Post nephrectomy metachronous testicular metastasis in a case of clear cell renal cell carcinoma (ccRCC).

It is highly uncommon for solid tumours to metastasise to the testis. Here, we report a case of metachronous testicular metastasis from clear cell renal cell cancer (RCC) in a male patient 3 years after left radical nephrectomy. Ultrasound of the scrotum showed a 3.5 cm × 4 cm left testicular mass with normal serum tumour markers. The patient underwent left high inguinal orchidectomy, which revealed metastatic renal cell carcinoma. CT of the chest, abdomen and pelvis showed multiple liver secondaries. Cabozantinib was started for metastatic RCC, and the patient showed no evidence of disease progression in a follow-up of 1 year.

Germline BRCA1-Mutated Synchronous and Metachronous Pancreatic Acinar Cell Carcinoma With Long-Term Survival.

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic neoplasm. Recently, molecular analysis revealed that PACC shows a high frequency of the BRCA1/2 mutation and is likely to be considered a cancer associated with hereditary breast and ovarian cancer (HBOC). Hereditary cancers, including HBOC, are characterized by multifocal and/or metachronous tumors. However, no case reports exist of germline BRCA1-mutated synchronous and metachronous PACC. CASE: A 58-year-old man was diagnosed with synchronous and metachronous PACC at the age of 56 and underwent two surgeries. Ten months after the second surgery, the patient developed multiple liver metastases. Gemcitabine plus nab-paclitaxel therapy was administered as first-line chemotherapy. After seven cycles, computed tomography examination revealed progressive disease (PD). Therefore, modified FOLFIRINOX (mFFX) was administered as second- line chemotherapy. After 19 cycles of mFFX, comprehensive cancer genomic profiling (CGP) identified a BRCA1 pathogenic variant that was confirmed to be germline origin. Accordingly, we treated the patient with olaparib; however, he was diagnosed with PD after 4 months. He subsequently died 5 years and 9 months after the initial surgery, and 3 years and 10 months after chemotherapy. Based on the genetic data of the patients, his family members received genetic counseling followed by cascade testing. Consequently, the same gBRCA1 pathogenic variant was detected in the son and his surveillance for HBOC-related cancers was initiated. CONCLUSION: We diagnosed a 58-year-old man with a synchronous and metachronous PACC with germline BRCA1 pathogenic variant. Considering that PACC is likely to have BRCA1/2 mutations responsible for HBOC, we need to be aware of the possible presence of multifocal and/or metachronous tumors in patients with PACC. Additionally, patients with PACC should undergo genetic examinations, which would be beneficial in determining treatment strategies and health care for blood relatives.

Predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancer.

OBJECTIVES: We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: From EGC patients who underwent ESD, bulk RNA sequencing was performed on non-cancerous gastric mucosa samples at the time of initial EGC diagnosis. This included 23 patients who developed MGC, and 23 control patients without additional gastric neoplasms for over 3 years (1:1 matched by age, sex, and Helicobacter pylori infection state). Candidate differentially-expressed genes were identified, from which biomarkers were selected using real-time quantitative polymerase chain reaction and cell viability assays using gastric cell lines. An independent validation cohort of 55 MGC patients and 125 controls was used for marker validation. We also examined the severity of gastric intestinal metaplasia, a known premalignant condition, at initial diagnosis. RESULTS: From the discovery cohort, 86 candidate genes were identified of which KDF1 and CDK1 were selected as markers for MGC, which were confirmed in the validation cohort. CERB5 and AKT2 isoform were identified as markers related to intestinal metaplasia and were also highly expressed in MGC patients compared to controls (p < 0.01). Combining these markers with clinical data (age, sex, H. pylori and severity of intestinal metaplasia) yielded an area under the curve (AUC) of 0.91 (95% CI, 0.85-0.97) for MGC prediction. CONCLUSION: Assessing biomarkers in non-cancerous gastric mucosa may be a useful method for predicting MGC in EGC patients and identifying patients with a higher risk of developing MGC, who can benefit from rigorous surveillance.

