Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Blastic plasmacytoid dendritic cell neoplasm in Jinhua,China:Two case reports

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.

Blastic Plasmacytoid Dendritic Cell Neoplasm:Progress in Cell Origin,Molecular Biology,Diagnostic Criteria and Therapeutic Approaches

Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor prognosis with poor overall survival.BPDCN is derived from plasmacytoid dendritic cells(pDCs)and its pathogenesis is unclear.The tumor cells show aberrant expression of CD4,CD56,interleukin-3 receptor alpha chain(CD 123),blood dendritic cell antigen 2(BDCA 2/CD303),blood dendritic cell antigen 4(BDCA4)and transcription factor(E protein)E2-2(TCF4).The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma.Relapse with drug resistance generally occurs quickly.Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy.In this review,we summarize the differentiation of BPDCN from its cell origin,its connection with normal pDCs,clinical characteristics,genetic mutations and advances in treatment of BPDCN.This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.

Effects of Antisense Oligodeoxynucleotide to Follicle-stimulating Hormone Receptor on the Cell Proliferation and Apoptosis in Cells Derived from Human Ovarian Mucinous Cystadenocarcinoma in Vitro

The human ovarian mucinous cystadenocarcinoma （hOMC） cells were co-cultured with antisense oligodeoxynucleotide （antisense ODN）, nonsense ODN, and follicle-stimulating hormone （FSH） at different concentrations for the purpose of observing the effects of antisense ODN to FSH receptor （FSHR） on the proliferation and apoptosis of cultured hOMC cells in vitro. The inhibitory rates of growth were measured by using MTT method on the 2nd, 4th, 6th, 8th and 10th days after the interference of antisense ODN, nonsense ODN, and FSH, respectively. The apoptotic rates and the cell cycles were determined by means of flow cytometry, the apoptosis indexes were detected by using TUNEL, and the expression of caspase-3 was measured by using SP immunohistochemistry. Compared with that in the control group, the proliferative activity of hOMC cells was increased obviously in FSH groups （P〈0.05 or P〈0.01）, decreased distinctly in antisense ODN groups （P〈0.05 or P〈0.01）, and unchanged in nonsense ODN groups, respectively. Meanwhile, antisense ODN could significantly antagonize the FSH-promoted cell proliferative activity （P〈0.01）. Compared with those in the control group, the apoptotic rates and the expression of caspase-3 were dramatically increased in the mid- and high-dose antisense ODN groups （P〈0.05 or P〈0.01）, while the number of cells in G1/G0 phase was significantly decreased and that in S phase distinctly increased （P〈0.01）, There was no change in nonsense ODN groups （P〉0.05）, It was suggested that FSH may improve the development of hOMC cells, However, antisense ODN could inhibit proliferative activity and the FSH-promoted proliferative activity in hOMC cells, at the same time, antisense ODN could inhibit hOMC cell growth by inducing apoptosis.

Blastic plasmacytoid dendritic cell neoplasm with skin and bone marrow involvement: Report of three cases

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and highly aggressive hematopoietic malignancy.BPDCN is difficult to diagnose because of the overlap in morphologic and immunophenotypic features with various cutaneous lymphatic hematopoietic tumors.CASE SUMMARY We report on three BPDCN cases,all characterized by skin nodules and examined by histology,immunohistochemical detection,in situ hybridization for Epstein-Barr virus,and follow-up.We also review the relevant literature.All patients were positive for CD56 and negative for Epstein-Barr encoded small RNA.Two patients had bone marrow involvement.Chemotherapy is the main treatment for BPDCN,but case 1 showed bone marrow suppression and case 2 developed recurrence after chemotherapy.Case 1 survived for 7 mo,case 2 for 17 mo,and case 3 for 9 mo.CONCLUSION An accurate pathological diagnosis is a precondition for treatment,and the diagnosis of BPDCN should be based on a combination of clinical symptoms,pathological characteristics,immunophenotype,and other auxiliary examinations.It is necessary to clarify the clinicopathological features and biological behavior of BPDCN to improve its understanding by both clinicians and pathologists.Case 2 survived significantly longer than the other two cases,suggesting that the treatment received by case 2 was more effective.

