The intracellular Ca2+ channel TRPML3 is a PI3P effector that regulates autophagosome biogenesis.

Autophagy is a multiple fusion event, initiating with autophagosome formation and culminating with fusion with endo-lysosomes in a Ca2+-dependent manner. The source of Ca2+ and the molecular mechanism by which Ca2+ is provided for this process are not known. The intracellular Ca2+ permeable channel transient receptor potential mucolipin 3 (TRPML3) localizes in the autophagosome and interacts with the mammalian autophagy-related protein 8 (ATG8) homolog GATE16. Here, we show that lipid-regulated TRPML3 is the Ca2+ release channel in the phagophore that provides the Ca2+ necessary for autophagy progress. We generated a TRPML3-GCaMP6 fusion protein as a targeted reporter of TRPML3 compartment localization and channel function. Notably, TRPML3-GCaMP6 localized in the phagophores, the level of which increased in response to nutrient starvation. Importantly, phosphatidylinositol-3-phosphate (PI3P), an essential lipid for autophagosome formation, is a selective regulator of TRPML3. TRPML3 interacted with PI3P, which is a direct activator of TRPML3 current and Ca2+ release from the phagophore, to promote and increase autophagy. Inhibition of TRPML3 suppressed autophagy even in the presence of excess PI3P, while activation of TRPML3 reversed the autophagy inhibition caused by blocking PI3P. Moreover, disruption of the TRPML3-PI3P interaction abolished both TRPML3 activation by PI3P and the increase in autophagy. Taken together, these results reveal that TRPML3 is a downstream effector of PI3P and a key regulator of autophagy. Activation of TRPML3 by PI3P is the critical step providing Ca2+ from the phagophore for the fusion process, which is essential for autophagosome biogenesis.

Augmented interpretation of HER2, ER, and PR in breast cancer by artificial intelligence analyzer: enhancing interobserver agreement through a reader study of 201 cases.

BACKGROUND: Accurate classification of breast cancer molecular subtypes is crucial in determining treatment strategies and predicting clinical outcomes. This classification largely depends on the assessment of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) status. However, variability in interpretation among pathologists pose challenges to the accuracy of this classification. This study evaluates the role of artificial intelligence (AI) in enhancing the consistency of these evaluations. METHODS: AI-powered HER2 and ER/PR analyzers, consisting of cell and tissue models, were developed using 1,259 HER2, 744 ER, and 466 PR-stained immunohistochemistry (IHC) whole-slide images of breast cancer. External validation cohort comprising HER2, ER, and PR IHCs of 201 breast cancer cases were analyzed with these AI-powered analyzers. Three board-certified pathologists independently assessed these cases without AI annotation. Then, cases with differing interpretations between pathologists and the AI analyzer were revisited with AI assistance, focusing on evaluating the influence of AI assistance on the concordance among pathologists during the revised evaluation compared to the initial assessment. RESULTS: Reevaluation was required in 61 (30.3%), 42 (20.9%), and 80 (39.8%) of HER2, in 15 (7.5%), 17 (8.5%), and 11 (5.5%) of ER, and in 26 (12.9%), 24 (11.9%), and 28 (13.9%) of PR evaluations by the pathologists, respectively. Compared to initial interpretations, the assistance of AI led to a notable increase in the agreement among three pathologists on the status of HER2 (from 49.3 to 74.1%, p < 0.001), ER (from 93.0 to 96.5%, p = 0.096), and PR (from 84.6 to 91.5%, p = 0.006). This improvement was especially evident in cases of HER2 2+ and 1+, where the concordance significantly increased from 46.2 to 68.4% and from 26.5 to 70.7%, respectively. Consequently, a refinement in the classification of breast cancer molecular subtypes (from 58.2 to 78.6%, p < 0.001) was achieved with AI assistance. CONCLUSIONS: This study underscores the significant role of AI analyzers in improving pathologists' concordance in the classification of breast cancer molecular subtypes.

