Diagnosis, treatment and prognosis of FH-deficient renal cell carcinoma with tumor thrombus / 中华泌尿外科杂志

Objective:To Explore the diagnosis, treatment and prognosis of FH-deficient renal cell carcinoma (FH-deficient RCC) with tumor thrombus, and share surgical experience.Methods:From August 2019 to October 2022, 6 cases of FH-deficient RCC with tumor thrombus were diagnosed and treated in our center, including 4 males and 2 females. The patients were aged 22 to 57 years, with 2 cases younger than 40 years, icluding 5 cases on the left and 1 case on the right. The median maximum diameter of the tumor is 8 (4.8, 14.0) cm. Operations were performed after complete examination (enhanced CT and other related examinations). One case underwent open surgery and palliative resection of the left kidney was performed because of severe adhesion of the inferior vena cava. Among the remaining 5 cases, 1 case underwent retroperitoneal laparoscopic right radical nephrectomy with inferior vena cava thrombectomy, 1 case underwent transabdominal laparoscopic left radical nephrectomy with inferior vena cava thrombectomy, and 3 cases underwent robot assisted laparoscopic left radical nephrectomy with inferior vena cava thrombectomy.Results:The median surgical time was 293 (185, 366) min, with blockage of the vena cava for 13 min and 28 min in 2 of 6 cases, respectively. The pathological report of renal tumor and tumor thrombus was FH-deficient renal carcinoma. The pathological features were as follows: the gross section of the specimen was gray yellow solid, often accompanied by necrosis, and the cystic cavity could be seen locally. Microscopically, the tumor extensively involved the renal parenchyma, with papillary, cribriform and tubular cystic structures. Immunohistochemistry showed FH (-), 2SC (+ ). The median postoperative hospital stay was 8 (4, 15) days. The median follow-up time was 13 (4, 27) months. One patient undergoing palliative resection of the left kidney underwent targeted therapy and radiotherapy after surgery (died 15 months after surgery due to gastrointestinal perforation). During the follow-up process, 4 cases experienced metastasis and received systematic treatment, with 1 death 27 months after surgery. Uterine leiomyomas were found in the remaining 1 case during follow-up.Conclusions:FH-deficient RCC with tumor thrombus is very rare. This disease is highly invasive, difficult to be diagnosed preoperatively and poor clinically prognostic. Operation combined with systemic therapy is an effective way to treat FH-deficient RCC with tumor thrombus.

Fluid overload in critically ill children and advances in its treatment / 国际儿科学杂志

Fluid overload(FO)is significantly associated with survival in critically ill children.Excessive fluid accumulation in the body causes tissue oedema, which may lead to heart failure, acute kidney injury(AKI)and acute pulmonary oedema, affecting length of hospital stay, readmission rates and prognosis.According to the cause of the FO, the main treatments are fluid restriction, diuretics, and ultrafiltration.Diuretics are often used clinically to treat patients with FO.International guidelines recommend ultrafiltration to remove excess water when diuretic therapy is not effective or when diuretic resistance occurs, or when life-threatening complications arise.However, there is no conclusion on the setting for the net ultrafiltration intensity in ultrafiltration, particularly in critically ill children.With the development of ultrafiltration technology, the application of ultrafiltration in the treatment of FO patients will be further carried out.This article provides a review of the FO and its treatment in critically ill children.

