Revisiting the relevance of Hirano bodies in neurodegenerative diseases.

AIMS: Hirano bodies (HBs) are eosinophilic pathological structures with two morphological phenotypes commonly found in the hippocampal CA1 region in Alzheimer's disease (AD). This study evaluated the prevalence and distribution of HBs in AD and other neurodegenerative diseases. METHODS: This cross-sectional study systematically evaluated HBs in a cohort of 193 cases with major neurodegenerative diseases, including AD (n = 91), Lewy body disease (LBD, n = 87), progressive supranuclear palsy (PSP, n = 36), multiple system atrophy (MSA, n = 14) and controls (n = 26). The prevalence, number and morphology of HBs in the stratum lacunosum (HBL) and CA1 pyramidal cell layer were examined. In addition, we investigated the presence of HBs in five additional hippocampal subregions. RESULTS: The morphological types of HBs in CA1 were divided into three, including a newly discovered type, and were evaluated separately, with their morphology confirmed in three dimensions: (1) classic rod-shaped HB (CHB), (2) balloon-shaped HB (BHB) and the newly described (3) string-shaped HB (SHB). The prevalence of each HB type differed between disease groups: Compared with controls, for CHB in AD, AD + LBD, PSP and corticobasal degeneration, for BHB in AD + LBD and PSP, and SHB in AD + LBD and PSP were significantly increased. Regression analysis showed that CHBs were independently associated with higher Braak NFT stage, BHBs with LBD and TDP-43 pathology, SHBs with higher Braak NFT stage, PSP and argyrophilic grain disease and HBLs with MSA. CONCLUSIONS: This study demonstrates that HBs are associated with diverse neurodegenerative diseases and shows that morphological types appear distinctively in various conditions.

Enterocolic granulomatous phlebitis associated with epidermal growth factor-containing fibulin-like extracellular matrix protein 1 deposition and focal amyloid properties: A case report.

A woman in her 60s with rheumatoid arthritis was admitted with fever and abdominal pain. Laparoscopic examination with the differential diagnosis of peritoneal neoplasm and infection revealed granulomatous phlebitis in the resected greater omentum. Amorphous eosinophilic deposits observed in the resected tissue exhibited focal, weak positivity for Congo red but were strongly positive for thioflavin S, confirming their focal amyloid properties. Marked degeneration of elastic fibers was also evident. Electron microscopy revealed deposits around the affected elastic fibers. Immunohistochemistry revealed the deposition of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) along with T-cell-predominant lymphocytic inflammation. The definitive diagnosis was granulomatous enterocolic lymphocytic phlebitis (ELP) associated with EFEMP1 deposition exhibiting focal amyloid properties (EFEMP1/AEFEMP1), supported by proteomics analysis. This type of vasculitis is similar to amyloid-ß-related angiitis of the central nervous system. Thus, we speculate that granulomatous ELP also results from an immune response that recognizes EFEMP1/AEFEMP1 deposits as foreign material and attempts to remove them. Confirmation of EFEMP1/AEFEMP1 deposition with Congo red staining is challenging, particularly in the presence of inflammation, and warrants comprehensive evaluation.

Neuropathology of patients with preclinical or early clinical Alzheimer's disease with pathogenic PSEN1_p. L392V: Comparison of advanced siblings.

INTRODUCTION: Neuropathological investigation of presymptomatic or early symptomatic presenilin-1 (PSEN1) mutation carriers in familial Alzheimer's disease (AD) is extremely scarce. METHODS: We report the autopsy findings of brothers with familial AD. Case 1 is a 45-year-old man without obvious cognitive impairment, who committed suicide. Case 2 is a 57-year-old older brother of Case 1 with advanced AD symptoms, who died of hypothermia during wondering. RESULTS: In both cases, abundant amyloid plaques positive for amyloid ß (Aß) were found throughout the brain. Progression of neuronal loss and increasing amount and extension of neurofibrillary tangle pathology were evident in Case 2. Genetic investigation revealed a PSEN1_p. L392V mutation in both cases. DISCUSSION: The present study shows a possible neuropathological boundary between symptomatic and preclinical AD with pathogenic PSEN1 mutation. Additional clinicopathological investigation for familial AD-related mutation carriers may be significant to explore the association between familial AD and suicide.

