Prognostic impact of lymph node invasion levels in patients with bladder cancer undergoing radical cystectomy and pelvic lymphadenectomy.

Extranodal extension in metastatic lymph nodes (LNs) is a poor prognostic factor in bladder cancer (BC). Furthermore, cancer invasion levels in sentinel LNs are associated with prognosis in melanoma. The present study aimed to evaluate the LN invasion level, defined as the extent of cancer invasion in anatomical and immunological LN substructures, and compare it with the pathological node (pN) stage of the tumor-node-metastasis staging system in BC. A total of 98 patients with BC who underwent radical cystectomy and pelvic lymphadenectomy were retrospectively assessed. The LN invasion level was classified as follows: Level 0, no cancer cell within the resected LNs; Level 1, cancer cells confined to intracapsular lymph vessels and subcapsular or transverse sinuses; Level 2, cancer cells infiltrating the cortex, paracortex or medulla; and Level 3, cancer cells infiltrating or beyond the LN capsule. The proportion of patients with Levels 0, 1, 2 and 3 was 70.4% (69/98), 8.2% (8/98), 14.3% (14/98) and 7.1% (7/98), respectively. Kaplan-Meier survival curves of recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) with LN invasion levels better stratified outcome patient when using Levels 1-3 compared with pN1-3. In addition, LN invasion levels better predicted RFS, CSS and OS, in comparison with the pN stage (c-index of 0.672 vs. 0.646, 0.688 vs. 0.665, and 0.702 vs. 0.661, respectively). Finally, multivariate analysis revealed that the predictive accuracy of the model integrating pathological tumor (pT) stage and LN invasion levels in RFS, CSS and OS was greater than that of the conventional model that included pT and pN stage (c-index of 0.723 vs. 0.703, 0.710 vs. 0.694, and 0.725 vs. 0.692, respectively). In conclusion, the model with LN invasion levels accurately predicted the prognosis of patients with BC after radical cystectomy and pelvic lymphadenectomy.

H3 K27-altered diffuse midline glioma of the thalamus with formation of glio-fibrillary globular structures.

A case of diffuse midline glioma (DMG), H3 K27-altered, that arose in the right thalamus of a 14-year-old boy is reported. The patient died of tumor spread after a progressive clinical course of approximately 13 months. Histopathologically, the tumor consisted of a mixture of loose proliferation of stellate cells and compact fascicular growth of spindle cells showing a "piloid" feature. Aggregates of globular structures composed of entangled fine glial fibrils ("glio-fibrillary globules, GFGs") were observed. Tumor cells were immunoreactive for S-100 protein and glial fibrillary acidic protein (GFAP), and showed nuclear immunoreactivity for histone H3 K27M and loss of expression of H3 K27me3. Tumor cell nuclei were also negative for alpha-thalassemia/mental retardation syndrome X-linked protein (ATRX) and p16. Although GFGs morphologically resembled "neuropil-like islands" or "neurocytic rosettes" seen in glial or glio-neuronal tumors, they showed immunoreactivity for GFAP, but not for synaptophysin. A GFG is a unique structure that has been described in DMG, H3 K27-altered, by a few investigators. To the best of our knowledge, this structure has not previously been reported in other glial or glio-neuronal tumors. It could be added as a new feature in the histopathological variations of DMG, extending its morphological spectrum. Familiarity with this feature can help prevent misdiagnosis of DMG.

Efficacy of Minor Salivary Glands as Indicators of Depth of Resection for Superficial Hypopharyngeal Carcinoma.

