Peculiar Pathological Features Research Articles

Humanin gene expression in subjects with Parkinson's disease.

Bradykinesia, tremor, rigidity and postural instability are the hallmark of Parkinson's disease (PD). Non-motor symptoms including cognitive, behavioral, and neuropsychiatric changes, sensory and sleep disturbances that may precede the motor symptoms by years. The peculiar pathological features of PD are decreased dopaminergic neurons and dopamine levels in the substantia nigra pars compacta and pontine locus coeruleus. Humanin is produced by a small gene peptide, which is located in the mitochondria genome. Inflammation, oxidative stress, mitochondrial dysfunction and altered transcription have been recognized as causative factors of PD. This evidence has prompted many researchers to focus on studying the functions of DNA and mitochondria. The purpose of the present study was to evaluate Humanin mRNA levels in peripheral blood mononuclear cells (PBMCs) of PD subjects, compared with those in PBMCs of normal control (NC) subjects. A total of 220 participants, including 154 PD patients (57 females and 97 males; mean age 71.54 years, SD 7.8) and 66 CN (28 females and 38 males; mean age 70.54 years, SD 9.45) were enrolled for the qRT-PCR analysis. Increased Humanin mRNA levels were found in PD samples, compared to controls. In conclusion, the present data confirm the tendency of mitochondria to overexpress mRNA in PD, which could be a cellular attempt to reduce apoptotic damage in PD subjects. Humanin might be useful as a marker for a better diagnosis of PD, and we cannot exclude that in the future it might also play a role on prognosis and in the possible therapies for PD.

Intentional Carbofuran poisoning in 7 dogs

BackgroundCarbofuran is a widely used broad-spectrum pesticide that, despite strict regulation and being banned for more than a decade, is still encountered in cases of intentional poisoning in dogs and wildlife. The objective of the study was to provide a complete and detailed description of the pathological, histological and toxicological findings of 7 cases of intentional carbofuran poisoning in dogs.ResultsIn this retrospective study, 7 cases of carbofuran intoxication recorded from July 2015 to June 2017 were analyzed. Following complete history recording, all cases were examined by complete necropsy and histopathology. Carbofuran intoxication was confirmed in all cases by gas chromatography. The postmortem examination revealed extensive hemorrhaging and congestion located mainly within the respiratory, nervous and cardiovascular systems, accompanied by degeneration and necrosis within the lungs, heart, and kidneys.ConclusionsAlthough carbamates have been banned in the European Union, carbamate poisoning is still frequently encountered, especially in wild animals. This paper will contribute to a better understanding of the occurrence and pathogenesis of acute carbofuran exposure in dogs and contribute some peculiar pathological features of this type of poisoning to the current literature.

ODLURO syndrome: personal experience and review of the literature.

The O'Donnell-Luria-Rodan (ODLURO) syndrome, caused by heterozygous mutation in the lysine N-methyltransferase2E (KMT2E) gene in chromosome 7q22, has been recently described. Mutation of KMT2E produces a protein-truncating variant gene that may be responsible for both developmental delay and intellectual disability disorders commonly defined by an Intelligence Quotient < 70 and usually unspecific pathologic brain features demonstrated by brain Magnetic Resonance imaging. The symptoms of ODLURO syndrome include variably developmental and speech delay, autism, seizures, hypotonia, and dysmorphic features. The aim of the study is to search for correlation between this specific gene mutation and clinical/radiological features, trying to provide new insights in this recently described pathological condition. We reviewed the 38 cases collected by O'Donnel-Luria et al., adding three cases of a familial heterozygosis novel mutation in KMT2E gene; different degrees of neurological disorder, subtle dysmorphic features, intellectual disability, epilepsy, and various brain Magnetic Resonance features are described. Magnetic Resonance data were integrated by genetic analysis and clinical features. Brain Magnetic Resonance study of our patients confirmed peculiar pathologic features previously reported in ODLURO syndrome; cerebellar dysplasia was identified in one of them. All 3 patients had epilepsy, intellectual disability, and mild dysmorphisms. Our study adds 3 new patients genetically, clinically, and radiologically evaluated to the ODLURO syndrome case series. While CC hypoplasia and widening of subarachnoid spaces are already reported in literature, we document for the first time the presence of cerebellar dysplasia in ODLURO syndrome. We also highlight the extremely low IQ value and the presence of epilepsy in all 3 patients.

