Artificial intelligence-based real-time histopathology of gastric cancer using confocal laser endomicroscopy.

There has been a persistent demand for an innovative modality in real-time histologic imaging, distinct from the conventional frozen section technique. We developed an artificial intelligence-driven real-time evaluation model for gastric cancer tissue using confocal laser endomicroscopic system. The remarkable performance of the model suggests its potential utilization as a standalone modality for instantaneous histologic assessment and as a complementary tool for pathologists' interpretation.

Age-related Differences in Spatially Resolved Transcriptomic Profiles of Patients With Hormone Receptor-positive Breast Carcinoma.

BACKGROUND/AIM: Patients' age may influence the response to chemotherapy and the clinical course of breast carcinoma. This study aimed to compare the spatial transcriptomic profiles between younger (≤50 years) and older (>50 years) patients with hormone receptor (HR)-positive breast carcinoma. PATIENTS AND METHODS: Seven cases of breast carcinoma were included. We performed digital spatial profiling and bioinformatic analysis to investigate the spatial transcriptomes of the epithelial and stromal compartments. RESULTS: In the epithelial compartment of three young-age breast carcinoma (YABC) cases, we found 21 up-regulated and 7 down-regulated genes. The top two most up-regulated genes were serpin peptidase inhibitor clade A member 1 and serine protease. The gene ontology enrichment analysis revealed a significant up-regulation of genes defining ribosomal structures and functions in YABCs. The gene set enrichment analysis revealed that gene sets defining early and late responses to estrogen, response to interferon-α, and tumor necrosis factor-α signaling were significantly enriched in YABCs. CONCLUSION: We described for the first time the age-related differences in spatially resolved transcriptomic profiles and up-regulated transcriptional pathways of HR-positive breast carcinoma. Our observations highlight the critical need for age-specific treatment strategies for breast carcinoma management.

Clinicopathological Significance of Nucleosome Remodeling and Deacetylase Complex Expression in Endometrial Carcinoma.

BACKGROUND/AIM: Only a few studies have examined the expression of nucleosome remodeling and deacetylase complex in endometrial carcinoma (EC). The aim of this study was to analyze the expressions of histone deacetylase (HDAC1), HDAC2, and chromodomain helicase DNA-binding protein 4 (CHD4) in EC. PATIENTS AND METHODS: Sixty cases of EC were categorized into two clusters based on the expression levels of the three proteins. RESULTS: Cluster 1 (C1) exhibited elevated expressions of HDAC2 and CHD4 compared with cluster 2 (C2). Notably, 75% of cases in C2 represented non-aggressive histological types, whereas 37.5% of cases in C1 manifested aggressive types. C2 exclusively comprised pathological tumor stage 1 (pT1) tumors, whereas C1 included pT2 and pT3 tumors. In C1, 25% of cases displayed aberrant p53 expression, contrasting with the absence of such expression in C2. Furthermore, only one patient in C2 experienced disease recurrence, whereas 20.8% of patients in C1 developed recurrent tumors. CONCLUSION: High HDAC2 and CHD4 expression may be associated with adverse clinicopathological characteristics in EC. Further studies are needed to validate these results.

Real-time Histological Evaluation of Gastric Cancer Tissue by Using a Confocal Laser Endomicroscopic System.

BACKGROUND/AIM: The need for instant histological evaluation of fresh tissue, especially in cancer treatment, remains paramount. The conventional frozen section technique has inherent limitations, prompting the exploration of alternative methods. A recently developed confocal laser endomicroscopic system provides real-time imaging of the tissue without the need for glass slide preparation. Herein, we evaluated its applicability in the histologic evaluation of gastric cancer tissues. MATERIALS AND METHODS: A confocal laser endomicroscopic system (CLES) with a Lissajous pattern laser scanning, was developed. Fourteen fresh gastric cancer tissues and the same number of normal gastric tissues were obtained from advanced gastric cancer patients. Fluorescein sodium was used for staining. Five pathologists interpreted 100 endomicroscopic images and decided their histologic location and the presence of cancer. Following the review of matched hematoxylin and eosin (H&E) slides, their performance was evaluated with another 100 images. RESULTS: CLES images mirrored gastric tissue histology. Pathologists were able to detect the histologic location of the images with 65.7% accuracy and differentiate cancer tissue from normal with 74.7% accuracy. The sensitivity and specificity of cancer detection were 71.9% and 76.1%. Following the review of matched H&E images, the accuracy of identifying the histologic location was increased to 92.8% (p<0.0001), and that of detecting cancer tissue was also increased to 90.9% (p<0.001). The sensitivity and specificity of cancer detection were enhanced to 89.1% and 93.2% (p<0.0001). CONCLUSION: High-quality histological images were immediately acquired by the CLES. The operator training enabled the accurate detection of cancer and histologic location raising its potential applicability as a real-time tissue imaging modality.