Microchanneling and ultrasonic delivery of gold and platinum nanoparticles for selective photothermolysis of sebaceous follicles in the treatment of acne: a pilot study using porcine skin.

PURPOSE: Several treatment options for acne vulgaris are limited by their associated adverse effects. An innovative approach involves introducing light-absorbing nanoparticles into sebaceous follicles before destroying the follicles using selective photothermolysis. We aimed to investigate efficient methods for introducing gold and platinum nanoparticles into sebaceous follicles and to identify suitable laser equipment and parameters for the effective destruction of these follicles. METHODS: We used porcine skin as the experimental model. We compared the efficacies of a thulium laser, ultrasound, and manual massage and evaluated the optimal method for delivering nanoparticles in close proximity to sebaceous follicles. Subsequently, a 1064-nm-wavelength neodymium-doped yttrium aluminum garnet (Nd: YAG) laser was employed to induce selective photothermolysis. We compared different parameters to identify the optimal pulse duration and fluence of the Nd: YAG laser. The extent of penetration and destruction of sebaceous follicles was assessed using hematoxylin and eosin (H&E) staining, and a numerical evaluation was conducted. RESULTS: H&E staining showed that irradiation with a long-pulsed Nd: YAG laser following a combination of thulium laser and sonophoresis effectively destroyed sebaceous follicles, with destruction rates exceeding 50%. These results were valid with a long pulse duration and a high fluence of the Nd: YAG laser. CONCLUSION: This study demonstrated that sebaceous follicles can be effectively destroyed through a mixture of gold and platinum nanoparticle delivery by a combination of microchanneling and sonophoresis, followed by selective thermal damage induced by a 1064-nm long-pulsed high-fluence Nd: YAG laser.

Proximal dendritic localization of NALCN channels underlies tonic and burst firing in nigral dopaminergic neurons.

In multipolar nigral dopamine (DA) neurons, the highly excitable proximal dendritic compartments (PDCs) and two Na+ -permeable leak channels, TRPC3 and NALCN, play a key role in pacemaking. However, the causal link between them is unknown. Here we report that the proximal dendritic localization of NALCN underlies pacemaking and burst firing in DA neurons. Our morphological analysis of nigral DA neurons reveals that TRPC3 is ubiquitously expressed in the whole somatodendritic compartment, but NALCN is localized within the PDCs. Blocking either TRPC3 or NALCN channels abolished pacemaking. However, only blocking NALCN, not TRPC3, degraded burst discharges. Furthermore, local glutamate uncaging readily induced burst discharges within the PDCs, compared with other parts of the neuron, and NALCN channel inhibition dissipated burst generation, indicating the importance of NALCN to the high excitability of PDCs. Therefore, we conclude that PDCs serve as a common base for tonic and burst firing in nigral DA neurons. KEY POINTS: Midbrain dopamine (DA) neurons are slow pacemakers that can generate tonic and burst firings, and the highly excitable proximal dendritic compartments (PDCs) and two Na+ -permeable leak channels, TRPC3 and NALCN, play a key role in pacemaking. We find that slow tonic firing depends on the basal activity of both the NALCN and TRPC3 channels, but that burst firing does not require TRPC3 channels but relies only on NALCN channels. We find that TRPC3 is ubiquitously expressed in the entire somatodendritic compartment, but that NALCN exists only within the PDCs in nigral DA neurons. We show that NALCN channel localization confers high excitability on PDCs and is essential for burst generation in nigral DA neurons. These results suggest that PDCs serve as a common base for tonic and burst firing in nigral DA neurons.

Idiopathic Myointimal Hyperplasia of the Mesenteric Veins Is a Peculiar Venous Ischemia That May Be Diagnosed Before Surgery.