Perivascular epithelioid cell tumors of the liver misdiagnosed as hepatocellular carcinoma:Three case reports

BACKGROUND Hepatic perivascular epithelioid cell neoplasms(PEComas)are rare.Diagnostic and treatment experience with hepatic PEComa remains insufficient.CASE SUMMARY Three hepatic PEComa cases are reported in this paper:One case of primary malignant hepatic PEComa,one case of benign hepatic PEComa,and one case of hepatic PEComa with an ovarian mature cystic teratoma.During preoperative imaging and pathological assessment of intraoperative frozen samples,patients were diagnosed with hepatocellular carcinoma(HCC),while postoperative pathology and immunohistochemistry subsequently revealed hepatic PEComa.Patients with hepatic PEComa which is misdiagnosed as HCC often require a wider surgical resection.It is easy to mistake them for distant metastases of hepatic PEComa and misdiagnosed as HCC,especially when it’s combined with tumors in other organs.Three patients eventually underwent partial hepatectomy.After 1-4 years of follow-up,none of the patients experienced recurrence or metastases.CONCLUSION A clear preoperative diagnosis of hepatic PEComa can reduce the scope of resection and prevent unnecessary injuries during surgery.

Diagnosis and treatment of primary seminoma of the prostate:A case report and review of literature

BACKGROUND Primary seminoma of the prostate(PSP)is a rare type of extragonadal germ cell tumour that is easily misdiagnosed,owing to the lack of specific clinical features.It is therefore necessary for clinicians to work toward improving the accuracy of PSP diagnosis.CASE SUMMARY A 59-year-old male patient presenting with acute urinary retention was admitted to a local hospital.A misdiagnosis of benign prostatic hyperplasia led to an improper prostatectomy.Histopathology revealed PSP invading the bladder neck and bilateral seminal vesicles.Further radiotherapy treatment for the local lesion was performed,and the patient had a disease-free survival period of 96 mo.This case was analysed along with 13 other cases of PSP identified from the literature.Only four of the cases(28.6%)were initially confirmed by prostate biopsy.In these cases,imaging examinations showed an enlarged prostate(range 6-11 cm)involving the bladder neck(13/14).Of the 14 total cases,11(78.6%)presented typical pure seminoma cell features,staining strongly positive for placental alkaline phosphatase,CD117,and OCT4.The median age at diagnosis was 51(range 27-59)years,and patients had a median progression-free survival time of 48(range 6-156)mo after treatment by cisplatin-based chemotherapy combined with surgery or radiotherapy.The remaining three were cases of mixed embryonal tumours with focal seminoma,which had clinical features similar to those of pure PSP,in addition that they also had elevated serum alpha fetoprotein,beta-human chorionic gonadotropin,and lactose dehydrogenase.CONCLUSION PSP should be considered in patients younger than 60 years with an enlarged prostate invading the bladder neck.Further prostate biopsies may aid in proper PSP diagnosis.Cisplatin-based chemotherapy is still the main primary therapy for PSP.

Current surgical management of pancreatic endocrine tumor liver metastases

BACKGROUND: The management of metastatic disease in pancreatic endocrine tumors (PETs) demands a multidisciplinary approach and the cooperation of several medical specialties. The role of surgery is critical, even when a radical excision cannot always be achieved. DATA SOURCES: A PubMed search of relevant articles published up to February 2011 was performed to identify current information about PET liver metastases regarding diagnosis and management, with an emphasis on surgery. RESULTS: The early diagnosis of metastases and their accurate localization, most commonly in the liver, is very important. Surgical options include radical excision, and palliative excision to relieve symptoms in case of failure of medical treatment. The goal of the radical excision is to remove the primary tumor bulk and all liver metastases at the same time, but unfortunately it is not feasible in most cases. Palliative excisions include aggressive tumor debulking surgeries in well-differentiated carcinomas, trying to remove at least 90% of the tumor mass, combined with other additional destructive techniques such as hepatic artery embolization or chemoembolization to treat metastases or chemoembolization to relieve symptoms in cases of rapidly growing tumors. The combination of chemoembolization and systemic chemotherapy results in better response and survival rates. Other local destructive techniques include ethanol injection, cryotherapy and radiofrequency ablation. CONCLUSION: It seems that the current management of PETs can achieve important improvements, even in advanced cases.

Ultrasound-guided fine needle aspiration biopsy in differential diagnosis of portal vein tumor thrombosis

