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Journal of Clinical Pathology Jun 2020Paraneoplastic leukemoid reaction (PLR) is the extreme leukocytosis that occurs due to a non-haematolymphoid cytokine-secreting tumour (CST) in the absence of bone... (Review)
Review
Paraneoplastic leukemoid reaction (PLR) is the extreme leukocytosis that occurs due to a non-haematolymphoid cytokine-secreting tumour (CST) in the absence of bone marrow infiltration by that solid tumour. The clinical presentation is widely variable, and therefore challenging. If the underlying malignancy is not clinically apparent, PLR could be mistaken for myeloproliferative neoplasms, altering the patient's management. CSTs are highly aggressive tumours associated with a poor prognosis due to multiple mechanisms. Localising and treating the underlying malignancy is the mainstay of treatment. Both the treating clinician and the pathologist should keep a high level of suspicion for this entity in patients having unexplained leukocytosis. We herein discuss the underlying mechanisms, clinical presentation, pathological features, differential diagnosis and prognosis of this rare entity. An emphasis on the role of the pathologist is provided since the lack of knowledge on this entity can lead to dramatic effects on the patient, including unnecessary diagnostic testing and treatments.
Topics: Cytokines; Diagnosis, Differential; Humans; Leukemia, Myeloid; Leukemoid Reaction; Leukocytes; Myeloproliferative Disorders; Neoplasms; Prognosis
PubMed: 31941653
DOI: 10.1136/jclinpath-2019-206340 -
EBioMedicine May 2023Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies....
BACKGROUND
Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies. However, defining the presence of neuroinflammation, and monitoring the effects of therapy is important given its reversible and potentially damaging nature. We investigated the utility of CSF metabolites in the diagnosis of primary neuroinflammatory disorders such as encephalitis and explored the potential pathogenic role of inflammation in epilepsy.
METHODS
Cerebrospinal fluid (CSF) collected from 341 paediatric patients (169 males, median age 5.8 years, range 0.1-17.1) were examined. The patients were separated into a primary inflammatory disorder group (n = 90) and epilepsy group (n = 80), who were compared with three control groups including neurogenetic and structural (n = 76), neurodevelopmental disorders, psychiatric and functional neurological disorders (n = 63), and headache (n = 32).
FINDINGS
There were statistically significant increases of CSF neopterin, kynurenine, quinolinic acid and kynurenine/tryptophan ratio (KYN/TRP) in the inflammation group compared to all control groups (all p < 0.0003). As biomarkers, at thresholds with 95% specificity, CSF neopterin had the best sensitivity for defining neuroinflammation (82%, CI 73-89), then quinolinic acid (57%, CI 47-67), KYN/TRP ratio (47%, CI 36-56) and kynurenine (37%, CI 28-48). CSF pleocytosis had sensitivity of 53%, CI 42-64). The area under the receiver operating characteristic curve (ROC AUC) of CSF neopterin (94.4% CI 91.0-97.7%) was superior to that of CSF pleocytosis (84.9% CI 79.5-90.4%) (p = 0.005). CSF kynurenic acid/kynurenine ratio (KYNA/KYN) was statistically decreased in the epilepsy group compared to all control groups (all p ≤ 0.0003), which was evident in most epilepsy subgroups.
INTERPRETATION
Here we show that CSF neopterin, kynurenine, quinolinic acid and KYN/TRP are useful diagnostic and monitoring biomarkers of neuroinflammation. These findings provide biological insights into the role of inflammatory metabolism in neurological disorders and provide diagnostic and therapeutic opportunities for improved management of neurological diseases.
FUNDING
Financial support for the study was granted by Dale NHMRC Investigator grant APP1193648, University of Sydney, Petre Foundation, Cerebral Palsy Alliance and Department of Biochemistry at the Children's Hospital at Westmead. Prof Guillemin is funded by NHMRC Investigator grant APP 1176660 and Macquarie University.