Prediction of Oncotype DX Recurrence Score by Evaluating the Peritumoral Tumor Budding in Early-stage Breast Carcinoma.

BACKGROUND/AIM: The Oncotype DX Recurrence Score (ORS) predicts the likelihood of recurrence and the benefit of chemotherapy in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast carcinoma (ESBC). Tumor budding (TB) is a poor prognostic factor in breast carcinoma. This study aimed to determine the clinicopathological significance of TB in predicting ORS in patients with ESBC. PATIENTS AND METHODS: We included 359 patients with ER-positive, HER2-negative ESBC. The number of peritumoral TB was assessed, and the cases were categorized into TB-low (<10 buds) and TB-high (≥10 buds) groups. RESULTS: Patients with TB-high ESBC (170/359; 47.4%) showed a significantly higher median ORS (15.0 vs. 13.0) than those with TB-low tumors (189/359; 52.6%). Multivariate analysis revealed that high TB level was an independent predictive factor for higher ORS in patients with ESBC. CONCLUSION: High TB in ESBC independently predicted higher ORS. TB may serve as a surrogate marker for predicting ORS in patients with ESBC.

Clinicopathological Factors Influencing Resection Margin Involvement During Mohs Micrographic Surgery for Skin Tumors.

BACKGROUND/AIM: Mohs micrographic surgery (MMS) is a specialized procedure for removing skin tumors. Intraoperative assessment of the resection margin (RM) status using frozen section examination is a crucial component of MMS. This study aimed to identify significant clinicopathological characteristics that could help surgeons determine the optimal surgical extent. PATIENTS AND METHODS: One hundred and fifty-one patients with primary skin tumors were included. The relationship between RM involvement and the clinico-pathological characteristics was analyzed for each histological type. RESULTS: Basal cell carcinoma (BCC) was significantly more likely to exhibit positive RMs and required additional excision during MMS compared to squamous cell carcinoma. In addition, the probability of RM involvement was significantly higher in high-risk BCC subtypes. CONCLUSION: When planning MMS, considering the histological type and presence of high-risk morphology may help surgeons perform more effective procedures.

Clinicopathological Significance and Predictive Value of High Intratumoral Tumor Budding in Patients With Breast Carcinoma Treated With Neoadjuvant Chemotherapy.

BACKGROUND/AIM: The clinicopathological significance and predictive value of tumor budding (TB) in patients with breast carcinoma (BC) treated with neoadjuvant chemotherapy (NAC) have not been fully elucidated. This study aimed to evaluate the role of TB in predicting the response to NAC in patients with BC. PATIENTS AND METHODS: We reviewed the pre-NAC biopsy slides obtained from 81 patients with BC and assessed the number of intratumoral TB. The association between TB and response to NAC and clinicopathological characteristics was evaluated. RESULTS: High TB (≥10 per 20× objective field), which was associated with more frequent lymph node metastasis and lower pathological complete response (pCR) rate, was observed in 57 (70.2%) cases. Multivariate logistic regression analysis revealed that high TB independently predicted non-pCR. CONCLUSION: High TB is associated with adverse features of BC. High TB on pre-NAC biopsy can be used as a predictive biomarker for non-pCR in NAC-treated patients with BC.

High PPFIA1 expression promotes cancer survival by suppressing CD8+ T cells in breast cancer: drug discovery and machine learning approach.

