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Avian Diseases Jun 2023A cerebral tumor was identified in an adult female domestic chicken (). On gross examination, the cut surface of the cerebrum revealed a poorly circumscribed, pale tan...
A cerebral tumor was identified in an adult female domestic chicken (). On gross examination, the cut surface of the cerebrum revealed a poorly circumscribed, pale tan soft mass within the thalamus and midbrain. On histologic examination, there was an unencapsulated, multilobulated neoplasm composed of spindle cells on a loose fibrovascular stroma. Neoplastic cells had variably distinct cell borders, abundant fibrillar eosinophilic cytoplasm, oval nuclei with finely stippled chromatin, and 1-2 distinct nucleoli. There was moderate anisocytosis and anisokaryosis with <1 mitoses per 2.37 mm. The morphologic features of the neoplastic cells were consistent with an astrocytic neoplasm. PCR was performed on formalin-fixed paraffin-embedded sections of brain tissue, which was negative for subgroup A avian leukosis virus. Based on these findings, the tumor was diagnosed as a presumed spontaneous astrocytoma.
Topics: Female; Animals; Chickens; Poultry Diseases; Astrocytoma
PubMed: 37556301
DOI: 10.1637/aviandiseases-D-22-00068 -
The Canadian Veterinary Journal = La... Feb 2022A 12-year-old, spayed female, Maltese dog with a round and firm mass on the dorsal part of the left rear paw and a cervical mass was brought to the clinic. The paw mass...
A 12-year-old, spayed female, Maltese dog with a round and firm mass on the dorsal part of the left rear paw and a cervical mass was brought to the clinic. The paw mass was contiguous to the adjacent tendon; it was composed of neoplastic mesenchymal cells and had scattered foci of calcification with chondroid differentiation microscopically. The neoplastic cells were positive for vimentin and S100, but negative for desmin and smooth muscle actin. Microscopic features and immunohistochemistry results were consistent with calcifying aponeurotic fibroma (CAF). The cervical mass was composed of polygonal cells forming acini with marked anisocytosis and anisokaryosis and diagnosed as thyroid follicular carcinoma. No recurrence or metastasis occurred during follow-up. To the best of our knowledge, this is the first case of canine CAF with features identical to its human counterparts. Key clinical message: This report describes the rare case of calcifying aponeurotic fibroma on the paw in a dog. This is apparently the first case in the veterinary literature with identical clinical and pathological features to the human counterpart.
Topics: Animals; Calcinosis; Dog Diseases; Dogs; Female; Fibroma; Fibroma, Ossifying; Soft Tissue Neoplasms
PubMed: 35110769
DOI: No ID Found -
The American Journal of Surgical... Nov 2018In our routine and consultative pathology practices, we have repeatedly encountered an unusual subcutaneous fatty tumor with notable anisocytosis, single-cell fat...
Dysplastic Lipoma: A Distinctive Atypical Lipomatous Neoplasm With Anisocytosis, Focal Nuclear Atypia, p53 Overexpression, and a Lack of MDM2 Gene Amplification by FISH; A Report of 66 Cases Demonstrating Occasional Multifocality and a Rare Association With Retinoblastoma.
