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Signet ring cell lymphoma (SRCL) is a non-Hodgkin's lymphoma with a very rare variant. Although this morphology is frequently seen in follicular lymphoma, it can also be observed in the group of diffuse large B-cell lymphomas. A seventy-six year old woman with known diagnosis of gastric adenocarcinoma, tubular type, moderately differentiate presented with a mesenteric lymphadenopathy with high FDG uptake (SUVmax: 21.3) in PET/CT during follow-up. A tru-cut biopsy was performed for histopathological diagnosis. Diffuse infiltrative singet ring neoplastic cells showed negativity for PanCK, CK7, CK20, S100, SMA, calretinin and vimentin. The panel was then expanded to include SRCL, a rare variant of lymphoma. Additional immunohistochemical evaluation revealed positivity for CD20, CD19, PAX-5 and Bcl-2. Ki-67 proliferation index was about 80%. CD3, CD30, Myc, Bcl-6, ALK, Cyclin-D1, CD23, CD10, CD21, and MUM-1 were negative. EBER was also negative by chromogen in situ hybridization (CISH). Based on these data, diffuse large B-cell lymphoma (DLBCL) was considered. We herein reported a case of signet ring cell lymphoma discussed its clinical and morphological features with regard to the literature. [ABSTRACT FROM AUTHOR]

Abstract Background Most metastatic lung tumors present as solid nodules on chest computed tomography (CT). In contrast, ground-glass opacity on chest computed tomography usually suggests low-grade malignant lesions such as adenocarcinoma in situ or atypical adenomatous hyperplasia of the lung. Case presentation A 75-year-old woman with a history of gastric cancer surgery approximately 5 years prior was referred to the Department of Thoracic Surgery at our hospital because of two newly appearing pulmonary ground-glass opacity-dominant nodules on chest computed tomography. She had two ground-glass opacities in the right lower lobe, one in the S6 segment was 12 mm and the other in the S10 segment was 8 mm. On chest computed tomography 15 months prior to referral, the lesion in the S6 segment was 8 mm, and the lesion in the S10 segment was 2 mm. She was suspected to have primary lung cancer and underwent wide-wedge resection of the nodule in the S6 segment. In the resected specimen, polygonal tumor cells infiltrated the alveolar septa, with some tumor cells exhibiting signet ring cell morphology. Based on morphological similarities to the tumor cells of previous gastric cancers and the results of immunostaining, the patient was diagnosed with lung metastases of gastric cancer. Conclusions Pulmonary nodules in patients with a history of cancer in other organs, even if ground-glass opacity is predominant, should also be considered for the possibility of metastatic pulmonary tumors if they are growing rapidly.

Background: Most metastatic lung tumors present as solid nodules on chest computed tomography (CT). In contrast, ground-glass opacity on chest computed tomography usually suggests low-grade malignant lesions such as adenocarcinoma in situ or atypical adenomatous hyperplasia of the lung. Case presentation: A 75-year-old woman with a history of gastric cancer surgery approximately 5 years prior was referred to the Department of Thoracic Surgery at our hospital because of two newly appearing pulmonary ground-glass opacity-dominant nodules on chest computed tomography. She had two ground-glass opacities in the right lower lobe, one in the S6 segment was 12 mm and the other in the S10 segment was 8 mm. On chest computed tomography 15 months prior to referral, the lesion in the S6 segment was 8 mm, and the lesion in the S10 segment was 2 mm. She was suspected to have primary lung cancer and underwent wide-wedge resection of the nodule in the S6 segment. In the resected specimen, polygonal tumor cells infiltrated the alveolar septa, with some tumor cells exhibiting signet ring cell morphology. Based on morphological similarities to the tumor cells of previous gastric cancers and the results of immunostaining, the patient was diagnosed with lung metastases of gastric cancer. Conclusions: Pulmonary nodules in patients with a history of cancer in other organs, even if ground-glass opacity is predominant, should also be considered for the possibility of metastatic pulmonary tumors if they are growing rapidly. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To determine the general state of scientific evidence published in the last 20 years on gastric signet ring cell (SRC) adenocarcinoma metastatic to the breast, and present a case. Materials and methods: The case of a patient who attended a high-complexity reference institution in Bogotá for a breast metastasis from a gastric SRC adenocarcinoma is reported. A Systematic Review of the literature was carried out, including cohort studies, reports and case series of patients with gastric SRC adenocarcinoma metastatic to the breast, which will present information on the epidemiology, clinical, radiological and histopathological characteristics, and the treatment and prognostic of this disease. Results: There were identified 363 references, twenty-six of which met the eligibility criteria. Gastric SRC adenocarcinoma metastatic to the breast predominated in the Asian continent (75.9%). The mean age at presentation was 42.5 years. In 62% (n=18) of cases this condition manifested clinically as a breast mass. From a radiological point of view, the majority of breast lesions presented as one or several nodules with suspicious characteristics (55.2%; n=16). In the biopsy of breast lesions, positivity for cytokeratin 7 and cytokeratin 20 occurred in 41.4% (n=12) and 37.9% (n=11) of cases, respectively. Only nine patients (31%) underwent any type of breast surgery. There is a lack of information on the treatment and prognosis of gastric SRC adenocarcinoma metastatic to the breast. Conclusions: The frequency of cases of gastric SRC adenocarcinoma metastatic to the breast published in the last 20 years is low. The general practitioner and the gynecologist could be the first medical professionals to face this rare condition, so knowing it and suspecting it is essential, especially if we take into account that the median overall survival of these patients is low. [ABSTRACT FROM AUTHOR]

Background: Colorectal signet-ring cell carcinoma (SRCC) is a rare subtype of malignant adenocarcinoma, accounting for approximately 1 % of colorectal cancer (CRC) cases. Its biomarkers and molecular characteristics remain controversial, and there are no specific therapeutic targets or strategies for its clinical treatment. Methods: A retrospective study was conducted between January 2010 and December 2021. 1058 colorectal cancer cases from the Sun Yat-sen University Cancer Center and 489 cases from the Tumor Genome Atlas Project were included in the analysis, of which 64 were SRCC. Data extraction included patient demographics, blood types and risk factors, including clinical variables and genomics (either a 19-gene panel NGS or 1021-gene panel NGS). Univariate analyses were performed to identify factors significantly associated with overall survival. Results: The blood groups of 27 (42.2 %), 18 (28.1 %), 12 (18.8 %), and seven (10.9 %) patients were classified as O, A, B, and AB, respectively. We found that O was a unique blood group characterized by a low frequency of KRAS mutations, a high frequency of heterozygosity at each HLA class I locus, and a high tumor mutational burden (TMB). Patients in blood group A with high-frequency KRAS mutations and those in blood group B with anemia and metabolic abnormalities required targeted treatment. Furthermore, genetic alterations in SRCC differed from those in adenocarcinoma and mucinous adenocarcinoma. Conclusions: Our study revealed genomic changes in SRCC patients across different blood groups, which could advance the understanding and precise treatment of colorectal SRCC.

