Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases / 中华病理学杂志

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

Value of albumin RNAscope in situ hybridization in diagnosis and differential diagnosis of hepatocellular carcinoma / 中华病理学杂志

Objective: To investigate the utility of albumin RNAscope in situ hybridization in the diagnosis and differential diagnosis of hepatocellular carcinoma and its mimics. Methods: One hundred and fifty-two cases of hepatocellular carcinoma and its mimics and 33 cases of normal tissue were selected from the pathology database of the Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2019. Tissue microarrays were constructed and RNAscope in situ hybridization was performed to detect the expression of albumin mRNA. Results: No albumin mRNA expression was detected in normal tissues except for the liver. All hepatocellular carcinoma regardless of its degree of differentiation and primary or metastatic nature had detectable albumin mRNA, with strong and diffuse staining in 90.7% (49/54) of cases. While the positive rate of HepPar-1, Arg-1 or one of them by immunohistochemistry was 87.0% (47/54), 85.2% (46/54) and 92.6% (50/54) respectively. The positive rates of albumin mRNA in intrahepatic cholangiocarcinoma and biphenotypic hepatocellular carcinoma were 7/15 and 9/10, respectively. The former showed focal or heterogeneous staining, while the latter showed strong and diffuse staining. The positive rate of hepatoid adenocarcinoma was 8/19, and the albumin expression could be diffuse or focal. Sporadic cases of poorly differentiated gastric adenocarcinoma and metastatic colon adenocarcinoma showed focal staining of albumin mRNA. Conclusions: Detection of albumin mRNA by RNAscope in situ hybridization is of great value for the diagnosis and differential diagnosis of HCC, and the sensitivity may be improved by combining with HepPar-1 and Arg-1. It also offers different diagnostic clues according to different expression patterns.

Clinicopathological characteristics analysis on 10 cases of blastic plasmacytoid dendritic cell neoplasm / 临床与实验病理学杂志

Purpose To study the clinicopathological characteristics of blastic Plasmacytoid dendritic cell neoplasms, and improve the acknowledgement and diagnostic level. Methods The clinicopathological features, immunohistochemistry and EBV test results of 10 cases with BPDCN were analyzed retrospectively, with review of literature. Results Skin lesions were the first symptom in 10 patients, tumor cells expression of CD43, CD56, CD4 was positive in 8 cases, CD123 were positive in 5 cases, the T and B cell specific markers is not expression. EB virus encoded small RNA(EBER ) in situ hybridization is negative;no clonal rearrangement of B cell receptor(BCR) or T cell receptor(TCR) gene. Conclusion BPDCN is a rare malignant tumor of the skin, easy to involve the skin. It is necessary to combine clinical with pathological for definite diagnosis.

A nomogram to predict Gleason sum upgrading of clinically diagnosed localized prostate cancer among Chinese patients / 癌症

Although several models have been developed to predict the probability of Gleason sum upgrading between biopsy and radical prostatectomy specimens, most of these models are restricted to prostate-specific antigen screening-detected prostate cancer. This study aimed to build a nomogram for the prediction of Gleason sum upgrading in clinically diagnosed prostate cancer. The study cohort comprised 269 Chinese prostate cancer patients who underwent prostate biopsy with a minimum of 10 cores and were subsequently treated with radical prostatectomy. Of all included patients, 220 (81.8%) were referred with clinical symptoms. The prostate-specific antigen level, primary and secondary biopsy Gleason scores, and clinical T category were used in a multivariate logistic regression model to predict the probability of Gleason sum upgrading. The developed nomogram was validated internally. Gleason sum upgrading was observed in 90 (33.5%) patients. Our nomogram showed a bootstrap-corrected concordance index of 0.789 and good calibration using 4 readily available variables. The nomogram also demonstrated satisfactory statistical performance for predicting significant upgrading. External validation of the nomogram published by Chun et al. in our cohort showed a marked discordance between the observed and predicted probabilities of Gleason sum upgrading. In summary, a new nomogram to predict Gleason sum upgrading in clinically diagnosed prostate cancer was developed, and it demonstrated good statistical performance upon internal validation.

