Distinct clinical phenotype and genetic testing strategy for Lynch syndrome in China based on a large colorectal cancer cohort

Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) predisposition syndrome. We performed a large-scale study to assess a screening strategy for identifying LS in Chinese CRC patients in routine clinical testing. A total of 4,195 eligible CRCs were universally screened. Then, 8.7% of CRCs were detected with dMMR. The incidence of LS was 2.7% (115 of 4,195) in this cohort; among patients over 70 years of age, only 0.3% (2 of 678) were diagnosed as LS. Then, 17.4% of LS cases showed large genomic deletions/duplications. LS probands developed CRCs predominantly at proximal colon location. The frequency of BRAF V600E mutation among Chinese CRCs was significantly lower than that among Western populations, and MLH1 promoter methylation significantly improved the efficiency of genetic screening for LS among MLH1-deficient patients. A comprehensive molecular testing strategy that includes detection of large genomic rearrangements is imperative for the diagnosis of LS. Among CRC patients aged 70 years or younger, a selective strategy for LS screening might be considered for routine clinical testing.     

Phase II trial to evaluate laparoscopic surgery for Stage 0/I rectal carcinoma

Recently reported randomized controlled trials demonstrated that laparoscopic surgery (LS) was comparable or superior to open surgery with regard to the long-term outcome for colon and rectosigmoidal carcinoma; however, controversy persists with regard to the appropriateness of LS for patients with rectal carcinoma. To examine the technical and oncological feasibility of LS for rectal carcinoma, a phase II trial was started in patients with a preoperative diagnosis of Stage 0/I rectal carcinoma, under the direction of the Japan Society of Laparoscopic Colorectal Surgery. Surgeons in 39 specialized institutions will recruit 350 patients. The primary end-point in the first stage is the anastomotic leakage rate by double-stapling technique and that in the second stage is overall survival. Secondary end-points are relapse-free survival, short-term clinical outcome, adverse events, the rate of histologically curative operation, the proportion of completion of LS and the conversion rate.     

Comparison of clinical schemas and morphologic features in predicting Lynch syndrome in mutation-positive patients with endometrial cancer encountered in the context of familial gastrointestinal cancer registries

BACKGROUND:

Endometrial cancer (EC) is the most common extraintestinal malignancy in Lynch syndrome (LS) and often is the sentinel malignancy, yet there is no consensus regarding LS‐EC detection algorithms. In this study, the authors determined the efficacy of family/personal history and tumor morphology in predicting LS in a cohort of patients with EC who had mutation‐proven LS.

METHODS:

Amsterdam II (AmII) criteria, revised Bethesda guidelines (rBG), and Society of Gynecologic Oncologists (SGO) clinical screening criteria were applied to the pedigrees of 76 patients with mutation‐proven LS who had pathology‐proven EC. When tumors were tested for microsatellite instability (MSI) phenotype status or mismatch‐repair protein‐immunohistochemical (MMR‐IHC) expression, those results also were reviewed, and LS‐associated histopathologic features were documented in 38 available patients.

RESULTS:

Of 76 patients, 36%, 58%, 71%, and 93% would have been selected for further testing for LS by pedigree screening at the time of EC diagnosis with rBG, AmII, SGO 20%‐to‐25%, and SGO 5%‐to‐10% criteria, respectively. Ninety percent (18 of 20 tumors) of tested ECs had high MSI, and 96% (22 of 23 tumors) had abnormal MMR‐IHC expression. At least 1 LS‐EC morphologic feature was present in 16 of 38 tumors (42%).

CONCLUSIONS:

Clinical screening criteria had variable efficacy for the identification of LS‐associated EC, and SGO 5%‐to‐10% criteria performed best. Characteristic pathologic features were present in a minority of patients. Although a high proportion of LS‐ECs had the MSI phenotype and were MMR deficient, the specificity of these tests and of clinical screening for LS in unselected patients with EC has been poorly described. Prospective studies to determine the optimal combination of these screening modalities are required. Cancer 2012;. © 2011 American Cancer Society.     

