Multiple Primary Tumors Research Articles

Bladder Adenocarcinoma in a Constellation of Multiple Site Malignancies: An Unusual Case and Systematic Review

Background and Objectives: Multiple primary malignant tumors represent a small percentage of the total number of oncological cases and can involve either metachronous or synchronous development and represent challenges in diagnosis, staging, and treatment planning. Our purpose is to present a rare case of bladder adenocarcinoma in a female patient with multiple primary malignant tumors and to provide systematic review of the available literature. Materials and Methods: A 67-year-old female patient was admitted with altered general condition and anuria. The past medical history of the patient included malignant melanoma (2014), cervical cancer (2017), colon cancer (2021), obstructive anuria (2023), and liver metastasectomy (2023). Transurethral resection of bladder tumor was performed for bladder tumors. Results: Contrast CT highlighted multiple pulmonary metastases, a poly nodular liver conglomerate, retroperitoneal lymph node, II/III grade left ureterohydronephrosis, and no digestive tract tumor masses. The pathological result of the bladder resection showed an infiltrative adenocarcinoma. Conclusions: The difference between primary bladder adenocarcinoma tumor and metastatic colorectal adenocarcinoma is the key for the future therapeutic strategy. Identification and assessment of risk factors such as viral infection, radiotherapy, chemotherapy, smoking, and genetics are pivotal in understanding and managing multiple primary malignant tumors. Personalized prevention strategies and screening programs may facilitate the early detection of these tumors, whether synchronous or metachronous. The use of multicancer early detection (MCED) blood tests for early diagnosis appears promising. However, additional research is needed to standardize these techniques for cancer detection.

Unveiling the Enigma: Multiple Primary Neoplasms Mimicking Metastatic Disease

Unveiling the Enigma: Multiple Primary Neoplasms Mimicking Metastatic Disease

Developmental mosaicism underlying EGFR-mutant lung cancer presenting with multiple primary tumors.

Although the development of multiple primary tumors in smokers with lung cancer can be attributed to carcinogen-induced field cancerization, the occurrence of multiple tumors at presentation in individuals with EGFR-mutant lung cancer who lack known environmental exposures remains unexplained. In the present study, we identified ten patients with early stage, resectable, non-small cell lung cancer who presented with multiple, anatomically distinct, EGFR-mutant tumors. We analyzed the phylogenetic relationships among multiple tumors from each patient using whole-exome sequencing (WES) and hypermutable poly(guanine) (poly(G)) repeat genotyping as orthogonal methods for lineage tracing. In four patients, developmental mosaicism, assessed by WES and poly(G) lineage tracing, indicates a common non-germline cell of origin. In two other patients, we identified germline EGFR variants, which confer moderately enhanced signaling when modeled in vitro. Thus, in addition to germline variants, developmental mosaicism defines a distinct mechanism of genetic predisposition to multiple EGFR-mutant primary tumors, with implications for their etiology and clinical management.

Association between microsatellite instability status, clinicopathological features and mitochondrial DNA amplification in patients with colorectal cancer.

The relationship between BRAF-V600E mutations, mitochondrial DNA amplification and microsatellite instability-high (MSI-H) in colorectal cancer (CRC) has yet to be fully elucidated. The aim of the present study was to assess the association between the MSI status and BRAF-V600E gene mutations/clinicopathological features/mitochondrial DNA amplification in CRC. A non-interventional study analysis was performed using the clinicopathological features of 455 patients with CRC. Immunohistochemistry was used to evaluate four mismatch repair proteins (MutS homolog 2, MutS homolog 6, MutL homolog 1 and postmeiotic segregation increased 2), Ki-67 index, and programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) expression. Additionally, PCR coupled with capillary electrophoresis were used to ascertain the MSI status. Moreover, amplification refractory mutation system-PCR was used to detect BRAF-V600E gene mutation and fluorescence in situ hybridization analysis was used to assess mitochondrial DNA. A total of 455 patients were divided into the MSI high (MSI-H) group (n=52) and microsatellite stability (MSS) group (n=403) based on their MSI status. Compared with the results of immunohistochemistry of four mismatch repair proteins, the consistency rate between mismatch repair protein deficiency and MSI was 94.23%. There were significant differences in PD-L1, primary tumor site, clinical stage, degree of differentiation, tumor size, lymph node metastasis and the occurrence of multiple primary tumors between the MSI-H group and MSS group (P<0.05 or P<0.001). However, there were no significant differences for sex, age, PD-1, Ki-67 expression and BRAF-V600E. The 24-60-month survival rate of the patients in the MSI-H group was significantly higher than that of those in the MSS group (P<0.05). Furthermore, the number of mitochondrial DNA was significantly amplified in the MSI-H group. In conclusion, the present study demonstrated that the combined detection of PD-L1 and MSI in patients with CRC can provide more accurate and effective guidance for personalized treatment.