Clinicopathological analysis of patients with dual malignancies: A retrospective study.

BACKGROUND: This study aims to report the increasing incidence of second primary malignancies to better understand the association of multiple primary cancers and the duration of their occurrence. Keeping in view the current trends in dual malignancies and to further emphasize the importance of screening and follow-up diagnosis, we reviewed the records of patients who were diagnosed with dual malignancies. MATERIAL AND METHODS: This is a retrospective observational study. We collected data from the hospital database, of patients presenting with either histologically proven synchronous or metachronous double primaries between January 1, 2017, and December 31, 2021. The time interval to differentiate between synchronous and metachronous has been taken as 6 months. RESULTS: During the period of five years, twenty-three patients presented with dual malignancy. Out of 23 cases, seven were synchronous (30.43%), and 16 were metachronous (69.56%). In the synchronous malignancy group, the most common site of first and second primary malignancy was breast [5 cases (71.4%) and 3 cases (42.8%), respectively]. In the metachronous malignancy group, the most common site of the first primary was breast (7 cases; 43.75%), followed by the head and neck (4 cases; 25%), and the most common site of the second primary was also the breast (6 cases; 37.5%), followed by the lung (5 cases; 31.25%). CONCLUSION: Second primary malignancies are not rare and can occur at any age. Regular follow-up and screening procedures by the treating oncologist can play a major role in early detection followed by appropriate treatment of second primary tumors.

A prospective observational study to assess the epidemiological profile of multiple primary cancers in Eastern India.

BACKGROUND: Multiple primary cancers once thought to be rare have become increasingly common as the lifespan of cancer survivors has increased with availability of better and more effective cancer treatment. However, their exact incidence is not known and data on their epidemiological characteristics are not available. AIM: The aim of this study is to study the epidemiologic characteristics of multiple primary cancers in the eastern region of India. MATERIALS AND METHOD: The study was conducted in the Department of Surgical Oncology, Medical College, Kolkata, from 2017 to 2020 over a period of 3 years. All patients with a diagnosis of second primary as per International Agency for Research on Cancer (IARC) definition or those developing a second primary within the study period were included for analysis. Data were recorded in form of preformed questionnaires. All the cases were followed up for at least 12 months. RESULT: Fifty cases of multiple primary tumors were identified, out of which 21 were synchronous while rest 29 were metachronous type. The male-female ratio was 1:1.2. The median age at presentation for index malignancy was 50 years. The most common malignancy in the synchronous group was a combination of variety of GI cancers (six cases). In the metachronous category, a combination of reproductive cancers (breast, ovary, cervix, and endometrium) along with Gastrointestinal cancer (GI) cancers (colon, rectum) was most frequently found (eight cases). Definite risk factors for multiple primary tumors were identifiable in 10 cases: arsenic exposure in 5 cases, hereditary in 4 cases, and immunosuppression in 1, while in 8 cases, risk factors were only speculative (radiation 5 cases, chemotherapy 3). At the time of the last follow-up, 36 subjects were alive and 3 dead while the status of 11 subjects was unknown. CONCLUSION: This is the first comprehensive study on multiple primary cancers and the largest so far in India. Our study overcomes the shortcoming of previous case series from our subcontinent. The merits of our study include the use of the most accepted IARC definition, updated staging guidelines with long follow-up, and reliable survival data. Additionally, we could identify risk factors in 50% of our subjects. And our study shows various new combinations of cancers not reported before. Clustering of cases in the young adolescent group (25-49) years is also a new finding. We also highlight the existing ambiguity in the way this entity is defined. Demerits include the loss of follow-up data in a significant number of patients.

[Three Cases of Bilateral Metachronous Testicular Tumors].

