Invasive Component Research Articles

All that is squamoid is not squamous: A rare case of Squamoid Eccrine Ductal Carcinoma presenting as an intranasal mass

Abstract Introduction/Objective Squamoid eccrine ductal carcinoma (SEDC) is a rare adnexal tumor that poses diagnostic challenges because of the rarity, variable clinical presentation, and misdiagnosis on superficial biopsy sampling. Methods/Case Report We report a 52-year-old immunosuppressed male, status-post kidney and heart transplants who presented with an anterior nasal mass, the biopsy of which was interpreted as squamous cell carcinoma (SCC). Resection revealed a 2.5cm intranasal mass eroding through the hard palate. Histology showed a biphasic tumor arising from nasal vestibular skin with a superficial squamoid component (p40 positive) and a deeply invasive component demonstrating ductal differentiation (CEA positive) consistent with SEDC. SEDC has a predilection towards skin of head and neck region but SEDC presenting as an intranasal mass has not been reported. In our case, the tumor arose from nasal vestibular skin with destructive bony invasion within the nasal cavity. The patient’s long- term immunosuppression likely played a role in the etiopathogenesis and aggressive progression of this tumor. Interestingly, he also had history of multiple sebaceous carcinomas and cutaneous T-cell lymphoma with no known genetic predisposition, further implicating immunosuppression as the key risk factor for development of his cutaneous malignances. Results (if a Case Study enter NA) N/A Conclusion This case exemplifies the potential diagnostic pitfalls in squamoid lesions of the head and neck. Given the overwhelming prevalence of conventional SCC, rarer tumors with squamous differentiation often are not considered in the differential diagnosis, especially of an intranasal mass. A superficial biopsy often is misdiagnosed as SCC due to the lack of representation of deep-seated ductal components. A high index of suspicion and adequate examination of deeper aspects of the lesion are imperative for accurate diagnosis.

Sneaky DCIS-looking Invasive Ductal Carcinoma of the Breast in the Extensive DCIS Background

Abstract Introduction/Objective In the most cases, invasive ductal carcinoma (IDC) of the breast is identifiable when they present with classic infiltrative growth pattern. However, subset of IDC can occur in a very sneaky way, significantly mimicking the appearance of ductal carcinoma in situ (DCIS). In this condition, it’s much more easier to miss the invasive component without pulling ancillary staining when morphologic findings are extremely compatible with DCIS, especially the diagnosis of DCIS was made on the previous biopsy. Methods/Case Report Retrospective analysis of the histologic and immunohistochemical findings of pure DCIS and DCIS-looking invasive ductal carcinoma. Results (if a Case Study enter NA) Here, we reported a 55 year-old female who was noted to have microcalcification at the 11:00 o’clock of the right posterior breast on routine mammographic examination in 09/2023. Biopsy of the calcification area in 10/2023 reported high grade DCIS (ER+ PR-). Histologic examination of subsequent mastectomy specimen showed two separate DCIS-looking areas. Immunohistochemical (IHC) staining showed that myoepithelial markers, p63 and smooth muscle myosin heavy chain (SMMHC), were retained at the periphery of all the expanded acini in one area. Unexpectedly and surprisingly, p63 and SMMHC were completely lost at the periphery of part of the DCIS-looking acini in another area, immunohistochemically compatible with the diagnosis of invasive ductal carcinoma admixed with DCIS. Conclusion Knowing that invasive ductal carcinoma of the breast can present as DCIS-looking morphology, especially given the condition that the diagnosis of DCIS was rendered on the previous biopsy, will enhance awareness of pathologists to recognize sneaky DCIS-looking invasive ductal carcinoma in the extensive DCIS background. In turn, this will prevent misdiagnosis and under-treatment of patients with invasive ductal carcinoma of the breast.

Is Immunohistochemical Galectin-3 Expression Associated with the Epithelial-Mesenchymal Transition in High- and Low-Grade Invasive Urothelial Carcinomas of the Bladder?

