Loss of SMAD4 protein expression in gastrointestinal and extra-gastrointestinal carcinomas.

AIMS: SMAD4 (DPC4) is a tumour suppressor gene that is dysregulated in various tumour types, particularly pancreaticobiliary and gastrointestinal carcinomas. Corresponding loss of protein expression has been reported in approximately 50% of pancreatic and 25% of colonic adenocarcinomas. In the evaluation of carcinoma of unknown primary site, immunohistochemical loss of SMAD4 expression is often used to suggest pancreaticobiliary origin, but there are limited data on the spectrum of SMAD4 expression in carcinomas of other sites. This study evaluates the frequency of SMAD4 loss in a large cohort of carcinomas from diverse anatomical sites. METHODS AND RESULTS: Immunohistochemistry for SMAD4 was performed on tissue microarrays or whole tissue sections of 1210 carcinomas from various organs: gastrointestinal tract, liver, pancreas/biliary tract, lung, breast, thyroid, kidney, ovary and uterus. Expression was considered lost when there was complete absence of staining in tumour cell nuclei, in the presence of intact staining in non-neoplastic cells. SMAD4 loss was seen in 58% of pancreatic adenocarcinomas, 27% of appendiceal adenocarcinomas, 19% of colorectal adenocarcinomas, 16% of cholangiocarcinomas, 10% of lung adenocarcinomas and <5% of oesophageal, breast, gastric and mucinous ovarian adenocarcinomas. All papillary thyroid, hepatocellular, non-mucinous ovarian, endometrial and renal cell carcinomas showed intact SMAD4 nuclear expression. CONCLUSION: In addition to pancreaticobiliary, appendiceal and colonic tumours, SMAD4 loss is also seen in a small subset of other carcinomas, specifically breast, lung, oesophageal and gastric adenocarcinomas, all of which are typically CK7-positive, similar to pancreaticobiliary carcinoma. Awareness of SMAD4 loss in these other carcinoma types is helpful in the evaluation of carcinomas of unknown or uncertain primary site.

Differences in immune contextures among different molecular subtypes of gastric cancer and their prognostic impact.

BACKGROUND: Gastric cancers have been recently classified in accordance with their molecular characteristics, thus demonstrating the complex nature of cancers and an association with the immune contexture within the tumor microenvironment. This study aimed to investigate the correlation between the molecular subtype and immune contexture of gastric cancers. METHODS: The immune contexture, including the type, density, and location of tumor-infiltrating lymphocytes (TILs), of gastric cancer patients was examined and immune subtypes were classified based on it. In particular, PD-L1 expression on tumor cells and TILs and Foxp3+ TILs was assessed in accordance with molecular subtypes. RESULTS: High levels of visual TIL estimates and Foxp3+ TILs were markedly associated with increased overall survival (P = 0.001, P < 0.001, separately). Immune subtypes were associated with tumor size, gross type, depth of invasion, lymph node metastatic status, lymphovascular invasion, perineural invasion, and microsatellite instability status. EBV-positive (C1) and MSI (C2) gastric cancers, considered subtypes with better prognosis, were significantly associated with high TIL levels (P < 0.05). In contrast, epithelial-mesenchymal transition (EMT, C3) gastric cancers with poor overall survival displayed low levels of Foxp3+ TILs. Type II tumors (low level of TILs/low PD-L1 expression) displayed a significant correlation with poor overall survival (P = 0.004) and accounted for the highest proportion in the aberrant p53-expressing (C4) gastric cancers. CONCLUSION: The molecular subtype of gastric cancers is correlated with the immune subtype, including immune contexture and PD-L1 expression, within the tumor microenvironment.

Standardized pathology report for breast cancer.

Given the recent advances in management and understanding of breast cancer, a standardized pathology report reflecting these changes is critical. To meet this need, the Breast Pathology Study Group of the Korean Society of Pathologists has developed a standardized pathology reporting format for breast cancer, consisting of 'standard data elements,' 'conditional data elements,' and a biomarker report form. The 'standard data elements' consist of the basic pathologic features used for prognostication, while other factors related to prognosis or diagnosis are described in the 'conditional data elements.' In addition to standard data elements, all recommended issues are also presented. We expect that this standardized pathology report for breast cancer will improve diagnostic concordance and communication between pathologists and clinicians, as well as between pathologists inter-institutionally.

