Acute interstitial nephritis with acute kidney injury after COVID-19 vaccination: a case report.

In the context of the massive spread of coronavirus disease 2019 (COVID-19), the development of a COVID-19 vaccine is urgently needed. The Pfizer-BioNTech COVID-19 vaccine has been widely applied across global populations. Herein, we report a case of acute interstitial nephritis with acute kidney injury in a young healthy subject after administration of the COVID-19 vaccine. A 20-year-old man was admitted with abdominal discomfort and nausea. He had received the Pfizer-BioNTech COVID-19 vaccine 6 days before. At 9 days after vaccination, his kidney function was decreased, with serum creatinine levels of 1.8 mg/dL. Even with supportive care with hydration, his kidney function worsened, and he underwent a kidney biopsy. The pathology findings revealed diffuse interstitial infiltration of inflammatory cells, predominantly comprising lymphocytes, with preservation of the glomerulus. No abnormal findings were noted by immunofluorescence or electron microscopy. Based on a diagnosis of drug-related acute interstitial nephritis, we treated the patient with high-dose prednisolone. After administration of prednisolone, kidney function slowly improved. A close linkage between COVID-19 vaccination and acute interstitial nephritis should be considered in the clinic, despite the low incidence.

Molecular classification of follicular thyroid carcinoma based on TERT promoter mutations.

Follicular thyroid carcinoma (FTC) has different clinicopathological characteristics than papillary thyroid carcinoma. However, there are no independent systems to predict cancer-specific survival (CSS) in FTC. Telomerase reverse transcriptase (TERT) promoter mutations are associated with tumor aggressiveness. Thus, it could be a potential prognostic marker. The aim of this study was to refine the CSS risk prediction using TERT promoter mutations in combination with the fourth edition of World Health Organization (WHO 2017) morphological classification. We investigated 77 FTC patients between August 1995 and November 2020. Cox regression was used to calculate hazard ratios to derive alternative groups. Disease-free survival (DFS) and CSS predictability were compared using Proportion of variation explained (PVE) and C-index. CSS was significantly different in encapsulated angioinvasive (EA)-FTC patients stratified by TERT promoter mutations [wild-type (WT-TERT) vs. mutant (M-TERT); P < 0.001] but not in minimally invasive (MI)-FTC and widely invasive (WI)-FTC patients (P = 0.691 and 0.176, respectively). We defined alternative groups as follows: Group 1 (MI-FTC with WT-TERT and M-TERT; EA-FTC with WT-TERT), Group 2 (WI-FTC with WT-TERT), and Group 3 (EA-FTC with M-TERT; WI-FTC with M-TERT). Both PVE (22.44 vs. 9.63, respectively) and C-index (0.831 vs. 0.731, respectively) for CSS were higher in the alternative groups than in the WHO 2017 groups. Likewise, both PVE (27.1 vs. 14.9, respectively) and C-index (0.846 vs. 0.794, respectively) for DFS were also higher in the alternative groups than in the WHO 2017 groups. Alternative group harmonizing of the WHO 2017 classification and TERT promoter mutations is effective in predicting CSS in FTC patients, thereby improving DFS predictability.

Prognostic Impact of Tumor-Associated Macrophages on Long-Term Oncologic Outcomes in Colorectal Cancer.

This study evaluated the correlation between tumor-associated macrophages (TAMs) and long-term oncologic outcomes in colorectal cancer (CRC). We evaluated TAMs based on the expression of CD68, CD11c, and CD163 as optimal markers via immunohistochemistry in 148 patients with CRC who underwent surgical resection between September 1999 and August 2004. A high proportion of CD68-positive macrophages were associated with the occurrence of distant metastasis. A low proportion of CD11c-positive macrophages were associated with unfavorable overall survival (OS) and disease-free survival. CD11c-positive macrophages were found to act as independent prognostic factors for OS. An analysis of our long-term data indicated that TAMs are significantly associated with OS and prognosis in CRC.

Transmitral resection of left ventricular lipoma by right mini-thoracotomy using a rolled up flexible ruler.

Left ventricular lipoma is a rare intracardiac tumour that is usually resected through sternotomy to effectively explore the left ventricular cavity. We introduce a simple technique to expose the left ventricular cavity and resect the intraventricular lipoma using a rolled up flexible ruler through right mini-thoracotomy. Imaging studies and gross and microscopic photography of intraventricular lipoma are presented in this report.

