Clinicopathological features, prognostic factor analysis, and survival nomogram of patients with double primary cancers involving lung cancer.

BACKGROUND: Although the incidence of double primary cancers (DPCs) involving lung cancer is rising, they have not been studied sufficiently. This study retrospectively analyzed the clinicopathological and prognostic characteristics of DPC patients with lung cancer and developed a survival nomogram to predict the individual OS rates. METHODS: We included 103 DPC patients with lung cancer from Shengjing Hospital between 2016 and 2021. Based on the 6-month cancer occurrence interval, the cases were categorized as synchronous DPCs (sDPCs) or metachronous DPCs (mDPCs). Furthermore, the mDPCs were subdivided based on whether the lung cancer occurred first (LCF cohort) or the other cancer occurred first (OCF cohort). RESULTS: Among the patients, 35 (33.98%) and 68 (66.02%) had sDPCs and mDPCs, respectively. In the mDPCs cohort, 18 (26.47%) belonged to the LCF cohort and 50 (73.53%) to the OCF cohort. The most frequent primary cancer sites were the breast (27.18%), colorectum (22.33%), and urinary system (18.45%). Independent risk factors for progression-free survival were Stage IV lung cancer (p = 0.008) and failure to undergo radical lung cancer surgery (p = 0.028). The risk factors for OS included squamous carcinoma (p = 0.048), Stage IV lung cancer (p = 0.001), single cancer resection plus drug therapy (p < 0.001), drug therapy alone (p = 0.002), failure to undergo radical lung cancer surgery (p = 0.014), and chemotherapy (p = 0.042). The median OS was 37 months, with 3- and 5-year rates of 50.9% and 35.9%, respectively. CONCLUSION: DPCs involving lung cancer account for 1.11% of cases. The breast, colorectum, and urinary system were the most common extra-pulmonary sites, and mDPCs were more frequent than sDPCs. Radical lung cancer surgery significantly affects prognosis, and drug therapy alone may be preferable when only one tumor is operable. The developed nomogram can accurately predict individual 3-year and 5-year OS rates.

Detection of two synchronous histologically different renal cell carcinoma subtypes in the same kidney: a case report and review of the literature.

INTRODUCTION: Renal cell carcinoma (RCC) is the dominant primary renal malignant neoplasm, encompassing a significant portion of renal tumors. The presence of synchronous yet histologically distinct ipsilateral RCCs, however, is an exceptionally uncommon phenomenon that is rather under-described in the literature regarding etiology, diagnosis, management, and later outcomes during follow-up. CASE PRESENTATION: We aim to present the 9th case of a combination chromophobe RCC (ChRCC) and clear cell RCC (ccRCC) in literature, according to our knowledge, for a 69-year-old North African, Caucasian female patient who, after complaining of loin pain and hematuria, was found to have two right renal masses with preoperative computed tomography (CT) and underwent right radical nephrectomy. Pathological examination later revealed the two renal masses to be of different histologic subtypes. CONCLUSION: The coexistence of dissimilar RCC subtypes can contribute to diverse prognostic implications. Further research should focus on enhancing the complex, yet highly crucial, preoperative detection and pathological examination to differentiate multiple renal lesions. Planning optimal operative techniques (radical or partial nephrectomy), selecting suitable adjuvant regimens, and reporting long-term follow-up outcomes of patients in whom synchronous yet different RCC subtypes were detected are of utmost importance.

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.

Mature cystic teratoma with co-existent mucinous cystadenocarcinoma: describing a diagnostic challenge-a case report.

BACKGROUND: Mature cystic teratoma co-existing with a mucinous cystadenocarcinoma is a rare tumor that few cases have been reported until now. In these cases, either a benign teratoma is malignantly transformed into adenocarcinoma or a collision tumor is formed between a mature cystic teratoma and a mucinous tumor, which is either primarily originated from epithelial-stromal surface of the ovary, or secondary to a primary gastrointestinal tract tumor. The significance of individualizing the two tumors has a remarkable effect on further therapeutic management. CASE PRESENTATION: In this case, a mature cystic teratoma is co-existed with a mucinous cystadenocarcinoma in the same ovary in a 33-year-old Iranian female. Computed Tomography (CT) Scan with additional contrast of the left ovarian mass suggested a teratoma, whereas examination of resected ovarian mass reported an adenocarcinoma with a cystic teratoma. A dermoid cyst with another multi-septate cystic lesion including mucoid material was revealed in the gross examination of the surgical specimen. Histopathological examination revealed a mature cystic teratoma in association with a well-differentiated mucinous cystadenocarcinoma. The latter showed a CK7-/CK20 + immune profile. Due to the lack of clinical, radiological, and biochemical discoveries attributed to a primary lower gastrointestinal tract tumor, the immune profile proposed the chance of adenocarcinomatous transformation of a benign teratoma. CONCLUSIONS: This case shows the significance of large sampling, precise recording of the gross aspects, histopathological examination, immunohistochemical analysis, and the help of radiological and clinical results to correctly diagnose uncommon tumors.