Objective: This study aimed to investigate the utility of minor salivary glands in the hypopharynx as novel indicators for safe resection of superficial hypopharyngeal carcinomas with fewer complications. Study Design: Cadaveric study. Setting: Cadavers were stored in the pathology laboratory at Kansai Medical University. Methods: Twenty-three cadaveric specimens were examined for minor salivary glands in the pyriform sinus, posterior wall, and postcricoid regions of the hypopharynx. Their count, size, and depth were assessed. Resected specimens from 5 consecutive patients with superficial hypopharyngeal carcinomas were pathologically analyzed to determine the positional relationship between cancer and minor salivary glands. Results: Minor salivary glands were present in more than 70% of patients in each region during autopsy, with the postcricoid region having a larger count and size. The glands were universally present, regardless of sex, height, or body mass index. Minor salivary glands in the pyriform sinus and postcricoid region were present at a depth of 30% from the bottom of the submucosal layer, whereas those in the posterior wall were present in the shallow muscularis. During surgery, endoscopic findings revealed minor salivary glands as small white nodules in the submucosal layer. Pathological examination of the resected specimen confirmed that the white nodule was a minor salivary gland. In addition, tumor position in relation to minor salivary glands provided an adequate margin for resection. Conclusion: Minor salivary glands may serve as reliable indicators for determining adequate deep safety margins during surgery for superficial hypopharyngeal carcinoma.

Effectiveness and outcomes of endoscopic resection for superficial pharyngeal squamous cell carcinomas.

BACKGROUND: With the development of endoscopic imaging, superficial pharyngeal squamous cell carcinoma can now be detected during routine endoscopy. Recently, the effectiveness of endoscopic resection for superficial pharyngeal squamous cell carcinoma have been reported. METHODS: This study had a retrospective single-center design that included patients with superficial pharyngeal squamous cell carcinoma who underwent endoscopic resection. A total 47 patients with 53 lesions were analyzed. RESULTS: En bloc and R0 resection rates were 83.0% and 56.6%. Local recurrence and cervical lymph node metastasis (CLNM) were detected in 1 and 3 patients during follow-up. The macroscopic type 0-I was an independent factor for CLNM. The 3-year cumulative incidence of metachronous pharyngeal squamous cell carcinoma following endoscopic resection was 33.0%, and the 5-year overall survival rate was 89.2%. CONCLUSIONS: Endoscopic resection is an effective treatment for superficial pharyngeal squamous cell carcinomas, and the macroscopic type 0-I is a useful predictor of CLNM.

Impact of LAG-3/FGL1 pathway on immune evasive contexture and clinical outcomes in advanced urothelial carcinoma.

BACKGROUND: Anti-programmed death-1 (PD-1)/anti-PD-ligand-1 (PD-L1) pathway inhibition is a standard regimen for advanced urothelial carcinoma (UC); however, its limited efficacy has been reflected in reported medium response rates. This study explored the role of next-generation coinhibitory receptors (IRs; lymphocyte activation gene 3 (LAG-3), T-cell immunoglobulin and mucin domain 3 (TIM-3), and T-cell immunoreceptor with Ig and ITIM domains (TIGIT)) and their ligands (LGs) in the response to PD-(L)1 blockade therapy and the oncological outcomes in patients with UC. METHODS: We investigated metastatic UC cases who underwent PD-(L)1 therapy (cohort 1: n=348, cohort 2: n=89, and cohort 4: n=29) or advanced UC cases involving surgery (cohort 3: n=293 and cohort 5: n=90). We assessed the mRNA expression profiles and corresponding clinical information regarding IRs and LGs using cohorts 1, 2, and 3. Additionally, we elucidated the spatial features of these targeted markers using multiplex immunohistochemistry (mIHC) on formalin-fixed paraffin-embedded samples from cohorts 4 and 5. Survival, differential expressed gene, and Gene Set Enrichment analyses were performed. For mIHC, quantitative analyses were also performed to correlate immune and tumor cell densities with patient survival. RESULTS: LAG-3 expression was strongly associated with the responsiveness of PD-(L)1 blockade compared with the expression of TIM-3 and TIGIT. In tumors with high LAG-3 levels, the increased expression of fibrinogen-like protein 1 (FGL1) had a significantly negative effect on the response to PD-(L)1 blockade and overall survival. Moreover, high FGL1 levels were associated with elevated CD4+ regulatory T-cell gene signatures and the upregulation of CD39 and neuropilin-1, with both indicating CD8+ T-cell exhaustion. mIHC analyses revealed that patients with stromal CD8+LAG-3+cellshigh-tumor FGL1+cellshigh exhibited a significant negative correlation with survival rates compared with those with stromal CD8+LAG-3+cellshigh-tumor FGL1+cellslow. CONCLUSIONS: LAG-3 expression and high FGL1 coexpression are important predictive factors of adverse oncological outcomes related to the presence of immunosuppressive contextures. These findings are hypothesis-generating, warranting further mechanistic and clinical studies aimed to evaluate LAG-3/FGL1 blockade in UC.