Characterization of Immune Cell Subsets of Tumor Infiltrating Lymphocytes in Brain Metastases.

The heterogeneity of tumor infiltrating lymphocytes (TILs) is not well characterized in brain metastasis. To address this, we performed a targeted analysis of immune-cell subsets in brain metastasis tissues to test immunosuppressive routes involved in brain metastasis. We performed multiplex immunofluorescence (mIF), using commercially available validated antibodies on formalin-fixed paraffin embedded whole sections. We quantitated the subsets of immune-cells utilizing a targeted panel of proteins including PanCK, CD8, CD4, VISTA and IBA-1, and analyzed an average of 15,000 cells per sample. Classifying tumors as either high (>30%) or low (<30%) TILs, we found that increased TILs density correlated with survival. Phenotyping these TILs we found tumors with low TILs had significantly higher expression of the immune-checkpoint molecule VISTA in tumor cells (p < 0.01) as well as in their microenvironment (p < 0.001). Contrastingly, the tumors with high TILs displayed higher levels of microglia, as measured by IBA-1 expression. Low TILs-tumors displayed CD8+ T-cells that co-express VISTA (p < 0.01) significantly more compared to high TILs group, where CD8+cells significantly co-express IBA-11 (p < 0.05). These results were supported by RNA analysis of a publicly available, independent cohort. Our work contributes to a growing understanding of the immune surveillance escape routes active in brain metastasis.

Standardized Pathology Report for Breast Cancer.

Given the recent advances in management and understanding of breast cancer, a standardized pathology report reflecting these changes is critical. To meet this need, the Breast Pathology Study Group of the Korean Society of Pathologists has developed a standardized pathology reporting format for breast cancer, consisting of 'standard data elements,' 'conditional data elements,' and a biomarker report form. The 'standard data elements' consist of the basic pathologic features used for prognostication, while other factors related to prognosis or diagnosis are described in the 'conditional data elements.' In addition to standard data elements, all recommended issues are also presented. We expect that this standardized pathology report for breast cancer will improve diagnostic concordance and communication between pathologists and clinicians, as well as between pathologists inter-institutionally.

A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification.

BACKGROUND: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. METHODS: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). RESULTS: On WHO classification, H&E staining exhibited 'fair agreement' (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. CONCLUSIONS: Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Pitfalls and controversies in pathology impacting breast cancer management.

Introduction: Breast cancer is a heterogeneous disease, at morphological, molecular, and clinical levels and this has significant implications for the diagnosis and management of the disease. The introduction of breast screening, and the use of small tissue sampling for diagnosis, the recognition of new morphological and molecular subtypes, and the increasing use of neoadjuvant therapies have created challenges in pathological diagnosis and classification.Areas covered: Areas of potential difficulty include columnar cell lesions, particularly flat epithelial atypia, atypical ductal hyperplasia, lobular neoplasia and its variants, and a range of papillary lesions. Fibroepithelial, sclerosing, mucinous, and apocrine lesions are also considered. Established and newer prognostic and predictive markers, such as immune infiltrates, PD-1 and PD-L1 and gene expression assays are evaluated. The unique challenges of pathology assessment post-neoadjuvant systemic therapy are also explored.Expert opinion: Controversies in clinical management arise due to incomplete and sometimes conflicting data on clinicopathological associations, prognosis, and outcome. The review will address some of these challenges.

Sonographic Features of Flat Epithelial Atypia Manifesting as a Non-Mass-Like Lesion: A Case Report.

BACKGROUND The incidence of flat epithelial atypia of the breast has been increasing owing to the increasing use of ultrasonography (US) and US-guided core needle biopsy. However, reports describing the sonographic features of flat epithelial atypia are fewer than those on its mammographic features. CASE REPORT A 47-year-old female had a regular 6 month-interval follow-up US for multiple bilateral breast masses detected on US. A new focal non-mass-like lesion measuring 2 cm in maximum diameter was noted in the 10 o'clock direction of the right breast on the follow-up US. Mammography was not performed during the follow-up period. The patient had no breast symptoms and no family history of breast cancer or other pertinent medical history. US-guided 14-gauge core needle biopsy yielded a pathological diagnosis of flat epithelial atypia without upgrade to malignancy, and this was further confirmed after complete excision of the non-mass-like lesion. CONCLUSIONS Flat epithelial atypia can present as a focal non-mass-like lesion on US, which has not been reported previously.