Prevalence and clinicopathological features of primary age-related tauopathy (PART): A large forensic autopsy study.

INTRODUCTION: Primary age-related tauopathy (PART), often regarded as a minimally symptomatic pathology of old age, lacks comprehensive cohorts across various age groups. METHODS: We examined PART prevalence and clinicopathologic features in 1589 forensic autopsy cases (≥40 years old, mean age ± SD 70.2 ± 14.2 years). RESULTS: PART cases meeting criteria for argyrophilic grain diseases (AGD) were AGD+PART (n = 181). The remaining PART cases (n = 719, 45.2%) were classified as comorbid conditions (PART-C, n = 90) or no comorbid conditions (pure PART, n = 629). Compared to controls (n = 208), Alzheimer's disease (n = 133), and AGD+PART, PART prevalence peaked in the individuals in their 60s (65.5%) and declined in the 80s (21.5%). No significant clinical background differences were found (excluding controls). However, PART-C in patients inclusive of age 80 had a higher suicide rate than pure PART (p < 0.05), and AGD+PART showed more dementia (p < 0.01) and suicide (p < 0.05) than pure PART. DISCUSSION: Our results advocate a reevaluation of the PART concept and its diagnostic criteria. HIGHLIGHTS: We investigated 1589 forensic autopsy cases to investigate the features of primary age-related tauopathy (PART). PART peaked in people in their 60s in our study. Many PART cases over 80s had comorbid pathologies in addition to neurofibrillary tangles pathology. Argyrophilic grain disease and Lewy pathology significantly affected dementia and suicide rates in PART. Our results suggest that the diagnostic criteria of PART need to be reconsidered.

Clinicopathological Appearance of Epidermal Growth-Factor-Containing Fibulin-like Extracellular Matrix Protein 1 Deposition in the Lower Gastrointestinal Tract: An Autopsy-Based Study.

This study examined the patterns of epidermal growth-factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) deposition in the small intestine and colon to evaluate the association between the histopathological severity of EFEMP1 deposition and constipation and determine the colocalization of amyloid transthyretin (ATTR) and EFEMP1 deposits. In 40 older cases (≥80 years of age), EFEMP1 deposition in the small intestine initiated in the submucosal and subserous vessels, subserous interstitium, and serosa (early stage), progressing to the muscularis propria and peri-Auerbach plexus area (intermediate stage), and finally spreading diffusely to other areas, excluding the mucosa and muscularis mucosa (advanced stage). The colon had a similar pattern of progression. During the middle-to-advanced stages, amyloid formation was observed in some vascular and serous deposits. A subgroup of cases was identified in which EFEMP1 deposition was the only presumed cause of constipation. Additionally, we demonstrated the colocalization of ATTR and EFEMP1 deposition. Apple-green birefringence was detected under polarized light only in approximately one-half of the cases in the small intestine and one-third of the cases in the colon. These findings strongly suggest that EFEMP1 deposits are correlated with pathological conditions of the lower gastrointestinal tract. As the histopathological diagnosis using Congo red-stained specimens is challenging, the combined use of elastic fiber staining and EFEMP1 immunohistochemistry is recommended to identify EFEMP1 deposition.

Distinctive Deposition Patterns of Sporadic Transthyretin-Derived Amyloidosis in the Atria: A Forensic Autopsy-Based Study.