Evaluating Cellularity Estimation Methods: Comparing AI Counting with Pathologists' Visual Estimates.

The development of next-generation sequencing (NGS) has enabled the discovery of cancer-specific driver gene alternations, making precision medicine possible. However, accurate genetic testing requires a sufficient amount of tumor cells in the specimen. The evaluation of tumor content ratio (TCR) from hematoxylin and eosin (H&E)-stained images has been found to vary between pathologists, making it an important challenge to obtain an accurate TCR. In this study, three pathologists exhaustively labeled all cells in 41 regions from 41 lung cancer cases as either tumor, non-tumor or indistinguishable, thus establishing a "gold standard" TCR. We then compared the accuracy of the TCR estimated by 13 pathologists based on visual assessment and the TCR calculated by an AI model that we have developed. It is a compact and fast model that follows a fully convolutional neural network architecture and produces cell detection maps which can be efficiently post-processed to obtain tumor and non-tumor cell counts from which TCR is calculated. Its raw cell detection accuracy is 92% while its classification accuracy is 84%. The results show that the error between the gold standard TCR and the AI calculation was significantly smaller than that between the gold standard TCR and the pathologist's visual assessment (p<0.05). Additionally, the robustness of AI models across institutions is a key issue and we demonstrate that the variation in AI was smaller than that in the average of pathologists when evaluated by institution. These findings suggest that the accuracy of tumor cellularity assessments in clinical workflows is significantly improved by the introduction of robust AI models, leading to more efficient genetic testing and ultimately to better patient outcomes.

Emergency right lower lobectomy for severe pulmonary abscess in a pregnant woman at the 25th week of gestation: a case report.

BACKGROUND: Pulmonary abscess is a severe infection commonly seen in patients with chronic obstructive pulmonary disease, interstitial pneumonia, immune deficiency disease, drug-induced immunocompromised state, and congenital pulmonary disease. The treatment strategy in pregnant women with a pulmonary abscess is considered challenging since adverse effects on the fetus must be avoided to ensure safe delivery. CASE PRESENTATION: A 34-year-old female patient at 24 weeks of gestation (G2P1) was admitted to the Department of Obstetrics and Gynecology due to sudden right chest pain. The patient had no significant medical history, including congenital anomalies, and no history of drug addiction or smoking. Laboratory data indicated high levels of inflammation (white blood cell 12,000/µL, C-reactive protein 16.0 mg/dL), and computed tomography demonstrated a large intrapulmonary cyst located in the middle of the right lower lobe, with some fluid collection. As the patient had no medical history of congenital pulmonary anomalies, she was initially diagnosed with a pulmonary cyst infection and treated with intravenous antibiotics. However, the infection did not resolve for over a week, and a spike in fever developed after admission. There was no definitive evidence concerning the risk of preterm delivery and fetal abortion during non-obstetric surgery. However, to control the severely infected pulmonary abscess that was refractory to antibiotics and obtain a pathological diagnosis while saving the life of both the mother and fetus, we elected to perform an emergent right lower lobectomy by open thoracotomy with a fissureless maneuver after receiving informed consent. Postoperatively, the infection gradually improved, and the patient was discharged on the 16th postoperative day without any major complications in the mother or fetus. Although she later experienced coronavirus disease-19 at 29 weeks of gestation, a boy was born at 40th weeks of gestation without any complications. Pathologically, no infectious agents, malignancies, or congenital anomalies other than lung abscesses associated with the pulmonary infarction were observed. The mother and child were healthy 1 year postoperatively. CONCLUSIONS: We experienced a rare case of a pulmonary abscess in a pregnant woman who needed an emergent right lower lobectomy to control the severe infection and obtain a correct pathological diagnosis. Under cooperation from an obstetrician and anesthesiologist, emergency pulmonary resection can be performed safely for serious abscess formation even for pregnant women who have several months left until delivery.