Topics: Male; Humans; Child; Infant; Child, Preschool; Adolescent; Tryptophan; Kynurenine; Neopterin; Quinolinic Acid; Neuroinflammatory Diseases; Leukocytosis; Inflammation; Biomarkers; Nervous System Diseases
PubMed: 37119734
DOI: 10.1016/j.ebiom.2023.104589 -
Japanese Journal of Infectious Diseases Nov 2023Reverse-transcription polymerase chain reaction (RT-PCR)-confirmed enterovirus (EV) meningitis without pleocytosis has only been previously reported in children. In this... (Observational Study)
Observational Study
Reverse-transcription polymerase chain reaction (RT-PCR)-confirmed enterovirus (EV) meningitis without pleocytosis has only been previously reported in children. In this study, we examined the frequency of EV meningitis without pleocytosis in adults and compared its clinical features. We retrospectively analyzed the data of adult patients with EV meningitis confirmed using cerebrospinal fluid (CSF) RT-PCR. Among the 17 patients included in this study, 58.8% showed no pleocytosis. The median age and clinical symptoms did not differ between the pleocytosis and non-pleocytosis groups. There were no statistically significant differences in seasonal variation or time from the onset of meningitis symptoms to lumbar puncture. The peripheral white blood cell (WBC) count in patients with pleocytosis was significantly higher than that in patients without pleocytosis. The median CSF pressure showed a higher trend in the non-pleocytosis group. Patients with CSF pressures higher than normal were more common in the non-pleocytosis group. The median CSF protein values were higher than the normal values in both groups. We confirmed the high frequency of EV meningitis without pleocytosis in adults. Accurate diagnosis using RT-PCR is necessary when meningitis symptoms are prominent during an EV epidemic, and CSF protein levels and pressure are high, even if the CSF WBC count is normal.
Topics: Child; Humans; Adult; Infant; Leukocytosis; Retrospective Studies; Meningitis, Viral; Enterovirus Infections; Enterovirus
PubMed: 37394460
DOI: 10.7883/yoken.JJID.2023.123 -
Journal of Neurology Oct 2022To investigate the prognostic value of white blood cell count (WBC) on functional outcome, mortality and bleeding risk in stroke patients treated with intravenous...
OBJECTIVE
To investigate the prognostic value of white blood cell count (WBC) on functional outcome, mortality and bleeding risk in stroke patients treated with intravenous thrombolysis (IVT).
METHODS
In this prospective multicenter study from the TRISP registry, we assessed the association between WBC on admission and 3-month poor outcome (modified Rankin Scale 3-6), mortality and occurrence of symptomatic intracranial hemorrhage (sICH; ECASS-II-criteria) in IVT-treated stroke patients. WBC was used as continuous and categorical variable distinguishing leukocytosis (WBC > 10 × 10/l) and leukopenia (WBC < 4 × 10/l). We calculated unadjusted/ adjusted odds ratios with 95% confidence intervals (OR [95% CI]) with logistic regression models. In a subgroup, we analyzed the association of combined leukocytosis and elevated C-reactive protein (CRP > 10 mg/l) on outcomes.
RESULTS
Of 10,813 IVT-treated patients, 2527 had leukocytosis, 112 leukopenia and 8174 normal WBC. Increasing WBC (by 1 × 10/l) predicted poor outcome (OR 1.04[1.02-1.06]) but not mortality and sICH. Leukocytosis was independently associated with poor outcome (OR 1.48[1.29-1.69]) and mortality (OR 1.60[1.35-1.89]) but not with sICH (OR 1.17[0.94-1.45]). Leukopenia did not predict any outcome. In a subgroup, combined leukocytosis and elevated CRP had the strongest association with poor outcome (OR 2.26[1.76-2.91]) and mortality (OR 2.43[1.86-3.16]) when compared to combined normal WBC and CRP.
CONCLUSION
In IVT-treated patients, leukocytosis independently predicted poor functional outcome and death. Bleeding complications after IVT were not independently associated with leukocytosis.
