89Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer.

PURPOSE: Nivolumab is a human monoclonal antibody specific for programmed cell death-1 (PD-1), a negative regulator of T-cell activation and response. Acting as an immune checkpoint inhibitor, nivolumab binds to PD-1 expressed on the surface of many immune cells and prevents ligation by its natural ligands. Nivolumab is only effective in a subset of patients, and there is limited evidence supporting its use for diagnostic, monitoring, or stratification purposes. METHODS: 89Zr-Df-nivolumab was synthesized to map the biodistribution of PD-1-expressing tumor infiltrating T-cells in vivo using a humanized murine model of lung cancer. The tracer was developed by radiolabeling the antibody with the positron emitter zirconium-89 (89Zr). Imaging results were validated by ex vivo biodistribution studies, and PD-1 expression was validated by immunohistochemistry. Data obtained from PET imaging were used to determine human dosimetry estimations. RESULTS: The tracer showed elevated binding to stimulated PD-1 expressing T-cells in vitro and in vivo. PET imaging of 89Zr-Df-nivolumab allowed for clear delineation of subcutaneous tumors through targeting of localized activated T-cells expressing PD-1 in the tumors and salivary glands of humanized A549 tumor-bearing mice. In addition to tumor uptake, salivary and lacrimal gland infiltration of T-cells was noticeably visible and confirmed via histological analysis. CONCLUSIONS: These data support our claim that PD-1-targeted agents allow for tumor imaging in vivo, which may assist in the design and development of new immunotherapies. In the future, noninvasive imaging of immunotherapy biomarkers may assist in disease diagnostics, disease monitoring, and patient stratification.

A solitary uterine relapse in T-cell Acute Lymphoblastic Leukaemia: CT features and pathologic correlation.

T-cell Acute Lymphoblastic Leukemia (T-cell ALL) is a rare haematological neoplasia, that affects children and less commonly adults. Female genital tract and particularly uterus involvement in acute ALL is rare. This report presents the CT features of a 64-year-old woman with uterine relapse of T-cell ALL, occurring 11 months after the diagnosis, as a second, unique relapse of disease. The patient was asymptomatic when a CT examination showed a homogenous thickness of the uterine wall in comparison with the previous CT examination. Histology from biopsy specimens, obtained through hysteroscopy, confirmed T-cell ALL localisation (TdT+, CD10+, CD3c+ and CD2+). The uterus could be a site of relapse in patients suffering from ALL. Even though an MRI examination could better demonstrate the disease in cases of suspected female genital tract involvement by ALL, the comparison of differences between a present and a previous CT examination is sufficient to suspect the diagnosis.

Anatomic Approach to Common and Uncommon Manifestations of Thoracic Leukemias with Radiologic-Pathologic Correlation.

Leukemias are hematopoietic malignancies characterized by the production of abnormal leukocytes in the bone marrow. Clinical manifestations arise from either bone marrow suppression or leukemic organ infiltration. Lymphadenopathy is the most common direct manifestation of intrathoracic leukemia. However, leukemic cells may also infiltrate the lungs, pleura, heart, bones, and soft tissues. Pulmonary complications in patients with leukemia typically include pneumonia, hemorrhage, pulmonary edema, and sequelae of leukemia treatment. However, pulmonary abnormalities can also be related directly to leukemia, including leukemic pulmonary infiltration. The direct, non-treatment-related effects of leukemia on intrathoracic structures will be the focus of this imaging essay. Given the typical anatomic approach for image interpretation, an organ-based depiction of common and less common intrathoracic findings directly caused by leukemic involvement is presented, emphasizing imaging findings with pathologic correlations. Keywords: Leukemia, Pulmonary, Thorax, Soft Tissues/Skin, Hematologic, Bone Marrow © RSNA, 2023.

Asymptomatic leukemic-cell infiltration of the pancreas: US findings.

Pancreatic infiltration of leukemic cells is a very rare manifestation at the onset of acute lymphoblastic leukemia (ALL) in childhood. Pancreatic enlargement in this situation is unusual and pancreatic involvement is often associated with biliary obstruction, cholestasis and pancreatitis. We report a 3-month-old girl who presented with asymptomatic leukemic infiltration of the pancreas, demonstrated by US with heterogeneous pancreatic enlargement associated with multiple hypoechogenic lesions, without cholestasis. Although these manifestations are rare, ALL should be considered a cause of pancreatic enlargement.

