Undifferentiated high-grade pleomorphic sarcoma of the common bile duct:A case report and review of literature

BACKGROUND Undifferentiated pleomorphic sarcoma(UPS)is a rare malignant mesenchymal tumor with a poor prognosis.It mainly occurs in the extremities,trunk,head and neck,and retroperitoneum regions.Owing to the lack of specific clinical manifestations and imaging features,UPS diagnosis mainly depends on pathological and immunohistochemical examinations for exclusive diagnosis.Here we report an extremely rare case of high-grade UPS in the common bile duct(CBD).There are limited available data on such cases.CASE SUMMARY A 70-year-old woman was admitted to our department with yellow eyes and urine accompanied by upper abdominal distending pain for 2 wk.Her laboratory data suggested significantly elevated hepatorenal function levels.The imaging data revealed calculous cholecystitis,intrahepatic and extrahepatic bile duct dilation with extrahepatic bile duct calculi,and a space-occupying lesion at the distal CBD.After endoscopic biliary stenting and symptomatic support therapy,CBD exploration and biopsy were performed.The frozen section indicated malignant spindle cell tumor of the CBD mass,and further radical pancreaticoduodenectomy was performed.Finally,the neoplasm was diagnosed as a high-grade UPS combined with the light-microscopic morphology and immunohistochemical results.CONCLUSION This extremely rare case highlighted the need for increasing physicians'vigilance,reducing the odds of misdiagnosis,and providing appropriate treatment strategies.

PD-1 antibody in combination with chemotherapy for the treatment of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum:Two case reports

BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.

Long-term outcomes of endoscopic submucosal dissection for undifferentiated type early gastric cancer over 2 cm with R0 resection

BACKGROUND Endoscopic submucosal dissection(ESD)for over 2 cm in size undifferentiated type(UD type)early gastric cancer(EGC)confined to the mucosa is not only challenging,but also long-term outcomes are not well known.AIM To evaluate the long-term outcomes of ESD done for UD type EGCs confined to the mucosa over 2 cm in size and compare the results with those where the lesions were less than 2 cm.METHODS 143 patients with UD type EGC confirmed on histology after ESD at a tertiary hospital were reviewed.Cases with synchronous and metachronous lesions and a case with emergency surgery after ESD were excluded.A total of 137 cases were enrolled.79 cases who underwent R0 resection were divided into 2 cm or less(group A)and over 2 cm(group B)in size.RESULTS Among 79 patients who underwent R0 resection,the number in group A and B were 51 and 28,respectively.The mean follow-up period(SD)was 79.71±45.42 months.There was a local recurrence in group A(1/51,2%)and group B(1/28,3.6%)respectively.This patient in group A underwent surgery while the patient in group B underwent repeated ESD with no further recurrences in both patients.There was no regional lymph node metastasis,distant metastasis,and deaths in both groups.With R0 resection strategy for ESD on lesions over 2 cm,20.4%(28/137)of patients were able to avoid surgery compared with expanded indication.CONCLUSION If R0 resection is achieved by ESD,UD type EGCs over 2 cm also showed good and similar clinical outcomes as compared to lesions less than 2 cm when followed for over 5 years.With R0 resection strategy,several patients can avoid surgery.