Topics: Brain Ischemia; Fibrinolytic Agents; Humans; Leukocytosis; Leukopenia; Prospective Studies; Stroke; Thrombocytopenia; Thrombolytic Therapy; Treatment Outcome
PubMed: 35622132
DOI: 10.1007/s00415-022-11173-0 -
BMJ Case Reports May 2019A female aged 84 years with a history of -associated diarrhoea presented from an extended care facility with altered mental status and respiratory distress. She was...
A female aged 84 years with a history of -associated diarrhoea presented from an extended care facility with altered mental status and respiratory distress. She was haemodynamically unstable and initial laboratory results revealed hyperleucocytosis (110.3×10/L). The presence of immature myeloid precursors, thrombocytopenia and respiratory distress, raised concern for an acute leukaemic process requiring emergent leucapheresis. However, on evaluation of the peripheral smear, prominent left shift and toxic granulation were noted, along with absence of blast cells. Considering her history of infection, a CT scan of the abdomen and pelvis was obtained, which was suggestive of toxic megacolon. She was taken to the operating room for emergent colectomy. The pathology specimen showed pseudomembrane formation consistent with fulminant infection. She was treated with oral vancomycin and intravenous metronidazole, followed by clinical improvement and resolution of leucocytosis and thrombocytopenia.
Topics: Aged, 80 and over; Anti-Bacterial Agents; Clostridium Infections; Colectomy; Diagnosis, Differential; Female; Humans; Leukemia; Leukocytosis; Megacolon, Toxic; Metronidazole; Tomography, X-Ray Computed; Vancomycin
PubMed: 31129636
DOI: 10.1136/bcr-2018-228219 -
Cell Cycle (Georgetown, Tex.) Dec 2016
Topics: Leukemoid Reaction; Macrophages
PubMed: 27494148
DOI: 10.1080/15384101.2016.1216927 -
World Journal of Gastroenterology Feb 2017Lymphocytic esophagitis (LE) is a clinicopathologic entity first described by Rubio et al in 2006. It is defined as peripapillary intraepithelial lymphocytosis with... (Review)
Review
Lymphocytic esophagitis (LE) is a clinicopathologic entity first described by Rubio et al in 2006. It is defined as peripapillary intraepithelial lymphocytosis with spongiosis and few or no granulocytes on esophageal biopsy. This definition is not widely accepted and the number of lymphocytes needed to make the diagnosis varied in different studies. Multiple studies have described potential clinical associations and risk factors for LE, such as old age, female gender and smoking history. This entity was reported in inflammatory bowel disease in the pediatric population but not in adults. Other associations include gastroesophageal reflux disease and primary esophageal motility disorders. The most common symptom is dysphagia, with a normal appearing esophagus on endoscopy, though esophageal rings, webs, nodularities, furrows and strictures have been described. Multiple treatment modalities have been used such as proton pump inhibitors and topical steroids. Esophageal dilation seems to be therapeutic when dysphagia is present along with esophageal narrowing secondary to webs, rings or strictures. The natural history of the disease remains unclear and needs to be better delineated. Overall, lymphocytic esophagitis seems to have a chronic and benign course, except for two cases of esophageal perforation in the literature, thought to be secondary to this entity.
Topics: Biopsy; Botulinum Toxins, Type A; Endoscopy; Esophageal Motility Disorders; Esophagitis; Gastroesophageal Reflux; Glucocorticoids; Humans; Lymphocytosis; Proton Pump Inhibitors
PubMed: 28246468
DOI: 10.3748/wjg.v23.i6.949 -
International Maritime Health 2022Follow-up of patients who had coronavirus disease 2019 (COVID-19) proves that clinical symptoms persist for months after recovery. A complex of such persistent...
BACKGROUND
Follow-up of patients who had coronavirus disease 2019 (COVID-19) proves that clinical symptoms persist for months after recovery. A complex of such persistent manifestations is defined as the post-COVID-19 syndrome. One of the criteria for post-COVID-19 syndrome may be typical changes in white blood cell count and white blood cell (WBC) differential. The aim of the work is to study the frequency of haematological changes in sailors who had the acute coronavirus infection.
