Clinical analysis of multiple primary gastrointestinal malignant tumors:A 10-year case review of a single-center

BACKGROUND Multiple primary malignant tumors(MPMTs)was first described by Billroth as early as 1889,with the first report published by Warren and Gates in 1932.Since then,numerous cases have been reported.A literature review of 1104269 patients with cancer revealed that the incidence of MPMTs ranged from 0.73 to 11.7%.In recent years,however,there has been a significant upward trend in the incidence of this phenomenon,which may be associated with many different factors,including the advancement of modern diagnostic procedures facilitating the examination and diagnosis of more MPMTs,increased exposure to chemotherapy and radiotherapy that exacerbate the risk of new malignant tumors in patients with cancer,and prolonged survival of patients with cancer allowing sufficient time for the development of new primary cancers.AIM To analyze the incidence,clinical features,treatment factors,prevalence,and prognosis of patients with MPMTs in the gastrointestinal tract treated in a single center.Additionally,we analyzed the different tumor combinations,time interval between the occurrence of tumors,and staging.METHODS This retrospective cohort study analyzed 8059 patients with pathologically confirmed gastrointestinal malignant tumors treated at the Gansu Province Hospital in Lanzhou,Gansu,China between June 2011 and June 2020.Of these,85 patients had MPMTs.The clinical features,treatment factors,prevalence,and prognosis of this latter cohort were analyzed.RESULTS The incidence of MPMTs in patients with gastrointestinal malignant tumors was 1.05%(85/8059),including 83 double primary malignant tumors and two triple primary malignant tumors of which 57(67.06%)were synchronous MPMTs(SMPMTs)and 28(32.94%)were metachronous MPMTs(MMPMTs).The most frequent associations were found between the rectum colon cancers within the SMPMT category and the gastric-colon cancers within the MMPMT category.For the MMPMTs,the median interval was 53 months.The overall 1-,3-and 5-year survival rates from diagnosis of the first primary cancer were 91.36%,65.41%,and 45.97%,respectively;those from diagnosis of the second primary cancer were 67.90%,29.90%,and 17.37%,respectively.CONCLUSION MPMTs in the gastrointestinal tract have a high incidence and poor prognosis.Thus,it is necessary to perform both gastroscopy and colonoscopy in patients with gastrointestinal tumors.Multidisciplinary comprehensive diagnosis and treatment may improve the diagnosis rate and treatment efficiency of MPMTs.

Heterochronous multiple primary prostate cancer and lymphoma:A case report

BACKGROUND Multiple primary malignant tumors(MPMTs)are rare type of cancer,especially when solid tumors are the first and lymphoma is the second primary malignancy.We report a patient with heterochronous MPMTs consisting of prostate cancer and rectal diffuse large B-cell lymphoma(DLBCL).CASE SUMMARY We report a 77-year-old male patient diagnosed with prostate cancer who was treated with radiation therapy and one year of endocrine therapy with bicalutamide(50 mg per day)and an extended-release implant of goserelin(1/28 d).Seven years later,rectal DLBCL with lung metastases was found.CONCLUSION Although rare,the possibility of prostate cancer combined with a double primary cancer of DLBCL can provide a deeper understanding.

Synchronous multiple primary malignant neoplasms in breast,kidney,and bilateral thyroid:A case report

BACKGROUND Multiple primary malignant neoplasms(MPMNs)are rare,while synchronous MPMNs(SMPMNs)are even less common.Owing to the progression of medical technology and the extension of life expectancy,its incidence is gradually increasing.CASE SUMMARY Although reports of breast and thyroid dual cancers are common,cases of an additional diagnosis of kidney primary cancer within the same individual are rare.CONCLUSION We present a case of simultaneous MPMN of three endocrine organs,reviewing the relevant literature to enhance our understanding of SMPMNs while emphasizing the increasingly important need for accurate diagnosis and multidisciplinary management whenever this challenging situation arises.