Objective: To report an infrequent case of primary signet ring cell carcinoma of the cervix (PSRCC), review the literature and evaluate the clinicopathological characteristics. Material and methods: A 51-year-old female patient, with 3 years of disease characterised by gynaecologic bleeding and pelvic pain. On examination, cervix replaced by tumour and infiltrated parametria; with cytology and histology of adenocarcinoma with cells in a signet ring pattern. Disease extension studies were negative. Classified as PSRCC stage IIIB, chemotherapy and radiotherapy were indicated, but the patient died a month later. The bibliographic search included publications up to July 2023. Results: 32 cases with a mean age of 47.6 years were identified. The most frequent symptoms were uterine bleeding and abdominal and pelvic pain. The initial stages were treated surgically, some with adjuvant chemotherapy and/or radiotherapy, with favourable responses; a difference from advanced cases. The average survival was 17.6 months. Conclusion: PSRCC is rare, with 32 cases reported according to the review. The expression with immunohistochemical and molecular techniques for the human papilloma virus can help confirm the gynaecological primary, but its diagnosis is one of exclusion, since its morphological pattern is related to other primaries, mainly digestive. [ABSTRACT FROM AUTHOR]

Semantic segmentation of Signet Ring Cells (SRC) plays a pivotal role in the diagnosis of SRC carcinoma based on pathological images. Deep learning-based methods have demonstrated significant promise in computer-aided diagnosis over the past decade. However, many existing approaches rely heavily on stacking layers, leading to repetitive computational tasks and unnecessarily large neural networks. Moreover, the lack of available ground truth data for SRCs hampers the advancement of segmentation techniques for these cells. In response, this paper introduces an efficient and accurate deep learning framework (RGGC-UNet), which is a UNet framework including our proposed residual ghost block with ghost coordinate attention, featuring an encoder-decoder structure tailored for the semantic segmentation of SRCs. We designed a novel encoder using the residual ghost block with proposed ghost coordinate attention. Benefiting from the utilization of ghost block and ghost coordinate attention in the encoder, the computational overhead of our model is effectively minimized. For practical application in pathological diagnosis, we have enriched the DigestPath 2019 dataset with fully annotated mask labels of SRCs. Experimental outcomes underscore that our proposed model significantly surpasses other leading-edge models in segmentation accuracy while ensuring computational efficiency. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pulmonary adenocarcinoma is a common type of lung cancer that has been on the rise in recent years. Signet ring cell components (SRCC) can be present in various patterns of pulmonary adenocarcinoma, including papillary, acinar, and solid patterns. "Signet ring cell carcinoma" is a distinct subtype in the 2014 WHO classification of lung neoplasms, subsequent WHO classifications in 2015 and 2021 have deemed signet ring cells as accompanying morphological features with no clinical significance. The prognostic and clinical implications of SRCC in pulmonary adenocarcinoma remain controversial. Therefore, we conducted a meta-analysis to investigate the clinicopathological features and prognostic factors of SRCC in pulmonary adenocarcinoma. We conducted a comprehensive search in PubMed, EMBASE, and Web of Science to identify studies that examined the clinicopathological features and prognostic implications of pulmonary adenocarcinoma with SRCC. We used both fixed- and random-effects models to analyze the data and calculate the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). Additionally, we explored the prognostic significance of SRCC in pulmonary adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database. Our meta-analysis included 29 studies with pulmonary adenocarcinoma and SRCC components. The results showed that pulmonary adenocarcinoma with SRCC was associated with larger tumor size (OR = 1.99; 95% CI, 1.62–2.44, p < 0.001), advanced overall stage (OR = 5.18, 95% CI, 3.28–8.17, p < 0.00001) and lymph node stage (OR = 5.79, 95% CI, 1.96–17.09, p = 0.001), and worse overall survival (OS) compared to those without SRCC (HR = 1.80, 95% CI, 1.50–2.16, p < 0.00001). Analysis using the SEER dataset confirmed these findings. Our meta-analysis provides evidence that pulmonary adenocarcinoma with SRCC is associated with distinct clinicopathological features and a poorer prognosis. These findings have important implications for the management and treatment of patients. However, further studies are needed to validate these findings and explore the significance of SRCC in various subtypes of pulmonary adenocarcinoma. [ABSTRACT FROM AUTHOR]

Abstract Background This study investigated the clinicopathological features, immunophenotypic characteristics and differential diagnosis of primary breast carcinomas with signet ring cell differentiation, as well as differences in the traits of signet ring-like cell mucin. Methods A total of five cases of primary breast cancer diagnosed with signet ring cell differentiation and treated at The First People’s Hospital of Jingmen from January 2016 to December 2021 were collected. HE, immunohistochemical staining, and AB-PAS staining were used for the analysis. Results Although we strictly selected all the primary breast cancer cases with signet ring cell differentiation, there were differences in the arrangement of the cells and the grading of nuclei. Our immunohistochemical results showed that the ER was consistently strongly positive, and the PR expression was not consistent, while all the cases of HER2 were negative. CK7 was negative in one case, and CK20 and CK5/6 were not expressed in all the cases. The mucin MUC1 was positive and showed two patterns. MUC2 was strongly positive in all the cases. All the cases were negative for CDX2, SATB2, PAX8, TTF-1, and Napsin A, while the positive expression of COX2, Villin, and WT-1 was not constant. One case expressed neuroendocrine markers. The expression level of Ki67 was between 10 and 30%. AB (pH 2.5)-PAS staining revealed that the intracellular mucus contained more cells with neutral mucus, while the extracellular mucus was mainly acidic. Conclusion We found that histological morphology, cell morphology, and nuclear grading differentiate among different cases. The immunohistochemical characteristics of primary breast cancers diagnosed with signet ring cell differentiation are helpful for identification. The differences in the expression patterns of mucins may be related to unfavorable clinicopathological factors, but their usefulness as a prognostic marker remains to be further understood. The heterogeneity of cell mucus, the differentiation of tumor cells, and the phenotypic changes of tumors also need further study.