Left-to-right differences in the histopathologic patterns of transthyretin-derived amyloid (ATTR) deposition in the atria of older adults have not yet been investigated. Hence, this study evaluated heart specimens from 325 serial autopsy subjects. The amount of ATTR deposits in the seven cardiac regions, including both sides of atria and atrial appendages, was evaluated semiquantitatively. Using digital pathology, we quantitatively evaluated the immunohistochemical deposition burden of ATTR in the myocardium. We identified 20 sporadic ATTR cardiac amyloidosis cases (nine males). All patients had ATTR deposition in the left atrial regions of the myocardium. In the semiquantitative analysis, 14 of the 20 cases showed more severe ATTR deposition on the left atrial regions than on the right side, with statistically significant differences in the pathology grading (p < 0.01 for both the atrium and atrial appendage). Quantitative analysis further supported the difference. Moreover, six had ATTR deposition in the epineurium and/or neural fibers of the atria. Cluster analysis revealed that ATTR deposition in the myocardium was significantly more severe in males than in females. The heterogeneous distribution of amyloid deposits between atria revealed in this study may impair the orderly transmission of the cardiac conduction system and induce arrhythmias, which may be further aggravated by additional neuropathy in the advanced phase. This impairment could be more severe among males. These findings emphasize that atrial evaluation is important for individuals with sporadic ATTR cardiac amyloidosis, particularly for early detection.

Amyloid-Forming Corpora Amylacea and Spheroid-Type Amyloid Deposition: Comprehensive Analysis Using Immunohistochemistry, Proteomics, and a Literature Review.

This study aimed to elucidate the similarities and differences between amyloid-forming corpora amylacea (CA) in the prostate and lung, examine the nature of CAs in cystic tumors of the atrioventricular node (CTAVN), and clarify the distinctions between amyloid-forming CA and spheroid-type amyloid deposition. We conducted proteomics analyses using liquid chromatography-tandem mass spectrometry with laser microdissection and immunohistochemistry to validate the characteristics of CAs in the lung and prostate. Our findings revealed that the CAs in these organs primarily consisted of common proteins (ß2-microglobulin and lysozyme) and locally produced proteins. Moreover, we observed a discrepancy between the histopathological and proteomic analysis results in CTAVN-associated CAs. In addition, while the histopathological appearance of the amyloid-forming CAs and spheroid-type amyloid deposits were nearly identical, the latter deposition lacked ß2-microglobulin and lysozyme and exhibited evident destruction of the surrounding tissue. A literature review further supported these findings. These results suggest that amyloid-forming CAs in the lung and prostate are formed through a shared mechanism, serving as waste containers (wasteosomes) and/or storage for excess proteins (functional amyloids). In contrast, we hypothesize that while amyloid-forming CA and spheroid-type amyloid deposits are formed, in part, through common mechanisms, the latter are pathological.

Lack of difference between amyloid-beta burden at gyral crests and sulcal depths in diverse neurodegenerative diseases.

AIMS: The aim of this study is to clarify whether there is a difference in amyloid-beta burden between gyral crests (GCs) and sulcal depths (SDs) in different neurodegenerative proteinopathies. METHODS: We analysed the burden and distribution of amyloid-beta deposition in post-mortem brain samples from 138 autopsies, including Alzheimer's disease (n = 30), Down's syndrome (n = 11), Lewy body disease (LBD; n = 53), multiple system atrophy (n = 8) and progressive supranuclear palsy (n = 36). We applied quantitative amyloid-beta burden analysis to compare amyloid-beta deposition in both GCs and SDs. We also evaluated the prevalence of amyloid-beta plaques in both regions in samples exhibiting high or low amounts of amyloid-beta pathology. RESULTS: Amyloid-beta burden was evaluated in 67 and 84 samples of the frontal and temporal cortices, respectively. We did not find significant differences in the amyloid-beta burden between GCs and SDs in these regions in any examined disease. In addition, amyloid-beta plaques were almost evenly distributed in both regions in cases with low amounts of amyloid-beta pathology. Females in the LBD group showed significantly higher amyloid-beta burden than males (temporal cortex, p < 0.01). Furthermore, only one LBD case showed SD-predominant deposition associated with the coarse-grained plaques. CONCLUSIONS: We have shown that amyloid-beta is almost evenly distributed in both GCs and SDs in the frontal and temporal lobes from the early stage, in diverse neurodegenerative diseases. Sex may contribute to differences in the amyloid-beta burden. The coarse-grained plaque may show SD-predominant neuritic tau deposition that must be carefully distinguished from chronic traumatic encephalopathy-related SD tau pathology.

An autopsy case of infective aortic aneurysm with Pasteurella multocida infection: clinicopathological appearance and a review of literatures.