Clinical and Imaging Features of a Ruptured Epidermal Inclusion Cyst in the Subareolar Area: A Case Report.

BACKGROUND Epidermal inclusion cysts rarely develop in the breast. The cysts that do develop within the breast typically present as cutaneous or subcutaneous cysts. They more rarely present in a subareolar location or in a ruptured state. Thus far, 5 cases of ruptured epidermal inclusion cysts in subareolar locations have been reported in the English literature. Furthermore, clinical presentation of nipple discharge is rare in epidermal inclusion cysts of the breast; only 4 such cases has been reported. CASE REPORT A 58-year-old female presented with a 1-month history of bloody discharge from her left nipple. Mammography showed focal asymmetry in the left subareolar region; sonography showed a left subareolar mass with irregular shape, indistinct margin, heterogeneous echogenicity, and posterior enhancement. The mass was surgically excised; a pathological diagnosis of ruptured epidermal inclusion cyst with foreign body reaction and abscess formation was established. In this case, the clinical presentation of bloody nipple discharge was peculiar; furthermore, mammographic and sonographic features were indistinguishable from breast malignancy or typical breast abscess. CONCLUSIONS A ruptured epidermal inclusion cyst can present in an unusual subareolar location, combined with bloody nipple discharge; importantly, this can radiologically resemble breast malignancy.

Sonographic Features of a Myeloid Sarcoma of the Breast as a Relapse of Acute Myeloid Leukemia After Stem-Cell Transplantation: A Case Report.

BACKGROUND Myeloid sarcoma is a rarely observed extramedullary presentation of myeloid leukemia that seldom manifests in the breast. Myeloid sarcoma can occur before, concurrently with, or following acute myeloid leukemia presentation. Few reports have focused on the imaging findings in cases of myeloid sarcoma of the breast, and the existing findings are variable and nonspecific; the present case report aimed to bridge this gap. CASE REPORT A 24-year-old female presented with a palpable lump at the upper outer quadrant of her right breast. She had noticed the mass 2 days prior to presentation. She was first diagnosed with acute myelogenous leukemia 18 months before the lump presentation and had undergone haploidentical stem cell transplantation 6 months prior. At the time of the breast lump presentation, she was undergoing chemotherapy for relapsed acute myeloid leukemia. Ultrasonography of her right breast revealed a circumscribed, oval mass corresponding to the palpable lump. Ultrasonography-guided 14-gauge core needle biopsy was performed on the breast mass, leading to a pathological diagnosis of myeloid sarcoma. CONCLUSIONS We reported a case of myeloid sarcoma involving the breast. On sonography, although the internal echotexture resembled that of breast hamartoma, the observed hard elasticity and high vascularity raised suspicions of malignancy.

Ki-67 labeling index as a prognostic marker in advanced stomach cancer.

PURPOSE: Proliferation marker Ki-67 is widely used in cancer prognosis prediction. We tried to investigate the role of Ki-67 as a prognostic factor in stomach cancer after surgery in this study. METHODS: We retrospectively evaluated 251 patients who underwent curative resection for gastric cancer from 2010 to 2015. In pathologic examination, Ki-67 labeling index was defined as the percentage of Ki-67 antigen positive cells. Prognostic significance of Ki-67 for gastric cancer was evaluated. Disease-free survival (DFS) was assessed as a primary end-point. RESULTS: The median follow-up period was 28.0 months. Thirty-one patients (12.4%) showed Ki-67 labeling index (LI) lower than 25%. Sixty-eight patients (26.6%) showed recurrence during follow-up period. Recurrence was associated with Ki-67 LI level (≤25%, P = 0.016), and lymph node metastasis status (P = 0.002). High Ki-67 LI level (>25%) was also related to p53 positivity (P < 0.001) and poorly cohesive type (P = 0.002). The 3-year DFS was 69.4%. Low Ki-67 LI level (≤25%) was related with low DFS (47.6% vs. 72.6%, P = 0.016). T stage (P < 0.001), N stage (P = 0.006), lymphovascular invasion (P = 0.010), and neuronal invasion (P = 0.001) also affected the DFS. In addition, T stage (P = 0.03) and Ki-67 LI (P = 0.035) were independent prognostic factors for DFS. In patients treated with adjuvant chemotherapy (n = 239, 93.4%), low Ki-67 (≤25%) was a poor prognostic factor for DFS (P = 0.013). CONCLUSION: Low Ki-67 LI predicts high rate of progression and low DFS of stomach cancer. Ki-67 LI can be a predictive marker in resected stomach cancer treated with surgery and adjuvant chemotherapy.