BACKGROUND: Idiopathic myointimal hyperplasia of the mesenteric veins is a segmental ischemia associated with noninflammatory hyperplasia of the intimal smooth muscle of the mesenteric veins. Owing to its rarity, timely diagnosis is often difficult. OBJECTIVE: The goal of this study was to improve clinical practice in terms of the diagnosis of idiopathic myointimal hyperplasia of the mesenteric veins. DESIGN: This was a retrospective observational study. SETTINGS: This study was conducted in a single institution with case collection from clinical archives. PATIENTS: Data from 12 cases of idiopathic myointimal hyperplasia of the mesenteric veins were retrieved from 2006-2020. Most patients were elderly men, with a male-to-female ratio of 10:1. MAIN OUTCOME MEASURES: Clinical, endoscopic, radiologic, and pathologic characteristics of idiopathic myointimal hyperplasia of the mesenteric veins served as outcome measures. RESULTS: Radiologically, marked segmental mural thickening and poor enhancement involved the sigmoid colon and rectum in most cases, with extension to the descending colon in some cases. Typical cases showed obliteration of the inferior mesenteric veins and collateral vessels. Colonoscopic findings were reminiscent of ischemia or ulcerative colitis, but sharp demarcation from the uninvolved segment was the most distinguishing feature. Surgically resected specimens showed marked segmental mural thickening, edema, and mucosal discoloration grossly. Microscopically, thick-walled, tortuous veins were observed mainly in the submucosa and subserosa, and the submucosa was markedly thickened in all cases. The subserosal large veins showed myointimal hyperplasia, and pericolic fat necrosis was invariably observed. The most useful histologic finding in biopsy material was tortuous, arteriolized mucosal capillaries with occasional fibrinoid necrosis. LIMITATIONS: This study was limited by its small number of cases and selection bias; there was also no prospective external validation. CONCLUSIONS: Radiologic and pathologic features of idiopathic myointimal hyperplasia of the mesenteric veins are distinct from those of ulcerative colitis or nonspecific ischemic colitis. Careful interpretation of endoscopic and radiologic images and generous biopsies with interpretation by experienced pathologists might lead to an early diagnosis and prevent unnecessary medical treatment. See Video Abstract at http://links.lww.com/DCR/B806. LA HIPERPLASIA MIOINTIMAL IDIOPTICA DE LAS VENAS MESENTRICAS ES UNA PECULIAR ISQUEMIA VENOSA QUE PUEDE DIAGNOSTICARSE ANTES DE LA CIRUGA: ANTECEDENTES:La hiperplasia miointimal idiopática de las venas mesentéricas es una isquemia segmentaria asociada con hiperplasia no inflamatoria del músculo liso de la íntima de las venas mesentéricas. Debido a su rareza, el diagnóstico oportuno suele ser difícil.OBJETIVO:Mejorar la práctica clínica con respecto al diagnóstico de hiperplasia miointimal idiopática de venas mesentéricas.DISEÑO:Estudio observacional retrospectivo.AJUSTES:Institución única, colección de casos de archivos clínicos.PACIENTES:Se recuperaron datos de 12 casos de hiperplasia miointimal idiopática de las venas mesentéricas durante el período 2006-2020. La mayoría de los pacientes eran hombres de edad avanzada, con una proporción de hombres a mujeres de 10:1.PRINCIPALES MEDIDAS DE RESULTADO:Características clínicas, endoscópicas, radiológicas y patológicas de la hiperplasia miointimal idiopática de las venas mesentéricas.RESULTADOS:Radiológicamente, se vio marcado engrosamiento mural afectando de manera segmentaria y escaso realce que comprometieron al colon sigmoides y al recto en la mayoría de los casos, con extensión al colon descendente en algunos casos. Los casos típicos mostraron obliteración de las venas mesentéricas inferiores y vasos colaterales. Los hallazgos colonoscópicos recordaban a la isquemia o la colitis ulcerosa, pero la demarcación nítida del segmento no afectado fue la característica más distintiva. Las piezas quirúrgicas mostraron un marcado engrosamiento mural de manera segmentaria, edema y decoloración de la mucosa de forma macroscópica. Microscópicamente, se observaron venas tortuosas de paredes engrosadas principalmente en la submucosa y subserosa y la submucosa se encontraba marcadamente engrosada en todos los casos. Las grandes venas subserosas mostraban hiperplasia de la mioíntima e invariablemente se observaba necrosis grasa pericólica. El hallazgo histológico más útil en el material de biopsia fueron los tortuosos capilares arteriolizados de la mucosa con necrosis fibrinoide ocasional.LIMITACIONES:Pequeño número de casos; sesgo de selección; sin validación externa prospectiva.CONCLUSIONES:Las características radiológicas y patológicas de la hiperplasia miointimal idiopática de las venas mesentéricas son distintas a las de la colitis ulcerosa o la colitis isquémica no específica. La interpretación cuidadosa de las imágenes endoscópicas y radiológicas y múltiples biopsias de manera generosa con la interpretación de patólogos experimentados pueden conducir a un diagnóstico temprano y prevenir tratamientos médicos innecesarios. Consulte Video Resumen en http://links.lww.com/DCR/B806. (Traducción-Dr Osvaldo Gauto).