Considerations for multidisciplinary management of synchronous primary breast cancer and primary lung cancer - Analysis of thirty-one patients.

BACKGROUND: The simultaneous (synchronous) presence of primary breast cancer and primary lung cancer diagnosed in a single individual is not an uncommon phenomenon. However, reference data for treatment strategy is scarce and "chaotic". In the present study we discuss the management strategy for this group of patients. METHODS: We retrospectively reviewed patients in the primary breast cancer database of the Breast Center and the primary lung cancer database of the Thoracic Surgery Department I of Peking University Cancer Hospital. Patients with synchronous primary breast cancer and primary lung cancer who underwent surgery between December 2010 and December 2023 were included in the study. The sequence of outpatient visits, recommendations of multidisciplinary teams, perioperative treatment, and surgical procedures were reviewed. Meanwhile, survival analysis based on propensity score matching with 1:1 ratio was performed between the 31 patients and those with lung cancer only during the same period. RESULTS: A total of 31 patients with synchronous primary breast cancer and primary lung cancer were identified; all of the patients were women. The average age was 61 years. A total of 24 of the patients had visited the breast center first, and routine chest computed tomography (CT) showed evidence of primary lung cancer. The other seven patients had visited the thoracic surgery clinic first, and routine positron emission tomography (PET)-CT revealed the coexistence of primary breast cancer. All the patients had multidisciplinary team consultations, after which 20 patients were recommended to have preoperative treatment for breast cancer, two patients were recommended to have preoperative treatment for lung cancer, and nine patients were recommended to undergo surgery directly. After surgery, 23 patients received postoperative adjuvant treatment for breast cancer, and no patients needed postoperative adjuvant treatment for lung cancer. Survival analysis showed that there was no significant difference between the 31 patients and those with lung cancer only. CONCLUSION: Routine chest CT is needed for breast cancer patients before surgery, and PET-CT is required for the accurate staging of lung cancer patients. A multidisciplinary expert team should manage synchronous primary breast cancer and primary lung cancer. Emphasis should be placed on patients who need preoperative treatment before surgery. Particularly, for patients who need preoperative chemotherapy, a regimen should be chosen that balances the treatment of lung cancer and breast cancer.

Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer.

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

Synchronous Double Primary Angiosarcoma Originating from the Stomach and Rectum: A Case Report and a Literature Review.

Angiosarcomas originating from the gastrointestinal tract are rare but highly aggressive tumors with poor prognosis. These tumors can be misdiagnosed as benign and malignant gastrointestinal tract lesions. The definitive histological diagnosis of angiosarcomasis made by pathologists based on immunohistochemical analysis demonstrating cluster of differentiation 31 (CD31), factor VIII-related antigen (FVIIIRAg), erythroblast transformation specific related gene (ERG), and cluster of differentiation 34 (CD34). Angiosarcomas are treated with a single or multimodality approach that may include resection, radiotherapy, chemotherapy, and palliative care, depending on the stage of disease and the condition of the patient. No matter the treatment option, metastasis and death rates are substantially highin patients with angiosarcoma. In this context, a 59-year-old male with synchronous double primary angiosarcoma arising from the gastric and rectum who presented with the complaint of abdominal pain and distention to the outpatient clinic is presented in this case report, along with a brief literature review.

The characteristics and prognosis of different disease patterns of multiple primary lung cancers categorized according to the 8th edition lung cancer staging system.

