Clinicopathological characteristics of Klinefelter syndrome: a testicular biopsy analysis of 87 cases / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of testicular biopsies from Klinefelter syndrome (KS) patients. Methods: The testicular biopsy specimens of 87 patients with KS (a total of 107 biopsy specimens) were collected from the Department of Pathology, Peking University Third Hospital, Beijing, China from January 2017 to July 2022. All patients were diagnosed as KS by peripheral blood karyotyping analysis. The testicular histopathologic features, testicular volume and hormone levels were evaluated retrospectively. The histopathologic analysis was used to assess the quantity and morphology of Leydig cells, the spermatogenic state of seminiferous tubules, the thickening of the basement membrane of seminiferous tubules and the changes of stroma. Results: Leydig cell proliferative nodules were seen in 95.3% (102/107) of KS testicular biopsy tissues. The eosinophilic inclusion bodies and lipofuscin in Leydig cells were found in 52.3% (56/107) and 57.9% (62/107) of specimens, respectively. The Sertoli cell only seminiferous tubules and the hyalinized tubules were found in 66.4% (71/107) and 76.6% (82/107) of the examined tissues, respectively. The tubules with complete spermatogenic arrest were found in 15.9% (17/107) of specimens, and 5.6% (6/107) of the specimens showed low spermatogenesis or incomplete spermatogenic arrest. In 85.0% (91/107) of the specimens, increased thick-walled small vessels with hyaline degeneration were identified. Conclusions: The most common features of KS testicular specimens are Leydig cell proliferative nodules, hyaline degeneration of seminiferous tubules and proliferation of thick-walled blood vessels. Testicular biopsy specimens of KS are rare. The pathologists can make a tentative diagnosis of KS based on the histological findings, combined with the ultrasound and laboratory results, which is helpful for further diagnosis and treatment of KS.

Clinical and pathological features of renal cell carcinoma with urinary tract tumor thrombus: 6 cases report and literature review / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical characteristics, diagnosis and treatment of renal cell carcinoma with urinary tract tumor thrombus.@*METHODS@#From January 1, 2015 to December 31, 2019, patients with renal cell carcinoma complicated with urinary tract tumor thrombus who were hospitalized in the Peking University Third Hospital and Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. Meanwhile, we reviewed the literature, and the reported patients of renal cell carcinoma with urinary tract tumor thrombus were also included in our study. The basic information, clinical manifestations, treatment, pathological characteristics and follow-ups of all the patients were analyzed.@*RESULTS@#In our study, 6 patients from the two hospitals and 16 patients from previous literature reports were included. There were 13 males and 9 females with an average age of 54.7 years (22-79 years). Fifteen patients had renal cell carcinoma on the left side, 6 on the right side, and 1 on the unknown side. Gross hematuria was the most common chief complaint, including 18 patients. One patient complained of weight loss, 1 patient complained of microscopic hematuria, and 1 patient was found by ultrasound examination. Tumor thrombus was classified as grade Ⅰ in 9 cases (the tumor embolus protruded into the renal pelvis, but did not reach the ureteropelvic junction), grade Ⅱ in 10 cases (the tumor embolus protruded into the ureter, but not into the bladder), and grade Ⅲ in 3 cases (the tumor embolus passed through the ureter and protruded into the bladder). Only 11 patients were diagnosed with renal cell carcinoma before operation. Radical nephrectomy was performed in 9 cases and nephroureterectomy in 12 cases. In pathological diagnosis, there were 15 cases of clear cell renal cell carcinoma, 1 case of papillary renal cell carcinoma, 1 case of chromophobe cell carcinoma, 1 case of mixed cell renal cell carcinoma, 4 cases of renal cell carcinoma with undetermined classification. Eleven patients were followed up for 3-31 months, and 3 patients had lung metastasis within 6 months.@*CONCLUSION@#Renal cell carcinoma with urinary tract tumor thrombus is rare in clinic. It needs to be differentiated from renal pelvis carcinoma in diagnosis. The treatment principle can refer to general renal carcinoma. For locally advanced cases, complete resection is the best treatment, and its oncological prognosis needs more long-term and large-scale follow-up observation.

Correlation between the phenotype and genotype of tooth agenesis patients by tooth agenesis code / 中国医学科学院学报

<p><b>OBJECTIVE</b>To analyze the correlation between the phenotype and genotype of tooth agenesis using the tooth agenesis code (TAC) and the traditional descriptor for missing teeth.</p><p><b>METHODS</b>Patients with isolated hypodontia caused by PAX9 or MSX1 mutation reported before May 2007 were enrolled. The teeth missing rate and TAC code were recorded. The missing teeth patterns caused by the two mutations were compared.</p><p><b>RESULTS</b>The teeth missing rates in each teeth positions were significantly different between maxillary and mandibular except maxillary central incisor, lateral incisor and mandibular canine, first molar (P<0.05, P<0.001). MSX1 gene mutation often led to the loss of maxillary first premolar, maxillary second premolar, and mandibular second premolar, while PAX9 gene mutation often led to the loss of the first, second, and third molars. The results were similar when analyzed either by TAC code analysis or by traditional descriptor.</p><p><b>CONCLUSIONS</b>PAX9 and MSX1 gene mutation can cause different phenotypes of tooth agenesis. The TAC code can be used in the analysis of the correlation between phenotype and genotype of the missing teeth patients.</p>