Combined analysis of three lynch syndrome cohorts confirms the modifying effects of 8q23.3 and 11q23.1 in MLH1 mutation carriers

Two colorectal cancer (CRC) susceptibility loci have been found to be significantly associated with an increased risk of CRC in Dutch Lynch syndrome (LS) patients. Recently, in a combined study of Australian and Polish LS patients, only MLH1 mutation carriers were found to be at increased risk of disease. A combined analysis of the three data‐sets was performed to better define this association. This cohort‐study includes three sample populations combined totaling 1,352 individuals from 424 families with a molecular diagnosis of LS. Seven SNPs, from six different CRC susceptibility loci, were genotyped by both research groups and the data analyzed collectively. We identified associations at two of the six CRC susceptibility loci in MLH1 mutation carriers from the combined LS cohort: 11q23.1 (rs3802842, HR = 2.68, p ≤ 0.0001) increasing risk of CRC, and rs3802842 in a pair‐wise combination with 8q23.3 (rs16892766) affecting age of diagnosis of CRC (log‐rank test; p ≤ 0.0001). A significant difference in the age of diagnosis of CRC of 28 years was observed in individuals carrying three risk alleles compared to those with 0 risk alleles for the pair‐wise SNP combination. A trend (due to significance threshold of p ≤ 0.0010) was observed in MLH1 mutation carriers towards an increased risk of CRC for the pair‐wise combination (p = 0.002). This study confirms the role of modifier loci in LS. We consider that LS patients with MLH1 mutations would greatly benefit from additional genotyping of SNPs rs3802842 and rs16892766 for personalized risk assessment and a tailored surveillance program.     

Ovarian cancer in Lynch syndrome; a systematic review

ObjectiveThe aim was to systematically review the characteristics of ovarian cancer in women with Lynch syndrome (LS) and evaluate the role of surveillance in detection of ovarian cancer in LS.MethodsAll studies between 1979 and 2015 of women with ovarian cancer and LS or at 50% risk of LS were evaluated. Two reviewers independently evaluated eligible studies and extracted data on age at diagnosis, histological type, FIGO stage, and way of detection according to pre-specified criteria. The studies were assessed for quality using the Newcastle-Ottawa quality assessment scales.ResultsThe quality score of the 49 identified studies was at least 6 out of 8 and provide clinical information on 747 LS women with ovarian cancer. The mean age at diagnosis was 45.3 (range 19–82) years. Most frequent mutations were MSH2 (47%) and MLH1 (38%). Histopathological data were available for 445 women. The most frequently reported histological type was mixed type (mucinous/endometrioid/clear cell carcinomas) (n = 136; 31%). Most tumours (281, 65%) were diagnosed at an early stage (FIGO I/II). Six studies evaluating the effect of surveillance of ovarian cancer, reported that seven of 22 (32%) ovarian cancers were found during surveillance, 6/7 (86%) were detected at an early stage.ConclusionThis systematic review describes that ovarian cancer in women with LS has a wide age-range of onset, is often diagnosed at an early stage with frequently endometrioid/clear cell histology. Data about the role of surveillance in detection of ovarian cancer in women with LS are scarce however detection at an early stage seems possible.     

Lynch‐like syndrome: Characterization and comparison with EPCAM deletion carriers