Clinical analysis of multiple primary malignancies in the digestive system: A hospital-based study

AIM： To analyze the characteristics of multiple primary malignancies （MPMs） of digestive system; including incidence, types of tumor combinations, time intervals between development of multiple tumors, clinical course,and prognostic factors affecting survival and mortality.METHODS： Data from a total of 129 patients treated from January 1991 to December 2000 for pathologically proved MPMs, including at least one originating from the digestive system, were reviewed retrospectively.RESULTS： Among 129 patients, 120 （93.02%） had two primary cancers and 9 （6.98%） had three primary cancers. The major sites of MPMs of the digestive system were large intestine, stomach, and liver. Associated nondigestive cancers included 40 cases of gynecological cancers, of which 31 were carcinoma of cervix and 10 cases of genitourinary cancers, of which 5 were bladder cancers. Other cancers originated from the lung, breast,nasopharynx, larynx, thyroid, brain, muscle, and skin.Reproductive tract cancers, especially cervical, ovarian,bladder, and prostate cancers were the most commonlyassociated non-G! cancers, followed by cancer of the lung and breasts. Forty-three cases were synchronous, while the rest （86 cases） were metachronous cancers. Staging of MPMs and treatment regimes correlated with the prognosis between survival and non-survival groups.CONCLUSION： As advances in cancer therapy bring about a progressively larger percentage of long-term survivors, the proportion of patients with subsequent primary lesions will increase. Early diagnosis of these lesions, based on an awareness of the possibility of second and third cancers, and multidiscipiinary treatment strategies will substantially increase the survival of these patients.

Clinical features and survival of patients with multiple primary malignancies

BACKGROUND Multiple primary malignancies(MPM)are characterized by two or more primary malignancies in the same patient,excluding relapse or metastasis of prior cancer.We aimed to elucidate the clinical features and survival of MPM patients.AIM To elucidate the clinical features and survival of MPM patients.METHODS A retrospective study of MPM patients was conducted in our hospital between June 2016 and June 2019.Overall survival(OS)was calculated using the Kaplan-Meier method.The log-rank test was used to compare the survival of different groups.RESULTS A total of 243 MPM patients were enrolled,including 222 patients with two malignancies and 21 patients with three malignancies.Of patients with two malignancies,51(23.0%)had synchronous MPM,and 171(77.7%)had metachronous MPM.The most common first cancers were breast cancer(33,14.9%)and colorectal cancer(31,14.0%).The most common second cancers were non-small cell lung cancer(NSCLC)(66,29.7%)and gastric cancer(24,10.8%).There was no survival difference between synchronous and metachronous MPM patients(36.4 vs 35.3 mo,P=0.809).Patients aged>65 years at diagnosis of the second cancer had a shorter survival than patients≤65 years(28.4 vs 36.4 mo,P=0.038).Patients with distant metastasis had worse survival than patients without metastasis(20.4 vs 86.9 mo,P=0.000).Following multivariate analyses,age>65 years and distant metastasis were independent adverse prognostic factors for OS.CONCLUSION During follow-up of a first cancer,the occurrence of a second or more cancers should receive greater attention,especially for common concomitant MPM,to ensure early detection and treatment of the subsequent cancer.

High incidence combination of multiple primary malignant tumors of the digestive system