We present three cases of bilateral metachronous testicular tumors. The patient in case 1 had a history of left orchiectomy for undescended testis at the age of 19. The pathological findings revealed germ cell neoplasia in situ. Twenty-four years later (age＝43), he was diagnosed with right testicular tumor with lymph node and lung metastasis (stage IIIc). Right orchiectomy was performed, and the pathological finding showed nonseminomatous germ cell tumor. He underwent chemotherapy, followed by lymph node dissection and lung metastasectomy. The patient in case 2 had a history of left orchiectomy for testicular tumor at the age of 41. The pathological finding of the left testis revealed seminoma (stage IA). Nineteen years later (age＝60), he was diagnosed with right testicular tumor and underwent right orchiectomy. Herein, the pathological finding showed seminoma (stage IA). The patient in case 3 had a history of right orchiectomy for testicular tumor at the age of 25. The pathological findings revealed seminoma (stage IS), and he underwent adjuvant radiation of the para-aortic field without subsequent recurrence. Fourteen years later (age＝39), he was diagnosed with left testicular tumor and underwent left orchiectomy. The pathological finding revealed seminoma (stage IB). The patient underwent adjuvant carboplatin monotherapy to prevent recurrence. Due to the long interval between the occurrence of bilateral metachronous testicular tumors (mean＝19 years ; three cases), long-term observation is necessary to detect the possible occurrence of contralateral testicular tumors. Contralateral testicular biopsy might be considered at the time of orchiectomy for unilateral testicular tumor if associated with testicular atrophy and/or a history of undescended testis.

Characteristics of Metachronous Remnant Gastric Cancer After Proximal Gastrectomy: A Retrospective Analysis.

PURPOSE: Despite annual endoscopy, patients with metachronous remnant gastric cancer (MRGC) following proximal gastrectomy (PG) are at times ineligible for endoscopic resection (ER). This study aimed to clarify the clinical risk factors for ER inapplicability. MATERIALS AND METHODS: We reviewed the records of 203 patients who underwent PG for cT1 gastric cancer between 2006 and 2015. The remnant stomach was categorized as a pseudofornix, corpus, or antrum. RESULTS: Thirty-two MRGCs were identified in the 29 patients. Twenty MRGCs were classified as ER (ER group, 62.5%), whereas 12 were not (non-ER group, 37.5%). MRGCs were located in the pseudo-fornix in 1, corpus in 5, and antrum in 14 in the ER group, and in the pseudo-fornix in 6, corpus in 4, and antrum in 2 in the non-ER group (P=0.019). Multivariate analysis revealed that the pseudo-fornix was an independent risk factor for non-ER (P=0.014). In the non-ER group, MRGCs at the pseudo-fornix (n=6) had more frequent undifferentiated-type histology (4/6 vs. 0/6), deeper (≥pT1b2; 6/6 vs. 2/6) and nodal metastasis (3/6 vs. 0/6) than non-pseudo-fornix lesions (n=6). We examined the visibility of the region developing MRGC on an annual follow-up endoscopy one year before MRGC detection. In seven lesions at the pseudofornix, visibility was only secured in two (28.6%) because of food residues. Of the 25 lesions in the non-pseudo-fornix, visibility was secured in 21 lesions (84%; P=0.010). CONCLUSIONS: Endoscopic visibility increases the chances of ER applicability. Special preparation is required to ensure the complete clearance of food residues in the pseudo-fornix.

Epidemiology, Pattern, and Survival of Multiple Primary Malignant Neoplasms in Southeast Iran: Results of Kerman Population-Based Cancer Registry 2014-2020.