Morphological basis of the lung adenocarcinoma subtypes.

Lung adenocarcinoma (LUAD), which accounts for a large proportion of lung cancers, is divided into five major subtypes based on histologic characteristics. The clinical characteristics, prognosis, and responses to treatments vary among subtypes. Here, we demonstrate that the variations of cell-cell contact energy result in the LUAD subtype-specific morphogenesis. We reproduced the morphologies of the papillary LUAD subtypes with the cellular Potts Model (CPM). Simulations and experimental validations revealed modifications of cell-cell contact energy changed the morphology from a papillary-like structure to micropapillary or solid subtype-like structures. Remarkably, differential gene expression analysis revealed subtype-specific expressions of genes relating to cell adhesion. Knockdown experiments of the micropapillary upregulated ITGA11 gene resulted in the morphological changes of the spheroids produced from an LUAD cell line PC9. This work shows the consequences of gene mutations and gene expressions on patient prognosis through differences in tissue composing physical forces among LUAD subtypes.

Alveolar adenoma with a single cyst: A case report.

Alveolar adenoma is a rare and benign pulmonary tumor, which originates from type II pneumocytes and is often incidentally identified on radiographic images. Alveolar adenoma presents as a peripleural, solitary and cystic nodule in the lung and may mimic other types of lung tumors, thus rendering its differential diagnosis difficult. Alveolar adenoma is diagnosed based on histopathological and immunohistochemical analyses. The present study describes the case of a 50-year-old male patient with alveolar adenoma. He visited a local doctor ~3 years prior due to left chest pain. A chest computed tomography scan revealed a cystic lesion in segment 8 of the left lung. A nodular shadow appeared in the cyst and gradually increased in size; the patient was thus referred to the authors' hospital. The nodule was well-defined, solitary and solid; thus, lung cancer or aspergilloma were suspected. Thoracoscopic wedge resection was performed as diagnostic therapy. The frozen sections were non-diagnostic, and a pathological examination revealed an alveolar adenoma with no evidence of malignancy and a negative culture. The patient had a good post-operative course, with no sign of recurrence at the follow-up evaluation 46 months later. On the whole, alveolar adenoma is a rare, benign pulmonary tumor that is difficult to diagnose pre-operatively.

Downregulated expression of PBRM1 in sarcomatoid hepatocellular carcinoma.

Sarcomatoid hepatocellular carcinoma (SHCC) is a rare and highly lethal subtype of HCC. The present study aimed to explore the unique markers of SHCC using whole gene expression analysis. Subsequently, gene expression analysis was performed using five sarcomatoid and seven carcinomatoid components of seven tissues from patients with SHCC. The results demonstrated a significant downregulation of polybromo 1 (PBRM1) gene expression in the sarcomatoid components. Immunohistochemical staining also indicated a decreased expression of PBRM1 in the sarcomatoid components. Moreover, gene ontology enrichment analysis revealed that most of the 336 differentially expressed genes between the sarcomatoid and carcinomatoid components were involved in functions associated with DNA replication and histone methylation, which was consistent with the loss of function of PBRM1 which encodes Switch/sucrose-non-fermentable chromatin remodeling complex protein. Therefore, the results of the present study suggested that PBRM1 may be a candidate biomarker for the evaluation of SHCC.

Giant cell glioblastoma with lipogenic differentiation in a patient with neurofibromatosis type 1: A case report.

A 45-year-old woman with neurofibromatosis type 1 (NF1) developed a tumor in the left frontal lobe that showed features of giant cell glioblastoma (GC-GB). In addition to the typical GC-GB features, the tumor showed lipogenic differentiation, with many atypical lipoblasts and mature adipocytes. Tumor cells, including the lipogenic cells, were immunoreactive for GFAP, S-100 protein, ATRX, and p53. They were negative for IDH1-R132H, BRAF V600E, synaptophysin, NeuN, p16, mismatch repair proteins, and CD34. The patient is free from recurrence at approximately two years postoperatively. This is the fifth reported case of NF1-associated GC-GB (the second adult case). NF1 gene mutation might have played a role in the pathogenesis of lipogenic differentiation of GC-GB. The differential diagnosis of lipidized GC-GB from gliosarcoma or anaplastic pleomorphic xanthoastrocytoma is briefly discussed.