A case of metachronous triple primary carcinoma complicated with pulmonary tuberculosis: Case report and review.

Multiple primary malignant neoplasms with tuberculosis are rare. The interaction between tuberculosis and tumor remains unclear. Moreover, the treatment of multiple primary tumors combined with tuberculosis is relatively complicated. Herein, we report a case of metachronous triple primary carcinoma complicated with pulmonary tuberculosis. This report aims to analyze the clinical characteristics of 3 primary tumors combined with tuberculosis. We report the long-term survival of this patient after personalized treatment and this patient have a good quality of life. A 55-year-old male patient was diagnosed with squamous cell carcinoma of the lower thoracic esophagus (cT4bN1M0 IVA) and received concurrent chemoradiotherapy, followed by 2 cycles consolidate chemotherapy. During the follow-up, he was diagnosed with secondary tuberculosis (TB) and accepted anti-TB treatment. During anti-TB treatment, he was diagnosed with squamous cell carcinoma of the oropharynx (cT1N0M0 I P16(-)), then he received radical radiation therapy. However, within a year, the patient was diagnosed with oral squamous cell carcinoma (cT3N0M0 IIIA). He accepted an individualized chemotherapy with paclitaxel combined with capecitabine. Moreover, immunohistochemistry of the patient's 3 biopsies indicated positive P53 expression. Since the patient suffered from esophageal cancer, oropharyngeal cancer, and oral floor cancer, no tumor recurrence or metastasis was observed. And he has a good quality of life. Tuberculosis, TP53 mutation, radiotherapy, smoking, and drinking history may be risk factors for multiple primary tumors. The treatment of multiple primary tumors combined with pulmonary tuberculosis is complicated. Individualized treatment allows patients to achieve long-term survival while also having a good quality of life. Limitations in this case: surgery may be an alternative strategy for the patient, but the patient refused surgery.

Comparison of prognosis between oncocytic thyroid carcinoma and follicular thyroid carcinoma: a population-based propensity score matching analysis.

Oncocytic thyroid carcinoma (OTC) is a rare subtype of thyroid cancer known for its distinctive morphology and high likelihood of recurrence, setting it apart from follicular thyroid carcinoma (FTC). Despite this, there is limited research comparing the clinicopathological characteristics and outcomes of OTC and FTC. We retrospectively searched through the Surveillance, Epidemiology, and End-Results (SEER) database (2004-2015) for histologically diagnosed OTC and FTC patients. Kaplan-Meier analysis, propensity score matching (PSM), univariate Cox proportional risk regression model, and subgroup analysis were employed to investigate the prognostic effect of clinicopathological features and treatment regimens on survival outcomes of OTC and FTC patients. 2329 OTC patients and 5679 FTC patients were included in the study. OTC patients were prone to older age, white race, lymph node metastasis, distal metastasis, extension and multiple primary tumors compared with FTC patients. After using a 1:1 PSM matching ratio, there were no significant differences in demographic and clinicopathological characteristics between the matched groups. Further Cox regression analysis showed that OTC patients had lower overall survival (OS) and cancer-specific survival (CSS) in contrast with FTC patients. Subgroup survival analysis suggested that the OTC patients were related to lower OS in subgroups including those over 55years old, male sex, white ethnicity, extrathyroidal extension, single primary tumor, surgery and without chemotherapy compared with the FTC patients in these subgroups. In addition, the OTC patients were connected with lower CSS in subgroups including male sex, white ethnicity, married status, tumor size is less than 20mm or more than 40mm, N0 stage, localized stage, single primary tumor, surgery, radiotherapy, and without chemotherapy compared with the FTC patients in these subgroups. Meanwhile, the OTC patients had lower CSS compared to FTC patients regardless of age and extrathyroidal extension. The results suggested that OTC patients have unique clinical features and poorer prognoses compared to FTC patients. Surgical resection and radioactive iodine therapy are recommended for OTC patients and FTC patients. It is worth noting that the prognosis of OTC relies largely on the selection of treatment strategies. Therefore, our results highlighted the clinical significance of the early distinguishment and the correct choice of treatment in OTC patients.