Clinicopathologic features of glomus tumor of the kidney / 中华病理学杂志

Objective@#To investigate the clinicopathologic and differential diagnostic features of glomus tumor of the kidney.@*Methods@#Four cases of glomus tumor of the kidney were collected from the archives of Peking University Third Hospital, the Second Hospital of Tianjin Medical University, Ningbo Yinzhou Second Hospital and Zhejiang Provincial People′s Hospital between January 2012 to June 2017; the clinical and radiologic features, histomorphology, immunohistochemistry, ultrastucture and prognosis were analyzed and the relevant literature was reviewed.@*Results@#Patients consisted of 2 men and 2 women with ages ranging from 37 years to 66 years (mean 55 years). Three patients had history of hypertensive disease (grade Ⅱ, 3 to 10 years). The tumors measured in maximum diameter from 3.0 cm to 4.0 cm (mean 3.6 cm) and showed gray-white to yellow and tan on cut surface. Macroscopical examinations showed all tumors were circumscribed but non-encapsulated. Histologically, 1 tumor presented as glomus tumor with extensive myxoid change, 1 as cellular and solid pattern glomus tumor, 1 as glomangioma with focal myopericytoma-like pattern and 1 as symplastic glomus tumor with areas resembling myopericytoma. The tumor cells in two cases showed scant cytoplasm and uniform, bland-appearing nuclei without mitoses. In one case, the tumor cells were epithelioid with abundant eosinophilic cytoplasm and relatively well-defined cell borders. There was an increased mitosis of 4/50 HPF; however, no evidence of atypical mitosis or nuclear atypia was noted. In the symplastic glomus tumor the tumor cells showed frequently nuclear pleomorphism without mitoses. By immunohistochemistry, all tumors showed strong and diffuse reactivities to at least 3 of the 4 muscle-associated markers (SMA, h-Caldesmon, MSA and Calponin), 3 tumors strongly and diffusely expressed collagen Ⅳ, 2 expressed CD34 and 1 focally expressed desmin; whereas markers including epithelial, neuroendocrine, nephrogenic, melanoma-associated, STAT6, S-100 protein, CD117 and β-catenin all were negative in all the 4 tumors. Ultrastuctural analysis was done in 2 cases and showed prominent cytoplasmic actin bundles and pericellular basement membrane, and lacking of rhomboid renin crystals in both tumors. The hypertension persisted after surgical resection for all the 3 patients with this medical history. Follow-up information (range: 6-64 months, mean: 44 months)showed that no evidence of local recurrence or distant metastasis was identified in all 4 patients.@*Conclusions@#Glomus tumor rarely occurs in the kidney and usually has a good prognosis. Careful attention to its morphology with the judicious use of immunohistochemistry and ultrastuctural analysis can be helpful for its diagnosis and differential diagnosis.

Clinicopathologic and molecular characterizations of Sertoli cell tumor, not otherwise specified of the testis / 中华病理学杂志

Objective@#To investigate the histomorpholgic spectrum, immunophenotypic, and molecular genetic features of Sertoli cell tumor, not otherwise specified (SCT, NOS) of the testis.@*Methods@#Seven cases of SCT, NOS of the testis were analyzed(4 from Peking University Third Hospital and 3 from Zhejiang Provincial People′s Hospital) between 2008 and 2017. The histopathologic features were examined based on HE staining, and EnVision method was used for immunohistochemistry staining of calretinin, inhibin, β-catenin, cyclinD1, CD10, CKpan, neuroendocrine markers, WT1, Melan A, vimentin, SALL4, GATA3, PAX8, and S-100 protein. Mutational analysis of exon 3 of the CTNNB1 gene by polymerase chain reaction (PCR)-amplified sequences and direct sequencing was performed.@*Results@#Patients ages ranged from 22 to 65 years (mean 43 years). The clinical manifestation in all was a slowly enlarging, painless testicular mass.The maximum diameter of the tumor ranged from 1.5 cm to 3.0 cm (mean 2.1 cm). Sectioning usually disclosed a tan-gray to white mass with vague lobular cut-surface. Microscopically, the tumors were well circumscribed and non-encapsulated; the tumor cells were rearranged in multiple growth patterns from diffuse solid sheets to trabeculae and cords, ribbon and solid or hollow tubules setting in variable amount of acellular fibrous stroma. Two cases showed acellular collagenous stroma constituted >50% of the tumor confirming to the diagnosis of sclerosing SCT. One case demonstrated a prominent myxoid stromal change. The tumor cells typically had moderate amounts of pale to lightly eosinophilic cytoplasm, 2 tumors had variable cells with abundant lipid-rich cytoplasm, and 1 other tumor showed scattered aggregates of multinucleated tumor cells. The tumor cells were bland-appearing without any evidence of atypia, mitoses were noted in 2 tumors (both were 1/50 HPF), but necrosis was absent. Immunohistochemical staining results as follows: vimentin (diffuse, 7/7), CD10 (diffuse membrane, 7/7); diffuse β-catenin nuclear and cytoplasm staining in 5 of 7 cases, and all the 5 cases showed diffuse cyclin D1 nuclear staining, β-catenin membrane staining in 2 of 7 cases, CKpan (5/7, focal or diffuse), calretinin (focal, 5/6), inhibin (focal, 3/7), synaptophysin (focal, 2/6), CD56 (focal or diffuse, 4/5), WT1 (diffuse nuclear, 4/5), and S-100 protein (diffuse, 3/7), and chromogranin A, Melan A, PAX8, GATA3 and SALL4 all were negative. Molecular genetic studies of PCR and direct sequencing showed CTNNB1 mutations in 4 of 7 (4/7) cases, 4 of the four mutation-carrying cases showed diffuse β-catenin nuclear and cytoplasm immunoreactivity and diffuse cyclin D1 nuclear immunoreactivity in the tumor cells.@*Conclusions@#SCT, NOS of the testis typically shows significant heterogeneities in both morphology and immunohistochemistry, thus causing differential diagnostic confusions. Molecular analyses showed mutations of exon 3 of CTNNB1 in more than half of these tumors, and nuclear accumulation of β-catenin and over expression of cyclin D1 can be useful for the differential diagnosis of SCT, NOS.