SMARCA4-deficient undifferentiated thoracic tumor:A case report

BACKGROUND SMARCA4-deficient undifferentiated tumors(SMARCA4-DUTs)present with diverse clinical manifestations and progress to metastasis and even cause death within a few months.This novel subset of undifferentiated tumors occurs in the middle-aged population and is strongly associated with a smoking history.Distin-guishing it from other malignancies is challenging.CASE SUMMARY A 62-year-old man presented with chest pain for 7 d.The patient had no respiratory symptoms and normal pulmonary function test results.The patient had been a smoker for 8 years and quit smoking 2 years ago.Chest computed tomography revealed a huge mass involving the left upper and lower lung lobes with pericardial invasion and multiple metastases.Tumor samples were obtained using open frozen biopsy,after several unsuccessful attempts.The tumor was composed of sheets of undifferentiated disclosive cells with vesicular nuclei and prominent nucleoli.The differential diagnosis included high-grade lymphoma,germ cell tumor,NUT carcinoma,undifferentiated carcinoma,and sarcoma.The tumor cells were large,arranged in sheets,and did not exhibit glandular or squamous differentiation.Frequent foci of necrosis were noted.There was no evidence of epithelial differentiation on immunohistochemical staining.The SMARCA4 stain showed complete loss of expression of SMARCA4,which is diagnostic.CONCLUSION In the present case,thoracic SMARCA4-DUT was diagnosed based on clinical features,absence of epithelial differentiation,and negative SMARCA4 expression.

Argon-helium cryoablation treatment of undifferentiated pleomorphic sarcoma of the thyroid:A case report and literature review

Undifferentiated pleomorphic sarcoma is an extremely rare malignant thyroid tumor.Thyroid sarcoma differs from common malignant thyroid tumors,such as thyroid follicular cell carcinoma.It is usually highly malignant,progresses rapidly,and is prone to remote metastasis.Currently,there is no standard protocol for the treatment of thyroid sarcomas,and most treatment effects are unsatisfactory.Argon-helium cryoablation is an important method of local treatment that is widely used in patients with unresectable advanced tumors.However,owing to the low incidence of thyroid sarcomas,there are no relevant literature reports on the treatment of thyroid sarcomas using cryoablation in China.This study reports the case of a patient with undifferentiated pleomorphic sarcoma of the thyroid gland who was treated with argon-helium cryoablation,and the immediate outcome was good.Based on a review of relevant literature,we discussed the effectiveness and safety of argon-helium cryoablation treatment,to provide clinical guidance and references for the treatment of patients with thyroid sarcoma.

Locally advanced undifferentiated carcinoma with osteoclast-like giant cells of the pancreas

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas(UCOGCP) is an unusual pancreatic neoplasm that represents < 1% of all pancreatic malignancies. Moreover, the giant cells of UCOGCP morphologically resemble the benign giant cells of bone tumors. Due to the rarity of this tumor type, the histogenesis and biologic behavior of UCOGCP remain controversial. Here, we report a case of UCOGCP that exhibited an invasive growth pattern involving infiltration of the adjacent bowel loop and portal vein,as well as superior mesenteric vein thrombosis. The patient underwent a distal pancreatectomy with splenectomy and partial colectomy, followed by four cycles of gemcitabine chemotherapy. No evidence of recurrence was detected after ten years. In addition to this case, clinical information on other UCOGCP cases reported in the English literature is summarized.

Undifferentiated liver embryonal sarcoma in adults: A report of four cases and literature review

AIM: To evaluate the undifferentiated embryonal sarcoma of liver (UESL) in adults in order to improve its diagnosis and treatment. METHODS: Four primary and one recurrent cases of UESL were clinicopathologically evaluated and immunohistochemically investigated with a panel of antibodies using the EnVision+ system. Relevant literature about UESL in adults was reviewed. RESULTS: Three males and one female were enrolled in this study. Their chief complaints were abdominal pain, weight loss, or fever. Laboratory tests, imaging and pathological features of UESL in adults were similar to those in children. Immunohistochemistry showed evidence of widely divergent differentiation into mesenchymal and epithelial phenotypes. The survival time of patients who underwent complete tumor resection followed by adjuvant transcatheter arterial chemoembolization (TACE) was significantly longer than that of those who underwent surgical treatment alone.CONCLUSION: UESL in adults may undergo pluripotential differentiation and its diagnosis should be made based on its morphological and immunohistochemical features. Complete tumor resection after adjuvant TACE may improve the survival time of such patients.

Endoscopic submucosal dissection for undifferentiated-type early gastric cancer: Do we have enough data to support this?

