Perineural Invasion Research Articles

Survival Benefits of Postoperative Chemotherapy in Patients With Colorectal Mucinous Adenocarcinoma: An Analysis Utilizing Propensity Score Matching From the Surveillance, Epidemiology, and End Results Database.

This study aimed to investigate the characteristics of patients with colorectal mucinous adenocarcinoma (MAC) who benefit from postoperative chemotherapy (POCT) and to develop effective postoperative survival nomograms for predicting overall survival (OS) in colorectal MAC patients. Data of colorectal MAC patients who underwent surgery from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2020 were collected. Patients were grouped based on POCT, and intergroup analysis was performed using 1:1 propensity score matching (PSM). Kaplan-Meier (K-M) curves were used to compare the prognosis between the 2 groups. Cox analysis was employed to identify factors associated with OS in patients with colorectal MAC who underwent POCT. The variance inflation factor (VIF) and bilateral stepwise regression were used to determine factors included in the model. Additionally, a nomogram was constructed to predict postoperative survival outcomes for patients. The discriminative ability of the nomograms was evaluated using the C-index and calibration curve analysis, the decision curve analysis (DCA) assessed the clinical utility of the nomogram, and the receiver operating characteristic (ROC) curve evaluated the nomograms' performance. This study encompassed 6829 patients with colorectal MAC, among whom 2258 received POCT, and 4571 did not. Whether pre or post PSM, patients in the POCT group consistently exhibited a superior median OS compared to those in the postoperative non-chemotherapy group (P < .0001). For colorectal MAC patients undergoing POCT, OS was correlated with factors such as patient age, carcinoembryonic antigen levels, tumor deposits, perineural invasion (PNI), lymph node examination count, T staging, and Grade staging. Notably, a significant chemotherapy advantage was observed in patients without perineural invasion, those with lymph node examination counts exceeding 12, and patients with moderately differentiated tumors. The overall colorectal MAC patient postoperative OS predictive nomogram demonstrated a C-index of .74, with a calibration curve near the diagonal and a DCA curve indicating positive net benefits. In comparison to TNM staging, the ROC curves of the nomogram at 1 year, 3 years, and 5 years demonstrated superior predictive capabilities (AUC: .80 vs .71, .78 vs .71, .77 vs .70). This study revealed the characteristics of colorectal MAC patients who benefit from POCT and established effective prognostic nomograms, which can aid clinicians in designing personalized treatment plans for individual patients and promote precision medicine.

An Artificial Intelligent System for Prostate Cancer Diagnosis in Whole Slide Images

In recent years a significant demand to develop computer-assisted diagnostic tools to assess prostate cancer using whole slide images has been observed. In this study we develop and validate a machine learning system for cancer assessment, inclusive of detection of perineural invasion and measurement of cancer portion to meet clinical reporting needs. The system analyses the whole slide image in three consecutive stages: tissue detection, classification, and slide level analysis. The whole slide image is divided into smaller regions (patches). The tissue detection stage relies upon traditional machine learning to identify WSI patches containing tissue, which are then further assessed at the classification stage where deep learning algorithms are employed to detect and classify cancer tissue. At the slide level analysis stage, entire slide level information is generated by aggregating all the patch level information of the slide. A total of 2340 haematoxylin and eosin stained slides were used to train and validate the system. A medical team consisting of 11 board certified pathologists with prostatic pathology subspeciality competences working independently in 4 different medical centres performed the annotations. Pixel-level annotation based on an agreed set of 10 annotation terms, determined based on medical relevance and prevalence, was created by the team. The system achieved an accuracy of 99.53% in tissue detection, with sensitivity and specificity respectively of 99.78% and 99.12%. The system achieved an accuracy of 92.80% in classifying tissue terms, with sensitivity and specificity respectively 92.61% and 99.25%, when 5x magnification level was used. For 10x magnification, these values were respectively 91.04%, 90.49%, and 99.07%. For 20x magnification they were 84.71%, 83.95%, 90.13%.

Adjuvant Modified FOLFIRINOX for Resected Pancreatic Adenocarcinoma (PDAC): Clinical Insights and Genomic Features from a Large Contemporary Cohort.