Solid Pseudopapillary Neoplasm of Pancreas: a Rare Entity with Excellent Outcomes

Solid pseudopapillary neoplasm (SPN) is an uncommon entity with excellent prognosis. Despite having peculiar imaging and pathological features, diagnosis in men remains challenging due to low reported incidence. Surgery remains the mainstay of treatment and survival reaches approximately 95%, making it worth to identify preoperatively from other aggressive pancreatic counterparts. Here, we report a case of SPN in a 52-year-old gentleman presented with large pancreatic head mass and managed successfully with pancreaticoduodenectomy.

Peculiar pathological, radiological and clinical features of skull-base de-differentiated chordomas. Results from a referral centre case-series and literature review.

De-differentiated chordoma is an uncommon and incompletely characterised aggressive neoplasm. Only a few cases originating from the skull base have been reported. All consecutive cases of skull-base de-differentiated chordomas treated surgically in a referral centre from January 1990 to June 2019 were retrospectively evaluated to assess peculiar pathological, radiological and clinical features. Patient data were retrieved from paper and electronic records. Six cases (two male, four female; mean age at surgery=46years, range=35-64), treated surgically at our institution were identified. Transformation to de-differentiated chordomas occurred after radiation therapy in three cases (mean=13.6years after treatment, range=5-25), two during tumour progression, while one was de-novo. Magnetic resonance imaging and surgical examination revealed the presence of two different tumour components, corresponding to the conventional and de-differentiated portion on histological examination. The de-novo case presented a PIK3CA mutation. DNA methylation analysis revealed consistent epigenetic changes in TERT, MAGEA11 and UXT. Prognosis was poor, as five of six patients died after surgery and radiation therapy, with a mean overall survival of 29months (range=11-52). Skull-base de-differentiated chordomas are extremely rare and aggressive neoplasms with characteristic magnetic resonance imaging, surgical and histological features. Therefore, an early and accurate histological diagnosis is of paramount relevance. Molecular analysis appears promising to define mechanisms involved in tumour de-differentiation.

Bitter Taste Receptors: an Answer to Comprehensive Asthma Control?

Asthma is marked by peculiar pathological features involving airway contraction, an impinging inflammation in the lungs, and an inexorably progressive remodeling of pulmonary architecture. Current medications for management of asthma exacerbations fail to optimally mitigate these pathologies, which is partly due to the intrinsic heterogeneity in the development and progression of asthma within different populations. In recent years, the discovery of the ectopic expression of TAS2Rs in extraoral tissues and different cell types, combined with significant strides in gaining mechanistic understanding into receptor signaling and function, has revealed the potential to target TAS2Rs for asthma relief. TAS2R activation leads to relaxation of airway smooth muscle cells and bronchodilation. In addition, findings from preclinical studies in murine model of asthma suggest that TAS2R agonists inhibit allergen-induced airway inflammation, remodeling, and hyperresponsiveness. In this review, we expand on the opportunity presented by TAS2Rs in the development of a comprehensive asthma treatment that overcomes the limitations set forth by current asthma therapeutics.

Retrospective Multicenter Study Investigating the Role of Targeted Next-Generation Sequencing of Selected Cancer Genes in Mucinous Adenocarcinoma of the Lung

IntroductionMucin-rich lung adenocarcinomas (ADCs), namely mucinous and colloid ADCs, are classified as ADC variants according to the World Health Organization 2015 classification. A correlation between morphological patterns and mutational status of these rare entities is not well established. MethodsWe investigated the mutational profile of mucin-rich lung ADCs in correlation with histopathological and morphological features with the goal of identifying biological tumor characteristics of potential prognostic and therapeutic interest. A series of 54 surgically resected primary mucinous lung ADC samples were retrospectively analyzed for clinicopathological characteristics and by targeted next-generation sequencing. ResultsFifty cases were invasive mucinous ADCs (32 pure and 18 mixed) and four were colloid-predominant ADCs. Invasive mucinous ADC cases with a pure mucinous pattern were associated with a lower risk of vascular invasion (p = 0.01), absence of signet ring cells (p = 0.03), negative nodal status (p = 0.006), and early clinical stage (p = 0.02). The most prevalent mutations involved the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) and tumor protein p53 gene (TP53). Most mutations clustered in the mitogen-activated protein/protein kinase B pathway and in the p53/DNA repair pathway. A few uncommon epidermal growth factor receptor gene (EGFR) mutations were found. A correlation between a higher number of mutations and favorable clinical outcome was seen (p < 0.001). ConclusionsOur data showed that mucinous ADCs have peculiar pathological and molecular features that might suggest the need for a differentially tailored therapeutic approach compared with that to conventional lung ADC.