Although endoscopic submucosal dissection (ESD) is now accepted for treatment of early gastric cancers (EGC) with negligible risk of lymph node (LN) metastasis, ESD for intramucosal undifferentiated type EGC without ulceration and with diameter &#x02264; 2 cm is regarded as an investigational treatment according to the Japanese gastric cancer treatment guidelines. This consideration was largely based on the analysis of surgically resected EGCs that contained undifferentiated type EGCs; however, results from several institutes showed some discrepancies in sample size and incidence of LN metastasis. Recently, some reports about the safety and efficacy of ESD for undifferentiated type EGC meeting the expanded criteria have been published. Nonetheless, only limited data are available regarding long-term outcomes of ESD for EGC with undifferentiated histology so far. At the same time, endoscopists cannot ignore the patients&#x02019; desire to guarantee quality of life after the relatively non-invasive endoscopic treatment when compared to conventional surgery. To satisfy the needs of patients and provide solid evidence to support ESD for undifferentiated EGC, we need more delicate tools to predict undetected LN metastasis and more data that can reveal predictive factors for LN metastasis.

Important considerations when contemplating endoscopicresection of undifferentiated-type early gastric cancer

Endoscopic resection(ER) of undifferentiated-type early gastric cancer(UD-EGC) has a lower curative resection(CR) rate than does ER of differentiated-type EGC(D-EGC). However, a low CR rate does not mean that it is unreasonable to schedule ER of UD-EGC. If ER is in fact curative, the long-term outcomes including survival rate are excellent. Quality of life is good because maximal stomach preservation is possible. However, UD-EGC and D-EGC differ histologically. Thus, when ER is contemplated to treat UD-EGC, a careful approach employing strict criteria is essential because the biology of UD-EGC and D-EGC differ.

Undifferentiated embryonal sarcoma of liver in an old female:Case report and review of the literature

The clinical characteristics of undifferentiated(embryonal) sarcoma of the liver(UESL) were investigated and the best treatment modalities were recommended.Both histology and immuno-histochemistry demonstrated the cellular features of this peculiar tumor.The tumor size was 12 cm × 9 cm × 8 cm in the right liver lobe.The patient underwent surgical resection of the tumor.The postoperative recovery was uneventful and she died eight months after diagnosis.The tumor showed mixed spindle and polygonal cells within the myxoid matrix.Some tumor cells contained eosinophilic hyaline globules that were positive for resistant diastase.Immunohistochemistry showed positive vimentin.Stellate and spindle cells were positively stained with alpha-1-antichymotrypsin(AACT) and CD68.This case indicates that UESL is not obviously differentiated in old-aged adults.

Undifferentiated embryonal sarcoma of the liver:Clinical characteristics and outcomes

BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a rare liver malignancy originating from primary mesenchymal tissue.The clinical manifestations,laboratory tests,and imaging examinations of the disease lack specificity and the preoperative misdiagnosis rate is high.The overall prognosis is poor and survival rate is low.AIM To investigate the diagnosis,treatment,and prognosis of UESL.METHODS We performed a retrospective,single-center cohort study in Shengjing Hospital of China Medical University,which is a central hospital in northeast China.From 2005 to 2017,we recruited 14 patients with pathologically confirmed UESL.We analyzed the clinical manifestations,laboratory tests,imaging examinations,pathological examinations,therapy,and prognosis of these patients.RESULTS There were nine males and five females aged 2-60 years old included in the study.The major initial symptoms were abdominal pain(71.43%)and fever(57.14%).Preoperative laboratory tests revealed that seven patients had increased leukocyte levels,four showed a decrease in hemoglobin levels,seven patients had increased glutamyl transpeptidase levels,nine had increased lactate dehydrogenase levels,and three showed an increase in carbohydrate antigen 199.There was no difference in the rate of misdiagnosis in preoperative imaging examinations of UESL between adults and children(6/6 vs 5/8,P=0.091).The survival rate after complete resection was 6/10,while that after incomplete resection was 0/4(P=0.040),suggesting that complete resection is important to improve survival rate.In total,five out of the eight children achieved survival.During the follow-up,the maximum survival time was shown to be 11 years and minimum survival time was 6 mo.Six adult patients relapsed late after surgery and all of them died.CONCLUSION Preoperative imaging examination for UESL has a high misdiagnosis rate.Multidisciplinary collaboration can improve the diagnostic accuracy of UESL.Complete surgical resection is the first choice for treatment of UESL.