Blastic plasmacytoid dendritic cell neoplasm: a clinicopathologic study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and differential diagnosis of blastic plasmacytoid dendritic cell neoplasm.</p><p><b>METHODS</b>The clinical, morphology and immunophenotypic features were analyzed in 3 cases of blastic plasmacytoid dendritic cell neoplasm, with review of literature.</p><p><b>RESULTS</b>The pathologic changes of these tumors accorded with that of blastic plasmacytoid dendritic cell neoplasm, and they also had new characteristics, including lineage other than T, B, myeloid and NK cells, and immunophenotypes of CD56(+) CD4(-) CD123(+) TdT(+) CD43(+) CD68(+) , CD56(+) CD4(+) CD123(-) TdT(+) CD43(+) CD68(-) and CD56(+) CD4(+) CD123(-/+) TdT(-) CD43(+) CD68(+) in the 3 cases, respectively. Bone marrow involvement was found 5 years later in case 1, and was then stable after chemotherapy; case 2 and case 3 were died 5 and 2 months after diagnosis, respectively.</p><p><b>CONCLUSION</b>Blastic plasmacytoid dendritic cell neoplasm is a heterogeneous group of lymphoproliferative disorders, with different clinical, morphologic and immunophenotypic features.</p>

A combined clinicopathologic analysis of 658 urothelial carcinoma cases of urinary bladder / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To study the clinicopathological features of patients with urothelial carcinoma of the urinary bladder (UCB), and analyze the association of clinicopathological characteristics with tumor recurrence and progression.</p><p><b>METHODS</b>Altogether 658 UCB cases in Fudan University Shanghai Cancer Center were collected from January 2006 to December 2010. The histopathologic materials and the clinical records were reviewed. Univariate and multivariate analyses were preformed to detect the association.</p><p><b>RESULTS</b>The mean age of the patients was 61.97 +/- 12.97 years (range, 20-90 years). Male to female ratio was about 5:1. A total of 517 cases (78.6%) were superficial at the time of diagnosis (stage Ta/T1). The mean follow-up period was 22.36 +/- 24.92 months. Twenty-five patients lacking follow-up information were excluded in calculating recurrence and progression rates, the recurrence rate was about 37.0% (234/633), and progression rate about 6.2% (39/633). Three variables (grade, tumor growth pattern, and pathological stage) were found to be significant risk factors for tumor progression in univariate and multivariate analyses (P < 0.05).</p><p><b>CONCLUSIONS</b>Most of the newly diagnosed UCB cases may be superficial diseases. Grade, tumor growth pattern, and pathological stage are associated with tumor progression of UCB.</p>