In our routine and consultative pathology practices, we have repeatedly encountered an unusual subcutaneous fatty tumor with notable anisocytosis, single-cell fat necrosis, and patchy, often mild, adipocytic nuclear atypia. Because of the focal atypia, consultative cases have most often been received with concern for a diagnosis of atypical lipomatous tumor. Similar tumors have been described in small series under the designations "subcutaneous minimally atypical lipomatous tumors" and "anisometric cell lipoma." Sixty-six cases of this tumor type were collected and reviewed. Immunohistochemistry for p53, MDM2, CDK4, Retinoblastoma 1 (RB1) protein, CD34, S100, and CD163 was performed. Cases were tested for MDM2 gene amplification and RB1 gene deletion with fluorescence in situ hybridization (FISH) and for TP53 mutations by Sanger sequencing. Next-generation sequencing analysis using a panel of 271 cancer-related genes, including TP53, RB1, and MDM2, was also carried out. Our patient cohort included 57 male patients, 8 female patients, and 1 patient of unstated sex, who ranged in age from 22 to 87 years (mean: 51.2 y). All tumors were subcutaneous, with most examples occurring on the upper back, shoulders, or posterior neck (86.4%). Ten patients had multiple (2 to 5) lipomatous tumors, and the histology was confirmed to be similar in the different sites in 4 of them, including 1 patient who had a retinoblastoma diagnosed at age 1. The tumors were generally well circumscribed. At low magnification, there was notable adipocytic size variation with single-cell fat necrosis in the background associated with reactive histiocytes. Adipocytic nuclear atypia was typically patchy and characterized by chromatin coarsening, nuclear enlargement, and focal binucleation or multinucleation. Focal Lochkern change was frequent. In most instances, the degree of atypia was judged to be mild, but in 3 instances, it was more pronounced. Spindle cells were sparse or absent, and when present, cytologically bland. Thick ropy collagen bundles were absent. In all cases, p53 immunoexpression was noted (range: 2% to 20% of adipocytic nuclei), characteristically highlighting the most atypical cells. Twenty of 50 cases had MDM2 immunoreactivity, usually in <1% of the neoplastic cells, but in 4 cases, up to 10% of the cells were positive. Of 32 cases tested, 22 showed a near total loss of RB1 immunoexpression, and the remainder showed partial loss. Three of 13 cases showed RB1 gene deletion in >45% of the cells by FISH (our threshold value for reporting a positive result) with an additional 3 cases being very close to the required cutoff value. MDM2 gene amplification was absent in all 60 cases tested, including those with the greatest MDM2 immunoexpression and most pronounced atypia. All 5 tested cases showed no TP53 mutation with Sanger sequencing. Because of material quality issues, next-generation sequencing analysis could be performed in only 3 cases, and this did not reveal any recurrent mutations. All tumors were managed by simple local excision. Follow-up was available for 47 patients (range: 1 to 192 mo; mean: 27 mo) and revealed 2 local recurrences and no metastases. Dysplastic lipoma is a distinctive atypical fatty tumor variant that has p53 overexpression and RB1 gene abnormalities and lacks MDM2 gene amplification by FISH. These tumors have a strong male predominance and a notable tendency to involve the subcutaneous tissue of the shoulders, upper back and posterior neck. Multifocality is frequent (18.9% of patients with follow-up information), and there is a rare association with retinoblastoma. This tumor warrants separation from ordinary lipoma with fat necrosis, fat-rich spindle cell lipoma and the conventional form of atypical lipomatous tumor that features MDM2 gene amplification.
Topics: Adipocytes; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; DNA Mutational Analysis; Diagnosis, Differential; Europe; Fat Necrosis; Female; Gene Amplification; Genetic Predisposition to Disease; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Liposarcoma; Male; Middle Aged; Mutation; Neoplasms, Multiple Primary; Predictive Value of Tests; Proto-Oncogene Proteins c-mdm2; Retinoblastoma; Retinoblastoma Binding Proteins; Retrospective Studies; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases; Up-Regulation; Young Adult
PubMed: 30001242
DOI: 10.1097/PAS.0000000000001129 -
Infection and Drug Resistance 2023Information about dynamic changes occurring in the parameters and morphology of erythrocytes and platelets during the coronavirus disease 2019 (COVID-19) infection and...
PURPOSE
Information about dynamic changes occurring in the parameters and morphology of erythrocytes and platelets during the coronavirus disease 2019 (COVID-19) infection and convalescence is scarce. To explore potential associations between dynamic erythrocyte and platelet parameters, morphological changes, and the course or severity of the disease is essential.
PATIENTS AND METHODS
From January 17th, 2020, to February 20th, 2022, we followed up on 35 patients with non-severe and 11 patients with severe COVID-19 following their discharge. We collected clinical features, dynamic complete blood count (CBC), and peripheral blood smears (PBS) and analyzed parameter and morphological changes of erythrocytes and platelets depending on the course or severity of the disease. The course of the disease included four periods, namely onset (T1), discharge (T2), 1-year follow-up (T3), and 2-year follow-up (T4).
RESULTS
Red blood cell (RBC) counts and hemoglobin were the lowest in T2, followed by T1, and lower in T1 and T2 than in T3 and T4. Inversely, the red blood cell distribution width (RDW) was the highest in T2, followed by T1, and higher than in T3 and T4. Compared to non-severe patients, the platelet of severe patients was lower in T1 and T2. In contrast, the mean platelet volume (MPV) and platelet distribution width (PDW) tended to be higher in severe patients. Similarly, anisocytosis was more common in peripheral blood smears at early stages and in severe patients. Finally, large platelets were more common in severe patients.