BACKGROUND Clinical reports of multiple primary malignant tumors(MPMTs)in the digestive system are increasing.In China,although the survival rate of patients with MPMTs is increasing,the quality of life is very low.Many patients have reached the advanced stage when the second primary tumor is found,resulting in no early intervention and treatment.This is due to the misunderstanding of MPMTs by clinicians,who treat such tumors as metastases.Therefore,before a patient has a second primary tumor,doctors should understand some common combinations of digestive system MPMTs to provide clinical guidance to the patient.AIM To explore the high incidence combination of digestive system MPMTs under heterochronism and synchronization.METHODS A total of 1902 patients with MPMTs at Peking Union Medical College Hospital were analyzed retrospectively.They were divided into metachronous MPMT and synchronous MPMT groups,and then the high incidence combinations of the first primary cancer and the second primary cancer in metachronous cancer and synchronous cancer were sorted.Sex and age differences between metachronous and synchronous tumors were tested by the chi square test and t test,respectively.A P value<0.05 was considered as statistically significant,and SPSS version 26.0(SPSS Inc.,Chicago,Illinois,United States)was used for statistical analysis.RESULTS Among the 1902 patients with MPMTs confirmed by pathology,1811(95.2%)cases were secondary primary cancers,89(4.7%)cases were tertiary primary cancers,and 2(0.1%)cases were quaternary primary cancers.Most(88.2%)of the secondary primary cancers were identified as metachronous multiple primary cancers six months after diagnosis of the first primary cancer.The top ten most common MPMTs in the first primary cancer group ranged from high to low as follows:Breast cancer,thyroid cancer,nonuterine cancer,lung cancer,colon cancer,kidney cancer,uterine cancer,bladder cancer,rectal cancer,and gastric cancer.The highest incidence rate of the first primary cancer in male metachronous cancer was lung cancer(11.6%),the highest incidence rate of the second primary cancer was still lung cancer(24.9%),the highest incidence rate of the first primary cancer in female metachronous cancer was breast cancer(32.7%),and the highest incidence rate of the second primary cancer was lung cancer(20.8%).Among them,breast cancer,nonuterine cancer and uterine cancer were female-specific malignant tumor types,and thyroid cancer also accounted for 79.6%of female patients.The top five metachronous cancer combinations,independent of female-specific malignant tumor types and thyroid cancer,were colon cancer and lung cancer(26 cases),kidney cancer and lung cancer(25 cases),rectal cancer and lung cancer(20 cases),gastric cancer and lung cancer(17 cases),and bladder cancer and lung cancer(17 cases).The most common synchronous cancer combination was colon cancer and rectal cancer(15 cases).CONCLUSION Screening for lung cancer should be performed six months after the detection of colon cancer while rectal cancer screening should be performed within six months.

Multiple primary malignancies-hepatocellular carcinoma combined with splenic lymphoma:A case report

BACKGROUND Primary liver cancer is one of the most common malignant tumours,while primary splenic lymphoma is a rare malignancy.Thus,cases of hepatocellular carcinoma(HCC)combined with splenic lymphoma are extremely rare.CASE SUMMARY We present a 62-year-old woman who was admitted to the Interventional Radiology Department with a lump in the spleen and liver as well as multiple enlarged lymph nodes visible by ultrasound.Contrast-enhanced computed of the abdomen revealed a circular,low-density,shallow mass(approximately 2.6 cm in diameter)in the left intrahepatic lobe and multiple round,low-density shadows in the spleen with clear boundaries(maximum diameter 7.6 cm).Based on the characteristic clinical symptoms and explicit radiological findings,the clinical diagnosis was HCC with metastasis to the liver portal,retroperitoneal lymph nodes,and spleen.After transcatheter arterial chemoembolization and sequential radiofrequency ablation,the-fetoprotein level returned to the normal range,and the hepatitis B cirrhosis improved.In addition,splenic tumour biopsy confirmed the diagnosis of primary malignant lymphoma,which went into remission after chemotherapy.CONCLUSION HCC with primary splenic non-Hodgkin lymphoma is extremely rare and easily misdiagnosed.Better understanding would facilitate early diagnosis,treatment and prognosis.

Simultaneous multiple primary malignancies diagnosed by endoscopic ultrasound-guided fine-needle aspiration:A case report

