Anti-C5 monoclonal antibody treatment showing pathological resolution of complement-mediated atypical hemolytic uremic syndrome: a case report.

BACKGROUND: No reports have shown histological changes before and after anti-C5 monoclonal antibody treatment in patients with atypical hemolytic uremic syndrome (aHUS). Here, we report a rare case of complement-mediated aHUS with a complement factor H (CFH) mutation and anti-CFH antibodies who underwent multiple kidney biopsies. CASE PRESENTATION: A 53-year-old woman developed aHUS with CFH gene mutation [c.3572C > T (p. Ser1191 Leu)] and anti-CFH antibodies. Her father had succumbed to acute kidney injury (AKI) in his 30 s. She exhibited AKI, thrombocytopenia, and hemolytic anemia with schistocytes. After improving the platelet count with one session of plasma exchange, a kidney biopsy was performed one month after the onset of symptoms. Blood vessel thrombosis, obvious endothelial swelling, endocapillary hypercellularity, and subendothelial exudative lesions in the glomeruli and arterioles were detected. Anti-C5 monoclonal antibody treatment with eculizumab immediately improved disease activity. A second biopsy 3 months later revealed marked improvement of endothelial injuries with residual membrane double contours and exudative lesions. A third biopsy at 17 months after gradual improvement of kidney function showed a further decrease of double contours along with alterations of the exudative lesions to fibrous intimal thickening. CONCLUSIONS: This is the first report showing the pathophysiology of aHUS in the kidneys and the efficacy of anti-C5 monoclonal antibody treatment by presenting serial kidney pathological features before and after anti-C5 monoclonal antibody treatment. Since her CFH mutation was considered the most important pathological condition, treatment centered on eculizumab was administered, resulting in a good long-term prognosis. In addition, kidney pathological resolution in aHUS occurred over 1 year after anti-C5 monoclonal antibody treatment.

Heterozygous missense variant in TRPC6 in a boy with rapidly progressive infantile nephrotic syndrome associated with diffuse mesangial sclerosis.

Transient receptor potential channel C6 encoded by TRPC6 is involved in slit diaphragm formation in podocytes, and abnormalities of the TRPC6 protein cause various glomerular diseases. The first identified pathogenic variant of TRPC6 was found to cause steroid-resistant nephrotic syndrome that typically developed in adulthood and then slowly led to end-stage renal disease, along with a renal pathology of focal segmental glomerulosclerosis. Here, we report a patient with rapidly progressing infantile nephrotic syndrome and a heterozygous missense TRPC6 variant. The patient, a 2-year-old Japanese boy, developed steroid-resistant nephrotic syndrome at age 11 months. His renal function deteriorated rapidly, and peritoneal dialysis was introduced at age 1 year and 6 months. His renal pathology, obtained at age 1 year and 1 month, was consistent with diffuse mesangial sclerosis (DMS). Clinical exome analysis and custom panel analysis for hereditary renal diseases revealed a reported heterozygous missense variant in TRPC6 (NM_004621.5:c.523C > T:p.Arg175Trp). This is the first report of a patient with a TRPC6-related renal disorder associated with DMS.

Immune-complex glomerulonephritis with a membranoproliferative pattern in Frasier syndrome: a case report and review of the literature.

BACKGROUND: Mutations in the Wilms tumor 1 gene cause a spectrum of podocytopathy ranging from diffuse mesangial sclerosis to focal segmental glomerulosclerosis. In a considerable fraction of patients with Wilms tumor 1 mutations, the distinctive histology of immune-complex-type glomerulonephritis has been reported. However, the clinical relevance and etiologic mechanisms remain unknown. CASE PRESENTATION: A 5-year-old child presented with steroid-resistant nephrotic range proteinuria. Initial renal biopsy revealed predominant diffuse mesangial proliferation with a double-contour and coexisting milder changes of focal segmental glomerulosclerosis. Immunofluorescence and electron microscopy revealed a full-house-pattern deposition of immune complexes in the subendothelial and paramesangial areas. Serial biopsies at 6 and 8 years of age revealed that more remarkable changes of focal segmental glomerulosclerosis had developed on top of the initial proliferative glomerulonephritis. Identification of a de novo Wilms tumor 1 splice donor-site mutation in intron 9 (NM_024426.6:c.1447 + 4C > T) and 46,XY-gonadal dysgenesis led to the diagnosis of Frasier syndrome. CONCLUSIONS: Our findings, together with those of others, point to the importance of heterogeneity in clinicopathological phenotypes caused by Wilms tumor 1 mutations and suggest that immune-complex-mediated membranoproliferative glomerulopathy should be considered as a histological variant.