Clinicopathological features and CD57 expression in renal cell carcinoma in acquired cystic disease of the kidneys: with special emphasis on a relation to the duration of haemodialysis, the degree of calcium oxalate deposition, histological type, and possible tumorigenesis

Acquired cystic disease of the kidney (ACDK) in patients undergoing haemodialysis is known to develop into renal cell carcinoma (RCC), but its pathogenesis remains unclear. The aims were to analyse the histological findings of ACDK-RCC and to determine its histogenesis. Twenty-nine RCCs in 23 patients with ACDK were classified into three groups according to the duration of haemodialysis and were analysed for histological type, calcium oxalate (Oxa) deposition, and cyst and atypical cyst (AC) formation. Histologically, 21 tumours were ACDK-RCC and eight were clear cell carcinoma (CCC). The ratio of ACDK-RCC and the numbers of cysts and ACs increased as the duration of haemodialysis was prolonged. The degrees of intratumoral Oxa deposition and cyst and AC formation of ACDK-RCCs were higher than those of CCCs (Oxa, P=0.028; cyst, P<0.0001; AC, P=0.0002). Many ACDK-RCCs (85.7%) and some CCCs (50%) had characteristics of the thin ascending loop of Henle as assessed by CD57 (HNK-1) expression, which was rarely expressed in the 29 control cases. ACDK-RCCs reveal characteristics of Henle's loop, which may be related to their peculiar pathological features, including intratumoral oxalate deposition and cyst and AC formation.

Atypical cell clusters expressing both neuronal and oligodendrocytic markers: Novel histological pattern of glioneuronal tumors?

Glioneuronal tumors are a group of brain tumors that consist of both neuronal and glial cells. The spectrum of glioneuronal tumors is currently expanding, and many atypical glioneuronal tumors require further characterization. Two patients are described who had an atypical glioneuronal tumor with peculiar pathological features. One patient was a 7-year-old girl with a tumor in the right cerebellar hemisphere. This patient had no recurrence after total resection. The other was a 37-year-old man with a tumor in the spinal cord. He suffered incessant recurrence and received operative treatment four times. Although the clinical features (age at diagnosis, tumor location, and recurrence) were very different in these patients, the tumors had a characteristic common feature of atypical cell clusters. Intriguingly, the tumor cells in the clusters expressed both neuronal and oligodendroglial markers, indicating aberrant differentiation. Furthermore, the cluster-forming cells had modest proliferative indices and CD133 expression, indicating their role in the growth of the tumor. It is believed that these atypical cell clusters are a novel pattern of differentiation of glioneuronal tumors and that they need further investigation.

Natural history of early colorectal cancer.

Since superficial tumors have been found, their peculiar pathologic features have evoked questions concerning their biologic behavior, their natural history. The aim of the present study was to elucidate the natural history of colorectal cancers (CRCs) including superficial cancers, using a retrospective radiologic method. Forty nine cancers that had had initial configurations of early cancer seen by previous radiography and that were examined pathologically were the subject of the present study. Growth speeds [doubling time (DT) calculation] and configurational changes at the various stages (invasion depth) were compared between polypoid growth (PG) and nonpolypoid growth (NPG). Growth speeds of mucosal cancer and submucosal cancer were also compared. The results showed that early CRC grows slowly (DT 31.2 months) when the cancer is limited to the mucosa. However, as tumors grow down to the submucosa, their growth speed accelerates (DT 25.8 months). The DT of these early cancers were longer than that of advanced cancers. The pathologic growth pattern (NPG or PG) of the CRCs did not affect the tumor growth speed. In respect to tumor configuration, when the tumor is limited to the submucosa the antecedent growth pattern may be easily deduced. It seems difficult, however, to know the initial growth patterns in advanced cancers because cancers with polyloid growth frequently change to a nonpolypoid growth pattern when in advanced stages. Among 32 advanced cancers, only 6 (19%) derived from IIc/IIc + IIa cancer. The most common (more than 70%) origin of advanced cancer seems to be IIa, Is, and Isp lesions. These results suggest that NPG cancers or superficial depressed cancers are not the main origins of advanced cancers, and that these cancer do not show extraordinarily rapid growth.