BACKGROUND Multiple primary malignancies(MPMs)refer to more than one primary malignancy in the same or separate organs of the same patient,and MPMs are considered when different histological characteristics are detected in epidemiological studies.Herein,we report a case presumed to be primary pancreatic cancer with multiple liver metastases by positron-emission tomography/computed tomography(PET/CT)and confirmed to be synchronous liver and pancreatic MPMs by endoscopic ultrasound-guided fine-needle aspiration(EUSFNA).CASE SUMMARY A 50-year-old man was referred to our hospital due to abdominal discomfort for 2 mo.Abdominal CT at a local hospital revealed a pancreatic mass with multiple liver nodules.After being transferred to our hospital,PET/CT confirmed all these lesions to have elevated metabolic activity,and therefore primary pancreatic cancer with multiple liver metastases was considered.EUS-guided liver aspiration unexpectedly found signet-ring cells with a high Ki-67 positive rate(20%),while EUS-guided pancreatic aspiration detected pancreatic neuroendocrine cells with a relatively low Ki-67 positive rate(1%).The final diagnosis from the multidisciplinary team was simultaneous liver and pancreatic MPMs.The patient returned to his local hospital for neoadjuvant chemotherapy and surgery,and he is still alive during the 6-mo postoperative follow-up.CONCLUSION Although rare,MPMs should be considered when treating pancreatic mass with suspected metastatic lesions,and EUS-FNA has proved minimally invasive and accurate.

Genetic characteristics of a patient with multiple primary cancers:A case report

BACKGROUND Two or multiple primary malignant neoplasms(MPMNs)rarely occur in the same patient.It has been reported that MPMNs are easily misdiagnosed as the recurrence or metastasis of malignancies in clinical practice,affecting the choice of treatment for the patients,thereby resulting in the delay of optimal diagnosis.Next generation sequencing(NGS)can be used to distinguish between multiple primary lung cancers and intrapulmonary metastasis,and may distinguish the origin of tumours in different sites of the body.CASE SUMMARY We report the case of 66-year-old woman who suffered from different malignant neoplasms in the rectum and esophageal and gastrointestinal tract.The first neoplasm rectal adenocarcinoma was diagnosed and removed in 2016.The second and third lesions were diagnosed with esophageal squamous-cell carcinoma(ESCC)and gastrointestinal stromal tumour(GIST),respectively,in 2019.Nextgeneration whole exome sequencing was performed on the tissue specimens of rectal carcinoma,esophageal cancer,GIST,and white blood cells to investigate the relationship between malignancies at different timeframe and determine whether the ESCC and GIST evolved from the rectal adenocarcinoma.Mutations including v-Ki-ras2-Kirsten rat sarcoma viral oncogene homolog,adenomatosis polyposis coli,and mothers against decapentaplegic homolog 4 were detected in rectal adenocarcinoma sample,mast/stem cell growth factor receptor was detected in GIST tissue,and lysine methyltransferase 2D was detected in ESCC specimen.Overall,ESCC and GIST were not genetically evolved from rectal adenocarcinoma,and this patient did not have a trunk driven clone.CONCLUSION NGS is an effective tool to study clonal evolution of tumours and distinguish between MPMNs and intrapulmonary metastasis.

Synchronous multiple primary malignancies of the esophagus, stomach, and jejunum: A case report

BACKGROUND Treatment of synchronous multiple primary malignancies is quite often very challenging.Herein,we report on a rare case of synchronous multiple primary malignancies in the esophagus,stomach,and jejunum.CASE SUMMARY A 50-year-old man who was a heavy drinker and smoker with a poor diet,and had a family history of cancer sought treatment due to dysphagia lasting for 4 mo.He was finally diagnosed with lower esophageal squamous cell carcinoma(pT3N2M0,G2,stage IIIB),gastric angular adenocarcinoma(pT3N2M0,G2-G3,stage IIIA)with greater omental lymph node metastasis,and jejunal stromal tumor(high risk).The high-risk jejunal stromal tumor was found during surgery.In spite of radical resection and adjuvant chemotherapy,lymph node metastasis occurred 21 mo later.The patient responded poorly to additional chemotherapy and refused further examination and therapy.He died of widespread metastases 33 mo after surgery.CONCLUSION This case indicates a poor prognosis of synchronous multiple advanced primary malignancies and the importance of comprehensive assessment in the population at high risk for cancer.