Successful endoscopic resection for well-differentiated neuroendocrine tumor, Grade 1, in the hypopharynx.

Well-differentiated neuroendocrine tumor, Grade 1 (NET, G1), in the hypopharynx is extremely rare. A 62-year-old woman was referred to our clinic with a tumor in the postcricoid area. The tumor was diagnosed NET on biopsy and there were no metastatic findings on CT, therefore we performed endoscopic resection. Histologic examination revealed well-differentiated neuroendocrine tumor, Grade 1. This case was an extremely rare and valuable case in which endoscopic images can be observed in detail. Endoscopic resection was performed and successful endoscopic and histological resection was achieved.

Adult cerebral high-grade glioneuronal tumor with perivascular or pseudopapillary growth co-existing with low-grade tumor: a case report.

An unusual, small cell-predominant, high-grade glioneuronal tumor in the occipital lobe of a 49-year-old man that co-existed with a low-grade tumor is reported. The tumor consisted of two distinct components: the major component was a dense proliferation of primitive small cells showing bidirectional neuronal and glial differentiation; and the minor component consisted of a proliferation of well-differentiated astrocytes intermingled with mature neuronal cells. In the former component, perivascular pseudorosette-like or pseudopapillary growth reminiscent of ependymoma or papillary glioneuronal tumor (PGNT), respectively, was prominent, and hypertrophic astrocytic cells were located just outside the central blood vessels. Small cells were immunoreactive for Olig2, synaptophysin, and, less frequently, for glial fibrillary acidic protein. The low-grade component included Rosenthal fibers, hemosiderin deposition, and perivascular lymphocytic infiltration, thus closely resembling ganglioglioma. Cytogenetic studies did not demonstrate any mutations or rearrangements of the genes IDH1, IDH2, H3F3A, BRAF, FGFR1, or TERT promoter. The tumor recurred and spread along the ventricular surface three years after total removal. The small cell-predominant, high-grade component was considered to have evolved from the ganglioglioma-like, low-grade component. The histopathologic resemblance of the high-grade component to PGNT was a special feature.

Direct specimen collection during routine operation improves nucleic acid quality in genetic analysis samples for head and neck tumors: A retrospective study.

The nucleic acid integrity of head and neck squamous cell carcinoma (HNSCC) samples is poor, and the material available for genetic analysis is limited. Therefore, to expand the effectiveness of personalized medicine in patients with HNSCC, a new sampling method is needed. In total, 128 samples from 44 patients with HNSCC were studied: 32 genetic analysis samples (GASs) collected as 5 × 5 × 5 mm tissue fragments from resected large tumors and immediately embedded in a small formalin bottle within 10 min (i.e., the ischemic time), 43 primary tumor components (primary), 14 decalcified tumor (DC) samples, 32 metastatic tumors in lymph nodes (LNs), and 7 parakeratinized components (PKCs). The nucleic acid quality in the GAS, primary, DC, LN, and PKC groups was compared and next-generation sequencing (NGS) was performed. DNA integrity number and percentage of RNA fragments with > 200 nucleotides were significantly higher in the GAS group than those in the other groups. RNA integrity number decreased first in LN, followed by GAS, primary, and DC. No significant differences were observed in DIN, RIN and DV200 among the PKC, primary and LN. Following methyl green-pyronin staining, preserved DNA and RNA were not visualized in DC samples. Most NGS metrics did not differ significantly among primary, LN, and PKC samples. In conclusion, GASs should be collected during routine hospital activities. When the volume of viable materials is limited, PKCs should be considered for genetic analysis.

Hypoxia-inducible factor 2α protein and mRNA expression correlate with histomorphological features in clear cell renal cell carcinoma.