Adjuvant mFOLFIRINOX (mFFX) is standard of care for fit individuals with resected pancreatic ductal adenocarcinoma (PDAC). There are limited data on adjuvant mFFX outcomes outside clinical trials. Institutional databases queried to identify patients with resected PDAC who received ≥1 dose adjuvant mFFX. Primary endpoints: recurrence free survival (RFS), overall survival (OS). Secondary endpoints: clinical factors, genomic features associated with outcomes. RFS and OS were estimated with Kaplan-Meier. Cox proportional hazards regression model was used to associate clinico-genomic features correlated with survival outcomes. N = 147 identified between 01/2015-01/2023. Median age: 67 years; N = 57 (39%) >70 years. Unfavorable prognostic features: N = 52 (36%) N2 nodal status, N = 115 (78%) lymphovascular invasion), and N = 133 (90%) perineural invasion. Median time from surgery to start mFFX: 1.78 months (m) (IQR 1.45, 2.12). N = 124 (84%) completed 12 doses; N = 98 (67%) stopped oxaliplatin early for neuropathy (median 10 doses; range 4-12). Further dosing characteristics are summarized in Supplementary Table 3. With median follow up of 35.1 m, median RFS (mRFS) 26 m (95% CI 19, 39) and median OS (mOS) not reached. For >70 cohort, mRFS 23 m (95% CI 14, NR) and mOS 51 m (95% CI 37, NR). mFFX started <8 weeks from resection associated with improved RFS (HR 0.62; 95% CI 0.41, 0.96; p = .033) and OS (HR 0.53; 95% CI 0.3, 0.94; p = .030). KRAS mutation and whole genome doubling trended to shorter RFS and OS. Homologous recombination deficiency status did not confer improved survival outcomes. Adjuvant mFFX is effective and tolerable in resected PDAC in a non-trial setting, including for patients >70 years.

Association of gene polymorphisms with biological features of gastric cancer

Aim of the investigation. To evaluate associations of polymorphic variants of TNF (G308A), XPC (Lys939Gln), MTHFR (Ala222Val) genes with some biological features of gastric cancer. Materials and Methods. We evaluated polymorphic gene variants in 74 patients with verified gastric cancer or gastriesophageal junction cancer (Siewert III). Genotyping was performed by DNA isolation from venous blood leukocytes of the subjects followed by PCR with electrophoretic detection of the result. The association of polymorphic variants of genes with such biological features of the tumor as localization of the process, morphological type, degree of differentiation, type of tumor growth, presence or absence of lymphovascular or perineural invasion was evaluated. Results. Lys/Gln genotype of XPC gene (Lys939Gln) are 3.3 times more likely to develop gastric body cancer (p=0.04). Genotype GG of TNF gene (G308A) 5.3 times increases the development of gastric adenocarcinoma in comparison with other histological types (p=0.018), genotype GA of the same gene 5.2 times more often develop tumor with high-grade differentiation degree (p=0.032). Val/Val genotype of the MTHFR gene (Ala222Val) are significantly less likely to develop lymphatic/vascular invasion compared to carriers of the other genotype (p=0,029). Conclusion. The obtained data suggest that the genetic status of the patient itself may affect the biological characteristics of gastric cancer, which in turn may lead to a change in the patient’s treatment tactics.

A Single-Center Analysis of Patient Characteristics and Overall Survival in Patients with Resectable Gallbladder Cancer.