Successful surgical treatment of metachronous carcinoma of the appulla of Vater and ductal carcinoma of the distal parts of the pancreas

Background. Currently, there is a steady trend towards an increase in the incidence of both synchronous and metachronous multiple primary malignant tumors (MPMT). However, metachronous polyneoplasia of the pancreatobiliary tract is relatively rare, and there have been very few reports on successful treatment of this malignancy. Case presentation. In September 2014, the patient K. was diagnosed with adenocarcinoma of the ampulla of Vater (T2N0M0, stage Ib) and underwent gastropancreatoduodenal resection with the creation of pancreatic-gastric anastomosis at the Abdominal Department of Cancer Research Institute of Tomsk National Research Medical Center. There were no complications in the postoperative period. At a 6.5-year followup, no evidence of disease progression was found. In April 2021, a follow-up examination conducted at the Cancer Research Institute revealed a large lesion on the distal part of the pancreatic stump with no clinically significant manifestations. Diagnosis of MPMT was confirmed by transgastric endoscopic ultrasound-guided biopsy. Histological and immunohistochemical examinations revealed undifferentiated ductal carcinoma of the pancreas. Considering the metachronous tumor localization, pancreatic stump extirpation with resection of the posterior wall of the stomach and splenectomy was performed. No complications occurred in the postoperative period. The patient received replacement therapy for exocrine pancreatic insufficiency and individual correction of carbohydrate metabolism. At a 15-month follow-up, liver metastases were detected, and palliative chemotherapy was administered. The patient died 6 months later due to disease progression. The survival time was 99 months after the first surgery and 21 months after the second surgery. Conclusion. We report a rare case of metachronous cancers of the ampulla of Vater and pancreatic stump developed with an interval of 6.5 years. The patient underwent successful curative resections consecutively. The overall survival time from the date of diagnosis was 99 months.

ABCL-075 Primary multiple tumors, metachronous course: late relapse of DLBCL. MDS. Squamous cell kidney cancer

ABCL-075 Primary multiple tumors, metachronous course: late relapse of DLBCL. MDS. Squamous cell kidney cancer

A case of Ph+ acute lymphoblastic leukemia and EGFR mutant lung adenocarcinoma synchronous overlap: may one TKI drug solve two diseases?

BackgroundPhiladelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) refers to ALL patients with t(9;22) cytogenetic abnormalities, accounting for about 25% of ALL. Lung adenocarcinoma (LUAD) is the most common pathological type of non-small-cell lung cancer, which has a frequency of approximately 45% cases with mutations in EGFR. Both Ph+ ALL and EGFR mutant LUAD are involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway. Although the second primary hematological malignancy after the treatment of solid tumors is common in clinics, the synchronous multiple primary malignant tumors of hematological malignancy overlap solid tumors are uncommon, even both tumors involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway are extremely rare.Case presentationAn 84-year-old man with fatigue and dizziness was diagnosed with Ph+ ALL. Meanwhile, a chest CT indicated a space-occupying lesions, characterized by the presence of void, in the right lower lope with the enlargement of mediastinal lymph node and right pleural effusion. After a few weeks, the patient was diagnosed with LUAD with EGFR exon 19 mutation. Both tyrosine kinase inhibitors (TKI) (Flumatinib) and EGFR-TKI (Oxertinib) was used for the patients, and finally have controlled both diseases.ConclusionAs far as we know, we for the first time reported a case of Ph+ ALL and EGFR mutant LUAD synchronous overlap, of which pathogenesis is related to abnormal tyrosine kinase activation. This patient was successfully treated with two different TKIs without serious adverse events.

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.

Exploring the Susceptibility to Multiple Primary Tumors in Patients with Differentiated Thyroid Cancer.