Clinicopathologic characteristics and prognosis of early onset prostate cancer / 中华病理学杂志

Objective@#To observe the clinicopathologic features and prognosis of prostate cancer (PCa) in young men.@*Methods@#Twenty-eight early onset (≤55 years) patients with PCa pathologically confirmed in the Peking University Third Hospital and Peking University Shougang Hospital from January 1st 2000 to August 31st 2016 were collected. There were 18 radical prostatectomy (RP) cases and 10 transrectal prostatic biopsy cases. Contemporaneously, 445 elderly (>55 years) patients were collected, of which 385 had detailed pathological information, were chosen as control group. The mean age of young group was 51 years (29-55 years). Follow-up data for 22 cases were available (1-110 months). The correlation of the clinicopathological features and prognosis were analyzed retrospectively.@*Results@#Presurgical prostatic specific antigen (PSA) level was abnormal in young patients, with 18 cases (64.3%) had elevated fPSA level, 26 (92.9%) had increased tPSA level, and 26 (92.9%) had decreased fPSA/tPSA ratio. Gleason score (GS) was 8 in 10.7% (3/28) of cases, and 9 in 42.9% (12/28) of cases. Of the 18 patients with RP, 17 (94.4%) had pT stage ≥pT2c. PSA level (P=0.006) and GS (P=0.001) were positively correlated with pT stage. Family history of PCa in 1st degree relatives was found in 9.1% of the cases. During follow-up, 2 patients died of PCa, 7 patients showed progression within 24 months. There were no significant differences in PSA level and GS between young patients and elderly patients, while the former group was more likely to have incontinence (P=0.023), higher PSA levels (P=0.001), and lower overall survival (P=0.049). Only postsurgical PSA level was found to be negatively associated with overall survival (P=0.030) and cancer specific survival (P=0.021) in young patients.@*Conclusions@#Presurgical PSA level and GS are positively correlated with pT stage of early onset PCa. Compared with elderly patients, young patients are more likely to have incontinence, higher postsurgical PSA level, and lower overall survival. Among all the parameters, only postsurgical PSA level shows an adverse impact on prognosis of early onset PCa. Young patients, especially those with family history, may benefit from studies on the susceptibility loci and phenotype of PCa.