Signet ring cell (SRC) carcinoma is a particularly serious type of cancer that is a leading cause of death all over the world. SRC carcinoma has a more deceptive onset than other carcinomas and is mostly encountered in its later stages. Thus, the recognition of SRCs at their initial stages is a challenge because of different variants and sizes and illumination changes. The recognition process of SRCs at their early stages is costly because of the requirement for medical experts. A timely diagnosis is important because the level of the disease determines the severity, cure, and survival rate of victims. To tackle the current challenges, a deep learning (DL)-based methodology is proposed in this paper, i.e., custom CircleNet with ResNet-34 for SRC recognition and classification. We chose this method because of the circular shapes of SRCs and achieved better performance due to the CircleNet method. We utilized a challenging dataset for experimentation and performed augmentation to increase the dataset samples. The experiments were conducted using 35,000 images and attained 96.40% accuracy. We performed a comparative analysis and confirmed that our method outperforms the other methods. [ABSTRACT FROM AUTHOR]

BackgroundGastric signet ring cell carcinoma (GSRC) is a rare but increasingly prevalent tumor histotype whose clinical features and natural history are poorly understood, particularly in the USA and minorities.AimsTo examine the occurrence, clinico-demographic characteristics, oncologic features, treatment, and outcomes of GSRC in a predominantly minority county hospital setting and benchmark them against data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program.MethodsWe queried biopsy-proven GSRC cases at a Los Angeles County hospital, from 2004 to 2017. Clinical characteristics, treatment, and survival data were collected and compared to SEER data.ResultsWe identified 63 patients with GSRC. Compared to SEER, our cohort was significantly younger (52.6 vs. 63.5 years, p

Abstract Background Diffuse large B-cell lymphoma (DLBCL) with signet ring cell components is extremely rare. Here, we present a case of DLBCL with signet ring cell components involving the breast, which can be easily confused with invasive lobular carcinoma of the breast or metastatic signet ring cell carcinoma of gastrointestinal origin. Case presentation A 66-year-old woman presented with a painless mass in her left breast. Enhanced magnetic resonance imaging (MRI) of the breast revealed a 42 × 29 × 28 mm mass in the left breast. Histological examination revealed a diffuse or scattered arrangement of round cells mixed with signet ring-like cells. Immunohistochemically, the neoplastic cells were positive for PAX-5, CD79a, CD20, Bcl-6, and MUM-1 but and negative for cytokeratin, ER, PR, E-cadherin, and P120. The Ki-67 proliferation index was approximately 70%. Fluorescence in situ hybridisation (FISH) demonstrated non-rearrangement of Bcl-2, Bcl-6, and c-MYC genes. Immunohistochemistry and FISH examination confirmed the diagnosis of DLBCL. Subsequently, immunofluorescence showed both IgM and IgG deposits in the signet ring-like lymphocytes. After confirming the diagnosis, the patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy in a specialist hospital and achieved partial remission; however, she unfortunately died of secondary pneumocystis pneumonia infection 3 months later. Conclusion Malignant lymphoma with signet ring cell morphology is quite uncommon, and this variant can be a diagnostic pitfall. We emphasise that pathologists should consider lymphoma in the differential diagnosis of malignant breast tumours.

Primary signet ring cell carcinoma (PSRCC) of the prostate is an extremely rare variant of prostatic adenocarcinoma. A PubMed search of the English language literature from January 2000 to June 2020 using the keywords "signet ring cell carcinoma" and "prostate," identified 20 cases of PSRCC of the prostate. On the basis of the combined data from this study and the literature review, 21 such patients were evaluated for clinical characteristics, histologic diagnoses, special and immunohistochemical staining, and treatment. The mean age at the diagnosis was 68.47 years (range 50-85 years). The prostate-specific antigen (PSA) levels varied from 0.19 to 6658 ng/mL, with a mean of 509.15 ng/mL. Most (50%) presented with Stage 3 cancer. The most common Gleason grade group was 5 (Gleason score 9 to 10), seen in 61.5%. The extent of signet ring cell involvement of the specimen when reported was documented as more than 20% of the tumor-containing signet ring cells, with a range of 25%-90%. For pathologic diagnosis, the most common special stains performed were periodic acid-Schiff and Alcian blue, and among the immunohistochemical stains, the most common were PSA, CK20, and prostate-specific acid phosphatase. A detailed clinicoradiological and pathological workup is essential to rule out primary from other common sites, in view of its grave prognosis and lack of an established treatment protocol. [ABSTRACT FROM AUTHOR]

Introduction: Signet ring cell carcinoma accounts for 35% to 45% of all gastric cancer. Despite the acknowledgment of its more aggressive pathological features, various controversies surrounding this topic still exist. Thus, we investigate the clinical pathological characteristics and survival prognostic significance of signet ring cell components in patients affected by gastric cancer. Methods: From January 2004 to December 2020, in a retrospective study, we enrolled 404 patients with gastric cancer who were curatively treated in our department. The male-to-female ratio was 249/142, and the median age was 75 (range 37–94). We dichotomized patients into two groups (75 patients vs. 316 patients) based on the signet ring cell presence; according to preoperative, operative, and postoperative characteristics, we performed a univariate and multivariate analysis for overall survival. Results: Signet ring cell carcinoma indicated an increasing incidence trend over the time analyzed. Overall median survival of signet ring cell and non-signet ring cell carcinoma were, respectively, 16 vs. 35 months, p < 0.05. In early gastric cancer, the prognosis of the signet ring cell is better than that of the non-signet ring cell, as opposed to advanced cancer. Among the entire population in the multivariate analysis, the only independent factors were preoperative serum albumin level, complete surgical resection, level of lymphadenectomy, and pathological stage. Recurrence occurred more frequently in patients affected by signet ring cell, but in our data, we could not identify a peculiar site of recurrence. Conclusions: Signet ring cell carcinoma has a specific oncogenetic phenotype and treatment resistance heterogeneity; however, it is not always associated with poor prognosis. According to our results, a radical surgical procedure associated with an adequate lymphadenectomy should be advocated to improve patients survival. Gastric cancer patients with signet ring cell components should draw clinicians' attention. [ABSTRACT FROM AUTHOR]

Background: This study investigated the clinicopathological features, immunophenotypic characteristics and differential diagnosis of primary breast carcinomas with signet ring cell differentiation, as well as differences in the traits of signet ring-like cell mucin. Methods: A total of five cases of primary breast cancer diagnosed with signet ring cell differentiation and treated at The First People's Hospital of Jingmen from January 2016 to December 2021 were collected. HE, immunohistochemical staining, and AB-PAS staining were used for the analysis. Results: Although we strictly selected all the primary breast cancer cases with signet ring cell differentiation, there were differences in the arrangement of the cells and the grading of nuclei. Our immunohistochemical results showed that the ER was consistently strongly positive, and the PR expression was not consistent, while all the cases of HER2 were negative. CK7 was negative in one case, and CK20 and CK5/6 were not expressed in all the cases. The mucin MUC1 was positive and showed two patterns. MUC2 was strongly positive in all the cases. All the cases were negative for CDX2, SATB2, PAX8, TTF-1, and Napsin A, while the positive expression of COX2, Villin, and WT-1 was not constant. One case expressed neuroendocrine markers. The expression level of Ki67 was between 10 and 30%. AB (pH 2.5)-PAS staining revealed that the intracellular mucus contained more cells with neutral mucus, while the extracellular mucus was mainly acidic. Conclusion: We found that histological morphology, cell morphology, and nuclear grading differentiate among different cases. The immunohistochemical characteristics of primary breast cancers diagnosed with signet ring cell differentiation are helpful for identification. The differences in the expression patterns of mucins may be related to unfavorable clinicopathological factors, but their usefulness as a prognostic marker remains to be further understood. The heterogeneity of cell mucus, the differentiation of tumor cells, and the phenotypic changes of tumors also need further study. [ABSTRACT FROM AUTHOR]

Signet-ring squamous cell carcinoma is a rare histological subtype of squamous cell carcinoma. The distinct morphologic appearance of this variant can mimic metastatic adenocarcinoma and impose a diagnostic challenge. Unlike its glandular counterpart, signet-ring cell variant of squamous cell carcinoma has a poorly characterized histopathogenesis with no known prognostic implication. We describe an additional case and review the literature.