CONCLUSION
Anisocytosis of erythrocytes and large platelets are found in patients with severe COVID-19, these changes may help primary hospitals to identify patients with a high risk of severe COVID-19 at an early stage.
PubMed: 36992967
DOI: 10.2147/IDR.S400735 -
Clinical Chemistry and Laboratory... Jul 2023Extracellular histone levels are associated with the severity of many human pathologies, including sepsis and COVID-19. This study aimed to investigate the role of...
OBJECTIVES
Extracellular histone levels are associated with the severity of many human pathologies, including sepsis and COVID-19. This study aimed to investigate the role of extracellular histones on monocyte distribution width (MDW), and their effect on the release of cytokines by blood cells.
METHODS
Peripheral venous blood was collected from healthy subjects and treated with different doses of a histone mixture (range 0-200 μg/mL) to analyze MDW modifications up-to 3 h and digital microscopy of blood smears. Plasma obtained after 3 h of histone treatment were assayed to evaluate a panel of 24 inflammatory cytokines.
RESULTS
MDW values significantly increased in a time- and dose-dependent manner. These findings are associated with the histone-induced modifications of cell volume, cytoplasmic granularity, vacuolization, and nuclear structure of monocytes, promoting their heterogeneity without affecting their count. After 3 h of treatment almost all cytokines significantly increased in a dose-dependent manner. The most relevant response was shown by the significantly increased G-CSF levels, and by the increase of IL-1β, IL-6, MIP-1β, and IL-8 at the histone doses of 50, 100, and 200 µg/mL. VEGF, IP-10, GM-CSF, TNF-α, Eotaxin, and IL-2 were also up-regulated, and a lower but significant increase was observed for IL-15, IL-5, IL-17, bFGF, IL-10, IFN-γ, MCP-1, and IL-9.
CONCLUSIONS
Circulating histones critically induce functional alterations of monocytes mirrored by MDW, monocyte anisocytosis, and hyperinflammation/cytokine storm in sepsis and COVID-19. MDW and circulating histones may be useful tools to predict higher risks of worst outcomes.
Topics: Humans; Histones; Monocytes; Cytokine Release Syndrome; COVID-19; Cytokines; Sepsis
PubMed: 36847604
DOI: 10.1515/cclm-2023-0093 -
Pathogens & Immunity 2017Treated HIV infection is associated with heightened inflammation which can contribute to increased risk of cardiovascular disease (CVD). We have previously shown that...
BACKGROUND
Treated HIV infection is associated with heightened inflammation which can contribute to increased risk of cardiovascular disease (CVD). We have previously shown that anisocytosis, as measured by red cell distribution width (RDW), is independently associated with prevalent CVD in people living with HIV (PLHIV). In this study, we sought to identify immune correlates of RDW in PLHIV receiving antiretroviral therapy.
METHODS
We performed a cross-sectional and longitudinal analysis of 147 virally-suppressed PLHIV, who had LDL < 130 mg/dL and evidence of heightened inflammation, in a randomized trial of statin therapy. A complete blood count and biomarkers of inflammation and immune activation/exhaustion were measured in peripheral blood at entry and after 24 and 48 weeks. Associations with RDW were estimated using linear regression and linear mixed models.
RESULTS
The median age (IQR) for the cohort at enrollment was 46 (40-53) years; 78% were male and 68% were African American. The median RDW for the cohort was 13.4% (12.9-14.0). Compared with the lowest RDW tertile, patients in the highest tertile were less likely to be male, and more likely to be African American, have lower hemoglobin, lower mean corpuscular volume, and higher platelet counts (all < 0.05). At baseline, RDW weakly correlated with C-reactive protein (r = 0.196), d-dimer (r = 0.214), fibrinogen (r = 0.192), IL-6 (r = 0.257), CD4+DR+38+ T cells (r = 0.195), and CD4+PD1+ T cells (r = 0.227), all < 0.05. Only IL-6, CD4+38+DR+ T cells, and CD4+PD1+ T_cells remained associated after adjustment for clinical factors known to affect RDW in the general population. Over 48 weeks, RDW did not change and there was no significant effect of statin ( = 0.45). After adjustment for clinical parameters, RDW remained positively associated with CD4+38+DR+ and CD4+PD1+ T cells across all time points ( = 0.05).