Research progress on the relationship between KPNA2 and tumors / 中国肿瘤临床

KPNA2 is a member of the karyopherin family. Given its function in nucleocytoplasmic transport, KPNA2 mediates the trans-location of various proteins and is involved in numerous cellular processes, such as cellular differentiation, proliferation and apoptosis, transcriptional regulation, immune response, and viral infection. Several studies have recently demonstrated that KPNA2 is upregulat-ed in multiple malignancies. Its aberrant expression is often associated with adverse outcomes in affected patients, indicating that KP-NA2 plays a significant role in carcinogenesis and tumor progression. These findings are supported by previous studies, which reported that KPNA2 may have a functional role in the malignant transformation of cells. This study provides an overview of the research prog-ress in KPNA2 and its functional roles in multiple cancers.

EDA mutation screening and phenotype analysis in patients with tooth agenesis / 北京大学学报(医学版)

Objective:To screen the ectodysplasin A (EDA)gene mutation in the patients with non-syndromic tooth agenesis and ectodermal dysplasia,and to analyze the phenotype of missing teeth pattern in these two groups of patients.Methods:In the study,174 patients with tooth agenesis (143:non-syn-dromic,31:ectodermal dysplasia)and 451 health control volunteers were enrolled from the clinic,and the genome DNA was extracted from either peripheral blood or oral mucosal swab.The coding region of EDA gene was then amplified by PCR,sequenced and blasted to online NCBI database.The missing teeth were recorded for all patients,and the missing teeth from patients with EDA mutation were com-pared among the different dentition sites.Results:33 patients were identified with EDA mutation.In the non-syndromic patients,13 /143(9.09%)were identified with EDA mutation,while in patients with ec-todermal dysplasia,20 /31 (64.52%)were found with EDA mutation.Ten novel EDA mutations were identified (c.769G >C[p.G257R],c.936C >G[p.I312M],c.223G >A[p.E75K],c.1166C >T[p. P389L],c.133G >C[p.G45R],c.1109G >A[p.E370K],c.914G >T[p.S305I],c.916C >T[p. Q306X],c.602G >T[p.G201V],c.88 -89insG[p.A30GfsX69]).For each dentition site there was no statistic difference in the number of missing teeth between the left and right sides,so the number from both sides were combined later in the analysis.In the patients with EDA mutation,the non-syndromic pa-tients had fewer missing teeth (15.9 ±6.4 missing teeth for each,207 /364 in total)than the patients with ectodermal dysplasia (23.9 ±4.3,478 /560).In the non-syndromic patients with EDA mutation, the maxillay central incisors and first molars were less affected,with the same missing rate as 19.2% (5 /26).While the mandibular central incisors (with a missing rate of 76.9%,20 /26),the maxillary late-ral incisors (the missing rate:88.5%,23 /26 ),the mandibular lateral incisors (the missing rate:80.8%,21 /26),and the maxillary first premolars (the missing rate:80.8%,21 /26)were more likely to be missing.In the ectodermal dysplasia patients with EDA mutation,only maxillary central incisors (the missing rate:60%,24 /40),maxillary canines (the missing rate:70%,28 /40),mandibular ca-nines (the missing rate:67.5%,27 /40),maxillary first molars (the missing rate:65%,26 /40)and mandibular first molars (the missing rate:72.5%,29 /40)had higher possibility of persistence.Teeth at other dentition sites were more likely to be affected (the minimum missing rate:87.5%,35 /40). Conclusion:The findings would help to reveal the EDA gene and its function in ectodermal organogene-sis.

IMP3 and CD44 protein expression in recurrent bladder urothelial carcinoma / 中国肿瘤临床