Here, we showed our clinicopathological findings of infected aortic aneurysm (IAA) with Pasteurella multocida, which is a Gram-negative coccobacillus and is part of the normal oral flora of many animals. The patient was a 76-year-old male animal owner with a history of diabetes mellitus, alcoholic liver damage, and laryngeal cancer. He died 16 days after admission without undergoing operation because of poor general condition. Autopsy showed saccular outpouching with loss of the existing aortic wall and marked neutrophilic infiltration in the suprarenal abdominal aorta. Rupture was not evident. A polymerase chain reaction assay using DNA extracted from formalin-fixed paraffin-embedded specimen of the aneurysmal wall detected the Pasteurella multocida gene, therefore we conclude that the present case was IAA of native aorta with Pasteurella multocida infection. A review of the literature showed that IAA of native aorta with Pasteurella multocida infection is opportunistic and that liver disorder, alcohol addiction, diabetes mellitus, and animal bite may increase its risk. On the other hand, aortic endograft infection with Pasteurella multocida frequently occurred without an immunocompromised state. Pasteurella multocida may be a distinct causative microorganism in IAA, and/or sepsis when the participant is an animal owner.

Prevalence and Distribution of Lewy Pathology in a Homeless Population.

BACKGROUND: The homeless population experience significant inequalities in health, and there is an increasing appreciation of the potential of lifestyle factors in the development of neurodegenerative diseases, including Parkinson's disease. We performed a study on the prevalence and distribution of pathological alpha-synuclein deposition throughout the central and peripheral nervous systems in a homeless population. METHODS: Forty-four homeless individuals consecutively available for autopsy were recruited. Immunohistochemistry was performed using 5G4 antibody recognizing disease-associated forms of alpha-synuclein, complemented by phospho-synuclein antibody on autopsy tissues collected from 18 regions of the brain and spinal cord, as well as the right and left olfactory bulb, the cauda equina, the extramedullary portion of the vagus nerve, and 27 sites of peripheral organs. RESULTS: The study cohort consisted of 38 males and 6 females, median age 58 years (range 32-67). Lewy-related pathology was present in the brains of three male cases. One showed Braak stage 2 (60 years old), and two stage 4 (56 and 59 years old). One of the Braak stage 4 cases had Lewy-related pathology in the spinal cord, the cauda equina, and the extramedullary portion of the vagus nerve. Examination of 27 sites of peripheral organs found that all three cases with Lewy-related pathology present in the brain were devoid of peripheral organ alpha-synuclein pathology. Multiple system-type alpha-synuclein pathology was not found. CONCLUSION: Our study, representing a snapshot of the homeless population that came to autopsy, suggests that alpha-synuclein pathology is prevalent in the homeless supporting further study of this vulnerable population.

Distinct Molecular Signatures of Amyloid-Beta and Tau in Alzheimer's Disease Associated with Down Syndrome.

Limited comparative data exist on the molecular spectrum of amyloid-beta (Aß) and tau deposition in individuals with Down syndrome (DS) and sporadic Alzheimer's disease (sAD). We assessed Aß and tau deposition severity in the temporal lobe and cerebellum of ten DS and ten sAD cases. Immunohistochemistry was performed using antibodies against eight different Aß epitopes (6F/3D, Aß38, Aß39, Aß40, Aß42, Aß43, pyroglutamate Aß at third glutamic acid (AßNp3E), phosphorylated- (p-)Aß at 8th serine (AßpSer8)), and six different pathological tau epitopes (p-Ser202/Thr205, p-Thr231, p-Ser396, Alz50, MC1, GT38). Findings were evaluated semi-quantitatively and quantitatively using digital pathology. DS cases had significantly higher neocortical parenchymal deposition (Aß38, Aß42, and AßpSer8), and cerebellar parenchymal deposition (Aß40, Aß42, AßNp3E, and AßpSer8) than sAD cases. Furthermore, DS cases had a significantly larger mean plaque size (6F/3D, Aß42, AßNp3E) in the temporal lobe, and significantly greater deposition of cerebral and cerebellar Aß42 than sAD cases in the quantitative analysis. Western blotting corroborated these findings. Regarding tau pathology, DS cases had significantly more severe cerebral tau deposition than sAD cases, especially in the white matter (p-Ser202/Thr205, p-Thr231, Alz50, and MC1). Greater total tau deposition in the white matter (p-Ser202/Thr205, p-Thr231, and Alz50) of DS cases was confirmed by quantitative analysis. Our data suggest that the Aß and tau molecular signatures in DS are distinct from those in sAD.