Aldo–keto reductase family 1 member B10 (AKR1B10) is associated with several cancers, but the prognostic role in gastric cancer (GC) remains unclear. We enrolled 359 GC patients who underwent a gastrectomy with D2 lymph node dissection. AKR1B10 expression was scored using an immunoreactive scoring system based on immunohistochemistry. Adjuvant chemotherapy with S-1 or oxaliplatin plus capecitabine was administered to pathological stage II or III disease patients. There were 117 (32.6%) and 242 (67.4%) patients with AKR1B10 overexpression and low expression, respectively. Patients overexpressing AKR1B10 had worse 5-year disease-free survival (DFS) and overall survival (OS) rates than those with low expression of AKR1B10. Pathological T3–T4 stage, pathological stage III, lymph node ratio ≥25%, and AKR1B10 overexpression were independent prognostic factors for worse DFS and OS in univariate and multivariate analyses. For 162 stage II or III patients who received adjuvant chemotherapy after surgical resection and 59 patients with signet ring cell carcinoma histology, AKR1B10 overexpression was also associated with inferior DFS and OS. AKR1B10 was not associated with clinical survival in stage I GC patients. In conclusion, AKR1B10 overexpression may be an independent prognostic factor for worse survival in GC patients who underwent gastrectomy with D2 lymph node dissection.

Background: Diffuse large B-cell lymphoma (DLBCL) with signet ring cell components is extremely rare. Here, we present a case of DLBCL with signet ring cell components involving the breast, which can be easily confused with invasive lobular carcinoma of the breast or metastatic signet ring cell carcinoma of gastrointestinal origin. Case presentation: A 66-year-old woman presented with a painless mass in her left breast. Enhanced magnetic resonance imaging (MRI) of the breast revealed a 42 × 29 × 28 mm mass in the left breast. Histological examination revealed a diffuse or scattered arrangement of round cells mixed with signet ring-like cells. Immunohistochemically, the neoplastic cells were positive for PAX-5, CD79a, CD20, Bcl-6, and MUM-1 but and negative for cytokeratin, ER, PR, E-cadherin, and P120. The Ki-67 proliferation index was approximately 70%. Fluorescence in situ hybridisation (FISH) demonstrated non-rearrangement of Bcl-2, Bcl-6, and c-MYC genes. Immunohistochemistry and FISH examination confirmed the diagnosis of DLBCL. Subsequently, immunofluorescence showed both IgM and IgG deposits in the signet ring-like lymphocytes. After confirming the diagnosis, the patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy in a specialist hospital and achieved partial remission; however, she unfortunately died of secondary pneumocystis pneumonia infection 3 months later. Conclusion: Malignant lymphoma with signet ring cell morphology is quite uncommon, and this variant can be a diagnostic pitfall. We emphasise that pathologists should consider lymphoma in the differential diagnosis of malignant breast tumours. [ABSTRACT FROM AUTHOR]

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.

Semantic segmentation of Signet Ring Cells (SRC) plays a pivotal role in the diagnosis of SRC carcinoma based on pathological images. Deep learning-based methods have demonstrated significant promise in computer-aided diagnosis over the past decade. However, many existing approaches rely heavily on stacking layers, leading to repetitive computational tasks and unnecessarily large neural networks. Moreover, the lack of available ground truth data for SRCs hampers the advancement of segmentation techniques for these cells. In response, this paper introduces an efficient and accurate deep learning framework (RGGC-UNet), which is a UNet framework including our proposed residual ghost block with ghost coordinate attention, featuring an encoder-decoder structure tailored for the semantic segmentation of SRCs. We designed a novel encoder using the residual ghost block with proposed ghost coordinate attention. Benefiting from the utilization of ghost block and ghost coordinate attention in the encoder, the computational overhead of our model is effectively minimized. For practical application in pathological diagnosis, we have enriched the DigestPath 2019 dataset with fully annotated mask labels of SRCs. Experimental outcomes underscore that our proposed model significantly surpasses other leading-edge models in segmentation accuracy while ensuring computational efficiency.

BACKGROUND:The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented. METHODS:Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score ≥ 1. Cohort 2 (combination therapy) received pembrolizumab 200 mg on day 1, cisplatin 80 mg/m2 on day 1 (up to 6 cycles), and 5-fluorouracil 800 mg/m2 on days 1-5 of each 3-week cycle (or capecitabine 1000 mg/m2 twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy). RESULTS:In the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8 months (range 1.8-24.1) and 17.5 months (range 1.7-20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0%); none were fatal. In the monotherapy cohort, grade 3-5 treatment-related adverse events occurred in seven patients (22.6%); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0% [95% confidence interval (CI), 38.7-78.9] (combination therapy) and 25.8% (95% CI 11.9-44.6) (monotherapy). CONCLUSIONS:Pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma. CLINICAL TRIAL:ClinicalTrials.gov NCT02335411.

The tumor suppressor p16Ink4a, encoded by the INK4a gene, is an inhibitor of cyclin D-dependent kinases 4 and 6, CDK4 and CDK6. This inhibition prevents the phosphorylation of the retinoblastoma protein (pRb), resulting in cellular senescence through inhibition of E2F-mediated transcription of S phase genes required for cell proliferation. The p16Ink4a plays an important role in tumor suppression, whereby its deletion, mutation, or epigenetic silencing is a frequently observed genetic alteration in prostate cancer. To assess its roles and related molecular mechanisms in prostate cancer initiation and progression, we generated a mouse model with conditional deletion of p16Ink4a in prostatic luminal epithelium. The mice underwent oncogenic transformation and developed prostatic intraepithelial neoplasia (PIN) from eight months of age, but failed to develop prostatic tumors. Given the prevalence of aberrant androgen signaling pathways in prostate cancer initiation and progression, we then generated R26hARL/wt:p16L/L: PB-Cre4 compound mice, in which conditional expression of the human AR transgene and deletion of p16Ink4a co-occur in prostatic luminal epithelial cells. While R26hARL/wt:PB-Cre4 mice showed no visible pathological changes, R26hARL/wt:p16L/L: PB-Cre4 compound mice displayed an early onset of high-grade PIN (HGPIN), prostatic carcinoma, and metastatic lesions. Strikingly, we observed tumors resembling human sarcomatoid carcinoma with intermixed focal regions of signet ring cell carcinoma (SRCC) in the prostates of the compound mice. Further characterization of these tumors showed they were of luminal epithelial cell origin, and featured characteristics of epithelial to mesenchymal transition (EMT) with enhanced proliferative and invasive capabilities. Our results not only implicate a biological role for AR expression and p16Ink4a deletion in the pathogenesis of prostatic SRCC, but also provide a new and unique genetically engineered mouse (GEM) model for investigating the molecular mechanisms for SRCC development.