Rheumatoid arthritis: sequences

Objective: Rheumatoid arthritis (RA) is an autoimmune disorder of unknown etiology characterized by symmetric, erosive synovitis and sometimes multisystem involvement. It affects 1% of the adult population and exhibits a chronic fluctuating course which may result in progressive joint destruction, deformity, disability and premature death. We review the literature data relative to the peculiar pathologic features of the disease shown by diagnostic imaging techniques. Methods: All our patients were classified according to the diagnostic criteria of the American Rheumatism Association (1987). Plain radiography remains the diagnostic technique of choice, but ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) are also used. Results: Clinically articular involvement presents as pain, swelling, stiffness and motion impairment. The patients with positive rheumatoid factor are >70% likely to develop joint damage or erosions within 2 years of disease onset. Any joint can be involved, but the proximal interphalangeal and metacarpophalangeal joints of the hand and the wrist are preferential sites, as well as the metatarsophalangeal joint of the foot, the knee and the joints of the shoulder, the ankle and the hip. Symmetry is the hallmark of joint involvement. The synovium of bursae and tendon sheaths is also affected. Soft tissue (subcutaneous nodules), muscles (weakness and atrophy) and vessels (vasculitis) may also be involved. Systemic involvement may result in Felty's syndrome, metabolic bone disorders (i.e. osteoporosis), Sjögren syndrome and pleuropulmonary abnormalities (pleural effusion, fibrosing alveolitis, constrictive bronchiolitis). The earliest abnormalities consist in synovial proliferation, soft tissue swelling, and osteoporosis. At a slightly later stage, the inflamed synovial tissue (`pannus') extends across the cartilage surface, leading to chondral erosions and small bone erosions at the joint margin (bare areas). Marginal and central erosions follow in advanced stages and finally fibrous ankylosis, joint deformities (subluxations and dislocations), fractures and fragmentations are typical findings of more advanced RA. Conclusion: RA is a frequent joint disorder with a characteristic radiographic picture. Joint involvement patterns are sufficiently common to permit accurate diagnosis, especially when fusiform soft tissue swelling, regional osteoporosis, marginal and central erosions and diffuse loss of interosseous space are present. Conventional radiography remains the standard imaging technique for joint studies in the patients with suspected RA. US is recommended to diagnose soft tissue involvement (joint effusion). CT is very useful for showing abnormal processes in complex joints (sacroiliac and temporomandibular joints and craniocervical junction) which are difficult to depict completely with conventional radiography. Magnetic resonance applications include the assessment of disease activity: in particular, this technique may be the only tool differentiating synovial fluid and inflammatory pannus.

Anisakidae and anisakidosis.

During the 1950s, Ishikura noticed in the fishing town of Iwanai, Hokkaido, an intestinal disease that frequently occurred in winter with clinical and histopathologic characteristics different from those of ordinary ileitis terminalis. He reported eight such cases, which occurred within a 2-month period in 1955, as acute ileitis terminalis showing peculiar pathologic features (1). By 1959, thirty cases of this disease had been reported (2). Ishikura, Kikuchi, and their coworkers considered the lesion peculiar because this regional enteritis (or terminal ileitis) caused severe allergic tissue reaction with extensive eosinophilic infiltration. On histologic examination, cross sections of a nematode-like worm were sometimes found, and the specimens were sent to parasitologists for identification. The parasitologists regarded these structures as roundworm larvae, not realizing that they were Anisakis larvae. Meanwhile Otsuru et al. (3), based on a description by Beaver (4), warned that visceral larva migrans might occur in Japan.