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

Background: 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). Methods: 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. Results: 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. Conclusion: 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.

The confusing pelvic mass: A case of small intestine lesion diagnosed by endoscopic ultrasound-guided fine-needle biopsy through the sigmoid colon.

Here we report a successful case of a small bowel lesion obtained through EUS-FNB via the sigmoid colon after routine small bowel endoscopy failed due to bowel volvulus. This case highlights the feasibility of EUS-FNB in small intestine lesion acquisition through sigmoid colon.

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

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

A rare occurrence of breast, thyroid, and stomach tumors in a single patient: A case report.

INTRODUCTION AND IMPORTANCE: There are only a few case reports to date that have described patients with three or more multiple primary tumors. However, they have been reported more in the last decade, so a precise screening in patients with or without risk factors could be helpful in early diagnosis and treatment. This work has been reported in line with the SCARE criteria. CASE PRESENTATION: Here, we presented a 44-year-old female patient without any history of smoking, alcohol consumption, or cancer in her family. She had three metachronous primary tumors; breast, thyroid, and gastric cancer, which had metastasized to both her ovaries and colon. She died in January 2023 due to complex pneumonia and septic shock. To our knowledge, this article is the second case in which breast, thyroid, and stomach cancer are reported together. CLINICAL DISCUSSION: When it comes to Multiple primary malignancies (MPMs), not only screening in patients with risk factors should be considered, but patients without any other risk factors except current or past history of tumors should be screened precisely for early diagnosis and treatment. In this study, we discuss prevalence and causes of MPMs, prevalence of breast, thyroid, and stomach cancer, and also their possible relations with each other that may affect their occurrence. CONCLUSION: Reporting other cases with MPMs by physicians could lead to establish an evidence based approach to these patients.

The heterogeneous cancer phenotype of individuals with biallelic germline pathogenic variants in CHEK2.

PURPOSE: Females with biallelic CHEK2 germline pathogenic variants (gPVs) more often develop multiple breast cancers than individuals with monoallelic CHEK2 gPVs. This study is aimed at expanding the knowledge on the occurrence of other malignancies. METHODS: Exome sequencing of individuals who developed multiple primary malignancies identified 3 individuals with the CHEK2 (NM_007194.4) c.1100del p.(Thr367MetfsTer15) loss-of-function gPV in a biallelic state. We collected the phenotypes of an additional cohort of individuals with CHEK2 biallelic gPVs (n = 291). RESULTS: In total, 157 individuals (53.4%; 157/294 individuals) developed ≥1 (pre)malignancy. The most common (pre)malignancies next to breast cancer were colorectal- (n = 19), thyroid- (n = 19), and prostate (pre)malignancies (n = 12). Females with biallelic CHEK2 loss-of-function gPVs more frequently developed ≥2 (pre)malignancies and at an earlier age compared with females biallelic for the CHEK2 c.470T>C p.(Ile157Thr) missense variant. Furthermore, 26 males (31%; 26/84 males) with CHEK2 biallelic gPVs developed ≥1 (pre)malignancies of 15 origins. CONCLUSION: Our study suggests that CHEK2 biallelic gPVs likely increase the susceptibility to develop multiple malignancies in various tissues, both in females and males. However, it is possible that a substantial proportion of individuals with CHEK2 biallelic gPVs is missed as diagnostic testing for CHEK2 often is limited to individuals who developed breast cancer.

Corrigendum: Risk and prediction of multiple primary malignancies after early gastric cancer.

[This corrects the article DOI: 10.3389/fonc.2023.1205358.].

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 comprehensive analysis of MPMNs regarding multi-omics and the tumor microenvironment (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.

A Rare Case of a Chylous Pleural Effusion as the Initial Manifestation of Synchronous Tumors.

Multiple primary malignancies (MPMs) are defined as two or more histopathologically distinct malignancies in the same individual. MPMs are classified as synchronous when tumors are diagnosed within six months of each other. The most common malignancies in MPMs are melanoma, breast, lung, and prostate cancer. Synchronous lymphoma and solid tumors are relatively rare. In these cases, a multi-disciplinary approach to treatment is essential. The early detection of additional primary malignancies such as myeloid and lymphatic tumors will enable prompt management with curative intent. The authors present a case of diffuse B-cell non-Hodgkin lymphoma and invasive lobular breast carcinoma presented as a chylous pleural effusion.

Successful Treatment of Concurrent Follicular Lymphoma and Triple-Negative Breast Cancer Using Rituximab Plus Nab-Paclitaxel and Cisplatin: A Case Report and Literature Review.