Background: Mature teratomas belong to the group of germ line ovarian tumors; they generally have benign behavior. Malignant transformation occurs in 0.2% to 1% of tumors. The objective is to show the results of peritonectomy with HIPEC in the treatment of a mature teratoma with malignant differentiation with signet ring cells. Clinical case: 43-year-old woman diagnosed with mature malignant teratoma with signet ring cells. It was performed optimal primary cytoreduction surgery, total hysterectomy, bilateral salpingo-oophorectomy, peritonectomy, appendectomy, cholecystectomy and splenectomy adding intraoperative hyperthermic chemotherapy (HIPEC). Conclusions: Malignant transformation of a mature teratoma of the ovary is a rare event, but not exceptional. HIPEC was used after optimal cytoreduction, with good results, since the patient is in a disease-free period of 36 months. It is necessary to report cases in order to compare different types of treatment to improve oncological results. [ABSTRACT FROM AUTHOR]

Aldo–keto reductase family 1 member B10 (AKR1B10) is associated with several cancers, but the prognostic role in gastric cancer (GC) remains unclear. We enrolled 359 GC patients who underwent a gastrectomy with D2 lymph node dissection. AKR1B10 expression was scored using an immunoreactive scoring system based on immunohistochemistry. Adjuvant chemotherapy with S-1 or oxaliplatin plus capecitabine was administered to pathological stage II or III disease patients. There were 117 (32.6%) and 242 (67.4%) patients with AKR1B10 overexpression and low expression, respectively. Patients overexpressing AKR1B10 had worse 5-year disease-free survival (DFS) and overall survival (OS) rates than those with low expression of AKR1B10. Pathological T3–T4 stage, pathological stage III, lymph node ratio ≥25%, and AKR1B10 overexpression were independent prognostic factors for worse DFS and OS in univariate and multivariate analyses. For 162 stage II or III patients who received adjuvant chemotherapy after surgical resection and 59 patients with signet ring cell carcinoma histology, AKR1B10 overexpression was also associated with inferior DFS and OS. AKR1B10 was not associated with clinical survival in stage I GC patients. In conclusion, AKR1B10 overexpression may be an independent prognostic factor for worse survival in GC patients who underwent gastrectomy with D2 lymph node dissection. [ABSTRACT FROM AUTHOR]

Signet ring cell (SRC) carcinoma is a particularly serious type of cancer that is a leading cause of death all over the world. SRC carcinoma has a more deceptive onset than other carcinomas and is mostly encountered in its later stages. Thus, the recognition of SRCs at their initial stages is a challenge because of different variants and sizes and illumination changes. The recognition process of SRCs at their early stages is costly because of the requirement for medical experts. A timely diagnosis is important because the level of the disease determines the severity, cure, and survival rate of victims. To tackle the current challenges, a deep learning (DL)-based methodology is proposed in this paper, i.e., custom CircleNet with ResNet-34 for SRC recognition and classification. We chose this method because of the circular shapes of SRCs and achieved better performance due to the CircleNet method. We utilized a challenging dataset for experimentation and performed augmentation to increase the dataset samples. The experiments were conducted using 35,000 images and attained 96.40% accuracy. We performed a comparative analysis and confirmed that our method outperforms the other methods.

Abstract The endoscopic findings of gastric metastases from breast carcinoma are nonspecific, and often difficult to distinguish from primary gastric signet ring cell carcinoma. Therefore, pathological findings are key to diagnosis.

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Mucinous adenocarcinoma with signet cell features originating from Meckel diverticulum (MD) is an extremely rare primary malignant tumor. A woman in her 30s presented with multiple episodes of vomiting, abdominal pain, and constipation. She had a history of stricturing Crohn's disease and managed well with steroids, azathioprine, and infliximab. This time, a computed tomography scan showed distal ileal small-bowel obstruction. Urgent surgery for a nonsettling small bowel obstruction was performed. MD was incidentally found and was concerning for malignancy. This case report illustrates how this extremely rare malignancy was behaving like Crohn's disease, which delayed the diagnosis and treatment., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objectives: To determine the general state of scientific evidence published in the last 20 years on gastric signet ring cell (SRC) adenocarcinoma metastatic to the breast, and present a case., Material and Methods: The case of a patient who attended a high-complexity reference institution in Bogotá for a breast metastasis from a gastric SRC adenocarcinoma is reported. A Systematic Review of the literature was carried out, including cohort studies, reports and case series of patients with gastric SRC adenocarcinoma metastatic to the breast, which will present information on the epidemiology, clinical, radiological and histopathological characteristics, and the treatment and prognostic of this disease., Results: There were identified 363 references, twenty-six of which met the eligibility criteria. Gastric SRC adenocarcinoma metastatic to the breast predominated in the Asian continent (75.9%). The mean age at presentation was 42.5 years. In 62% (n=18) of cases this condition manifested clinically as a breast mass. From a radiological point of view, the majority of breast lesions presented as one or several nodules with suspicious characteristics (55.2%; n=16). In the biopsy of breast lesions, positivity for cytokeratin 7 and cytokeratin 20 occurred in 41.4% (n=12) and 37.9% (n=11) of cases, respectively. Only nine patients (31%) underwent any type of breast surgery. There is a lack of information on the treatment and prognosis of gastric SRC adenocarcinoma metastatic to the breast., Conclusions: The frequency of cases of gastric SRC adenocarcinoma metastatic to the breast published in the last 20 years is low. The general practitioner and the gynecologist could be the first medical professionals to face this rare condition, so knowing it and suspecting it is essential, especially if we take into account that the median overall survival of these patients is low.

Primary signet ring neuroendocrine tumors of the liver are extremely rare tumors. Morphologically, they mimic signet ring cell adenocarcinomas; however, the absence of mucin by special stains and the expression of neuroendocrine markers help to diagnose these tumors. We herein report a case of a 47-year-old female who presented with multiple solid and cystic lesions in both liver lobes, which were initially suggested to be biliary cystadenocarcinoma on imaging. Liver biopsy of the lesion revealed the presence of a signet ring neoplasm with diffuse expression of synaptophysin and pan-cytokeratin. The case was subsequently diagnosed as a primary hepatic signet ring neuroendocrine tumor. The patient was offered 3 cycles of chemotherapy and is well preserved after 14 months of diagnosis. Although this is an extremely rare entity, its possibility should be considered in the differential diagnosis of neoplasms characterized by signet ring cell morphology.

