Molecular GBM versus Histopathological GBM: Radiology-Pathology-Genetic Correlation and the New WHO 2021 Definition of Glioblastoma.

Given the recent advances in molecular pathogenesis of tumors, with better correlation with tumor behavior and prognosis, major changes were made to the new 2021 WHO (CNS5) classification of CNS tumors, including updated criteria for diagnosis of glioblastoma. Diagnosis of GBM now requires absence of isocitrate dehydrogenase and histone 3 mutations (IDH-wildtype and H3-wildtype) as the basic cornerstone, with elimination of the IDH-mutated category. The requirements for diagnosis were conventionally histopathological, based on the presence of pathognomonic features such as microvascular proliferation and necrosis. However, even if these histological features are absent, many lower grade (WHO grade 2/3) diffuse astrocytic gliomas behave clinically similar to GBM (grade 4). The 2021 WHO classification introduced new molecular criteria that can be used to upgrade the diagnosis of such histologically lower-grade, IDH-wildtype, astrocytomas to GBM. The three molecular criteria include: concurrent gain of whole chromosome 7 and loss of whole chromosome 10 (+7/-10); TERT promoter mutation; epidermal growth factor receptor (EGFR) amplification. Given these changes, it is now strongly recommended to have molecular analysis of WHO grade 2/3 diffuse astrocytic, IDH-wildtype, gliomas in adult patients, as identification of any of the above mutations allows for upgrading the tumor to WHO grade 4 ("molecular GBM") with important prognostic implications. Despite at an early stage, there is active ongoing research on the unique MRI features of molecular GBM. This paper highlights the differences between "molecular" and "histopathological" GBM, with the aim of providing a basic understanding about these changes.ABBREVIATIONS: GBM=Glioblastoma; TERT=telomerase reverse transcriptase; EGFR=epidermal growth factor receptor; MGMT= methylguanine-DNA methyltransferase; NGS= next-generation sequencing; IDH= isocitrate dehydrogenase.

An Unexpected Diagnosis Uncovered by Quantitative Molecular Findings: A Case Report.

A 74-year-old male presented with rectal pain; workup uncovered an anal mass, and a diagnosis of melanoma was rendered via histologic examination and immunohistochemical (IHC) studies. Droplet digital PCR (ddPCR)-based BRAF testing was performed and revealed the presence of BRAF V600E, which is a common targetable genetic alteration in melanoma. Interestingly, the ratio of mutant to wild-type copy number was low (0.3%), whereas tumor cell percentage on tissue slides was 90%. With additional workup, BRAF V600E IHC confirmed a very small subset of BRAF V600E-positive cells, and a next-generation sequencing (NGS) panel revealed a pathogenic KIT variant, p.L576P, with an allele frequency of 63%. It was initially hypothesized that the main driver of the melanoma was the KIT alteration, whereas a small subclone (not detected by NGS, which has a 5% limit of detection) was driven by the BRAF V600E detected by ddPCR. To determine whether there were morphologic differences between the 2 clones, a careful review of the histology was performed and revealed distinct morphology of the BRAF V600E-positive cells, including pale cytoplasm, nuclear grooves, and infiltrating eosinophils. Additional IHC workup of the BRAF V600E-positive cells showed coexpression of CD1a, Langerin, and S100, diagnostic of Langerhans cell histiocytosis (LCH). This diagnosis was unexpected and would have been missed without highly sensitive molecular testing; yet it is of clinical importance for the patient. This case raises interesting biology questions regarding the relationship between melanoma and LCH; moreover, it highlights the importance of integrating quantitative information in molecular data interpretation.

An Excellent Response of Microsatellite Instability-High Pancreatic Adenocarcinoma to Pembrolizumab Treatment: The Role of Circulating Tumor DNA Testing.