Background: Co-occurrence of breast cancer and non-Hodgkin's lymphoma is a rare condition with diagnostic and therapeutic challenges. The coexistence of follicular lymphoma (FL) and triple-negative breast cancer (TNBC) has not been described previously. Case Presentation: A 46-year-old woman, already suffering a history of untreated, advanced-stage, high tumor burden FL, was admitted for a rapidly progressing right breast mass. Ultrasonography showed an 8.3 × 3.6 × 4.1 cm fungating mass in the right breast with enlarged lymph nodes (LNs) in bilateral axillae. PET-CT demonstrated increased 18F- FDG activity in right breast mass, LNs on both sides of the diaphragm, enlarged spleen, and bone marrow. Biopsy of the right breast mass revealed TNBC. The patient underwent neoadjuvant therapy with R-CHOP and achieved partial response of breast tumor. However, TNBC progressed after three cycles of R-CHOP. According to the next-generation sequencing (NGS) assay on breast mass showing a homologous recombination repair (HRR) deficiency (HRD) score of 72, the neoadjuvant regimen was changed to rituximab plus nab-paclitaxel and cisplatin (R-TP) and resulted in significant tumor regression. The patient then underwent right mastectomy with an axillary LN dissection. After the surgery, she was regularly monitored and given adjuvant therapy with R-TP and radiotherapy. Conclusion: The coexistence of FL and HRD-positive TNBC poses diagnostic and treatment challenges. Well-founded neoadjuvant strategy based on multidisciplinary team (MDT) discussion and NGS warranted a good outcome in this case.

Nomogram for predicting survival of patients with gastric cancer and multiple primary malignancies: a real-world retrospective analysis using the Surveillance, Epidemiology and End Results database.

OBJECTIVES: Gastric cancer combined with multiple primary malignancies (GCM) is increasingly common. This study investigated GCM clinical features and survival time. METHODS: Patients with GCM and GC only (GCO) were selected from the Surveillance, Epidemiology and End Results (SEER) database. Survival was compared between GCM and GCO groups using propensity score matching. Then, the GCM group was divided into a training cohort and a validation cohort. These cohorts were used to establish a nomogram for survival prediction in patients with GCM. RESULTS: Survival time was significantly longer in the GCM group than in the GCO group. All-subsets regression was used to identify four variables for nomogram establishment: age, gastric cancer sequence, N stage, and surgery. The concordance index and time-dependent receiver operating characteristic curve indicated that the nomogram had favorable discriminative ability. Calibration plots of predicted and actual probabilities showed good consistency in both the training and validation cohorts. Decision curve analysis and risk stratification showed that the nomogram was clinically useful; it had favorable discriminative ability to recognize patients with different levels of risk. CONCLUSIONS: Compared with GCO, GCM is a relatively indolent malignancy. The nomogram developed in this study can help clinicians to assess GCM prognosis.

Risk and prediction of multiple primary malignancies after early gastric cancer.

Background: Patients with early gastric cancer have increased risk of developing multiple primary malignancies (MPM) due to improved survival rates. The purpose of this study was to evaluate the clinicopathological features of MPM and to generate a useful tool for predicting the development of MPM after early gastric cancer. Methods: We selected 1025 early gastric cancer patients with complete medical records for a retrospective analysis. The Cox proportional risk regression model was used to analyze the independent risk factors for the development of MPM in early gastric cancer. RStudio software was used to compare the OS of early gastric cancer patients with and without MPM, and a nomogram was established to predict the probability of MPM 1-, 2-, 3-year after early gastric cancer. The predictive effectiveness of the nomogram was evaluated by the C-index and calibration curve. Decision curve analysis (DCA) measured the applicability of the nomogram to clinical practice. Results: Of the 1025 patients with early gastric cancer, 66 patients (6.4%) had 69 primary cancers other than early gastric cancer. They had a median follow-up of 41 months, and their cumulative incidence of MPM was 4.9%, 5.4% and 5.9% after 1-, 2-, and 3- year, respectively. Oesophageal cancer was the most frequently detected MPM, followed by lung and colorectal cancers. Male (p=0.038), age ≥65 years (p=0.003), smoking history (p=0.036), and lymph node metastasis (p=0.013) were independent risk factors for MPM in patients with early gastric cancer. Patients with early gastric cancer with MPM had a worse OS prognosis than patients with early gastric cancer without MPM (p<0.001). The internally validated nomogram predicted the probability of developing MPM after early gastric cancer (C index= 0.697). The calibration chart showed that the predicted probability of MPM in early gastric cancer was similar to the observed result, and the DCA showed strong clinical practicability. Conclusion: After the diagnosis and treatment of early gastric cancer, we should be alert to the possibility of MPM and perform regular and careful monitoring.

Clinical and genetic characteristics in lymphoma patients with a second solid malignancy.