Metachronous primary esophageal squamous cell carcinoma and duodenal adenocarcinoma:A case report and review of literature

BACKGROUND The prevalence of multiple primary malignant neoplasms(MPMNs)is increasing in parallel with the incidence of malignancies,the continual improvement of diagnostic models,and the extended life of patients with tumors,especially those of the digestive system.However,the co-existence of MPMNs and duodenal adenocarcinoma(DA)is rarely reported.In addition,there is a lack of compre-hensive analysis of MPMNs regarding multi-omics and the tumor microenvir-onment(TME).CASE SUMMARY In this article,we report the case of a 56-year-old man who presented with a complaint of chest discomfort and abdominal distension.The patient was diagnosed with metachronous esophageal squamous cell carcinoma and DA in the Department of Oncology.He underwent radical resection and chemotherapy for the esophageal tumor,as well as chemotherapy combined with a programmed death-1 inhibitor for the duodenal tumor.The overall survival was 16.6 mo.Extensive evaluation of the multi-omics and microenvironment features of primary and metastatic tumors was conducted to:(1)Identify the reasons responsible for the poor prognosis and treatment resistance in this case;and(2)Offer novel diagnostic and therapeutic approaches for MPMNs.This case demonstrated that the development of a second malignancy may be independent of the location of the first tumor.Thus,tumor recurrence(including metastases)should be distinguished from the second primary for an accurate diagnosis of MPMNs.CONCLUSION Multi-omics characteristics and the TME may facilitate treatment selection,improve efficacy,and assist in the prediction of prognosis.Core Tip:Multiple primary malignant neoplasms(MPMNs)are increasingly prevalent in clinical practice,most frequently in the digestive system.We report a rare case of MPMN with a combination of esophageal squamous cell carcinoma and duodenal adenocarcinoma.According to PubMed-indexed literature,there are no standard guidelines or expert consensus on the etiology and comprehensive treatment.We also conducted a detailed study of the features of primary and metastatic tumors.The aim of this report was to identify the reasons responsible for the poor prognosis and treatment resistance in this case through histological data and provide new diagnostic and treatment directions for MPMNs.INTRODUCTION Multiple primary malignant neoplasms(MPMNs),also termed multiple primary cancers,refer to two or more primary tumors that occur simultaneously or sequentially in a single or multiple organs[1].According to the time interval from the diagnosis of the first tumor,MPMNs are divided into synchronous cancer(SC)(<6 mo)and metachronous cancer(MC)(≥6 mo)[2].The detection rate of the second or multiple primary tumors is also on the rise due to newer diagnostic methods and treatments,as well as the longer survival times of patients with cancer.MPMNs are most commonly reported in the digestive system;however,their occurrence in combination with duodenal adenocarcinoma(DA)is extremely rare.In this article,we describe the case of a patient who had metachronous esophageal squamous cell carcinoma(ESCC)and DA with multiple metastases.In this analysis,we thoroughly examined the multi-omics features and tumor-related immune microenvironment.OUTCOME AND FOLLOW-UP The patient was eventually followed up until clinical death on June 18,2022(Figure 2),with an overall survival 16.6 mo.

Heterochronic triple primary malignancies with Epstein-Barr virus infection and tumor protein 53 gene mutation:A case report and review of literature

BACKGROUND The diagnosis and etiology of multiple primary malignant neoplasms(MPMNs)are difficult to establish.Here,we report a case of heterochronic triple primary malignancies with gastric cancer,nasopharyngeal squamous cell cancer,and then rectal cancer.CASE SUMMARY The patient was first diagnosed with gastric cancer at the age of 33 in 2014 and underwent distal gastrectomy and gastrojejunostomy and six cycles of adjuvant chemotherapy.Three years later,he was diagnosed with nasopharyngeal cancer and treated with radical chemoradiotherapy in 2017.Recently,a mass in the middle of the rectum was resected and reported as ulcerative,moderately to poorly differentiated adenocarcinoma.Research on the etiology of MPMNs showed that Epstein-Barr virus(EBV)infection may be the cause of gastric cancer and nasopharyngeal squamous cell cancer since these two primary lesions were positive for transcripts of EBV-encoded ribonucleic acid using an in situ hybridization EBV-encoded ribonucleic acid probe in formalin-fixed,paraffinembedded tissue.The cause of rectal cancer may be due to a somatic mutation of tumor protein 53 gene in exon 8(c.844C>T,p.Arg282Trp)through highthroughput sequencing for the rectal cancer.Appropriate standard therapy for each primary cancer was administered,and the patient has no evidence of cancer disease to date.CONCLUSION To our knowledge,this is the first report on heterochronic triple primary malignancies whose cause may be associated with EBV infection and tumor protein 53 genetic mutations.The etiological research may not only elucidate the cause of MPMN but also has implications in clinical management.