The role of circulating tumor DNA (ctDNA) is expanding in oncology practices, and it is increasingly being used for targeted therapies and disease monitoring. It is minimally invasive and provides data from both primary and secondary sites of disease. Herein, we report a unique case of a patient with microsatellite instability-high (MSI-H) pancreatic adenocarcinoma (PDAC) treated with neoadjuvant chemotherapy and pembrolizumab who achieved a pathologically confirmed complete resolution of the tumor. A 75-year-old female was diagnosed with pancreatic adenocarcinoma (PDAC) in the uncinate process with aortocaval and retrocrural adenopathy. Next-generation sequencing was obtained via ctDNA testing, and the patient was initiated on cytotoxic chemotherapy while awaiting results. ctDNA revealed MSI-H status, and pembrolizumab was added to the cytotoxic chemotherapy regimen. At follow-up after five cycles of treatment, excellent treatment response was noted on magnetic resonance imaging (MRI) of the abdomen, demonstrating the resolution of the pancreatic mass and adenopathy. Six months of neoadjuvant treatment was given in total, after which the patient underwent resection with curative intent and achieved a complete pathological response with no evidence of disease. The role of ctDNA testing in directing treatment and influencing follow-up has already demonstrated great value. In our case, ctDNA adequately replaced conventional tissue biopsy, alleviating the burden of invasive testing on the patient. This is of great value, especially for patients with non-resectable tumors as well as in several other clinical scenarios. Our case also contributes to the growing body of literature demonstrating the role of immune-directed therapy for MSI-H PDAC.

A case report of 2 distinct primary sarcomas arising in an extremity in rapid succession.

A 59-year-old male presented with a primary synovial sarcoma around his knee. Two months after resection, he presented with a new, rapidly-growing mass in the ipsilateral proximal thigh. A biopsy of the new mass demonstrated a pleomorphic liposarcoma, distinct from the prior synovial sarcoma. He underwent neoadjuvant radiation, followed by wide resection. He is now undergoing surveillance for recurrence. While 2 distinct primary sarcomas developing in rapid succession is rare, this case emphasizes the need for a complete work-up, including obtaining a tissue diagnosis for suspected recurrent lesions as this may alter treatment and follow-up recommendations.

Arthropod Bite Mastitis as a Mimicker of Breast Cancer.

Arthropod bite mastitis is rarely encountered in imaging practices but can occur in all regions of the world. Diagnosis is often challenging as the offending agent is rarely identified. While most manifestations are self-limited, severe presentations can mimic malignant processes such as Paget's disease and inflammatory breast cancer (IBC). This case demonstrates the diagnostic challenges sometimes encountered with arthropod bite mastitis as well as imaging findings both prior to and after interventions.

NTRK-rearranged spindle cell neoplasm of the lower extremity: radiologic-pathologic correlation.

Neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm is a recently characterized soft tissue tumor and has been classified as provisional by the World Health Organization. Detection of the genetic rearrangement is important because these tumors are amenable to targeted tyrosine kinase inhibitor therapy, which can play a key role in patients with unresectable or advanced disease. Although the spectrum of histopathology associated with this entity is broad, one notable feature is the infiltrative growth pattern, which is most reminiscent of lipofibromatosis-like neural tumor. Description of their diverse histologic attributes has aided recognition, but so far little attention has been paid to correlating the gross appearance and imaging features of these lesions. In this report, we describe the clinical, imaging, histopathological, and genetic features of a soft tissue NTRK-rearranged spindle cell neoplasm. Inclusion of this more recently identified entity into the imaging differential of tumors with intratumoral relatively hypovascular nodules and infiltrative margins is important because testing for NTRK rearrangement is not routinely performed.

Epithelioid osteoblastoma with secondary aneurysmal bone cyst and FOS gene rearrangement.

Epithelioid osteoblastoma, sometimes equated with aggressive osteoblastoma, is a variant of osteoblastoma that typically demonstrates more worrisome imaging and pathological features compared to conventional osteoblastoma. These more aggressive features can overlap with those seen in osteosarcoma, creating a diagnostic challenge for radiologists and pathologists. Recent identification of FOS and FOSB gene rearrangements in osteoid osteoma and osteoblastoma has allowed for greater diagnostic confidence following biopsy, but careful radiological-pathological correlation remains a key component for guiding appropriate management. Although the imaging features of conventional osteoblastoma have been previously described, there are limited examples in the literature of the imaging appearance of epithelioid osteoblastoma, and none with secondary aneurysmal bone cyst. In this case report, we detail the clinical, imaging, and histological characteristics of a proximal femoral epithelioid osteoblastoma which was pathologically confirmed by FOS and FOSB genetic testing. The initial imaging impression favored a malignancy, but when the biopsy results were correlated in a multidisciplinary fashion with the imaging, epithelioid osteoblastoma became the leading diagnosis which was subsequently genetically confirmed. This case emphasizes the value of multidisciplinary radiology-pathology correlation in routine practice.