BACKGROUND: Portal vein tumor thrombosis(PVTT) is a serious complication and a major metastatic way of hepa- tocellular carcinoma (HCC). But portal vein benign throm- bosis(PVBT) always appears in patients with hepatocirrho- sis, and PVTT should be differentiated from PVBT. The aim of this study was to probe the value of ultrasound- guided fine needle aspiration biopsy in differential diagnosis of PVTT. METHODS: Twenty-two HCC patients with portal vein thrombosis and 8 hepatocirrhosis patients with portal vein thrombosis were studied by ultrasound-guided fine needle aspiration biopsy. Twelve portal vein thrombosis filling portal vein embranchment of the 30 portal vein thrombosis patients were examined by 18G automatic biopsy. The positive rates of aspiration biopsy cytology and histology were calculated and compared with those of automatic biopsy. RESULTS: The positive rates of fine needle aspiration biop- sy cytology and histology were 93.3% (28/30) and 90.0% (27/30), respectively. They were not different markedly from that of automatic biopsy 91.7% (11/12). In aspira- tion biopsy of 22 HCC patients with PVTT, HCC cellular was found in 19 portal vein thrombosis patients (86.4%) by cytology examination and in 18 portal vein thrombosis patients (81.8%) by histology examination. In total, 20 tumor thrombi were detected. The other two were diag- nosed as benign thrombosis. No HCC cell and/or tissue was observed in 8 patients with hepatocirrhosis associated with portal vein thrombosis. CONCLUSIONS: Ultrasound-guided fine needle biopsy in detecting PVTT shows a high positive rate and is of diag- nostic value. The positive rate is not apparently different from that of automatic biopsy. Hence the case that fails to be diagnosed by color Doppler flow imaging ( CDFI) and pulsed Doppler can be detected early by ultrasound-guided fine needle aspiration biopsy.

甲状腺许特莱氏细胞腺瘤1例及相关文献分析

甲状腺许特莱氏细胞肿瘤(Hürthle cell neoplasms, HCNs)是甲状腺肿瘤的一种特殊类型。该疾病在临床上较为罕见,在诊断方面缺乏特异性,术中快速冰冻检查可提高该病检出率,最终确诊需要在术后进行石蜡切片检查,同时在治疗上目前提倡个体化治疗原则。本文就在临床所见1例做一报告。

Single-center Experience in the Diagnosis and Treatment of Hepatic Perivascular Epithelioid Cell Neoplasm

Background and Aims:Perivascular epithelioid cell neo-plasms(PEComas)are a rare type of mesenchymal neo-plasm and their preoperative diagnosis is challenging.In this study,we summarized the experience from a single medical center to study the examinations,clinical presen-tations,and pathological and histological characteristics of PEComas in the liver in order to optimize overall un-derstanding of the diagnosis and treatment of these neo-plasms.Methods:We conducted a retrospective analysis to investigate the clinical and pathological characteristics as well as imaging presentations of 75 patients diagnosed with hepatic PEComa in The First Affiliated Hospital of Zhe-jiang University between April 2010 and April 2020.Re-sults:Among the 75 patients,52 were women,and the median age was 48 years.Most patients had no specific symptoms,and two were admitted to the hospital for a second time owing to relapse.All patients underwent surgi-cal resection.Histologically,38 patients had classical angio-myolipoma(AML)and 37 had epithelioid AML.The PECo-mas were accompanied by positive immunohistochemical expression of HMB45,Melan-A,and smooth muscle actin.Follow-up data were obtained from 47 of the total 75 pa-tients,through October 2020.Two patients had metastasis after surgery.Conclusions:AML is the most common type of hepatic PEComa.There are no specific symptoms of he-patic PEComa,and serological examinations and imaging modalities for accurate preoperative diagnosis are lacking.Epithelioid AML should be considered a tumor of uncertain malignant potential;however,the prognosis of PEComa af-ter resection is promising.

Growth inhibiting effects of antisense eukaryotic expression vector of proliferating cell nuclear antigen gene on human bladder cancer cells

Objective To explore the growth inhibiting effects on human bladder cancer by antisense RNA targeting the proliferating cell nuclear antigen (PCNA) gene. Methods The eukaryotic expression vector for antisense PCNA cDNA was constructed and transferred into a bladder cancer EJ cell line. The PCNA expression in the cancer cells was detected by RT-PCR and Western blotting assays. The in vitro proliferation activities of the transferred cells were observed by growth curve,tetrazolium bromide (MTT) colorimetry,tritiated thymidine ( 3H-TdR)incorporation, flow cytometry and clone formation testing,while its in vivo anti-tumor effects were detected on nude mice allograft models.Results After the antisense vector,pLAPSN,was transferred,cellular PCNA expression was inhibited at both protein and mRNA levels. The growth rates of EJ cells were reduced from 27.91% to 62.07% ( P <0.01),with an inhibition of DNA synthesis rate by 52.31% ( P <0.01). Transferred cells were blocked at G 0/G 1 phases in cell-cycle assay,with the clone formation ability decreased by 50.81% ( P <0.01). The in vivo carcinogenic abilities of the transferred cancer cells were decreased by 54.23% ( P <0.05). Conclusions Antisense PCNA gene transfer could inhibit the growth of bladder cancer cells in vitro and in vivo,which provided an ideal strategy for gene therapy of human cancers.

