Utility of 18F-FDG PET/CT in medical care of a promyelocytic sarcoma.

Promyelocytic sarcoma is an uncommon solid tumor made up of myeloblasts. It is characterized, like acute promyelocytic leukemia (APL), by a chromosomal translocation t(15;17) involving the retinoic acid receptor alpha (RARalpha) and the promyelocytic gene (PML). The diagnosis and monitoring of promyelocytic sarcoma is a challenge due to the rarity and severity of the disease. We describe a case with several initial sites and without APL. The patient was monitored with regular 18F-FDG PET/CT from diagnosis to complete response. The evolution of PET/CT imageries was compared to the quantification of PML-RARα fusion gene by RQ-PCR. In promyelocytic sarcoma medical care, 18F-FDG PET/CT appears to be an attractive tool for finding targets for biopsy, for the primary staging, for assessing therapeutic response and for detecting early relapse.

Diagnosing acute promyelocytic leukemia by using convolutional neural network.

PURPOSE: To evaluate the efficacy of diagnosis systems based upon instance segmentation with convolutional neural networks (CNNs) for diagnosing acute promyelocytic leukemia (APL) in bone marrow smear images. MATERIALS AND METHODS: A self-established dataset was used in this study that was exempted from review by the institution review board, which consisted of 13,504 bone marrow smear images. One subset of the dataset with 12,215 labeled images was split into training (80%) and validation (20%), another with 1289 labeled images was used to test, in which each test entry consists of about 130 images. An instance segmentation method named Mask R-CNN was used to detect and classify the nucleated cells. Here, we train a trained neural network from scratch; for comparison, we also use a network pre-trained on MS COCO (common objects in context, a data set provided by Microsoft which can be used for image recognition, the images in MS coco dataset are divided into training, validation and test sets) and fine-tuned with our dataset and both were trained with same data augmentation scheme. Diagnosis systems based on trained models and "FAB Classification" (French-American-British classification systems, a series of diagnostic criteria for acute leukemia, which was first proposed in 1976) were developed for diagnosing the test entry as APL or as not. Average precision (AP) and average recall (AR) were used to evaluate model performance. RESULTS: The best-performing model had an average precision of 62.5%, which was the augmented pre-trained Mask R-CNN with average recall 84.1%. The average precision of the pre-trained model was greater than that of the model trained from scratch (P < 0.05). Augmenting the dataset further increased accuracy (P < 0 0.03). CONCLUSION: Deep learning technology such as instance segmentation with Mask R-CNN may accurately diagnose APL in bone marrow smear images with an average precision of 62.5% when 0.5 as IoU thresholds. A data augmentation and pre-trained approach further improved accuracy.

Differentiation syndrome in acute promyelocytic leukaemia.

Acute promyelocytic leukaemia differentiation syndrome (APL DS) is seen when patients with APL are treated with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). Presenting symptoms are varied but frequently include dyspnoea, unexplained fever, weight gain >5 kg, unexplained hypotension, acute renal failure and a chest radiograph demonstrating pulmonary infiltrates or pleural or pericardial effusion. Immediate treatment with steroids at the first clinical suspicion is recommended and ATRA/ATO should be stopped in severe cases or if there is no response to treatment. The utility of steroid prophylaxis in order to prevent APL DS is less certain. Here we provide a detailed review of the pathogenesis, clinical signs and symptoms as well as management and prophylaxis strategies of APL DS.

An extracellular pH-driven targeted multifunctional manganese arsenite delivery system for tumor imaging and therapy.

Expanding the use of arsenic trioxide (ATO, As2O3) in cancer chemotherapy has received extensive attention in recent years owing to its remarkable efficacy in treating acute promyelocytic leukemia (APL). To date, the use of ATO for clinical treatment of solid tumors is still limited by its poor biocompatibility and severe toxic side effects. To address these limitations, here we developed a pH-low insertion peptide (pHLIP) modified ATO-based multifunctional drug-delivery system (DDS), which is termed MnAs@SiO2-pHLIP. With the coating of pHLIP, MnAs@SiO2-pHLIP could efficiently target the acidic tumor microenvironment, resulting in high intracellular accumulation of the DDS. As a "smart" nanoparticle (NP) platform, the DDS could controllably discharge the loaded ATO in response to acidic environments, which promotes the apoptosis of cancer cells. The features of controlled release capacity and the outstanding targeting ability contribute to better anticancer efficacy and less toxicity towards normal tissues compared with free ATO. It is worth noting that the acidic tumor microenvironment would also trigger the release of manganese ions (Mn2+) that brighten the T1 signal, which is exploited for real-time monitoring via contrast-enhanced magnetic resonance imaging (MRI). These multifunctional features, as demonstrated by both in vitro and in vivo experiments, could potentially expand the use of ATO to the treatment of solid tumors. We believe that MnAs@SiO2-pHLIP could serve as an auspicious agent for cancer theranostics and find tremendous applications in cancer management.

Applications of imaging flow cytometry in the diagnostic assessment of acute leukaemia.

Automated imaging flow cytometry integrates flow cytometry with digital microscopy to produce high-resolution digital imaging with quantitative analysis. This enables cell identification based on morphology (cell size, shape), antigen expression, quantification of fluorescence signal intensity and localisation of detected signals (i.e. surface, cytoplasm, nuclear). We describe applications of imaging flow cytometry for the diagnostic assessment of acute leukaemia. These bone marrow malignancies are traditionally diagnosed and classified by cell morphology, phenotype and cytogenetic abnormalities. Traditionally morphology is assessed by light microscopy, phenotyping by conventional flow cytometry and genetics by karyotype and fluorescence in situ hybridisation (FISH) on interphase nuclei/metaphase spreads of cells on slides. Imaging flow cytometry adds a new dimension to the diagnostic assessment of these neoplasms. We describe three specific applications: From this we conclude that imaging flow cytometry offers benefits over conventional diagnostic methods. Specifically the ability to visualise the cells of interest, the pattern and localisation of expressed antigens and assess cytogenetic abnormalities in one integrated automated high-throughput test. Imaging flow cytometry presents a new paradigm for the diagnostic assessment of leukaemia.