Long-term outcomes of endoscopic submucosal dissection and surgery for undifferentiated intramucosal gastric cancer regardless of size

BACKGROUND The clinical outcomes of endoscopic submucosal dissection(ESD)for undifferentiated(UD)intramucosal early gastric cancer(EGC)compared with those of surgery,regardless of lesion size,are not well known.Furthermore,there is a concern regarding the treatment plan before and after ESD in cases of UD intramucosal EGC within expanded indications.AIM To evaluate clinical outcomes of ESD compared with those of surgery in UD intramucosal EGC patients regardless of tumor size.METHODS We enrolled patients with UD intramucosal EGC after ESD with complete resection or surgery from January 2005 to August 2020 who met the within or beyond expanded indications with lesion size>2 cm(the only non-curative factor).Overall,123 and 562 patients underwent ESD and surgery,respectively.After propensity-score matching,clinical and long-term outcomes,i.e.,recurrencefree survival(RFS)and overall survival(OS),were analyzed.The multivariable Cox proportional hazard model with treatment modality and ESD indication was used to evaluate the recurrence risk.RESULTS After matching,119 patients each were finally enrolled in the ESD and surgery groups.The median length of hospital stay was shorter in the ESD group than surgery group(4.0 vs 9.0 days,P<0.001).Four cases of recurrence after ESD were local recurrences,all of which occurred within 1 year.Total recurrence was seven(5.9%)and two(1.7%)in the ESD and surgery groups,respectively.No difference was observed between the two groups with respect to OS(P=0.948).However,the ESD group had inferior RFS compared with the surgery group(P=0.031).ESD was associated with the risk of recurrence after initial treatment in all enrolled patients(hazard ratio,5.2;95%confidence interval:1.0-25.8,P=0.045).CONCLUSION Although OS was similar between the two groups,surveillance endoscopy was important for the ESD than for the surgery group because RFS was inferior and local recurrence was an issue.

Machine learning-based gray-level co-occurrence matrix signature for predicting lymph node metastasis in undifferentiated-type early gastric cancer

BACKGROUND The most important consideration in determining treatment strategies for undifferentiated early gastric cancer(UEGC)is the risk of lymph node metastasis(LNM).Therefore,identifying a potential biomarker that predicts LNM is quite useful in determining treatment.AIM To develop a machine learning(ML)-based integral procedure to construct the LNM gray-level co-occurrence matrix(GLCM)prediction model.METHODS We retrospectively selected 526 cases of UEGC confirmed through pathological examination after radical gastrectomy without endoscopic treatment in four tertiary hospitals between January 2015 to December 2021.We extracted GLCM-based features from grayscale images and applied ML to the classification of candidate predictive variables.The robustness and clinical utility of each model were evaluated based on the following factors:Receiver operating characteristic curve(ROC),decision curve analysis,and clinical impact curve.RESULTS GLCM-based feature extraction significantly correlated with LNM.The top 7 GLCM-based factors included inertia value 0°(IV_0),inertia value 45°(IV_45),inverse gap 0°(IG_0),inverse gap 45°(IG_45),inverse gap full angle(IG_all),Haralick 30°(Haralick_30),Haralick full angle(Haralick_all),and Entropy.The areas under the ROC curve(AUCs)of the random forest classifier(RFC)model,support vector machine,eXtreme gradient boosting,artificial neural network,and decision tree ranged from 0.805[95%confidence interval(CI):0.258-1.352]to 0.925(95%CI:0.378-1.472)in the training set and from 0.794(95%CI:0.237-1.351)to 0.912(95%CI:0.355-1.469)in the testing set,respectively.The RFC(training set:AUC:0.925,95%CI:0.378-1.472;testing set:AUC:0.912,95%CI:0.355-1.469)model that incorporates Entropy,Haralick_all,Haralick_30,IG_all,IG_45,IG_0,and IV_45 had the highest predictive accuracy.CONCLUSION The evaluation results indicate that the method of selecting radiological and textural features becomes more effective in the LNM discrimination against UEGC patients.Additionally,the MLbased prediction model developed using the RFC can be used to derive treatment options and identify LNM,which can hence improve clinical outcomes.