Perinephric myxoid pseudotumor of fat: A very rare entity that can mimic a renal cyst and retroperitoneal liposarcoma on imaging.

We present a case of perinephric myxoid pseudotumor of fat, a rare benign entity that often occurs in patients with non-neoplastic renal disease. In our case, an 80 year old man with end-stage renal disease was imaged over the course of 5 years during evaluation for renal transplantation. Imaging identified a left perinephric mass whose appearance over time and on different imaging modalities variably suggested a simple cyst, cystic neoplasm, and liposarcoma. Contrast enhanced examination was necessary to discern the solid nature of this mass, and ultimately, tissue sampling with histopathologic evaluation and molecular testing were required to make the diagnosis of myxoid pseudotumor of fat and exclude the imaging mimics.

Recurrent Loss of SMARCA4 in Sinonasal Teratocarcinosarcoma.

Molecular analysis has reshaped the landscape of high grade sinonasal tumors by defining novel entities and identifying recurrent mutations in established tumor types. However, sinonasal teratocarcinosarcoma (TCS), a rare and aggressive tumor with intermixed teratomatous, carcinomatous, and sarcomatous elements, remains poorly understood. The multiphenotypic differentiation of TCS has engendered persistent controversy about its histogenesis and leads to diagnostic overlap with several other malignancies. In this study, we evaluated the molecular underpinnings of TCS to clarify its pathogenesis and diagnosis. We performed SMARCA4 immunohistochemistry (IHC) on 22 TCS and 153 other sinonasal tumors. We identified loss of SMARCA4 expression in 18 TCS (82%), including 15 (68%) with complete loss and 3 (14%) with partial loss. Although we also identified partial SMARCA4 loss in 1 of 8 SMARCB1-deficient sinonasal carcinomas (13%), SMARCA4 was intact in all other sinonasal carcinomas and neuroendocrine tumors. We then selected 3 TCS with complete SMARCA4 loss by IHC for a targeted next-generation sequencing panel that included 1425 cancer-related genes. We confirmed biallelic somatic inactivation of SMARCA4 without other known oncogenic mutations in these 3 cases. Overall, these findings suggest that SMARCA4 inactivation may be the dominant genetic event in TCS, expanding understanding of this gene's role in sinonasal tumorigenesis. They also raise the possibility that TCS is on a diagnostic spectrum with the newly described SMARCA4-deficient sinonasal carcinoma, blurring the lines between established and emerging sinonasal entities. In addition, SMARCA4 IHC may provide a useful adjunct for confirming a diagnosis of TCS in limited material.

Ectopic ACTH Syndrome With Association of Multiple Pulmonary Sclerosing Pneumocytomas and Multiple Carcinoid Tumorlets.

We present the case of multiple sclerosing pneumocytomas (SPs) associated with ACTH-secreting carcinoid tumorlets responsible for an ectopic Cushing syndrome (ECS). SP is a rare benign tumor originating from pulmonary epithelial cells. An 18-year-old male presented with shortness of breath and right-sided chest pain after exercise. Chest radiograph indicated right pneumothorax and bilateral lung nodules. CT imaging showed innumerable bilateral hypodense pulmonary nodules and a wedge resection gave the definitive diagnosis of SP with associated carcinoid tumorlets. Two years later, he presented with severe back pain in context of thoracic vertebral compression fracture. He had central fat accumulation, violaceous striae, proximal muscle weakness, hypertension, and diabetes. MRI of the pituitary gland showed a 7-mm adenoma. Inferior petrosal sinus sampling with no central-to-periphery gradient suggested an ectopic origin of ACTH, which was confirmed by ACTH expression in a subset of tumorlet cells in the lung lesions. The patient was started on ketoconazole and subsequently underwent a bilateral adrenalectomy. During follow-up, CT scans showed no growth of the lesions, except for the most recent CT scan, in which an increase in the size of the largest nodule was described. Ten years after the diagnosis, the patient remains asymptomatic of his pulmonary lesions. This article provides a case of ECS in the setting of multiple SP with associated carcinoid tumorlets.

Increase in PD-L1 expression after pre-operative radiotherapy for soft tissue sarcoma.