Objective:To evaluate the expression of IMP3 and CD44 proteins in recurrent urothelial carcinoma (UC) and to deter-mine the correlation between the two proteins. Methods: Data from transurethral resection of bladder (TURB) cancer cases between January 2002 and December 2012 were reviewed. Of the 54 UC recurrent cases in this study, one group of 25 had experienced recur-rence within 6 months after surgery, and the other group of 29 had their first recurrence after more than 3 years. IMP3 and CD44 immu-noreactivities were increased, which correlated with the clinicopathologic parameters. The relationship between IMP3 and CD44 pro-tein expressions was also explored. Results:Six of the 25 short-term recurrent UC cases were tested positive for IMP3 and all belonged to high-grade UC. Among the 29 long-term recurrent patients, only one case of low-grade UC tested positive for IMP3. IMP3 expres-sion rate [24%(6/25)] and intensity [weak staining at 16%(4/25) and strong staining at 8%(2/25)] were higher in the short-term recur-rent group than those in the long-term group, which had an expression rate of 3.45% (1/29) and intensity rates for weak staining at 3.45%(1/29) and without strong staining (0/29). No difference was observed in the CD44 expression between the two groups. In addi-tion, the high expression of IMP3 correlated with higher tumor stage and grade, whereas the CD44 expression tended to be inversely correlated with the tumor grade in recurrent UC patients. Furthermore, no correlation existed between the expression of IMP3 and CD44 proteins in the bladder carcinoma specimens. Conclusion:IMP3 exhibited a significantly higher expression rate in short-term re-current UC specimens than in the long-term recurrent cases. Therefore, IMP3 could be used as a novel marker, together with the other factors including tumor stage and grade, for predicting the high risk of short-term recurrence in UC patients who underwent TURB.

Histologic subtyping and clinicopathologic features of papillary renal cell carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the morphologic characteristics and prognostic significance of 2 histologic subtypes of papillary renal cell carcinoma (PRCC).</p><p><b>METHODS</b>A series of 48 tumors previously diagnosed as PRCC during the period from 2003 to 2013 were evaluated. All available slides were reviewed and 39 cases were confirmed to be PRCC. The detailed histomorphologic features were evaluated. The tumors were subtyped using the WHO classification and a novel mechanism suggested in recent literature, with prognostic correlation. Type 1 PRCC was assigned for tumors demonstrating simple cuboidal epithelium, irrespective of nuclear grade or other histomorphologic features. Tumors demonstrating cellular pseudostratification and high-grade nuclei were classified as type 2 PRCC.</p><p><b>RESULTS</b>The novel subtyping mechanism was more practical and correlated with the outcome of patients. The scope of type 1 PRCC was expanded. Type 2 PRCC demonstrated high tumor stage and high nuclear grade, and was more likely to have perinephric/renal sinus fat invasion and sarcomatoid differentiation. Follow-up information was available in 32 patients, including 4 deaths in patients haboring type 2 PRCC. The survival rate of patients with type 2 PRCC was significantly lower than that of type 1 PRCC.</p><p><b>CONCLUSIONS</b>The novel subtyping mechanism is more practical than WHO classification. Type 1 and type 2 PRCCs share many overlapping histomorphologic features. Type 2 PRCC is notably associated with worse prognosis. Recognizing the histomorphologic diversity of PRCC and classifying subtypes accurately are important in predicting the prognosis of patients with PRCC.</p>

Classification and Pathological Analysis of Immunophenotype of 76 Cases of Non-Hodgkin Lymphoma in Shenyang / 中国医科大学学报

Objective: Our aim was to discuss the pathological characteristics and immunophenotype of non-Hodgkin lymphoma (NHL) in Shenyang. Methods: Histopathological observation was performed with immunohistochemical methods (SP method). We used 10 antibodies as B,T markers to analyze 76 cases of NHL according to the new WHO classification. Results: The B-NHL was more prevalent than the T-NHL. In B-NHL, the Diffuse Large B cell Lymphoma (DLBL) was the most common, next was the mucosa-associated lymphoid tissue lymphoma (+/-monocytoid B-cells) and lymphoplasmacytic lymphoma (LPL). In T-NHL, the peripheral T cell lymphoma unspecificly accounted most. The positivity rates of CD79a in B-NHL were 100% and its cross-reactivity was 0. The straining rates of polyclonal CD3 with T cell were 88% and CD3 only reacted with 5% of B-NHL. Conclusion: The NHL in Shenyang was marked by the most common DLBL and peripheral T cell lymphoma, unspecificly. The rates of monocytoid lymphoma and LPL were higher. The CD79a and CD3 were antibodies of B-cell and T-cell markers with high sensitivity and specificity, respectively.