Secretory carcinoma or mammary analog secretory carcinoma is an entity of salivary gland carcinoma that is characterized by the ETV6‐NTRK3 gene fusion. Although it is generally considered to be a ...low‐grade malignancy, some cases of secretory carcinoma with high‐grade transformation (SCHG) have been reported. We herein describe a case of SCHG composed almost exclusively of the high‐grade component. The patient presented with a growing mass in the buccal mucosa and underwent surgery. Tumor cells showing high‐grade nuclear atypia were arranged in solid or cribriform nests with comedo‐like necrosis. A differential diagnosis included high‐grade salivary gland carcinoma, such as salivary duct carcinoma. Immunohistochemically, tumor cells were focally positive for S‐100 and negative for mammaglobin and showed nuclear positivity for pan‐Trk. A reverse transcription polymerase chain reaction assay showed that the tumor harbored the ETV6‐NTRK3 gene fusion. A histological review of microscopic slides of the tumor did not reveal a typical secretory carcinoma component, except for a very focal area. We ultimately diagnosed this tumor as SCHG. This case underscores the importance of recognizing the histological spectrum of SCHG and the utility of pan‐Trk immunohistochemistry to detect secretory carcinoma, which may be targeted by tyrosine kinase inhibitors.
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a primary liver carcinoma with both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) components. We examined the ...clinicopathological characteristics and recurrence patterns of cHCC-CCA. Because of the rarity of cHCC-CCA, its etiology, clinicopathological features, and prognosis in comparison with other primary liver carcinoma remain unknown. Its recurrence pattern and sites in particular also need to be elucidated.
All patients who underwent hepatectomy for primary liver malignancies between 2005 and 2015 were retrospectively included in this study.
Eight hundred and ninety-four hepatectomies were performed. Nineteen cases of cHCC-CCA (2.1%) in 16 patients were enrolled. Three patients underwent re-hepatectomy. The background of hepatitis viruses and tumor marker patterns of cHCC-CCA were similar to those of HCC and dissimilar to those of intrahepatic CCA (iCCA). Biliary invasion was common in cHCC-CCA and iCCA. The 5-year overall survival values of the cHCC-CCA, HCC, and iCCA patients were 44.7%, 56.6%, and 38.5%, respectively. The 5-year recurrence-free survival values of the cHCC-CCA, HCC, and iCCA patients were 12.2%, 28.7%, and 32.9%, respectively. The liver was the most common recurrence site. Unlike HCC, however, the lymph node was the second-most common recurrence site in both cHCC-CCA and iCCA. Pathological samples of the recurrent lesions were obtained in six patients, and four had cHCC-CCA recurrence pathologically.
cHCC-CCA had a mixture of characteristics of HCC and iCCA. Many cases of cHCC-CCA remained cHCC-CCA pathologically even after recurrence.
The prognosis of patients with relapsed osteosarcoma is extremely poor and the optimal treatment remains to be identified. Here, we retrospectively analysed the clinical outcomes of nine patients ...with relapsed osteosarcoma treated with temozolomide/etoposide. Of the two patients who received temozolomide/etoposide as palliative therapy for unresectable tumours, one remained alive with stable disease for >4 years. The remaining seven patients received temozolomide/etoposide as adjuvant therapy following resection of relapsed metastatic disease; of these, one was free from disease for 41 months. Potentially beneficial effects were observed in two of three O6-methylguanine-DNA methyltransferase protein-negative patients, whereas all five O6-methylguanine-DNA methyltransferase-positive patients experienced subsequent relapse. None of the patients experienced severe adverse effects requiring hospitalization. Temozolomide/etoposide is a feasible candidate as salvage therapy for relapsed osteosarcoma. Further studies are needed to verify the utility of O6-methylguanine-DNA methyltransferase protein expression as a biomarker for predicting the response to this treatment.
Discohesive growth pattern (Disco-p) is often observed in lung adenocarcinoma (ADC) and mimics tumor budding (TB), stromal invasive-type micropapillary pattern (SMPP), and complex glandular pattern. ...However, the clinical impact of Disco-p in lung ADC has not been well studied. To investigate the prognostic significance of Disco-p, we analyzed 1062 Japanese patients with resected lung ADC. Disco-p was defined as an invasive growth pattern composed of single tumor cells, or trabeculae or small nests of tumor cells associated with desmoplastic fibrous stroma. We recorded the percentage of Disco-p in 5% increments independent of the major histologic pattern and investigated its correlation with different clinicopathological factors. We also analyzed the overall survival (OS) and disease-free survival (DFS). Disco-p was observed in 203 tumors (19.1%). Disco-p was significantly associated with male sex, smoking, lymph node metastasis, large tumor size, high TNM stage, lymphovascular and pleural invasion, spread through air spaces, and TB (all, p < 0.001). Of the total cases, only eight cases exhibited a dubious pattern between SMPP and Disco-p. Disco-p was also associated with wild-type EGFR (p < 0.001) and ALK fusion (p = 0.008). Patients harboring tumors with Disco-p had significantly worse prognoses (OS and DFS (both, p < 0.001)) compared with those without Disco-p. On multivariate analysis, Disco-p was an independent prognostic factor of worse OS (hazard ratio (HR), 2.572; 95% confidence interval (CI), 1.789–3.680; p < 0.001), and DFS (HR, 3.413; 95% CI, 2.482–4.683; p < 0.001), whereas TB was not an independent unfavorable prognostic factor. Disco-p was an independent unfavorable prognostic factor in patients with resected lung ADC, although a careful evaluation is necessary to distinguish it from similar patterns. We proposed that Disco-p should be recognized as a new invasive pattern and accurately recorded for the better management of patients with lung ADCs.