Usefulness of gastroduodenal biopsy in the differential diagnosis of systemic AH amyloidosis from systemic AL amyloidosis.

AIMS: The aim of this study is to examine the usefulness of gastroduodenal biopsy for the detection of immunoglobulin (Ig) heavy-chain amyloid deposition. Ig heavy-chain amyloidosis (AH amyloidosis) is Ig-related amyloidosis classified together with Ig light-chain amyloidosis (AL amyloidosis). Compared with AL amyloidosis, patients with AH amyloidosis exhibit a better prognosis and they may not need an aggressive treatment. Thus, the accurate diagnosis is essential for management of Ig-related amyloidosis patients. For the definite diagnosis of AH amyloidosis, biochemical analyses are usually needed. However, these analyses are not widely available. Therefore, the characteristic deposition pattern of AH amyloidosis in routine histopathological examination of biopsy specimens, such as gastrointestinal biopsy, if present, may help in the selection of cases for further biochemical analyses. METHODS AND RESULTS: Gastroduodenal biopsy specimens obtained from three cases of biochemically confirmed AH amyloidosis and 21 cases of immunohistochemically confirmed AL amyloidosis were examined, and the following distinctive histopathological features of AH amyloidosis were pointed out: (i) AH amyloid deposition was detectable with Congo red staining in the gastroduodenal biopsy specimens; and (ii) AH amyloid deposition was observed characteristically on the capillary wall of duodenal villi (dotted line-like deposition in the villi), and this pattern was not observed in AL amyloidosis. CONCLUSION: These findings help to select cases for biochemical analyses for definite diagnosis of AH amyloidosis, and may lead to the accumulation of cases and improve our understanding of systemic AH amyloidosis.

Chronic Pressure Overload Induces Cardiac Hypertrophy and Fibrosis via Increases in SGLT1 and IL-18 Gene Expression in Mice.

Increased gene expression levels of sodium-glucose cotransporter 1 (SGLT1) are associated with hypertrophic and ischemic cardiomyopathy. However, it remains unclear whether chronic pressure overload increases SGLT1 expression, which in turn induces hypertrophic cardiomyopathy. We hypothesized that pressure overload could increase SGLT1 gene expression, leading to the development of hypertrophic cardiomyopathy.To create pressure overload-induced cardiomyopathy, transverse aortic constriction (TAC) was performed in SGLT1-deficient (SGLT1-/-) and wild-type (WT) mice. Six weeks after surgery, all mice were investigated. We observed a reduction of left ventricular fractional shortening and left ventricular dilatation in TAC-operated WT but not in TAC-operated SGLT1-/- mice. SGLT1, interleukin 18, connective tissue growth factor, and collagen type 1 gene expression levels were increased in TAC-operated WT mouse hearts compared with that of sham-operated WT mouse hearts. Moreover, heart/body weight ratio and ventricular interstitial fibrosis were increased in TAC-operated WT mice compared with that of sham-operated WT mice. Interestingly, these factors did not increase in TAC-operated SGLT1-/- mice compared with that of sham-operated WT and SGLT1-/- mice. Phenylephrine, an adrenergic α1 receptor agonist, caused cardiomyocyte hypertrophy in neonatal WT mouse hearts to a significantly larger extent than in neonatal SGLT1-/- mouse hearts.In conclusion, the results indicate that chronic pressure overload increases SGLT1 and IL-18 gene expressions, leading to the development of hypertrophic cardiomyopathy. These results make SGLT1 a potential candidate for the therapeutic target for hypertension-induced cardiomyopathy.

Gastric gland mucin-specific O-glycan expression decreases with tumor progression from precursor lesions to pancreatic cancer.