Gallbladder cancer (GBC) is a rare and aggressive hepatobiliary malignancy with poor prognosis. The symptoms of GBC are insidious and non-specific in its early stages, and most patients are diagnosed at advanced or late stages. Surgical resection is the only potentially curative treatment for GBC for select patients. There is a lack of robust data for patients with GBC, leading to heterogenous practices in management strategies and outcomes. In this study, we aimed to identify patient characteristics and cumulative overall survival (OS) in patients with GBC who underwent surgical resection with curative intent. All adult patients (age ≥18 years) with localized or locoregionally advanced GBC who underwent definitive surgery with curative intent at our tertiary institution between 1/2013 and 12/2023 were retrospectively identified. Clinical, laboratory, radiology, histopathology, treatment, and survival data were collected from electronic medical records. Postoperative data included the use of adjuvant chemotherapy or radiotherapy, and patient survival mortality at a cut-off date of 1 February, 2024, calculated from the date of curative surgery. Continuous variables are reported as median and quartile 1 (Q1) and quartile 3 (Q3), while categorical variables are reported as counts and percentages. A total of 94 patients with GBC were included in the study. Median age was 71 (62-77) years and 58 (61.7%) patients were female. Median tumor size was 3.3 (1.9-5.0) cm. Perineural invasion was seen in 48.9% and vascular invasion in 38.3% of patients. A positive surgical margin was present in 50% of the patients, and incidental GBC (IGBC) was seen in 48.9% of patients. Tumor grade was well differentiated in 7.6%, moderately differentiated in 53.3%, and poorly differentiated in 39.1% of the patients. Patients with stage T1a (2.1%) and T1b (11.7%) tumors comprised the minority, and the majority of the tumors were stage T2 (55.3%), followed by T3 (31.9%). A total of 60.6% of patients with GBC underwent adjuvant chemotherapy, and 17% underwent adjuvant radiotherapy after surgical resection. Overall, 62 (66.0%) patients died, and the median OS was 1.88 years. The 1-year OS was 68.7%, 3-year OS was 37.4%, and 5-year OS was 32.2%. A higher absolute median OS was seen in patients who had adjuvant chemotherapy (2.1 years) compared to no chemotherapy (1.9 years); however, this finding was not statistically significant (p = 0.36). The median survival was 2.3 years in IGBC compared to 1.6 years in non-IGBC (p = 0.63). GBC is an aggressive hepatobiliary malignancy that is often diagnosed at advanced stages. Our study showed high rates of local and systemic involvement and high mortality, and the need for prospective and randomized studies on adjuvant therapies to assess their survival benefit. Real-world patient data remain important to identify patients at risk of worse outcomes and to stratify risks prior to surgery.

Pseudomyogenic hemangioendothelioma presenting as a penile lesion.

Pseudomyogenic hemangioendothelioma (PHE) is a rare, usually multifocal neoplasm typically affecting individuals in the second-to-fourth decade of life, with a male predominance. It often arises in the distal extremities and characteristically involves multiple tissue planes. Presentation of this neoplasm as a primary penile lesion is exceedingly rare, with only five cases previously documented in the literature. We report the clinicopathologic features of five additional PHEs presenting as primary penile tumors and review previously published cases. Tumors affected young to middle-aged adult patients and had a relatively bland clinical appearance, mimicking indolent lesions such as epidermal inclusion cysts. Microscopically, they were ill-defined nodules composed of plump spindle cells and round neoplastic cells with abundant, densely eosinophilic cytoplasm and eccentric nuclei resembling rhabdomyoblasts. Neoplastic cells demonstrated infiltrative growth, including foci of perineural invasion. Immunohistochemistry demonstrated invariable co-expression of keratins, endothelial markers (CD31 and/or ERG), and FOSB. In conclusion, penile PHE is rare but should be considered in the differential diagnosis of penile lesions with spindle cell and/or rhabdomyoblast-like morphology affecting young to middle-aged adult patients.

Cancer cell-derived exosomal miRNA induces and reprograms Schwann cells to augment the perineural invasion of salivary adenoid cystic carcinoma.

Cancer cell-derived exosomal miRNA induces and reprograms Schwann cells to augment the perineural invasion of salivary adenoid cystic carcinoma.

The relationship between the Prognostic Nutritional Index and lymphovascular and perineural invasion of the tumor in patients diagnosed with gastric cancer, and its effect on overall survival.

A low Prognostic Nutritional Index (PNI) value, lymphovascular invasion (LVI), and perineural invasion (PeNI) have been identified as indicators of poor prognosis for many malignancies. We aimed to evaluate the relationship between PNI and LVI/PeNI, their prognostic significance, and their effect on overall survival in gastric cancer patients who underwent curative gastrectomy. A cutoff value of 39.8 was taken for the PNI, and PNI < 39.8 was defined as moderate to severe malnutrition. Patients were grouped as PNI-low (PNI < 39.8) and PNI-high (PNI ≥ 39.8). Paraffin-embedded tissue sections of surgical specimens were used to evaluate PeNI as defined by previously reported criteria. The study included 270 patients with ages ranging from 23 to 90 years. The mean PNI was calculated as 39.8 ± 6.35. PeNI was detected in 232 patients (85.93%), and LVI was identified in 248 patients (91.85%). It was observed that the PNI value of patients with an expired status in the PNI < 39.8 group was lower compared to those who survived, and in patients with PNI > 39.8, those without PeNI had better survival. The presence of PeNI in patients with PNI > 39.8 increased the mortality risk by 2.088 units, while in patients with PNI > 39.8, it was found that those without LVI had better survival, and the presence of LVI increased the mortality risk by 3.171 units. Mortality developed in 166 patients (61.48%) during the five-year follow-up period. The five-year overall survival was found to be 31.02 ± 21.73 months. In patients with gastric cancer, the PNI, LVI, and PeNI are independent prognostic factors for overall survival in postoperative patients. A low PNI score is an inherently poor prognostic factor. In patients with a high PNI score, the presence of positive LVI and PeNI negatively impacts survival. We found that in patients with a low PNI, the rates of PeNI and LVI are higher compared to those with a high PNI, and this significantly affects mortality.