Summary Inflammatory cell infiltration in tumor stroma may represent the interaction between the tumor and the immune system. The significance of immunoglobulin (Ig) G4+ plasmacytic infiltration, ...however, is poorly understood. Here, we analyzed the number of stromal IgG4+ plasma cells and the IgG4/IgG ratio of plasma cells in 294 primary non–small cell lung cancers (NSCLCs) using tissue microarray (TMA) and conventional surgical specimens. In TMA, 35 (12%) cases of NSCLC revealed more than 20 IgG4+ plasma cells per high-power field. In surgical specimens, most (97%) of those IgG4+ plasma cell–enriched cases showed obliterative phlebitis or arteritis, one of the key morphologic features of IgG4-related disease, within or at the periphery of the tumor. Clinically, none of the patients showed symptoms associated with IgG4-related systemic diseases. In patients with stage I squamous cell carcinoma, IgG4-enriched stroma was significantly associated with a favorable prognosis ( P = .04). In conclusion, considerable IgG4+ plasma cell infiltration can be seen in a minority of cases of NSCLC and might contribute to prognostic modulation of NSCLC.
Background Chronic kidney disease (CKD) is associated with increased risk of coronary heart disease. However, information regarding the histopathologic characteristics of coronary atherosclerosis in ...individuals with CKD is scarce. This study investigated the relationship between CKD and severity of coronary atherosclerosis in population-based autopsy samples. Study Design Cross-sectional study. Setting & Participants 126 individuals randomly selected from 844 consecutive population-based autopsy samples. Predictor Estimated glomerular filtration rate (eGFR) calculated using the 6-variable Modification of Diet in Renal Disease (MDRD) Study equation. Outcomes Severity of atherosclerosis in 3 main coronary arteries, including atherosclerotic lesion types defined using the American Heart Association classification; stenosis rates; and coronary calcified lesions. Measurements The relationship between CKD and severity of coronary atherosclerosis was evaluated using generalized estimating equation methods. Results Frequencies of advanced atherosclerotic lesions increased gradually as eGFR decreased (33.6%, 41.7%, 52.3%, and 52.8% for eGFRs ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2 , respectively; P for trend = 0.006). This relationship was substantially unchanged even after adjustment for potential confounding factors (ORs, 1.40 95% CI, 0.76-2.55, 2.02 95% CI, 0.99-4.15, and 3.02 95% CI, 1.22-7.49 for eGFRs of 45-59, 30-44, and <30 mL/min/1.73 m2 , respectively). Frequencies of calcified lesions of coronary arteries also increased gradually with lower eGFRs ( P for trend = 0.02). Hypertension and diabetes were associated with increased risk of advanced coronary atherosclerosis and calcification of coronary arteries in individuals with decreased eGFR. Limitations Cross-sectional study, absence of data for proteinuria, and extremely high proportion of aged people. Conclusions The autopsy findings presented here suggest that CKD is associated significantly with severity of coronary atherosclerosis. Patients with CKD should be considered a high-risk population for advanced coronary atherosclerosis.
High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS) is an emerging application for the comprehensive and detailed analysis of the spatial distribution ...of ionized molecules in situ on tissue slides. HR-MALDI-IMS in negative mode in a mass range of m/z 500-1000 was performed on optimal cutting temperature (OCT) compound-embedded human prostate tissue samples obtained from patients with prostate cancer at the time of radical prostatectomy. HR-MALDI-IMS analysis of the 14 samples in the discovery set identified 26 molecules as highly expressed in the prostate. Tandem mass spectrometry (MS/MS) showed that these molecules included 14 phosphatidylinositols (PIs), 3 phosphatidylethanolamines (PEs) and 3 phosphatidic acids (PAs). Among the PIs, the expression of PI(18:0/18:1), PI(18:0/20:3) and PI(18:0/20:2) were significantly higher in cancer tissue than in benign epithelium. A biomarker algorithm for prostate cancer was formulated by analyzing the expression profiles of PIs in cancer tissue and benign epithelium of the discovery set using orthogonal partial least squares discriminant analysis (OPLS-DA). The sensitivity and specificity of this algorithm for prostate cancer diagnosis in the 24 validation set samples were 87.5 and 91.7%, respectively. In conclusion, HR-MALDI-IMS identified several PIs as being more highly expressed in prostate cancer than benign prostate epithelium. These differences in PI expression profiles may serve as a novel diagnostic tool for prostate cancer.
A 32-year-old male patient was initially diagnosed with fibrosing mediastinitis. The patient subsequently developed severe dyspnea and was further diagnosed with constrictive pericarditis due to the ...extent of fibrosing mediastinitis around the heart. Therefore, the patient underwent surgical resection of the fibrotic tissue in the anterior mediastinum including the pericardium and the pleura. Postoperative histological and immunohistochemical analyses revealed angiosarcoma. Seven years after the diagnosis, he is still alive. Herein, we report a case of atypical primary angiosarcoma of the anterior mediastinum causing constrictive pericarditis and restrictive pulmonary dysfunction.
A 74-year-old man with no overt symptoms was referred for a chest computed tomography (CT) that revealed multiple bilaterally pulmonary ground-glass nodules (GGNs) with subtle changes in size over ...eight months. Surgical lung biopsies were performed in the left upper lobe. A pathologic study confirmed the intravascular large B-cell lymphoma (IVLBCL). This lesion was a nodule-like cluster of atypical cells, meaning that it had been localized for several months. Pulmonary IVLBCL may form focal lesions presenting as GGN on chest CT and progress slowly without apparent symptoms.
PDF
