Cytomorphological spectrum of metastatic bone tumors: Experience at a tertiary care center

Objectives: Bone is a frequent site of metastases and typically indicates a short-term prognosis in cancer patients. The majority of skeletal metastases are due to breast and prostate cancer. Bone metastasis is actually much more common than primary bone cancers, especially in adults. Fine-needle aspiration cytology (FNAC) provides reasonably accurate pre-operative diagnosis in vast majority of cases. This study aims to elicit the cytomorphological detail of various metastatic bone tumors. Material and Methods: A total of 109 cases of tumors metastatic to bone have been included in this study. The details of the cases were available from the archives of the department of cytology. May Grunwald Giemsa and hematoxylin and eosin stained smears were studied and examined for the cytomorphological spectrum. Cell block and immunohistochemistry tests were done, wherever feasible. Results: Among 109 patients, the mean age was 54.52 years. There was male preponderance with 90 males and 19 females. The most common site of metastases was in the vertebra (82 cases), and 76 cases were in the dorsolumbar region. The most common type of tumor metastasizing was adenocarcinoma. Conclusion: FNAC is a very useful, economical procedure. There are characteristic cytological features of the metastatic lesions and the basic diagnostic categorization of the malignant tumors is possible on FNAC. Regarding the primary source clinical history, radiological features of the primary tumor, if any, and immunocytochemistry may be needed.

Detection and Segmentation of Pelvic Bones Metastases in MRI Images for Patients With Prostate Cancer Based on Deep Learning

ObjectiveTo establish and evaluate the 3D U-Net model for automated segmentation and detection of pelvic bone metastases in patients with prostate cancer (PCa) using diffusion-weighted imaging (DWI) and T1 weighted imaging (T1WI) images.MethodsThe model consisted of two 3D U-Net algorithms. A total of 859 patients with clinically suspected or confirmed PCa between January 2017 and December 2020 were enrolled for the first 3D U-Net development of pelvic bony structure segmentation. Then, 334 PCa patients were selected for the model development of bone metastases segmentation. Additionally, 63 patients from January to May 2021 were recruited for the external evaluation of the network. The network was developed using DWI and T1WI images as input. Dice similarity coefficient (DSC), volumetric similarity (VS), and Hausdorff distance (HD) were used to evaluate the segmentation performance. Sensitivity, specificity, and area under the curve (AUC) were used to evaluate the detection performance at the patient level; recall, precision, and F1-score were assessed at the lesion level.ResultsThe pelvic bony structures segmentation on DWI and T1WI images had mean DSC and VS values above 0.85, and the HD values were <15 mm. In the testing set, the AUC of the metastases detection at the patient level were 0.85 and 0.80 on DWI and T1WI images. At the lesion level, the F1-score achieved 87.6% and 87.8% concerning metastases detection on DWI and T1WI images, respectively. In the external dataset, the AUC of the model for M-staging was 0.94 and 0.89 on DWI and T1WI images.ConclusionThe deep learning-based 3D U-Net network yields accurate detection and segmentation of pelvic bone metastases for PCa patients on DWI and T1WI images, which lays a foundation for the whole-body skeletal metastases assessment.

To B (Bone Morphogenic Protein-2) or Not to B (Bone Morphogenic Protein-2): Mesenchymal Stem Cells May Explain the Protein’s Role in Osteosarcomagenesis

Osteosarcoma (OS), a primary malignant bone tumor, stems from bone marrow-derived mesenchymal stem cells (BMSCs) and/or committed osteoblast precursors. Distant metastases, in particular pulmonary and skeletal metastases, are common in patients with OS. Moreover, extensive resection of the primary tumor and bone metastases usually leads to bone defects in these patients. Bone morphogenic protein-2 (BMP-2) has been widely applied in bone regeneration with the rationale that BMP-2 promotes osteoblastic differentiation of BMSCs. Thus, BMP-2 might be useful after OS resection to repair bone defects. However, the potential tumorigenicity of BMP-2 remains a concern that has impeded the administration of BMP-2 in patients with OS and in populations susceptible to OS with severe bone deficiency (e.g., in patients with genetic mutation diseases and aberrant activities of bone metabolism). In fact, some studies have drawn the opposite conclusion about the effect of BMP-2 on OS progression. Given the roles of BMSCs in the origination of OS and osteogenesis, we hypothesized that the responses of BMSCs to BMP-2 in the tumor milieu may be responsible for OS development. This review focuses on the relationship among BMSCs, BMP-2, and OS cells; a better understanding of this relationship may elucidate the accurate mechanisms of actions of BMP-2 in osteosarcomagenesis and thereby pave the way for clinically safer and broader administration of BMP-2 in the future. For example, a low dosage of and a slow-release delivery strategy for BMP-2 are potential topics for exploration to treat OS.