Ovarian mass combined with pancreatic neoplasm in pregnancy: A rare case report and literature review.

A 35-year-old woman presented with abdominal discomfort at 26 weeks gestation. The magnetic resonance imaging demonstrated a huge unilocular cystic mass with mural nodules originated from body and tail of pancreas. There was also a cystic mass in the left ovary with suppressed intensity on fat saturated image. One week later, she complained of worsening left lower abdominal pain and dyspnea as a new symptom. Hence, distal pancreatectomy with splenectomy and left ovarian cystectomy were performed. The huge cystic mass of pancreas was compressing the diaphragm, and left tubo-ovarian torsion was observed. This is the second case wherein an MCN of the pancreas with mature cystic teratoma of the ovary caused different symptoms. The management of MCNs in pregnant women should consider multiple aspects such as the malignancy potential of imaging findings, severity of symptoms, and fetal well-being.

Distribution pattern of tumor infiltrating lymphocytes and tumor microenvironment composition as prognostic indicators in anorectal malignant melanoma.

Anorectal malignant melanoma (ARMM) is a rare disease with poor prognosis. Determining ARMM prognosis precisely is difficult due to the lack of proper assessment techniques. Immunotherapy has proven effective against cutaneous malignant melanoma and may show efficacy in ARMM. Herein, we assessed the immune profile of ARMM to identify possible prognostic biomarkers. Twenty-two ARMM formalin-fixed and paraffin-embedded samples were evaluated using an nCounter® PanCancer Immune Profiling Panel. Validation was performed through immunohistochemical staining for CD3, CD8, Foxp3, CD68, CD163, and PD-L1. RNA analysis revealed significantly decreased scores for pathways involved in cell regulation and function, as well as chemokines, in recurrent patients compared to nonrecurrent patients. In cell-type profiling, the recurrent cases displayed significantly low tumor infiltrating lymphocyte (TIL) scores. Recurrence/death prediction models were defined using logistic regression and showed significantly lower scores in recurrent and deceased patients (all, P < 0.001) compared to those in nonrecurrent and surviving patients. The high total TIL and tumor-associated macrophage (TAM) groups had significantly better overall survival outcomes compared to the low total TIL and TAM groups (P = 0.007 and P = 0.035, respectively). In addition, the presence of CD3 + TILs in the invasion front was an independent favorable prognostic indicator (P = 0.003, hazard ratio = 0.21, 95% confidential interval, 0.01-0.41). Patients with inflamed or brisk-infiltration type tumors also had a significantly better overall survival than that of patients with immune-desert/excluded and absent/non-brisk type tumors (P = 0.03 and P = 0.0023, respectively). In conclusion, TILs have a strong prognostic value in ARMM, and the quantification of TILs and an analysis of the TIL phenotype and infiltration pattern during pathological diagnosis are essential to guide treatment strategies and accurate prognosis in ARMM.