Background/Objectives: Bladder cancer, predominantly urothelial carcinoma, is an important malignancy of the urinary system. Despite the same histologic grade and stage, some patients seem to have a worse prognosis. In this context, the epithelial-mesenchymal transition (EMT), characterized by the loss of E-cadherin and gain of vimentin expression, is an important process in tumor progression. Galectin-3, a lactose-binding protein involved in various cellular processes, has been associated with increased tumor cell migration, invasion, and treatment resistance. Methods: In this study, 223 bladder cancer cases were examined, and E-cadherin, vimentin, and galectin-3 expression was evaluated by immunohistochemical staining in tumor budding areas and invasive components. These markers were also correlated with clinicopathological parameters, including tumor grade and stage. Results: The results indicated a significant decrease in E-cadherin expression and an increase in vimentin staining in higher-grade and higher-stage tumors, supporting EMT involvement. Galectin-3 expression was notably higher in T1 high-grade tumors but decreased in T2 stage tumors. Despite this, no significant correlation was found between galectin-3 and E-cadherin or vimentin, suggesting a complex role of galectin-3 in EMT. Conclusions: High galectin-3 expression in T1 high-grade tumors highlights its potential role in early tumor progression and as a therapeutic target. However, the decrease in its expression in advanced stages underscores the need for further research to understand its multifaceted involvement in bladder cancer. These findings suggest that while galectin-3 may contribute to the EMT and early tumor progression, its exact role and potential as a therapeutic target require more detailed investigation.

Total versus Partial Pancreatectomy in Patients with Pancreatic Cancer Arising from Multifocal or Diffuse Intraductal Papillary Mucinous Neoplasia - A Multicenter Observational Study.

To investigate the impact of total pancreatectomy (TP) on oncological outcomes for patients at high-risk of local recurrence or secondary progression in the remnant gland after partial pancreatectomy (PP) for IPMN-associated cancer. Major risk factors for invasive progression in the remnant gland include multifocality, diffuse main duct dilation, and the presence of invasive cancer. In these high-risk patients, a TP may be oncologically beneficial. However, current guidelines discourage TP, especially in elderly patients. This international multicenter study compares TP versus PP in patients with adenocarcinoma arising from multifocal or diffuse IPMN (2002-2022). Log-rank test and multivariable Cox-analysis with interaction analysis was performed to assess overall survival (OS), disease-free survival (DFS), and local-DFS. Of 359 included patients, 162 (45%) were treated with TP, whereas 197 (55%) underwent PP. Despite TP and PP having similar R0-rates (59% vs. 58%, P=0.866), patients undergoing a TP had significantly longer local-DFS compared to PP (P=0.039). However, no difference in OS was observed between the two surgical approaches (P=0.487). In a multivariable analysis, young age (optimal cut-off ≤63.6yrs) was associated with an OS benefit derived from TP (HR:0.44, 95%CI:0.22-0.89), whereas no significant difference was observed in elderly patients (HR:1.24, 95%CI:0.92-1.67, Pinteraction=0.007). Since overall, patients with diffuse or multifocal IPMN with an invasive component do not benefit from TP in terms of OS, the indication for TP may be individualized to young patients who have sufficient life expectancy to benefit from the prevention of secondary progression or local recurrence.

The prognostic value of lymphovascular invasion for stage I lung adenocarcinoma based on the presence of ground-glass opacity.