Purpose: Data about optimal management of plasmacytoid (PCV) bladder cancer patients are extremely scarce and limited by sample size. We focused on PCV bladder cancer patients to explore the effect of radical cystectomy (RC) and chemotherapy in non-metastatic (T 2–4N0–3M0), as well as in metastatic (TanyNanyM1) subgroups. Methods: Using the Surveillance, Epidemiology and End Results database (2000–2016), we identified 332 PCV patients with muscle-invasive disease or higher (≥ T2N0M0). Kaplan–Meier plots and Cox regression models addressed cancer-specific mortality (CSM). Results: In 332 PCV patients, median age was 68 years (Interquartile range [IQR]:58–76). Of those, 252 were non-metastatic patients (76%) vs 80 were metastatic patients (24%), at presentation. Of non-metastatic patients, 142 (56%) underwent RC and 131 (52%) underwent chemotherapy. Chemotherapy did not improve CSM in non-metastatic PCV. Conversely, RC was associated with lower CSM (hazard ratio [HR]: 0.51, p = 0.002). Median CSM-free survival was 48 vs 38 months for RC treated vs RC not treated. Of metastatic patients, 22 (28%) underwent RC and 42 (52%) underwent chemotherapy. Both chemotherapy and RC improved CSM in metastatic PCV. Median CSM-free survival was 12 vs 7 months for RC treated vs RC not treated (HR: 0.27, p < 0.001). Median CSM-free survival was 11 vs 4 months for chemotherapy exposed vs chemotherapy naïve (HR: 0.32, p = 0.002). Conclusions: Although RC resulted in lower CSM, chemotherapy failed to show that effect in non-metastatic PCV patients. Conversely, both chemotherapy and RC resulted in statistically significantly lower CSM in metastatic PCV patients. [ABSTRACT FROM AUTHOR]

A growing body of evidence suggests that L-selectin ligands presented on circulating tumor cells facilitate metastasis by binding L-selectin presented on leukocytes. Commonly used methods for detecting L-selectin ligands on tissues, e.g., immunostaining, are performed under static, no-flow conditions. However, such analysis does not assay for functional L-selectin ligands, specifically those ligands that promote adhesion under shear flow conditions. Recently our lab developed a method, termed dynamic biochemical tissue analysis (DBTA), to detect functional selectin ligands in situ by probing tissues with L-selectin-coated microspheres under hemodynamic flow conditions. In this investigation, DBTA was used to probe human colon tissues for L-selectin ligand activity. The detection of L-selectin ligands using DBTA was highly specific. Furthermore, DBTA reproducibly detected functional L-selectin ligands on diseased, e.g., cancerous or inflamed, tissues but not on noncancerous tissues. In addition, DBTA revealed a heterogeneous distribution of functional L-selectin ligands on colon cancer tissues. Most notably, detection of L-selectin ligands by immunostaining using HECA-452 antibody only partially correlated with functional L-selectin ligands detected by DBTA. In summation, the results of this study demonstrate that DBTA detects functional selectin ligands to provide a unique characterization of pathological tissue.

Breast metastasis from gastric signet ring cell carcinoma is extremely rare in clinical practice. The estimated incidence is 0.5–1.3%. There are few cases reported in the literature (approx. less than 60) of breast metastasis from gastric signet ring cell carcinoma, and due to the rare association between gastric cancer and its extension to the breast, it is difficult to establish the diagnosis. Clinical history, histological findings, and immunohistochemical markers are helpful in distinguishing primary breast cancer from breast metastasis of gastric cancer. The treatment for breast metastasis from gastric carcinoma remains controversial. The prognosis of breast metastasis from gastric carcinoma is generally poor. We report a case of breast metastasis of gastric signet ring cell carcinoma in a 38-year-old woman. She started chemotherapy with ramucirumab, paclitaxel, and irinotecan. Three months later, a combined 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography showed a complete response. This is the first reported case of breast metastasis from gastric signet ring cell carcinoma with a complete response.

Simple Summary: The classification of signet ring cell (SRC) carcinoma has been inconsistent and SRC carcinoma was classified as a subtype gastric cancer of poorly cohesive (PC) carcinoma. SRC and PC gastric carcinomas are morphologically similar but has been suggested to exhibit different biological behavior. We compared clinical and molecular characteristics of SRC and PC carcinomas. SRC and PC carcinomas showed significantly different clinical behavior that SRC carcinoma was associated with favorable clinical factors, suggesting that these subtypes should be classified and treated differently. SRC and PC carcinomas shared common transcriptome expression patterns, however, PC carcinomas showed an increased expression of genes related to cancer progression. Among genes differentially expressed between PC and SRC carcinomas, protein tyrosine phosphatase receptor type M (PTPRM) was overexpressed in PC and related to unfavorable clinical factors. PTPRM was identified as a potential diagnostic and prognostic biomarker for PC carcinoma. Background and aims. Signet ring cell (SRC) and poorly cohesive (PC) gastric carcinomas are morphologically similar but exhibit different biological behavior. We compared the clinical and molecular characteristics of SRC and PC carcinomas. Methods. Diffuse-type gastric cancer (GC) cases were classified into SRC carcinomas (>90% of SRCs), PC carcinomas (<10% of SRCs), and combined PC/SRC carcinomas (≤90% but ≥10% of SRCs). The gene expression patterns in SRC and PC carcinomas were examined by transcriptome and protein immunohistochemistry analyses, and diagnostic and prognostic biomarkers were identified. Results. SRC and PC carcinomas showed significantly different clinical behaviors but shared common RNA expression patterns. PC carcinomas showed an increased expression of genes related to cancer progression. Among genes differentially expressed between PC and SRC carcinomas, protein tyrosine phosphatase receptor type M (PTPRM) was overexpressed in PC and related to unfavorable clinical factors. Conclusion. We found that PC and SRC carcinomas had distinct clinical characteristics and should be classified as different carcinoma types. PTPRM was identified as a potential diagnostic and prognostic biomarker for PC carcinomas and could represent a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Signet ring cells (SRC) are widely acknowledged as a prognostically unfavorable histotype amongst poorly cohesive gastric cancer. In this study we evaluated the impact of SRC percentage on the clinical, pathological and prognostic features of these tumors according to the classification by the European Chapter of the IGCA. We retrospectively reviewed records of patients with poorly cohesive gastric cancer that underwent surgery between 1995 and 2016, whose tissue specimens were available in a biological bank. All slides were put under revision, patients were reclassified into three groups according to the proportion of signet ring cells: "pure" SRC (containing ≥90% of SRCs), Poorly Cohesive-Not Otherwise Specified (PC–NOS) (containing ≤10% of SRCs), and PC-NOS/SRC (containing <90% but >10% of SRCs). The clinicopathological factors between different types were analyzed and prognostic differences were compared. Among 143 enrolled patients, 51% were male and 49% were female. The mean (±SD) age at diagnosis was 61 ± 13.9 years. Eighty-seven patients (60.8%) were reclassified as PC-NOS, 56 (39.2%) as PC-NOS/SRC and none as "pure" SRC. Five-years overall survival was significantly higher in PC-NOS/SRC group (63.3%) compared with PC-NOS group (12.7%). The increase in mortality risk was more than four-fold in patients with PC-NOS pattern compared to those with PC-NOS/SRC (HR 4.32 [95% CI 2.5–7.4]. After adjustment for potential confounding factors, SRC pattern was still an independent predictor of survival. The percentage of SRCs is inversely related to tumor aggressiveness, confirming the role of SRC pattern as an independent predictor of survival. [ABSTRACT FROM AUTHOR]