Correlation of tumor budding with a novel and other established prognostic parameters in patients with invasive breast carcinoma.

Breast cancer is the most common malignancy among women. Established prognostic markers in breast carcinomas include tumor size, histologic grade, nodal status, lymphovascular invasion, perineural invasion, hormone receptor status, HER-2 status, and age. To correlate peripheral tumor budding (pTB) with stromal tumor-infiltrating lymphocytes (sTILs) and established prognostic factors in invasive breast carcinoma. It is a retrospective study conducted at multiple centers including a tertiary care center. 100 cases were included over a period of 2.5 years. All cases of invasive breast carcinoma (IBC) in which excision specimens with lymph node dissection were available were studied. Slides were reviewed for pTB and sTILs. Tumor budding of ≤20/10 hpf was considered low tumor budding, and >20 buds/10 hpf was considered high tumor budding. Tumor budding was correlated with age, tumor size, lymphovascular invasion, perineural invasion, tumor stage (pT, pN), stromal tumor-infiltrating lymphocytes, tumor grade, ductal carcinoma in situ, hormonal receptors, and HER2neu. Fisher exact test and Chi-square test were used. We found that high tumor budding was seen in 34 cases and low tumor budding in 66 cases. There was a statistically significant association between high tumor budding and tumor size (P = 0.007), lymphovascular invasion (P < 0.001), perineural invasion (P = 0.004), tumor staging/pT (P = 0.006), nodal staging/pN (P = 0.001), and low sTILs (P < 0.001). However, the association of high tumor budding with parameters like age (P = 0.979), histological type (P = 0.243), tumor grade (P = 0.052), DCIS (P = 0.478), and ER (P = 0.633), and PR (P = 0.544), HER2Neu status (P = 0.171) was not significant. This study suggests tumor budding score can be used as a prognostic indicator for breast cancer.

Comprehensive Next Generation Sequencing Reveals that Purported Primary Squamous Cell Carcinomas of the Parotid Gland are Genetically Heterogeneous.

Squamous cell carcinoma (SCC) is one of the most common malignancies involving the parotid gland, but it has been recognized that the vast majority of parotid SCC represents metastases, especially from the ipsilateral facial skin. Bona fide primary SCC of the parotid is so rare that it is unclear whether it truly exists at all. We sought to molecularly characterize cases diagnosed as primary parotid gland SCC to see if they possess a unique genetic makeup.We identified cases in our archives which had been diagnosed as primary SCC of the parotid gland. In all cases, metastatic disease was excluded by a thorough history and physical examination. Cases with histologic evidence of a precursor neoplasm (e.g., carcinoma ex-pleomorphic adenoma) were also excluded. Targeted next-generation sequencing (NGS) was attempted on all cases.Six cases diagnosed as primary parotid SCC were identified, arising in 4 males and 2 females ranging from 8 to 73 years (mean, 51.8 years). All cases exhibited keratinization and unequivocal invasion. Four of 6 appeared to be arising from cystically dilated ducts. Five of 6 exhibited well-developed cellular atypia; the remaining case, while cytologically bland, demonstrated perineural invasion. Targeted NGS was successful in 5 of 6 cases. Two SCC harbored several mutations in a mutational profile reminiscent of SCCs seen in other organs. One case harbored YAP1::MAML2, a fusion previously reported in porocarcinoma and other neoplasms. One case harbored IRF2BP2::RUNX2, and presumably represents keratocystoma or SCC ex-keratocystoma. Finally, one case an increase of C > T mutations consistent with ultraviolet damage, suggesting that this case represented a cryptic metastasis from cutaneous SCC.Our analysis did not confirm a unifying genetic signature for purported primary parotid SCC. Indeed, our findings suggest that true primary parotid gland SCC is even rarer than already believed. In our 5 cases with results, NGS findings demonstrated that one was likely a keratocystoma, one a cryptic metastasis from a cutaneous SCC, and one a porocarcinoma, either metastatic or primary. The two remaining cases had complex genotypes reminiscent of SCCs from other sites. This may be the signature of genuine parotid primary SCC, but metastasis from an SCC from another organ cannot be excluded. Accordingly, a diagnosis of primary parotid gland SCC should be viewed with skepticism.

