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.

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.

Transcriptomic and genomic profiling of multiple primary colorectal cancers reveals intratumor heterogeneity and a distinct immune microenvironment.

This study reported on the intratumor genomic and immunological heterogeneity of different tumor lesions from a single patient with multiple primary colorectal cancer (MPCC). The goal of this study was to explore the molecular and microenvironment characteristics of tumor lesions from different primary sites in a patient with MPCC. A total of three tumor lesions located in the hepatic flexure of the transverse colon, sigmoid colon, and rectum were collected from a 72-year-old male patient with MPCC. All three tumor samples were examined by using whole-exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq). The transcriptome data of The Cancer Genome Atlas (TCGA) colon cancer (COAD) dataset were explored to characterize the biological impacts of certain immune cells. Only three nonsynonymous mutations were shared by all of the tumor lesions, whereas a number of single nucleotide variant (SNV) and copy number variation (CNV) mutations were shared by tumor samples from the sigmoid colon and rectum. Transcriptomic analysis showed that tumor lesions derived from the transverse colon had decreased levels of RTK, ERK, and AKT pathway activity, thus suggesting lower oncogenic properties in the transverse lesion compared to the other two samples. Further immune landscape evaluation by using single-cell transcriptomic analysis displayed significant intratumor heterogeneity in MPCC. Specifically, more abundant mucosal-associated invariant T (MAIT) cell infiltration was found in transverse colon tumor lesions. Afterwards, we found that higher MAIT cell infiltration may correlate with a better prognosis of patients with colon cancer (immunohistochemical status was MSI-L/pMMR) by using a publicly available TCGA dataset.

Metachronous colorectal cancer metastasis: Who, what, when and what to do about it.

Metachronous colorectal cancer (CRC) metastasis occurs due to micrometastatic disease, in up to 23% of patients who have undergone curative-intent treatment. Metachronous metastasis tends to occur within 2 years of initial treatment. Diagnosis relies on posttreatment surveillance strategies. Care for patients with metachronous CRC metastasis is complex and requires careful multidisciplinary consideration. Those with isolated and technically resectable diseases are recommended to undergo metastasectomy with adjunct chemotherapy, however, survival, even after curative-intent resection, is poor.

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.

[Recent Advances in Diagnosis and Treatment Strategies for Multiple Primary Lung Cancer].

As the utilization of computed tomography in lung cancer screening becomes more prevalent in the post-pandemic era, the incidence of multiple primary lung cancer (MPLC) has surged in various countries and regions. Despite the continued application of advanced histologic and sequencing technologies in this research field, the differentiation between MPLC and intrapulmonary metastasis (IM) remains challenging. In recent years, the specific mechanisms of genetic and environmental factors in MPLC have gradually come to light. Lobectomy still predominates in the treatment of MPLC, but the observation that tumor-specific sublobar resection has not detrimentally impacted survival appears to be a viable option. With the evolution of paradigms, the amalgamated treatment, primarily surgical, is an emerging trend. Among these, stereotactic ablative radiotherapy (SABR) and lung ablation techniques have emerged as efficacious treatments for early unresectable tumors and control of residual lesions. Furthermore, targeted therapies for driver-positive mutations and immunotherapy have demonstrated promising outcomes in the postoperative adjuvant phase. In this manuscript, we intend to provide an overview of the management of MPLC based on the latest discoveries.
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The pregnancy and oncology outcome of fertility-sparing management for synchronous primary neoplasm of endometrium and ovary.