PURPOSE: Cancer survivors may experience a subsequent primary cancer that affects their survival and quality of life. This study aimed to investigate the epidemiology of multiple primary malignant neoplasms (MPMNs) in Kerman province, southeast Iran during 2014-2020. MATERIALS AND METHODS: In this retrospective cohort study, all patients who had been diagnosed with primary cancers and registered with the Kerman Cancer Registry Program (KPBCR) during 2014-2020 were included. MPMNs were defined as primary malignant tumors arising in different sites and/or were of different histological or morphological origins. If the second malignancy was diagnosed within the first six months from the diagnosis of the first tumor it was considered synchronous, and if after six months it was defined as metachronous. Logistic regression was used to analyze the relationship between age, sex, and primary cancer site with incidence and survival of secondary in the entire population. RESULTS: Of 26,315 patients registered with a primary cancer diagnosis, 492 (1.86%) developed subsequent primary cancers. The most common type of secondary cancer was skin and mucosa (n=131, 26.63%) followed by urogenital (n=115, 23.37%), followed by, gastrointestinal (n=62, 14.45%), and breast neoplasms (n=57, 11.59%). Most patients had metachronous tumors (n=350, 71.13%). The primary cancer site (Skin and mucosa, urogenital, and breast) was significantly associated with developing subsequent cancer among cancer survivors. The overall 5-year survival of MPMNs cases was over 50%. Older age at diagnosis (HR= 1.02) and having synchronous tumors (HR=1.41) were negatively associated with the survival time of patients with MPMNs. CONCLUSION: Both patients and physicians should be taught about the importance of prevention and the provision of care and screening services among cancer survivors. Studying the epidemiology, susceptibility, and risk factors of MPMNs among cancer survivors will open windows to a better understanding of this phenomenon and policy making.

Gastric microbiome signature for predicting metachronous recurrence after endoscopic resection of gastric neoplasm.

BACKGROUND: Changes in gastric microbiome are associated with gastric carcinogenesis. Studies on the association between gastric mucosa-associated gastric microbiome (MAM) and metachronous gastric cancer are limited. This study aimed to identify gastric MAM as a predictive factor for metachronous recurrence following endoscopic resection of gastric neoplasms. METHOD: Microbiome analyses were conducted for 81 patients in a prospective cohort to investigate surrogate markers to predict metachronous recurrence. Gastric MAM in non-cancerous corporal biopsy specimens was evaluated using Illumina MiSeq platform targeting 16S ribosomal DNA. RESULTS: Over a median follow-up duration of 53.8 months, 16 metachronous gastric neoplasms developed. Baseline gastric MAM varied with Helicobacter pylori infection status, but was unaffected by initial pathologic diagnosis, presence of atrophic gastritis, intestinal metaplasia, or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence but showed significant difference in ß-diversity. The study population could be classified into two distinct gastrotypes based on baseline gastric MAM: gastrotype 1, Helicobacter-abundant; gastrotype 2: Akkermansia-abundant. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype (Cox proportional hazard analysis, adjusted hazard ratio [95% confidence interval]: 5.10 [1.09-23.79]). CONCLUSIONS: Gastric cancer patients can be classified into two distinct gastrotype groups by their MAM profiles, which were associated with different risk of metachronous recurrence.

Cytoreductive surgery without intra-peritoneal chemotherapy for metachronous colorectal peritoneal metastases.

BACKGROUND: Cytoreductive surgery and chemotherapy reportedly improve the prognosis of patients with metachronous peritoneal metastases. However, the types of peritoneal metastases indicated for cytoreductive surgery remains unclear. Therefore, we aimed to clarify the category of cases for which cytoreductive surgery would be effective and report the prognosis associated with cytoreductive surgery for metachronous peritoneal metastases. METHODS: This study included 52 consecutive patients who underwent cytoreductive surgery for metachronous peritoneal metastases caused by colorectal cancer between January 2005 and December 2018 and fulfilled the selection criteria. The median follow-up period was 54.9 months. Relapse-free survival was calculated as the time from cytoreductive surgery of metachronous peritoneal metastases to recurrence. Overall survival was defined as the time from cytoreductive surgery of metachronous peritoneal metastases to death or the end of the follow-up period. RESULTS: The 5-year relapse-free survival rate was 30.0% and the 5-year overall survival rate was 72.3%. None of the patients underwent hyperthermic intraperitoneal chemotherapy. The analysis indicated no potential risk factors for 5-year relapse-free survival. However, for 5-year overall survival, the multivariate analysis revealed that time to diagnosis of metachronous peritoneal metastases of < 2 years after primary surgery (hazard ratio = 4.1, 95% confidence interval = 2.0-8.6, p = 0.0002) and number of metachronous peritoneal metastases ≥ 3 (hazard ratio = 9.8, 95% confidence interval = 2.3-42.3, p = 0.002) as independent factors associated with a poor prognosis. CONCLUSIONS: Long intervals of more than 2 years after primary surgery and 2 or less metachronous peritoneal metastases were good selection criteria for cytoreductive surgery for metachronous peritoneal metastases from colorectal cancer.