Pancreatic cancer is lethal, as it is often detected late. Thus, novel biomarkers of precursor lesions are needed to devise timely therapies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) are major precursors of pancreatic cancer. In normal gastric mucosa, gastric gland mucin-specific O-glycans are unique in having α1,4-linked N-acetylglucosamine (αGlcNAc) residues attached to MUC6. Recently we reported that αGlcNAc functions as a tumor suppressor for differentiated-type gastric adenocarcinoma (Karasawa et al., J Clin Invest 122, 923, 2012). MUC6 is also expressed in pancreatic neoplasms, including PanIN and IPMN, but the role of αGlcNAc expression in pancreatic neoplasms remains unknown. Here, we analyze expression patterns of αGlcNAc, MUC6 and MUC5AC in pancreatic neoplasms and compare them with progression from PanIN to invasive ductal adenocarcinoma (IDAC) (the PanIN-IDAC sequence; 20 cases) and from IPMN to IPMN with associated invasive carcinoma (IPMNAIC) (the IPMN-IPMNAIC sequence; 20 cases). At both sequences, the frequency of MUC6-positive and αGlcNAc-positive lesions decreased with tumor progression. We then compared expression levels of αGlcNAc and MUC6 at each step of the progression. At the PanIN-IDAC sequence, αGlcNAc expression significantly decreased relative to MUC6 in low-grade PanIN (P = 0.021), high-grade PanIN/intraductal spread of IDAC (P = 0.031) and IDAC (P = 0.013). At the IPMN-IPMNAIC sequence, decreased αGlcNAc expression was also observed in low-grade IPMN exhibiting gastric-type morphology (P = 0.020). These results suggest that decreased expression of αGlcNAc relative to MUC6 occurs early and marks the initiation of tumor progression to pancreatic cancer.

Epithelioid trophoblastic tumor of the uterus: A case report with radiologic-pathologic correlation.

Herein, we report a rare case of an epithelioid trophoblastic tumor of the uterus with radiologic-pathologic correlation in a 56-year-old postmenopausal woman. On T2-weighted magnetic resonance (MR) imaging, the tumor appeared as a hypointense irregular mass compared with the surrounding myometrium of the uterine corpus and encircled the cavity of the lower uterine segment. On dynamic contrast-enhanced MR images, the tumor appeared as a hypovascular mass and an inhomogeneously hyperintense mass in the delayed phase. In addition, non-contrast computed tomography images showed some spotty areas of very high density within the tumor. These radiologic findings were well correlated with the histological features, such as abundant hyalinization and calcification within the tumor. Accurate interpretation of MR and computed tomography findings was helpful to differentiate epithelioid trophoblastic tumor from other gestational trophoblastic diseases and uterine carcinomas.

Tumour and immune cell dynamics explain the PSA bounce after prostate cancer brachytherapy.

BACKGROUND: Interstitial brachytherapy for localised prostate cancer may be followed by transient increases in prostate-specific antigen (PSA) that resolve without therapy. Such PSA bounces may be associated with an improved outcome but often cause alarm in the patient and physician, and have defied explanation. METHODS: We developed a mathematical model to capture the interactions between the tumour, radiation and anti-tumour immune response. The model was fitted to data from a large cohort of patients treated exclusively with interstitial brachytherapy. Immunohistological analysis for T-cell infiltration within the same tumours was also performed. RESULTS: Our minimal model captures well the dynamics of the tumour after therapy, and suggests that a strong anti-tumour immune response coupled with the therapeutic effect of radiation on the tumour is responsible for the PSA bounce. Patients who experience a PSA bounce had a higher density of CD3 and CD8 cells within the tumour that likely contribute to the PSA bounce and the overall better outcomes observed. CONCLUSIONS: Our observations provide a novel and unifying explanation for the PSA bounce in patients with early prostate cancer and also have implications for the use of immune-based therapies in such patients to improve outcomes.

Peroxisome proliferator-activated receptor α-dependent renoprotection of murine kidney by irbesartan.

Activation of renal peroxisome proliferator-activated receptor α (PPARα) is renoprotective, but there is no safe PPARα activator for patients with chronic kidney disease (CKD). Studies have reported that irbesartan (Irbe), an angiotensin II receptor blocker (ARB) widely prescribed for CKD, activates hepatic PPARα. However, Irbe's renal PPARα-activating effects and the role of PPARα signalling in the renoprotective effects of Irbe are unknown. Herein, these aspects were investigated in healthy kidneys of wild-type (WT) and Ppara-null (KO) mice and in the murine protein-overload nephropathy (PON) model respectively. The results were compared with those of losartan (Los), another ARB that does not activate PPARα. PPARα and its target gene expression were significantly increased only in the kidneys of Irbe-treated WT mice and not in KO or Los-treated mice, suggesting that the renal PPARα-activating effect was Irbe-specific. Irbe-treated-PON-WT mice exhibited decreased urine protein excretion, tubular injury, oxidative stress (OS), and pro-inflammatory and apoptosis-stimulating responses, and they exhibited maintenance of fatty acid metabolism. Furthermore, the expression of PPARα and that of its target mRNAs encoding proteins involved in OS, pro-inflammatory responses, apoptosis and fatty acid metabolism was maintained upon Irbe treatment. These renoprotective effects of Irbe were reversed by the PPARα antagonist MK886 and were not detected in Irbe-treated-PON-KO mice. These results suggest that Irbe activates renal PPARα and that the resultant increased PPARα signalling mediates its renoprotective effects.