Urothelial hyperplastic lesion with endophytic growth pattern: a clinicopathologic study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of urothelial hyperplastic lesion with an endophytic growth pattern and the role of immunohistochemistry and multitargeted fluorescence in situ hybridization (FISH) in the differential diagnosis.</p><p><b>METHODS</b>Forty-one cases of urothelial lesions exhibiting endophytic growth patterns were reviewed and reclassified as inverted papilloma, urothelial carcinoma with an endophytic growth pattern, and florid von Brunn nest. The gains of chromosomes 3, 7, and 17 and loss of 9p21 was detected by FISH, and performed immunohistochemical staining for CK20, p53, and Ki-67. Follow-up data of 12 cases were obtained.</p><p><b>RESULTS</b>(1) Twelve inverted papillomas sized 1.2 cm in average, consisted of anastomosing cords and nests with uniform width distribution involving the lamina propria, the central portion contained streaming cells with squamous metaplasia, and the periphery showed palisading. No or rare atypia and mitosis were found. Focal exophytic papillary component lined by less than 6 layers of normal urothelium were observed in 4 cases. (2) Twenty-four urothelial carcinomas with an endophytic growth pattern sized 2.1 cm in average, demonstrated the similar architecture with inverted papilloma, but exhibited thick columns and variable thickness of the cords, irregular size and shape of large nests with transition into solids. Mild to moderate cytologic atypia was shown, and mitotic figures ranged 1 to 8 per 10 HPFs. Exophytic papillary component was not observed in 3 cases, but the superficial urothelium showed dysplasia, while coexisted exophytic component in other cases was associated with low malignant potential or low grade tumor. (3) Five florid von Brunn nests sized 0.9 cm in average, had normal or hyperplastic urothelium, variable nests with cysts compacted in lamina propria, no cytologic atypia and mitosis. Twenty-one of 24 (79.1%) urothelial carcinomas with an endophytic growth pattern displayed abnormally positive results by multitargeted FISH, whereas all inverted papillomas and florid von Brunn nests were negative. Immunohistochemically, CK20 was weakly positive in 2 cases of urothelial carcinoma with an endophytic growth pattern, and negative in all inverted papillomas and florid von Brunn nests. p53 weakly stained 5% to 50% nuclei of the tumor cells in 16 cases of urothelial carcinomas with an endophytic growth pattern and 1 inverted papilloma. 1%-5% tumor cells expressed Ki-67 in urothelial carcinoma with an endophytic growth pattern, and less than 1% in inverted papilloma and florid von Brunn nests. Follow-up study revealed that 2 cases of urothelial carcinoma with an endophytic growth pattern had developed invasive carcinoma, underwent cystectomy, and metastasized remotely. No recurrence occurred in cases of inverted papilloma.</p><p><b>CONCLUSIONS</b>Benign and malignant urothelial lesions with an endophytic growth pattern present histologic overlapping. Urothelial carcinoma with an endophytic growth pattern displays unique characteristics in morphology and immunohistochemistry. Multitargeted FISH analysis is helpful in the differential diagnosis.</p>

Angiomatoid fibrous histiocytoma: report of 5 cases with review of literature / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype and differential diagnosis of angiomatoid fibrous histiocytoma (AFH).</p><p><b>METHODS</b>The clinicopathologic features of 5 cases of AFH were analyzed. Immunohistochemical study was carried out and the literature was reviewed.</p><p><b>RESULTS</b>There were a total of 3 males and 2 females. The average age of patients was 21.4 years old. The average duration of symptoms was 13 months. The patients primarily presented with a slowly enlarging painless deep dermal or subcutaneous mass. The mass was located in the head and neck region in 3 cases, elbow in 1 case and foot in 1 case. The patients underwent complete resection of the tumor, with no adjuvant chemotherapy and/or radiotherapy given. During a period of follow up for 10 to 29 months, all of them had no recurrence or distant metastasis. Gross examination showed that the tumor was well-circumscribed and had a grey-colored cut surface, with focal hemorrhagic cystic changes. The average tumor dimension was 1.9 cm. Histologically, the tumor was composed of histiocytoid or spindly cells arranged in nodular pattern. Fibrillary neuropil-type intercellular material was identified in all cases and a fibrous pseudocapsule surrounded by lymphocytes and plasma cells was demonstrated in 3 cases. Immunohistochemical study showed that all of them were positive for vimentin and negative for S-100 protein, pan-cytokeratin, CD34 and CD31. Three of the cases expressed desmin and CD68. Two cases were epithelial membrane antigen and CD99-positive.</p><p><b>CONCLUSIONS</b>AFH is a rare tumor of intermediate malignant potential. Definitive diagnosis requires thorough histologic examination and clinical correlation. Immunohistochemistry is also helpful for diagnosis and differential diagnosis. Wide local excision with post-operative follow up is the main modality of treatment.</p>