Colorectal cancers (CRCs) with microsatellite instability‐high (MSI+) but without detectable germline mutation or hypermethylation in DNA mismatch repair (MMR) genes can be classified as Lynch‐like syndrome (LLS). The underlying mechanism and clinical significances of LLS are largely unknown. We measured MSI and MMR protein expression in 4,765 consecutive CRC cases. Among these, MSI+ cases were further classified based on clinical parameters, germline sequencing of MMR genes or polymerase ε (POLE) and δ (POLD1) and promoter methylation analysis of MLH1 and MSH2. We found that MSI+ and MMR protein‐deficient CRCs comprised 6.3% (N = 302) of this cohort. On the basis of germline sequencing of 124 cases, we identified 54 LS with MMR germline mutation (LS‐MMR), 15 LS with EPCAM deletions (LS‐EPCAM) and 55 LLS patients. Of the 55 LLS patients, six (10.9%) had variants of unknown significance in the genes tested, and one patient had a novel somatic mutation (p.S459P) in POLE. In patients with biallelic deletions of EPCAM, all tumors and their matched normal mucosa showed promoter hypermethylation of MSH2. Finally, we found that patients with LLS and LS‐EPCAM shared clinical features that differed from LS‐MMR patients, including lower frequency of fulfillment of the revised Bethesda guidelines (83.6 and 86.7% vs. 98.1% for LS‐MMR) and older mean age at CRC diagnosis (52.6 and 52.7 years vs. 43.9 years for LS‐MMR). We identified somatic mutation in POLE as a rare underlying cause for MMR deficiency in LLS. The similarity between LLS and LS‐EPCAM suggests LLS as a subset of familial MSI+ CRC.     

郎格罕氏组织细胞增生症的诊断与治疗

目的：总结郎格罕氏组织细胞增生症（LCH）的诊断与治疗经验。方法；根据临床表现，X线，皮疹印片。皮疹和淋巴结活检，分析26例LCH的临床资料。结果：勒雪氏病（LS）18例。韩雪柯氏综合征（HSC）4例，骨嗜酸细胞内芽肿（EGB）4例。诊断后给予放，化疗，1例尚未治疗即死亡，1例治疗中病情加重而死亡，6例放弃治疗失访，3例治疗不久尚未好转即放弃失访，9例治疗好转出院后失访，6例完成疗程无复发。结论：重视临床表现，特征性皮疹和皮疹印片。充分认为典型X线片有助于早期诊断，LS，HSC和多发骨损害的EGB联合化疗，单发EGB手术或放疗可改善预后。长春新碱（V），足叶乙甙（E），强的松（P）联合化疗效果好，不良反应轻。     

Frequency of extracolonic tumors in Brazilian families with Lynch syndrome: analysis of a hereditary colorectal cancer institutional registry

Lynch syndrome (LS) is caused by inherited germline mutations in mismatch repair (MMR) genes. It is one of the commonest forms of inherited predisposition to colorectal cancer (CRC), accounting for 2–5% of all CRC. LS is characterized by early age of onset, with a tendency for multiplicity and an increased risk for extra-colonic tumors at particular sites. In this study we have evaluated the frequency of extra-colonic tumors in 60 unrelated LS families fulfilling the Amsterdam criteria (ACI. ACII) from the Oncotree database of the Hereditary Colorectal Cancer Registry of the AC Camargo Hospital. All families’ pedigree was extensively analyzed, varying from 2 to 6 generations with a total of 2,095 individuals evaluated. As expected, colorectal cancer was the most frequent tumor in the families (334 cases). We found 200 extracolonic tumors among all individuals with a higher ratio in women (123 cases) than men (77 cases). By far, breast cancer (32 cases) was the most frequent extracolonic manifestation in women followed by endometrial (20 cases) and uterine cervix cancer (20 cases). For man, prostate (16 cases) and stomach (12 cases) cancer were the most frequent extracolonic tumors. It is well know that establishing the diagnosis is challenging and requires knowledge and surveillance. Thus, recognition of individuals and families with hereditary predisposition to cancer according to clinical and molecular features, combined with intensive surveillance and management programs, can contribute substantially to improve results related to the diagnosis and characterization of LS.     

