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World Journal of Gastrointestinal... May 2024Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies...
BACKGROUND
Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies concerning this specific topic have been published in the past decades, the pathogenesis, associated risk factors, and potential implications on treatment are still poorly understood. Besides the low incidence, historically confusing histological criteria have resulted in confusing data. Nevertheless, the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis, highlight the actual interest to synthesize the known literature regarding CSRCC.
AIM
To provide an updated overview of risk factors, prognosis, and management of CSRCC.
METHODS
A literature search in the MEDLINE/PubMed database was conducted with the following search terms used: 'Signet ring cell carcinoma' and 'colorectal'. Studies in English language, published after January 1980, were included. Studies included in the qualitative synthesis were evaluated for content concerning epidemiology, risk factors, and clinical, diagnostic, histological, and molecular features, as well as metastatic pattern and therapeutic management. If possible, presented data was extracted in order to present a more detailed overview of the literature.
RESULTS
In total, 67 articles were included for qualitative analysis, of which 54 were eligible for detailed data extraction. CSRCC has a reported incidence between 0.1%-2.4% and frequently presents with advanced disease stage at the time of diagnosis. CSRCC is associated with an impaired overall survival (5-year OS: 0%-46%) and a worse stage-corrected outcome compared to mucinous and not otherwise specified adenocarcinoma. The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised. Surgery is the mainstay of treatment, although the rates of curative resection in CSRCC (21%-82%) are lower compared to those in other histological types. In case of peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients.
CONCLUSION
CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation. As such, diagnostic modalities and therapeutic approach should be tailored accordingly.
PubMed: 38764832
DOI: 10.4251/wjgo.v16.i5.2141 -
The American Journal of Surgical... Jul 2024Pancreatic ductal adenocarcinoma (PDAC) develops from 2 known precursor lesions: a majority (∼85%) develops from pancreatic intraepithelial neoplasia (PanIN), and a...
Pancreatic ductal adenocarcinoma (PDAC) develops from 2 known precursor lesions: a majority (∼85%) develops from pancreatic intraepithelial neoplasia (PanIN), and a minority develops from intraductal papillary mucinous neoplasms (IPMNs). Clinical classification of PanIN and IPMN relies on a combination of low-resolution, 3-dimensional (D) imaging (computed tomography, CT), and high-resolution, 2D imaging (histology). The definitions of PanIN and IPMN currently rely heavily on size. IPMNs are defined as macroscopic: generally >1.0 cm and visible in CT, and PanINs are defined as microscopic: generally <0.5 cm and not identifiable in CT. As 2D evaluation fails to take into account 3D structures, we hypothesized that this classification would fail in evaluation of high-resolution, 3D images. To characterize the size and prevalence of PanINs in 3D, 47 thick slabs of pancreas were harvested from grossly normal areas of pancreatic resections, excluding samples from individuals with a diagnosis of an IPMN. All patients but one underwent preoperative CT scans. Through construction of cellular resolution 3D maps, we identified >1400 ductal precursor lesions that met the 2D histologic size criteria of PanINs. We show that, when 3D space is considered, 25 of these lesions can be digitally sectioned to meet the 2D histologic size criterion of IPMN. Re-evaluation of the preoperative CT images of individuals found to possess these large precursor lesions showed that nearly half are visible on imaging. These findings demonstrate that the clinical classification of PanIN and IPMN fails in evaluation of high-resolution, 3D images, emphasizing the need for re-evaluation of classification guidelines that place significant weight on 2D assessment of 3D structures.
Topics: Humans; Imaging, Three-Dimensional; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Pancreatic Intraductal Neoplasms; Female; Carcinoma in Situ; Male; Middle Aged; Aged; Tomography, X-Ray Computed; Tumor Burden; Predictive Value of Tests
PubMed: 38764379
DOI: 10.1097/PAS.0000000000002245 -
European Journal of Surgical Oncology :... Jul 2024For peritoneal metastases from a primary appendiceal mucinous neoplasm to exist, the thin wall of the appendix must perforate to allow mucus or mucus plus tumor cells to... (Review)
Review
For peritoneal metastases from a primary appendiceal mucinous neoplasm to exist, the thin wall of the appendix must perforate to allow mucus or mucus plus tumor cells to gain access to the peritoneal spaces. The proportion of specimens containing tumor cells within mucus as compared to mucus only outside the appendix may have prognostic significance. The histopathology of tumor masses was determined from the specimens resected at the cytoreductive surgery (CRS). The presence versus absence of tumor cells in mucus and the proportion of specimens with tumor cells was determined and correlated with the overall survival of these patients. In 418 patients with a complete cytoreduction for a low-grade appendiceal mucinous neoplasm (LAMN), the cellularity of all resected specimens was determined. The hazard ratio of overall survival of patients whose specimens had no cells as compared to specimens with cells in mucus by histology was 4.41 (1.61, 12.1) (p = 0.0039). If overall survival of patients with all specimens without tumor cells was compared to patients with specimens with 1-99 % tumor and compared to patients with 100 % of specimens with tumor cells, the hazard ratios were 4.3 (1.34, 13.8) (p = 0.0143) and 9.62 (2.93, 31.6) (p = 0.0002), respectively. The cellularity of mucus within the specimens removed by a complete CRS has strong prognostic implications in LAMN patients. LAMN with acellular specimens (LAMNa) as compared to LAMN with tumor cells in specimens (LAMNb) should be staged as different histologic subtypes of mucinous appendiceal neoplasms.