PURPOSE: To investigate the efficacy of fertility-preserving treatment for young women with synchronous primary neoplasm of endometrium and ovary. METHODS: We retrospectively reviewed eight patients with concurrent primary grade 1 presumed stage IA endometrioid endometrial adenocarcinoma (EEA) or endometrial atypical hyperplasia (EAH) and primary stage I ovarian tumors who underwent fertility-sparing treatment in the Obstetrics and Gynecology Hospital of Fudan University between April 2016 and December 2022. RESULTS: Synchronous endometrial and ovarian cancers (SEOC) accounted for 50% of these eight patients. The median age of patients was 30.5 years (range, 28-34 years). None of them received chemotherapy. The median treatment time was 4 months (range, 3-8 months). 87.5% (7/8) cases achieved complete response (CR), and the median time to CR was 3.8 months (range, 1.5-7.7 months). Among patients who got CR, none of them showed any signs of recurrence. Pregnancies and successful deliveries were achieved in 4 of 5 patients. Till September 2023, the median follow-up period was 50.5 months (range:15.2-85.2 months). CONCLUSION: Fertility-sparing treatment is feasible for highly selected patients with synchronous neoplasm of the endometrium and ovary, but strict screening and monitoring are mandatory. Though the results of our limited cases are encouraging, long follow-up and more clinical data are required. Enrolled patients must be fully informed of the risks during conservative treatment.

CD8-Lymphocytic Phenotype Significance in Primary Multiple and Familial Melanoma with Various CDKN2A Mutational Status.

Background and Objectives: In the realm of the rising incidence of cutaneous and mucous melanoma, CDKN2A mutations characterize familial and multiple primary melanoma cases. The involvement of tumor-infiltrating lymphocytes (TILs) is interconnected with survival rates, but may extend even further. The aim of this study is to verify the accuracy of the classical "naked eye" count of CD8-positive T cells comprised within the tumoral population and peritumoral infiltrate versus that obtained via a special software run by the aid of artificial intelligence (AI), used to determine the percentage of CD8-positive TILs. Materials and Methods: The present retrospective cross-sectional study conducted over a period of 5 years (2018-2022) focused on patients diagnosed with mucous and/or cutaneous melanoma, with a positive family history for melanoma, or personal antecedents of primary malignant melanocytic lesions. The 23 selected cases were diagnosed histopathologically, tested for CDKN2A mutations through fluorescent hybridization in situ, and CD8 immunohistochemistry was performed. The included slides were evaluated both manually (naked-eye examination) and automatically (via QuPath platform) for quantifying the CD8-positive TILs. Results: The number of CD8-positive TILs in melanoma samples has been more accurately identified through the use of an AI-mediated software as compared to the human-eye evaluation performed by experimental pathologists. A higher percentage of CD8-positive intratumoral lymphocytes versus stromal lymphocytes was positively associated with more numerous metastatic sites. Conclusions: The CD8 lymphocytic phenotype harbors major significance in the context of familial and multiple primary melanoma and may comprise a cost-effective investigation meant to help in the establishment of melanoma prognosis and response to immunotherapy.

Ultrasonographic and pathological findings of syringocystadenoma papilliferum in the skin.

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Uncommon Coexistence of Pleomorphic Adenoma and Warthin's Tumor in a Painfully Swollen Left Parotid Gland: A Surgical Case Report.

BACKGROUND Benign pleomorphic adenoma is the most common primary tumor of the salivary glands and mainly arises in the parotid gland. Warthin's tumor, or papillary cystadenoma lymphomatosum, represents <30% of benign parotid tumors. The simultaneous occurrence of multiple parotid tumors is rarely described - depending on the corresponding histology (different/identical), the time of their occurrence (synchronous/metachronous), as well as their location (unilateral/bilateral), multiple parotid tumors can be further sub-classified. CASE REPORT We describe the case of a 54-year-old female patient with progressive and painful swelling of the left parotid gland for the last 6 months. During extra-oral examination, a bulging, displaceable mass of approximately 3 cm was determined. A subsequent MRI (magnetic resonance imaging) examination revealed a multifocal lesion but failed to provide a decisive clue as to the tumor entity of the lesion, and a lateral (superficial) parotidectomy was performed. Postoperative histomorphological interpretation allowed the final pathological diagnosis of synchronous, unilateral occurrence of a pleomorphic adenoma as well as a Warthin's tumor. CONCLUSIONS This report presents a rare case of synchronous unilateral parotid tumors and supports that benign pleomorphic adenoma and Warthin's tumor are the most common associations. Since clinical examination, MRI imaging, and even cytological assessment could be misleading in the detection of synchronous ipsilateral multiple parotid gland tumors, our report also highlights the importance of timely and accurate diagnosis with histopathology to plan surgery and to exclude malignant transformation, which is a rare but important association with both types of primary salivary gland tumor.

