Metastasis of Rectal Signet Ring Cell Carcinoma to Typical Lipoma: A Rare Presentation of the Tumor-to-Tumor Metastasis Phenomenon.

Rectal signet ring cell carcinoma represents a rare subtype of colorectal adenocarcinoma known for its aggressive biological nature and poor prognosis. Although the co-occurrence of colorectal carcinoma with other tumors has been reported, the uncommon phenomenon of tumor-to-tumor metastasis, first described in 1930, remains rare. The most frequent donor neoplasms are lung or breast carcinomas, whereas cerebral meningiomas have been reported to be the most frequent recipient neoplasms. Here we report a case of a typical lipomatous tumor harboring metastatic signet ring cell rectal carcinoma. It is about a 42-year-old man diagnosed with rectal signet ring cell carcinoma and treated with concurrent radiotherapy and chemotherapy followed by an anterior resection and manual coloanal anastomosis with a temporary ileostomy. During the surgery, an abdominal wall lipoma was discovered and excised. A histopathological examination revealed infiltration of the fibro adipose tissue by a mucinous adenocarcinoma with a contingent of signet ring cells. The patient died 12 months after adjuvant chemotherapy due to peritoneal progression. To the best of our understanding, this represents the initial documented instance of tumor-to-tumor metastasis from rectal signet cell carcinoma to a conventional nonvascular lipoma. Consequently, even if one of these tumors appears clinically and radiologically benign, it is prudent to entertain the prospect of tumor-to-tumor metastasis. Thus, a comprehensive pathologic study of both tumors is highly recommended.

Clinicopathological features and cancer transcriptomic profiling of poorly cohesive gastric carcinoma subtypes.

Gastric poorly cohesive carcinoma (PCC) manifests with a diffuse pattern and diverse tumor cell morphologies, often indicating a more unfavorable prognosis. Recent consensus has reclassified PCC based on the proportion of signet-ring cells (SRCs) in tumors for research purposes. The two most distinct subtypes, poorly cohesive carcinoma not otherwise specified (PCC-NOS) and signet-ring cell carcinoma (SRCC), are characterized by less than 10% and more than 90% SRCs, respectively. However, research comparing the clinicopathological and transcriptomic differences between these subtypes remains limited. In this study, we conducted a comparative analysis of clinicopathological features in 55 advanced-stage PCCs, consisting of 43 PCC-NOS and 12 SRCC cases. Subsequently, 12 PCC-NOS and 5 SRCC cases were randomly selected for initial cancer-related gene expression profiling and pathway enrichment analysis using the GeoMx digital spatial profiler, followed by validation in a separate validation group comprising 16 PCC-NOS and 6 SRCC cases. These transcriptomic findings were then correlated with tumor morphology and clinicopathological data. PCC-NOS cases exhibited larger tumor size, a higher prevalence of pathological N3 disease, and a worse 1-year progression-free survival rate compared to SRCC cases. Clustering of PCC-NOS and SRCC was successfully achieved using the GeoMx Cancer Transcriptome Atlas. Among all studied genes, only MMP7 showed differential expression, with its overexpression significantly associated with the PCC-NOS subtype, increased perineural invasion, and earlier disease progression. Pathway analysis revealed significantly enriched pathways in PCC-NOS related to vesicle-mediated transport, adaptive immune systems, oncogenic signaling, and extracellular matrix organization, while SRCC displayed significant enrichment in pathways associated with respiratory electron transport and the cell cycle. In conclusion, this study compares and correlates clinicopathological features and transcriptomic data between PCC-NOS and SRCC at advanced stages, employing the latest consensus classification and a novel platform for analysis.

Prostate Adenocarcinoma with Signet-Ring Cells and Features of Mucin: A Clinical Case and Literature Review.

Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium; thus, they are most commonly found in the gastrointestinal tract, but not exclusively. Primary signet-ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical Case: In June of 2023, a 54-year-old Caucasian male presented with a complaint of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups, including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma stage IV. Unfortunately, due to the advanced stage of the disease, PE, and third-degree thrombocytopenia, the patient was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results, which may contribute to its late diagnosis. Inconsistent immunohistochemical findings and an unpredictable response to hormonal treatment together pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusions: This study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease, which may positively influence the prognosis.

Effect of chemotherapy on prognosis in patients with primary pancreatic signet ring cell carcinoma: A large real-world study based on machine learning.