Multiple primary malignancies including colon, stomach, lung, breast, and liver cancer： a case report and literature review

Multiple primary malignancies in a single patient are relatively rare but have increase in frequency in recent decades. This may be a result of medical advancements in diagnostic and therapeutic strategies, a possible effect of new carcinogens in the industrial environment, and longer life span allowing another primary cancer to develop. Among those with multiple primary malignancies, double cancer is commonly seen, while triple cancers occur in 0.5% of patients, and quadruple or quintuple cancers occur in only less than 0.1% of the population.

Multiple primary malignant neoplasms of three early cancer lesions： a case report

Multiple primary malignant neoplasms （MPMNs） are rarely reported and it is important to give early diagnosis and proper therapy for these patients. Here reported a case of 62-year-old man with concomitant three early stage cancer lesions in upper gastrointestinal tract, all of which were detected by endoscopy. The first one was an llc-type lesion at angular part of stomach under endoscopy, which was histologically confirmed to be a mucosal well-differentiated adenocarcinoma.The patient underwent a standard radical gastrectomy for the lesion after the failure of endoscopic treatment. The other two neoplasms were observed during follow-up and were indicated as early stage lesions by synthesizing information from endoscopy, endoscopic ultrasonography, computed tomography and biopsy. One displayed as a hyperemic patch （3cm×4 cm in size） located at the part of esophagus 27 cm away from the incisor teeth and was proved to be moderately differentiated squamous cancer by histopathological examination. The other was an llc-type lesion （3.0 cm×3.5 cm in size） located at the part of esophagus 36 cm away from the incisor teeth, and the biopsy result showed a poorly differentiated squamous carcinoma. Both the two lesions were treated with radical radiation because the patient refused surgery management. No recurrence of former lesions or occurrence of novel lesions were observed during post-treatment follow-up, suggesting radical radiation might be effective for this patient.

Synchronous colorectal and lung cancer:Report of three cases

The incidence of synchronous colorectal and lung cancer is relatively rare. We report three cases of patients with tumors located in the rectum, ascending colon, the lower lobe of the left lung, and the upper lobe of the right lung. Synchronous curative resection of the two lesions was performed in two patients, whereas colectomy was performed in an elderly patient with a poor lung function. Pathological examination showed the colorectal cancer was a moderately differentiated adenocarcinoma and the lung cancer was a squamous cell carcinoma. Surgical treatment and postoperative adjuvant chemotherapy for the lung cancer were different from those for colorectal cancer with pulmonary metastasis. If possible, radical resection should be performed for each cancer when synchronicity is found.

Malignant fibrous histiocytoma of the axilla with breast cancer:A case report

BACKGROUND Multiple primary malignant neoplasms refer to multiple tumors with different origins.They may be synchronous or metachronous.The incidence is 0.73%–11.7%.Synchronous cases of breast cancer with sarcoma are rare.CASE SUMMARY Here,we report a 78-year-old female patient admitted to hospital after accidental discovery of a left axillary mass.Preoperative examination revealed a breast mass.Pathology showed left breast cancer and left axillary sarcoma.The patient underwent surgery,endocrine therapy and radiotherapy.She has been followed up for 1 year,and no local recurrence or distant metastasis was observed.CONCLUSION Attention should be paid to multiple primary malignant neoplasms,not limited to the current diagnosis and analysis,avoiding missed diagnosis and misdiagnosis.