Juxtaglomerular cell tumor of the kidney: a clinicopathological analysis of five cases

Juxiaglomerular cell tunor (JGCT)is a kind of rare renal neoplasm that was first deseribed by Robertson in

Detailed deletion mapping of loss of heterozygosity on 9p13-23 in laryngeal squamous cell carcinoma by microsatellite analysis

Background This study was designed to investigate the hot spots of microsatellite loss of heterozygosity (LOH) on 9p13-23 in laryngeal squamous cell carcinoma and to find out the correlation between the incidence of microsatellite LOH and the clinicopathological parameters Methods Tumor tissues were obtained from paraffin embedded sections with microdissection Genomic DNA was extracted from tumor tissues and peripheral blood lymphocytes with the phenol-chloroform Polymerase chain reaction (PCR) amplification and denaturing gel electrophoresis were carried out in a set of 42 squamous cell carcinoma (SCC) of larynx and corresponding peripheral blood lymphocytes using 13 highly polymorphic microsatellite markers on 9p13-23 The correlation was analyzed between microsatellite LOH at the high frequency on 9p13-23 and clinicopathological parameters in the patients with squamous cell carcinoma of larynx KH*2/5DResults Of the 42 laryngeal cancers, 41 (97 6%) showed LOH in at least one of the microsatellite markers tested on 9p13-23 The most frequently deleted marker was D9S162 in 17 of the 19 (89 5%) informative samples The marker D9S171, which is located on 9p21, had LOH detected in 12 of the 15 informative cases (80 0%) LOH at the D9S1748 marker (closest to the p16 gene locus) was detected in 18 of the 36 informative cases (50 0%) Allelic deletion mapping revealed two minimal regions of LOH encompassing markers D9S161-D9S171 on 9p21 and IFNA-D9S162 on 9p22-23 Multiple LOH (≥4) on 9p21-23 was found more frequently in the patients under 60 years, with supraglottic SCC or cervical lymph node metastasis than those over 60 years, with glottic SCC or without cervical lymph node metastasis ( P <0 01 or 0 01, 0 05, respectively) On the contrary, there was no correlation between T stages or pathologic classification and the frequency of LOH on 9p21-23 in 42 SCC of Larynx Conclusions These findings imply the presence of at least two putative tumor suppressor genes on 9p13-23 in laryngeal SCC Multiple genetic alterations are probably implicated in supraglottic SCC with cervical lymph node metastasis in younger patients

Experimental study on anti-neoplastic activity of epigallocatechin-3-gallate to digestive tract carcinomas

Background Epigallocatechin-3-gallate （EGCG） has been demonstrated to have anti-neoplastic activity, but the effective concentration of EGCG and its possible mechanisms are uncertain. The study on the killing effects of EGCG on different digestive tract cancer cell lines can find target sites of its anti-neoplastic effect and provide a theoretical basis for its clinical application in the treatment of cancers. Methods Methyl thiazolyl tetrazolium （MTT） analysis was made to detect the differential sensitivities of eight digestive tract cancer cell lines to EGCG. The effect of EGCG on cell cycle distribution of sensitive cancer cell line was measured by flow cytometry. By polymerase chain reaction （PCR）-enzyme linked immunosorbent assay （ELISA） protocol, the influence of EGCG on telomerase activity of sensitive cancer cell line was also investigated. RT-PCR method was employed to detect the influence of EGCG on the expressions of hTERT, cmyc, p53 and madl genes in sensitive cancer cell line. Results EGCG exhibited dose-dependent killing effects on all eight disgestive tract cancer cell lines. The 50% inhibitory concentration （IC50） of SW1116, MKN45, BGC823, SGC7901, AGS, MKN28, HGC27 and LoVo cells were 51.7 μmol/L, 55.9 μmol/L, 68.5 μmol/L, 79. 1 μmol/L, 83.8 μmol/L, 119.8 μmol/L, 183.2 μmol/L and 194. 6 μmol/L, respectively. There were no apparent changes in cell cycle distribution of sensitive cancer cell line MKN45 48 hours after incubating with three different concentrations of EGCG compared with the controls. It was found that EGCG could suppress the telomerase activity of MKN45 cells, and the effects were dose- and time-dependent. After EGCG administration, the expression of hTERT and c-myc genes in MKN45 cells was decreased, that of the madl gene increased, and that of the p53 gene unchanged. Conclusions EGCG has dose-dependent killing effects on different digestive tract cancer cell lines. Administration of EGCG has no obvious effect on cell cycle distribution of sensitive cancer cell line MKN45. The anti-neoplastic activity of EGCG might be due to the inhibition of telomerase activity by means of its influence on hTERT and the up-stream regulation genes.