BACKGROUND: Primary pancreatic signet ring cell carcinoma (PSRCC), an extremely rare histologic variant of pancreatic cancer, has a poor prognosis. This study aimed to investigate the prognostic value of chemotherapy in PSRCC. METHODS: Patients with PSRCC between 2000 and 2019 were identified using the Surveillance Epidemiology and End Results (SEER) database. The main outcomes in this study were cancer-specific survival (CSS) and overall survival (OS). The baseline characteristics of patients were compared using Pearson's Chi-square test. Kaplan-Meier analysis was used to generate the survival curves. Least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression models, and Random Survival Forest model were used to analyze the prognostic variables for OS and CSS. The variance inflation factors (VIFs) were used to analyze whether there was an overfitting problem. RESULTS: A total of 588 patients were identified. Chemotherapy was an independent prognostic factor for OS and CSS, and significantly associated with OS (HR = 0.33, 95% CI = 0.27-0.40, P <0.001) and CSS (HR = 0.32, 95% CI = 0.26-0.39, P <0.001). CONCLUSIONS: Chemotherapy showed beneficial effects on OS and CSS in patients with PSRCC and should be recommended in clinical practice.

Contemporary outcomes for resected type 1-3 gastroesophageal junction adenocarcinoma: a single-center experience.

BACKGROUND: Surgical resection remains the mainstay of treatment for tumors of the gastroesophageal junction (GEJ). However, contemporary analyses of the Western experience for GEJ adenocarcinoma are sparsely reported. METHODS: Patients with GEJ adenocarcinoma undergoing resection between 2012 and 2022 at a single institution were grouped based on Siewert subtype and analyzed. Pathologic and treatment related variables were assessed with relation to outcomes. RESULTS: A total of 302 patients underwent resection: 161 (53.3%) with type I, 116 (38.4%) with type II, and 25 (8.3%) with type III tumors. Most patients received neoadjuvant therapy (86.4%); 86% of cases were performed in a minimally invasive fashion. Anastomotic leak occurred in 6.0% and 30-day mortality in only 0.7%. The rate of grade 3+ morbidity was lower for the last 5 years of the study than for the first 5 years (27.5% vs 49.3%, P < .001), as was median length of stay (7 vs 8 days, P < .001). There was a significantly greater number of signet ring type tumors among type III tumors (44.0%) than type I/II tumors (11.2/12.9%, P < .001). Otherwise, there was no difference in the distribution of pathologic features among Siewert subtypes. Notably, there was a significant difference in 3-year overall survival based on Siewert classification: type I 60.0%, type II 77.2%, and type III 86.3% (P = .011). Siewert type I remained independently associated with worse survival on multivariable analysis (hazard ratio, 4.5; P = .023). CONCLUSIONS: In this large, single-institutional series, operative outcomes for patients with resected GEJ adenocarcinoma improved over time. On multivariable analysis, type I tumors were an independent predictor of poor survival.

Inherited KDM6AA649T facilitates tumor-immune escape and exacerbates colorectal signet-ring cell carcinoma outcomes.

Childhood onset of colorectal signet-ring cell carcinoma (CR-SRCC) is extremely rare and featured as highly malignant with poor prognosis. Here we reported a CR-SRCC case of 11-year-old boy with a novel inherited X-linked KDM6AA694T mutation. The H3K27me3 demethylase KDM6A was frequently mutated in varieties of tumors and acts as a tumor suppressor. In vivo H3K27me3 demethylation assay demonstrated that KDM6AA694T had dampened H3K27me3 demethylase activity. Overexpression of KDM6AA694T in SRCC cell line KATO3 promoted cell proliferation, invasion and migration, which were further confirmed in vivo by constructing orthotopic tumor growth and lung metastasis model. Besides, expression of KDM6AA694T in immune cells suppresses inflammatory macrophage response and effector T cell response. In conclusion, we characterized a novel inherited KDM6AA694T mutant from a childhood-onset SRCC case and demonstrated that the mutant with impaired H3K27me3 demethylase activity could potentiate tumor malignancy and suppress antitumor immunity.

A novel web-based dynamic prognostic nomogram for gastric signet ring cell carcinoma: a multicenter population-based study.