Hypoxia-inducible factor 2α (HIF2α) has been identified as a potential biomarker and novel target for systemic therapy in clear cell renal cell carcinoma (ccRCC). The present study aims to evaluate the association of HIF2α protein and HIF2A mRNA expression with clinicopathological factors and histomorphological features related to vasculature and inflammation of ccRCC using a localized ccRCC cohort (n = 428) and The Cancer Genome Atlas (TCGA)-KIRC cohort (n = 433). HIF2α protein expression was immunohistochemically assessed using tissue microarrays and HIF2A mRNA expression was assessed using the TCGA RNA-sequencing data. Positive HIF2α protein and high HIF2A mRNA expression were observed in 145 (33.9 %) and 142 (32.8 %) patients, respectively. Positive nuclear HIF2α protein expression was significantly associated with the clear histological phenotype and architectural patterns related to rich vascular networks (p < 0.001), and no tumor-associated immune cells status (p < 0.05) in addition to favorable prognostic factors such as lower TNM stage, lower WHO/ISUP grade, or the absence of necrosis (p < 0.001). The HIF2A mRNA expression profile by the TCGA cohort showed similar trends as the HIF2α protein profile. In addition, positive HIF2α protein and high HIF2A mRNA expression were associated with higher recurrence-free survival and overall survival, respectively (both p < 0.001). In conclusion, we comprehensively demonstrated the association of HIF2α profiles with clinicopathological factors and histomorphological features related to vasculature and inflammation at both protein and mRNA levels. Histomorphological features expressing HIF2α may provide information on HIF2α targeted therapeutic response as well as prognosis in ccRCC patients.

Cell Block-Based Two-Dimensional and Immunocytochemical Analyses Could Reduce Atypical/Indeterminate Case Frequency in Breast Fine-Needle Aspiration Cytology: A Retrospective Analysis.

INTRODUCTION: In fine-needle aspiration of the breast (FNAB), the "atypical" category encompasses both benign and malignant lesions, particularly papillary proliferative lesions, as per the latest WHO classification. We aimed to reduce atypical cases and improve diagnostic accuracy by investigating the utility of cell block (CB) analysis. METHODS: FNAB CB samples (2018-2022) were reviewed using smear only or CBs. CB-based diagnosis was performed with 2D morphological analysis and immunocytochemistry using ER, CK5/6, p63, SMA, and CD56. Samples were reclassified as "benign," "atypical," "suspicious of malignancy," "malignant," or "insufficient/inadequate." Atypical cases were reexamined. Diagnoses were validated histologically. RESULTS: On examining the FNAB samples (n = 149; 32 atypical), 2D CB sectioning achieved a clearer definition of myoepithelial cells and fibrovascular cores than Papanicolaou staining. Immunocytochemistry was evaluated for 36 cases: estrogen receptor (ER)- and CK5/6+ tumors were reclassified as benign; ER+ and CK5/6- tumors as malignant; p63- tumors as invasive; papillary malignant tumors with a smooth muscle actin (SMA)+ fibrovascular core and p63- myoepithelial cells as encapsulated papillary carcinoma; and CD56+ carcinomas as neuroendocrine carcinoma. Diagnostic rates were as follows: benign (44% FNAB, 51% CB), atypical (21% FNAB, 3% CB), suspicious of malignancy and malignant (28% FNAB, 40% CB), and insufficient/inadequate (7% FNAB, 6% CB). CB achieved >85% sensitivity, specificity, and positive and negative predictive values. CONCLUSION: CBs represent 3D FNA cell morphology using 2D sections, enabling adaption of pathology criteria to the cytological material. Immunocytochemical staining of CBs can predict low nuclear grade papillary tumors and reduce atypical case frequency, improving diagnostic accuracy.

[Radiofrequency Ablation for Pulmonary Metastasis of Ovarian Cancer Caused Iatrogenic Pneumothorax, Leading to Empyema].

A female patient in her 40s who underwent surgery for recurrent right lung metastasis from resected ovarian cancer was referred to our department because of the right pneumothorax due to radiofrequency ablation for multiple lung metastases. Methicillin-resistant Staphylococcus epidermidis( MRSE) was detected from the tip of the drainage catheter indicated persistent pulmonary fistula with right empyema, and surgical treatment was performed. A white coat of the whole lung surface and air leakage were observed at radiofrequency ablation (RFA) treated lesion and partial resection of the right lung, debridement, and irrigation were performed. A pathological examination revealed residual viable ovarian cancer cells and pleural fistula.

