Paraneoplastic leukemoid syndrome in squamous cell carcinoma of the forearm.

The paraneoplastic leukemoid reaction is a rare haematological paraneoplastic syndrome, which is typically seen with solid tumours and squamous cell carcinomas. As an indication of bone marrow infiltration and malignancy involvement, it indicates a poor outcome and a grave prognosis. We report a woman in her 50s, who presented with an ulcer over the right forearm. Biopsy revealed squamous cell carcinoma. The patient underwent radiological investigations, which showed the presence of metastatic squamous cell carcinoma. Incidentally, the patient was found to have leucocytosis, which was attributed to a paraneoplastic leukemoid reaction, after ruling out all other causes of leukemoid reaction. Due to metastatic disease, the patient was planned for palliative radiotherapy and the best supportive care.

Epithelioid Inflammatory Myofibroblastic Sarcoma with Leukemoid Reaction.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare and aggressive inflammatory myofibroblastic tumour (IMT) variant. This report identifies the first case of EIMS with leukemoid reaction. This is also the first case in which pancreatic infiltration occurred from the disease onset. A 14-year male patient presented with an 18×18×10 cm mass at the retroperitoneal space and a white blood cell (WBC) count of 85×109/L. The mass and the invaded tissues were surgically removed with tumour-free margins. Histopathology and bone marrow aspiration confirmed the diagnosis of EIMS with leukemoid reaction. The tumour recurred with hepatic and pulmonary metastasis one month after the surgery. WBC count also increased progressively with the tumour recurrence. There is no consensus on the treatment of EIMS. Since ALK rearrangement presents in all the EIMS cases, surgical resection combined with crizotinib or other targeted drugs may improve the prognosis. Key Words: Sarcoma, Soft tissue neoplasms, Leukemoid reaction, Crizotinib.

Trastornos mieloproliferativos y leucemia en síndrome de Down. Presentación de dos casos clínicos en el período neonatal / Myeloproliferative disorders and leukemia related to Down syndrome. Report of two clinical cases in neonatal period

ElsíndromedeDownpredisponeatrastornosmieloproliferativos. Se estima que del 5 % al 30 % de los neonatos con esta condición desarrollarán mielopoyesis anormal transitoria. El tratamiento no está estandarizado; la exanguinotransfusión y la citarabina podrían ser efectivos. Se describen dos casos de pacientes con síndrome de Down, quienes durante el período neonatal presentaron leucemia mieloide aguda y mielopoyesis anormal transitoria, los tratamientos utilizados y sus desenlaces. Se considera que la sospecha y el diagnóstico temprano de esta entidad son factores determinantes en el pronóstico.

Down syndrome predisposes to haematological disorders. It is estimated that 5-30% of neonates with this condition will develop transient abnormal myelopoiesis. Treatment is not standardized; exchange transfusion and the use of cytarabine could be effective. We present two clinical cases of patients with Down syndrome, who during the neonatal period showed acute myeloid leukemia and transient abnormal myelopoiesis, the treatments used and their outcomes. Suspicion and early diagnosis of this entity are considered determining factors in prognosis.

[Myeloproliferative disorders and leukemia related to Down syndrome. Report of two clinical cases in neonatal period]. / Trastornos mieloproliferativos y leucemia en síndrome de Down. Presentación de dos casos clínicos en el período neonatal.

Down syndrome predisposes to haematological disorders. It is estimated that 5-30% of neonates with this condition will develop transient abnormal myelopoiesis. Treatment is not standardized; exchange transfusion and the use of cytarabine could be effective. We present two clinical cases of patients with Down syndrome, who during the neonatal period showed acute myeloid leukemia and transient abnormal myelopoiesis, the treatments used and their outcomes. Suspicion and early diagnosis of this entity are considered determining factors in prognosis.

El síndrome de Down predispone a trastornos mieloproliferativos. Se estima que del 5 % al 30 % de los neonatos con esta condición desarrollarán mielopoyesis anormal transitoria. El tratamiento no está estandarizado; la exanguinotransfusión y la citarabina podrían ser efectivos. Se describen dos casos de pacientes con síndrome de Down, quienes durante el período neonatal presentaron leucemia mieloide aguda y mielopoyesis anormal transitoria, los tratamientos utilizados y sus desenlaces. Se considera que la sospecha y el diagnóstico temprano de esta entidad son factores determinantes en el pronóstico.

Using the in vitro drug sensitivity test to identify candidate treatments for transient abnormal myelopoiesis.

Approximately 20% of patients with transient abnormal myelopoiesis (TAM) die due to hepatic or multiorgan failure. To identify potential new treatments for TAM, we performed in vitro drug sensitivity testing (DST) using the peripheral blood samples of eight patients with TAM. DST screened 41 agents for cytotoxic properties against TAM blasts. Compared with the reference samples of healthy subjects, TAM blasts were more sensitive to glucocorticoids, the mitogen-activated protein kinase kinase (MAP2K) inhibitor trametinib, and cytarabine. Our present results support the therapeutic potential of glucocorticoids and the role of the RAS/MAP2K signalling pathway in TAM pathogenesis.