INTRODUCTION: The 8th edition lung cancer staging system was the first to describe the detailed diagnosis and staging of multiple primary lung cancers (MPLC). However, the characteristics and prognosis of MPLC categorized according to the new system have not been evaluated. METHOD: We retrospectively analyzed data from surgically treated MPLC patients in a single center from 2011 to 2013 and explored the characteristics and outcomes of different MPLC disease patterns. RESULTS: In total, 202 surgically treated MPLC patients were identified and classified into different groups according to disease categories and diagnostic time (multifocal ground glass/lepidic (GG/L) nodules: n = 139, second primary lung cancer (SPLC): n = 63, simultaneous MPLC (sMPLC): n = 171, and metachronous MPLC (mMPLC): n = 31). There were significant differences in clinical characteristics between SPLC and GG/L nodule patients and simultaneous and metachronous MPLC patients. The overall 1-, 3-, and 5-year lung cancer-specific survival rates of MPLC were 97.98%, 90.18%, and 82.81%, respectively. Five-year survival was better in patients with multiple GG/L nodules than in those with SPLC (87.94% vs. 71.29%, P < 0.05). Sex was an independent prognostic factor for sMPLC (5-year survival, female vs. male, 88.0% vs. 69.5%, P < 0.05), and in multiple tumors, the highest tumor stage was an independent prognostic factor for all categories of MPLC. CONCLUSIONS: The different disease patterns of MPLC have significantly different characteristics and prognoses. Clinicians should place treatment emphasis on the tumor with the highest stage as it is the main contributor to the prognosis of all categories of MPLC patients.

Synchronous versus metachronous spinal metastasis: a comparative study of survival outcomes following neurosurgical treatment.

PURPOSE: Patients with spinal metastases (SM) from solid neoplasms typically exhibit progression to an advanced cancer stage. Such metastases can either develop concurrently with an existing cancer diagnosis (termed metachronous SM) or emerge as the initial indication of an undiagnosed malignancy (referred to as synchronous SM). The present study investigates the prognostic implications of synchronous compared to metachronous SM following surgical resection. METHODS: From 2015 to 2020, a total of 211 individuals underwent surgical intervention for SM at our neuro-oncology facility. We conducted a survival analysis starting from the date of the neurosurgical procedure, comparing those diagnosed with synchronous SM against those with metachronous SM. RESULTS: The predominant primary tumor types included lung cancer (23%), prostate cancer (21%), and breast cancer (11.3%). Of the participants, 97 (46%) had synchronous SM, while 114 (54%) had metachronous SM. The median overall survival post-surgery for those with synchronous SM was 13.5 months (95% confidence interval (CI) 6.1-15.8) compared to 13 months (95% CI 7.7-14.2) for those with metachronous SM (p = 0.74). CONCLUSIONS: Our findings suggest that the timing of SM diagnosis (synchronous versus metachronous) does not significantly affect survival outcomes following neurosurgical treatment for SM. These results support the consideration of neurosurgical procedures regardless of the temporal pattern of SM manifestation.

Development and Validation of a Nomogram for Prognosis Prediction in Patients with Synchronous Primary Thyroid and Breast Cancer Based on SEER Database.

This study aimed to develop prognostic prediction models for patients diagnosed with synchronous thyroid and breast cancer (TBC). Utilizing the SEER database, key predictive factors were identified, including T stage of thyroid cancer, T stage of breast cancer, M stage of breast cancer, patient age, thyroid cancer surgery type, and isotope therapy. A nomogram predicting 5-year and 10-year survival rates was constructed and validated, exhibiting strong performance (C-statistic: 0.79 in the development cohort (95% CI: 0.74-0.84), and 0.82 in the validation cohort (95% CI: 0.77-0.89)). The area under the Receiver Operator Characteristic (ROC) curve ranged from 0.798 to 0.883 for both cohorts. Calibration and decision curve analyses further affirmed the model's clinical utility. Stratifying patients into high-risk and low-risk groups using the nomogram revealed significant differences in survival rates (P < 0.0001). The successful development and validation of this nomogram for predicting 5-year and 10-year survival rates in patients with synchronous TBC hold promise for similar patient populations, contributing significantly to cancer research.

Triple Primary Cancers: An Analysis of Genetic and Environmental Factors.