Clinical features of biliary tract cancer in Japanese individuals with Lynch syndrome

BackgroundBiliary tract cancer (BTC) is a Lynch syndrome (LS)-associated cancer with a high mortality rate. This study aimed to clarify the clinical features of BTC in individuals with LS and to discuss its management.MethodsWe obtained data from genetically verified Japanese individuals with LS who were diagnosed at a single institution, between January 2003 and April 2021. Moreover, 21 individuals with sporadic BTC (n=15) and LS associated BTC (n=6) underwent microsatellite instability (MSI) testing.ResultsAmong 92 individuals with LS, 6 individuals with MLH1 variants developed BTCs (10 lesions, male/female, 2:1). The median age at diagnosis of initial BTC was 69 years (range, 34–78 years). Histological examination revealed a predominance of differentiated adenocarcinoma (89%). Then, 2 individuals had multiple BTCs. All available 7 BTC lesions showed high-frequency of microsatellite instability (MSI-H). MLH1 carriers showed a 7.2% cumulative risk of BTC development at an age of 70 years. Five of the six individuals died of BTC.ConclusionsMSI analysis could facilitate LS identification in individuals with BTC. Surveillance for BTC should be considered for MLH1 carriers in Japan.     

Lichen sclerosus and risk of cancer

Malignant potential of lichen sclerosus (LS) has been suspected, but evidence is sparse. We used the population‐based Finnish Cancer Registry data to further study this connection. We identified all women with the diagnosis of LS (n = 7,616) listed in the Finnish Hospital Discharge Registry from 1970 to 2012. The cohort was followed through the Finnish Cancer Registry for subsequent cancer diagnoses until 2014. Standardized incidence ratios (SIRs) were calculated for different cancers by dividing the observed numbers of cancers by expected ones. The expected numbers were based on national cancer incidence rates. During the follow‐up period, we found 812 cancers among patients with LS (SIR: 1.13, 95% CI 1.05–1.21). LS was associated with an increased risk of vulvar (182 cases, SIR: 33.6, 95% CI 28.9–38.6) and vaginal cancer (4 cases, SIR: 3.69, 95% CI 1.01–9.44). The risk of cancers of the uterine cervix and lung was significantly decreased. LS is associated with an increased risk for vulvar and vaginal cancer. These data are important when designing the care of women diagnosed with LS.     

Limited‐Stage Small Cell Lung Cancer: Current Chemoradiotherapy Treatment Paradigms

In the U.S., the prevalence of small cell lung cancer (SCLC) is declining, probably reflecting the decreasing prevalence of tobacco use. However, a significant number of patients will receive a diagnosis of SCLC, and approximately 40% of patients with SCLC will have limited‐stage (LS) disease, which is potentially curable with the combination of chemotherapy and radiation therapy. The standard therapy for LS‐SCLC is concurrent chemoradiotherapy, and the 5‐year survival rate observed in clinical trials is approximately 25%. The standard chemotherapy remains cisplatin and etoposide, but carboplatin is frequently used in patients who cannot tolerate or have a contraindication to cisplatin. Substantial improvements in survival have been made through improvements in radiation therapy. Concurrent chemoradiotherapy is the preferred therapy for patients who are appropriate candidates. The optimal timing of concurrent chemoradiotherapy is during the first or second cycle, based on data from meta‐analyses. The optimal radiation schedule and dose remain topics of debate, but 1.5 Gy twice daily to a total of 45 Gy and 1.8–2.0 Gy daily to a total dose of 60–70 Gy are commonly used treatments. For patients who obtain a near complete or complete response, prophylactic cranial radiation reduces the incidence of brain metastases and improves overall survival. The ongoing Radiation Therapy Oncology Group and Cancer and Leukemia Group B and the European and Canadian phase III trials will investigate different radiation treatment paradigms for patients with LS‐SCLC, and completion of these trials is critical.     

Socioeconomic factors associated with limb salvage versus amputation for adult extremity bone sarcomas in patients with insurance coverage