Reconstruction of a pathologic fracture following osteomyelitis of the mandible using a fibula osteocutaneous flap.

The use of a fibula osteocutaneous flap is currently the mainstay of segmental mandibular reconstruction. This type of flap is used to treat tumors, trauma, or osteoradionecrosis of the mandible. However, a fibula osteocutaneous flap may also be a good option for reconstructing the mandible to preserve oropharyngeal function and facial appearance in cases of pathological fracture requiring extensive segmental bone resection. Chronic osteomyelitis is one of the various causes of subsequent pathologic mandibular fractures; however, it is rare, and there have been few reports using free flaps in osteomyelitis of the mandible. We share our experience with a 76-year-old patient who presented with a pathologic fracture following osteomyelitis of the mandible that was reconstructed using a fibula osteocutaneous flap after wide segmental resection.

High-grade mucoepidermoid carcinoma in the thyroid gland with poor prognosis.

Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of the salivary gland, but primary thyroid MEC has rarely been reported and usually has a good prognosis. Herein, I report a case of thyroidal MEC with a poor prognosis in an 82-year-old woman with an anterior neck mass. Ultrasonography and computed tomography revealed a thyroid mass. The patient initially underwent fine-needle aspiration, was diagnosed with malignancy, and underwent a right lobectomy. On gross examination, a 4.0×3.6×2.6 cm-sized ill-defined, unencapsulated, and infiltrative tan to whitish mass with necrosis was identified. Microscopically, epidermoid tumor cell nests or solid sheets were identified. Mucous cells that were positive for periodic acid-Schiff and mucicarmine stains were also identified within epidermoid cell nests. Frequent mitosis and necrosis were observed. Immunohistochemical staining for p40 and p63 was positive, and that for thyroid transcription factor-1 and paired box gene 8 was focally positive. According to the Armed Forces Institute of Pathology grading system for salivary gland MEC, the current case was classified as high-grade MEC. After surgery, the patient suffered from dyspnea due to a remnant neck mass that compressed and obstructed the trachea; therefore, the patient refused further treatment. Thyroidal MECs are considered low-grade with a favorable prognosis, but there are several reported cases of thyroidal MEC with poor prognosis. The current case is a rare presentation of high-grade thyroidal MEC with a poor prognosis.

Digital image analysis in pathologist-selected regions of interest predicts survival more accurately than whole-slide analysis: a direct comparison study in 153 gastric carcinomas.

Automatic quantification of biomarkers such as tumor-infiltrating lymphocytes and PD-L1 is one of the most studied topics in digital pathology image analysis (DIA). However, direct comparison between the DIA of a whole-slide image (WSI) and that of regions of interest (ROIs) chosen by pathologists has not been performed. In this study, we aimed to compare the prognostic value of tumor microenvironment markers CD8 and PD-L1, measured by DIA of WSIs and ROIs. We selected 153 primary gastric cancer tissues and stained them with CD8 and PD-L1. All IHC slides were scanned at ×200 magnification and ratios of CD8 and PD-L1 were measured in WSIs and ROIs from the invasive front, within the tumor, and the mucosa. Patients with high CD8 and PD-L1 ratios showed more favorable outcomes compared to those with low ratios. Pathologist-aided DIA predicted the survival of patients more accurately than WSI analysis (CD8, p = 0.025 versus p = 0.068; PD-L1, p = 0.008 versus p = 0.2). Although a high density of CD8+ T cells at the invasive front correlated best with patient survival, CD8 ratio in the mucosa could also predict patient outcome. In conclusion, CD8 and PD-L1 ratios measured by pathologist-aided DIA predicted survival more accurately than WSI analyses and ROIs at the invasive front correlated best with patient outcome.

Favorable Long-Term Outcomes of Endoscopic Submucosal Dissection for Differentiated-Type-Predominant Early Gastric Cancer with Histological Heterogeneity.

