-
Diagnostics (Basel, Switzerland) Aug 2022Tumor-associated leukocytosis has been associated with poor prognosis in cervical cancer. Leukemoid reaction (i.e., white blood cell count > 40,000/μL) is defined... (Review)
Review
Pathogenic and Prognostic Roles of Paraneoplastic Leukocytosis in Cervical Cancer: Can Genomic-Based Targeted Therapies Have a Role? A Literature Review and an Emblematic Case Report.
Tumor-associated leukocytosis has been associated with poor prognosis in cervical cancer. Leukemoid reaction (i.e., white blood cell count > 40,000/μL) is defined paraneoplastic (PLR) when it occurs in the presence of a cytokine-secreting tumor (CST) without neoplastic bone marrow infiltration. Cervical cancers displaying PLR represent a peculiar entity characterized by a rapidly progressive behavior typically associated with chemo-radioresistance. The present paper aims to review the literature about the pathogenetic mechanisms of PLR and its prognostic role in cervical cancer. Moreover, it reports the emblematic case of a patient with an advanced cervical cancer associated with PLR that was chemotherapy resistant. The patient underwent a palliative cytoreductive surgery of high complexity, obtaining a temporary regression of PLR. The tumor sample stained positive for G-CSF and IL-6, thus indicating a CST. Notably, the tumor genomic analysis revealed a PI3CKA mutation. Therefore, at the instrumental evidence of a rapidly progressive disease relapse, which was accompanied by reappearance of PLR, we started a targeted treatment with a selective PIK3 inhibitor alpesilib combined with the JAK1-2 inhibitor ruxolitinib. We achieved a relief of symptoms and leukocytosis; however, severe side effects necessitated the treatment suspension. In conclusion, as therapeutic strategies for cancer with PLR are scarcely reported in literature, our study could contribute to expand our understanding of the topic and provide a basis for further research.
PubMed: 36010260
DOI: 10.3390/diagnostics12081910 -
Haematologica Apr 2021The megakaryocyte/erythroid Transient Myeloproliferative Disorder (TMD) in newborns with Down Syndrome (DS) occurs when N-terminal truncating mutations of the...
The megakaryocyte/erythroid Transient Myeloproliferative Disorder (TMD) in newborns with Down Syndrome (DS) occurs when N-terminal truncating mutations of the hemopoietic transcription factor GATA1, that produce GATA1short protein (GATA1s), are acquired early in development. Prior work has shown that murine GATA1s, by itself, causes a transient yolk sac myeloproliferative disorder. However, it is unclear where in the hemopoietic cellular hierarchy GATA1s exerts its effects to produce this myeloproliferative state. Here, through a detailed examination of hemopoiesis from murine GATA1s ES cells and GATA1s embryos we define defects in erythroid and megakaryocytic differentiation that occur relatively late in hemopoiesis. GATA1s causes an arrest late in erythroid differentiation in vivo, and even more profoundly in ES-cell derived cultures, with a marked reduction of Ter-119 cells and reduced erythroid gene expression. In megakaryopoiesis, GATA1s causes a differentiation delay at a specific stage, with accumulation of immature, kit-expressing CD41hi megakaryocytic cells. In this specific megakaryocytic compartment, there are increased numbers of GATA1s cells in S-phase of cell cycle and reduced number of apoptotic cells compared to GATA1 cells in the same cell compartment. There is also a delay in maturation of these immature GATA1s megakaryocytic lineage cells compared to GATA1 cells at the same stage of differentiation. Finally, even when GATA1s megakaryocytic cells mature, they mature aberrantly with altered megakaryocyte-specific gene expression and activity of the mature megakaryocyte enzyme, acetylcholinesterase. These studies pinpoint the hemopoietic compartment where GATA1s megakaryocyte myeloproliferation occurs, defining where molecular studies should now be focussed to understand the oncogenic action of GATA1s.
Topics: Animals; Cell Differentiation; Down Syndrome; GATA1 Transcription Factor; Humans; Infant, Newborn; Leukemoid Reaction; Megakaryocytes; Mice
PubMed: 32527952
DOI: 10.3324/haematol.2019.244541 -
BMJ Case Reports Aug 2019Leukemoid reaction is a paraneoplastic phenomenon associated predominantly with solid tumours. Malignancies presenting with leukemoid reaction have a grave prognosis. It...