Diabetes as a prognostic factor in HER-2 positive breast cancer patients treated with targeted therapy.

PURPOSE: Recent studies revealed that metabolic stress influences the outcomes of breast cancer treatment. We sought to evaluate the prognostic effect of type 2 diabetes and find the molecular mechanism of relapses in postoperative HER-2+ breast cancer patients treated with HER-2 targeted therapy. MATERIALS AND METHODS: We evaluated 190 HER-2+ breast cancer patients (pT1-4N0-2M0) who were treated with surgical resection and trastuzumab (HER-2 targeted therapy) between 2006 and 2015. Survival outcomes and failure patterns were compared between such patients with (n = 12) and without (n = 178) type 2 diabetes. RESULTS: The median follow-up period was 42.4 months (range 12.0-124.7 months). Twenty-one patients (11.1%) showed relapse (including nine patients with locoregional failure), and three patients (1.6%) died as a result of cancer relapse. One-third of the patients with diabetes experienced relapse (4/12, 33.3%). The 3-year disease-free survival (DFS) and overall survival (OS) rates were 90.7% and 98.6%, respectively. Diabetic patients showed shorter DFS compared with non-diabetic patients (p = 0.006, 74.1% vs. 91.9%). OS was also shorter in diabetic patients compared with non-diabetic patients (p = 0.017, 91.7% vs. 99.1%). Of our interest, the levels of HER-3 and its ligand neuregulin-1 were significantly increased in the tumor specimen in HER-2+ breast cancer patients suffering with type 2 diabetes than that in the euglycemic control group. CONCLUSIONS: Type 2 diabetes was associated with detrimental effects on survival in postoperative HER-2+ breast cancer patients who were treated with trastuzumab. The poor prognostic effect of diabetes in HER-2+ breast cancer patients could be associated with the high levels of HER-3 and neuregulin 1, thus it should be considered and evaluated more.

Imaging and Clinical Features of an Unusual Unilateral Breast Enlargement Diagnosed as Fibrocystic Change: A Case Report.

BACKGROUND Breasts are assumed to be symmetrical bilaterally, and abnormal findings on breast imaging are largely based on such an assumption. Clinically noticeable breast asymmetry beyond that of normal range is rarely encountered. CASE REPORT A 38-year-old female presented with unilateral enlargement of her left breast for 3 months and complained of polymenorrhea twice a month. Mammography and ultrasonography revealed that the left breast had a larger volume of fibroglandular tissue than the right breast, without accompanying signs of malignancy or abnormality. Magnetic resonance imaging demonstrated unilateral, diffuse, stippled enhancement in the left breast, which was located peripherally in the early phase and propagated centrally in the delayed phase with a persistent kinetic pattern. Ultrasonography-guided core needle biopsy was performed for the left breast, leading to a pathological diagnosis of fibrocystic change. The condition could be presumably due to a different response of the breasts to imbalance in endogenous hormones. CONCLUSIONS Based on our findings, we believe that radiologists should consider that the breast has a unique dynamic physiology and that features on breast imaging can be affected by hormonal alteration.

Potential protective effect of ALDH-1 stromal expression against early recurrence of operable breast cancers.

BACKGROUND: The emerging cancer stem cell (CSC) model proposes that the stem cell niche plays a major role in the risk of cancer recurrence. Enzymatic activity of aldehydes, including aldehyde dehydrogenase 1 (ALDH-1), has been used as a marker of normal and malignant breast stem cells (BSCs). However, the clinical implications of the expression of stem cell markers in the stroma have not yet been investigated. METHODS: To determine the relationships of ALDH-1 expression, the currently reliable BSCs marker, with clinical characteristics and survival, we used immunohistochemical staining of tissue microarrays from 180 stroma and epithelial cancer tissues in patients diagnosed with operable early breast cancer (stage 0-III). RESULTS: ALDH-1 expression was observed in 93.4% of the stromal cells and in 37.2% of the epithelial cells, and the expression levels between the two cell types were significantly correlated (P=0.001). The stromal expression of ALDH-1 was not correlated with any clinical factors, whereas epithelial expression was significantly correlated with a negative estrogen-receptor status (P<0.001), high proliferation based on Ki-67 expression (P<0.001), and younger age (P=0.04). After 27.8 months of follow up, negative stromal expression of ALDH-1 was significantly correlated with shorter overall survival (positive, 56.9±3.0 months vs. negative, 30.5±3.0 months; P=0.01). CONCLUSIONS: Stromal ALDH-1 expression was not directly correlated with known clinical factors, but its expression may play a protective role against early recurrence. Further observation and large-scale studies are needed to validate the clinical implications of ALDH-1 in breast cancer.