MATERIALS AND METHODS
The retrospective study covered 30 candidate sailors aged 21 to 60 years with a history of COVID-19 and persistent changes in the WBC count and WBC differential and who did not have haematological abnormalities during the previous medical examinations.
RESULTS
Analysis of WBC and WBC count at the long-term period after COVID-19 confirmed persistent changes in the form of neutrophilia, lymphopenia, changes in the neutrophils and lymphocytes ratio. The revealed changes in the WBC count were typical and fit into several patterns: A. Absolute leukocytosis, absolute and relative neutrophilia, relative lymphopenia; B. Relative and absolute lymphopenia, relative neutrophilia; C. Relative and absolute lymphocytosis, relative neutropenia; D. Relative lymphopenia, without other changes in WBC differential.
CONCLUSIONS
The most typical laboratory change in WBC count in patients with the past COVID-19 is relative or absolute leukopenia. Persistent changes in WBC count are not always outside of the reference range for absolute values and should be assessed by a complex of typical changes. The presence of typical changes in WBC count in a patient with the past COVID-19 requires a profound examination for the post-COVID-19 syndrome.
Topics: Humans; COVID-19; Post-Acute COVID-19 Syndrome; Retrospective Studies; Military Personnel; Leukocytosis; Lymphopenia
PubMed: 36583404
DOI: 10.5603/IMH.2022.0031 -
Blood Cancer Journal Jan 2024We describe 1000 patients with essential thrombocythemia seen at the Mayo Clinic between 1967 and 2023: median age 58 years (18-90), females 63%, JAK2/CALR/MPL-mutated...
We describe 1000 patients with essential thrombocythemia seen at the Mayo Clinic between 1967 and 2023: median age 58 years (18-90), females 63%, JAK2/CALR/MPL-mutated 62%/27%/3%, triple-negative (TN) 8%, extreme thrombocytosis (ExT; platelets ≥1000 × 10/L) 26%, leukocytosis (leukocyte count >11 × 10/L) 20%, and abnormal karyotype 6%. JAK2-mutated patients were older (median 71 years), and CALR mutated (52 years), and TN (50 years) younger (p < 0.01). Female gender clustered with TN (73%) and JAK2 (69%) vs. CALR/MPL (49%/47%) mutations (p < 0.01). ExT clustered with CALR (type-2 more than type-1) and TN and leukocytosis with JAK2 mutation (p < 0.01). In multivariable analysis, risk factors for overall survival were older age (p < 0.01), male gender (HR 1.8), absolute neutrophil count (ANC) ≥ 8 × 10/L (HR 1.6), absolute lymphocyte count (ALC) < 1.7 × 10/L (HR 1.5), hypertension (HR 1.7), and arterial thrombosis history (HR 1.7); for leukemia-free survival, ExT (HR 2.3) and abnormal karyotype (HR 3.1); for myelofibrosis-free survival, ANC ≥ 8 × 10/L (HR 2.3) and MPL mutation (HR 3.9); for arterial thrombosis-free survival, age ≥60 years (HR 1.9), male gender (HR 1.6), arterial thrombosis history (HR 1.7), hypertension (HR 1.7), and JAK2 mutation (HR 1.8); for venous thrombosis-free survival, male gender (HR 1.8) and venous thrombosis history (HR 3.0). Associations between ExT and leukemic transformation and between ANC and fibrotic progression were limited to JAK2-mutated cases. Aspirin therapy appeared to mitigate both arterial (HR 0.4) and venous (HR 0.4) thrombosis risk. HR-based risk models delineated patients with median survivals ranging from 10 years to not reached and 20-year leukemia/myelofibrosis incidences from 3%/21% to 12.8%/49%. The current study provides both novel and confirmatory observations of essential thrombocythemia.