Vascular Resection for Pancreas Cancer - 10-year Experience from a Single High Volume-center.

Combined pancreatic and vascular resections are increasingly performed for pancreatic ductal adenocarcinoma (PDAC). We evaluated the outcomes after pancreatectomy with non-vascular resection (NVR), venous resection (VR), and arterial resection (AR). Retrospective review (2011-2023) of 715 PDAC patients treated with curative-intent surgery. Associations among clinicopathological data, perioperative therapy, time to recurrence (TTR), and overall survival (OS) were evaluated. Initial staging revealed 533 resectable, 98 borderline, and 84 locally advanced PDAC cases. Pancreaticoduodenectomy was the most common procedure (n=467). NVR was performed in 351 (58.2%) patients, VR in 181 (30.0%), and AR in 70 (11.8%). The median TTR and OS did not significantly differ according to the initial staging or type of pancreas resection. Median TTR and OS were significantly shorter for VR (14.5 and 22.7mo) compared to NVR (18.6 and 30.5mo, P<0.001) and AR (20.6 and 30.9mo, P=0.004 and P=0.017). Chemotherapy or chemoradiation significantly prolonged TTR (20.1 vs. 10.2mo, P<0.001 and 25.3 vs. 16.4mo, P<0.001) and OS (31.5 vs. 17.2mo, P<0.001 and 35.5 vs. 27.5mo, P=0.030). AR was associated with higher 90-day mortality rates. In the multivariable analysis, vascular resection was not associated with OS. Perioperative therapy, pathological N0 status, and absence of perineural invasion were the key predictors of longer TTR and OS. Pancreatectomy with AR was not associated with worse oncological outcomes when controlling for perioperative therapy. However, AR was associated with higher 90-day mortality rates. Patient selection is crucial when performing AR in patients with PDAC.

The Prognostic Significance of Tumor Deposits in Non-Metastatic Colorectal Cancer: Comparing Risk of Recurrence and Metastasis with High-Risk Features

Abstract Introduction/Objective Tumor deposit (TD) is a prognostic factor in colorectal cancer (CRC) patients. This study aims to determine if TD poses a similar risk of local recurrence and distant metastasis as known high-risk (HR) features in non-metastatic CRC. Methods/Case Report An analytical cross-sectional design was employed. Our hospital clinical and pathology databases were queried for stage I-III CRC patients from January 2016 to December 2018 and divided into two groups: TD only group defined by TD on histopathology and HR group defined by obstruction, perforation, or T4- stage. The following variables were collected from each case; biological factors (age, gender, race, and BMI), tumor features (tumor size, tumor grade, presence of LVI, PNI, lymph node status and TN staging) and postoperative follow up (development of recurrence, adjuvant chemotherapy, and overall survival (OS) duration). Data were analyzed using Kruskal-Wallis test for continuous variables and chi-square and Fisher’s exact test for categorical variables. Survival analysis was conducted using Kaplan-Meier estimate graphs. Results (if a Case Study enter NA) A total of 138 non-metastatic CRC patients who underwent surgery and chemotherapy were identified. The TD group consisted of 79 (57.2%) patients with a median age of 67 y (range 35 - 94 y), including 40 (50.6%) males and 39 (49.4%) females. The HR group comprised 59 (42.7%) patients with a median age of 70 y (range 28 - 103 y), including 25 (42.4%) males and 34 (57.6%) females. There were no significant demographic differences between the groups (P&amp;gt;0.05). However, tumor size, tumor grade, presence of lymphatic vessel invasion (LVI), perineural invasion (PNI), and tumor-node (TN) staging exhibited statistically significant differences between the groups (P&amp;lt;0.05). Local tumor recurrence and/ distant metastasis occurred in 29 patients (36.7%) in the TD group and 18 patients (30.5%) in the HR group, with median time for recurrence and/or metastasis 11 months and 12 months, respectively. There was no significant difference between the groups (P&amp;gt;0.05). TD patients had a median survival duration of 42 months, whereas HR group patients had a median survival of 51 months, although this difference was not statistically significant (P&amp;gt;0.05). Conclusion In non-metastatic CRC patients, TD poses a similar risk of local tumor recurrence and distant metastasis as HR factors. HR patients may have a longer survival than TD counterpart. Based on these findings both groups should be subjected to enhanced surveillance.