Undifferentiated pleomorphic sarcoma of the liver presenting as a unilocular cyst

BACKGROUND:A malignant fibrous histiocytoma,recently referred to as an undifferentiated pleomorphic sarcoma (UPS),is very rare in the liver,and only 34 cases of primary hepatic malignant fibrous histiocytoma have been reported in the English literature. METHODS:We report a rare case of a hepatic UPS presenting as a unilocular cystic lesion with respect to histopathologic features,the newly revised diagnostic criteria,and the differential diagnosis. RESULTS:A 60-year-old man presented for evaluation of epigastric pain of 7 months duration.Abdominal computed tomography revealed a hypodense,unilocular cystic mass in the right lobe of the liver,measuring 14.0×11.1 cm.A right lobectomy was performed.Grossly,the cut surface showed a single,well-circumscribed unilocular cystic tumor mass containing dark red-brown necrotic debris and blood clots, which occupied most of the mass.Microscopically,the tumor consisted of haphazardly arranged mononuclear pleomorphic tumor cells,admixed with abundant osteoclast- like multinucleated giant cells.Immunohistochemically,the tumor cells expressed vimentin only.The histopathologic and immunohistochemical findings were compatible with a UPS.The patient is alive and well 41 months after surgery without recurrence. CONCLUSIONS:Clinically,most of the hepatic UPSs are solid masses.Only two cases have presented as multilocular cystic masses.A primary hepatic UPS presenting as a unilocular cyst has never been reported.A UPS should be included in the differential diagnosis of unilocular cystic lesions in the liver.

Reevaluation of the expanded indications in undifferentiated early gastric cancer for endoscopic submucosal dissection

BACKGROUND Although the criteria for the indication of endoscopic submucosal dissection(ESD)for undifferentiated early gastric cancer(UD-EGC)have been recently proposed,accumulating reports on the non-negligible rate of lymph node metastasis(LNM)after indicated ESD raise questions on the reliability of the current criteria.AIM To investigate the prevalence and risk factors of LNM in UD-EGC cases meeting the expanded indication for ESD.METHODS We retrospectively reviewed 4780 UD-EGC cases that underwent surgical resection between January 2008 and February 2019 at Asan Medical Center,a tertiary university hospital in Korea.To identify the risk factors of LNM of UDEGC meeting the expanded criteria for ESD,we performed a case-control study by matching the cases with LNM to those without at a ratio of 1:4.We reviewed the clinical,endoscopic,and histologic features of the cases to identify features with a significant difference according to the presence of LNM.Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios(ORs).RESULTS Of the 4780 UD-EGC cases,1240(25.9%)were identified to meet the expanded indication for ESD.Of the 1240 cases,14(1.1%)cases had LNM.Among the various clinical,endoscopic,and histopathological features that were evaluated,mixed histology(tumors consisting of 10%-90%of signet ring cells)had a marginally significant association(P=0.059)with the risk of LNM.Moreover,diffuse blurring of the muscularis mucosae(MM)underneath the tumorous epithelium,a previously unrecognized histologic feature,had a significant association with the absence of LNM(P=0.028).Multivariate logistic regression analysis showed that the blurring of MM was the only explanatory variable significantly associated with a reduced risk of LNM(OR:0.12,95%CI:0.02-0.95;P=0.045).CONCLUSION The risk of LNM is higher than expected when using the current expanded indication for UDEGC.Histological evaluation could provide useful clues for reducing the risk of LNM.