Ipsilateral synchronous papillary renal neoplasm with reverse polarity and urothelial carcinoma in a renal transplant recipient: a rare case report with molecular analysis and literature review.

BACKGROUND: Renal transplant recipients (RTRs) have a 3- to 5-fold higher risk of developing malignant tumors than the general population, with new malignant tumors after transplantation considered to be the leading cause of death in RTRs. In pathological practice, it is rare for neoplasms with different histology to be located in the same organ. We report the first case of a synchronous papillary renal neoplasm with reverse polarity (PRNRP) and urothelial carcinoma (UC) in the ipsilateral kidney in an RTR. Molecular detection was conducted by next-generation sequencing. CASE PRESENTATION: A 68-year-old female suffered from uremia 19 years ago and underwent renal transplantation (RT) after receiving dialysis for 6 months. Hematuria occurred one month ago and an enhanced CT showed that there were two abnormal density foci in the middle and lower parts of the autologous left kidney. A laparoscopic left nephrectomy and ureterectomy were performed. Gross examination revealed a mass (I) in the left renal parenchyma, 2*1.8*1.5 cm in size, that protruded from the renal capsule, and a cauliflower-like mass (II), 5*2.5*2 cm in size, adjacent to the mass (I). Microscopic findings revealed these lesions were PRNRP and UC, respectively. PCR analysis revealed a KRAS gene mutation (G12D in exon 2) in the PRNRP, while NGS analysis revealed FGFR3 (S249C in exon 7) and KDM6A (Q271Ter in exon 10 and A782Lfs in exon 17) mutations in the UC. CONCLUSIONS: We report here for the first time an extraordinarily rare case of synchronous renal tumors of a PRNRP and UC in the ipsilateral kidney of an RTR. We identified simultaneous KRAS, FGFR3, and KDM6A mutations in two different renal masses in the ipsilateral kidney. Pathologic assessment with comparative molecular analysis of mutational profiles facilitates tumor studies after RT and may be of great value in clinical management strategies.

[Synchronous association of two primary lung tumors: a case report]. / Association synchrone de deux tumeurs pulmonaires primitives: à propos d'un cas.

Synchronous multiple primary lung tumors are a relatively rare entity with an increasing incidence in recent years due to the development of thoracic imaging and immunohistochemical techniques. The second lesion is considered in most cases as a secondary location, which partly explains the decrease in the incidence of this entity. We report the observation of a 74-year-old patient with two synchronous primary lung tumors, an adenocarcinoma and an epidermoid carcinoma. Through this clinical observation, we highlight the difficulty of diagnosing synchronous tumors and the major interest of new imaging modalities and immunohistochemical techniques for the optimal management of these tumors.

Synchronous and metachronous primary colorectal cancers with concordant and discordant mismatch repair status.

Multiple primary colorectal carcinomas (CRCs) synchronous, when detected approximately at the same time, or metachronous, when a significant amount of time has elapsed between diagnoses can show both mismatch repair (MMR) status concordance and discordance between primary tumors. The aim was to evaluate the MMR status of a monoinstitutional, retrospective cohort of synchronous and metachronous CRCs, with a focus on the frequency of cases with discordant MMR status, and explore the MMR status of metastatic nodal deposits. All synchronous and metachronous CRCs diagnosed in our institution between 2011 and 2023 were collected. Clinicopathologic characteristics were evaluated, including MMR status of all CRCs, BRAF mutation, and MLH1 promoter methylation analyses. MMR status discordant cases were further analyzed, and MMR testing was performed on nodal metastases. Of 3671 patients, 107 (2.9%) had multiple CRCs (94 synchronous and 13 metachronous; total number of CRCs 220). Sixty CRCs were MMR deficient (dMMR) (27.3%), and most were right-sided and high-grade and showed special histologic features (P < .00001). Ninety-three patients showed intertumoral MMR concordance: 70 (65.4%) with MMR-proficient (pMMR) CRCs, and 23 (21.5%) were dMMR. Fourteen patients (13.1%) showed intertumoral MMR discordance (at least one dMMR and one pMMR), and in 5 patients, nodal metastases were present: 2 patients harbored metastases only from their pMMR cancer, 2 only from their dMMR cancer, and in 1 patient both pMMR and dMMR metastases were present. In conclusion, all multiple primary CRCs should be analyzed for MMR status as discordant MMR is possible as well as discordant metastatic nodal deposits, and this may be important for patient management.