There is still a debate regarding the prognostic implication of lymphovascular invasion (LVI) in stage I lung adenocarcinoma. Ground-glass opacity (GGO) on CT is known to correlate with a less invasive or lepidic component in adenocarcinoma, which may influence the strength of prognostic factors. This study aimed to explore the prognostic value of LVI in stage I lung adenocarcinoma based on the presence of GGO. Stage I lung adenocarcinoma patients receiving lobectomy between 2010 and 2019 were retrospectively categorized as GGO-positive or GGO-negative (solid adenocarcinoma) on CT. Multivariable Cox regression analyses were performed for disease-free survival (DFS) and overall survival (OS) to evaluate the prognostic significance of pathologic LVI based on the presence of GGO. Of 924 patients included (mean age, 62.5 ± 9.2 years; 505 women), 525 (56.8%) exhibited GGO-positive adenocarcinoma and 116 (12.6%) were diagnosed with LVI. LVI was significantly more frequent in solid than GGO-positive adenocarcinoma (20.1% vs. 6.9%, p < 0.001). Multivariable analysis identified LVI and visceral pleural invasion (VPI) as significant prognostic factors for shorter DFS among solid adenocarcinoma patients (LVI, hazard ratio (HR): 1.89, p = 0.004; VPI, HR: 1.65, p = 0.003) but not GGO-positive patients (p = 0.76 and p = 0.87). In contrast, LVI was not a significant prognostic factor for OS in either group (p > 0.05). In stage I lung adenocarcinoma, pathologic LVI was associated with DFS only in patients with solid lung adenocarcinoma. Lymphovascular invasion (LVI) significantly affects disease-free survival in solid-stage I lung adenocarcinoma patients, but not those with ground-glass opacity (GGO) adenocarcinoma. Risk stratification considering both GGO on CT and LVI may identify patients benefiting from increased surveillance. The presence of ground-glass opacity portends different prognoses for lung adenocarcinoma. In stage I lung adenocarcinoma, lymphovascular invasion (LVI) was significantly more frequent in solid adenocarcinomas than in ground-glass opacity (GGO)-positive adenocarcinomas. LVI was not associated with overall survival in patients with either solid adenocarcinomas or GGO adenocarcinomas.

Enhancing identification of early-stage lung adenocarcinomas through solid component analysis of three-dimensional computed tomography images.

As the role of segmentectomy expands in managing early-stage lung adenocarcinoma, precise preoperative assessments of tumor invasiveness via computed tomography become crucial. This study aimed to evaluate the effectiveness of solid component analysis of three-dimensional (3D) computed tomography images and establish segmentectomy criteria for early-stage lung adenocarcinomas. This retrospective study included 101 cases with adenocarcinoma diagnoses, with patients undergoing segmentectomy for clinical stage 0 or IA between 2012 and 2017. The solid component volume (3D-volume) and solid component ratio (3D-ratio) of tumors were calculated using 3D computed tomography. Additionally, based on two-dimensional (2D) computed tomography, the solid component diameter (2D-diameter) and solid component ratio (2D-ratio) were calculated. The area under the receiver-operating characteristic curve (AUC) was calculated for each method, facilitating predictions of mortality and recurrence within 5years. The AUC of each measurement was compared with those of invasive component diameter (path-diameter) and invasive component ratio (path-ratio) obtained through pathology analysis. The predictive performance of 3D-volume did not differ significantly from that of path-diameter, whereas 2D-diameter exhibited less predictive accuracy (AUC: 3D-volume, 2D-diameter, and path-diameter: 0.772, 0.624, and 0.747, respectively; 3D-volume vs. path-diameter: p = 0.697; 2D-diameter vs. path-diameter: p = 0.048). Results were similar for the solid component ratio (AUC: 3D-ratio, 2D-ratio, path-ratio: 0.707, 0.534, and 0.698, respectively; 3D-ratio vs. path-ratio: p = 0.882; 2D-ratio vs. path-ratio: p = 0.038). Solid component analysis using 3D computed tomography offers advantages in prognostic prediction for early-stage lung adenocarcinomas.

Identification and molecular characterization of a novel Babesia orientalis rhoptry neck protein 4 (BoRON4).

Babesia orientalis, a protozoan parasite transmitted by the tick Rhipicephalus haemaphysaloides, holds significant economic importance along the Yangtze River. Key factors in the host invasion process include rhoptry neck proteins (RON2, RON4, and RON5) and apical membrane antigen 1 (AMA1). However, the intricacies of the interaction between AMA1 and RONs remain incompletely elucidated in B. orientalis. To better understand these crucial invasion components, the RON4 gene of B. orientalis (BoRON4) was cloned and sequenced. RON4 is 3468 base pairs long, encodes 1155 amino acids, and has a predicted molecular weight of 130kDa. Bioinformatics analysis revealed a unique region (amino acid residues 109-452) in BoRON4, which demonstrates higher sensitivity to epitope activity. The BoRON4 gene was strategically truncated, amplified, and cloned into the pGEX-6p-1 vector for fusion expression. We successfully used the mouse polyclonal antibody to identify native BoRON4 in B. orientalis lysates. Furthermore, the corresponding BoRON4 protein band was detected in the water buffalo serum infected with B. orientalis, while no such band was observed in the control. Additionally, I-TASSER and Discovery Studio software were used to predict the tertiary structures of BoRON4 and its ligands, CH-PKA and CH-complex. These ligands can serve as lead compounds for the development of anti-babesiosis drugs. In conclusion, BoRON4 emerges as a promising candidate antigen for distinguishing water buffalo infected with B. orientalis from their normal counterparts. This study positions BoRON4 as a potential diagnostic antigen for babesiosis in water buffalo, contributing valuable insights to the field of parasitology.