Soft tissue sarcomas (STS) have minimal expression of PD-L1, a biomarker for PD-1 therapy efficacy. Radiotherapy (RT) has been shown to increase PD-L1 expression pre-clinically. We examined the expression of PD-L1, pre- and post-RT, in 46 Stage II-III STS patients treated with pre-operative RT (50-50.4 Gy in 25-28 fractions) followed by resection. Five additional patients who did not receive RT were utilized as controls. PD-L1 expression on biopsy and resection samples was evaluated by immunochemistry using the anti PD-L1 monoclonal antibody (E1L3 N clone; Cell Signaling). Greater than 1% membranous staining was considered positive PD-L1 expression. Changes in PD-L1 expression were analyzed via the Fisher exact test. Kaplan-Meier statistics were used to correlate PD-L1 expression to distant metastases (DM) rate. The majority of STS were T2b (87.0%), high-grade (80.4%), undifferentiated pleomorphic histology (71.7%), and originated from the extremities (84.6%). Zero patients demonstrated PD-L1 tumor expression pre-RT. Post-RT, 5 patients (10.9%) demonstrated PD-L1 tumor expression (p = 0.056). Tumor associated macrophages (TAM) expression of PD-L1 increased after RT: 15.2% to 45.7% (p = 0.003). Samples from controls demonstrated no baseline (0%) or change in tumor PD-L1 expression. Freedom from DM was lower for patients with PD-L1 TAM expression post-RT (3 years: 49.7% vs. 87.8%, log-rank p = 0.006); TAM PD-L1 positivity remained an independent predictor for DM on multivariate analyses (Hazard ratio - 0.16, 95% confidence interval: 0.034-0.721, p = 0.042). PD-L1 expression on human STS tumor and TAM appears to elevate after pre-operative RT. Expression of PD-L1 on TAM after RT was associated with a higher rate of DM.

Dedifferentiated chondrosarcoma of the larynx: Radiological, gross, microscopic and clinical features.

Laryngeal chondrosarcoma is an uncommon malignancy with a predilection for the cricoid cartilage of adult male patients. Although rare, identification of aggressive chondrosarcoma variants, such as dedifferentiated chondrosarcoma (DDCS) may influence preoperative patient counseling, definitive surgical management, potential implementation of post-operative adjuvant therapy and prognosis. Herein we describe clinical and imaging features of laryngeal DDCS, the unique perspective of fresh and formalin fixed macroscopic examination, a spectrum of histopathologic findings, and detail the full course of the patient's disease.

MDM2 and CDK4 Immunohistochemistry: Should It Be Used in Problematic Differentiated Lipomatous Tumors?: A New Perspective.

Although most cases of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) can be diagnosed solely on the basis of histologic features, those lacking diagnostic histologic features require ancillary studies for accurate classification. Fluorescent in situ hybridization (FISH) for amplification of MDM2 has been considered the gold standard for diagnosis in these situations. Immunostaining for MDM2 and/or CDK4 has been adopted as a surrogate method because of its high concordance rate with FISH and lower cost. However, studies examining the concordance of the 2 methods have been based preferentially on cases in which the diagnosis could be established histologically. No study has explored the concordance between the 2 methods in histologically ambiguous cases or in cases in which the diagnosis of ALT/WDL is not apparent after a review of all slides. To address this, we performed immunostaining for MDM2 and CDK4 on 183 well-differentiated lipomatous tumors that could not be diagnosed on purely histologic grounds and that were, therefore, subjected to FISH analysis. These included ALT/WDLs (n=56), lipomas (n=96), and lipoma variants (n=31). Staining for MDM2 and CDK4 was noted in 25/56 and 23/56 ALT/WDL, respectively, giving a sensitivity of 45% and 41% and a specificity of 98% and 92%. Staining was noted exclusively in the nuclei of atypical cells and not in the nuclei of adipocytes. Staining for MDM2 and CDK4 occurred in 2/125 and 10/117 benign lipomatous lesions, respectively. False-positive staining was equivalent in intensity to ALT/WDL. We conclude that MDM2 and CDK4 staining is a relatively insensitive method for diagnosing ALT/WDL in cases that are histologically ambiguous, as staining is restricted to neoplastic cells with atypia that are underrepresented in these cases. Therefore, in cases like ours that closely simulate clinical practice, FISH is the more reliable and cost-effective option.

Cytologic features of angiosarcoma: A review of 26 cases diagnosed on FNA.