It was demonstrated that differentiated thyroid cancer (DTC) patients may develop multiple primary tumors (MPT) during follow-up. Many studies showed an association between reduced telomere length and cancer phenotype; in particular, the short telomeres were associated with the development of a primary tumor. However, the role of altered telomere length in MPT development has not yet been demonstrated. The aim of this study was to evaluate the possible correlation between a short telomere length in blood leukocytes and the risk of developing MPT in DTC patients. We retrospectively evaluated 167 DTC patients followed up for a median of 13.6 years. Our control group was represented by 105 healthy subjects without any thyroid disease or present or past history of tumors. Our study groups, age-matched, were evaluated for the relative telomere length measured in leukocytes of peripheral venous blood. The relative telomere length (RTL) was significantly different in healthy subjects compared to the total group of differentiated thyroid cancer patients [p < 0.0001]. Shorter telomeres length was observed in DTC patients with (n = 32) and without (n = 135) MPT compared to healthy subjects (p < 0.0001 and p = 0.0002, respectively). At multivariate analysis, the parameters independently associated with the presence of MPT were RTL [OR: 0.466 (0.226-0.817), p = 0.018] and the familial DTC [OR: 2.949 (1.142-8.466), p = 0.032]. The results of this study suggest a role of the relative telomere length in predicting MPT development in DTC patients. Our results contribute to increasing the knowledge of the genetic mechanisms underlying MPT development in DTC patients, considering relative telomere length as a possible prognostic marker.

Comparative analysis through propensity score matching in thyroid cancer: unveiling the impact of multiple malignancies.

The incidence of thyroid cancer is on the rise worldwide, with childhood exposure to radiation being the sole acknowledged catalyst for its emergence. Nonetheless, numerous other factors that may pose risks are awaiting thorough examination and validation. This retrospective study aims to explore the malignancies linked to thyroid cancer and contrast the survival rates of those afflicted with a solitary tumor versus those with multiple primary neoplasms (MPN). This retrospective study examined data from King Hussein Cancer Center (KHCC), Jordan. Among 563 patients diagnosed with thyroid cancer, 30 patients had thyroid malignancy as part of MPN. For a 1:3 propensity score-matched analysis, 90 patients with only a primary thyroid malignancy were also enrolled. Hematologic and breast malignancies were among the most frequent observed cancers alongside thyroid neoplasm. Patients who had MPN were diagnosed at older age, had higher body mass index and presented with higher thyroglobulin antibody levels (p < 0.05 for each). Additionally, MPN patient displayed a stronger family history for cancers (p= 0.002). A median follow-up duration of 135 months unveiled that MPN patients faced a worse 5-year survival compared to their counterparts with a singular neoplasm (87% vs 100% respectively; p < 0.01). However, no distinction emerged in the 5-year event-free survival between these two groups. MPN correlates with a significantly altered survival outcome of thyroid cancer patients. The diagnosis of thyroid carcinoma at an older age, accompanied by elevated initial thyroglobulin antibody levels and a notable familial predisposition, may raise concerns about the potential occurrence of synchronous or metachronous tumors.

Multiple anaplastic lymphoma kinase-positive primary inflammatory myofibroblastic tumors with spontaneously expanding and shrinking nodules in both lungs: a case report

BackgroundInflammatory myofibroblastic tumors (IMTs) are uncommon neoplasms most prevalent in individuals under 40 years old and predominantly in the lungs. Despite their rarity, multiple anaplastic lymphoma kinase (ALK)-positive IMTs, especially those of various sizes, have not been widely reported. This report describes a case of multiple ALK-positive IMTs in the lungs, aiming to further our understanding of their behavior and management.Case presentationHerein, we present the case of a 64-year-old woman who presented with an abnormal shadow on chest examination. Chest computed tomography revealed a main tumor in the right middle lobe and multiple irregularly shaped small nodules in both lungs. Thus, thoracoscopic wedge resection of the left lower lobe was performed for diagnosis. Pathological findings indicated smooth muscle proliferation without malignancy. IMT was diagnosed following thoracoscopic right middle lobectomy. Twenty months postoperatively, one residual nodule shrank, but another grew.ConclusionsThis is the first report of multiple ALK-positive IMTs in both lungs, highlighting the need for definitive diagnosis and treatment of IMTs based on surgical resection. Although caution is required in patients with lymph node metastases or distant metastases, careful follow-up is acceptable unless there is a tendency for nodules to increase in size on imaging.