Cutaneous metastases of breast cancer during adjuvant chemotherapy correlates with increasing CD44+/CD24- and ALDH-1 expression: a case report and literature review.

Cancer stem cells (CSCs) within a tumor are scarce and self-sustaining and they have the abilities for self-renewal and the potential of giving rise to diverse types of cells that compose the tumor. These cells are suggested to be associated with therapeutic failure, and therefore they remain as an important issue in this regard. We report the cases of two breast cancer patients diagnosed with rapid cutaneous metastases during adjuvant cytotoxic chemotherapy after curative mastectomy. For elucidating a relationship between CSCs and resistance to chemotherapy, we evaluated primary tumor and metastatic cutaneous lesions by CSC markers in immunohistochemical stains (CD44+/CD24- and ALDH-1). Either CD44+/CD24- or ALDH-1 expression increased compared to primary breast cancer during chemotherapy. This case report shows that CD44+/CD24- or ALDH-1 expression in primary or cutaneous metastatic breast cancer may be associated with rapid onset chemoresistance.

Axillary Skip Metastases and the False-Negative Rate of Sentinel Lymph Node Biopsy in Patients With Breast Cancer Are Related to Negative ALDH-1 Expression and Ki-67 Expression.

Breast cancer stem cells (CSCs) have been hypothesized to be the driving force behind tumorigenesis and metastasis. In this study, we evaluated the relationships between CSC expressions in primary breast cancers and corresponding metastatic sentinel and nonsentinel lymph nodes (SLNs and NSLNs). The clinical implications of these relationships were also investigated. CSC expressions were evaluated in 167 breast cancer specimens and associated lymph node biopsies (when present). We used double immunohistochemistry of CD44/CD24 and single immunohistochemistry of ALDH-1 on paraffin-embedded breast tissue, SLN, and NSLN specimens. Seven cases had metastatic NSLNs without SLN involvement-so-called "skip metastasis." Fifty cases of SLNs (29.9%) and 33 cases of NSLNs (25.7%) had metastases. In the breast cancers, metastatic SLNs, and NSLNs, the expression rates of CD44+/CD24- were 47.9%, 26.1%, and 34.6 %, respectively, while the expression rates of ALDH-1+ were 42.5%, 36.4%, and 33.3%, respectively. Significant relationships were not observed between CSC expressions in breast cancer and metastatic SLNs or NSLNs. The presence of skip metastasis correlated with negative ALDH-1 in breast cancer ( P = .04), as well as several clinicopathologic factors: age >50 years ( P = .004), negative lymphovascular tumor emboli ( P = .02), and high Ki-67 expression ( P = .04). Axillary lymph node metastasis showed no significant relationship with any CSC marker. However, CD44+/CD24- and ALDH-1 expressions of metastatic SLNs correlated with CSCs of primary breast cancers. In summary, skip metastasis correlated with negative expression of ALDH-1 in primary breast cancers, which could be promising as a means of assessing the risk of skip metastasis.

Simple classifiers for molecular subtypes of colorectal cancer.