Uncovering factors predicting BRAF mutation in cutaneous melanoma

Abstract Introduction/Objective BRAF mutations are considered to be the most common genetic alteration in cutaneous melanoma (CM). Patient management relies on assessing molecular biomarkers enabling the personalization of patients’ treatment. The goal of this study was to develop the tools for predicting BRAF mutation using routine clinical and histological features. Methods/Case Report A total of 2041 CM cases were enrolled in the study to identify factors associated with BRAF mutation. Variables included sex, age, primary location, stage, histological type, ulceration, mitosis, Clark level, Breslow thickness, lymphocytes, lymphovascular invasion (LVI), perineural invasion (PNI), regression, microsatellite, association with nevus. Results (if a Case Study enter NA) The Ukrainian population demonstrated a high rate of BRAF mutation in CM, associated with the younger age and location at non-sun-expose skin. This study also revealed gender-specific differences in CM anatomic distribution and BRAF mutation subtype prevalence. By using the genetic selection method, the minimal set of variables related to BRAF mutations was defined and included age, primary tumor location, histological type, ulceration, LVI, and association with nevus. To encounter non- linear links, the non-linear neural network modeling was applied. For this aim multilayer perceptron (MLP) with one hidden layer was used. The hidden layer architecture included 4 neurons with a logistic activating function. The AUROCMLP6 of the model was 0.79 (0.74 – 0.84). When applying the optimal threshold, the following characteristics of the model were reached: sensitivity - 89.4% (84.5 – 93.1%); specificity - 50.7% (42.2% – 59.1%); positive predictive value (PPV) - 73.1% (69.6% – 76.3%) and NPV - 76.0% (67.6% – 82.8%) respectively. The developed MLP model allows the prediction of BRAF status in CM, facilitating decisions concerning further patient management. Conclusion The developed MLP model, relying on 6 variables analysis allows the prediction of BRAF status in melanoma, facilitating decisions concerning further patient management.

Construction and interpretation of machine learning-based prognostic models for survival prediction among intestinal-type and diffuse-type gastric cancer patients

BackgroundGastric cancer is one of the most common malignant tumors worldwide, with high incidence and mortality rates, and it has a complex etiology and complex pathological features. Depending on the tumor type, gastric cancer can be classified as intestinal-type and diffuse-type gastric cancer, each with distinct pathogenic mechanisms and clinical presentations. In recent years, machine learning techniques have been widely applied in the medical field, offering new perspectives for the diagnosis, treatment, and prognosis of gastric cancer patients.MethodsThis study recruited 2158 gastric cancer patients and constructed prognostic prediction models for both intestinal-type and diffuse-type gastric cancer. Clinical pathological data were collected from patients, and machine learning algorithms were used for feature selection and model construction. The performance of the models was validated with training and testing datasets. The Shapley additive explanations (SHAP) values were used to interpret the model predictions and identify the main factors that influence patient survival.ResultsIn the prognostic model for intestinal-type gastric cancer, the gradient boosting decision tree (GBDT) model demonstrated the best performance, with key features including pTNM, CA125, tumor size, CA199, and PALB. Similarly, in the prognostic model for diffuse-type gastric cancer, the GBDT model was utilized, with key features comprising pTNM, Borrmann type IV disease, lymphocyte (LYM), lactate dehydrogenase (LDH), potassium (K), perineural invasion (PNI), tumor size, and whole stomach location. Risk stratification analysis revealed that the prognosis of high-risk patients was significantly worse than that of low-risk patients.ConclusionMachine learning shows great potential in predicting survival outcomes of gastric cancer patients, providing strong support for the development of personalized treatment plans.

Parathyroid carcinoma: molecular pathology and correlation with clinicopathologic features, a single center experience