It remains unclear whether endoscopic submucosal dissection (ESD) can be indicated for differentiated-type-predominant early gastric cancer mixed with a minor undifferentiated component (EGC with histological heterogeneity (HH)). Here, we reviewed and compared clinicopathologic characteristics and long-term outcomes of ESD of 257 patients with EGC-HH and those of 2386 patients with pure differentiated-type EGC (PuD-EGC). After ESD, EGC-HH was managed in the same way as PuD-EGC. EGC-HHs were significantly associated with larger tumor size, more frequent submucosal invasion, and lymphovascular invasion compared to PuD-EGCs. Despite these aggressive features of EGC-HH, no local recurrence or gastric cancer-related death occurred during a median of 58 months of follow up after ESD for EGC-HH, if curative resection was achieved. After curative ESD for EGC-HH, six patients had metachronous recurrence (5.0%) and one patient underwent extragastric recurrence in a regional lymph node (0.8%). All these recurrence cases were curatively treated with ESD or gastrectomy. For patients with EGC-HH, five-year overall survival and recurrence-free survival rates after curative ESD were 97.0% and 94.8%, respectively, which were comparable to those of patients with PuD-EGC. In conclusion, ESD showed favorable long-term outcomes after curative resection and may be an acceptable treatment option for EGC-HH meeting curative endoscopic resection criteria.

Cancer Panel Assay for Precision Oncology Clinic: Results from a 1-Year Study.

Next-generation sequencing (NGS)-based cancer panel tests are actively being applied in the clinic for precision oncology. Given the importance of NGS panel tests in the palliative clinical setting, it is critical to understand success rates, factors responsible for test failures, and the incidence of clinically meaningful genetic alterations. We performed NGS cancer panel test with tumors from the stomach (n = 234), colorectum (n = 196), and rare tumors (n = 105) from 535 recurrent or metastatic cancer patients for 1 year. Sequencing was successful in 483 (95.3%) archival tumor samples to find single nucleotide variant (SNV), copy number alteration (CNA), and fusion. NGS testing was unsuccessful in 52 (9.7%) specimens due to inadequate tissue (n = 28), low tumor volume (n = 19), and poor quality of nucleic acid (n = 5). According to the Tier system, variants were classified as Tier IA, 0.8%; IIC, 10.3%; IID, 2.0%; III, 66.7% for gastric: Tier IA, 3.6%; IIC, 11.6% for colorectal: Tier IA, 1.6%; IIC, 13.5%; IID, 0.5%; III, 70.8% for melanoma, and Tier IA, 9.1%; IIC, 1.8%; IID, 1.0%; III, 66.4% for GIST. In total, 30.8% of 483 sequenced cases harbored clinically meaningful variants. In Tier IA, KRAS and ERBB2 were the most commonly altered genes. Interestingly, we identified CD274 (PD-L1) amplification, PTPN11 (SHP2) SNV, TPM3-NTRK1 fusion, and FGFR3-TACC3 fusion as a rare (<2%) alteration having therapeutic targets. In conclusion, although small biopsy samples constitute half of cases, informative NGS results were successfully reported in >90% of archival tissue samples, and 30.8% of them harbored clinically meaningful variants.

CCNE1 amplification is associated with liver metastasis in gastric carcinoma.

With targeted therapies becoming the new standard of care in oncology, next generation sequencing (NGS) is emerging as a valuable method for analyzing the molecular underpinnings of individual tumors. Cyclin E1, encoded by CCNE1 causes activation of E2F mediated transcription and drives cells from G1 into S phase with cyclin-dependent kinase 2 (CDK2). CCNE1 amplification has been found in 11-12% of gastric cancers, but the clinical significance of this amplification remains controversial, and its association with liver metastasis has not been studied. This study included 226 patients diagnosed with advanced gastric adenocarcinoma. We performed multi-gene panel tests containing 143 genes using DNA and RNA obtained from primary (n = 197; 120 endoscopic biopsies and 77 resections) or metastatic cancer tissues (n = 29; 26 biopsies, 2 excisions, and 1 fin. needle aspiration). Among the 226 cases, 28 cases (12.4%) had CCNE1 amplification, almost half of which (n = 13, 46.4%) showed liver metastasis. In patients with CCNE1 amplification (n = 28), TP53 mutations (n = 23, 82.1%) and ERBB2 amplification (n = 8, 28.6%) were the most frequent concurrent genetic alterations. In contrast, 42 (21.2%) of 198 patients without CCNE1 amplification showed liver metastasis. CCNE1 amplification was significantly associated with liver metastasis (p = 0.004; odds ratio, 3.219). Our results show that CCNE1 amplification is significantly associated with liver metastasis in a TP53-mutated gastric cancer subtype. Given the frequent association of CCNE1 amplification with liver metastasis, close follow up for liver metastasis and further clinical trials targeting CDK2 inhibitors are warranted.

Tumor-Associated Macrophages as Potential Prognostic Biomarkers of Invasive Breast Cancer.