Background: Gastric signet ring cell carcinoma (GSRCC) is a rare and highly malignant disease with a poor prognosis. To assess the overall survival (OS) and cancer-specific survival (CSS) of patients with GSRCC, prognostic nomograms were developed and validated using common clinical factors. Methods: This retrospective cohort study included patients diagnosed with GSRCC between 2011 and 2018 from the National Cancer Center (n = 1453) and SEER databases (n = 2745). Prognostic nomograms were established by identifying independent prognostic factors using univariate and multivariate Cox regression analyses. The calibration curve and C-index were used to assess the predictions. The clinical usefulness of the survival prediction model was further evaluated using the DCA and ROC curves. The models were internally validated in the training cohort and externally validated in the validation cohort. Two web servers were created to make the nomogram easier to use. Results: Patients with GSRCC were divided into training (n = 2938) and validation (n = 1260) cohorts. The nomograms incorporated six predictors: age, race, tumor site, tumor size, N stage, T stage, and AJCC stage. Excellent agreement was observed between the internal and exterior calibration plots for the GSRCC survival estimates. The C-index and area under the ROC curve were roughly greater than 0.7. Both nomograms had adequate clinical efficacy, as demonstrated by the DCA plots. Furthermore, we developed a dynamic web application utilizing the constructed nomograms available at https://jiangyujuan.shinyapps.io/OS-nomogram/ and https://jiangyujuan.shinyapps.io/DynNomapp-DFS/. Conclusion: We developed web-based dynamic nomograms utilizing six independent prognostic variables that assist physicians in estimating the OS and CSS of patients with GSRCC.

Prognostic and predictive value of tumor deposits in advanced signet ring cell colorectal cancer: SEER database analysis and multicenter validation.

BACKGROUND: Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer with a bleak prognosis. The relationship between its clinicopathological features and survival remains incompletely elucidated. Tumor deposits (TD) have been utilized to guide the N staging in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual, but their prognostic significance remains to be established in colorectal SRCC. PATIENTS AND METHODS: The subjects of this study were patients with stage III/IV colorectal SRCC who underwent surgical treatment. The research comprised two cohorts: a training cohort and a validation cohort. The training cohort consisted of 631 qualified patients from the SEER database, while the validation cohort included 135 eligible patients from four independent hospitals in China. The study assessed the impact of TD on Cancer-Specific Survival (CSS) and Overall Survival (OS) using Kaplan-Meier survival curves and Cox regression models. Additionally, a prognostic nomogram model was constructed for further evaluation. RESULTS: In both cohorts, TD-positive patients were typically in the stage IV and exhibited the presence of perineural invasion (PNI) (P < 0.05). Compared to the TD-negative group, the TD-positive group showed significantly poorer CSS (the training cohort: HR, 1.87; 95% CI, 1.52-2.31; the validation cohort: HR, 2.43; 95% CI, 1.55-3.81; all P values < 0.001). This association was significant in stage III but not in stage IV. In the multivariate model, after adjusting for covariates, TD maintained an independent prognostic value (P < 0.05). A nomogram model including TD, N stage, T stage, TNM stage, CEA, and chemotherapy was constructed. Through internal and external validation, the model demonstrated good calibration and accuracy. Further survival curve analysis based on individual scores from the model showed good discrimination. CONCLUSION: TD positivity is an independent factor of poor prognosis in colorectal SRCC patients, and it is more effective to predict the prognosis of colorectal SRCC by building a model with TD and other clinically related variables.

Impact of pCR after neoadjuvant chemotherapy and radical D2 dissection in locally advanced gastric cancers: Analysis of 1001 cases.

BACKGROUND: Advances in perioperative chemotherapy have improved outcomes in patients with gastric cancers (GC). This strategy leads to tumour downstaging and may result in a pathologic complete response (pCR). The study aimed to evaluate the predictors of pCR and determine the impact of pCR on long-term survival. METHODS: At the Department of Gastrointestinal and HPB Oncology at the Tata Memorial Centre, Mumbai, 1001 consecutive patients with locally advanced GCs undergoing radical resection following neoadjuvant chemotherapy from January 2005 to June 2022 were included. RESULTS: At a median follow-up of 61 months, the median OS was 53 months with a 5-year OS of 46.8 %. Ninety-five patients (9.49 %) realized pCR. Non-signet and well-differentiated histology were associated with pCR. pCR was significantly associated with improved OS, 5-year OS 79.2 % vs 43.2 % (HR 0.30, p < 0.001). On multivariable analysis, the realization of pCR and completion of adjuvant chemotherapy had superior OS. Whereas, signet-ring histology, linitis-like tumours, and high lymph node ratio had adverse outcomes. CONCLUSION: Tumour grade and signet-ring histology predict achievement of pCR in locally advanced GCs after neoadjuvant chemotherapy. Patients with pCR have significantly improved survival. Future neoadjuvant strategies should focus on enhancing pCR rates to improve overall outcomes.