Paraneoplastic leukemoid reaction: Case report and review of the literature.

OBJECTIVES: We recently encountered a patient with unexplained hyperleukocytosis (105.4 K/µL at presentation), subsequently found to have colon cancer with a marked tumor-associated neutrophilic infiltrate; the leukocytosis abruptly improved after tumor removal. Paraneoplastic leukemoid reaction (PLR) is a rare entity, occurring due to tumor cytokine secretion (typically granulocyte-colony stimulating factor [G-CSF]). We describe a case and aggregate results of previously published cases. METHODS: We reviewed the English-language literature for all prior reports of PLR, recording age, gender, histologic diagnosis, WBC count, G-CSF level, and overall survival. We analyzed clinicopathologic variables' impact on survival. RESULTS: We identified 179 cases (mean age 64; 72 % M). Adeno-, squamous cell, sarcomatoid, and undifferentiated carcinomas accounted for >70 %. Esophagus, gallbladder, lung, liver, and pancreas were the most common primaries. At time of publication 81 % of patients had died, with mean overall survival of 4 months. There was no correlation between WBC count and G-CSF level. On univariate analysis, WBC count was the only variable associated with survival (P = 0.03). Patients with WBC counts >100 K/µL were twice as likely to die as those with counts from 11 K to 40 K/µL. CONCLUSIONS: PLR, typically carcinoma-associated, is characterized by dismal prognosis. The WBC count is inversely related to survival. Knowledge of this phenomenon militates against protracted, expensive work ups. In malignant neoplasms with prominent neutrophilic stroma, the pathologist should correlate with the WBC count and, if markedly elevated (>40 K/µL), raise consideration for PLR.

MicroRNA-155-5p Plays a Critical Role in Transient Leukemia of Down Syndrome by Targeting Tumor Necrosis Factor Receptor Superfamily Members.

BACKGROUND/AIMS: Down syndrome associated disorders are caused by a complex genetic context where trisomy 21 is a central component in relation to other changes involving epigenetic regulators and signaling molecules. This unique genetic context is responsible for the predisposition of people with Down syndrome to acute leukemia. Although, the research in this field has discovered some important pathogenic keys, the exact mechanism of this predisposition is not known. METHODS: In this study we applied functional enrichment analysis to evaluate the interactions between genes localized on chromosome 21, genes already identify as having a key role in acute leukemia of Down syndrome, miRNAs and signaling pathways implicated in cancer and cell development and found that miR-155 has a high impact in genes present on chromosome 21. Forward, we performed next generation sequencing on DNA samples from a cohort of patients diagnosed with acute leukemia of Down syndrome and in vitro functional assay using a CMK-86 cell line, transfected with either mimic or inhibitor of the microRNA-155-5p. RESULTS: Our results show that the epigenetic alteration of the TNF superfamily receptors in Down syndrome, which can be correlated to microRNA-155-5p aberrant activity, may play an important role in cell signaling and thus be linked to acute myeloid leukemia. CONCLUSION: Some genes, already shown to be mutated in AML-DS, are potential targets for miR-155. Our results show that the epigenetic alteration of the TNF superfamily receptors in Down syndrome may play an important role in cell signaling and thus be linked to acute myeloid leukemia.

Leukemoid reaction causing arterial thrombus in a patient with lung adenocarcinoma.

A leukemoid reaction is typically defined as white blood cell (WBC) count >50×109/L, predominantly neutrophil precursors, that are not due to tumour involvement in the bone marrow and not derived from clones. Leukemoid reactions associated with malignancy, known as paraneoplastic leukemoid reactions, are less common and are most notably seen with non-small cell lung cancer. A 64-year-old woman presented with right leg painful ulceration. On examination, she had multiple venous stasis ulcers more severe on the right, with no palpable pulses in her lower extremities. Her WBC count was 124×109/L and platelets were 517×109/L. Arterial dopplers showed limb-threatening arterial insufficiency which prompted right femoral endarterectomy. Few months earlier she was diagnosed with metastatic lung adenocarcinoma to the bone and she had leukemoid reaction with WBC 43.920× 109/L with 90% neutrophils. Repeat imaging showed progression of her malignancy and she passed shortly after. Inflammation is a key element of carcinogenesis and cancer progression. Among the different tumours, lung cancer is a non-haematologic malignancy that is most closely associated with leucocytosis. Some studies have found that leucocytosis was significantly associated with metastasis and shorter survival irrespective of other factors such as age or sex. The mechanism remains unclear however elevated levels of granulocyte colony-stimulating factor (CSF), granulocyte macrophage-CSF and interleukin 6 have been linked to this phenomena. The degree of leucocytosis seen in our patient is suggestive of CSF production leading to a paraneoplastic leukemoid reaction.

Paraneoplastic leukemoid reaction in a localised squamous cell oesophageal cancer with paracrine G-CSF production.