Diagnosis and treatment of multiple primary malignancies are becoming a new challenge in clinical practice worldwide. The present study aimed to characterize the clinical and genetic features of multiple primary malignancies in patients with synchronous or metachronous lymphoma and another solid tumor. We retrospectively analyzed 11 cases with lymphoma and another solid tumor. The germline mutations in plasma cell-free DNA samples and somatic mutations in lymphoma and solid tumor tissue samples were identified using targeted next-generation sequencing. In the 11 lymphoma patients, the most common type of concurrent solid tumor was colon adenocarcinoma (case 3, 5, 9 11) followed by papillary thyroid carcinoma (case 1, 7, 10). Metachronous lymphoma and solid tumor in 6 patients were treated with corresponding standard therapy asynchronously. Chemotherapy for colon adenocarcinoma during the interval of lymphoma chemotherapy led to excellent outcome in two patients. Immediate chemotherapy for lymphoma plus elective surgery for synchronous papillary thyroid carcinoma also yielded good prognosis in two patients with synchronous double primaries. Interestingly, we found that 10 of 11 patients with lymphoma and another solid tumor harbored germline mutations in Fanconi anemia complementation group (FANC) genes, including FANCI, FANCA, FANCG, FANCL, FANCD1, FANCF, FANCJ, and FANCS. In summary, comprehensive study of the clinical and genetic features of patients with multiple primary malignancies may improve diagnosis and treatment in the future. Mutations in FANC genes might be a predisposition to tumorigenesis of lymphoma patients with a second solid malignancy.

Synchronous multiple primary malignancies of clear cell renal cell carcinoma with sarcomatoid, thyroid carcinoma: a case report.

Multiple primary malignant neoplasms (MPMNs) are defined as the presence of two or more malignancies with different histologies in the same patient. MPMNs are rare, accounting for fewer than 4% of all tumor cases. Depending on the time interval between the diagnosis of the different malignancies, they are classified as either simultaneous or metachronous MPMNs, with simultaneous being rarer in MPMNs. Here, we present a 63-year-old female patient presenting with multiple primary renal and thyroid carcinomas and discuss the risk factors, treatment options, and prognosis of rare dual carcinomas. We focus on managing multidisciplinary teams and selecting individualized treatment options to deliver valuable treatment strategies to patients.

A Decade of Therapeutic Challenges in Synchronous Gynecological Cancers from the Bucharest Oncological Institute.

The aim of our study is to present the particularities of a specific subset of gynecological cancer patients in Romania. We present a review of synchronous gynecological neoplasia (SGN) treated in the Bucharest Oncological Institute's surgery departments over a decade. Between 2012 and 2022, 7419 female patients with genital malignancies were treated. We identified 36 patients with invasive synchronous primary gynecological cancers (0.5%) and 12 cases with one primary gynecological and another primary invasive pelvic cancer (rectal/bladder). All recurrent, metastatic, or metachronous tumors detected were excluded. Demographic data, personal history, presenting symptoms, pathologic findings, staging, treatment, and evolution for each case were recorded. Usually, the most common SGN association is between ovarian and endometrial cancer of endometrioid differentiation (low-grade malignancies with very good prognosis). However, we noticed that, given the particularities of the Romanian medical system, the most frequent association is between cervical and endometrial, followed by cervical and ovarian cancers. Moreover, the cancer stage at diagnosis is more advanced. In countries with low HPV vaccination rate and low adherence to screening programs, SGNs can present as extremely advanced cases and require extensive surgery (such as pelvic exenterations) to achieve radicality. This multimodal treatment in advanced cases with high tumor burden determines a reduction in survival, time until progression, and quality of life.

Synchronous primary gastric and renal tumors: a case report.

Synchronous multiple primary cancers of the stomach and kidney are very rare, only 45 cases of synchronous multiple primary cancers of the stomach and kidney had been reported in the literature up until 2020. Thus far, no particular risk factors have been identified. We present a case of synchronous multiple primary cancers of the stomach and kidney in a 67-year-old female presenting with a 3-month history of vomiting and abdominal pain. The diagnosis of gastric adenocarcinoma with signet ring cells was confirmed through upper endoscopy with biopsies, while CT-guided biopsies of the renal tumor confirmed the diagnosis of primary kidney neoplasm.

Having more than one cancer at the same time is known as multiple primary malignancies. Having cancers in both the stomach and kidney at the same time is even rarer, with only 45 cases reported in literature. The exact causes of such cancers occurring together are not yet known. We present a 67-year-old woman who was diagnosed with synchronous multiple primary cancers of the stomach and kidney. She presented with vomiting and abdominal pain. The diagnosis of gastric cancer was confirmed through upper endoscopy with biopsies, while biopsies of the renal tumor confirmed the diagnosis of primary kidney cancer.

Multiple Rare Primary Malignancies: A Mixed Squamous Neuroendocrine Adenocarcinoma of the Cervix, Metastasized Carcinosarcoma and Extramammary Vulvar Paget's Disease Case Report.