Expression of the immune checkpoint molecule V-set immunoglobulin domain-containing 4 is associated with poor prognosis in patients with advanced gastric cancer.

BACKGROUND: Recent clinical studies on immune checkpoint (IC) inhibitors in the context of advanced gastric cancer (AGC) have failed to show significant survival benefits but have suggested the possible role of IC inhibitors in anti-AGC immunity. Considering the low efficacy of targeted drugs in AGC, there is an urgent need for the discovery of new targets for the development of immunotherapeutics and prognostic markers for patient selection. This study aimed to investigate the expression of a new IC molecule, V-set Ig domain-containing 4 (VSIG4), and its clinical significance in AGC and other major cancers. METHODS: We analyzed the expression of VSIG4 and its correlation with survival in various carcinomas, including 882 surgically resected samples from patients with stage II-III AGC (two academic hospitals). RESULTS: VSIG4 positivity in AGC was significantly associated with overall survival (OS; Hazard ratio (HR) = 2.661, 95% confidence interval [CI] = 2.012-3.519, P < 0.001) and event-free survival (HR = 2.8, 95% CI = 2.18-3.72, P < 0.001). These findings were successfully validated in independent cohorts. VSIG4 expression was also significantly correlated with low intratumoral CD8 + T-cell infiltration (CD8i) (P = 0.029) and high Foxp3 + /CD8i ratio (P = 0.026), which is consistent with the previously reported immunological function of VSIG4. However, VSIG4 expression was not associated with survival in other cancers (colon, P = 0.459; lung, P = 0.275; kidney, P = 0.121; breast, P = 0.147). CONCLUSION: Our results suggest that VSIG4 is an independent prognostic factor in AGC and also implies that VSIG4 is a second-tier IC molecule in AGC, thus, providing an important basis for the development of gastric cancer-specific immunotherapeutics.

Lymphoepithelioma-like carcinoma of the vagina: A rare case report and review of the literature.

A 78-year-old woman with the chief complaint of vaginal bleeding was referred to our institution. Pelvic magnetic resonance imaging showed a 2.1 cm × 2.0 cm soft tissue mass in the left vaginal area with left inguinal lymph node enlargement. A positron emission tomography/computer tomography scan showed a focal hypermetabolic lesion in the left vaginal area with involvement of vulvar area. Pelvic examination showed a vaginal wall mass and the patient underwent surgical excision of the mass. The results of pathology indicated lymphoepithelioma-like carcinoma (LELC) in the vagina. The patient was admitted subsequently in the oncological department for additional chemoradiation treatment. LELC is extremely rare in the vagina, and only three cases have been reported in the literature. Here we report an extremely rare case of this tumor and review of the previous literature.

Tracheitis Caused by Coinfection with Cytomegalovirus and Herpes Simplex Virus.

Clinically significant isolated viral tracheitis is scarce in adults, and upper airway obstruction caused by viral tracheitis is even more infrequent. A 74-year-old woman, who was administered low-dose steroids for two months for chronic obstructive pulmonary disease (COPD), developed dyspnea with stridor and required mechanical ventilation for respiratory failure. Chest computed tomography showed a diffuse tracheal wall thickening with luminal narrowing and peribronchial consolidation in the right upper lobe. Bronchoscopy revealed a proximal tracheal narrowing with multiple ulcerations of the tracheal mucosa surrounded by an erythematous margin. Pathologic examinations of the tracheal mucosal tissue, including immunohistochemistry, revealed a cytomegalovirus (CMV) and herpes simplex virus (HSV) infection. Furthermore, the bronchial alveolar lavage fluid was positive on the CMV real-time polymerase chain reaction. The patient was treated with intravenous ganciclovir for 44 days. The follow-up bronchoscopy 49 days after the initiation of ganciclovir revealed improved multiple ulcerations with scars. We report a rare case of tracheitis caused by coinfection with CMV and HSV in a patient with COPD who had been taking low-dose steroids for months. The case showed that CMV and HSV are potential causes of serious tracheitis and respiratory failure.