Neoadjuvant transcatheter arterial chemoembolization and systemic chemotherapy for the treatment of undifferentiated embryonal sarcoma of the liver in children

BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a rare and aggressive mesenchymal tumor in children.Herein,we describe our experience in neoadjuvant therapy(NAT)and subsequent surgery for the treatment of UESL in children.AIM To evaluate the efficacy of NAT and explore a new choice for successful operation of UESL in children.METHODS We retrospectively analyzed six patients newly diagnosed with unresectable UESL who received NAT and then surgery at our center between January 2004 and December 2019.The tumor was considered unresectable if it involved a large part of both lobes of the liver or had invaded the main hepatic vessels or inferior vena cava.The NAT included preoperative transcatheter arterial chemoembol ization(TACE)and systemic chemotherapy.The patients were 4 boys and 2 girls with a mean age of 7 years.The longest tumor at presentation ranged from 8.6 to 14.8 cm(mean,12 cm).Extrahepatic metastases were present in 2 cases.Preoperative systemic chemotherapy was administered 3 wk after TACE.Tumor resection was performed 3 wk after one or two cycles of NAT.The patients received systemic chemotherapy after surgery.RESULTS All patients successfully underwent NAT and complete resection.The tumor volumes decreased by 18.2%–68.7%,with a mean decrease of 36%after 1 cycle of NAT(t=3.524,P=0.017).According to the Response Evaluation Criteria In Solid Tumors criteria,4 patients had a partial response and underwent surgery,while 2 had stable disease and received another cycle of NAT before surgery.Massive tumor necrosis was seen on pathological examination of the surgical specimen:>90%necrosis in two,>50%necrosis in three,and 25%necrosis in 1,with an average of 71.8%.Post-NAT complications included fever,nausea and vomiting,and mild bone marrow suppression.Elevated alanine transaminase levels occurred in all patients,which returned to normal within 7–10 d after treatment.No cardiac or renal toxicity,severe hepatic dysfunction,bleeding and nontarget embolization were observed in the patients.The median follow-up period was 8 years with an overall survival of 100%.CONCLUSION NAT effectively reduced tumor volume,cleared the tumor margin,and caused massive tumor necrosis.This may be a promising choice for successful surgery of UESL in children.

Undifferentiated (embryonal) sarcoma of liver in adult: A case report

We report a case of undifferentiated (embryonal)sarcoma of the liver (UESL), which showed cystic formation in a 20-year-old man with no prior history of any hepatitis or liver cirrhosis. He was admitted with abdominal pain and a palpable epigastric mass. The physical examination findings were unremarkable except for a tenderness mass and the results of routine laboratory studies were all within normal limits. Abdominal ultrasound and computed tomography (CT) both showed a cystic mass in the left hepatic lobe. Subsequently, the patient underwent a tumor excision and another two times of hepatectomy because of tumor recurrence.Immunohistochemical study results showed that the tumor cells were positive for vimentin, alpha-1-antichymotrypsin (AACT) and desmin staining, and negative for alphafetoprotein (AFP), and eosinophilic hyaline globules in the cytoplasm of some giant cells were strongly positive for periodic acid-Schiff (PAS) staining. The pathological diagnosis was UESL. The patient is still alive with no tumor recurrence for four months.