Topics: Humans; Male; Female; Middle Aged; Thrombocythemia, Essential; Leukocytosis; Thrombosis; Mutation; Primary Myelofibrosis; Abnormal Karyotype; Hypertension; Janus Kinase 2; Calreticulin
PubMed: 38238303
DOI: 10.1038/s41408-023-00972-x -
Cephalalgia : An International Journal... Apr 2023Headache with neurologic deficits and cerebrospinal fluid lymphocytosis, previously also termed pseudomigraine with temporary neurologic symptoms and lymphocytic... (Review)
Review
BACKGROUND
Headache with neurologic deficits and cerebrospinal fluid lymphocytosis, previously also termed pseudomigraine with temporary neurologic symptoms and lymphocytic pleocytosis, is a self-limiting syndrome characterized by moderate to severe headache associated with focal neurological deficits occurring in the context of lymphocytosis in the cerebrospinal fluid. As a consequence of its rarity, data regarding headache with neurologic deficits and cerebrospinal fluid lymphocytosis is sparse. Therefore, we conducted this review to analyze data related to 93 patients of headache with neurologic deficits and cerebrospinal fluid lymphocytosis, to characterize their demographics, clinical manifestations, investigations and treatment options.
METHODS
We performed a systematic review of cases reported through PubMed and Google scholar database, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Keywords used were 'Headache with Neurologic Deficits and cerebrospinal fluid lymphocytosis', 'Headache with neurologic deficits and cerebrospinal fluid lymphocytosis syndrome'. The quality of the included studies was assessed using the Joanna Briggs Institute Critical Appraisal Tool.
RESULTS
We analyzed a total of 93 cases of headache with neurologic deficits and cerebrospinal fluid lymphocytosis with a mean age of 28.8 years at onset. Seventy patients (75.2%) were adults, while 23 (24.7%) belonged to the pediatric age group. Comparing these groups, mean age at onset was 32.5 years and 14.3 years, respectively. The average duration of follow-up was 11.08 months. Thirty percent of patients experienced relapsing episodes of headache with neurologic deficits and cerebrospinal fluid lymphocytosis symptoms. The most common type of headache reported was unilateral severe throbbing episodic headache. Other associated symptoms included sensory deficit (60%) and motor deficits (54.8%). The least common symptoms were nystagmus and agraphia, which were reported in one patient each. Antiviral agents were a common treatment option in the acute phase (n = 23 patients [23.6%]), while Flunarizine was the most commonly used agent in the chronic setting (n = 3 patients [3.2%]). While most of the patients had normal brain magnetic resonance imaging, 20 patients had magnetic resonance imaging abnormalities, including (but not limited to) non-specific white matter lesions (eight patients) and meningeal enhancement (six patients). The most common electroencephalographic findings included diffuse and focal slowing. The mean cerebrospinal fluid opening-pressure was 240.5 mmHO. Cerebrospinal fluid protein was elevated in 59 (63.4%) patients, with a mean value of 114 mg/dL. Two patients in our cohort were found to have cerebrospinal fluid oligoclonal bands.
CONCLUSION
Headache with neurologic deficits and cerebrospinal fluid lymphocytosis tends to affect young individuals with a slight male predominance. Unilateral severe throbbing episodic headache with associated hemi-paresthesia and hemiparesis were the most common symptoms based on our review. Elevated cerebrospinal fluid opening-pressure can be seen in headache with neurologic deficits and cerebrospinal fluid lymphocytosis syndrome. Early recognition of the syndrome is paramount. Antivirals were found to be among the most widely used treatments in the acute setting. Magnetic resonance imaging of the brain is mostly normal. Diffuse and focal slowing were among the most common electroencephalographic findings. Cerebral flow abnormalities on perfusion scans are not uncommon in headache with neurologic deficits and cerebrospinal fluid lymphocytosis. Prospective studies with a larger sample size are needed to validate our findings and guide the clinical care of these patients.
Topics: Adult; Humans; Male; Child; Female; Lymphocytosis; Prospective Studies; Headache; Cerebrospinal Fluid Pressure; Brain
PubMed: 36856002
DOI: 10.1177/03331024231157694