BackgroundLimb salvage (LS) has become the preferred treatment for adult patients with bone sarcoma of the extremities. The decision to perform LS versus an amputation is often dictated by tumor characteristics, however there may be socioeconomic factors associated with LS. Previously this has been linked to insurance status, however currently there is a paucity of data examining socioeconomic factors in patients with medical insurance at the time of sarcoma diagnosis. Therefore, the purpose of the current study was to examine socioeconomic factors which could be associated with the decision to perform LS versus amputation for adult bone sarcoma patients.MethodsData from Optum Labs Data Warehouse, a national administrative claims database, was analyzed to identify patients with extremity bone sarcomas from 2006 to 2017. Bivariate regression was used to identify factors associated with LS versus amputation.ResultsOf 1,390 (743 males, 647 female) patients, 252 (18%) under amputation while 1,138 (82%) underwent LS. Lower extremity tumors (OR 4.72, p < 0.001), income <$75,000 (OR 1.85, p = 0.03), being treated a public hospital (OR 1.41, p = 0.04) and a hospital with <200 beds (OR 1.90, p = 0.006) were associated with amputation. Income ≥$125,000 (OR 0.62, 0.04) were associated with LS.ConclusionIn adult patients with medical insurance at the time of diagnosis, socioeconomic and hospital factors were associated with an amputation for bone sarcoma, with poorer patients, and those treated at smaller, and public hospitals more likely to undergo amputation.     

结直肠癌化疗敏感性相关蛋白的蛋白质组学初步研究

目的:本研究应用蛋白质组学技术建立化疗敏感性不同的结直肠癌组织总蛋白双向凝胶电泳(two-dimensional gel electrophoresis,2-DE)图谱,并鉴定部分差异表达蛋白,以发现与结直肠癌化疗敏感性有关的蛋白.方法:收集临床诊断为晚期结直肠癌的病例,肠镜活检获取新鲜结直肠癌标本后液氮保存备用,根据肿瘤药物敏感实验分为化疗高敏感组和化疗低敏感组.提取组织总蛋白,采用双向凝胶电泳技术得到各组凝胶图谱;采用PD-quest 7.3软件进行图像的合成、对比和差异分析,识别化疗高敏感组和化疗低敏感组之间差异表达的蛋白斑点;选取差异蛋白质点,胶内酶解后行肽指纹图分析及网上数据库检索,鉴定差异蛋白质;应用Western印迹法检测部分差异蛋白的表达情况.结果: 建立了化疗高敏感组和化疗低敏感组的双向凝胶电泳图谱,多数蛋白质点集中于pH 4～8、相对分子质量为(20～100)×10~3.高敏感组和低敏感组的电泳图谱中平均蛋白质点数分别为(842±23)个和(793±19)个,2组平均匹配率为90.7%,2组间差异表达蛋白质点数为(79.00±13.56)个;选择30个差异蛋白质点进行质谱分析,经数据库查询鉴定出9个差异表达蛋白.结论:在化疗敏感性不同的结直肠癌中存在蛋白质表达的差异,这些差异表达蛋白可能与化疗敏感性有关,并可能用于化疗敏感性的预测.     

Present laparoscopic surgery for colorectal cancer in Japan

In many clinical studies, laparoscopic surgery (LS) for colon cancer has been shown to be less invasive than open surgery (OS) while maintaining similar safety. Furthermore, there are no significant differences between LS and OS in long-term outcomes. Thus, LS has been accepted as one of the standard treatments for colon cancer. In the treatments of rectal cancer as well, LS has achieved favorable outcomes, with many reports showing long-term outcomes comparable to those of OS. Furthermore, the magnification in laparoscopy improves visualization in the pelvic cavity and facilitates precise manipulation, as well as providing excellent educational effects. For these reasons, rectal cancer has seemed to be well indicated for LS, as has been colon cancer. The indication for LS in the treatment of locally advanced rectal cancer, which is relatively unresectable (e.g., cancer invading other organs), remains an open issue. In recent years, new techniques such as single-port and robotic surgery have begun to be introduced for LS. Presently, various clinical studies in our country as well as in most Western countries have demonstrated that LS, with these new techniques, are gradually showing long-term outcomes.     

