Predominance of T-bet-positive Th1 cells in infiltrating T-lymphocytes in most of active arteritis lesions of giant cell arteritis.

Immunological mechanisms through the activation of CD4-positive T-cells have been assumed to be involved in the pathogenesis of giant cell arteritis (GCA). Many studies employing frozen tissues of temporal artery biopsy, peripheral blood lymphocytes, and plasma of GCA patients have revealed the contribution of interferon-γ and interleukin-17 in both protein and mRNA levels. However, the analyses using formalin-fixed and paraffin-embedded (FFPE) tissue specimens, in which the correlation between histopathologic pictures and immunological circumstances would be elucidated, have been limited. Here, we performed the immunohistochemical analyses of infiltrating small lymphocytes in GCA lesions using FFPE specimens, especially of the subsets of CD4-positive T-cells by immunohistochemistry with antibodies against T-bet, GATA-3, RORγT, and Foxp3, which is the differentiation-specific transcription factor for Th1, Th2, Th17, and Treg cells, respectively. In these slides, the nuclear-positive staining is much more clearly and easily identifiable than the cytoplasmic staining for cytokines. The results indicate the predominance of T-bet-positive Th1 cells in infiltrating T-cells in most of active arteritis lesions of GCA. Furthermore, our data suggest the possible immunosuppressive microenvironment induced by T-reg cells and M2-type macrophages in the arteritis lesions throughout the course of GCA inflammation.

Hilar lymphadenopathy, development of tubulointerstitial nephritis, and dense deposit disease following Pfizer-BioNTech COVID-19 vaccination.

Despite the reports on glomerulonephritis associated with COVID-19 mRNA vaccines, no study has reported about the dense deposit disease (DDD). Here, we present a case of hilar lymphadenopathy after the COVID-19 mRNA vaccination, following which the patient developed tubulointerstitial nephritis (TIN) and DDD. A 74-year-old man received his second dose of mRNA vaccine, and on the next day, he developed fever, urticaria, and dyspnea. On further examination, he had pleural effusion and right hilar lymphadenopathies, which were improved with conservative therapy. After 48 days of the second vaccination, he developed renal dysfunction and new-onset hematuria. Light microscopy findings by renal biopsy revealed apparent mesangial cell proliferation, increased mesangial matrix in the glomeruli, and diffuse inflammatory cell infiltration in the interstitium. Immunofluorescence analysis revealed 1 + positive results for IgG and IgM, negative results for IgA, and 2 + positive results for C3 with a garland pattern on the capillary walls. Electron microscopy revealed that severe cell proliferation in the capillary rumen, and continuous, thickened, and highly dark-stained spotty dense deposits in the glomerular basement membrane; and noncontinuous spotty dense deposits in the tubular basement membrane. Based on the decrease in C3 and pathological findings, TIN accompanied with DDD was diagnosed. The mRNA vaccine might have contributed to the development of lymphadenopathies, TIN, and DDD in this case. Moreover, TIN and DDD might be associated with the activated alternative pathway induced by the mRNA vaccine.

[An autopsy case of nasal-type primary gastric extranodal NK/T-cell lymphoma with early liver failure].

An 82-year-old woman was admitted to the hospital because of tiredness and fever. She was diagnosed with acute hepatitis. Although the cause of acute hepatitis was undetermined, her health condition and liver function improved, and she was discharged. Four weeks later, she was hospitalized again because of anorexia. Laboratory data revealed worsened anemia. Endoscopy results revealed a huge ulcerative lesion in the lesser curvature of the stomach. After 4 days, she vomited blood and died of hemorrhagic shock. The autopsy revealed a nasal-type primary gastric extranodal NK/T-cell lymphoma (ENKTL). Although no lymphoma cells were found in the liver biopsy collected during the first hospitalization, lymphoma cells and lymphocytes in the liver tissue were identified during autopsy because the lymphoma had infiltrated the liver. Primary gastric ENKTL is extremely rare and poorly understood. However, the general prognosis of progressive ENKTL is poor. Early diagnosis of liver metastasis of lymphoma cells is difficult;thus, in some cases, lymphoma metastases to the liver are diagnosed during autopsy. Although further experiments are required, we report a rare case of primary gastric ENKTL.

Immunostaining With Immunoglobulin G Subclass Antibody Cocktail for Diagnosis of Type 1 Autoimmune Pancreatitis.