BACKGROUND: PTPRF-interacting protein alpha 1 (PPFIA1) plays an important role as a regulator of cell motility and tumor cell invasion and is frequently amplified in breast cancer. The aim of this study was to investigate the clinicopathologic features, survival, anticancer immunities and specific gene sets related to high PPFIA1 expression in patients with breast cancer. We verified the importance of PPFIA1 and survival rates using machine learning and identified drugs that can effectively reduce breast cancer cells with high PPFIA1 expression. METHODS: This study analyzed clinicopathologic factors, survival rates, immune profiles and gene sets according to PPFIA1 expression in 3457 patients with breast cancer from the Kangbuk Samsung Medical Center cohort (456 cases), Molecular Taxonomy of Breast Cancer International Consortium (1904 cases) and The Cancer Genome Atlas (1097 cases). We applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analyses, in vitro drug screening, and gradient boosting machine (GBM) analysis. RESULTS: High PPFIA1 expression in breast cancer was associated with worse prognosis, with reduced tumor-infiltrating lymphocytes, especially CD8+ T cells, and increased PD-L1 expression. In pathway network analysis, PPFIA1 was linked directly to the tyrosine-protein phosphatase pathway and indirectly to immune pathways. The importance of PPFIA1's association with survival in GBM analysis was higher than that of perineural and lymphovascular invasion. In in vitro drug screening, expression of PPFIA1 on mRNA level positively correlated with sensitivity of cell lines to erlotinib. CONCLUSION: High PPFIA1 in patients with breast cancer is related to poor prognosis and decreased anticancer immune response, and erlotinib may be promising for development of therapeutic approaches in patients with tumors overexpressing PPFIA1.

Clinicopathological and Prognostic Significance of Programmed Death Ligand-1 SP142 Expression in 132 Patients With Triple-negative Breast Cancer.

BACKGROUND/AIM: The prognostic value of programmed death ligand-1 (PD-L1) expression in triple-negative breast cancer (TNBC) has not been sufficiently investigated. In this study, we examined whether PD-L1 expression status is associated with clinicopathological features and outcomes of patients with TNBC. PATIENTS AND METHODS: Immunostaining for PD-L1 SP142 was performed on tissue microarrays containing 132 TNBC samples. High PD-L1 expression was defined as ≥10% of the tumor area occupied by PD-L1-expressing cells. RESULTS: Thirty-five (26.5%) patients showed high PD-L1 SP142 expression on immune cells (ICs). High IC PD-L1 expression was significantly correlated with smaller tumor size (p=0.030), absence of lymphovascular invasion (p=0.024), and fewer lymph node metastases (p=0.002). Multivariate survival analysis revealed that high IC PD-L1 expression independently predicted better disease-free survival (DFS) of TNBC patients. CONCLUSION: High PD-L1 SP142 expression on ICs was significantly associated with favorable clinicopathological parameters and better outcomes in patients with TNBC. Our observations suggest that high IC PD-L1 expression can be used as an independent prognostic marker for predicting better DFS in patients with TNBC.

Assessing Resection Margin Status in Breast-conserving Surgery Specimens: Comparison Among Gross Evaluation, Frozen Section Analysis, and Permanent Section Diagnosis in 725 Patients With Breast Cancer.

BACKGROUND/AIM: An accurate evaluation of resection margin (RM) is critical in breast-conserving surgery (BCS) as negative RM status is critical for successful local control. We compared gross and microscopic methods for RM evaluation and analyzed their concordances. PATIENTS AND METHODS: Gross evaluation (GE), frozen section analysis (FSA), and permanent section diagnosis (PSD) were compared for specimens from 725 breast cancer patients. RESULTS: The RM was grossly involved in 74 cases (10.2%). The sensitivity and specificity of GE were 22.9% and 96.1%, respectively. FSA revealed positive RM in 290 cases (40.0%), with high sensitivity (86.7%) and specificity (83.1%). With PSD, 240 cases (33.1%) showed RM involvement. Discordant results between gross and microscopic methods were observed in 104 cases (14.3%). CONCLUSION: Our observations of the low sensitivity of GE, high discordance rate between gross and microscopic methods, and high sensitivity and specificity of FSA support the necessity of intraoperative FSA for assessing RM status during BCS.

Factors associated with radiologic-pathologic discordance in magnetic resonance imaging after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Although breast MRI is known to be the best imaging modality for assessing the response after neoadjuvant chemotherapy (NAC), discordance still remains between MRI findings and final pathology findings. PURPOSE: To evaluate imaging and clinicopathologic factors associated with radiologic-pathologic discordance in breast cancer patients after NAC. MATERIAL AND METHODS: This retrospective study included 104 breast cancer patients (mean age: 50.2 years) who underwent breast MRI examinations before and after NAC between June 2015 and December 2019. Radiologic complete response (rCR) was defined as equal or lesser enhancement compared with breast tissue in post-NAC MRI. Pathologic CR (pCR) was defined as absence of invasive cancer in final pathology. Imaging and clinicopathologic factors associated with radiologic-pathologic discordance were analyzed with logistic regression analysis. RESULTS: Overall rCR and pCR rates were 37.5% (39/107) and 40.2% (43/107), respectively. Multivariate analysis revealed that the presence of non-mass enhancement (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.1-11.2; P = 0.03) and multicentric lesions on pre-NAC MRI (OR, 4.2; 95% CI, 1.2-14.9; P = 0.03) were independently associated with radiologic-pathologic discordance. False-positive rate for predicting residual tumor was the most prevalent in HER2-positive cancers (86.7%). CONCLUSION: When determining rCR, the presence of non-mass enhancement and multicentric lesions on pre-NAC MRI, and HER2-positive cancers should be interpreted with caution.