Ultrastructural features and platelet-derived growth factor receptor A gene mutations in CD117-negative gastrointestinal stromal tumor / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the ultrastructural features and mutation status of platelet-derived growth factor receptors A (PDGFRA) and c-kit in gastrointestinal stromal tumors that were immunohistochemically negative for CD117 antigen.</p><p><b>METHODS</b>Six cases of gastrointestinal stromal tumors that were CD117 immunostain negative were studied by electron microscopy. Direct PCR sequencing was used to investigate the mutation status of c-kit gene exons 9, 11, 13, 17 and PDGFRA gene exons 12 and 18.</p><p><b>RESULTS</b>The ultrastructural features of all 6 cases were similar to those of the interstitial cell of Cajal (ICC). None of the 6 cases were found to have c-kit gene mutations. However, three tumors were found to harbor PDGFRA exon 18 activating mutations, including two tumors having an Asp-->Val842 missense mutation and one having an Arg-->Ser841 missense mutation.</p><p><b>CONCLUSIONS</b>PDGFRA mutations may provide an important alternative molecular mechanism for the development of gastrointestinal stromal tumor.</p>

Status and clinical implication of c-kit and PDGFRA mutations in 165 cases of gastrointestinal stromal tumor (GIST) / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the status of c-kit and PDGFRA mutations of GIST in a the large sample of Chinese patients.</p><p><b>METHOD</b>One hundred and sixty-five cases were evaluated for the presence of c-kit and PDGFRA mutations. Exon 9, 11, 13, 17 of c-kit and exon 12, 18 of PDGFRA were analyzed by PCR amplification and direct sequencing.</p><p><b>RESULTS</b>Immunohistochemical demonstrations of KIT (CD117) were seen in 94% of the cases (155/165). Overall, c-kit mutations were identified in 76.1% (118/155) of CD117 positive cases: 67.1% (104/155) involving exon 11, 7.1% (11/155) involving exon 9, 1.3% (2/155) involving exon 13 and 0.6% (1/155) involving exon 17. The c-kit exon 11 mutations were mostly heterogeneous and clustered in the classic "hot spot" at the 5' end of the exon, including in-frame deletion and point mutation. The second "hot spots" were internal tandem duplications (ITD) at the 3' end of the exon, which were associated with female patient, older age, stomach location and low mitotic counts. The exon 9 mutations correlated with a distinct subset of GISTs involving the small bowel of young male patients. A new point mutation of L641P was identified in exon 13. PDGFRA mutations were present in 50% (5/10) of CD117-negative GISTs, all involving exon 18 with the majority of mutations being D842V. One novel in-frame deletion of IMHD mutation at codon 843 - 846 with S847T was identified. GISTs with PDGFRA mutations were often larger tumors arising from the omentum/mesentery of young male patients with high risk of aggressive behavior.</p><p><b>CONCLUSIONS</b>The vast majority of GISTs in this study harbored c-kit and PDGFRA mutations, there were non-random relations between the gene mutation patterns and the locations of GISTs. It appears that Chinese GIST patients have some unique mutation patterns. It is necessary to evaluate the gene mutations status of GISTs to guide target therapy.</p>

SHP2 and MKP5 in P2Y purinergic receptor-mediated prostate cancer invasion / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of protein tyrosine phosphatase-SHP2 and dual-specificity MAPK phosphatase-MKP5 on the activation of MAPKs and cell invasion induced by P2Y purinergic receptor in human prostate cancer cell lines with different metastatic potentials.</p><p><b>METHODS</b>The wide type (-wt) SHP2, mutant type (-cs) SHP2 and wide type (-wt) MKP5 cDNA expression vectors were constructed and stably transfected into 1E8 cells (highly metastatic) and/or 2B4 cells (non-metastatic). The tyrosine phosphorylation of SHP2 was examined by immunoprecipitation. The activation of ERK1/2 and p38 induced by P2Y receptor agonist ATP was analyzed by Western blot with phospho-specific antibodies against the dually phosphorylated, active forms of ERK1/2 and p38. The in-vitro invasive ability through Matrigel was measured by boyden-chamber assay.</p><p><b>RESULTS</b>ATP induced significant SHP2 phosphorylation, which was stronger and lasted longer in 1E8 than in 2B4. SHP2-wt enhanced the ERK1/2 activation induced by ATP in 2B4 cells, while SHP2-cs delayed and decreased this effect in 1E8 cells. Both SHP2-wt and SHP2-cs had no obvious influence on p38 activation. ATP stimulated cell invasion of both 1E8 and 2B4, while transfection of SHP2-wt into 2B4 cells further increased the invasive-stimulating ability of ATP (18.7% increase compared with ATP treatment alone). Transfection of SHP2-cs into 1E8 cells, however, antagonized the invasive-stimulating ability of ATP (40.9% decrease compared with ATP treated group). Up-regulation of MKP5-wt inhibited phosphorylation of p38 by ATP and reduced cell invasion stimulated by ATP (22.4% and 28.7% decrease compared with ATP treated group of 1E8 and 2B4, respectively).</p><p><b>CONCLUSIONS</b>Both SHP2 and MKP5 play some roles in P2Y receptor-mediated activation of MEK/ERK, p38 signaling pathways and prostate cancer invasion. SHP2 positively regulates ERK activation and prostate cancer invasion, whereas MKP5 inhibits the invasion by suppressing p38 activation.</p>