BACKGROUND.: Immunoglobulin (Ig) G4-related diseases (RDs) are systemic diseases in which serum IgG4 levels are frequently elevated. They can cause diffuse or focal tumor formation, organ swelling, and tissue thickening in organs infiltrated by IgG4+ plasma cells. The diagnostic criteria for IgG4-RDs include an IgG4/IgG ratio >40%, but counting IgG+ cells can be difficult because of the weakness of IgG staining density. We hypothesized that an antibody cocktail of mixed IgG1, IgG2, IgG3, and IgG4 (AC-IgG) might give immunohistochemistry results comparable with those of IgG in IgG4-RD. METHODS.: We compared AC-IgG reactivity with IgG expression in type 1 autoimmune pancreatitis (AIP), a representative IgG4-RD. We compared immunohistochemistry results using AC-IgG and IgG-only in 10 cases of AIP. The coefficient of variation (Cv) was used to analyze differences between AC-IgG and IgG findings in AIP by 13 board-certified pathologists. RESULTS.: Although mean values for IgG+ cells did not significantly differ between AC-IgG (34.3; range = 27.4-37.1) and IgG (30.0; range = 23.0-45.6; P = .6254), Cv was lower for AC-IgG (33.4%) than for IgG (51.4%; regression equation; y[IgG] = 0.988x + 0.982; correlation coefficient = 0.907). The data showed that the results of both methods were largely consistent. CONCLUSION.: AC-IgG could replace IgG to count IgG+ cells because of its lower Cv.

Atypical Hemolytic Uremic Syndrome Associated with Complement Factor H Mutation and IgA Nephropathy: A Case Report Successfully Treated with Eculizumab.

We present a rare case of IgA nephropathy in a patient who developed atypical hemolytic uremic syndrome (aHUS) associated with a complement factor H (CFH) gene mutation, and who was successfully treated with eculizmab. A 76-year-old man was admitted as the patients had thrombotic microangiopathies findings. The patient was treated with plasma exchange, hemodialysis and methylprednisolone. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 level was not decreased. Light microscopy findings were consistent with hemolytic uremic syndrome and immunofluorescence analysis revealed IgA and C3 were detected. Genetic analysis revealed that mutation of p.Arg1215Gln in CFH was identified. The diagnosis of aHUS was confirmed and eculizmab therapy was currently effective for 5 months.

Autonomic and sensory ganglionopathy occurring in a patient with fulminant type 1 diabetes mellitus.

A 63-year-old male with a previous infection was admitted to our hospital because of acute pancreatitis. Although he had no history of diabetes mellitus, laboratory examinations revealed marked hyperglycemia on admission, and intensive insulin treatment was required. After 2 weeks, he developed severe pandysautonomia and sensory impairment, and eventually died from colonic perforation caused by paralytic ileus at 1 year after onset. Autopsy findings showed a complete loss of pancreatic islet beta cells with mild fibrosis of the exocrine pancreas. Neuropathological examination showed myelin loss of the dorsal fasciculus at all levels of the spinal cord and ganglionopathy of the dorsal root and sympathetic truncus, revealing degeneration of ganglion cells and a decrease in their number with the formation of Nageotte nodules. On the basis of this clinicopathological evidence, fulminant type 1 diabetes mellitus (T1DM) and idiopathic immune-mediated autonomic neuropathy were suspected. Here, we suggest a close etiological relationship between both diseases.

Endoscopic ultrasonography-guided drainage of infected intracystic papillary adenocarcinoma of the liver.

We describe a case of effective use of endoscopic ultrasonography (EUS)-guided drainage of an infected intracystic papillary adenocarcinoma (ICPA) of the liver. The patient was an 84-year-old woman who was admitted with complaints of continuous epigastric pain and a slight fever. Laboratory data revealed severe inflammation. Computed tomography scanning showed a 110-mm cystic lesion with enhanced papillary tumors in the medial segment of the liver associated with a cyst in the right lobe and subcapsular cyst of the liver. Streptococcus species were detected in the culture of cystic fluid, and a diagnosis of infected ICPA was suspected. Although the patient was medicated by antibiotics, the fever did not resolve. EUS-guided transgastric drainage was performed for the abscess of the medial segment of the liver. Fourteen days after the endoscopic procedure, the plastic drainage tube was replaced with a metal stent. Inserting an endoscope into the liver cyst through the metal stent permitted observation and biopsy of an intracystic tumor, and the diagnosis of ICPA was confirmed. The patient was discharged with the internal metal stent still in place.

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.