Adding contrast-enhanced ultrasound can improve the predictive ability of breast conventional ultrasound and mammography for pathological upgrade of biopsy-confirmed ductal carcinoma in situ

ObjectivesTo evaluate the added value of contrast-enhanced ultrasound (CEUS) on top of breast conventional imaging for predicting the upgrading of ductal carcinoma in situ (DCIS) to invasive cancer after surgery. MethodsThis retrospective study enrolled 140 biopsy-proven DCIS lesions in 138 patients and divided them into two groups based on postoperative histopathology: non-upgrade and upgrade groups. Conventional ultrasound (US), mammography (MMG), CEUS and clinicopathological (CL) features were reviewed and compared between the two groups. The predictive performance of different models (with and without CEUS features) for histologic upgrade were compared to calculate the added value of CEUS. ResultsFifty-nine (42.1 %) lesions were histologically upgraded to invasive cancer after surgery. By logistic regression analyses, we found that high-grade DCIS at biopsy (P=0.004), ultrasonographic lesion size > 20 mm (P=0.007), mass-like lesion on US (P=0.030), the presence of suspicious calcification on MMG (P=0.014), the presence of perfusion defect (P=0.005) and the area under TIC>1021.34 ml (P<0.001) on CEUS were six independent factors predicting concomitant invasive components after surgery. The CL+US+MMG model made with the four predictors in the clinicopathologic, US and MMG categories yielded an area under the receiver operating curve (AUROC) value of 0.759 (95 % CI: 0.680–0.828) in predicting histological upgrade. The combination model built by adding the two CEUS predictors to the CL+US+MMG model showed higher predictive efficacy than the CL+US+MMG model (P=0.018), as the AUROC value was improved to 0.861 (95 % CI: 0.793–0.914). ConclusionsThe addition of contrast-enhanced ultrasound to breast conventional imaging could improve the preoperative prediction of an upgrade to invasive cancer from CNB −proven DCIS lesions.

An international multi-institutional validation of T1 sub-staging of intraductal papillary mucinous neoplasm-derived pancreatic cancer.

Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared with its biologically distinct counterpart, pancreatic intraepithelial neoplasia (PanIN)-derived PDAC. Thus, experts proposed T1 sub-staging for IPMN-derived PDAC. However, this has never been validated. Consecutive upfront surgery patients with IPMN-derived PDAC from 5 international high-volume centers were classified by the proposed T1 sub-staging classification (T1a ≤0.5, T1b >0.5 and ≤1.0, and T1c >1.0 and ≤2.0 cm) using the invasive component size. Kaplan-Meier and log-rank tests were used to compare overall survival (OS). A multivariable Cox regression was used to determine hazard ratios (HRs) with confidence intervals (95% CIs). Among 747 patients, 69 (9.2%), 50 (6.7%), 99 (13.0%), and 531 patients (71.1%), comprised the T1a, T1b, T1c, and T2-4 subgroups, respectively. Increasing T-stage was associated with elevated CA19-9, poorer grade, nodal positivity, R1 margin, and tubular subtype. Median OS for T1a, T1b, T1c, and T2-4 were 159.0 (95% CI = 126.0 to NR), 128.8 (98.3 to NR), 77.6 (48.3 to 108.2), and 31.4 (27.5 to 37.7) months, respectively (P < .001). OS decreased with increasing T-stage for all pairwise comparisons (all P < .05). After risk adjustment, older than age 65, elevated CA19-9, T1b [HR = 2.55 (1.22 to 5.32)], T1c [HR = 3.04 (1.60 to 5.76)], and T2-4 [HR = 3.41 (1.89 to 6.17)] compared with T1a, nodal positivity, R1 margin, and no adjuvant chemotherapy were associated with worse OS. Disease recurrence was more common in T2-4 tumors (56.4%) compared with T1a (18.2%), T1b (23.9%), and T1c (36.1%, P < .001). T1 sub-staging of IPMN-derived PDAC is valid and has significant prognostic value. Advancing T1 sub-stage is associated with worse histopathology, survival, and recurrence. T1 sub-staging is recommended for future guidelines.