Clonal Hematopoiesis Without Malignant Transformation Lasting Over 2 Years in a 9-Year-old Boy, Following Treatment for Acute Lymphocytic Leukemia.

Children with acute lymphocytic leukemia rarely develop secondary hematological neoplasms. A 5-year-old boy was diagnosed with standard-risk precursor B-cell acute lymphocytic leukemia. The patient exhibited aberrant chromosomal changes in the bone marrow at 6 months postchemotherapy: 46,XY,der(6) t(1;6)(q12;p22) dup(6)(p22p12)[15]. Clinically, the patient has sustained complete remission and has not developed myeloid malignancy over the subsequent period (27 mo). The cytogenetic aberration was observed in 11% of CD34+ cells isolated from the bone marrow. We infer that the abnormal clone acquires self-renewal potency, differentiation, and growth advantage. Further long-term observation is needed to determine the nature of this cytogenetic aberration.

Analyzing risk factors for second malignancies in early gastric carcinoma from the SEER database.

This retrospective study analyzed a large population of gastric cancer (GC) patients treated between 2010 and 2015 to investigate the clinical features and predictive risk factors for developing secondary primary malignancies (SPMs). The cumulative incidence of SPM was assessed using Kaplan-Meier analysis. Competing risk analyses adjusted for mortality were conducted using stratified Cox proportional hazard regression models and multivariate analyses to identify independent predictors of SPM. A total of 3289 out of 167,747 GC patients were included in the analytic cohort, with 155 patients diagnosed with SPM. Patients whose histologic type other than adenocarcinomas (AC) and signet ring cell carcinoma (SRCC) emerged as an independent risk factor for developing SPM (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.146-4.465, P = 0.019) in multivariate Cox regression analysis. The surgical method, including biopsy/local excision (HR 2.3, [CI] 1.291-4.095, P = 0.005) and subtotal/total resection ([HR] 1.947, [CI] 1.028-3.687, P = 0.041), chemotherapy ([HR] 1.527, [CI] 1.006-2.316, P = 0.047), and histologic type ([HR] 2.318, [CI] 1.193-4.504, P = 0.013)), were identified as independent risk factors in the competitive risk model. Subgroup analyses, stratified by chemotherapy, revealed an increased risk of SPM among older patients. Furthermore, a nomogram was developed and internally validated to predict the cumulative incidence of SPM in GC patients (C-index = 0.73 for 72 months). These findings suggested that in specific histologic types of GC, the lymph node infiltration region missed after local surgical resection, and concomitant chemotherapy would have an increased risk of SPM for cancer survivors.

[Cowden syndrome in a male patient with metachronous triple cancers and various clinical features:a case report].

A 66-year-old male patient with a thyroid and nasopharyngeal cancer history visited our hospital because of a positive fecal occult blood test. Total colonoscopy detected sessile or subpedunculated polyps in the ascending colon, sigmoid colon, and rectum. These polyps were endoscopically resected, and the rectal polyp was pathologically diagnosed as adenocarcinoma in adenoma and the others as adenomas. Additionally, multiple sessile lesions were revealed in the sigmoid colon and rectum. A complete gastrointestinal tract examination revealed multiple foci of glycogenic acanthosis in the esophagus, multiple sessile lesions in the stomach, multiple sessile lesions, clubbings (rod-shaped lesions), and venous malformations in the small bowel. Mucocutaneous examination indicated hemangiomas on the body trunk, patchy pigmentation on the glans penis, and keratotic papules in the inguinal region. The National Comprehensive Cancer Network diagnostic criteria for Cowden syndrome were used in this case. The patient met four major and two minor criteria;thus, Cowden syndrome was diagnosed. Moreover, the patient was had phosphatase and tensin homolog deleted on chromosome 10 gene mutation. This is the first reported case of metachronal triple cancers in a male patient with Cowden syndrome, and our results indicate the importance of cancer surveillance.