Background and ObjectivesOnly recently the percentage of signet ring cells (SRCs) in gastric cancer (GC) has been proposed as an independent predictor of survival. High amounts of SRCs have been related to lower recurrence and mortality rates, better prognosis, and favorable clinicopathological features in a poorly cohesive histotype. It is not known what the effect of SRC percentage in mixed-type GC is. We investigate the role of SRCs as a prognostic marker in mixed-histotype GC.MethodsA retrospective analysis was performed through a prospectively maintained database of patients with diagnosed “mixed-type” gastric carcinoma, defined according to 2019 WHO classification. These patients underwent surgery between 1995 and 2016, and their tissue samples were stored in a tissue bank. All slides were analyzed, and patients were divided into three groups according to the percentage of SRCs: “Group 1” (displaying ≤10% of SRCs), “Group 2” (displaying 10% of SRCs), and “Group 3” (displaying ≥90% of SRCs). We compared clinical and pathological features as well as prognostic factors between the different groups.ResultsAmong 164 enrolled patients, 68.9% were male and 31.1% were female (p = 0.612). The mean (±SD) age at diagnosis was 71.4 ± 9.6 years. Ninety-eight (59.7%) patients were classified as “Group 1”, 66 (40.3%) as “Group 2”, and none as “Group 3”. Five-year overall survival was remarkably higher in Group 2 (73.8%) in comparison to Group 1 (35.4%), p < 0.001. Mortality risk was three times higher in patients with ≤10% SRC pattern compared to those with >10% [HR 2.70 (95% CI 1.72–4.24)]. After adjusting according to potential confounding factors, SRC percentage was still an independent predictor of survival.ConclusionsThe proportion of SRCs is inversely related to aggressive behavior and poor prognosis in mixed-type GCs, highlighting the role of SRC amount as an independent predictor of survival.

The endoscopic findings of gastric metastases from breast carcinoma are nonspecific, and often difficult to distinguish from primary gastric signet ring cell carcinoma. Therefore, pathological findings are key to diagnosis. [ABSTRACT FROM AUTHOR]

Background: Primary breast signet ring cell carcinoma (SRCC) is a rare type of breast cancer with typical morphological characteristics, high aggressiveness, and poor prognosis. SRCC is different from mucinous breast adenocarcinoma (MBC). However, only a few studies have explored the clinicopathological features and prognosis of SRCC and MBC. Methods: Data retrieved from the Surveillance, Epidemiology, and End-Results (SEER) database (2004–2015) were used to explore the prognostic effect of clinicopathological features and treatment modalities on survival outcomes of SRCC and MBC patients. Kaplan–Meier plot analysis, multivariate Cox proportional risk model, propensity score matching (PSM), and subgroup analysis were performed. Results: A total of 167 patients with SRCC and 11,648 patients with MBC were included in the study. SRCC patients exhibited higher histological grade (p < 0.001), larger tumor volume (p < 0.001), higher rate of lymph node metastasis (p < 0.001), and higher frequency of distal metastasis (p < 0.001) compared with MBC patients. Cox proportional hazards regression analysis showed that SRCC patients had lower overall survival (OS) and breast cancer-specific survival (BCSS) compared with MBC patients. Subgroup survival analysis showed that the SRCC patients had lower OS and BCSS in subgroups including younger than 60 years old, white race, married, without chemotherapy, and received radiotherapy compared with the MBC patients in these subgroups. In addition, the SRCC patients had lower BCSS in subgroups including other races (including Asian or Pacific Islander and American Indian/Alaska Native), without surgery, and lymph node metastasis. Conclusion: The findings showed that primary breast SRCC patients have unique clinical characteristics and worse prognosis compared with MBC patients. Notably, different treatment methods resulted in different prognosis for SRCC and MBC types; therefore, SRCC patients should be distinguished from MBC patients to improve efficacy of treatment. [ABSTRACT FROM AUTHOR]

Signet ring cell carcinoma (SRCC) is a poorly cohesive subtype of gastric cancer. It is more aggressive than other types of gastric cancer. There is no special method for its treatment, but gastrectomy and lymphadenectomy is the standard approach. The aim of this study is to investigate postoperative outcomes of D1 lymphadenectomy and D1(+)lymphadenectomy in gastric SRCC. A total of 358 cases whohad a gastrectomy performed forthe diagnosis of gastric cancer between 2013 and 2019 in Ankara University Medical Faculty, Surgical Oncology Department were retrospectively investigated. In all, 128 of the cases had SRCC in the final pathology. We separated the cases into two types,D1 lymphadenectomy and D1(+) lymphadenectomy. The 5-year survival, early mortality, hospital mortality and postoperative complication rates were evaluated. There were 59 patients in the D1 group and 64 patients in the D1(+) group.Metastatic lymph node amount and therefore N stage was found to be significantly higher in the D1(+) group (p=0.00 and p=0.03, respectively). Postoperative chyle fistula was found to be significantly higher in the D1(+) group (p=0.003). There was no statistically significant difference between the groups with regard tomean survival (p=0.065);the 5-year mean survival was 21% in the D1 group and 7% in the D1(+) group. Present findings suggest that extended lymphadenectomy does not provide a benefit in cases of SRCC. [ABSTRACT FROM AUTHOR]

Abstract Background Congenital goiter is a common thyroid metabolic disorder characterized by low levels of thyroid hormone, subsequent secretion of excess thyroid-stimulating hormone (TSH) from the pituitary gland, and compensatory hyperplasia of the glands. The presence of signet ring cells (SRCs) does not provide sufficient evidence for the diagnosis of a thyroid tumor, making histopathological diagnosis challenging. In addition, SRCs can also appear in congenital goiter. Therefore, a comprehensive diagnosis of congenital goiter is warranted based on clinical symptoms, autopsy, histopathology, and laboratory examination. Case presentation A juvenile giraffe at the Ordos Zoo in Ordos presented with symptoms of loss of appetite, serious salivation, and slow growth rate since birth. Its height and weight were significantly lower than those of other giraffes of the same age. The animal ultimately died at 17 months of age. Autopsy revelaed that the thyroids were hard, with an uneven surface and with the presence of many small raised follicles, and dense in cross-section. Other organs were visibly atrophic. Histopathologically, diffuse follicles were irregular in size and shape in the hyperplastic goiter. Some follicles were collapsed due to lack of colloids. The follicles were lined by single or multiple layers of hyperplastic follicular cells (HFCs), some of which were exfoliated in the lumen. The HFCs were either cuboidal with eosinophilic cytoplasm and many red small granules or showed SRC differentiation, with nuclei pressed to one edge of the cell and distorted by cytoplasmic mucin that appeared as a single clear vacuole HFCs and as a foamy, multivesicular cytoplasmic material in others. Scattered necrosis of myocardial cells and hepatocytes, cerebral hemorrhage, necrosis of intestinal villi, and obvious atrophy of organs were also observed. Immunohistochemical tests were strongly positive for thyroglobulin and thyroid transcription factor-1 (TTF-1) in the cytoplasm of HFCs. Conclusions Here we present a case of congenital goiter with areas of SRC differentiation in the thyroid of a juvenile giraffe.