Intra-ampullary Papillary Tubular Neoplasm (IAPN): Clinicopathologic Analysis of 72 Cases Highlights the Distinctive Characteristics of a Poorly Recognized Entity.

The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from other ampullary tumors remain limited. A detailed clinicopathologic analysis of 72 previously unpublished IAPNs was performed. The patients were: male/female=1.8; mean age=67 years (range: 42 to 86 y); mean size=2.3cm. Gross-microscopic correlation was crucial. From the duodenal perspective, the ampulla was typically raised symmetrically, with a patulous orifice, and was otherwise covered by stretched normal duodenal mucosa. However, in 6 cases, the protrusion of the intra-ampullary tumor to the duodenal surface gave the impression of an "ampullary-duodenal tumor," with the accurate diagnosis of IAPN established only by microscopic correlation illustrating the abrupt ending of the lesion at the edge of the ampulla. Microscopically, the preinvasive component often revealed mixed phenotypes (44.4% predominantly nonintestinal). The invasion was common (94%), typically small (mean=1.2cm), primarily pancreatobiliary-type (75%), and showed aggressive features (lymphovascular invasion in 66%, perineural invasion in 41%, high budding in 30%). In 6 cases, the preinvasive component was pure intestinal, but the invasive component was pancreatobiliary. LN metastasis was identified in 42% (32% in those with ≤1cm invasion). The prognosis was significantly better than ampullary-ductal carcinomas (median: 69 vs. 41months; 3-year: 68% vs. 55%; and 5-year: 51% vs. 35%, P =0.047). In conclusion, unlike ampullary-duodenal carcinomas, IAPNs are often (44.4%) predominantly nonintestinal and commonly (94%) invasive, displaying aggressive features and LN metastasis even when minimally invasive, all of which render them less amenable to ampullectomy. However, their prognosis is still better than that of the "ampullary-ductal" carcinomas, with which IAPNs are currently grouped in CAP protocols (while IAPNs are kindreds of intraductal tumors of the pancreatobiliary tract, the latter represents the ampullary counterpart of pancreatic adenocarcinoma/cholangiocarcinoma).

Giant Bowen’s disease of anterior abdominal wall with invasive squamous cell carcinoma-A rare case report

A 65 years old male presented to the out-patient department of Dermatology with complaints of a large verruco-erosive lesion on left anterior abdominal wall for 15 years. A wedge incision biopsy was done which showed features of Bowen’s disease. The patient was referred to department of General Surgery where a complete excision was done. The final histopathology report confirmed the diagnosis of Bowen disease with a focus of invasive carcinoma component. This case report is unusual for its clinical presentation, duration and location of the lesion.

Rare tumours of the pancreas: monocentric study

PurposeThe biology of rare pancreatic tumours, which differs from that of ductal pancreatic cancer, requires increased attention. Although the majority of rare pancreatic tumours are benign, it is difficult to decide whether an invasive component exists without complete removal of the lesion, despite considerable progress in diagnosis. We are investigating a large cohort of patients with histologically confirmed epithelial non-ductal non-neuroendocrine neoplasms of the pancreas.MethodsHere we analyze long-term survival from patients, who underwent resection of histologically confirmed epithelial non-ductal non-neuroendocrine neoplasms of the pancreas. At our department between Jan 1st, 1999, and Dec 31st, 2019. The median follow-up was 61 (range 0–168) month. All statistical analyses were performed using SPSS 26.0 (IBM, Chicago, IL, USA) software.Results46 patients (48%) were followed up for more than 5 years, 18 patients (19%) for more than 10 years. The 5-year and 10-year survival rates for rare non-invasive pancreatic tumours were 72% and 55% respectively. The proportion of rare tumour entities (non-ductal and non-neuroendocrine) increased continuously and statistically significantly (p = 0.004) from 4.2 to 12.3% in our clinic between 1999 and 2019. If there is no invasive growth yet, there is a varying risk of malignant degeneration in the course of the disease. Therefore, the indication for pancreatic resection is still the subject of discussion.ConclusionThe long-term prognosis of rare epithelial pancreatic tumours after R0 resection—even if they are already malignant—is much better than that of ductal pancreatic cancer.