Pathological and Comprehensive Genetic Investigation of Autopsy Cases of Idiopathic Bradyarrhythmia.

BACKGROUND: Idiopathic bradyarrhythmia is considered to be due to pathological degeneration of the cardiac conduction system (CCS) during aging. There appears to have been no comprehensive genetic investigations in patients with idiopathic bradyarrhythmia.Methods and Results: Ten autopsy cases with advanced bradyarrhythmia (6 men and 4 women; age: 70-94 years, 81.5±6.9 years; 5 cases each of sinus node dysfunction [SND] and complete atrioventricular block [CAVB]) were genetically investigated by using whole-exome sequencing. Morphometric analysis of the CCS was performed with sex-, age- and comorbidity-matched control cases. As a result, severe loss of nodal cells and distal atrioventricular conduction system were found in SND and CAVB, respectively. However, the conduction tissue loss was not significant in either the atrioventricular node or the proximal bundle of His in CAVB cases. A total of 13 heterozygous potential variants were found in 3 CAVB and 2 SND cases. Of these 13 variants, 4 were missense in the known progressive cardiac conduction disease-related genes: GATA4 and RYR2. In the remaining 9 variants, 5 were loss-of-function mutation with highly possible pathogenicity. CONCLUSIONS: In addition to degenerative changes of selectively vulnerable areas in the heart during advancing age, the vulnerability of the CCS, which may be associated with "rare variants of small effect," may also be a contributing factor to the degeneration of CCS, leading to "idiopathic" bradyarrhythmia.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) associated with neurenteric cyst. An autopsy case showing unusual fatal outcome.

A 53-year-old man with a history of an untreated brain mass was taken to Toyama Prefectural Central Hospital by emergency transport. Computed tomography revealed an intracranial hypo-attenuated lesion exhibiting mass effect. Several calcified foci were observed around the lesion. His radiographical diagnosis was meningioma with calcification and edema. He suddenly showed tonic seizure after admission; therefore an emergency craniotomy was performed. However, he unfortunately died due to advanced cerebral edema. Microscopic findings of the surgically obtained materials were consistent with neurenteric cyst (NC). Intracranial hard masses were found adjacent to NCs, and the masses were composed of fibrous cartilage-like matrix with extensive linear calcification and the presence of surrounding round-to-oval epithelioid cells. Thus, calcifying pseudoneoplasm of the neuraxis (CAPNON) associated with NC was considered the most appropriate diagnosis of the present case. To the best of our knowledge, this is the first report of such a case. The present case suggests that delay of treatment might cause a poor outcome, at least in CAPNON associated with NC. Careful investigations, including the underlying pathology, may be essential when considering the etiology of CAPNON and its treatment strategies.

Histopathology of acute colchicine intoxication: novel findings and their association with clinical manifestations.

A 32-year-old woman attempted suicide by ingesting Gloriosa bulbs and died approximately 2 days later. Toxicological examination revealed a potentially fatal blood concentration of colchicine (0.096 mg/L). In addition to the increased mitotic figures in the gastrointestinal mucosa, a unique finding for acute colchicine intoxication, pathological examination showed microvesicular lipid droplets in the liver, kidney, heart, and conduction system. Furthermore, central chromatolysis of neurons was observed in the pontine nucleus, medial accessory olivary nucleus, nucleus of the solitary tract, and nucleus ambiguus. Grumose degeneration of the cerebellar dentate nucleus was also evident. These pathological findings may help identify colchicine intoxication, even in the absence of evidence suggesting ingestion during autopsy. Moreover, pathological changes in the heart and central nervous system may be associated with the development of serious complications of acute colchicine intoxication.