Yang Li,1 Zhikai Zhu,2 Fuhai Ma,1 Liyan Xue,3 Yantao Tian1 1Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2School of Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Yantao TianDepartment of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 17 South Panjiayuan Lane, Suite 806, Surgical Building, Chaoyang District, Beijing 100021, People’s Republic of ChinaTel +86 1087787120Email tianyantao@cicams.ac.cnAbstract: Recent advances in the epidemiology, pathology, molecular mechanisms, and combined modality therapy (CMT) fields have shown that gastric signet ring cell carcinoma (GSRC) should be considered a distinct cancerous entity. Clinical management of this cancer is challenging, with chemoradioresistance and poor outcomes in advanced stages. Pathological and molecular sets of GSRC demonstrate different features of poor cohesion and differentiation according to the WHO, Japanese Gastric Cancer Association, and Laurén classifications. These features also result in poor response to adjuvant and neoadjuvant chemoradiotherapy. Certain studies of GSRC showed the disputed effectiveness of hyperthermic intraperitoneal chemotherapy and immunotherapy. Our aim was to discuss how an improved understanding of these therapeutic benefits may provide better treatment selection for patients, and therefore improve survival. The challenges in the new understanding of GSRC in routine practice and pathology, and the current limitations of treatment will also be discussed.Keywords: gastric cancer, signet ring cell, pathology, combined modality therapy

Abstract Background There is no consistent evidence about the appropriate treatment strategies for gastric signet ring cell carcinoma (GSRC) to improve prognosis. We conducted a population‐based study to examine the effects of combined modality therapies on survival outcomes using the Surveillance, Epidemiology, and End Results (SEER) data. Methods Analyses included stage II‐III primary GSRC patients who were diagnosed between 2006 and 2016. Therapies were categorized as gastrectomy group, adjuvant chemotherapy (CT) group, neoadjuvant radiotherapy (RT) group, and adjuvant chemoradiotherapy (CRT) group. Survival analyses were conducted by Kaplan‐Meier method and Cox proportional hazards models and subgrouped by gender, tumor site, stage at diagnosis, and number of lymph nodes removed. Results Of the 1717 cases of stage II‐III primary GSRC, the mean (SD) age was 59.6 (13.3) years, and over a half were male (52.8%). A total of 39.9% patients received adjuvant CRT and the 5‐year overall survival (OS) rate was 34.6%. The median OS of patients treated with adjuvant CRT was significantly longer than that of the gastrectomy group (33 months vs 24 months, aHR = 0.71, 95% CI: 0.59, 0.84). Although the crude model showed a significant association between adjuvant CT and total survival (cHR = 0.81, 95% CI: 0.68, 0.96), the effect measure turned null in the multivariable and sub‐group analysis. We did not find the significant effect of neoadjuvant RT. Conclusions In this study, GSRC patients with stage II‐III experienced improved overall survival after receiving adjuvant CRT, which provides several treatment implications. More clinical trials will be needed to verify the conclusion derived from this study.

BackgroundPrimary breast signet ring cell carcinoma (SRCC) is a rare type of breast cancer with typical morphological characteristics, high aggressiveness, and poor prognosis. SRCC is different from mucinous breast adenocarcinoma (MBC). However, only a few studies have explored the clinicopathological features and prognosis of SRCC and MBC.MethodsData retrieved from the Surveillance, Epidemiology, and End-Results (SEER) database (2004–2015) were used to explore the prognostic effect of clinicopathological features and treatment modalities on survival outcomes of SRCC and MBC patients. Kaplan–Meier plot analysis, multivariate Cox proportional risk model, propensity score matching (PSM), and subgroup analysis were performed.ResultsA total of 167 patients with SRCC and 11,648 patients with MBC were included in the study. SRCC patients exhibited higher histological grade (p < 0.001), larger tumor volume (p < 0.001), higher rate of lymph node metastasis (p < 0.001), and higher frequency of distal metastasis (p < 0.001) compared with MBC patients. Cox proportional hazards regression analysis showed that SRCC patients had lower overall survival (OS) and breast cancer-specific survival (BCSS) compared with MBC patients. Subgroup survival analysis showed that the SRCC patients had lower OS and BCSS in subgroups including younger than 60 years old, white race, married, without chemotherapy, and received radiotherapy compared with the MBC patients in these subgroups. In addition, the SRCC patients had lower BCSS in subgroups including other races (including Asian or Pacific Islander and American Indian/Alaska Native), without surgery, and lymph node metastasis.ConclusionThe findings showed that primary breast SRCC patients have unique clinical characteristics and worse prognosis compared with MBC patients. Notably, different treatment methods resulted in different prognosis for SRCC and MBC types; therefore, SRCC patients should be distinguished from MBC patients to improve efficacy of treatment.

Background: Colorectal signet-ring cell carcinoma (SRCC) is a rare subtype of malignant adenocarcinoma, accounting for approximately 1 % of colorectal cancer (CRC) cases. Its biomarkers and molecular characteristics remain controversial, and there are no specific therapeutic targets or strategies for its clinical treatment., Methods: A retrospective study was conducted between January 2010 and December 2021. 1058 colorectal cancer cases from the Sun Yat-sen University Cancer Center and 489 cases from the Tumor Genome Atlas Project were included in the analysis, of which 64 were SRCC. Data extraction included patient demographics, blood types and risk factors, including clinical variables and genomics (either a 19-gene panel NGS or 1021-gene panel NGS). Univariate analyses were performed to identify factors significantly associated with overall survival., Results: The blood groups of 27 (42.2 %), 18 (28.1 %), 12 (18.8 %), and seven (10.9 %) patients were classified as O, A, B, and AB, respectively. We found that O was a unique blood group characterized by a low frequency of KRAS mutations, a high frequency of heterozygosity at each HLA class I locus, and a high tumor mutational burden (TMB). Patients in blood group A with high-frequency KRAS mutations and those in blood group B with anemia and metabolic abnormalities required targeted treatment. Furthermore, genetic alterations in SRCC differed from those in adenocarcinoma and mucinous adenocarcinoma., Conclusions: Our study revealed genomic changes in SRCC patients across different blood groups, which could advance the understanding and precise treatment of colorectal SRCC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)