Brain infarction and blasts with bilobed nuclei in a patient with monocytic acute myeloid leukemia mimicking acute promyelocytic leukemia.

We are presenting a case of an adult male patient with monocytic acute myeloid leukemia (AML) who had on presentation brain infarction and bilobed nuclei had been demonstrated in many of the leukemic blasts. There was no laboratory evidence of acute disseminated intravascular coagulopathy, on presentation or later on. Initially the diagnosis of acute promyelocytic leukemia (APL) was considered, so all trans-retinoic acid (ATRA) was added to induction chemo therapy. As the diagnosis of APL was ruled out, based on the flow cytometry, fluorescent in situ hybridization and polymerase chain reaction findings, the ATRA was discontinued and the patient continued on the standard AML chemo therapy induction regimen. Later on chromosomal analysis was also normal. Sever dehydration on presentation, would have contributed to brain infarction. AML particularly monocytic, can mimic APL, especially its microgranular variant. The possible ATRA therapy side effects, can be avoided by early confirmation of the diagnosis.

Rare presentation of pediatric acute promyelocytic leukemia as multiple lytic bone lesions: case report and review of literature.

Acute promyelocytic leukemia (APL) is an uncommon malignancy in the pediatric population, accounting for only 5-10% of pediatric acute myeloid leukemias, and for this disease to present with bone lesions at diagnosis is extremely unusual. We wish to convey that very rarely, in a pediatric cancer patient presenting with multiple extensive lytic bone lesions, the diagnosis can be APL. The treatment protocol and prognostic implications are vastly different. Histopathology is the gold standard in arriving at a correct diagnosis and delivering proper treatment in such cases. This patient had excellent response to chemotherapy.

ATRA-induced cerebral sinus thrombosis.

All-trans retinoic acid (ATRA) and Idarubicin are part of the AIDA protocol employed for the treatment of Acute promyelocytic leaukaemia (APML) and has been associated with marked improvement in the prognosis. However, it is known to worsen the haematological picture during the course of induction of therapy. Herein, we present a case of an APML patient who developed a rare documented incidence of cerebral sinus thrombosis, first noticed as an ophthalmology referral. This 22 year old lady, a known APML patient was then started on chemotherapy based on AIDA protocol but 17 days into the initiation of therapy, she began to complain of blurred vision on the right eye. Anterior segments were normal but both fundi showed papilloedema with peripapillary haemorrhages. A contrast MRI that was then ordered showed multiple filling defects in numerous venous sinuses. She was started on anticoagulant treatment and the findings resolved. Though a rare case of its side-effects, ATRA usage in APML has a multitude of presentations since its primary pathology lies in the inherent pro-coagulant potential.

Meckel's diverticulum findings on Tc-99m red blood cell scintigraphy in a bleeding leukemic patient confirmed by Tc-99m pertechnetate scintigraphy.

A 25-year-old Caucasian woman with a medical history of acute promyelocytic leukemia presented to the emergency department with massive gastrointestinal bleeding. A bone marrow biopsy excluded hemorrhagic leukemia. Esophagogastroduodenoscopy, colonoscopy, emergency abdominal angiography, abdominal CT scan, and wireless capsule endoscopy were performed but no source of bleeding could be detected. Tc-99m RBC scintigraphy was consistent with a small bowel bleeding focus. The persistent and focal images in the right abdomen were suggestive of Tc-99m RBC trapping in the lumen of a Meckel diverticulum (MD). In accordance with this suspicion, successive Tc-99m pertechnetate scintigraphy was performed after 3 days, consistent with the diagnostic hypothesis. Due to the persisting severe bleeding (with a drop in baseline hemoglobin from 10.4 to 7.1 g/dL), despite 8 units of blood transfusion, emergency surgery was performed. Through a minilaparotomy a segmental small bowel resection, including Meckel diverticulum, was performed. The postoperative course was uneventful.

Sivelestat relieves respiratory distress refractory to dexamethasone in all-trans retinoic acid syndrome: a report of two cases.

Treatment with all-trans retinoic acid (ATRA) improves the prognosis of patients with acute promyelocytic leukemia (APL), but ATRA syndrome may occur as a possible fatal side effect, especially in cases refractory to medication or involving pulmonary hemorrhage. We describe two patients with APL who suffered from intracranial hemorrhage. The first patient was a 16-yr-old girl who was treated with ATRA and then developed respiratory distress refractory to treatment with dexamethasone combined with anthracycline-cytarabine cytoreduction therapy. Treatment with Sivelestat, a small molecule inhibitor of neutrophil elastase, achieved rapid improvement in oxygenation and chest radiograph findings, and the patient has been in complete remission for 24 months. The second patient was a 10-yr-old boy in whom pulmonary hemorrhage developed following administration of ATRA, dexamethasone and cytoreduction therapy. Aspiration and administration of Sivelestat improved oxygenation and he remained stable. Hematological improvement was also achieved, but the patient died of brain dysfunction because of cerebral edema accompanied by intracranial bleeding. The two cases suggest that Sivelestat may be effective as an additional agent in the treatment of refractory ATRA syndrome, and, therefore, prospective randomized studies of treatment protocols are warranted.