Small cell lung cancer: patterns of care and their influence on survival - 25 years experience of a single Australian oncology unit

Aim: Evidence supporting improved outcomes for small cell lung cancer (SCLC) in recent decades is limited. This study aimed to identify patterns of care and survival over two time periods; 1 January 1987 to 31 December 1996 (cohort A) and 1 January 1997 to 31 December 2006 9 (cohort B). Methods: Patients' characteristics, management and outcome data were extracted from the Hospital Cancer Registry and clinical records. Survival analysis was determined using the Kaplan–Meier method and the log–rank test. Factors influencing survival outcome were assessed using Cox proportional hazards regression. Results: The total number of patients was 392 (224 in cohort A, 168 in cohort B). Overall 38% patients in cohort A and 24% in cohort B had limited stage (LS) disease at diagnosis. Combined chemoradiotherapy for LS increased from 5% in cohort A to 65% in cohort B. Overall 19% of patients in cohort A and 24% in cohort B received symptomatic treatment alone (STA). Median survival for LS in cohort B was significantly higher (19.5 months), than in cohort A (11.8 months) (P = 0.03). In extensive stage (ES) disease, median survival was 6.2 months in cohort A and 4.3 months in cohort B (P = 0.7). Variables for poorer outcome were STA, male gender, poor performance status, ES and whether the diagnosis was made in the earlier time period in cohort A. Conclusion: Outcomes for LS SCLC have improved with combined chemoradiotherapy, in keeping with worldwide data. The trends may also reflect recent improvements in staging and standardization of treatment. The outcome for ES‐SCLC remains poor.     

Is HLA type a possible cancer risk modifier in Lynch syndrome?

Lynch syndrome (LS) is the most common inherited cancer syndrome. It is inherited via a monoallelic germline variant in one of the DNA mismatch repair (MMR) genes. LS carriers have a broad 30% to 80% risk of developing various malignancies, and more precise, individual risk estimations would be of high clinical value, allowing tailored cancer prevention and surveillance. Due to MMR deficiency, LS cancers are characterized by the accumulation of frameshift mutations leading to highly immunogenic frameshift peptides (FSPs). Thus, immune surveillance is proposed to inhibit the outgrowth of MMR-deficient cell clones. Recent studies have shown that immunoediting during the evolution of MMR-deficient cancers leads to a counter-selection of highly immunogenic antigens. The immunogenicity of FSPs is dependent on the antigen presentation. One crucial factor determining antigen presentation is the HLA genotype. Hence, a LS carrier's HLA genotype plays an important role in the presentation of FSP antigens to the immune system, and may influence the likelihood of progression from precancerous lesions to cancer. To address the challenge of clarifying this possibility including diverse populations with different HLA types, we have established the INDICATE initiative (Individual cancer risk by HLA type, http://indicate-lynch.org/ ), an international network aiming at a systematic evaluation of the HLA genotype as a possible cancer risk modifier in LS. Here we summarize the current knowledge on the role of HLA type in cancer risk and outline future research directions to delineate possible association in the scenario of LS with genetically defined risk population and highly immunogenic tumors.     

腹腔镜手术治疗卵巢成熟型畸胎瘤的临床分析

目的探讨腹腔镜手术(LS)治疗卵巢成熟型畸胎瘤(MOCT)的临床疗效。方法2011年9月至2013年4月确诊的MOCT患者86例,分为LS组和开腹手术(OS)组,各43例。比较两组术中失血量、手术时间、术后住院时间、总费用、肛门排气时间、抗生素应用时间、止痛药应用情况和禁食时间,以及术后患者的月经和复发情况。结果 LS组患者的失血量、术后住院时间、肛门排气时间、抗生素应用时间、止痛药应用例数及禁食时间均明显少于OS组,两组手术时间无显著差异,LS组总费用明显高于OS组。随访结果显示,LS组月经异常3例,下腹痛5例,而OS组分别为9例和13例,差异有统计学意义(P<0.05)。结论 LS治疗MOCT,住院时间短,出血量更少,且疗效显著,值得进一步推广。     

Distinct molecular profiles in Lynch syndrome‐associated and sporadic ovarian carcinomas