Characterization of discordance between mismatch repair deficiency and microsatellite instability testing may prevent inappropriate treatment with immunotherapy.

In the Drug Rediscovery Protocol (DRUP), patients with cancer are treated based on their tumor molecular profile with approved targeted and immunotherapies outside the labeled indication. Importantly, patients undergo a tumor biopsy for whole-genome sequencing (WGS) which allows for a WGS-based evaluation of routine diagnostics. Notably, we observed that not all biopsies of patients with dMMR/MSI-positive tumors as determined by routine diagnostics were classified as microsatellite-unstable by subsequent WGS. Therefore, we aimed to evaluate the discordance rate between routine dMMR/MSI diagnostics and WGS and to further characterize discordant cases. We assessed patients enrolled in DRUP with dMMR/MSI-positive tumors identified by routine diagnostics, who were treated with immune checkpoint blockade (ICB) and for whom WGS data were available. Patient and tumor characteristics, study treatment outcomes, and material from routine care were retrieved from the patient medical records and via Palga (the Dutch Pathology Registry), and were compared with WGS results. Initially, discordance between routine dMMR/MSI diagnostics and WGS was observed in 13 patients (13/121; 11%). The majority of these patients did not benefit from ICB (11/13; 85%). After further characterization, we found that in six patients (5%) discordance was caused by dMMR tumorsthat did not harbor an MSI molecular phenotype by WGS. In six patients (5%), discordance was false due to the presence of multiple primary tumors (n = 3, 2%) and misdiagnosis of dMMR status by immunohistochemistry (n = 3, 2%). In one patient (1%), the exact underlying cause of discordance could not be identified. Thus, in this group of patients limited to those initially diagnosed with dMMR/MSI tumors by current routine diagnostics, the true assay-based discordance rate between routine dMMR/MSI-positive diagnostics and WGS was 5%. To prevent inappropriate ICB treatment, clinicians and pathologists should be aware of the risk of multiple primary tumors and the limitations of different tests. © 2024 The Pathological Society of Great Britain and Ireland.

On the Hunt for the Missed Genetic Causes of Multiple Primary Tumors.

Improved cancer screening and treatment programs have led to an increased survivorship of patients with cancer, but consequently also to the rise in number of individuals with multiple primary tumors (MPT). Germline testing is the first approach investigating the cause of MPT, as a positive result provides a diagnosis and proper clinical management to the affected individual and their family. Negative or inconclusive genetic results could suggest non-genetic causes, but are negative genetic results truly negative? Herein, we discuss the potential sources of missed genetic causes and highlight the trove of knowledge MPT can provide. See related article by Borja et al., p. 209.

Abstract PO5-08-07: Ki-67 Expression in Breast Cancer associated with ATM, BRCA1, BRCA2, CHEK2 and PALB2 Pathogenic Variants