Small undifferentiated intramucosal gastric cancer with lymph-node metastasis:Case report

It has been reported recently that small undifferentiated intramucosal early gastric cancer(EGC) < 20 mm in size without any lymphovascular involvement or ulcerative findings had virtually no risk of lymph-node(LN) metastasis.Consequently,the indications for endoscopic resection were expanded to include such undifferentiated EGC lesions.We describe herein a case of a small undifferentiated intramucosal EGC < 20 mm in size without lymphovascular involvement or ulcerative findings that involved lymph-node metastasis.A 57-year-old female underwent pylorus preserving gastrectomy as standard treatment for an undifferentiated EGC 15 mm in size without any ulcerative finding.The surgical specimen revealed a signet-ring cell carcinoma with a moderately to poorly differentiated adenocarcinoma limited to the mucosa that was 15 mm in size with no lymphovascular involvement or ulcerative findings.This case involved LN metastasis,however,and the lesion was diagnosed as pathological stage ⅡA(T1N2M0) according to the Japanese Classification of Gastric Carcinoma.

Non-keratinising undifferentiated nasopharyngeal-type carcinoma of the lacrimal sac

Dear Editor,We present a case of non-keratinising undifferentiated nasopharyngeal-type carcinoma(UNPC)of nasolacrimal sac and review the previously reported cases and their treatment options and prognosis.Squamous cell carcinoma with a characteristic lymphoid stroma is a type of poorly differentiated carcinoma typically occurring in the nasopharynx[1].Non-keratinising UNPC,so called lymphoepithelioma-like carcinoma(LELC),of the lacrimal

Neither hereditary periodic fever nor periodic fever, aphthae, pharingitis, adenitis: Undifferentiated periodic fever in a tertiary pediatric center

AIM To describe the frequency and clinical characteristics of patients with undifferentiated periodic fever(UPF) and to investigate whether a clinical classification of UPF based on the PRINTO-Eurofever score can help predicting the response to treatment and the outcome at follow-up.METHODS Clinical and therapeutic information of patients with recurrent fever who presented at a single pediatric rheumatology center from January 2006 through April 2016 were retrospectively collected. Patients with a clinical suspicion of hereditary periodic fever(HPF) syndrome and patients with clinical picture of periodic fever, aphthae, pharingitis, adenitis(PFAPA) who were refractory to tonsillectomy underwent molecular analysis of five HPF-related genes: MEFV(NM_000243.2), MVK(NM_000431.3), TNFRSF1 A(NM_001065.3), NLRP3(NM_001079821.2), NLRP12(NM_001277126.1). All patients who had a negative genetic result were defined as UPF and further investigated. PRINTO-Eurofever score for clinical diagnosis of HPF was calculated in all cases. RESULTS Of the 221 patients evaluated for periodic fever, twelve subjects with a clinical picture of PFAPA who were refractory to tonsillectomy and 22 subjects with a clinical suspicion of HPF underwent genetic analysis. Twenty-three patients(10.4%) resulted negative and were classified as UPF. The median age at presentation of patients with UPF was 9.5 mo(IQR 4-24). Patients with UPF had a higher frequency of aphthae(52.2% vs 0%, P = 0.0026) and musculoskeletal pain(65.2% vs 18.2%, P = 0.0255) than patients with genetic confirmed HPF. Also, patients with UPF had a higher frequency of aphthous stomatitis(52.2% vs 10.7%, P < 0.0001), musculoskeletal pain(65.2% vs 8,0%, P < 0.0001), and abdominal pain(52.2% vs 4.8%, P < 0.0001) and a lower frequency of pharyngitis(56.6% vs 81.3%, P = 0.0127) compared with typical PFAPA in the same cohort. Twenty-one of 23 patients with UPF(91.3%) received steroids, being effective in 16; 13(56.2%) were given colchicine, which was effective in 6. Symptoms resolution occurred in 2 patients with UPF at last follow-up. Classification according to the PRINTOEurofever score did not correlate with treatment response and prognosis. CONCLUSION UPF is not a rare diagnosis among patients with periodic fever. Clinical presentation place UPF half way on a clinical spectrum between PFAPA and HPF. The PRINTOEurofever score is not useful to predict clinical outcome and treatment response in these patients.