Ovarian carcinoma in Lynch syndrome (LS) is associated with unexpectedly high survival; yet, beyond DNA mismatch repair (MMR) defects, the developmental mechanisms are unknown. We used established (genetic) and new (epigenetic) classifiers of ovarian cancer to explore similarities and differences between LS‐associated and sporadic diseases. To this end, all available ovarian carcinomas (n = 20) from MMR gene mutation carriers ascertained through a nation‐wide registry and 87 sporadic ovarian carcinomas of the main histological types were molecularly profiled. LS‐ovarian carcinomas were mostly of nonserous histology (12 endometrioid, seven clear cell and one serous), diagnosed at a mean age of 45.7 years, and associated with a 10‐year survival of 87%. Among LS‐ovarian carcinomas, 19/20 (95%) were MMR‐deficient vs. 11/87 (13%) among sporadic cases (p < 0.0001). In a striking contrast to the sporadic cases, the expression of p53 was normal and KRAS/BRAF mutations absent in all LS‐ovarian carcinomas. PIK3CA mutations, suggested to be a favorable prognostic factor, occurred with a frequency of 6/20 (30%), which was comparable to sporadic tumors of endometrioid or clear cell type. Tumor suppressor genes were more frequently methylated and LINE‐1 hypomethylation less common in LS‐ovarian carcinomas compared to their sporadic counterparts. The patterns of genetic and epigenetic alterations reflected the origin as LS vs. sporadic cases on one hand and the histological type on the other hand. In conclusion, the significant molecular differences observed between LS‐associated and sporadic ovarian carcinomas help explain the different behavior of these tumors and emphasize the need for tailored clinical management.     

Endometrial cancer in Lynch syndrome

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes. LS-associated endometrial cancer (LS-EC) is the most common extraintestinal sentinel cancer caused by germline PVs in MMR genes, including MLH1, MSH2, MSH6 and PMS2. The clinicopathologic features of LS-EC include early age of onset, lower body mass index (BMI), endometrioid carcinoma and lower uterine segment involvement. There has been significant progress in screening, diagnosis, surveillance, prevention and treatment of LS-EC. Many studies support universal screening for LS among patients with EC. Screening mainly involves a combination of traditional clinical criteria and molecular techniques, including MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing. The effectiveness of endometrial biopsy and transvaginal ultrasound (TVS) for clinical monitoring of asymptomatic women with LS are uncertain yet. Preventive strategies include hysterectomy and bilateral salpingo-oophorectomy (BSO) as well as chemoprophylaxis using exogenous progestin or aspirin. Recent research has revealed the benefits of immunotherapy for LS-EC. The NCCN guidelines recommend pembrolizumab and nivolumab for treating patients with advanced or recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) EC.     

Liposarcoma of the tongue: clinico-pathologic correlations of a possible underdiagnosed entity

Liposarcoma (LS), one of the most common malignant tumors, is considered as a rarity in the oral cavity, the tongue being the most frequent site for its occurrence. The purpose of the present study was to review and analyze the clinico-pathologic correlations of 32 cases of LS of the tongue, including four new cases from the files of our department. A total of 32 cases of LS of the tongue were collected, 29 from a MEDLINE search of the English language literature (1966-2004). Since the histopathologic features of one of the four new cases have been presented previously, this case was counted only once. LS of the tongue is a tumor of adult and old age, with a mean age of approximately 62 years and a peak incidence in the seventh and eighth decades. Clinically, it is a long-standing tumor that commonly presents as a solitary nodular mass, but can also present as a multi-nodular lesion. The most common histopathologic type is that of atypical lipomatous tumor (ALT)/well-differentiated LS (75%). LS can be easily misdiagnosed with both benign and malignant lipomatous and non-lipomatous tumors. LS of the tongue was commonly treated by local excision, however, there were cases of (multiple) recurrences and dedifferentiation. When a lipomatous lesion is encountered in the oral cavity, and especially in the tongue, LS should certainly be among the lesions that top the list of differential diagnosis. The follow-up must be on a long-term basis since this tumor can recur years after initial surgical treatment and can also undergo dedifferentiation.