PURPOSE: Tumor-associated macrophages (TAMs) are activated macrophages associated with tumor progression in various cancers. TAMs can polarize M1 or M2 type. M1 has a pro-inflammatory function and kills pathogens. Conversely, M2 shows immunosuppressive action and promotes tumor growth. There are various markers of TAMs. CD11c is considered as a specific marker of M1. CD163 is an optimal marker for M2. CD68 is known as a pan-macrophage marker. We evaluated the relationship between the clinicopathological parameters and immunohistochemical expressions of CD11c, CD163, and CD68 in invasive breast cancer (IBC), and the prognostic value of macrophage localization within the tumor stroma (TS) and tumor nest (TN). METHODS: Immunohistochemistry of CD68, CD11c, and CD163 was analyzed on tissue microarrays of 367 IBCs. The number of CD68+, CD11c+, or CD163+ macrophages in TN vs. TS was counted by 2 pathologists. The correlations between the degree of macrophage (CD68+, CD11c+, or CD163+) infiltration and the clinicopathological parameters were analyzed. We also assessed the impact of macrophages (CD68+, CD11c+, or CD163+) on disease free survival (DFS) and overall survival (OS). RESULTS: High numbers of macrophages (CD68+, CD11c+, or CD163+) were associated with higher histologic grade, higher Ki-67 proliferating index, estrogen receptor negativity, and progesterone receptor negativity. High numbers of macrophages (CD11c+ or CD163+) in TS were associated with a larger tumor size. Furthermore, CD163+ macrophages in TN were an independent prognostic marker of reduced OS and DFS. Conversely, CD11c+ macrophages in TS were an independent prognostic marker for higher OS and DFS. CONCLUSION: TAMs, including M2 type, are associated with tumor progression in IBC. They can also act as a significant unfavorable or favorable prognostic factor. In addition to simply analyzing the degree of TAM infiltration, it is also important to analyze the location of TAMs.

MET is overexpressed in microsatellite instability-high gastric carcinoma.

BACKGROUND: MET is a tyrosine kinase receptor for the hepatocyte growth factor, and its overexpression is a poor prognostic factor in gastric carcinomas. Programmed death-ligand 1 (PD-L1) is an important biomarker of immunotherapy and is frequently positive in microsatellite instability-high (MSI-H) gastric carcinomas. In lung cancers, MET activation up-regulates PD-L1 expression. In this study, we investigated expression of MET and PD-L1 in MSI-H gastric carcinoma and the effects on prognosis. METHODS: MET and PD-L1 (SP142) immunohistochemistry was performed in 73 gastric carcinomas with MSI-H. In cases with MET overexpression, we performed fluorescent in situ hybridization (FISH). PD-L1 expression was calculated from both tumor cells (2+ and 3+ in > 10% of tumor cells was defined as PD-L1TC+) and immune cells (positive in >5% immune cells was PD-L1IC+), and also used a combined positive score (CPS; number of PD-L1 staining cells relative to all viable tumor cells; > 1 was PD-L1+). RESULTS: In 73 MSI-H gastric carcinomas, MET overexpression was observed in 11 cases (15.1%). In all 11 cases with MET overexpression,MET amplification was not found. MET overexpression was not related to any of clinico-pathological variables and PD-L1 expression. However, the PD-L1 CPS tended to be higher in tumors that were MET positive. Although MET overexpression alone was not a prognostic indicator, combined MET overexpression/PD-L1 predictive models showed that patients with MET+/PD-L1+ showed the best prognosis for overall survival as compared to other groups. CONCLUSION: MET overexpression was observed in 15% of MSI-H gastric carcinomas and was associated with high level expression of PD-L1.

Coexistence of gastrointestinal stromal tumor and inflammatory myofibroblastic tumor of the stomach presenting as a collision tumor: first case report and literature review.

Collision tumors of the stomach are rare. We report on a case of a collision tumor consisting of a gastrointestinal stromal tumor (GIST) and an inflammatory myofibroblastic tumor (IMT) of the stomach in a 16-year-old female. A polypoid mass located in the distal body of the stomach was observed on abdominal computed tomography. Laparoscopic wedge resection of the stomach and 4d lymph node biopsy was performed. On gross examination, a protruding submucosal mass, measuring 4 × 3.5 × 2.5 cm in size, was detected. Histological examination showed two distinct GIST and IMT component presenting a collision tumor. The small nodular area, composed of CD117-positive spindle cells, was typical of GIST, and the adjacent larger area, composed of myofibroblastic spindle cells with prominent chronic inflammatory cells infiltrate, mainly lymphocytes and plasma cells, had a characteristic appearance of IMT. The 4d lymph node showed metastatic inflammatory myofibroblastic tumor. To the best of our knowledge, this is the first case of a collision tumor consisting of a GIST and an IMT arising in the stomach.