Abstract Introduction/Objective Parathyroid Carcinomas are rare malignant neoplasms, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single center regarding the clinic-pathologic and genetic analysis of parathyroid carcinoma cases. Methods/Case Report The study is a retrospective review of all patients with parathyroid carcinoma that were evaluated at a tertiary oncologic center from 2001 until 2023. Results (if a Case Study enter NA) A total of nine cases (6 male and 3 female) were identified, with a mean age at diagnosis of 52 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 7), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and a mean PTH of 1123 pg/ml (&amp;lt;a href=“tel:276- 2500”&amp;gt;276-2500&amp;lt;/a&amp;gt;). En bloc surgical resection was performed in 6 patients and 3 patients underwent adjuvant radiotherapy. Recurrence was observed in 4 cases (44.4%) after a median of 24 months following surgery. Negative immunohistochemical staining of parafibromin was noted in 3/4 cases of recurrence. Parathyroid carcinoma was diagnosed on the basis of finding lesions with vascular or perineural invasion, capsular penetration, and/or documented metastases. Immunohistochemical staining for parafibromin, Ki-67, and E-cadherin was performed on formalin-fixed, paraffin-embedded tissue samples. Next generation sequencing (NGS) was performed in 6/9 cases and CDC73 mutations were present in 38.5% of analyzed patients. Loss of TP53 and RB1 alleles and CCND1 amplification were other reported genetic alterations in the study cohort. Conclusion Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Inactivating CDC73 alterations which include truncating or frameshift mutations, as well as missense mutations lead to the loss of parafibromin immunoreactivity. Other molecular alterations like PTEN and PIK3CA mutations may represent potential targets for molecular therapy. An IHC panel of parafibromin, Ki-67 and E-cadherin may help to distinguish parathyroid carcinoma from other parathyroid neoplasms.

Giant pilomatricoma with atypical features: report of a case of aggressive pilomatricoma in an adult

Abstract Introduction/Objective Pilomatricoma, also known as pilomatrixoma or calcifying epithelioma of Malherbe, is a relatively common, benign tumor of the hair matrix. It typically presents as a small (~1cm), dermal based mass in the head and neck region of children and young adults (under 20 years) with predominance for males, but can occur in any age. In contrast, malignant pilomatricoma is typically larger (1 to 10 cm) and occurs later in life (50-60 years). Aggressive pilomatricoma is a variant of pilomatricoma that tends to occur in children and demonstrates atypical features such as increased matrical cells and nuclear atypia, but insufficient for a classification as pilomatrical carcinoma. Here, we presented a case of a large (14.5 cm) aggressive/atypical pilomatricoma that occurred in an adult. Methods/Case Report A 45 year-old-female presented to the emergency department with a posterior neck mass which has been slowly enlarging for years. Recently, it became painful with sanguineous discharge which prompted her to seek medical attention. CT scan revealed a lobulated, pedunculated mass with fat and fluid components. An excision was performed. Gross examination revealed an ulcerated mass measured 14.5 cm in greatest dimension. Scattered calcifications were present. Microscopically, nests of basaloid cells with scattered shadow cells are present consistent with matrical differentiation. A multinodular growth pattern with central necrosis was evident. Nuclear atypia characterized by prominent nucleoli and nuclear overlapping was identified. Results (if a Case Study enter NA) NA Conclusion Histopathologic criteria to reliably differentiate between benign and malignant pilomatrical tumors are not well-established. Tumor ulceration, asymmetry, irregular borders, multinodular growth pattern, marked cytologic atypia, prominent necrosis, lymphovascular invasion, and perineural invasion may be used in favor of malignancy. Our case showed focal confluent necrosis, ulceration, multinodular growth pattern, and cellular atypia but lacked other features that indicative of unequivocal malignancy. The resection margins were negative for tumor. Clinical followup was negative for signs of recurrence or metastasis after two years. We presented this case to show the large size that aggressive pilomatricoma can reach and to emphasize the difficulty in differentiating benign from malignant pilomatrical tumors in borderline cases.

Squamoid eccrine ductal carcinoma of the vulva: A case report

Abstract Introduction/Objective A 53-year-old female sought medical attention for left vulvar pain and a vulvar lesion. Methods/Case Report Physical examination revealed a 1.0 x 1.0 cm lesion within a background of lichen sclerosus. Biopsy demonstrated a carcinoma with tubular and glandular architecture, areas of squamoid differentiation and widespread perineural invasion. Ancillary immunohistochemistry testing with keratin 7 highlighted foci of ductal differentiation. Tumor cells were also positive for p53, p63, pankeratin, and keratin 5/6. The Ki-67 proliferation index was approximately 15%. Tumor cells were negative for Keratin 20, PAX 8, p16, and CD 34. We diagnosed the lesion as a vulvar sweat gland adenocarcinoma of the squamoid eccrine ductal subtype. Results (if a Case Study enter NA) N/A Conclusion Carcinomas of vulvar sweat gland origin are extremely rare, comprising less than 1% of all vulvar cancers. To the best of our knowledge, this is the first case report of squamoid eccrine ductal carcinoma afflicting the vulva.