AI-based selection of individuals for supplemental MRI in population-based breast cancer screening: the randomized ScreenTrustMRI trial

Screening mammography reduces breast cancer mortality, but studies analyzing interval cancers diagnosed after negative screens have shown that many cancers are missed. Supplemental screening using magnetic resonance imaging (MRI) can reduce the number of missed cancers. However, as qualified MRI staff are lacking, the equipment is expensive to purchase and cost-effectiveness for screening may not be convincing, the utilization of MRI is currently limited. An effective method for triaging individuals to supplemental MRI screening is therefore needed. We conducted a randomized clinical trial, ScreenTrustMRI, using a recently developed artificial intelligence (AI) tool to score each mammogram. We offered trial participation to individuals with a negative screening mammogram and a high AI score (top 6.9%). Upon agreeing to participate, individuals were assigned randomly to one of two groups: those receiving supplemental MRI and those not receiving MRI. The primary endpoint of ScreenTrustMRI is advanced breast cancer defined as either interval cancer, invasive component larger than 15 mm or lymph node positive cancer, based on a 27-month follow-up time from the initial screening. Secondary endpoints, prespecified in the study protocol to be reported before the primary outcome, include cancer detected by supplemental MRI, which is the focus of the current paper. Compared with traditional breast density measures used in a previous clinical trial, the current AI method was nearly four times more efficient in terms of cancers detected per 1,000 MRI examinations (64 versus 16.5). Most additional cancers detected were invasive and several were multifocal, suggesting that their detection was timely. Altogether, our results show that using an AI-based score to select a small proportion (6.9%) of individuals for supplemental MRI after negative mammography detects many missed cancers, making the cost per cancer detected comparable with screening mammography. ClinicalTrials.gov registration: NCT04832594.

Comparison of the Structural, Cytological and Biomarker Expression in Carcinoma in situ and Invasive Components in Breast Carcinoma

Comparison of the Structural, Cytological and Biomarker Expression in Carcinoma in situ and Invasive Components in Breast Carcinoma

Low progesterone receptor levels in high-grade DCIS correlate with HER2 upregulation and the presence of invasive components.

In this study, we investigated pivotal molecular markers in human high-grade breast ductal carcinoma in situ (DCIS). Expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2) was measured among various subtypes (Luminal (Lum) A, LumB HER2-, LumB HER2+, HER2-enriched and triple-negative). In total, 357 DCIS cases were classified into respective subtypes, according to the 2013 St. Gallen guidelines. Each subtype was categorized into three subcategories: "Pure" (those without an invasive component), "W/invasive" (those with an invasive component), and "All" (the entire group of the given subtype). ER and PR expression were registered as intervals. Equivocal HER2 immunohistochemistry (IHC) cases (2+) were further investigated using dual-color in situ hybridization. The majority of patients (71%) were over the age of 50. We discovered no significant differences in the proportion of age between the "Pure" and "W/invasive" groups. There was no significant difference in ER/PR expression between "Pure" luminal subtypes of DCIS and "W/invasive" cases. We compared the HER2 IHC scores of "0", "1+", and "2+" among LumA and LumB HER2 subtypes and identified no statistically significant differences between "Pure" and "W/invasive" (p = 0.603). ER and PR expression ≥ 50% cutoff value was present in > 90% of all LumA cases. The incidences of cases with ER expression at cutoff values of < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). The proportion of cases with PR expression < 20% showed significant differences in the various luminal subtypes. In luminal B subtypes, low PR expression (< 20%) was significantly associated with both strong HER2 expression (3+) and the presence of an invasive component (p = 0.0001 and p = 0.0365, respectively). ER and PR expression at ≥ 50% cutoff values were found in more than 90% of LumA cases. Samples with ER < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). Low PR expression in high-grade DCIS was strongly associated with HER2 overexpression (3+) and an invasive component (p = 0.0001 and p = 0.0365, respectively).