Topics: Humans; Appendiceal Neoplasms; Mucus; Adenocarcinoma, Mucinous; Prognosis; Female; Male; Middle Aged; Cytoreduction Surgical Procedures; Peritoneal Neoplasms; Aged; Neoplasm Grading; Adult; Survival Rate; Retrospective Studies
PubMed: 38761511
DOI: 10.1016/j.ejso.2024.108373 -
Cureus Apr 2024We experienced a case of bilateral corneal thinning during the oral taking of S-1, a combination anti-cancer drug of tegafur, gimeracil, and oteracil-potassium. A...
We experienced a case of bilateral corneal thinning during the oral taking of S-1, a combination anti-cancer drug of tegafur, gimeracil, and oteracil-potassium. A 69-year-old man was prescribed oral S-1 for the treatment of duodenal papilla adenocarcinoma and intraductal papillary mucinous neoplasm. However, he developed a decrease in visual acuity in both eyes after three cycles of S-1 oral taking, and ophthalmic examination revealed corneal thinning exceeding 100 µm and an increase in high-order irregularity of cornea in both eyes. After one month after discontinuation of S-1, his visual acuity and corneal thickness returned to its previous levels. Besides corneal ulcers and perforations, corneal thinning can be recognized as a potential corneal side effect necessitating monitoring during S-1 treatment.
PubMed: 38756279
DOI: 10.7759/cureus.58356 -
Annals of Diagnostic Pathology Aug 2024The status of the lung adenocarcinoma (LUAD) grading system and the association between LUAD differentiation, driver genes, and clinicopathological features remain to be...
Real-world applications of the new grading system in lung adenocarcinoma: A study of 907 patients focusing on revealing the relationship between pathologic grade and genetic status.
BACKGROUND
The status of the lung adenocarcinoma (LUAD) grading system and the association between LUAD differentiation, driver genes, and clinicopathological features remain to be elucidated.
METHODS
We included patients with invasive non-mucinous LUAD, evaluated their differentiation, and collected available clinicopathological information, gene mutations, and analyzed clinical outcomes.
RESULTS
Among the 907 patients with invasive non-mucinous LUAD, 321 (35.4 %) were poorly differentiated, 422 (46.5 %) were moderately differentiated, and 164 (18.1 %) were well differentiated. EGFR mutation was more common in the LUADs accompanied without CGP (complex glandular pattern) than LUADs with CGP (p < 0.001). Correlation analysis between mutations and clinical characteristics showed that EGFR gene mutation (p < 0.001), KRAS gene mutation (p < 0.05), and ALK gene rearrangement (p < 0.001) were significantly related to the degree of tumor differentiation, and the KRAS and ALK gene mutation frequencies were higher in the low-differentiation group than in the high and medium differentiation groups. The EGFR mutation frequency was higher in the well/moderately differentiated adenocarcinoma group.
CONCLUSIONS
Our study adds to the evidence regarding the role of the grading system in prognosis. EGFR, KRAS, and ALK are related to the degree of tumor differentiation.
Topics: Humans; Male; Female; Adenocarcinoma of Lung; Lung Neoplasms; Middle Aged; Aged; Mutation; Neoplasm Grading; Proto-Oncogene Proteins p21(ras); ErbB Receptors; Adult; Aged, 80 and over; Anaplastic Lymphoma Kinase; Adenocarcinoma; Biomarkers, Tumor
PubMed: 38754357
DOI: 10.1016/j.anndiagpath.2024.152328 -
JCO Global Oncology May 2024Ovarian cancer can be categorized into distinct histologic subtypes with varying identifiable risk factors, molecular composition, clinical features, and treatment. The...