BACKGROUND AND STUDY AIM: Colorectal cancer (CRC) is a heterogeneous disease entity with a diverse biological pathogenesis. This study aims to validate the two studies published in 2013 which established a separate CRC molecular subtype classification by utilizing a rapidly accessible miniclassifier, and verify a simplified version thereof. PATIENTS AND METHODS: Participants diagnosed with CRC (n = 568) were subtyped in three classifications for characteristic, and prognostic purposes. Colorectal cancer subtypes (CCS) were classified as: i) CCS1 (CDX2+, microsatellite stable (MSS)/microsatellite instability (MSI)-low), ii) CCS2 (MSI-high), and iii) CCS3 (FRMD6/ZEB1/HTR2B +, CDX2-, MSS/MSI-low]. Simplified CCS (SiCCS) subtypes were grouped as: i) CDX2 (CDX2+, MSS/MSI-low, ZEB1 ≤ 2), ii) MSI-H (MSI-high, CDX2/FRMD6/ZEB1/HTR2B +/-), and iii) ZEB1 (ZEB1 ≥ 2, CDX2-, MSS/MSI-low). New molecular classification (NMC) subtypes were defined as: i) enterocyte (E-C) (MUC2 +), ii) goblet-like (G-L) (MUC2 + and TFF3 +), iii) transit-amplifying (T-A) (CFTR +), and iv) stem-like (S-L) (ZEB1 +). RESULTS: In total, 53.5% (n = 304) CCS, 58.3% (n = 331) SiCCS, and 37.7% (n = 214) NMC tumours could be evaluated. CCS2 and MSI-H CRCs had the most favourable survival outcome, whereas the CCS3, ZEB1 and S-L subtypes showed the poorest prognosis. A significant overlap between CCS3, ZEB1, and S-L tumours was demonstrated. CONCLUSION: There is still a need for a consensus gene expression-based subtyping classification system for CRCs, thereby allowing the categorization of most CRC tumours. This study reveals that a simple and rapidly accessible process could replace the complicated, costly and mostly inapproachable methods clinical practices that have been introduced in the majority of previous studies.

[Concomitant Drug Reaction with Eosinophilia and Systemic Symptom Syndrome from Ethambutol and Autoimmune Hepatitis from Isoniazid].

Anti-tuberculosis drugs can produce levels of hepatotoxicity ranging from mild elevation of aminotransferase to severe acute hepatitis. A few cases of drug-induced autoimmune hepatitis or the drug reaction with eosinophilia and systemic symptom (DRESS) syndrome by anti-tuberculosis medications have been reported. However, concomitant occurrence of these two disorders has not been reported. Here, we present a case of severe acute hepatitis with DRESS syndrome and autoimmune hepatitis resulting from primary standard anti-tuberculosis drugs. Both conditions were successfully treated with a systemic steroid regimen.

Right ventricle inflow obstructing mass proven to be a synovial sarcoma.

Soft tissue sarcoma is the most common malignant cardiac tumor. The chief modes of presentation are embolization, obstruction, and arrhythmogenesis. We describe an unusual case of a 27-year-old man who presented with nausea and dyspnea on exertion. Transthoracic echocardiography and computed tomography revealed a huge mass in the right heart that extended through the inferior vena cava and right renal vein to the right kidney. The cardiac mass was resected, and an immunohistochemical analysis revealed it to be a TLE1-positive synovial sarcoma. After surgery, the patient received serial adjuvant chemotherapy. We herein describe the case with a brief review.

Lymph node metastasis in early gastric cancer: evaluation of a novel method for measuring submucosal invasion and development of a nodal predicting index.

After endoscopic resection of early gastric cancer (EGC), it is imperative to accurately determine whether follow-up surgery is indicated, since this technique is used as a first line of treatment. Herein, we developed a scoring system to indicate the risk of lymph node metastasis in submucosal EGC (smEGC), and present a novel method to measure depth of submucosal invasion. In our series, 15.9% of the smEGC presented with lymph node metastasis. A nodal prediction index, based on the variables extracted from the univariate analysis and defined as nodal prediction index = (2.128 × lymphovascular tumor emboli) + (1.083 × submucosal invasion width ≥ 0.75 cm) + (0.507 × submucosal invasion depth ≥ 1000 µm) + (0.515 × infiltrative growth pattern), yielded an area under the receiver operating characteristic curve of 0.809 (P =.000, 95% CI = 0.713-0.096) in a training group, and showed comparable result in validation group (0.886, P =.000, 95% CI = 0.796-0.977). Depth of invasion was statistically higher in the metastatic group when measured from the lowest point of an imaginary line in continuity with the adjacent muscularis mucosa to the point of deepest tumor penetration, but not when using the classic measurement method. The area under the receiver operating characteristic curve of the alternative measurement method was 0.652 (P =.013, 95% CI = 0.550-0.754) compared to 0.620 for the classic measurement method (P =.0480, 95% CI = 0.509-0.731). In deciding whether surgery is indicated after endoscopic submucosal dissection for smEGCs, we recommend to test our alternative method of measuring submucosal invasion and to evaluate our nodal prediction index as an adjunct tool.