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

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

Detailed pathological analysis of the advancing edge of the tumour can effectively stratify clinical T4b colorectal cancer patients.

AIMS: Pathological staging of colorectal cancers (CRCs) that involve adhesion to adjacent organs (clinical stages T4b, cT4b) is sometimes difficult because the morphology of the invasive front varies. To resolve this issue, we reviewed 492 surgically resected CRC samples, comprising 96 cT4b tumours and, for comparison, 335 typical pathological stages (p) T3 and 61 pT4a tumours. METHODS AND RESULTS: Cases were subdivided into four groups according to the presence or absence of microscopic tumour invasion into the muscular wall of the adjacent organs and peritumoral abscess along invasive front. Those that directly invaded the wall of the adjacent organs without peritumoral abscess were associated with a significantly worse overall (OS) and recurrence-free survival (RFS) than the other three types of cT4b tumours. Those with peritumoral abscess showed similar prognosis to typical pT3 tumours, even when the advancing edge of the tumour invaded the wall of adjacent organs (staged as pT4b). Tumours showing fibrous adhesions without tumour cell invasion into the muscular wall of the adjacent organs showed a similar prognosis to typical pT3 tumours and showed a better prognosis than pT4a tumours. CONCLUSION: Only CRCs with tumour cell invasion into the muscular wall of the adjacent organs should be classified as pT4b, and it might be better to avoid 'the presence of tumour cells in fibrous adhesion' to define pathological T4b CRCs. In addition, the presence of a peritumoral abscess should be recorded as a predictor of better prognosis.

JOURNAL CLUB: Primary Anorectal Melanoma: MRI Findings and Clinicopathologic Correlations.

OBJECTIVE: The purpose of this study is to evaluate the MRI features of primary anorectal malignant melanoma and to correlate these features with its clinical and pathologic characteristics. MATERIALS AND METHODS: The medical records of 12 patients (five men and seven women; mean age [± SD], 60.8 ± 10.0 years) with pathologically proven primary anorectal melanoma were retrospectively reviewed. MRI findings were analyzed to determine the shape, size, distance from the anal verge, presence of perirectal or anal infiltration, signal intensity on T1- and T2-weighted images, presence of diffusion restriction, contrast enhancement pattern of the lesion, presence of lymphadenopathy, and occurrence of bowel obstruction. Subsequent follow-up data for the patients were recorded. RESULTS: The most common presentation was hematochezia (41.7% of patients). Common findings on MRI included a large intraluminal polypoid mass (75.0% of lesions) with little perirectal or anal infiltration (100.0%), T1 hyperintensity (66.7%), high T2 signal intensity (54.5%) or mixed T2 signal intensity (45.5%), restricted diffusion (100.0%), and hyper-enhancement (100.0%). The mean length, width, and depth of these masses were 3.5, 2.9, and 2.3 cm, respectively. The mean distance from the anal verge was 1.8 cm. Lymphadenopathy was frequently identified (75.0% of cases), with lymph nodes larger than 2 cm noted in 28.5% of cases and most commonly involving the perirectal area (77.8% of cases). No colonic obstructions were observed. The mean patient follow-up was 32.7 months. A total of 25.0% of patients died as a result of disease progression. CONCLUSION: The possibility of the presence of anorectal melanoma should be considered for patients with a bulky intraluminal polypoid mass in the anorectum without colonic obstruction, with the mass showing T1 hyperintensity, high or mixed signal T2 intensity, hyperenhancement, minimal perirectal or anal infiltration, and lymphadenopathy.