A novel log odds of positive lymph nodes-based nomogram for predicting overall survival in patients with colorectal signet ring cell carcinoma: a SEER population-based study.

PURPOSE: Considering the poor prognosis and high lymph node (LN) involvement rate of colorectal signet ring cell carcinoma (SRCC), this study aimed to construct a prognostic nomogram to predict overall survival (OS) with satisfactory accuracy and utility, based on LN status indicators with superior predictability. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we obtained cases of colorectal SRCC patients and employed univariate and multivariate Cox analyses to determine independent prognostic factors. Kaplan-Meier curves were utilized to visualize survival differences among these factors. Receiver operating characteristic curves were generated to assess predictive performances of models incorporating various LN status indicators. A novel nomogram, containing optimal LN status indicators and other prognostic factors, was developed to predict OS, whose discriminatory ability and accuracy were evaluated using calibration curves and decision curve analysis. RESULTS: A total of 1663 SRCC patients were screened from SEER database. Older patients and those with grades III-IV, tumor sizes > 39 mm, T3/T4 stage, N1/N2 stage, M1 stage, and higher log odds of positive lymph nodes (LODDS) values exhibited poorer prognoses. Age, grade, tumor size, TNM stage, and LODDS were independent prognostic factors. The model containing N stage and LODDS outperformed the one relying solely on N stage as LN status indicator, resulting in a validated nomogram for accurately predicting OS in SRCC patients. CONCLUSION: The integration of LODDS, N stage, and other risk factors into a nomogram offered precise OS predictions, enhancing therapeutic decision-making and tailored follow-up management for colorectal SRCC patients.

Unusual Metastasis of Signet-Ring Cell Gastric Cancer That Could Not Be Detected With 18 F-FDG PET But With 68 Ga-FAPI PET/CT.

ABSTRACT: A 70-year-old man who was scheduled for surgery because of the recurrence of gastric cancer was referred to our clinic preoperatively. The patient underwent a comprehensive evaluation through 18 F-FDG and 68 Ga-FAPI ( 68 Ga-labeled FAP inhibitors) PET/CT scans. The 68 Ga-FAPI PET/CT scan was particularly valuable in this case because of its ability to detect recurrent mass lesions and identify unusual metastatic sites compared with the 18 F-FDG PET/CT scan.

Prognostic significance of serum tumor markers in various pathologic subtypes of gastric cancer.

PURPOSE: This study aimed to assess the utility of 6 serum tumor markers in prognosis between gastric adenocarcinoma and gastric signet ring cell carcinoma (SRCC). METHODS: A cohort of 3131 cases of gastric adenocarcinoma and 275 cases of gastric SRCC was assembled. The serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125, alpha fetoprotein (AFP), carbohydrate antigen 242 (CA242), and carbohydrate antigen 724 (CA724) were measured in all cases. The study analyzed the association between the levels of these 6 tumor markers and the prognosis of gastric adenocarcinoma and SRCC. RESULTS: The study revealed that gastric SRCC exhibited lower concentrations of CEA (P < .001) and CA19-9 (P = .002), along with reduced positive rates of CEA (P = .041), CA19-9 (P = .003), AFP (P < .001), and CA242 (P = .006), while displaying higher positive rates of CA724 (P = .024) than gastric adenocarcinoma. Nevertheless, the receiver operating characteristic curve demonstrated that serum tumor markers did not hold clinical significance in differentiating between gastric adenocarcinoma and SRCC. Survival analysis substantiated that the combined criteria of serum tumor markers stood as an independent risk factor for both gastric adenocarcinoma and SRCC. Notably, the nomogram indicated that serum tumor markers exerted a more substantial influence on the prognosis of gastric adenocarcinoma than on gastric SRCC. CONCLUSION: The study concluded that the combined criteria of serum tumor markers emerge as independent risk factors for both subtypes of gastric cancer. Furthermore, this combined approach exhibited enhanced efficacy in prognosticating the outcome of gastric adenocarcinoma compared with gastric SRCC.