Extensive lanthanum deposition in the gastric mucosa: the first histopathological report.

Lanthanum carbonate is one of the new phosphate binders used for the treatment of hyperphosphatemia in patients with chronic kidney disease. It is poorly absorbed from the gastrointestinal tract, forms insoluble complexes within the lumen, and prevents the absorption of dietary phosphate. A 63-year-old female with a 7-year history of peritoneal dialysis, who was treated with lanthanum carbonate for four years, underwent endoscopic submucosal dissection for intramucosal gastric cancer. Resected specimens showed massive accumulation of macrophages containing fine, granular, brown material in the lamina propria. This was confirmed as lanthanum deposition by scanning electron microscopy with energy dispersive x-ray spectroscopy. Although lanthanum may be poorly absorbed, increased tissue accumulation of lanthanum, particularly in the liver and bone, has been reported in animals with chronic kidney disease. This report indicates enhanced gastrointestinal absorption of lanthanum in some patients or conditions, although its clinical significance awaits further studies.

A case of podocytic infolding glomerulopathy with multiple myeloma.

BACKGROUND: Podocytic infolding glomerulopathy (PIG) is a recently described condition causing rare pathological changes to the glomeruli, and has attracted considerable attention. PIG is characterized by specific changes to the thickened glomerular basement membrane (GBM), including microspheres, microtubular structures, and podocytic infolding. Only a small number of cases of PIG have been reported. The clinical features and pathogenesis of this condition are still unclear. To elucidate the characteristics of this glomerulopathy, it is necessary to accumulate information from reported cases. We present here the first reported case of PIG with multiple myeloma. CASE PRESENTATION: A 79-year-old Japanese man was admitted to his local hospital with proteinuria, hypergammaglobulinemia, hypoalbuminemia, and kidney dysfunction. Laboratory tests revealed monoclonal IgG(λ) M proteins in the serum and Bence-Jones proteins in the urine. Bone marrow aspiration showed monoclonal plasma cell proliferation, indicating a diagnosis of multiple myeloma. Renal biopsy was performed to determine the cause of the proteinuria and kidney dysfunction. Histological examination of the biopsy specimen showed glomeruli with an irregularly thickened GBM and bubble-like structures in the capillary walls. Immunofluorescence staining did not show glomerular deposition of immunoglobulins, light chains, or complement components. Congo red staining did not show amyloid deposition. Electron microscopy showed an irregularly thickened GBM with unusual structures in the glomerular capillary walls including podocytic infolding and microspheres, suggesting PIG. There were no electron-dense deposits in the GBM, while various findings indicating podocyte injury were detected. CONCLUSION: We present here the first reported case of PIG in a patient with multiple myeloma. The mechanisms underlying the development of PIG in multiple myeloma are unknown, but may be associated with podocyte injury.

Synchronous ipsilateral carcinoma of the accessory mammary gland and primary lymphoma of the breast with subsequent rectal carcinoma: report of a case.

A case of synchronous carcinoma of the accessory mammary gland and primary breast lymphoma with subsequent rectal carcinoma has not been reported previously. We present a very rare case of primary non-Hodgkin lymphoma of the left breast diagnosed simultaneously with invasive lobular carcinoma of the left axillary accessory mammary gland and rectal adenocarcinoma. An 82-year-old Japanese woman presented with two palpable masses on the left chest wall. She was given a diagnosis of suspected breast malignant tumor and axillary accessory mammary gland. She underwent excision of the axillary accessory mammary gland and left mastectomy with axillary lymph node dissection. Histopathological examination revealed diffuse large B-cell lymphoma of the breast and invasive lobular carcinoma of the axillary accessory mammary gland with lymph nodes metastasis. Three months after the surgery, primary rectal adenocarcinoma was also detected by F-18 fluorodeoxyglucose positron emission tomography. Hartmann's operation was performed, since which time the patient has been doing well.