BACKGROUND: This study describes the cytologic features of 26 angiosarcomas diagnosed on fine-needle aspiration. METHODS: Twenty-six angiosarcomas from 20 patients were confirmed by cytomorphology and immunocytochemical (immunohistochemistry) positivity for at least 2 of 3 vascular markers. Specimens were examined for spindled/epithelioid/plasmacytoid single cells, 3-dimensional clusters, multiple prominent/bar-shaped nucleoli (5 times longer than their width), chromatin strands, abnormal mitoses, necrosis, and vasoformative features. RESULTS: Eight males and 12 females with a mean age of 52 years (range, 2-94 years) underwent aspiration of tumors in the following: soft tissue or skin/subcutis (n = 10), bone (n = 4), nodes (n = 5), lung (n = 2), liver (n = 2), heart (n = 1), parotid gland (n = 1), and pleural fluid (n = 1). An angiosarcoma diagnosis was rendered for 24 of the 26 cases (92%); 1 was diagnosed as "atypical cells, cannot exclude angiosarcoma," and another was diagnosed as a malignant vascular neoplasm. Abnormal mitoses were most frequent (85%), and they were followed by single malignant cells (81%: epithelioid [69%], spindled [62%], and plasmacytoid [19%]), 3-dimensional clusters (54%), multiple prominent (62%) or bar-shaped nucleoli (54%), and chromatin strands (31%). Vasoformative features, including hemophagocytosis (54%), cytoplasmic lumina/vacuoles (69%) containing red blood cells (54%)/neutrophils (31%), and endothelial wrapping (69%), were seen in 88%; 23% had all vasoformative features, 88% had at least 1, and 12% had none. CONCLUSIONS: Angiosarcomas show a range of cytomorphologic features that make them potentially recognizable on cytology. Although vasoformative features are highly suggestive, they are not specific for angiosarcoma and may be seen in some nonvascular neoplasms. Immunohistochemistry and a high index of suspicion are required for an accurate diagnosis. Cancer Cytopathol 2016;124:659-68. © 2016 American Cancer Society.

MDM2 Amplification in Problematic Lipomatous Tumors: Analysis of FISH Testing Criteria.

To discriminate lipomas from atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) we perform fluorescence in situ hybridization (FISH) for MDM2 amplification in several problematic situations: "lipomas" >10 cm, lesions with equivocal atypia, recurrent "lipomas," all retroperitoneal/pelvic/abdominal "lipomas", and in cases not fitting the above criteria but having worrisome clinical or radiologic features. To ascertain the validity of these criteria, we have reviewed our experience with 301 consecutive differentiated lipomatous tumors in which the diagnosis of ALT could not be established on the basis of histologic sections and in which FISH was performed on the basis of the above criteria. The final diagnosis was based on MDM2 amplification status. Given the nature of this study to evaluate difficult lesions, most cases included (74%) were received in consultation. This enhanced our study series for borderline cases, and the data presented may not be generalizable to adipocytic tumors seen outside a subspecialty setting. Of 301 cases, 108 proved to be ALT/WDL (36%). The most common test indication was size >10 cm (n=187), followed by equivocal atypia (n=145), retroperitoneal/pelvic/abdominal location (n=86), recurrence (n=33), and clinical concern (n=12). Of the tumors >10 cm, 68 (36%) proved to be ALT/WDL, whereas the remainder were interpreted as lipoma or its variants (eg, spindle cell or pleomorphic lipoma). The 2 groups did not differ statistically in size, although ALTs consistently occurred in patients above 50 years of age. Of the cases with equivocal atypia, 72 (50%) proved to be ALT/WDL. Those in the retroperitoneum/abdomen/pelvis were ALT/WDL in 30 cases (35%), and those that had recurred were ALT in 18 cases (55%). Recurrence, atypia, and having multiple indications for testing were more common in ALT than in benign lesions (P=0.02, 0.0001, 0.0012, respectively). No ALT/WDL occurred in the hands and feet, and only a single ALT/WDL was superficial (1 ALT/WDL vs. 60 lipoma/spindle cell or pleomorphic lipoma). Small (<10 cm) retroperitoneal tumors without additional features were always benign (n=9). On the basis of our results, FISH testing is recommended for: (1) recurrent lesions; (2) deep extremity lesions that are >10 cm in patients over 50 years of age; (3) in cases with equivocal atypia; (4) in lesions of the retroperitoneum/pelvis/abdomen, and in special clinical situations as directed by treating clinicians. Testing is low yield in superficial lesions, in small extremity lesions without additional indicators for testing, in large extremity lesions without additional features in patients under the age of 50, and in lesions arising in the hands/feet. More evidence is needed regarding testing in small retroperitoneal lesions without additional features. By adopting these criteria, we could have avoided testing 74 cases, missing a single superficial ALT/WDL.