Adenoid Ameloblastoma with BRAF p.V600E Mutation Revealing Ameloblastomatous Origin: A First Case Report.

BACKGROUND: Adenoid ameloblastoma (AdAM) is a frequently recurrent tumor that shows hybrid histological features of both ameloblastoma and adenomatoid odontogenic tumor (AOT). AdAM is expected to be classified as a new subtype of ameloblastoma in the next revision of the World Health Organization (WHO) odontogenic tumor classification. However, whether AdAM is a histologic variant of ameloblastoma or AOT remains unclear. To establish a new category, genetic evidence indicating the tumor category is necessary. METHODS: We present a case of a 23-year-old Japanese woman with AdAM who underwent genetic/DNA analysis for ameloblastoma-related mutation using immunohistochemical staining, Sanger sequencing, and next-generation sequencing (NGS) analyses with reliable clinicopathological evidence. RESULTS: Immunohistochemical expression of BRAF p.V600E was diffusely positive for both ameloblastoma- and AOT-like components. Sanger sequencing and NGS analyses showed missense mutations in BRAF p.V600E (c.1799T > A), a gene that is commonly altered in ameloblastomas but not in KRAS, another gene associated with AOT. CONCLUSION: This case report is the first to provide genetic evidence on the ameloblastomatous origin of AdAM with a BRAF p.V600E mutation. A larger series of AdAM groups' molecular testing is needed to aptly classify them and prognosticate the best treatment.

Primary Gastric Rhabdomyosarcoma.

Primary gastric rhabdomyosarcoma is extremely rare. An 87-year-old man visited our clinic with a chief complaint of abdominal pain. Computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography-CT revealed a massive tumor originating from the muscularis propria of the stomach along with splenic vein tumor thrombosis. We diagnosed the patient with primary gastric rhabdomyosarcoma by an endoscopic ultrasound-guided fine-needle aspiration/biopsy.

Mucous Gland Adenoma of the Lung: A Neoplastic Counterpart of Mucinous Bronchial Glands.

Mucous gland adenoma (MGA) is a rare benign tumor that usually arises in the proximal airway and consists of mucus-secreting cells resembling bronchial glands. Here, we report 2 cases of MGAs and describe their morphologic, immunohistochemical, and molecular profiles in comparison with 19 pulmonary tumors of 5 other histologic types with mucinous cells (invasive mucinous adenocarcinoma, mucoepidermoid carcinoma, mixed squamous cell and glandular papilloma, bronchiolar adenoma/ciliated muconodular papillary tumor, and sialadenoma papilliferum). Two MGAs were found in 1 male patient and 1 female patient, located in the bronchus and trachea, respectively. One MGA was examined by RNA sequencing, and no putative driver mutations (including BRAF, KRAS, and AKT1 mutations) or gene fusions were identified. In another case of MGA, V600E mutations of BRAF and E17K mutations of AKT1 were not detected by allele-specific real-time PCR or digital PCR, respectively. However, a gene expression analysis revealed that the MGA presented a specific RNA expression profile with multiple genes enriched in the salivary gland. The gene expression of NKX3.1 was significantly higher in the MGA case in comparison to normal control lungs (P < .001). We then examined NKX3.1 immunohistochemistry for 2 MGAs and 19 tumors of 5 other histologic types. NKX3.1 was positive in MGA (2/2, 100%), whereas all constituent cells, including mucinous cells, were negative for NKX3.1 in other histologic types (0%, 0/19). In normal lung tissue, NKX3.1 was positive for mucinous acinar cells of the bronchial glands. In conclusion, the gene expression profile, taken together with the histologic similarity between MGA and bronchial glands, and the preferred location of the tumors (proximal airways with submucosal glands) suggest that MGA is a neoplastic counterpart of mucinous bronchial glands. NKX3.1 immunohistochemistry can be a sensitive and specific ancillary marker that distinguishes MGA from other histologic mimics.