Chronic receptor-mediated activation of Gi/o proteins alters basal t-tubular and sarcolemmal L-type Ca²âº channel activity through phosphatases in heart failure.

L-type Ca(2+) channels (LTCCs) play an essential role in the excitation-contraction coupling of ventricular myocytes. We previously found that t-tubular (TT) LTCC current density was halved by the activation of protein phosphatase (PP)1 and/or PP2A, whereas surface sarcolemmal (SS) LTCC current density was increased by the inhibition of PP1 and/or PP2A activity in failing ventricular myocytes of mice chronically treated with isoproterenol (ISO mice). In the present study, we examined the possible involvement of inhibitory heterotrimeric G proteins (G(i/o)) in these abnormalities by chronically administrating pertussis toxin (PTX) to ISO mice (ISO + PTX mice). Compared with ISO mice, ISO + PTX mice exhibited significantly higher fractional shortening of the left ventricle. The expression level of Gα(i2) proteins was not altered by the treatment of mice with ISO and/or PTX. ISO + PTX myocytes had normal TT and SS LTCC current densities because they had higher and lower availability and/or open probability of TT and SS LTCCs than ISO myocytes, respectively. A selective PKA inhibitor, H-89, did not affect LTCC current densities in ISO + PTX myocytes. A selective PP2A inhibitor, fostriecin, did not affect SS or TT current density in control or ISO + PTX myocytes but significantly increased TT but not SS LTCC current density in ISO myocytes. These results indicate that chronic receptor-mediated activation of G(i/o) in vivo decreases basal TT LTCC activity by activating PP2A and increases basal SS LTCC activity by inhibiting PP1 without modulating PKA in heart failure.

Simultaneous nodular lymphocyte-predominant Hodgkin lymphoma with papillary thyroid carcinoma: a case report.

We herein report the case of a 48-year-old man diagnosed with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL, Stage IA) and papillary thyroid carcinoma (PTC, Stage I). Total thyroidectomy, left modified neck dissection and biopsy of the right cervical lymph node were performed. Postoperatively, NLPHL treatment was prioritized, and external radiation (30.6 Gy) was applied to the right neck. PTC was considered a high-risk category for recurrence due to extranodal invasion of lymph node metastasis, and radioactive iodine therapy (ablative dose, 1110 MBq) was administered. Both PTC and NLPHL showed no recurrence 18 months after surgery.

Reduced glycosylation of α-dystroglycans on carcinoma cells contributes to formation of highly infiltrative histological patterns in prostate cancer.

BACKGROUND: α-Dystroglycan (DG) carries glycan chains that bind to laminin and thus function in homeostasis of not only skeletal muscle but also of various epithelial cells. Loss of glycosylation has been suggested to play important roles in tumor development, particularly in detachment and migration of carcinoma cells. We previously reported that glycosylation of α-DG, but not levels of α-DG core protein itself, is reduced in prostate carcinoma. In this study, we investigate the association between reduction of laminin-binding glycans on α-DG and the degree of tumor cell differentiation and/or infiltrative properties, as assessed by the Gleason grading system. METHODS: Immunohistochemical analysis of 146 biopsy specimens of prostate adenocarcinoma with various Gleason scores was carried out employing IIH6 and 6C1 antibodies, which recognize laminin-binding glycans on α-DG and α-DG core proteins, respectively. Double immunofluorescence staining was performed to evaluate colocalization of α-DG and laminin, and to determine which types of epithelial cells express laminin-binding glycans on α-DG. RESULTS: Reduction of α-DG glycosylation, rather than loss of α-DG core protein, was correlated with higher Gleason patterns. Reduction was most conspicuous at the interface between carcinoma cells and the basement membrane. In addition, in non-neoplastic prostate glands, laminin-binding glycans were expressed predominantly on the basolateral surface of basal cells. CONCLUSIONS: Reduced expression of laminin-binding glycans on α-DG may contribute to formation of highly infiltrative behavior of prostate carcinoma cells. Substantial reduction of laminin-binding glycans in carcinoma tissue could be partly ascribed to disappearance of pre-existing basal cells.

Decrease in the density of t-tubular L-type Ca2+ channel currents in failing ventricular myocytes.