CONCLUSION
In this population of treated HIV+ subjects, anisocytosis was associated with biomarkers of inflammation and T-cell activation/exhaustion over time and independent of clinical confounders. Therefore, RDW may be a useful prognostic biomarker of cardiovascular risk that partially reflects chronic inflammation and immune exhaustion in PLHIV receiving antiretroviral therapy.
PubMed: 28713869
DOI: 10.20411/pai.v2i1.199 -
Medicina (Kaunas, Lithuania) Mar 2022Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron...
Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron turnover: serum soluble transferrin receptor (sTfR) and hepcidin-25 in patients at various stages of MM in relation with markers of anemia, iron status, inflammation, renal impairment and burden of the disease and as predictors of mortality. Seventy-three MM patients (six with smoldering and 67 with symptomatic disease) were recruited and observed for up to 27 months. Control group included 21 healthy individuals. Serum sTfR and hepcidin were measured with immunoenzymatic assays. MM patients with and without anemia had higher sTFR compared to controls, while only anemic patients had higher hepcidin-25. Both hepcidin-25 and sTfR were higher in anemic than non-anemic patients. Higher hepcidin-25 (but not sTfR) was associated with increasing MM advancement (from smoldering to International Staging System stage III disease) and with poor response to MM treatment, which was accompanied by lower blood hemoglobin and increased anisocytosis. Neither serum hepcidin-25 nor sTfR were correlated with markers of renal impairment. Hepcidin-25 predicted blood hemoglobin in MM patients independently of other predictors, including markers of renal impairment, inflammation and MM burden. Moreover, both blood hemoglobin and serum hepcidin-25 were independently associated with patients' 2-year survival. Our results suggest that hepcidin-25 is involved in anemia in MM and its concentrations are not affected by kidney impairment. Moreover, serum hepcidin-25 may be an early predictor of survival in this disease, independent of hemoglobin concentration. It should be further evaluated whether including hepcidin improves the early diagnosis of anemia in MM.
Topics: Anemia; Hemoglobins; Hepcidins; Humans; Kidney Diseases; Multiple Myeloma; Receptors, Transferrin
PubMed: 35334593
DOI: 10.3390/medicina58030417 -
Journal of Comparative Pathology Jan 2018Merkel cell carcinoma is a rare and aggressive cutaneous neuroendocrine tumour reported only in man, dogs and cats. A 20-month-old Japanese black fattening steer was...
Merkel cell carcinoma is a rare and aggressive cutaneous neuroendocrine tumour reported only in man, dogs and cats. A 20-month-old Japanese black fattening steer was presented with necrotic protruding skin masses over the left thoracic area and a 20 × 25 cm subcutaneous mass in the left abdominal area. Microscopical evaluation of the masses revealed cords of small to medium-sized round tumour cells with marked anisocytosis and anisokaryosis and clear and vacuolated cytoplasm, which were separated by a delicate fibrovascular stroma and arranged in a trabecular and nested pattern. Necropsy examination revealed multiple solid white nodular masses in the lungs. Immunohistochemistry (IHC) for cytokeratin (CK) 20 and CKAE1/3 revealed focal perinuclear labelling of tumour cells. IHC for the neuroendocrine markers chromogranin A and neuron specific enolase, the neuroepithelial stem cell marker nestin and the hormonal markers adrenocorticotropic hormone and calcitonin revealed diffuse cytoplasmic labelling of all tumour cells. Ultrastructurally, the tumour cells contained few neurosecretory granules and abundant glycogen pools. The tumours were diagnosed as Merkel cell carcinoma with pulmonary metastases and this case represents the first such diagnosis in cattle.
Topics: Animals; Carcinoma, Merkel Cell; Cattle; Cattle Diseases; Male; Skin Neoplasms
PubMed: 29422311
DOI: 10.1016/j.jcpa.2017.10.177 -
Frontiers in Veterinary Science 2022Red blood cells (RBC) morphologic evaluation through microscopy optical (OM) and SEM, provides information to forecast, evaluate, and monitor the functioning of many...