Leukemoid reaction is a paraneoplastic phenomenon associated predominantly with solid tumours. Malignancies presenting with leukemoid reaction have a grave prognosis. It is defined as persistent neutrophil count greater than 50×103 cells/µL. We report a case of leukemoid reaction in a patient with metastatic penile cancer. A 60-year-old man with partial penectomy status for squamous cell carcinoma of penis on neoadjuvant chemotherapy, presented with left fungating inguinal lymphadenopathy and total leucocyte count 96×103 cells/µL and hypercalcaemia. Leucocytealkaline phosphatase (LAP) score was excessively elevated. The patient underwent left ilioinguinal block dissection along with vastus lateralis flap for defect reconstruction. Postoperatively, the neutrophil counts and serum calcium level normalised. The patient improved clinically and was discharged.
Topics: Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Humans; Hypercalcemia; Leukemoid Reaction; Leukocyte Count; Lymphadenopathy; Male; Middle Aged; Neoadjuvant Therapy; Penile Neoplasms
PubMed: 31409618
DOI: 10.1136/bcr-2019-230826 -
Pediatrics and Neonatology Jan 2024
Topics: Infant, Newborn; Humans; Leukemoid Reaction; Infant, Premature
PubMed: 37739873
DOI: 10.1016/j.pedneo.2023.05.007 -
Journal of Blood Medicine 2022Hematological disorders are heterogeneous conditions ranging from malignant to non-malignant disorders. Hematological malignancies comprise a collection of heterogeneous...
BACKGROUND
Hematological disorders are heterogeneous conditions ranging from malignant to non-malignant disorders. Hematological malignancies comprise a collection of heterogeneous conditions originating from cells of the bone marrow and the lymphatic system. Therefore, this study aimed to determine the pattern of bone marrow confirmed malignant and non-malignant hematological disorders in patients with abnormal hematological parameters.
METHODS
Institutional-based cross-sectional study was conducted in Dessie town from April 2020 to June 2021. A total of 228 study participants who had abnormal hematological parameters and referred for bone marrow examination were included consecutively. About 1.5 mL of bone marrow sample and 3 mL of venous blood sample were collected for bone marrow examination, complete blood count analysis and peripheral blood morphology examination. Wright stain, Sudan black B, and Prussian blue stains were used for staining the bone marrow and peripheral blood smears. The result was expressed in mean and standard deviation and presented in texts and tables. Ratio, frequency, and percentage were used to express the magnitude of malignant and non-malignant hematological disorders.
RESULTS
The overall prevalence of hematological malignancies among the study participants was 11.4% with 8.8% in male patients. The prevalence of hematological malignancies were 3.5% CML, 2.6% AML, 1.8% CLL and MM, 0.9% ALL and undifferentiated acute leukemia. On the other hand, 57.0% of the study participants had non-malignant hematological disorders. Regarding non-malignant hematological cases, 24.6% were erythroid hyperplasia, 10.5% aplastic anemia, 8.8% concomitant IDA and MBA, 7.0% MBA, 3.5% leukemoid reaction, 1.8% IDA, and 0.9% visceral leishmaniasis. In patients with HM, 66.7% of AML, 100% of CML and CLL, and 75% of MM patients had increased total WBC count, whereas 66.7% of AML, 62.5% of CML, 75% of CLL, and 50% of MM patients had decreased hemoglobin level. On the other hand, 66.7% of AML, and 50% of CML, ALL, and CLL patients had decreased platelet count.
CONCLUSION
In this study, 11.4% of the patients had hematological malignant cases, whereas 57% of the patients had non-malignant hematological cases. Therefore, in patients with hematological abnormalities and where conclusive diagnosis could not be made through clinical and other laboratory investigations, bone marrow examination should be done for definitive diagnosis, management and prognosis.
PubMed: 35210892
DOI: 10.2147/JBM.S346091 -
The American Journal of Case Reports Jan 2020BACKGROUND The presence of leukocytosis associated with non-hematological malignancy after ruling out other causes is defined as paraneoplastic leukemoid reaction (PLR)....
BACKGROUND The presence of leukocytosis associated with non-hematological malignancy after ruling out other causes is defined as paraneoplastic leukemoid reaction (PLR). PLR is a rare manifestation of various solid tumors. It is associated with poor prognosis unless receiving effective antineoplastic treatments. CASE REPORT A 72-year-old female was referred to a hematologist/oncologist for the evaluation of leukocytosis with neutrophilia. Initial workup was unremarkable; however, she had progressively worsening leukocytosis with neutrophilia, associated with severe anemia and dysphagia. Computed tomography (CT) scan revealed wall thickening at the gastroesophageal junction (GEJ) and multiple hypodensities of the liver. Esophagogastroduodenoscopy (EGD) confirmed the diagnosis of GEJ tumor and biopsy returned as adenocarcinoma with human epidermal growth factor receptor 2 (HER2) overexpression. Leukocytosis resolved after the first round of chemotherapy and the patient remains progression-free with the addition of trastuzumab to her chemotherapy regimen. CONCLUSIONS We report a rare case of PLR caused by GEJ adenocarcinoma. This is the first case of PLR in a patient with metastatic GEJ adenocarcinoma with HER2 overexpression in the Caucasian population. It is important to workup leukocytosis promptly, to keep malignancy in the differential diagnosis and to seek early hematology/oncology consultation.
Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Drug Therapy, Combination; Endoscopy, Digestive System; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Leukemoid Reaction; Liver; Paraneoplastic Syndromes; Receptor, ErbB-2; Trastuzumab
PubMed: 32001665
DOI: 10.12659/AJCR.919596 -
Cureus Feb 2024Alcoholic hepatitis (AH) is a clinicopathologic illness caused by excessive alcohol abuse and is a precursor of cirrhosis. The leukemoid reaction (LR) is characterized...
Alcoholic hepatitis (AH) is a clinicopathologic illness caused by excessive alcohol abuse and is a precursor of cirrhosis. The leukemoid reaction (LR) is characterized by a strikingly raised granulocyte count of 40,000-50,000 cells/mm. The LR usually suggests an acute inflammatory reaction. It is usually mistaken for chronic myeloid leukemia. The initial phase of leukocytosis occurs due to the releasing of cells from the bone marrow with more immature cells, causing a left upper shift in the ratio of immature to mature neutrophils and macrophages. The LR is usually seen in cases of leukemia but is rare to present in alcohol hepatitis. Excessive alcohol use causes AH in persons with or without underlying chronic liver disease. In severe AH, leukemoid responses have been associated with very poor prognosis and short-term mortality. We describe a case of a 35-year-old male with severe AH with an LR.
PubMed: 38481914
DOI: 10.7759/cureus.54039 -
Dermatology Reports Oct 2011This report presents a case of bullous mycosis fungoides associated with an extensive ulcer and a severe leukemoid reaction. The rash began as indurated erythema which...
This report presents a case of bullous mycosis fungoides associated with an extensive ulcer and a severe leukemoid reaction. The rash began as indurated erythema which was always followed by ulceration. The rashes initially responded to radiation therapy, but multiple recurrences appeared. Several bullae appeared on the trunk during the course of the illness, without any evidence of paraneoplastic pemphigus. Finally, the ulcer covered a large part of the trunk, and the patient died of sepsis with an extreme leukocyte count of 118,000/µL. A bone marrow analysis revealed a leukemoid reaction and an autopsy revealed pseudomembranous colitis.
PubMed: 25386305
DOI: 10.4081/dr.2011.e54 -
Cureus May 2017Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder characterized by the presence of the Philadelphia chromosome, t(9;22), which is a...
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder characterized by the presence of the Philadelphia chromosome, t(9;22), which is a constitutively active tyrosine kinase that causes excessive proliferation and differentiation of myeloid cells in the bone marrow. Most patients are either asymptomatic or present with fatigue, abdominal fullness, and splenomegaly. This is a case in which a 72-year-old Caucasian male's initial presentation of CML was new-onset atrial fibrillation, chronic obstructive pulmonary disease (COPD) exacerbation, and pneumonia. The severity of his symptoms of atrial fibrillation and dyspnea complicated his stabilization, which delayed his diagnosis of CML and initiation of tyrosine kinase inhibitor for treatment. Unregulated proliferation of leukemic cells increases blood viscosity and results in aberrations in blood circulation that may result in atypical presenting symptoms in myeloproliferative disease. Thus, it is important to have a high clinical index of suspicion for CML in patients with leukocytosis and concurrent symptomatology that is unusual for leukemia.
PubMed: 28656128
DOI: 10.7759/cureus.1280 -
Leukemia Research Reports 2020Acute myeloid leukemia (AML) is defined by the presence of ≥ 20% myeloblasts in the blood or bone marrow. Spontaneous remission (SR) of AML is a rare event, with few...
Acute myeloid leukemia (AML) is defined by the presence of ≥ 20% myeloblasts in the blood or bone marrow. Spontaneous remission (SR) of AML is a rare event, with few cases described in the literature. SR is generally associated with recovery from an infectious or immunologic process, and more recently possibly with clonal hematopoiesis. We review the literature and assess the trends associated with SR, and report a new case of a 58-year-old man with a morphologic diagnosis of AML associated with a severe gastrointestinal (GI) tract infection. The patient had an NF1 variant that was previously unreported in AML as the only clonal abnormality. After treatment of the infection, the increased blast population subsided with no leukemia-directed therapy, and the patient has remained in a continuous, spontaneous complete remission for > 2 years.
PubMed: 32477862
DOI: 10.1016/j.lrr.2020.100204