestinal borderline lesion and correlative lesion / 中国癌症杂志

One of the most problems is the diagnosis of the borderline lesion and/or borderline tumor to pathologists. It is necessary to make the correct diagnosis of the gastrointestinal borderline lesion and/or borderline tumor and correlative lesion such as gastrointestinal stromal tumors, gastrointestinal lymphoid proliferation and MALT lymphoma, IPSID, gastrointestinal adenoma and appendix carcinoid.[

Giant cell fibroblastoma: a clinicopathologic analysis of seven cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinical, pathological and immunohistochemical features of giant cell fibroblastoma (GCF), with emphasis on its differential diagnosis and histogenesis.</p><p><b>METHODS</b>Seven cases of GCF were investigated by light microscopy and immunohistochemistry.</p><p><b>RESULTS</b>Six cases occurred in children, and one occurred in a 35 year-old adult (mean 9.4 years). Five were male and two were female. Clinically, all cases appeared as slowly growing painless nodules located in the dermis or subcutis of the trunk and extremities. Microscopically, the poorly circumscribed tumor was composed of a proliferation of slightly to moderately atypical spindle cells which were arranged in parallel or wavy fascicles, and embedded in a fibromyxoid to collagenous background. The pathognomonic feature consisted of irregular distributed cleft-like or sinusoid-like pseudovascular spaces lined with a discontinuous layer of pleomorphic spindle cells and multinucleate giant cells. There was transition in shape between these two cells. Immunohistochemially, both cells expressed vimentin and CD34. Follow-up information in five cases showed local recurrences in two cases.</p><p><b>CONCLUSIONS</b>(1) GCF is a distinctive fibroblastic tumor of intermediate malignancy that occurs predominantly in children. Recognizing its clinical and pathological characteristics is important to avoid misdiagnosis with other lesions with similar features. (2) GCF shared clinical, immunohistochemical and cytogenetic features with its adult counterpart-dermatofibrosarcoma protuberans (DFSP). The additional coexistence of GCF and DFSP areas in some primary cases and the reciprocal transformation in recurrent tumors all suggest that they are two closely related entities, possibly representing two members of the CD34 positive dendritic neoplasms.</p>

Relationship between chromosomal translocation and synovial sarcoma / 中国癌症杂志

Synovial sarcoma is a high grade malignant soft tissue tumor. Its diagnosis and differential diagnosis are difficult. In most cases the reciprocal chromosomal translocation between chromosome X and chromosome 18 could be found and characterized synovial sarcoma. This article reviewed the relationship between chromosomal translocation and the diagnosis, histological type and prognosis of synovial sarcoma.

Benign glandular schwannoma / 中国癌症杂志

Purpose:To report a seldom case of benign glandular schwannoma and review its pathological characteristic. Methods:The tumor was observed by histology, histochemistry and immunohistochemistry. Results:Histologically, the tumor is composed of spindle cell component showing typical schwannoma and collections of glandular component with the expressions of Leu 7,GFAP,MBP,CEA,AE1/AE3 and 34?E12. Conclusions:The histogenesis of the glandular schwannoma remains uncertain. In our opinion, the glands within the tumor, when examined immunohistochemically, probably represent entrapped dermal appendageal glands with proliferation. [

Loss of heterozygosity on chromosome loci 2, 3, 5, 11, 17, and 18 in aberrant crypt foci of human colon / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the genetic basis of aberrant crypt foci (ACF), which serve as a very early morphological alteration during the development of carcinogenesis by analyzing the loss of heterozygosity (LOH).</p><p><b>METHODS</b>DNA from 35 colorectal carcinomas (CRC) and 34 matched ACF were isolated by microdissection. LOH of microsatellite loci at 18q12, 18q21, 5q12, 5q21, 3p21, 2p16, 17q21, 17q11 and 11p13 was detected by means of ABI-SEQUENCER and GeneScan software was applied for analysis.</p><p><b>RESULTS</b>The rate of LOH in ACF (41.18%) was less than that in carcinoma (68.57%) (P < 0.05). The profile of LOH rates at loci 18q12, 5q12, 3p21, 17q21, 17q11, 11p13 and 2p16 in ACF was similar to that in carcinoma. The LOH frequencies on 18q12, 18q21, 5q12, 5q21, and 3p21 were higher than that on 17q11 and 11p13. However the rate at 18q21 and 5q21 in ACF was much lower than that in the carcinoma (P < 0.05). The co-existing carcinomas displayed more polypoid growth pattern and located more at the sigmoid colon and rectum. LOH in carcinomas did not correlate with the location, size, type of the carcinoma and Duke's stage.</p><p><b>CONCLUSIONS</b>ACF are putative preneoplastic lesions that might represent the earliest morphological lesion with the alteration at molecular genetic level. Our study provides further genetic evidence in the pathogenesis of colorectal carcinomas.</p>

Sequence analysis of translocation t (X; 18) genomic breakpoints characterized in synovial sarcoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To analyze the DNA sequence characteristics of translocation t (X; 18) genomic breakpoints and to study the mechanism underlying chromosomal translocation t (X; 18) in synovial sarcoma.</p><p><b>METHODS</b>Two cases of synovial sarcoma were studied utilizing long-distance polymerase chain reaction (PCR) and sequence analysis to amplify the genomic DNA of translocation t (X; 18) breakpoints.</p><p><b>RESULTS</b>Translocation t (X; 18) was detected in both cases, which generated SYT-SSX1 and SYT-SSX2 fusion gene respectively. Sequence analysis revealed that intron 10 of SYT was fused to the intron 4 of SSX1 or SSX2. Sequences highly homologous to consensus recognition motifs of translin were found adjacent to breakpoints in all three genes. Breakpoints in the three genes were close to or even at several palindromic oligomer sequences. The breaks in intron 4 of SSX1 and SSX2 were near an Alu sequence. No Alu or other repetitive sequences were found 500 bp upstream or downstream from the break in intron 10 of SYT. One topoisomerase II consensus site was found between the two breakpoints but with considerable distance from intron 10 of SYT.</p><p><b>CONCLUSIONS</b>All three genes involved in synovial sarcomas contain characteristic sequence motifs in the breakpoint regions which may play an important role in the genesis of chromosomal translocation in synovial sarcoma.</p>

A clinicopathologic and immunohistochemical study of diffuse large B-cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic and immunohistochemical features of diffuse large B-cell lymphoma (DLBCL) and the significance of immunohistochemistry in diagnosis and differential diagnosis of DLBCL.</p><p><b>METHODS</b>60 cases of DLBCL were studied and immunohistochemical staining for LCA, L26, BLA-36, CD30, bcl-6 were carried out with the EnVision 2 step method.</p><p><b>RESULTS</b>The age range of 76.7% (46/60) patients was 40 - 70 years. The location of the lesion includes nodal and extranodal sites. 90.0% (54/60) were in clinical stages of II (24/54), III (21/54), IV (9/54). Histopathologic morphology presented as centroblastic (88.3%, 53/60), immunoblastic (3.3%, 2/60), anaplastic large B cell type (3.3%, 2/60) and T cell rich B cell type (5.0%, 3/60). Immunostaining showed 100% (60/60) DLBCL were positive for LCA, L26, BLA36, 3.3% (2/60) DLBCL positive for CD30, 95% (57/60) expressed bcl-6 protein.</p><p><b>CONCLUSIONS</b>DLBCL is an aggressive lymphoma which shows cytologic variability from case to case. The evaluation of pathologic features and immunohistochemistry in DLBCL are useful and practical for diagnostic purposes, but cannot delineate distinctive morphologic subtypes.</p>