In some forms of cardiac hypertrophy and failure, the gain of Ca(2+)-induced Ca(2+) release [CICR; i.e., the amount of Ca(2+) released from the sarcoplasmic reticulum normalized to Ca(2+) influx through L-type Ca(2+) channels (LTCCs)] decreases despite the normal whole cell LTCC current density, ryanodine receptor number, and sarcoplasmic reticulum Ca(2+) content. This decrease in CICR gain has been proposed to arise from a change in dyad architecture or derangement of the t-tubular (TT) structure. However, the activity of surface sarcolemmal LTCCs has been reported to increase despite the unaltered whole cell LTCC current density in failing human ventricular myocytes, indicating that the "decreased CICR gain" may reflect a decrease in the TT LTCC current density in heart failure. Thus, we analyzed LTCC currents of failing ventricular myocytes of mice chronically treated with isoproterenol (Iso). Although Iso-treated mice exhibited intact t-tubules and normal LTCC subunit expression, acute occlusion of t-tubules of isolated ventricular myocytes with osmotic shock (detubulation) revealed that the TT LTCC current density was halved in Iso-treated versus control myocytes. Pharmacological analysis indicated that kinases other than PKA or Ca(2+)/calmodulin-dependent protein kinase II insufficiently activated, whereas protein phosphatase 1/2A excessively suppressed, TT LTCCs in Iso-treated versus control myocytes. These results indicate that excessive ß-adrenergic stimulation causes the decrease in TT LTCC current density by altering the regulation of TT LTCCs by protein kinases and phosphatases in heart failure. This phenomenon might underlie the decreased CICR gain in heart failure.

Diacylglycerol kinase ζ inhibits ventricular tachyarrhythmias in a mouse model of heart failure.

BACKGROUND: Diacylglycerol kinase ζ (DGKζ) inhibited atrial tachyarrhythmias in a mouse model of heart failure (HF) in our study. However, whether DGKζ prevents the HF-induced ventricular tachyarrhythmia (VT) is unknown. METHODS AND RESULTS: Effects of DGKζ on VT using transgenic mice with transient cardiac expression of activated G protein α(q) (Gα(q)-TG; model of HF) were elucidated and double transgenic mice with cardiac-specific overexpression of both DGKζ and the activated Gα(q) (Gα(q)/DGKζ-TG) were used. Premature ventricular contraction (PVC) and/or VT were frequently observed in Gα(q)-TG mice but not in Gα(q)/DGKζ-TG and wild-type (WT) mice (P<0.01). Protein expressions of canonical transient receptor potential (TRPC) channels 3 and 6 increased in Gα(q)-TG hearts compared with WT and Gα(q)/DGKζ-TG hearts. SK&F96365, a TRPC channel blocker, decreased the number of PVC and prevented VT in anesthetized Gα(q)-TG mice (P<0.05). 1-oleoyl-2-acyl-sn-glycerol (OAG), a diacylglycerol analogue, increased the number of PVC in isolated Gα(q)-TG hearts compared with WT hearts and induced VT in Gα(q)-TG hearts (P<0.01). SK&F96365 decreased the number of PVC and prevented VT in isolated Gα(q)-TG hearts (P<0.01) even in the presence of OAG. Early afterdepolarization (EAD)-induced triggered activity was frequently observed in single Gα(q)-TG ventricular myocytes. Moreover, SK&F96365 prevented the EAD. CONCLUSIONS: These results demonstrated that DGKζ inhibited VT in a mouse model of HF and suggest that TRPC channels participate in VT induction in failing hearts.

Angiomatoid fibrosis histiocytoma in the pulmonary artery: A case report.

Angiomatoid fibrosis histiocytoma (AFH) is a rare neoplastic disease. Only one report has demonstrated an intraluminal tumor of the pulmonary artery (PA) corresponding to AFH to date. We describe the case of AFH with EWSR1-CREB1 fusion occurring in the ascending artery. A 42-year-old man exhibited an abnormal nodule on chest computed tomography (CT) during checkup. It revealed an intraluminal mass in the ascending artery with significant metabolic uptake in positron emission tomography (PET)/CT. Therefore, right upper lobectomy with wedge resection of the PA trunk was performed. Histologically, the tumor was multinodular and surrounded by a dense lymphoplasmacytic cuff. Each nodule was composed of myxoid stroma and comprised ovoid or spindle cell fascicles with mild atypia. Fluorescent in situ hybridization (FISH) analysis confirmed EWSR1-CREB1 fusion. A diagnosed as AFH was made. This report widens the spectrum of differential diagnoses of primary tumors occurring in the PA.