The occurrence of multiple primary cancers (MPC) is thought to reflect increased cancer susceptibility in patients due to a combination of genetic and environmental factors. Here we conducted a retrospective review of 2,894 consecutive patients evaluated at a single institution and identified 31 (1.14%) individuals with a history of three or more primary cancers, then analyzed the genetic and environmental influences associated with their propensity for developing malignancies. We found that 35.5% of patients had a hereditary cancer syndrome (HCS), with high penetrance HCS in 72.7% of cases, suggesting that monogenic causes underly a significant proportion of triple primary cancer risk. Analysis of cancer frequencies found that the diagnosis of breast cancer was associated with a significantly lower likelihood of HCS, while the diagnosis of colorectal, prostate, and pancreas cancer was associated with a significantly higher likelihood of HCS. Comparison of HCS-positive and HCS-negative patients revealed similar demographic characteristics, mean age at first diagnosis, and family history of cancer. Moreover, no significant differences in lifestyle behaviors, occupational exposures, chronic health conditions, or treatment with chemotherapy and radiation were observed between HCS-positive and -negative groups, though outliers in tobacco smoking, as well as systemic treatment after both first and second primary cancers were observed. These findings indicate a robust contribution of HCS to cancer susceptibility among patients with triple primary cancers while environmental influences were less evident. This emphasizes the need for larger MPC cohorts incorporating additional genetic and environmental factors to more comprehensively characterize drivers of cancer risk. PREVENTION RELEVANCE: In patients with three or more primary cancers, genetic predisposition explained a significant proportion of cases; however, treatment history, lifestyle habits, and other exposures appeared to play a less significant role. This highlights the value of early genetic screening and the need to develop more sensitive markers of cancer susceptibility. See related Spotlight, p. 193.

Simultaneous melanomas in the setting of multiple primary melanomas.

It is estimated that about 1-13% of melanoma patients will develop multiple primary melanomas. Although the occurrence of subsequent tumors has been described during the last few years, the development of simultaneous melanomas has not yet been extensively studied. We reviewed our registries to identify patients with multiple primary melanomas. We studied epidemiological, clinical, and histological characteristics of patients who were diagnosed with simultaneous melanomas and compared them with those of patients who developed non-synchronous multiple primary melanomas. As simultaneous were defined subsequent melanomas that were diagnosed either at the same visit or within a time-period of maximum of 1 month. Between 2000 and 2020, 2500 patients were diagnosed with melanoma at Andreas Syggros Hospital. 86 (3.4%) patients presented multiple primary melanomas and among them, 35 (40.7%) developed simultaneous melanomas. Patients with simultaneous melanomas developed more frequently more than 2 tumors. First tumors of patients with non-synchronous melanomas were significantly thicker than second tumors while those of patients with simultaneous melanomas did not differ significantly. Slight differences in the tumor localization, staging and histologic type were observed between the two groups. However significant differences were ascertained between first and second tumors in both groups. Simultaneous melanomas occupy an important proportion of multiple primary melanomas, affecting a non-negligible number of patients. Slight differences between simultaneous and non-synchronous multiple primary melanomas seem to define a distinct subcategory of multiple primary melanomas.

The correlation between the main and minor lesions of synchronous multiple gastric neoplasms assessed gastroscopically and microscopically.

BACKGROUND: Patients with early gastric cancer (EGC) are at high risk of developing synchronous multiple gastric neoplasms (SMGNs) after undergoing endoscopic submucosal dissection (ESD). However, most previous studies have had small sample sizes, and few have focused on association studies. AIMS: This study aimed to analyze the associations between SMGN lesion data from patients with EGC treated with ESD and their correlation coefficients. METHODS: The clinical ESD data from two hospitals from January 2008 to January 2021 were retrospectively analyzed. The main lesions were defined as those with a significant depth of infiltration. The larger tumor diameter was considered the main lesion if the lesions had the same infiltration depth. RESULTS: Of the 1013 post-ESD cases examined, 95 cases (223 lesions) had SMGN, and 25 patients had more than three lesions. For the correlation analysis, 190 lesions were included. The study revealed a similarity in pathological type between main and minor lesions (rs = 0.37) and a positive correlation in infiltration depth (rs = 0.58). The mean diameter sizes of the main and minor lesions were 20.7 ± 8.3 mm and 13.1 ± 6.4 mm, respectively, with statistically significant differences (P < 0.001). A linear correlation was observed between the diameter size and a linear regression model was constructed, producing r = 0.38 [95% confidence interval (CI) 0.19-0.54], b = 0.29 (95% CI 0.14-0.44), t = 3.94, P < 0.001]. A correlation was identified between the vertical distribution of the main and minor lesions, the horizontal distribution, and the gross endoscopic morphology (ϕc = 0.25, P = 0.02; ϕc = 0.32, P < 0.001; ϕc = 0.60, P < 0.001). CONCLUSIONS: The correlation coefficients for microscopic characteristics were higher than those for gastroscopy. There is a significant positive correlation between the main and minor lesions regarding pathological stage and depth of infiltration, respectively. The spatial distribution of the lesions and the gastroscopic morphology were similar.