An autopsy case of pure nigropathy with TUBA4A nonsense mutation.

We showed the results of pathological and genetic investigation for an autopsy case who was evaluated as longstanding Parkinson's disease (PD) in alive. Neuropathological investigation showed "pure nigropathy" without Lewy and tau pathology, and genetic analyses using next-generation sequencing detected novel TUBA4A nonsence mutation. Subsequent physiological study added to strength the hypothesis that the variant is pathogenic one. Present case showed TUBA4A is not only responsible gene for amyotrophic lateral sclerosis/frontotemporal dementia but also PD associated pure nigropathy. Also we found minimal but significant tau pathology high possibly associated with long-term deep brain stimulation in subthalamic nucleus.

Effects of sporadic transthyretin amyloidosis frequently on the gallbladder and the correlation between amyloid deposition in the gallbladder and heart: A forensic autopsy-based histopathological evaluation.

The aim of the study is to evaluate the clinicopathological features of cholecystic ATTR deposition in patients with cardiac involvement, investigate the correlation of amyloid deposition severity in the gallbladder and the heart, and compare its prevalence in the gallbladder and other organs. Fifty patients with sporadic ATTR amyloidosis were identified. Of these, we evaluated 15 patients who underwent gallbladder sampling accurately. Among 10 patients (67%) with cholecystic deposition, six exhibited detectable deposition in the hematoxylin and eosin-stained specimens, and all of them displayed obstructive vascular deposition (VD). The severity of gall bladder VD was statistically correlated with that of cardiac VD and atrial interstitial deposition (ID). Additionally, all patients exhibiting cholecystic ID displayed severe ventricular and atrial IDs. In visceral organs excluding the heart, amyloid deposition was commonly observed in the lungs (93%), followed by the gastrointestinal tract (47%-80%), liver (60%) and periosteal tissues (53%). The involvement of the gallbladder was prevalent and comparable to that of the gastrointestinal tract. Moreover, the severity of cholecystic deposition was correlated with that of cardiac deposition. Therefore, pathologists should be aware that sporadic ATTR amyloidosis is a common condition and should not be overlooked.

Sex-dependent expression of prostatic markers and hormone receptors in cystic tumor of the atrioventricular node: A histopathological study of three cases.

We pathologically investigated three autopsy cases of cystic tumor of the atrioventricular node (CTAVN) with sudden death. Case 1 was a 36-year-old woman without any clinical history. Case 2 was a 76-year-old man with an implanted pacemaker for complete atrioventricular block. Case 3 was a 45-year-old man with a history of first-degree AV block and sinus bradycardia. Microscopically, all three cases showed the bilayered structure of tumor glands and corpora amylacea in the glandular lumens. Immunohistochemically, the inner cells of the tumor glands were positive for cytokeratin CAM5.2, CEA, EMA, olfactomedin-4 and alpha-methylacyl-coenzyme A racemase; the outer cells were positive for p63 and cytokeratin high molecular weight. In Case 1, androgen receptor and estrogen receptor were negative; progesterone receptor was focally positive in both the inner and outer cells. In Case 2, androgen receptor showed intermediate positivity in the inner cells; estrogen receptor and progesterone receptor were positive in the outer cells. Positive expression of both prostate-specific antigen and prostate-specific acid phosphate were found in the inner cells of both male cases. Because CTAVN cells exhibit different degrees of the prostatic phenotype depending on the patient's sex, we believe that CTAVN may originate from urogenital sinus tissue in some cases.

Autopsy of a multiple lobar hemorrhage case with amyloid-ß-related angiitis.