Imaging Features of Pulmonary Leukemic Infiltration With Comparison of Lymphoid and Myeloid Leukemias.

PURPOSE: To describe the imaging findings of lung infiltration by leukemia and differential findings of lymphoid and myeloid leukemias. MATERIALS AND METHODS: Through a search of electronic medical records from 2005 to 2017, we identified 21 patients with pathologically proven lung involvement by leukemia. Concurrent CT findings were analyzed by 2 chest radiologists in consensus for ground glass or consolidative opacities, septal thickening, bronchovascular bundle thickening, pulmonary nodules, pulmonary masses, and hilar and mediastinal lymphadenopathy. RESULTS: There were 13 cases of lymphoid leukemias and 8 of myeloid leukemias. Nodules and masses were the most common imaging feature (n = 13, 62%). Bronchovascular bundle thickening and hilar lymphadenopathy were exclusively seen in lymphoid leukemias (P = 0.01 and P = 0.006). Centrilobular nodules were also exclusively seen in 3 patients with chronic lymphocytic leukemia. CONCLUSION: Lung infiltration by leukemia presents most commonly with nodules or masses, but interstitial abnormalities such as bronchovascular bundle thickening were seen as well. Radiologists should consider leukemic infiltration in the differential diagnosis for nodules, including centrilobular nodules, in these patients.

Acute myeloid leukaemia presenting with bilateral breast masses.

A 46-year-old woman with a known history of acute myeloid leukaemia presented with bilateral breast masses with pain and itchiness. The breast masses were hard on palpation. Mammogram was unremarkable. Ultrasound showed multiple conglomerated masses of heterogeneous hyperechogenicity and hypoechogenicity throughout all quadrants of bilateral breasts. Pathology showed mononuclear cells, suggestive of breast leukaemic infiltration. She was treated with decitabine and platelet transfusion.

Gingival leukemic infiltration as the first manifestation of acute myeloid leukemia.

Leukemic infiltration of the gingival tissue associated or not with gingival enlargement may be the first manifestation of acute leukemia, despite being rarely reported in the literature. A 10-year-old female patient presented with a 1-month history of an asymptomatic, firm, and pinkish-red generalized gingival overgrowth. There was no bone resorption. Incisional biopsy of the gingival tissue was performed, with histopathological examination revealing a diffuse and hypercellular infiltration of monocytoid cells. The patient was referred to a hematologist and underwent a bone marrow biopsy, which led to a conclusive diagnosis of acute myeloid leukemia. The patient was treated with chemotherapy and we observed regression of gingival enlargement after 4 weeks from the initial therapy.

Diagnosing neuroleukemiosis: Is there a role for 18F-FDG-PET/CT?

An imaging case is presented on a patient referred to our department for an 18F-FDG-PET/CT, as a paraneoplastic syndrome was suspected due to his clinical situation. He had a history of acute myeloid leukemia (AML) treated two years earlier, with sustained complete remission to date. 18F-FDG-PET/CT findings revealed hypermetabolism in almost all nerve roots, suggesting meningeal spread, consistent with the subsequent MRI findings. Cerebrospinal fluid (CSF) findings confirmed a leptomeningeal reactivation of AML. Although not many studies have evaluated the role of 18F-FDG-PET/CT in leukemia, it is a noninvasive tool for detecting extramedullary sites of disease and a good imaging alternative for those patients on whom an MRI cannot be performed.

The effectiveness of radiotherapy for leukemia cutis.

BACKGROUND: Leukemia cutis (LC) is a rare clinical presentation of leukemia that is associated with poor prognosisabs. To date, the value of radiotherapy (RT) for the treatment of LC remains controversial. Therefore, the aim of this study was to analyse the effectiveness of various RT doses for LC. METHODS AND MATERIALS: Between January 2000 and January 2016, 13 patients underwent RT at our institution after exhibiting progressive disease following other treatment modalities. RESULTS: A total of 36 radiation courses were administered to 13 patients (8 females, 5 males) with a median age of 41 years (range 2-76). Radiation modalities included 32 focal treatments, while total skin electron beam therapy was applied to four patients. The median RT dose was 27 Gy (range 8-34). A complete response rate (CRR) to RT was achieved for 32/36 (89%) lesions (100% for AML lesions versus 33% for the other leukemias; P < 0.001). The median duration of local control (DOLC) for the entire cohort was 38 months (range 0-98), while the median survival (MS) from the time of LC presentation was 13 months (range 2.5-106). The CRR for the LC lesions treated with high-dose regimens (>26 Gy) versus low-dose regimens (≤26 Gy) was 95 versus 83%, respectively (P = 0.26), and the median DOLC was 44 months versus 10 months, respectively (P = 0.019). AML patients had a better long-term outcome than the other patients according to median DOLC (40 months versus 2 months, respectively; P < 0.001) and MS (24 versus 6 months, P = 0.004). RT was well tolerated without significant adverse events. CONCLUSION: A radiation dose ≤26 Gy confer a comparable CRR to high-dose regimens and appears to be an effective treatment for controlling LC progression. However, radiation doses >26 Gy were associated with a longer DOLC. LC patients with underlying AML are associated with better outcome compared with other types of leukemia.