Epithelioid trophoblastic tumor: clinicopathologic and immunohistochemical analysis of three cases.

Epithelioid trophoblastic tumor is an unusual type of trophoblastic tumor. Here we report on the clinicopathologic and immunohistochemical features of three cases of epithelioid trophoblastic tumor. All three patients were of reproductive age and presented with vaginal bleeding and mild elevation of human chorionic gonadotropin (hCG). All patients underwent a hysterectomy. The tumors consisted of epithelioid intermediate trophoblastic cells that were mononucleated and eosinophilic, or showed clear cytoplasm on microscopic examination. One case presented with a focal choriocarcinoma component. Immunohistochemically, the tumors displayed diffuse positivity for cytokeratin 18, E-cadherin, epidermal growth factor receptor, and p53 and focal positivity for p63 and hCG. However, expression of α-inhibin and placental alkaline phosphatase was almost negative. Tests for human placental lactogen and epithelial membrane antigen were also negative in all cases.

Best immunohistochemical panel in distinguishing adenocarcinoma from squamous cell carcinoma of lung: tissue microarray assay in resected lung cancer specimens.

The emergence of the targeted therapies for non-small cell lung carcinoma (NSCLC) has generated a need for accurate histologic subtyping of NSCLC. In this study, we assessed the utility of immunohistochemical markers that could be helpful in distinction between adenocarcinoma (ADC) and squamous cell carcinoma (SCC). We performed a battery of immunohistochemistry using tissue microarray for napsin-A, Thyroid transcription factor 1 (TTF-1), p63, cytokeratin (CK) 5/6, thrombomodulin (CD141), Epithelial-related antigen (MOC-31), carcinoembryonic antigen (CEA), Cyclooxygenase 2 (COX-2), high-molecular-weight CK (HMWCK), p27kip1 (p27), and Rb protein in 129 resected primary NSCLC with 81 ADCs and 48 SCCs and 10 metastatic ADC to the lung (primary in colon, 7 cases; stomach, 2 cases; vagina, 1 case). Cases of ADC and SCC were morphologically unequivocal and solid tumors with no definite squamous or glandular differentiation were excluded for this analysis. Napsin-A and TTF-1 were positive in 81% and 70% of ADC and in 0% and 2% of SCC, respectively, whereas P63 and CK5/6 were positive in 91% and 90% of SCC and in 9% and 4% of ADC, respectively (P < .001). CD141 stained significantly higher in SCC over ADC (positive in 2% of ADC and 46% of SCC. MOC-31, CEA, COX-2, HMWCK, p27, and Rb appeared to be not useful markers in distinction between ADC and SCC because of their low specificity. None of metastatic ADC to the lung showed positive for napsin-A and TTF-1. It was evident that combination of napsin-A, TTF-1, CK5/6, and p63 was the best immunohistochemical panel in differentiating ADC from SCC of the lung in this study. CD141 appeared to be a potential new marker for SCC with high specificity. Cyclooxygenase 2, MOC-31, CEA, HMWCK, p27, and Rb showed less specificity for differentiation ADC from SCC.

Plexiform angiomyxoid myofibroblastic tumor of the stomach: a case report.

Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a recently described mesenchymal tumor of the stomach. We report the first case of PAMT in Korea. A 52-yr-old man underwent esophagogastroduodenoscopy due to dyspepsia for 2 yr. There was a submucosal mass with small mucosal ulceration in the gastric antrum. The tumor measured 3.5 × 2.3 cm in size and showed multinodular plexiform growth pattern of bland-looking spindle cells separated by an abundant myxoid or fibromyxoid matrix rich in small thin-walled blood vessels. The tumor cells were negative for CD117 (c-KIT), CD34 and S-100 protein, but diffusely positive for smooth muscle actin consistent with predominant myofibroblastic differentiation. The patient is doing well without recurrence or metastasis for 5 months after surgery. Although there have been limited follow-up data, PAMT is regarded as a benign gastric neoplasm with histological and immunohistochemical characteristics distinguished from gastrointestinal stromal tumor and other mesenchymal tumors of the stomach.