Verrucous gastritis-like lesion in intramucosal Helicobacter pylori-uninfected signet ring cell carcinoma with poorly differentiated adenocarcinoma.

In Japan, accessible Helicobacter pylori (Hp) eradication therapy is associated with an increase in the prevalence of gastric cancers (GCs) in Hp uninfected stomachs. Signet ring cell carcinoma (SRCC) is the most common of these GCs. Intramucosal SRCC with poorly differentiated adenocarcinoma (PDA) occurring in Hp uninfected gastric mucosa is rare; furthermore, many Hp uninfected pure SRCCs exhibit discoloration and flat or slightly depressed lesions, and morphological elevation is relatively rare. We report a case of intramucosal SRCC with PDA with an elevated, verrucous gastritis-like lesion in a 57-year-old male patient. In the present case, the PDA area showed dense tumor cell growth and coexisting desmoplastic and fibrotic reactions. Histopathology and immunohistochemical staining identified extensive fibromuscular obliteration with smooth muscle bundles extending from the muscularis mucosa into the lamina propria. The patient underwent curative endoscopic submucosal dissection. The reporting and analysis of such rare cases may lead to a better understanding of the characteristics of advanced Hp uninfected GCs.

Survival impact of gastrectomy and chemotherapy on gastric signet ring-cell carcinoma with different metastatic lesions: A population-based study.

BACKGROUND: A comprehensive understanding of gastric signet ring cell carcinoma (SRCC) is limited. The aim of our study was to analyze metastatic patterns of gastric SRCC and evaluate impacts of gastrectomy and chemotherapy for metastatic gastric SRCC. METHODS: We obtained data of gastric cancer patients between 2010 and 2017 in the Surveillance, Epidemiology, and End Results database. Chi-square tests were used to compare data significance. Kaplan-Meier, Cox proportional hazards regression and Fine-Gray competing risk analysis were used to analyze the difference in the overall survival (OS) and cancer-specific survival (CSS). Propensity-score matching was used to adjust numerical difference. RESULTS: Among 36,459 eligible gastric cancer patients, 6264 (17.2 %) were SRCC patients. Bone metastasis was more common in SRCC patients than in non-SRCC patients. The multivariate analysis showed that chemotherapy (HR = 0.30, 95 %CI = 0.27-0.33, p < 0.01) and gastrectomy (HR = 0.51, 95 %CI = 0.45-0.59, p < 0.01) were protective prognostic factors in certain stage Ⅳ SRCC patients. For the effect of gastrectomy, survival benefits could be found in patients with liver metastasis. The gastrectomy was not associated with improved OS in patients with lung or multiple metastases. In subgroup analysis, SRCC patients with metastasis who received gastrectomy and chemotherapy (HR = 0.17, p < 0.01; HR = 0.03, p < 0.01) had a better OS and CSS than those who had chemotherapy only (HR = 0.30, p < 0.01; HR = 0.18, p < 0.01). CONCLUSION: Our study analyzed the unique metastatic patterns of gastric SRCC and recommended chemotherapy as the first choice in metastatic SRCC. For patients with liver metastasis, gastrectomy plus chemotherapy can be considered.

A Prognostic Model for Survival in Patients with Gastric Signet Ring Cell Carcinoma.

INTRODUCTION: The objective of our study was to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRCC). METHODS: A total of 3,408 GSRCC patients between 1975 and 2017 were screened from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and validation cohorts. Univariate and multivariate Cox analyses were conducted to identify independent prognostic factors for the construction of a nomogram. The performance of the model was then assessed by the concordance index (C-index), calibration plot, and area under the receiver operating characteristic curve (AUC). Then, the novel nomogram was further assessed by 64 GSRCC patients from our hospital as the external cohort. RESULTS: We identified age, tumor lymph node metastasis (TNM) staging system, surgery, and chemotherapy as significant independent elements of prognosis. On this basis, a nomogram was constructed, with a C-index of OS in the training and validation cohorts of 0.763 (95% CI: 0.751-0.774) and 0.766 (95% CI: 0.748-0.784) and a C-index of CSS of 0.765 (95% CI: 0.753-0.777) and 0.773 (95% CI: 0.755-0.791), respectively. The AUCs of the nomogram for predicting 2- and 5-year OS were 0.848 and 0.885, respectively, and those for predicting CSS were 0.854 and 0.899, respectively, demonstrating the excellent predictive value of the constructed nomogram compared to the traditional AJCC staging system. Similar results were also observed in both the internal and external validation sets. CONCLUSION: The nomogram provided an accurate tool to predict OS and CSS in patients with GSRCC, which can assist clinicians in making predictions about individual patient survival.