Cardiac Manifestation of Acute Lymphoblastic Leukemia.

Here, we report on a 38-year-old man with unclear right heart failure. Imaging with cardiac MRI and combined PET/CT with F-FDG revealed a hypermetabolic mass extending from the right ventricle to the atrium. In addition, intense glucose utilization throughout the bone marrow was noted. Biopsies of both bone marrow and cardiac mass were performed and revealed precursor B-cell acute lymphoblastic leukemia with gross leukemic infiltration of the myopericardium, a rare manifestation of acute lymphoblastic leukemia at initial diagnosis.

Orbital mass secondary to precursor T-cell acute lymphoblastic leukemia: a rare presentation.

We describe a 40-year-old woman with a history of precursor T-cell acute lymphoblastic leukemia who developed an orbital mass associated with diffuse infiltration of the paranasal sinuses. The clinical and radiologic findings suggested an orbital abscess. Examination of orbital and ethmoid sinus biopsy specimens revealed relapse of precursor T-cell acute lymphoblastic leukemia. Although orbital involvement by granulocytic sarcoma (also known as extramedullary myeloid cell tumor and chloroma) with or without concurrent acute myeloid leukemia is well described in the literature, similar presence of acute lymphoblastic leukemia of either precursor T-cell or B-cell lineage is rare.

Role of radiation therapy to the brain in leukemic patients with cranial nerve palsies in the absence of radiological findings.

The value of brain radiotherapy for leukemic patients with cranial nerve palsies in the absence of radiological evidence of leukemic infiltration is not well defined. This retrospective study was undertaken to evaluate the effectiveness of brain irradiation in reversing the cranial nerve palsies in leukemic patients with no radiological evidence of intracranial leukemic infiltration. Records of leukemic patients who received brain radiotherapy between June 1980 and December 1993 were reviewed. Criteria for inclusion were 1) no evidence of intracranial leukemic infiltration by computed axial tomography (CT) or magnetic resonance imaging scan (MRI), 2) no evidence of leukemic infiltration on ophthalmologic examination, and 3) no previous radiotherapy to the brain. Actuarial survival rates were calculated using the Kaplan-Meier method. Pearson's chi-squared test was used to compare responses. Twenty-eight patients met these criteria. The median age was 38 years (range 3-75 years): Seventeen patients had acute lymphoblastic leukemia, nine had acute myelogenous leukemia, and two had chronic myelogenous leukemia. Four patients had initial presentation with leukemia, and 24 presented with relapse. Twenty-six patients had cerebrospinal fluid cytology that was positive for leukemic cells. Fifteen patients had involvement of more than one cranial nerve, and nine had bilateral involvement. The most commonly involved nerves were the facial (n = 18), oculomotor (n = 9), and abducens nerves (n = 8). Twenty-six patients received whole-brain radiotherapy. Two received radiation to the base of the skull only. The median radiation dose was 24 Gy (range 16-30 Gy) at 2-3 Gy per fraction. Every patient had either concomitant intrathecal (n = 6) or systemic (n = 5) chemotherapy or both (n = 17) with radiation. Fourteen patients had complete reversal of the cranial nerve deficit, eight had partial recovery, and four had no response or progression of the disease. The response was unknown in two patients. Factors associated with complete response were unilateral versus bilateral involvement (72% vs. 13%, P = 0.005) and single versus multiple nerve involvement (75% vs. 36%, P = 0.045). In conclusion, radiation therapy to whole brain was effective in reversing cranial nerve deficits from leukemia, although the leukemic infiltration may not be visualized by CT or MRI. No dose-response relationship was observed in the range we examined.