Red blood cells (RBC) morphologic evaluation through microscopy optical (OM) and SEM, provides information to forecast, evaluate, and monitor the functioning of many organs. Factors, such aging and diseases affect RBC morphology in both, human and animals. SEM is useful to evaluate RBC morphology, although its use in diagnosis and evaluation in dogs is limited, due to the availability and cost. The aim of this research was to assess the normal RBC morphology in adult, senior and geriatrician dogs, clinically healthy by OM and SEM. In addition to evaluating the age effect, sex, body size, and their interaction on erythrocyte morphometry. To carry out the research 152 blood samples were evaluated from dogs of different sexes and body sizes (small, medium, and large). Three groups were made based on dogs age: group I adults (1-7.9 years old), group II senior (8-11.9 years old), and group III geriatricians (>12 years old). Erythrocyte parameters were evaluated by OM (diameter, height, and axial ratio). Per each dog, the parameters of 20 erythrocytes were measured. A total of 2,600 cells were scanned with the AmScope™ Software scale. In addition, the RBC morphology was evaluated by SEM. Statistical analyses used analysis of variance and a general linear model, which allows the comparison of multiple factors at two or more levels ( < 0.05). The results of this study showed that diameter and height were lower in adult dogs than in senior and geriatrician dogs ( < 0.05). Whereas, sex, body size, and the interaction did not show a significant effect ( > 0.05). Additionally, some images of anisocytosis, polychromasia, and poikilocytosis (echinocytes, acanthocytes, codocytes, spherocytes, stomatocytes, dacryocytes quatrefoil, and elliptocytes) were obtained by OM and SEM. Our study provides information about the morphological and morphometry alterations of adult, senior, and geriatrician dogs RBC. This work contributes to future investigations and the diagnosing diseases, where it is necessary to evaluate the morphology of RBC.
PubMed: 36439358
DOI: 10.3389/fvets.2022.998438 -
Frontiers in Bioscience (Elite Edition) Jul 2023The advent of immune checkpoint inhibitors (ICIs) has revolutionized the metastatic renal cell carcinoma (mRCC) therapeutic landscape. Nevertheless, tyrosine-kinase... (Observational Study)
Observational Study
Integrating Red Blood Cell Features and Hemoglobin Levels in Metastatic Renal Cell Carcinoma Patients Treated with Pazopanib or Cabozantinib: An Easily Exploitable Prognostic Score.
BACKGROUND
The advent of immune checkpoint inhibitors (ICIs) has revolutionized the metastatic renal cell carcinoma (mRCC) therapeutic landscape. Nevertheless, tyrosine-kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) axis still play a key role. The aim of the present study was to explore the prognostic performance of an integrated blood score, based on hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and red cell distribution width (RDW), in mRCC patients treated with anti-VEGF TKIs. The primary endpoint was to correlate Hb, MCV, and RDW with progression-free survival (PFS) and overall survival (OS).
MATERIALS AND METHODS
Our multicenter retrospective observational study involved mRCC patients treated with pazopanib or cabozantinib from January 2012 to December 2020 in nine Italian centers. Clinical records and laboratory data, including Hb levels, MCV, and RDW, were collected at baseline. Descriptive statistics and univariate and multivariate analyses were performed.
RESULTS
We enrolled 301 mRCC patients of which 179 (59%) underwent pazopanib, and 122 (41%) cabozantinib. We considered baseline Hb ≥12 g/dL, MCV >87 fL, and RDW ≤16% as good prognostic factors; hence, developing a multiparametric score capable of delineating 4 different categories. The number of good prognostic factors was associated with significantly longer PFS and OS ( 0.001 for both). Therefore, we developed a red blood cell-based score by stratifying cases into two groups (2-3 0-1, good factors). The impact on PFS and OS was even more striking (median PFS (mPFS): 16.3 7.9 months; median OS (mOS): 33.7 14.1 months)), regardless of the TKI agent. When challenged with univariate and multivariate analysis, the blood score maintained its high prognostic significance in terms of OS (multivariate analysis HR for OS: 0.53, 95% CI 0.39-0.75; < 0.001, respectively), while the impact on PFS resulted in borderline significance.
CONCLUSIONS
Our analyses demonstrate the prognostic role of a multiparametric score based on easily exploitable blood parameters, such as Hb concentration, MCV, and RDW. The red blood cell-based score may underlie the upregulation of the HIF-1α pathway and VEGF axis, thereby identifying a selected population who is likely to benefit from TKI therapy.
Topics: Humans; Carcinoma, Renal Cell; Vascular Endothelial Growth Factor A; Prognosis; Kidney Neoplasms; Erythrocytes; Hemoglobins
PubMed: 37743233
DOI: 10.31083/j.fbe1503020