Clinicopathologic analysis of 52 cases of thymic epithelial tumor / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic characteristics of thymic epithelial tumors and to evaluate the diagnostic reproducibility and clinical relevance of the 2004 WHO histologic classification system.</p><p><b>METHODS</b>The morphology and immunophenotype of 52 cases of thymic epithelial tumor were reviewed. The tumors were classified according to the new WHO classification system and the clinical data were analyzed.</p><p><b>RESULTS</b>Of the 52 cases studied, 45 were thymomas and 7 were thymic carcinomas. Amongst the 45 cases of thymoma, 6 (13.4%) were type A, 15 (33.3%) were type AB, 4 (8.9%) were type B1, 9 (20.0%) were type B2, 9 (20.0%) were type B3 and 2 (4.4%) were metaplastic thymoma. Amongst the 7 cases of thymic carcinoma, 6 were squamous cell carcinomas and 1 was neuroendocrine carcinoma. The commonest presentations were cough and chest pain. Some cases were incidentally discovered by routine physical examination. Thirteen cases (25.0%) of thymoma were associated with myasthenia gravis. CT scan showed that 49 cases (94.2%) were located in the anterior mediastinum. All cases of type A, AB and B1 thymoma and most cases of B2 thymoma appeared as well-defined homogeneous mass, whereas a few cases of type B2 thymoma and most cases of type B3 thymoma and thymic carcinoma were poorly demarcated and heterogeneous. According to Masaoka staging system, 20 cases (41.7%) belonged to stage I, 15 cases (31.3%) stage II, 11 cases (22.9%) stage III and 2 cases (4.1%) stage IV. The histologic subtypes of thymic epithelial tumors significantly correlated with the clinical stages (chi(2) = 32.5, P < 0.01).</p><p><b>CONCLUSIONS</b>The 2004 revision of WHO histologic classification system for thymic epithelial tumors shows a high degree of reproducibility. Correlation with the radiologic, clinical and prognostic parameters is helpful in determining the management strategy for individual patients.</p>

Low-grade central osteosarcoma: a clinicopathologic analysis of nine cases / 中华病理学杂志

<p><b>OBJECTIVE</b>to study the clinicopathologic features and differential diagnosis of low-grade central osteosarcoma (LGCOS).</p><p><b>METHODS</b>nine cases of LGCOS were retrieved from the archival consultation files. The clinical, radiologic and pathologic features were analyzed, with literature review.</p><p><b>RESULTS</b>the mean age of the patients was 31 years. The male-to-female ratio was 3:6. All of the patients presented with painful mass and/or swelling. The sites of involvement included thigh (n = 4), tibia (n = 1), fibula (n = 1), cervical vertebra (n = 1), lumbar vertebra (n = 1) and maxilla (n = 1). Radiologic examination showed mixed lytic/blastic lesions with soft tissue shadow in 5 cases and associated periosteal reaction in 3 cases. The tumors were treated by surgical excision, with no adjuvant therapy given. The duration of follow up ranged from 2 to 43 months. Four cases had recurrence which occurred at 8 to 25 months after the operation. Gross examination showed that the tumors were fragmented on submission in 5 cases and en bloc in 4 cases. They had solid and firm cut surface, with various degree of grittiness. Histologically, LGCOS was characterized by the presence of hypocellular fibroblastic stroma associated with focal osteoid production. The spindly tumor cells showed mild degree of nuclear pleomorphism, with occasional mitotic figures demonstrated in all of the 9 cases. The newly formed neoplastic woven bone did not have any osteoblastic rimming. The bony trabeculae were slender and seam-like. Parallel arrays of woven bone were seen in 6 cases. Some of the bony trabeculae appeared irregularly branched and curved. The tumor cells permeated adjoining pre-existing bony trabeculae and bone marrow in all cases. Three cases also showed soft tissue involvement.</p><p><b>CONCLUSIONS</b>LGCOS often posses important diagnostic pitfalls due to the relatively bland-looking tumor cell morphology and associated large woven or longitudinal seams of lamellar-like bone. Thorough understanding of the histologic features, when coupled with clinical and radiologic findings, are essential in arriving at a correct diagnosis.</p>

External validation of the Partin tables 2007 in Chinese prostate cancer patients / 中华外科杂志