Efficacy of Neoadjuvant Chemotherapy in Lobular and Rare Subtypes of Breast Cancer.

OBJECTIVE: To determine the predictive factors for the pathological complete response (pCR) in patients with non-ductal invasive breast cancer (ND-BC) receiving neoadjuvant chemotherapy. STUDY DESIGN: Observational study. Place and Duration of the Study: Departments of Medical Oncology, Tekirdag Namik Kemal University, Sirnak State Hospital, Aydin Adnan Menderes University, Marmara University, Bakirkoy Sadi Konuk Hospital, Basaksehir Cam and Sakura Hospital, Sakarya University, Balikesir Ataturk Hospital, Turkiye, from April 2016 to December 2022. METHODOLOGY: A total of 222 non-metastatic breast cancer patients who received neoadjuvant chemotherapy were included in this retrospective multicentric study. The clinicopathologic data were obtained from the hospitals' electronic-record-system. The logistic regression models were used to identify predictive factors for pCR. RESULTS: One hundred and twenty-six patients (56.8%) had invasive lobular carcinoma and 28 patients (12.6%) had signet ring cell/mucinous carcinoma. A total of 45 patients (20.3%) achieved pCR. The pCR rate was 14.3% for lobular carcinoma and 17.9% for signet ring cell/mucinous carcinoma. The univariate analysis showed that estrogen receptor-negative tumours (p = 0.017), high Ki-67 (p = 0.008), high histologic grade (p<0.001), HER2+ expression (p<0.001), and non-lobular histologic type (p = 0.012) were predictive factors for pCR. The multivariate model revealed that HER2 expression (p<0.001) and Ki-67 (p = 0.005) were independent predictors. CONCLUSION: Neoadjuvant chemotherapy demonstrated effectiveness in ND-BC patients, leading to favourable pCR rates and enabling breast-conserving surgery. Predictive markers for pCR varied depending on histologic types, with HER2 expression, ER status, Ki-67, and histologic grade showing significance in non-ductal subtypes, while HER2 status alone was predictive in lobular carcinoma. KEY WORDS: Neoadjuvant chemotherapy, Non-ductal breast cancer, Lobular carcinoma.

Atypical Histopathological Aspects of Common Types of Lung Cancer-Our Experience and Literature Review.

Lung cancer is among the most common oncological diseases regarding incidence and mortality, with most of these having epithelial origins. Pathological reporting of these tumors is conducted according to the 5th edition of the World Health Organisation (WHO) classification of thoracic tumours. This study aims to draw the pathologist's attention to four rare, atypical microscopic aspects that some of the most common types of lung malignancies reveal upon standard evaluation (hematoxylin-eosin stain) that make histopathological diagnosis challenging: acantholytic, pseudoangiosarcomatous, signet ring cell, and clear cell features. Each of these aspects was exemplified by a case diagnosed in the pathology department of the "Marius Nasta" Institute. Furthermore, we analyzed the classification dynamics of different WHO editions and used PubMed to review articles written in English and published in the last eleven years on this subject. Pathologists should be familiar with these unusual aspects to avoid misdiagnoses and to ensure the correct classification of tumors, which is extremely important because these tumor phenotypes have been associated with specific molecular alterations and a worse clinical evolution. There is a need to clarify the histogenesis and associated genetic mutations, given the fact that the rarity of these tumor phenotypes makes their study difficult. Some authors consider these to be overlapping entities; however, we do not encourage this, as they may exhibit different prognoses and various molecular alterations with important therapeutic implications. The signet ring cell feature was associated with ALK rearrangement in lung adenocarcinoma; thus, these patients can benefit from tailored therapy with ALK-tyrosine kinase inhibitors (ALK-TKI). Recent studies associated clear cell morphology with FGFR3-TACC3 fusion, suggesting that patients with this diagnosis may be potentially eligible for FGFR inhibitors. We described, for the first time, the pseudoangiosarcomatous pattern in a case of lung adenocarcinoma; to our knowledge this aspect has only been described until now in the context of squamous cell carcinomas.