Coexistence of Colorectal Cancer and Immunoglobulin G4-Related Disease in the Same Lesion: A Rare Case with Molecular Classification.

Immunoglobulin G4-related disease (IgG4-RD) is a novel fibroinflammatory disorder characterized by enlargement of the involved organs, elevated IgG4 levels, and abundant infiltration of IgG4-positive plasma cells. Indeed, primary colon cancers arising from IgG4-RD are rare. This case report describes a rare occurrence of simultaneous colorectal cancer and IgG4-RD in the same lesion in a 62-year-old male patient. The patient underwent a right hemicolectomy under the suspicion of primary colon cancer. The mass was grossly well-defined and yellowish tan, and the background colon was fibrotic. Microscopically, the tumor cells showed glandular differentiation characteristic of adenocarcinoma in a background of dense lymphoplasmacytic infiltration with fibrosis and obliterative phlebitis in the pericolic fat tissue. IgG4 immunohistochemical staining showed diffuse positivity in infiltrating plasma cells. The patient was administered adjuvant chemotherapy and prednisolone therapy. The patient's serum IgG4 levels gradually decreased, and a follow-up positron emission tomography-computed tomography scan 1 year after surgery showed no evidence of local or distant recurrence of colorectal cancer. IgG4-RD occurring concurrently with primary colon adenocarcinoma has not been reported. Increased awareness of this rare coexistence can guide clinicians in navigating diagnostic complexities and selecting optimal therapeutic strategies.

Cytological Features of Fibrin-associated Diffuse Large B-cell Lymphoma Arising in Retroperitoneal Pseudocyst: The First Case Report.

BACKGROUND/AIM: Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is frequently associated with the Epstein-Barr virus (EBV) and manifests as non-mass-forming microscopic lesions within fibrin-rich lesions. Herein, we describe the cytological features of FA-DLBCL. CASE REPORT: A 72-year-old man presented with a large retroperitoneal cystic mass that was treated by cyst aspiration and laparoscopic excision. Individually dispersed large, atypical cells in a necrotic background contained scant cytoplasm and hyperchromatic nuclei with irregular nuclear contours, frequent karyorrhectic debris, and mitotic figures. A fibrinous exudate with necrotic material attached to the inner surface of the cystic mass contained large, atypical cells that were individually scattered or arranged in small clusters. These were positive for cluster of differentiation 20 and Epstein-Barr virus-encoded RNA in situ hybridization. CONCLUSION: We cytologically characterized FA-DLBCL as large, atypical cells that were individually scattered or arranged in small clusters in a necrotic background. To the best of our knowledge, we revealed the cytological features of FA-DLBCL.

Comparative Study on the Clinicopathologic and Molecular Characteristics of Primary and Secondary Diffuse Large B-cell Lymphoma in the Central Nervous System.

BACKGROUND/AIM: Diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) is an aggressive B-cell lymphoma with clinical and molecular heterogeneity. Primary CNS-DLBCL (PCNSL) affects the brain, eyes, leptomeninges, or spinal cord without systemic involvement. Secondary CNS-DLBCL (SCNSL) manifests concurrently with systemic lymphoma or as an isolated CNS relapse with poor prognosis. MATERIALS AND METHODS: Next-generation sequencing (NGS) was used to identify genomic alterations in 32 PCNSL and 9 SCNSL cases. Single nucleotide variants and copy number variations in addition to the clinicopathologic data and proposed risk predictive values were compared to aid in diagnostic differentiation between the two types of lymphomas. RESULTS: The MCD genotype, characterized by mutations in MYD88 and CD79B, is the most common alteration in PCNSL and is associated with lower survival rates. The frequency of MYD88 mutation was significantly higher in PCNSL compared to SCNSL (75.0% vs. 33.3%; p=0.042). Recurrent copy number loss of 6p21 occurred in 56.1% of cases, more often in PCNSL (65.6%) than in SCNSL (22.2%) (p=0.028). Diagnostic positive predictive values (PPV) of MYD88 mutation and 6p21 loss for PCNSL were 89% and 91%, respectively. PPV of both alterations was 93% for the diagnosis of PCNSL. CONCLUSION: MYD88 mutation and 6p21 loss were significantly higher in PCNSL than in SCNSL, and novel risk prediction models based on these distinct genomic profiles can aid in the clinical differentiation of PCNSL and SCNSL.