Low KIBRA Expression Is Associated with Poor Prognosis in Patients with Triple-Negative Breast Cancer.

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015-2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542-10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.

Tumor Heterogeneity Index to Detect Human Epidermal Growth Factor Receptor 2 Amplification by Next-Generation Sequencing: A Direct Comparison Study with Immunohistochemistry.

Intratumoral heterogeneity of human epidermal growth factor receptor 2 (HER2) is common in gastric cancer (GC). However, a direct comparison between the results of HER2 immunohistochemistry (IHC) and next-generation sequencing (NGS)-based cancer panel tests has not been explored in GC. We aimed to determine optimal thresholds of HER2 overexpression to be detected by NGS with the data of 168 metastatic GC cases with known expression levels of HER2 by IHC and the copy number alteration of ERBB2 obtained by NGS test by applying tumor heterogeneity index (THI) and receiver operating characteristic curve. GC tissues were obtained via biopsy (N = 103) and gastrectomy (N = 65). HER2 3+ by IHC was observed in 27 cases (16%), and 14 of 27 HER2 IHC 3+ cases (52%) showed intratumoral heterogeneity (<90% of tumor cells are HER2 3+). Of 27 HER2 3+ cases, 19 (70%) were detected by NGS. All eight cases with discrepant IHC and NGS results harbored intratumoral heterogeneity. The receiver operating characteristic curve analysis showed that the optimal value of THI to be detected by NGS was a score of 72 for biopsy specimens and 120 for resection specimens. In conclusion, intratumoral heterogeneity of HER2 expression is observed in 52% of metastatic GC cases. NGS laboratories should be aware that accuracy of ERBB2 copy number alteration detection by NGS is influenced by the THI.

Pathologic analyses of peritoneal nodules in gastric cancer patients during surgery-A single cancer center experience with diagnostic pitfalls.

BACKGROUND: Gastric carcinoma (GC) is the second most common cause of cancer-related deaths worldwide. During operations, nodular lesions of the peritoneum are often sent for frozen section (FS). For pathologists, FS of the peritoneum is challenging due to sparse and discohesive tumor cells in a fibrotic background. METHODS: To explore diagnostic accuracy and diagnostic pitfalls of FS in this setting, we retrospectively collected 252 peritoneal biopsies in cases with GC from January 2006 to May 2017 and compared corresponding permanent sections and patient prognosis. After review, 6 cases (2.4%) were discrepant: positive conversion was identified in 5 cases due to scarce tumor cells associated with severe fibrosis and inflammation; negative conversion was identified in one case due to papillary mesothelial cell proliferation masquerading as carcinoma. RESULTS: Two hundred cases were finally confirmed as positive for tumor cells. Of these, 185 (92.5%) patients died of GC, with survival times ranging from 7 to 3574 (mean 415) days after operation. Fifty-two (20.6%) cases were negative for tumor, and pathologic findings included chronic inflammation with fibrosis (N = 25: associated with previous operation, 10; idiopathic, 15) and papillary mesothelial cell proliferation (N = 9). All 5 patients with frozen diagnosis converted to positive results died of GC during follow up. A total of 19 patients with peritoneal nodules diagnosed as benign on FS died with GC (79.0%), and their survival times ranged from 87 to 3649 (mean 833) days. CONCLUSIONS: Peritoneal biopsies in patients with GC were mostly carcinoma, followed by chronic inflammation with fibrosis and papillary mesothelial cell proliferation. Deeper sections or intradepartmental consultations were helpful to reduce false negative diagnosis on FS.

The Prognostic Impact of Synchronous Ipsilateral Multiple Breast Cancer: Survival Outcomes according to the Eighth American Joint Committee on Cancer Staging and Molecular Subtype.