Abstract Background: Germline Pathogenic Variants (PVs) in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are known to increase breast cancer (BCa) risk, but the effect of these PVs on tumor biology is not well-understood. Ki-67 is an established prognostic marker in hormone receptor (HR) positive breast cancer but the distribution of Ki-67 in breast cancer associated with germline PVs is not known. Methods: The study included patients with loco-regional (Stage I-III) HR-positive (ER+ or PR+), HER2-negative invasive ductal or lobular breast cancer evaluated at Mayo Clinic for curative intent treatment between 2012 and 2021. PV carrier status was ascertained in more than two-thirds of cases from germline whole exome sequencing (Regeneron) of patients who participated in a prospective registry at Mayo Clinic. Additional PV carriers were identified through a review of the results of clinical germline genetic testing in electronic medical records aided by natural language processing. Clinically performed Ki-67 values were abstracted from electronic medical records and analyzed as continuous and categorical variables (low: &amp;lt; 20% vs. high: ≥20%). Throughout the timeline of the study, a consistent method for assessment of Ki-67 was utilized at Mayo Clinic, Rochester: Immunohistochemical staining of the Ki-67 antigen in formalin-fixed paraffin-embedded tissue was performed using MIB-1 clone, the scanned slides were reviewed by a technologist and traced areas further analyzed for Ki-67 using Aperio Software. Patients who received neoadjuvant therapy prior to the assessment of Ki-67, with metastatic disease at diagnosis, with PVs in two or more genes of interest, or unknown germline PV or Ki-67 status were excluded from the analysis. Multiple primary tumors in the same patient diagnosed within one year of each other were analyzed independently. The control (non-carrier) group included randomly selected patients from the prospective registry who tested negative for PVs in the five genes over the same time period. Ki-67 values were compared between germline PV carriers and non-carriers in a multivariable logistic regression analysis adjusting for sex, race, age at diagnosis, stage at presentation, and histology of the tumor. Results: A total of 113 HR+/HER2- tumors from 111 PV carriers (ATM: 27, BRCA1: 24, BRCA2: 28, CHEK2: 22, and PALB2:12) along with 431 HR+/HER2- tumors from 422 randomly selected non-carriers were evaluated. The majority (&amp;gt;95%) of patients were non-Hispanic White. Germline PV carriers in each gene were diagnosed at a significantly younger age (P&amp;lt; 0.05) compared to non-carriers. The median Ki-67 value was 12 (Range: 1 to 93) for non-carriers, 16 (Range: 0 to 79) for ATM, 31 (Range: 4 to 86) for BRCA1, 30 (Range: 6 to 80) for BRCA2, 13 (Range: 1 to 38) for CHEK2, and 20 (Range: 3 to 46) for PALB2 PV carriers. In multivariable analysis, compared to non-carriers, we observed significantly higher odds of a high Ki67 value (≥20%) for tumors arising from germline PV carriers in BRCA1 (Odds Ratio (OR): 7.3, 95%CI: 2.3 – 23.3, p&amp;lt; 0.001), BRCA2 (OR: 3.0, 95%CI: 1.2 – 7.4, p=0.02) and PALB2 (OR: 3.9, 95%CI: 1.1 – 14.5, p=0.04). No such relationship was observed with either ATM (OR: 1.1, 95%CI: 0.4 – 2.9, p=0.81) or CHEK2 (OR: 0.8, 95%CI: 0.3 – 2.2, p=0.63). Conclusion: This study reveals that HR+/HER2- tumors in BRCA1, BRCA2, and PALB2 PV carriers have a significantly higher Ki-67 expression compared to non-carriers. These findings have implications for understanding prognosis and endocrine response PV with HR+ breast cancer. Further exploration of the relationships between Ki67 and germline PV status is necessary to personalize systemic therapy options in germline PV carriers. Acknowledgments: Thank you to Regeneron Genetics Center. The study was funded in part by the NIH Specialized Program of Research Excellence in Breast Cancer [P50CA116201] to Mayo Clinic, Mayo Clinic Department of Oncology Small Grants Program, and the Paul Calabresi Program at Mayo Clinic Citation Format: Robert Scheel, Grace Choong, Tara Rao, Nicholas Boddicker, Chunling Hu, Jie Na, Vinod Kaggal, Sean Murphy, Karthik Giridhar, Saba Yasir, Matthew Goetz, Fergus Couch, Siddhartha Yadav. Ki-67 Expression in Breast Cancer associated with ATM, BRCA1, BRCA2, CHEK2 and PALB2 Pathogenic Variants [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-08-07.

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

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. 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. 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. 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. 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.

Multiple primary tumors in patients with surgically treated pancreatic cancer: a SEER population-based study.

With improving survival after pancreatic cancer (PC) resection, questions emerge concerning risk and patterns of metachronous tumors. We aimed to determine the incidence of multiple primary cancers among postoperative PC survivors. Patients undergoing PC surgery from 1975 to 2020 were identified in the Surveillance, Epidemiology, and End Results (SEER) registry. Standardized incidence ratios (SIRs) compared observed-to-expected cancers based on U.S. population rates. Cumulative incidence of secondary tumors was analyzed with Cox regression and cancer-specific survival with Kaplan-Meier curves. Of 6,100 resected PC patients, 267 (4.38%) developed multiple cancers over 6.2 years median follow-up period. Subsequent malignancies showed a rising cumulative incidence extending beyond 5 years. Lung cancer was the predominant second primary in both males (n=36, SIR 1.87) and females (n=32, SIR 2.17). Prostate (n=33) and breast (n=25) cancers were also common. Risk varied by latency period and gender. Postoperative PC patients face a measurable risk for secondary cancers. Enhanced long-term surveillance has the potential to improve early detection and outcomes in this survivor population. Our data provides real-world evidence which could help inform surveillance guidelines in the future.