Surgical Outcomes and Genomic Insights of Nonclear Cell Renal Cell Carcinoma With Synchronous and Metachronous Nodal Disease.

INTRODUCTION: Oncological outcomes in patients with nonclear cell renal cell carcinoma (non-ccRCC) treated with surgery for locoregional nodal disease (ND) remain incompletely characterized. The objective was to investigate the characteristics and outcomes of non-ccRCC patients treated with lymph node dissection (LND) and salvage-LND (S-LND). METHODS: A total of 1627 patients underwent nephrectomy for nonmetastatic non-ccRCC at Memorial Sloan Kettering Cancer Center between 2007 and 2023. Histology was grouped as papillary, chromophobe, unclassified, and rare subtypes. Retrospective evaluation identified 2.5% (n = 40) of patients with nodal disease at time of nephrectomy (synchronous-ND) and 1.1% (n = 18) with metachronous nodal disease limited to the retroperitoneum (metachronous-ND). Patients' demographics and tumor characteristics were recorded and evaluated by univariate and multivariate cox regression models. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Patients who underwent tumor DNA sequencing during their clinical course were considered for genomic analysis. RESULTS: OS trended toward longer in metachronous-ND (51 vs 105 months; P = .2), though 23% of patients with synchronous-ND were recurrence-free at 45 months median follow-up. In multivariate analysis, rare histologies were associated with decreased OS (P = .030) and metachronous-ND with improved OS (P = .036). RFS and OS after S-LND was 15 and 96 months, respectively. Late onset of metachronous-ND/recurrence was associated with improved OS (P = .008). Genetic alterations in SETD2, TP53, B2M, and FGFR3 were exclusively seen in synchronous-ND, and tumor mutation burden (TMB) was also higher in patients with synchronous-ND (P = .016). CONCLUSIONS: Patients with metachronous-ND tend to have prolonged OS compared to synchronous-ND, but a substantial portion of patients with synchronous-ND still enter a durable disease-free state following LND. S-LND can likewise provide long-term survival, particularly in patients with longer time to metachronous nodal recurrence. Synchronous-ND was associated with SETD2, TP53, and NF2 alteration as well as higher TMB.

Risk factors for advanced colorectal neoplasia and colorectal cancer detected at surveillance: a nationwide study in the modern era.

AIM: Recommendations for surveillance after colonoscopy are based on risk factors for metachronous advanced colorectal neoplasia (AN) and colorectal cancer (CRC). The value of these risk factors remains unclear in populations enriched by individuals with a positive faecal immunochemical test and were investigated in a modern setting. METHODS AND RESULTS: This population-based cohort study included all individuals in the Netherlands of ≥55 years old with a first adenoma diagnosis in 2015. A total of 22,471 patients were included. Data were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were metachronous AN and CRC. Patient and polyp characteristics were evaluated by multivariable Cox regression analyses. During follow-up, 2416 (10.8%) patients were diagnosed with AN, of which 557 (2.5% from the total population) were CRC. Adenomas with high-grade dysplasia (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.40-1.83), villous histology (HR 1.91, 95% CI 1.59-2.28), size ≥10 mm (HR 1.12, 95% CI 1.02-1.23), proximal location (HR 1.12, 95% CI 1.02-1.23), two or more adenomas (HR 1.28, 95% CI 1.16-1.41), and serrated polyps ≥10 mm (HR 1.67, 95% CI 1.42-1.97) were independent risk factors for metachronous AN. In contrast, only adenomas with high-grade dysplasia (HR 2.49, 95% CI 1.92-3.24) were an independent risk factor for metachronous CRC. CONCLUSIONS: Risk factors for metachronous AN and CRC were identified for populations with access to a faecal immunochemical test (FIT)-based screening programme. If only risk factors for metachronous CRC are considered, a reduction in criteria for surveillance seems reasonable.