BACKGROUND: In the current American Joint Committee on Cancer staging system of breast cancer, only tumor size determines T-category regardless of whether the tumor is single or multiple. This study evaluated if tumor multiplicity has prognostic value and can be used to subclassify breast cancer. METHODS: We included 5,758 patients with invasive breast cancer who underwent surgery at Samsung Medical Center, Seoul, Korea, from 1995 to 2012. RESULTS: Patients were divided into two groups according to multiplicity (single, n = 4,744; multiple, n = 1,014). Statistically significant differences in lymph node involvement and lymphatic invasion were found between the two groups (p < .001). Patients with multiple masses tended to have luminal A molecular subtype (p < .001). On Kaplan-Meier survival analysis, patients with multiple masses had significantly poorer disease-free survival (DFS) (p = .016). The prognostic significance of multiplicity was seen in patients with anatomic staging group I and prognostic staging group IA (p = .019 and p = .032, respectively). When targeting patients with T1-2 N0 M0, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative cancer, Kaplan-Meier survival analysis also revealed significantly reduced DFS with multiple cancer (p = .031). The multivariate analysis indicated that multiplicity was independently correlated with worse DFS (hazard ratio, 1.23; 95% confidence interval, 1.03 to 1.47; p = .025). The results of this study indicate that tumor multiplicity is frequently found in luminal A subtype, is associated with frequent lymph node metastasis, and is correlated with worse DFS. CONCLUSIONS: Tumor multiplicity has prognostic value and could be used to subclassify invasive breast cancer at early stages. Adjuvant chemotherapy would be necessary for multiple masses of T1-2 N0 M0, hormone-receptor-positive, and HER2-negative cancer.

Pulmonary Nodular Lymphoid Hyperplasia with Mass-Formation: Clinicopathologic Characteristics of Nine Cases and Review of the Literature.

BACKGROUND: Pulmonary nodular lymphoid hyperplasia (PNLH) is a non-neoplastic pulmonary lymphoid disorder that can be mistaken for malignancy on radiography. Herein, we present nine cases of PNLH, emphasizing clinicoradiological findings and histological features. METHODS: We analyzed radiological and clinicopathological features from the electronic medical records of nine patients (eight females and one male) diagnosed with PNLH. IgG and IgG4 immunohistochemical staining was performed in three patients. RESULTS: Two of the nine patients had experienced tuberculosis 40 and 30 years prior, respectively. Interestingly, none were current smokers, although two were ex-smokers. Three patients complaining of persistent cough underwent computed tomography of the chest. PNLH was incidentally discovered in five patients during examination for other reasons. The remaining patient was diagnosed with the disease following treatment for pneumonia. Imaging studies revealed consolidation or a mass-like lesion in eight patients. First impressions included invasive adenocarcinoma and mucosal-associated lymphoid tissue‒type lymphoma. Aspergillosis was suspected in the remaining patient based on radiological images. Resection was performed in all patients. Microscopically, the lesions consisted of nodular proliferation of reactive germinal centers accompanied by infiltration of neutrophils and macrophages in various degrees and surrounding fibrosis. Ultimately, all nine patients were diagnosed with PNLH and showed no evidence of recurrence on follow-up. CONCLUSIONS: PNLH is an uncommon but distinct entity with a benign nature, and understanding the radiological and clinicopathological characteristics of PNLH is important.

Peritumoral lymphoid cuff correlates well with lymph node enlargement in gastrointestinal schwannomas.

BACKGROUND/AIMS: To determine the incidence of regional lymphadenopathy in gastrointestinal (GI) schwannoma and to evaluate the relationship between peritumoral lymphoid cuff and lymphadenopathy. METHODS: We queried 118 GI tract schwannomas and reviewed radiologic findings, intraoperative findings, and electronic medical records of all cases for enlarged regional lymph nodes. RESULTS: Location of tumors included 85 gastric (72%), 11 colonic (9.3%), 7 esophageal (5.9%), 3 pancreatic (2.5%), 1 hepatic (0.8%), and 11 mesenteric (9.3%). The size of the tumors ranged from 0.2 to 11 cm (mean 3.8 cm). Histologically, 70.3% showed a peritumoral lymphoid cuff ranging in thickness from 0.3 to 6 mm (mean 1.6 mm). The peritumoral lymphoid cuff was significantly more frequent in gastric schwannomas (78.8%) followed by colonic (72.7%), esophageal (57.1%) and rare in other locations (p = 0.001). Of the 106 cases for which clinical or radiologic data was available for, 76 cases (71.7%) showed regional lymphadenopathy. The presence of peritumoral lymphoid cuff showed significant correlation with regional lymphadenopathy (p < 0.001) and the size of enlarged lymph nodes (p = 0.002). CONCLUSIONS: A peritumoral lymphoid cuff is frequently seen in GI tract schwannomas and correlates well with regional lymphadenopathy. However, in a significant subset (29.7%), a lymphoid cuff was not present warranting continued need for caution in the preoperative radiologic and postoperative pathologic diagnoses.