A 51-year-old-man presented with symptoms and baseline investigations suggestive of an infective process. Most strikingly, there was a pronounced neutrophil predominant leucocytosis. Lack of a clinical and biochemical response to empirical antibiotic therapy, prompted imaging for a deep-seated infective process, incidentally uncovering a gastro-oesophageal junction tumour. Resection of the tumour was followed by rapid resolution of the leucocytosis. He remains in clinical remission since tumour resection and adjuvant chemotherapy. Cancer-associated leukemoid reactions in non-disseminated tumours are rare. The role of polymorphonuclear (PMN) leucocytes both in the peripheral blood and the tumour itself is discussed herein. There is increasing recognition of the importance of the non-cancer cellular components of the tumour microenvironment. Myeloid suppressor cells are a subset of PMN leucocytes which play a role in tumour progression.The role of these cells and granulocyte colony-stimulating factor is highlighted in this case.

G-CSF Production by Undifferentiated Pleomorphic Sarcoma with Leukemoid Reaction Occurred in the Lower Leg: A Case Report.

CASE: A 46-year-old woman presented with a mass in the lower leg and severe leukocytosis. Diffuse uptake in the bones was detected with F-fluorodeoxyglucose positron emission tomography with computed tomography (F-FDG PET/CT) imaging. The serum granulocyte-colony stimulating factor (G-CSF) was elevated, and immunostaining for G-CSF was positive. When diagnosed as G-CSF-producing undifferentiated pleomorphic sarcoma (UPS), a wide resection was performed. The leukocytosis and serum G-CSF were remarkably improved after tumor resection. No local recurrence or metastasis was detected. CONCLUSION: We report the first case of inflammatory UPS in the extremity which demonstrated the neoplastic production of G-CSF. In our case, F-FDG PET/CT, the serum G-CSF, and immunostaining for G-CSF were useful for diagnosis.

Paraneoplastic Leukemoid Reaction in Gastroesophageal Junction Adenocarcinoma: A Case Report.

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.

Severe Leukemoid Reaction in a Case of Soft Tissue Sarcoma: A Case Report.

CASE: A 62-year-old woman presented with severe leukocytosis and systemic symptoms including fatigue, low appetite, and weight loss. After 4 months of evaluation by doctors with extensive laboratory tests and imaging studies, a soft tissue sarcoma in the left posterior distal thigh was revealed. Quickly after surgical excision of the soft tissue sarcoma, the leukocytosis and systemic symptoms were dramatically resolved. CONCLUSIONS: Leukemoid reaction can present as a paraneoplastic syndrome. Awareness of soft tissue sarcoma as a possible cause of leukemoid reaction may help improve the early diagnosis and subsequent early intervention in future cases.

Esophageal adenocarcinoma with leukemoid reaction: a case report.

BACKGROUND: Leukemoid reaction (LR) is defined as a reactive leucocytosis with WBC counts exceeding 50,000/mm3, and a significant increase in early neutrophil precursors. LR may be a paraneoplastic manifestation of various malignant tumors. Tumor-related LR is a kind of neoplastic syndrome, unrelated to an infection or other diseases. CASE PRESENTATION: A 74-year-old male visited a local doctor with a 20-day history of progressive dysphagia. The complete blood count revealed leucocytosis. Bone marrow aspirates and a biopsy confirmed LR and excluded chronic myelogenous leukemia. Following radical esophagectomy for an adenocarcinoma the WBC counts successively decreased to 10,450/mm3 and 8670/mm3 within 1 week and 1 month, respectively. CONCLUSION: We report a rare case of esophageal adenocarcinoma complicated with excessive leucocytosis caused by paraneoplastic LR; we also present a review of literature and an investigation of the clinical features. To our knowledge, this is the first report of LR associated with esophageal adenocarcinoma.

A prospective study of hospitalized patients with leukemoid reaction; causes, prognosis and value of manual peripheral smear review.

INTRODUCTION: Several diagnoses have been associated with leukemoid reaction (LR). In patients with LR the diagnostic and prognostic value of detailed manual blood smear counts (such as the percentage of band cells or grading of neutrophil toxic changes) has not been studied previously. METHODS: We prospectively recorded all hospitalized adult (> 18 years old) patients with LR (≥ 30000/ul) of neutrophilic predominance, excluding patients with pre-existing leukocytosis due to hematological malignancies. We examined the diagnoses and prognosis (in-hospital mortality and post-discharge mortality up to a year after the end of the study) of these patients as well as the value of manual peripheral smear review. RESULTS: We recorded a total of 93 patients with LR from January 2017 to December 2017. Infection was the most common diagnosis (70%), followed by malignancy (7.5%) and bleeding (6.5%). In-hospital mortality (45%) and post-discharge mortality (35% of those discharged) were very high. Among blood smear findings, only neutrophil vacuolation was significantly more common in patients with infections (34%), although it was also observed in many patients without any infection (13%). Blood smear findings were not associated with prognosis. CONCLUSION: Detailed manual smear review is a labor-intensive procedure and it has limited diagnostic and prognostic value in unselected hospitalized patients with neutrophilic LR.