The utility of ERG, CD31 and CD34 in the cytological diagnosis of angiosarcoma: an analysis of 25 cases.

AIMS: Erythroblast transformation specific related gene (ERG), a proto-oncogene member of the erythroblast transformation specific transcription factor family, is a sensitive marker of endothelial differentiation and is expressed in vascular tumours, including angiosarcomas (AS). Immunohistochemistry is necessary for the diagnosis of AS in fine needle aspirates where low cellularity and lack of preserved tissue architecture impedes diagnosis. The aim of this study was to assess the utility of an ERG-enriched immunohistochemistry panel in the cytological diagnosis of AS. METHODS: 25 AS diagnosed on fine needle aspirates were stained for ERG, CD31, CD34, and AE1/AE3. Staining intensity and percentage tumour cell positivity were evaluated. Spearman's correlation was assessed for significant correlations between antibodies. RESULTS: Sensitivities for ERG, CD31, CD34 and AE1/AE3 were 100%, 100%, 60% and 21%, respectively. Spearman's analysis revealed that ERG and CD31 staining correlated significantly; there was no significant correlation between CD31 and CD34 staining. CONCLUSIONS: With equal sensitivity to, and strong correlation with CD31, ERG staining is highly suitable for the cytological diagnosis of AS. ERG and CD31 are more sensitive vascular markers than CD34. ERG, a nuclear stain, complements the cytoplasmic/membranous staining of CD31. Used in conjunction with CD31, ERG can corroborate the diagnosis of AS.

Myofibromas with atypical features: expanding the morphologic spectrum of a benign entity.

Typical myofibromas are biphasic tumors composed of a central zone of immature spindled to rounded cells arranged in a pericytic pattern and a peripheral zone of myoid nodules. Central necrosis is occasionally seen. A small but undefined subset of myofibromas displays atypical features that may lead to a misdiagnosis of sarcoma. To more completely characterize these tumors and define their behavior, we analyzed our experience with myofibromas having 1 or more atypical features including hypercellularity, absent or inconspicuous, poorly demarcated myoid nodules, infiltrative growth pattern, and perineural invasion. Of 266 cases of myofibromas, 24 cases were retrieved on the basis of pathology reports in which atypical features were mentioned. The tumors presented in 16 male and 8 female individuals (mean age 17 y; range, 2 wk to 62 y) as masses of variable size (mean 3.0 cm; range, 1.5 to 6.5 cm). Fourteen cases arose on the head and neck and 10 cases on the limbs. The referring or suspected diagnosis was sarcoma in 8 cases. The tumors were typically more cellular than ordinary myofibroma with levels of cellularity similar to that expected in fibrosarcoma (22/24). In addition, they displayed inconspicuous, loosely cohesive (22/24) or absent myoid nodules (2/24), infiltrating borders (19/24), intravascular growth (5/24), and perineural invasion/nerve entrapment (6/24). The mean mitotic rate was 5 mitoses/10 high-power fields, but no tumor showed significant cytologic atypia. The tumors were positive for actins (11/11) and CD34 (2/8). Follow-up in 14 patients revealed no distant metastases. We conclude that a small subset of myofibromas shows atypical features that complicate the diagnosis but do not adversely affect outcome.

Vascular tumors of bone.

Vascular tumors of the bone represent a variety of neoplasms, ranging from benign hemangiomas and epithelioid hemangiomas to intermediate grade hemangioendotheliomas to frankly malignant angiosarcomas. Over the years, there has been considerable debate concerning the aggressivity, nomenclature, and mere existence of various nosologic entities, due to morphologic similarities and uncertainty regarding biologic behavior. Such debate has led to confusion among pathologists and clinicians, thus diminishing the prognostic implications in the diagnosis of these lesions. Here we review the current knowledge concerning the primary vascular neoplasms of the bone and correlate clinicopathologic features with tumor behavior.