Histologic characteristics of thymic adenocarcinomas: Clinicopathologic study of a nine-case series and a review of the literature.

Primary thymic adenocarcinoma is an extraordinarily rare malignancy; only 49 cases have been reported in the medical literature to date. Because of its rarity, clinical and pathologic characteristics of thymic adenocarcinoma are unclear. We present nine cases of primary thymic adenocarcinoma and discuss clinicopathologic findings in the context of the existing literature. Two-hundred twenty-six thymic carcinoma cases were diagnosed at Samsung Medical Center in Korea, from January, 2001 to July, 2016. Nine of these 226 cases were primary thymic adenocarcinomas. The mean age of primary thymic adenocarcinoma patients was 53.6 years, slightly younger than the mean age of patients with thymic squamous cell carcinomas. The male to female ratio was 2:1. Symptoms, if present, were usually due to compression by the tumor. Tumors showed an extra- or intra-cellular mucin and tubular growth pattern, with CK20- and CDX2-immunoreactivity, similar to adenocarcinomas of the lower intestinal tract. Twenty-five previously reported cases, classified as mucinous adenocarcinoma and adenocarcinoma, not otherwise specified, also had similar characteristics to enteric-type adenocarcinoma and generally expressed CK20, CDX2, CEA, and/or MUC2. Some of these cases had a thymic cyst. These characteristics are different from those of papillary thymic carcinomas, which are morphologically similar to papillary thyroid carcinomas, express CK7 but not CK20, and are often associated with thymoma. The prognosis of thymic adenocarcinoma, enteric type appeared to be worse than the prognosis of papillary thymic carcinoma or carcinoma with adenoid cystic carcinoma-like features. In summary, we demonstrated that common primary thymic adenocarcinomas show enteric-type differentiation with mucin. This tumor type has distinct clinical, pathological, immunohistochemical and prognostic characteristics and is different from other subtypes of thymic adenocarcinoma, papillary thymic carcinoma, and carcinoma with adenoid cystic carcinoma-like features.

Comprehensive Cytomorphologic Analysis of Pulmonary Adenoid Cystic Carcinoma: Comparison to Small Cell Carcinoma and Non-pulmonary Adenoid Cystic Carcinoma.

BACKGROUND: Cytologic diagnosis of pulmonary adenoid cystic carcinoma (AdCC) is frequently challenging and differential diagnosis with small cell carcinoma is often difficult. METHODS: Eleven cytologically diagnosed cases of pulmonary AdCC were collected and reviewed according to fifteen cytomorphologic characteristics: small cell size, cellular uniformity, coarse chromatin, hyperchromasia, distinct nucleolus, frequent nuclear molding, granular cytoplasm, organoid cluster, sheet formation, irregular border of cluster, hyaline globule, hyaline basement membrane material, individual cell necrosis or apoptotic body, and necrotic background. Twenty cases of small cell carcinoma and fifteen cases of non-pulmonary AdCC were also reviewed for the comparison. RESULTS: Statistically significant differences were identified between pulmonary AdCC and small cell carcinoma in fourteen of the fifteen cytomorphologic criteria (differences in sheet formation were not statistically significant). Cellular uniformity, distinct nucleolus, granular cytoplasm, distinct cell border, organoid cluster, hyaline globule, and hyaline basement membrane material were characteristic features of AdCC. Frequent nuclear molding, individual cell necrosis, and necrotic background were almost exclusively identified in small cell carcinoma. Although coarse chromatin and irregular cluster border were observed in both, they favored the diagnosis of small cell carcinoma. Hyaline globules were more frequently seen in non-pulmonary AdCC cases. CONCLUSIONS: Using the fifteen cytomorphologic criteria described by this study, pulmonary AdCC could be successfully distinguished from small cell carcinoma. Such a comprehensive approach to an individual case is recommended for the cytologic diagnosis of pulmonary AdCC.