[Multiple primary tumors in children: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.

Synchronous or metachronous breast and colorectal cancers in younger-than-average-age patients: a case series.

BACKGROUND: The incidence of breast and colorectal cancer (CRC) in younger-than-average-age patients is rising and poorly understood. This is the largest study on patients with both cancers who are less than 60 years old and aims to characterize demographic, clinicopathologic, and genetic features and describe therapeutic dilemmas and management strategies. MATERIALS AND METHODS: This is a retrospective medical records review of patients at the University of California San Francisco with both primary breast and CRC before age 60. RESULTS: Fifty-one patients were identified; 41 had detailed medical records. Median age of diagnosis with breast cancer was 43 (range 27-59) and CRC was 50 (28-59). Most were Caucasian (38, 74.5%) and never smokers (23, 56.1%); about half were current alcohol consumers (20, 48.8%) and about one-third had sedentary jobs (14, 34.1%). Average BMI was 25.8 (range: 14-49), and 30% were overweight or obese. Breast was the first cancer diagnosed in 36 patients (70.6%) and 44 (86.3%) had a metachronous CRC diagnosis. Breast cancer was early stage (0-2) in 32 (78.0%) patients whereas CRC was split between early stage (1-2) in 14 (34.1%) and later stage (3-4) in 19 (46.2%). Ten patients (24.3%) had a known germline mutation, although 23 (56.1%) had a family history of cancer in a first-degree relative. CONCLUSION: Younger patients with both breast and CRC are a unique cohort, often without known risk factors. Alcohol consumption and sedentary jobs were the most common risk factors, and about one-quarter had a known genetic predisposition. Comanagement of both cancers requires individualized, multidisciplinary care.

Serrated Polyps in Inflammatory Bowel Disease Indicate a Similar Risk of Metachronous Colorectal Neoplasia as in the General Population.

BACKGROUND: The risk of metachronous advanced neoplasia after diagnosing serrated polyps in patients with IBD is poorly understood. METHODS: A retrospective multicenter cohort study was conducted between 2010 and 2019 at three tertiary centers in Montreal, Canada. From pathology databases, we identified 1587 consecutive patients with serrated polyps (sessile serrated lesion, traditional serrated adenoma, or serrated epithelial change). We included patients aged 45-74 and excluded patients with polyposis, colorectal cancer, or no follow-up. The primary outcome was the risk of metachronous advanced neoplasia (advanced adenoma, advanced serrated lesion, or colorectal cancer) after index serrated polyp, comparing patients with and without IBD. RESULTS: 477 patients with serrated polyps were eligible (mean age 61 years): 37 with IBD, totaling 45 serrated polyps and 440 without IBD, totaling 586 serrated polyps. The median follow-up was 3.4 years. There was no difference in metachronous advanced neoplasia (HR 0.77, 95% CI 0.32-1.84), metachronous advanced adenoma (HR 0.54, 95% CI 0.11-2.67), and metachronous advanced serrated lesion (HR 0.76, 95% CI 0.26-2.18) risk. When comparing serrated polyps in mucosa involved or uninvolved with IBD, both groups had similar intervals from IBD to serrated polyp diagnosis (p > 0.05), maximal therapies (p > 0.05), mucosal inflammation, inflammatory markers, and fecal calprotectin (p > 0.05). CONCLUSION: The risk of metachronous advanced neoplasia after serrated polyp detection was similar in patients with and without IBD. Serrated polyps in IBD occurred independently of inflammation. This helps inform surveillance intervals for patients with IBD diagnosed with serrated polyps.