PURPOSE
Ovarian cancer can be categorized into distinct histologic subtypes with varying identifiable risk factors, molecular composition, clinical features, and treatment. The global incidence of ovarian cancer subtypes remains limited, especially in low- and middle-income countries (LMICs) without high-quality cancer registry systems.
MATERIALS AND METHODS
We used data from population-based cancer registries of the Cancer Incidence in Five Continents project to calculate the proportions of serous, mucinous, endometrioid, clear cell, and other histologic subtypes of ovarian cancer. Proportions were applied to the estimated numbers of patients with ovarian cancer from Global Cancer Observatory 2020. Age-standardized incidence rates were calculated.
RESULTS
Globally, an estimated 133,818 new patients of serous cancer, 35,712 new patients of mucinous cancer, 29,319 new patients of endometrioid cancer, and 17,894 new patients of clear cell cancer were identified in 2020. The distribution of ovarian cancer histologic subtypes exhibited regional variation. Eastern Europe had the highest rate of serous and mucinous carcinomas, whereas Northern Africa and Eastern Asia had the highest burden of endometrioid and clear cell carcinomas, respectively.
CONCLUSION
This study provides a global incidence landscape of histologic subtypes of ovarian cancer, particularly in LMICs lacking comprehensive registry systems. Our analysis offers valuable insights into disease burden and guidance for tailored strategies for prevention of ovarian cancer.
Topics: Humans; Female; Ovarian Neoplasms; Registries; Incidence; Middle Aged; Global Health; Adult; Aged; Adenocarcinoma, Mucinous; Carcinoma, Endometrioid; Adenocarcinoma, Clear Cell
PubMed: 38754054
DOI: 10.1200/GO.23.00393 -
BMC Medical Imaging May 2024The purpose of this research is to study the sonographic and clinicopathologic characteristics that associate with axillary lymph node metastasis (ALNM) for pure...
BACKGROUND
The purpose of this research is to study the sonographic and clinicopathologic characteristics that associate with axillary lymph node metastasis (ALNM) for pure mucinous carcinoma of breast (PMBC).
METHODS
A total of 176 patients diagnosed as PMBC after surgery were included. According to the status of axillary lymph nodes, all patients were classified into ALNM group (n = 15) and non-ALNM group (n = 161). The clinical factors (patient age, tumor size, location), molecular biomarkers (ER, PR, HER2 and Ki-67) and sonographic features (shape, orientation, margin, echo pattern, posterior acoustic pattern and vascularity) between two groups were analyzed to unclose the clinicopathologic and ultrasonographic characteristics in PMBC with ALNM.
RESULTS
The incidence of axillary lymph node metastasis was 8.5% in this study. Tumors located in the outer side of the breast (upper outer quadrant and lower outer quadrant) were more likely to have lymphatic metastasis, and the difference between the two group was significantly (86.7% vs. 60.3%, P = 0.043). ALNM not associated with age (P = 0.437). Although tumor size not associated with ALNM(P = 0.418), the tumor size in ALNM group (32.3 ± 32.7 mm) was bigger than non-ALNM group (25.2 ± 12.8 mm). All the tumors expressed progesterone receptor (PR) positively, and 90% of all expressed estrogen receptor (ER) positively, human epidermal growth factor receptor 2 (HER2) were positive in two cases of non-ALNM group. Ki-67 high expression was observed in 36 tumors in our study (20.5%), and it was higher in ALNM group than non-ALNM group (33.3% vs. 19.3%), but the difference wasn't significantly (P = 0.338).
CONCLUSIONS
Tumor location is a significant factor for ALNM in PMBC. Outer side location is more easily for ALNM. With the bigger size and/or Ki-67 higher expression status, the lymphatic metastasis seems more likely to present.
Topics: Humans; Female; Lymphatic Metastasis; Middle Aged; Breast Neoplasms; Axilla; Adult; Aged; Adenocarcinoma, Mucinous; Lymph Nodes; Ultrasonography; Biomarkers, Tumor
PubMed: 38745134
DOI: 10.1186/s12880-024-01290-9 -
Journal of the National Comprehensive... May 2024Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of...
BACKGROUND
Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties.
METHODS
Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC.
RESULTS
Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups.
CONCLUSIONS
Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.
Topics: Humans; Female; Receptor, ErbB-2; Breast Neoplasms; Middle Aged; Aged; Adenocarcinoma, Mucinous; Prognosis; Receptors, Estrogen; Adult; Receptors, Progesterone; Neoplasm Staging; Carcinoma, Ductal, Breast; Cohort Studies; Carcinoma, Lobular; Neoplasm Recurrence, Local
PubMed: 38744306
DOI: 10.6004/jnccn.2023.7121 -
Pancreas May 2024Krüppel-like transcription factor 4(KLF4) mutations are more frequently observed in low-grade lesions than in high-grade lesions of intraductal papillary mucinous...