Modern approaches to the treatment of primary multiple unilateral synchronous lung tumors (literature review)

The review article focuses on recent approaches to the treatment of primary multiple unilateral synchronous and metachronous lung tumors. Unilateral primary multiple lung cancer is diagnosed relatively rare. The introduction of modern computed tomography into clinical practice made it possible to diagnose a peripheral tumor at the initial stages. The second synchronous, usually central lung cancer is more often detected during surgery or during bronchoscopy. Despite the established criteria, differential diagnosis of primary tumor and intrapulmonary metastasis in synchronous PMRL remains a difficult task. Often histological signs do not allow differentiating the primary tumor from metastasis. The use of next generation genomic sequencing (NGS) makes it possible to distinguish a primary tumor from a metastasis. To date, there are no unambiguous recommendations for staging primary multiple unilateral lung cancer. There is no clear understanding of what criteria and classification to use to determine the stage of primary multiple cancer, and the type of surgical intervention depends on it. Based on the 8th classification of staging according to the TNM system, patients with primary multiple lung cancer often need to undergo extensive surgical interventions, up to pneumonectomy. Staging each tumor separately allows us to expand the indications for anatomical segmentectomies and reconstructive plastic surgery. For the treatment of PMLC, the main type of surgery is an operative manual with lobectomy. Reconstructive plastic surgeries and anatomical segmentectomies have little effect on increase in frequency of local relapses, on worsening of survival rates. However, the methods are a reasonable alternative for some types of tumors and poor functional indicators. Stereotactic radiation therapy is the standard of treatment for patients who refuse surgery or in patients with functional limitations with early stage primary multiple lung cancer. Moreover, systemic therapies such as targeted therapy in patients with driver mutations and immunotherapy have shown outstanding results.

DOPAMINE AND NOREPINEPHRINE CONTENT IN THE CEREBRAL CORTEX OF BALB/C NUDE MICE WITH MULTIPLE PRIMARY MALIGNANT TUMOURS

The increase in patients with multiple primary malignant tumors (MPMT) determines the need to study their pathogenesis. An important role in the functioning of brain neurons belongs to norepinephrine (NA) and dopamine (DA), which can contribute to tumor development in immunodeficient mice of both sexes.&#x0D; The purpose of our work was a comparative analysis of dopamine and norepinephrine content in the cerebral cortex of immunodeficient mice of both sexes during isolated and combined growth (MPMT model) of experimental tumors.&#x0D; Materials and Methods. 56 BALB/c Nude mice were divided into 7 groups: 4 groups of females (intact, mice with standard subcutaneous inoculation of B16/F10 melanoma or Lewis lung carcinoma (LLC), mice with MPMT model – subcutaneous injection of a tumor cell suspension); 3 groups of males (the same groups as for females, except LLC). ELISA technique was used to detect NA and DA content.&#x0D; Results. In the cerebral cortex of intact females, DA level was higher (3.7 times) and NA level was lower (1.8 times) when compared to males. In all types of tumor growth, monoamine level decrease was observed in animals of both sexes. In females, DA decrease was 57.2 % and 65.8 % with isolated B16/F10 melanoma growth and LLC, and with MPMT it reached 70 %. In males, DA decreased significantly only with MPMT – by 37.6 %. NA in females decreased in case of LLC and MPMT by 26.2 % and 28.1 %, respectively. In males, NA decreased with B16/F10 melanoma and MPMT by 53.3 % and 43 % respectively (p&lt;0.0001 in all cases). In females, there was a more than twofold increase in the ratio of stress-implementing NA and stress-limiting DA (NA/DA) levels, while in males there was a decrease in this index. This was consistent with the large tumor sizes (2–3 times larger) in case of MPMT in females.&#x0D; Conclusion. The results indicate the participation of brain neurotransmitters in the development of multiple primary malignant tumors in BALB/c Nude mice of both sexes and lower stress resistance in females.