<p><b>OBJECTIVE</b>To validate the 2007 Partin tables externally, which are based on the population of United States, using a cohort of Chinese prostate cancer patients.</p><p><b>METHODS</b>All of the patients enrolled and underwent radical prostatectomy between January 2006 and February 2010 were reviewed. The cases without preoperative hormone therapy and pelvic lymph node involvement according to radiologic tests were used for the external validation of the 2007 Partin tables. A comparative analysis of the clinical and pathological parameters of this Chinese cohort and Partin tables cohort was performed. Values of areas under the receiver operating characteristic (ROC) curve were used to assess predictive accuracy for the Chinese cohort.</p><p><b>RESULTS</b>The mean age of the whole cohort was 67 years. The serum prostate specific antigen level, Gleason score and clinical stage of this cohort were higher than the Partin tables cohort. The pathological outcomes analysis revealed that the rates of organ confined disease, capsular penetration, seminal vesicle involvement and lymph node involvement were 62.3%, 16.7%, 12.3% and 8.8%, respectively. The area under the ROC curve (AUC) for organ confined disease, capsular penetration, seminal vesicle involvement and lymph node involvement were 0.735, 0.653, 0.601 and 0.845.</p><p><b>CONCLUSIONS</b>The Partin tables discriminate well for Chinese patients at risk for positive lymph node. The discrimination of organ confined disease is also acceptable and the discrimination of capsular penetration and seminal vesicle involvement is more limited.</p>

The analysis for mRNA mutation of MLH1, MSH2 genes and the gene diagnosis for hereditary nonpolyposis colorectal cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify hereditary nonpolyposis colorectal cancer (HNPCC) families based on the germline mutations of MLH1 and MSH2 mRNA.</p><p><b>METHODS</b>RNA was extracted from the peripheral blood of the 14 members from 12 different families fulfilling Amsterdam Criteria II. The germline mutations of MLH1 and MSH2 mRNA were detected by cDNA sequencing analysis following reverse transcription-PCR(RT-PCR) with special primers, heat-resistance reverse transcriptase, and expand long template PCR. DNA was extracted from the peripheral blood of the 14 members, the corresponding exons, in which mutations were found using the above method, were amplified with Taq enzyme, sequencing analysis was followed.</p><p><b>RESULTS</b>Six germline mutations were detected and identified from the 6 different families based on mRNA, 4 of them to be in MLH1, the other 2 in MSH2. The MLH1 mutations distribute in the exon 8, 12, 16, and 19. The MSH2 mutations distribute in exons 1 and 2. The 6 mutations were identified from the corresponding exons respectively in genomic DNA sequencing analysis. The mutation types involve in 4 missense, 1 silent, and 1 non-coding area mutations. Five out of the 6 mutations have not been reported previously. Five out of the 6 mutations were pathological, involving in 5 different families. The five families were identified to HNPCC families.</p><p><b>CONCLUSION</b>HNPCC family can be identified with RNA-based sequencing of MLH1 and MSH2 from peripheral blood, which has the advantages of both cost, time saving and high sensitivity.</p>

Two novel germline mutations of MLH1 in hereditary nonpolyposis colorectal cancer family / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore germline mutations of MLH1 in hereditary nonpolyposis colorectal cancer (HNPCC), and to investigate the pathobiology of novel detectable mutations of MLH1.</p><p><b>METHOD</b>RNA was extracted from the peripheral blood of 12 patients from 12 different families fulfilling the Amsterdam II Criteria of HNPCC. Germline mutations of MLH1 were determined by RT-PCR with gene specific primers, heat-resistance reverse transcriptase and long-template PCR polymerase, followed by cDNA sequencing analysis. PCR-Genescan analysis was used to further investigate microsatellite instability with a panel of 5 microsatellite markers (BAT26, BAT25, D5S346, D2S123 and Mfd15), along with immunohistochemistry staining to detect the expression of MLH1 protein in the tumor tissues.</p><p><b>RESULTS</b>Four germline mutations were found in 4 patients, 2 of which were previously reported GTT-->GAT mutation at codon 384 of exon 12, and the other two were novel mutations: CGC-->TGC at codon 217 of exon 8 and CCG-->CTG at codon 581 of exon 16. Two tumors with the novel mutations had high frequency microsatellite instability showing more than 2 instable loci (RER + phenotype), and both tumors lost their MLH1 protein expression.</p><p><b>CONCLUSION</b>The two novel germline mutations of MLH1 identified in this study, i.e. CGC-->TGC at codon 217 of exon 8 and CCG-->CTG at codon 581 of exon 16, are very likely to have pathological significance.</p>