Remarks on Selected Morphological Aspects of Cancer Neuroscience: A Microscopic Photo Review.

This short review and pictorial essay presents a morphological insight into cancer neuroscience, which is a complex and dynamic area of the pathobiology of tumors. We discuss the different methods and issues connected with structural research on tumor innervation, interactions between neoplastic cells and the nervous system, and dysregulated neural influence on cancer phenotypes. Perineural invasion (PNI), the most-visible cancer-nerve relation, is briefly presented, focusing on its pathophysiology and structural diversity as well as its clinical significance. The morphological approach to cancer neurobiology further includes the analysis of neural density/axonogenesis, neural network topographic distribution, and composition of fiber types and size. Next, the diverse range of neurotransmitters and neuropeptides and the neuroendocrine differentiation of cancer cells are reviewed. Another morphological area of cancer neuroscience is spatial or quantitative neural-related marker expression analysis through different detection, description, and visualization methods, also on experimental animal or cellular models. Morphological studies with systematic methodologies provide a necessary insight into the structure and function of the multifaceted tumor neural microenvironment and in context of possible new therapeutic neural-based oncological solutions.

KLF15 Transcription Activated Tachykinin Precursor 1 to Induce Perineural Invasion in Head and Neck Squamous Cell Carcinoma.

In this study, we aimed to identify novel biomarkers related to Peripheral Neural Invasion (PNI) in head and neck squamous cell carcinoma (HNSCC). The PNI-related differentially expressed mRNAs (DE-mRNAs) in HNSCC were identified to construct a PNI-related risk score model. The expression level and ROC curve for Tachykinin Precursor 1 (TAC1) were calculated. Additionally, two kinds of in vitro models of PNI were established for investigation, including the Matrigel-PNI model and the Transwell-PNI model. Furthermore, the transcription factor of the TAC1 was predicted and verified by qRTPCR. A total of 139 DE-mRNAs were identified in PNI positive and negative groups of HNSCC patients. The risk-score marker model incorporating 20 PNI-related DE-mRNAs was established. The TAC1 was identified as a potential highly expressed PNI marker, which exhibited good performance in predicting PNI events. Patients with higher TAC1 expressions demonstrated significantly shorter survival rates compared to those with lower TAC1 expressions in HNSCC. Besides, the knockdown of TAC1 significantly repressed neural invasion in HNSCC cells in vitro, according to the Matrigel-PNI model and Transwell-PNI model. Furthermore, KLF15 was predicted and verified as a transcription activator of TAC1 in HNSCC. This study highlights that the activation of KLF15 transcription of TAC1 promotes PNI in HNSCC cells, which provides guidance regarding the molecular diagnosis of PNI in HNSCC cells.

Postoperative pathological findings and prognosis of early laryngeal and pharyngeal cancer treated with transoral surgery

ObjectiveTransoral surgery for early-stage pharyngeal and laryngeal cancer provides good local control and is less invasive than external incisions. Postoperative pathological findings are considered the most important indicators for determining postoperative treatment, but detailed criteria have not been established. In this study, we evaluated the impact of postoperative pathological findings on prognosis of patients undergoing transoral surgery. MethodsThis study included patients with oropharyngeal, hypopharyngeal, and supraglottic cancer who underwent transoral surgery at Gifu University Hospital from April 2016 to December 2023. Resection margins were pathologically evaluated with horizontal and vertical margins, and vascular invasion was evaluated in three categories: lymphatic invasion, venous invasion, and perineural invasion. The correlation between each postoperative pathological finding and prognosis was evaluated. ResultsA total of 70 cases were assessed in this study. Cases of horizontal margin positive were 38.6 %, and cases of vertical margin positive were 27.1 %. Prognoses were comparable to previous reports. Despite the high margin positive rate, the 5-year overall survival rate was 77.1 %. The 5-year disease-specific survival rate was 89.7 %, and the 5-year local control rate was 85.3 %. Notably, when evaluated by margin direction, cases with positive horizontal margins had significantly worse prognoses. Although no significant correlation was found between vascular invasion and prognosis, cases of venous invasion tended to have a higher local recurrence rate. ConclusionThis study suggests that transoral surgery has good prognosis despite a high positive-margin rate. However, detailed criteria for additional treatment have not been developed, and further case accumulation is required. Intriguingly, positive horizontal margins are correlated with significantly worse prognosis. This result may be related to a high risk of multiple cancers, and careful follow-up after surgery is recommended.