Successful implementation of handheld reflectance confocal microscopy as the standard of care in the (surgical) management of lentigo maligna (melanoma).

Reflectance confocal microscopy (RCM) has shown promise in predicting surgical outcomes by non-invasively detecting subclinical lentigo maligna (melanoma) (LM/LMM). To assess the effects of presurgical mapping using handheld RCM (HH-RCM) on surgical treatment, follow-up outcomes and management decisions. A total of 117 consecutive LM/LMM cases (2015-2023) were included. The diagnostic accuracy of HH-RCM in detecting subclinical LM and invasive components was evaluated. The primary endpoints included histological margin status and changes in management based on the outcomes of the HH-RCM mapping procedure. Margin and follow-up outcomes were compared to a historical cohort before HH-RCM was introduced in our center (n = 94) (2003-2014). HH-RCM detected subclinical LM in 60% (n = 60) of cases. The median mapping duration was 14 min (range 4-50). In 27% (n = 33), the mapping procedure resulted in modified management, the majority consisting of limited surgery with adjuvant imiquimod (n = 15) or imiquimod monotherapy (n = 14). The remaining cases (n = 84) underwent HH-RCM-assisted surgery. Histological margins were cleared in 96.5% of the patients with a median histological margin of 3.0 mm, significantly higher than 81% in the historical cohort (median 2.0 mm) (p = 0.001). The sensitivity and specificity for detecting the extent of subclinical LM were 94% (95% CI 80.4-99.3) and 84% (95% CI 70.3-92.7), respectively. The negative predictive value for the detection of LMM was 94% (95% CI 84.4-97.7), and 75% of the initially missed LMM (n = 12) were identified during the HH-RCM mapping procedure. The study cohort had a 1.6% local recurrence rate compared with 25% in the historical cohort. Integrating HH-RCM as the standard of care could lead to more personalized treatment strategies for LM/LMM and allows for the selection of patients suitable for nonsurgical treatment.

Endometrial endometrioid adenocarcinoma with a malignant squamous component: is the unusual metastatic pattern unique of these tumors?

The FIGO scheme is currently applied for tumor grading of endometrioid adenocarcinoma. The current report presents a series of ten cases of endometrioid carcinomas that when applying the FIGO grading does not fully convey the true biological nature of the disease. The squamous component of these tumors is malignant; it constitutes the predominant invasive component, and it often metastasizes to unconventional sites. Half of the cohort developed distant disease recurrence within 2 years, even those with early-stage disease. Somatic mutations were analyzed, targeting 101 genes in all ten cases, and mutations in PTEN, MMR, PIK3CA, ATM, RB1, and TP53 genes were detected, often multiple mutations in the same case. None of the cases revealed unique molecular signatures or previously unreported gene mutations. Immunohistochemical staining for beta-catenin showed aberrant nuclear staining in eight of ten cases and remaining two showed cytoplasmic and membranous staining. Aggressive behavior and unusual sites of metastases are observed in this series even in low-grade tumor. The FIGO grading on smaller samples may be deceptive for these cases. Even if FIGO is applied, the pathology report should emphasize the malignant squamous component and its potential significance so that the gynecologic oncology team can formulate appropriate adjuvant treatment upfront. This case series argues that this histology should be regarded as a high-grade endometrioid carcinoma and can show unusual metastatic patterns. Further research is needed with more cases within this histologic subtype to guide recommendations on adjuvant therapies for this aggressive tumor type.

Encapsulated papillary carcinoma of the breast clinicopathological features and management: Could sentinel lymph node biopsy be exempted?