Cross Talk Between Macrophages and Cancer Cells in the Bone Metastatic Environment

The skeleton is a common site for cancer metastases with the bone microenvironment providing the appropriate conditions for cancer cell colonization. Once in bone, cancer cells effectively manipulate their microenvironment to support their growth and survival. Despite previous efforts to improve treatment modalities, skeletal metastases remain with poor prognoses. This warrants an improved understanding of the mechanisms leading to bone metastasis that will aid development of effective treatments. Macrophages in the tumor microenvironment are termed tumor associated macrophages (TAMs) and their crosstalk with cancer cells is critical in regulating tumorigenicity in multiple cancers. In bone metastases, this crosstalk is also being increasingly implicated but the specific signaling pathways remain incompletely understood. Here, we summarize the reported functions, interactions, and signaling of macrophages with cancer cells during the metastatic cascade to bone. Specifically, we review and discuss how these specific interactions impact macrophages and their profiles to promote tumor development. We also discuss the potential of targeting this crosstalk to inhibit disease progression. Finally, we identify the remaining knowledge gaps that will need to be addressed in order to fully consider therapeutic targeting to improve clinical outcomes in cancer patients.

A Rare Manifestation of a Presumed Non-Osteophilic Brain Neoplasm: Extensive Axial Skeletal Metastases From Glioblastoma With Primitive Neuronal Components

BackgroundGlioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system. GBM with primitive neuronal component (GBM-PNC) is an aggressive variant identified in 0.5% of GBMs. Extracranial metastasis from GBM-PNC is a rare and challenging situation.MethodsA special case of early-onset GBM with systemic bone metastasis was enrolled. Clinical data, including patient characteristics, disease course, and serial radiological images were retrieved and analyzed. Tumor tissues were obtained by surgical resections and were made into formalin-fixed paraffin-embedded sections. Histopathological examinations and genetic testing were performed for both the primary and metastatic tumor specimens.ResultsA 20-year-old man suffered from GBM with acute intratumoral hemorrhage of the left temporal lobe. He was treated by gross total resection and chemoradiotherapy following the Stupp protocol. Seven months later, he returned with a five-week history of progressive neck pain and unsteady gait. The radiographic examinations identified vertebral collapse at C4 and C6. Similar osteolytic lesions were also observed at the thoracolumbar spine, pelvic, and left femur. Anterior spondylectomy of C4 and C6 was performed. The resected vertebral bodies were infiltrated with greyish, soft, and ill-defined tumor tissue. One month later, he developed mechanical low-back pain and paraplegia caused by thoracolumbar metastases. Another spine surgery was performed, including T10 total en-bloc spondylectomy, T7-9, L2-3, and L5-S1 laminectomy. After the operation, the patient’s neurological function and spinal stability remained stable. However, he finally succumbed to the rapidly increased tumor burden and died 15 months from onset because of cachexia and multiple organ failure. In addition to typical GBM morphology, the histological examinations identified monomorphic small-round cells with positive immunohistochemical staining of synaptophysin and CD99, indicating the coexistence of PNC. The next-generation sequencing detected pathogenic mutations in TP53 and DNMT3A. Based on above findings, a confirmed diagnosis of systemic metastases from GBM-PNC (IDH-wild type, WHO grade IV) was made.ConclusionsThe present case highlights the occurrence and severity of extensive axial skeletal metastases from GBM-PNC. This rare variant of GBM requires aggressive multimodal treatment including surgery and chemoradiotherapy targeting PNC. The pathological screening of PNC is recommended in patients with early-onset GBM and intratumoral hemorrhage. Surgery for spinal metastasis is appropriate in patients with chemoradioresistance and relatively good general status, with the objectives of restoring spinal stability and relieving spinal cord compression.

Diagnostic Value of PET/MR with DWI for Burkitt Lymphoma

18F-FDG-PET/MR images, including DWI, of a 46-year-old male admitted to the Emergency Room of our tertiary center, who was suffering from diplopia, left orbital pain, and a headache for two weeks, demonstrated multiple hepatic nodules, a pancreatic mass, and skeletal metastases, in addition to thrombosis of the left cavernous sinus, thickening of the small intestine, and a large hepatic lesion identified at head and neck MR and whole-body CT, respectively. Hepatic and bone marrow biopsies revealed the diagnosis of Burkitt lymphoma. After four cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, and high dose cytarabine (R- CODOX-M/IVAC), a complete metabolic response occurred.