The occurrence of more than one primary malignant tumor in a single patient is rare. Multiple primary malignancies can pose difficulties in differential diagnosis between primary tumors and metastasis. Here, we present a case report with multiple primary malignancies. The patient is a 45-year-old female who was diagnosed with cervical mixed squamous neuroendocrine adenocarcinoma, metastasized carcinosarcoma and extramammary vulvar Paget's disease. The patient was first diagnosed with a microinvasive squamous cervical carcinoma in situ. After a few months, the amputation of a small residual tumor and histological evaluation revealed an IA1-stage poorly differentiated (G3) mixed squamous and neuroendocrine cervical adenocarcinoma. After two years, the disease had progressed and biopsies from altered sites were taken. Histological diagnosis from an ulcerated vulvar region revealed extramammary vulvar Paget's disease. A biopsy from vagina polyp revealed an earlier diagnosed mixed squamous and neuroendocrine cervical adenocarcinoma. However, histological diagnosis from an inguinal lymph node biopsy was unexpected and revealed carcinosarcoma. It indicated either the development of another primary malignancy, or an unusual spread of metastasis. Clinical presentation as well as diagnostic and treatment challenges are discussed in this case report. This case report shows that multiple primary malignancy cases are difficult to manage both for clinicians and the patient because the therapeutic options can become limited. This complex case was managed by a multidisciplinary team.

Multiple primary malignancies in 788 Chinese patients with diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin lymphoma worldwide. The emergence of multiple primary malignancies (MPMs) has been described as a new prognostic factor in many types of tumors. METHODS: To investigate the morbidity, incidence, and survival of MPM in DLBCL, we retrospectively reviewed the characteristics of 788 patients with DLBCL. RESULTS: Forty-two patients were diagnosed with MPM, and 22 of them were diagnosed with subsequent primary malignancies (SPM) by pathologic biopsy. The incidence of SPM was associated with older age. Germinal center B-cell-like (GCB) subtype and earlier Ann Arbor stage DLBCL patients were more prone to SPM. MPM, age, lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group performance status (ECOG PS), Hans classification, and international prognostic index (IPI) score were prognostic risk factors for overall survival (OS). CONCLUSION: These data provide a comprehensive view of MPM in DLBCL. MPM was an independent prognostic factor of DLBCL in univariate analysis.

Research Progress of Multiple Primary Malignancies Associated With Esophageal Cancer.

With the improvement in survival of patients with tumors, and continuous advancement of diagnostic technology and treatment modalities, instances of multiple primary malignancies (MPMs) are becoming an increasingly common phenomenon. The occurrence of esophageal-relevant MPMs increases the difficulty of diagnosis and treatment, and the overall prognosis is poor. Esophageal cancer related-MPMs tend to occur in areas such as the head, neck, stomach, and lungs. "Field cancerization" is one theoretical basis for the disease, and chemoradiotherapy, environmental life factors, and gene polymorphism are etiological factors. However, the influence of new therapeutic methods on MPM is still unclear, and the relationship between gene polymorphism and MPMs related to esophageal cancer needs further elucidation. Additionally, there is a lack of unified standards for diagnosis and treatment. Therefore, this study aimed to review the causes, clinical features, and prognostic factors of MPMs related to esophageal cancer.

[Multiple primary malignancies combined with SWI/SNF complex-deficient gastric cancer: a case report and literature review].

Multiple primary malignancies combined with SWI/SNF complex-deficient gastric cancer is a rare clinical entity and poorly documented. Herein we report a case of this disease in an 81-year-old male patient treated in our hospital. Before the established diagnosis of metachronous multiple primary malignancies, the patient received left lower lobectomy for a spaceoccupying mass in the left lung, which was confirmed by postoperative pathology as early stage lung cancer. SWI/SNF complex-deficiency gastric cancer with metastasis was subsequently detected by gastroscopy, and high-throughput sequencing identified ARID1A and TMB-H gene mutations in the tumor tissues. The patient received chemotherapy combined with immunotherapy but failed to respond to the treatment, and died 13 months later. We conducted a literature review and analyzed the occurrence, pathological and immunohistochemical characteristics, diagnosis, treatment and prognosis of this disease.

Thrombocytosis as a paraneoplastic syndrome in metastatic malignant peritoneal mesothelioma of biphasic morphology mimicking ovarian adenocarcinoma: A case report.

Malignant peritoneal mesothelioma (MPM) is a rare malignancy, presenting with non-specific and potentially-misleading manifestations. It represents a diagnostic pitfall as it mimics ovarian carcinoma. Maintaining a low diagnostic threshold, obtaining a detailed history, and utilizing immunohistochemical markers to diagnose MPM is crucial as early diagnosis and treatment might improve survival.