Papillary lesions in the breast pose diagnostic and therapeutic challenges. Encapsulated papillary carcinoma (EPC) is a rare breast cancer. However, evidence-based guidelines are limited. For this reason, there is no complete clarity in diagnosis and treatment management, and there are insufficient studies in the literature. This study aimed to examine the necessity of sentinel lymph node sampling in the management of EPC, in line with patients' clinicopathological data. We retrospectively screened patients with EPC in our clinic between January 2012 and March 2022. We recorded and statistically evaluated patients' demographic, clinical, radiological, pathological, and treatment management. Sixty-four patients with EPCs were identified. The final pathologic evaluation revealed that 19 patients (18.7%) had pure EPC, 27 patients (43.7%) had EPC with associated ductal carcinoma in situ and 18 patients (37.5%) had EPC associated with invasion. The mean age was 61 years, and two patients were male. Breast-conserving surgery was performed in 62 patients, and simple mastectomy was performed in two patients. Sentinel lymph node biopsy (SLNB) was positive in only one patient. Sixty-three patients with EPC were hormone receptor-positive, and one patient was triple-negative and was associated with invasion. None of the patients died, one had a local recurrence, and a mastectomy was performed. The overall prognosis and long-term survival of patients with EPC were excellent. Our study and the current literature indicate that routine SLNB is overtreatment because surgical excision with negative margins is sufficient in EPC cases and lymph node metastasis is rare, even with an invasive component.

The identification of hub genes associated with pure ground glass nodules using weighted gene co-expression network analysis

BackgroundWhether there are invasive components in pure ground glass nodules(pGGNs) in the lungs is still a huge challenge to forecast. The objective of our study is to investigate and identify the potential biomarker genes for pure ground glass nodule(pGGN) based on the method of bioinformatics analysis.MethodsTo investigate differentially expressed genes (DEGs), firstly the data obtained from the gene expression omnibus (GEO) database was used.Next Weighted gene co-expression network analysis (WGCNA) investigate the co-expression network of DEGs. The black key module was chosen as the key one in correlation with pGGN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were done. Then STRING was uesd to create a protein-protein interaction (PPI) network, and the chosen module genes were analyzed by Cytoscape software.In addition the polymerase chain reaction (PCR) was used to evaluate the value of these hub genes in pGGN patients’ tumor tissues compared to controls.ResultsA total of 4475 DEGs were screened out from GSE193725, then 225 DEGs were identified in black key module, which were found to be enriched for various functions and pathways, such as extracellular exosome, vesicle, ribosome and so on. Among these DEGs, 6 overlapped hub genes with high degrees of stress method were selected. These hub genes include RPL4, RPL8, RPLP0, RPS16, RPS2 and CCT3.At last relative expression levels of CCT3 and RPL8 mRNA were both regulated in pGGN patients’ tumor tissues compared to controls.ConclusionsTo summarize, the determined DEGs, pathways, modules, and overlapped hub genes can throw light on the potential molecular mechanisms of pGGN.

A case report of MiNEN: concomitant primary small-cell neuroendocrine carcinoma and high-grade papillary urothelial carcinoma of the urinary badder. Composite or Collision Tumor?

Bladder cancer is the tenth most diagnosed cancer worldwide, and urothelial carcinoma is the most common histologic type. On the contrary, small primary cell neuroendocrine carcinoma of the bladder is sporadic and accounts for less than 1% of all bladder tumors. These malignancies can be observed in mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs), which have been studied more in the gastrointestinal tract and lungs but scarcely in this organ due to their low incidence. There are concerns about the pathogenic connection between these two tumors, and the limited evidence accounts for the lack of consensus regarding prognosis and treatment for these patients; therefore, they may need a multimodal approach. Here, we describe the case of a 63-year-old woman who presented with gross hematuria, weight loss, and hypogastric discomfort for the past five months. An intravesical mass was found, and transurethral resection was performed. The Histopathology revealed a high-grade papillary urothelial carcinoma with an invasive component through muscularis propria of the bladder, so she was taken to radical cystectomy with extended pelvic lymphadenectomy. The final pathology report revealed an accompanying primary small cell neuroendocrine carcinoma intermingled with the urothelial one. She received postoperative adjuvant chemotherapy and finally died six months after surgery.