A 92-year-old man died of multiple lobar hemorrhage with amyloid-ß protein (Aß)-related angiitis (ABRA) with an unusual pathological appearance. Although he had shown relatively rapid progressive dementia, starting 1 year before death, there was no detailed clinical investigation, and no immunosuppressive or anticoagulant therapy, because of his advanced age. The autopsy showed two lobar hemorrhagic lesions in the right parietal lobe and temporal lobes. Microscopically, almost all the brain's blood vessels showed cerebral amyloid angiopathy with many foci of transmural vasculitis. Infiltrating cells were predominantly CD8-positive T-lymphocytes, but we observed no granulomatous inflammation with appearance of multinucleated giant cells. We found fibrinoid necrosis in some blood vessels and disruption of these blood vessels in the arachnoid space-cerebral cortex junction in the hemorrhagic lesion at the temporal lobe. We also observed an unusual, neutrophil-predominant, abscess-like vasculitis in the subarachnoid space; almost all such unusual vasculitides were located at a short distance from the two lobar hemorrhagic lesions. Serum anti-neutrophil cytoplasmic myeloperoxidase and proteinase-3 antibodies were negative, and the genotype of the apolipoprotein E (ApoE) gene (ApoE) was ε2/ε3. Although we did not observe some of ABRA's typical histopathological findings, transmural and vascular destructive inflammation with Aß deposition was consistent with ABRA. Vulnerability of blood vessels to fibrinoid necrosis might be associated with disruption of the relevant blood vessels, leading to lobar hemorrhage. ABRA exhibits various clinical and histopathological findings, depending on the patient's age, immune function status, treatment, and ApoE genotype. This is the first case and the oldest (92 years old) autopsy of ABRA associated with ApoE-ε2/ε3 genotype.

A case of large cell neuroendocrine carcinoma exhibiting rhabdoid features in the esophagogastric junction.

We report a case of large cell neuroendocrine carcinoma with rhabdoid features in the esophagogastric junction. An 81-year-old man presented to Saku Central Hospital Advanced Care Center with a tumor in the esophagogastric junction. During upper gastrointestinal endoscopy, an ulcerative tumor, measuring 4 × 3 cm in diameter, was observed. Computed tomography revealed lymph node metastasis, but no metastasis to other organs was observed. A thoracoscopic subtotal esophagectomy was performed. Histopathologically, anaplastic large cells exhibited a solid growth pattern with focal and geographic necrosis. Approximately half of the tumor cells exhibited large nuclei with conspicuous nucleoli; an eosinophilic "rhabdoid" cytoplasmic inclusion; and a nucleus displaced eccentrically by the cytoplasmic inclusion body. Immunohistochemically, tumor cells, including rhabdoid cells, were focally positive for pan-cytokeratin and diffusely positive for vimentin and synaptophysin. Additionally, electron microscopy identified dense-core granules in the tumor cells. Therefore, a diagnosis of large cell neuroendocrine carcinoma with rhabdoid features was made. A few cases of esophageal neuroendocrine tumors with rhabdoid features have been reported in the lung and pancreas; however, this is the first report of large cell neuroendocrine carcinoma with rhabdoid features in the esophagogastric junction.

A fulminant case of classical Hodgkin lymphoma: A diagnostic dilemma of Epstein-Barr virus-positive large B-cell neoplasms.

We report a fulminant case of classical Hodgkin lymphoma (CHL). The patient died only approximately 2 months after the onset of subjective symptoms. Autopsy specimens revealed atypical cells resembling Hodgkin and Reed-Sternberg (HRS) cells in a rich inflammatory background in various organs. There were marked, characteristic angiodestructive lesions from infiltrating HRS-like cells and numerous macrophages. The HRS-like cells were infected with Epstein-Barr virus (EBV), immunohistochemically positive for PAX5 and CD30, and negative for CD3, CD20, and ALK. Most B-cell markers other than PAX5 were negative, and the HRS-like cells also expressed cytotoxic molecules. Monoclonal rearrangement of immunoglobulin heavy chain was detected by PCR analysis. According to the 2016 WHO classification, we diagnosed mixed cellularity CHL. However, EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified and EBV-positive B-cell lymphoma, unclassifiable with features intermediate between DLBCL and CHL were considered as differential diagnoses because both tumors are aggressive EBV-positive large B-cell neoplasms with reactive inflammatory cells and sometimes contains HRS-like cells. The clinical condition of the current case was closer to these two entities than to CHL. A diagnosis of EBV-positive large B-cell neoplasms was difficult because of overlapping morphological and immunohistochemical characteristics, but should be considered for prognosis.