OBJECTIVE
Krüppel-like transcription factor 4(KLF4) mutations are more frequently observed in low-grade lesions than in high-grade lesions of intraductal papillary mucinous neoplasms (IPMN) of the pancreas. However, the role of KLF4 mutations in IPMNs with concomitant pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study clarified the rate and effect of KLF4 mutations in IPMN with concomitant PDAC.
METHODS
DNA was extracted from 65 formalin-fixed and paraffin-embedded samples from 52 patients including 13 IPMN with concomitant PDAC and 39 IPMN alone. A comprehensive screening was performed using next-generation sequencing (NGS) for the 5 IPMNs with concomitant PDAC and 5 IPMNs alone, followed by targeted sequencing for KLF4, GNAS, and KRAS mutations.
RESULTS
In NGS screening, KRAS mutations were observed in all samples except for one, GNAS mutation in two IPMNs with concomitant PDAC, and a KLF4 mutation in one IPMN with concomitant PDAC. Targeted sequence detected KLF4 mutations in 11 of the 52 IPMNs. Concomitant PDAC developed only in the non-intestinal, non-invasive, and branch duct IPMN cases, and KLF4 mutations were more frequent in this IPMN type than in the other type (36% vs. 10%, p = 0.04). For this IPMN type with KLF4 mutation, PDAC-prediction sensitivity, specificity, and accuracy were 63%, 82%, and 79%, respectively.
CONCLUSION
For selected IPMNs with non-intestinal, non-invasive, and branch duct, genetic assessment might be a helpful tool for predicting the possible development of concomitant PDAC, although a prospective validation study using a larger study population is needed.
PubMed: 38743932
DOI: 10.1097/MPA.0000000000002373 -
International Journal of Surgery... May 2024Early-Onset Colorectal Cancer (EOCRC) is associated with a poorer prognosis relative to Late-Onset Colorectal Cancer (LOCRC), and its incidence has witnessed a gradual...
BACKGROUND
Early-Onset Colorectal Cancer (EOCRC) is associated with a poorer prognosis relative to Late-Onset Colorectal Cancer (LOCRC), and its incidence has witnessed a gradual escalation in recent years. This necessitates a comprehensive examination of the underlying pathogenesis and the identification of therapeutic targets specific to EOCRC patients. The present study aimed to delineate the distinct molecular landscape of EOCRC by juxtaposing it with that of LOCRC.
METHODS
A total of 11,344 colorectal cancer patients, diagnosed between 2003 and 2022, were enrolled in this study, comprising 578 EOCRC cases and 10,766 LOCRC cases. Next-generation sequencing technology was employed to assess the tumor-related mutation and tumor mutation burden (TMB) in these patients. PD-L1 expression was quantified using immunohistochemistry. Microsatellite instability (MSI) was determined via capillary electrophoresis (2B3D NCI Panel).
RESULTS
Upon comparing LOCRC with EOCRC patients, the latter group demonstrated a tendency towards advanced TNM stage, lower tumor differentiation, and less favorable histological types. Among LOCRC patients, those with MSI-H status were found to have an earlier TNM stage compared to those with MSI-L/MSS status. Significantly, the incidence of MSI-H was notably higher in EOCRC (10.2%) compared to LOCRC (2.2%). Mutations in the 7-gene panel (ARID1A, FANCI, CASP8, DGFRA, DPYD, TSHR, and PRKCI) were more prevalent in LOCRC. Within the EOCRC cohort, patients with the MSI-H subtype displayed an earlier TNM stage but concurrently exhibited poorer tissue differentiation and a higher frequency of mucinous adenocarcinoma. Among EOCRC patients, FBXW7, FAT1, ATM, ARID1A, and KMT2B mutations were significantly enriched in the MSI-H subgroup. A comparative analysis of MSI-H patients revealed heightened mutation frequencies of FGFBR2, PBRM1, RNF43, LRP1B, FBXW7, ATM, and ARID1A in the EOCRC group. Furthermore, EOCRC patients demonstrated a higher overall TMB, particularly in the MSI-H subtype. PD-L1 expression was elevated in EOCRC and positively associated with MSI status.
CONCLUSIONS
This study revealed a significantly higher MSI-H distribution rate in early-onset colorectal cancer, and EOCRC exhibits a distinct mutational signature coupled with higher PD-L1 expression. These findings hold promise in guiding personalized therapeutic strategies for improved disease management in EOCRC patients.
PubMed: 38742845
DOI: 10.1097/JS9.0000000000001584