A 42-year-old patient with renal cell carcinoma presenting as low back pain: A case report.

RATIONALE: Renal cell carcinoma (RCC) is the most common renal neoplasm, accounting for 2.4% of all cancers in Korea. Although the usual clinical manifestations of RCC include flank pain, hematuria, and palpable mass, RCC is generally characterized by a lack of early warning signs and is mostly discovered incidentally in advanced stage. This case report describes a 42-year-old Korean man diagnosed with giant RCC who presented with simple back pain. PATIENT CONCERNS: The clinical manifestation of a 42-year-old Korean man was chronic back pain. DIAGNOSES: Contrast-enhanced computed tomography showed a 19.1-cm sized heterogeneous enhancing mass on the right kidney and tumor thrombosis extending into inferior vena cava. INTERVENTION: Due to the large size of the tumor and extensive tumor thrombosis, the multidisciplinary team decided to administer neoadjuvant chemotherapy and an anticoagulant. Following 12 cycles of treatment with nivolumab and cabozantinib, he underwent a right radical nephrectomy with an adrenalectomy and tumor thrombectomy. OUTCOMES: Treatment was successful and posttreatment he started a cancer rehabilitation program. He was followed-up as an outpatient and no longer complains of back pain. LESSONS: RCC can manifest clinically as back pain, with diagnosis being difficult without appropriate imaging modalities. RCC should be included in the differential diagnosis of patients with low back pain, even at a young age.

Combination of GATA3, SOX-10, and PAX8 in a Comprehensive Panel to Diagnose Breast Cancer Metastases.

BACKGROUND/AIM: It can be difficult to establish the origin of a tumor in metastatic breast cancer (MBC), especially with triple-negative breast cancer (TNBC) or high-grade features. We evaluated the diagnostic utility of GATA3, SOX10, and PAX8 panels in MBC by comparing their expression in each molecular subtype of MBC. PATIENTS AND METHODS: We evaluated 84 MBC and 37 primary TNBC cases using GATA3, SOX10, and PAX8 staining in whole tissue sections. RESULTS: GATA3 was least sensitive in the detection of metastatic TNBC (metastatic non-TNBC, 0.95; metastatic TNBC, 0.37). SOX10 had the lowest overall sensitivity (0.12) but was elevated in metastatic TNBC, even higher than GATA3 (0.59 vs. 0.37). The combination of GATA3, SOX10, and PAX8 expression showed the highest detection rate (MBC, 0.94; metastatic non-TNBC, 0.95; metastatic TNBC, 0.93). CONCLUSION: We recommend combining GATA3, SOX10, PAX8 expression profiling to confirm breast as the site of origin in metastatic MBC.

Unusual cause of gastric outlet obstruction mimicking superior mesenteric artery syndrome: A case of infiltrative duodenal cancer arising from a choledochocele.

Choledochocele is a rare subtype of choledochal cyst and is associated with increased prevalence of periampullary cancers. Here, we report an unusual manifestation of infiltrative duodenal cancer arising from a choledochocele, involving superficial spreading (muscularis mucosae) of cancer cells along the duodenum causing gastric outlet obstruction, which clinically mimicked superior mesenteric artery syndrome. Histologically, wide spread of cancer cells was confirmed from periampullary region to duodenojejunal junction showing mismatch with radiologic findings, in which the cancer segment was mainly located in the distal duodenum. Clinical, radiologic, and pathologic findings are discussed with literature reviews.