Autopsy cases of miliary tuberculosis: clinicopathologic features including background factors.

To assist physicians, especially young physicians, in identifying tuberculosis (TB) infection before the terminal stage, we analyzed 7 cases of numerous tuberculous granulomas in multiple organs and compared clinical and autopsy findings between cases. Patients ranged in age from 41 to 86 years at the time of death. The main chief complaint was fever of unknown origin (3 of 7 cases [43%]). The main underlying conditions were liver cirrhosis (2 of 7 cases [29%]) and chronic renal failure (2 of 7 cases [29%]). Two patients (29%) had been given methylprednisolone pulse therapy for various lung disorders. Active TB was not diagnosed before autopsy in 4 of 7 (57%) patients. Calcified lesions indicative of old TB were present in 4 of 7 (57%) patients. Thus, miliary tuberculosis may represent a re-emergence of latent TB infection in these cases. Various histologic features of nonreactive exudative inflammation were seen, along with granulomas containing Langhans giant cells with or without caseous necrosis in hypervascular organs, such as the lung, liver, and bone marrow. Physicians should be mindful of the possibility of miliary TB when older patients with hepatorenal disease and a history of TB infection have undergone immunosuppressive treatment. Active tuberculous infection can depend on the presence of an underlying disease and immunocompromise.

A fulminant case of renal vein thrombosis in a patient with autoimmune disorder and membranous nephropathy.

A previously healthy middle-aged woman noted a rapid onset of flank pain with gross hematuria. Enhanced CT scan showed thrombosis of the inferior vena cava and right renal vein. Laboratory findings revealed nephrotic proteinuria, Sjogren's syndrome (SjS), and Graves' disease (GD). A right nephrectomy was performed because of progressive and refractory renal necrosis. Renal specimens showed venous infarction with diffuse hemorrhagic and severe congestive renal necrosis, and membranous nephropathy (MN). The present case was diagnosed as acute renal necrosis due to catastrophic thrombosis in a patient with SjS, GD, and MN. It was thought that sudden development of thrombosis may have been caused by the status of the autoimmune disorders, and the associated MN.

Ectopic nodal structures in a patient with atrial tachycardia originating from the mitral valve annulus.

We report a case, which we believe to be rare, of adenosine-sensitive atrial tachycardia (AT) originating from the mitral valve annulus. The patient, a 73-year-old woman, died of unrelated cause 4 years after radiofrequency (RF) ablation therapy. Histologically, fibrous replacement of atrial musculature by mature collagenous tissue produced by the RF current was observed at the left inferior atrioventricular junction. In serial sections that included the coronary sinus, two distinct nodal structures containing small, pale myocytes within the fibrous tissue matrix were identified around the region of the ablation lesion. Our case appears to be a unique representation of tissue that was associated with the occurrence and maintenance of AT.

Diverse myocardial extension and autonomic innervation on ligament of Marshall in humans.

INTRODUCTION: The ligament of Marshall (LOM) or the oblique vein of Marshall (VOM) in the left atrium (LA) is one of the origins of nonpulmonary vein ectopies causing atrial fibrillation. The distributions of myocardial bundles (Marshall bundles; MBs) and autonomic nerves adjacent to the LOM have not been completely elucidated. METHODS AND RESULTS: Twenty-eight human hearts were examined postmortem. The inferolateral LA myocardium was dissected en block and cut perpendicularly to the atrioventricular ring. The specimens were sectioned at 1-mm intervals and stained with hematoxylin and eosin, and Azan-Mallory. In addition, S-100 and tyrosine hydroxylase (TH) were employed for the immunohistochemical analysis of the sympathetic and parasympathetic fibers. In 25 cases, MBs were observed. Although the MBs surrounded the VOM at the coronary sinus (CS) juncture, they gradually diminished in density toward the distal venous branch. The connections of the MBs and LA myocardium were frequently observed in the CS juncture and anterior wall of the left pulmonary vein (PV)-LA junctions. TH-stained sympathetic nerve fibers were densely distributed around the PV-LA junctions. On the other hand, non-TH-stained parasympathetic ganglions were mainly observed at the CS juncture. CONCLUSIONS: MB-LA connections were mainly observed at the CS juncture and PV-LA junctions. The association between sympathetic nerve fibers and MBs was distinct at the PV-LA junctions. At the CS juncture, the regression of the sympathetic nerve fibers and the increase of parasympathetic ganglions were observed. The diverse arrangement and autonomic innervation of MBs seem to characterize the LOM region in humans.