Molecular biological analysis revealed a case of synchronous endometrial and ovarian cancer with different histological grade as metastatic ovarian cancer from endometrial cancer: Case report and review of literature.

The diagnosis of synchronous endometrial and ovarian cancer or metastatic cancer of the same histological type is difficult. In this study, molecular biology analysis was performed to determine ovarian metastasis from endometrial cancer. A 38-year-old woman had pathological evidence of endometrial cancer (endometrioid carcinoma, grade 1) and ovarian cancer (endometrioid carcinoma, grade 3); a disseminated nodule in the serosa uteri was also diagnosed as endometrioid carcinoma (grade 3). Customized panel sequencing revealed a common mutation pattern in ovarian cancer and disseminated nodules. Furthermore, endometrial cancer showed the same mutation patterns for FGFR3 and PTEN as ovarian cancer and disseminated nodules. All tumors were microsatellite instability high. Clinicopathological and molecular biology analyses suggested that the patient had ovarian metastasis from endometrial cancer. The patient underwent adjuvant chemotherapy with paclitaxel and carboplatin, with no recurrence. Molecular biology techniques may enable appropriate treatment based on clinically accurate diagnosis.

Case reports of collision and composite carcinomas of the thyroid: an insight into their origin and clinical significance.

BACKGROUND: Collision and composite carcinomas of the thyroid are extremely rare, and their clinical and biological characteristics are poorly understood. CASE PRESENTATION: The first case was a 41-year-old female patient with a right thyroid nodule. Pathological diagnosis was papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma composite carcinoma. Surgical treatment was right thyroid lobectomy + left partial thyroidectomy + right central neck lymph node dissection. The second case was a 60-year-old female with bilateral thyroid nodules. Total thyroidectomy was performed, and the pathological diagnosis was thyroid collision carcinoma involving follicular thyroid carcinoma on the left side and PTC on the right side. The clinical, histological and gene changes of collision and composite carcinomas of the thyroid are poorly described. With different biological invasion characteristics, the ideal treatment and the prognosis is currently unknown and individualized treatment is necessary. CONCLUSIONS: It is recommended that in composite carcinoma, each cancer is evaluated and treated according to the most severe tumor. Collision carcinoma should be treated as two separate synchronous primary tumors. For both collision and composite carcinomas of the thyroid, the follow-up after treatment should be extensive.

Multiple primary melanomas: A literature review.

Survival rates for melanoma have increased in recent years, a higher number of patients survive after diagnosis, and, therefore, are at an increased risk of developing second primary melanoma. The aim of this literature review is to identify and integrate the incidence rates and other characteristics of multiple primary melanomas. A total of 36 independent studies were included in this review. The incidence of multiple primary melanomas reported ranged from 1.1% to 20.4%. Synchronous melanomas account for 5% to 66% of the reported lesions. The most common site for both first and subsequent melanomas is the trunk. Superficial spreading melanoma is the most common histological type in both first and subsequent primary melanoma. Regarding the mean Breslow index, subsequent melanomas appeared to be thinner than first melanomas. Our review suggests that melanoma patients are at a higher risk of developing a second primary melanoma and long-term surveillance is needed.