ArticlePublisher preview availableLiterature Review

Primary osseous tumors of the orbit

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract and Figures

This review article focuses on the various primary osseous tumors of the orbit. Due to overlapping clinical, radiologic, and histologic features, differentiating these entities can pose significant challenges diagnostically. In this review, emphasis is placed on key distinguishing clinical, morphologic, immunophenotypic, and molecular characteristics. Also described are important prognostic details, recurrence risks, and the gold standard treatment methods for each entity. Relevant genetic syndrome associations are additionally covered. Orbital bone entities discussed include osteoma, osteoid osteoma, osteoblastoma, ossifying fibroma, fibrous dysplasia, aneurysmal bone cyst, osteosarcoma, Ewing sarcoma, and mesenchymal chondrosarcoma.
This content is subject to copyright. Terms and conditions apply.
Vol.:(0123456789)
Virchows Archiv
https://doi.org/10.1007/s00428-024-03975-6
REVIEW
Primary osseous tumors oftheorbit
MarielBedell1· RanaNaous1
Received: 31 July 2024 / Revised: 29 September 2024 / Accepted: 6 November 2024
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024
Abstract
This review article focuses on the various primary osseous tumors of the orbit. Due to overlapping clinical, radiologic, and
histologic features, differentiating these entities can pose significant challenges diagnostically. In this review, emphasis is
placed on key distinguishing clinical, morphologic, immunophenotypic, and molecular characteristics. Also described are
important prognostic details, recurrence risks, and the gold standard treatment methods for each entity. Relevant genetic
syndrome associations are additionally covered. Orbital bone entities discussed include osteoma, osteoid osteoma, osteo-
blastoma, ossifying fibroma, fibrous dysplasia, aneurysmal bone cyst, osteosarcoma, Ewing sarcoma, and mesenchymal
chondrosarcoma.
Keywords Bone tumors· Primary· Orbit
Introduction
Osseous tumors of the orbital bone are rare. Although both
benign and malignant bone tumors can affect the orbit, the
majority of orbital bone tumors are benign. Their clinical
presentation is variable and includes headaches, double
vision, vision loss, proptosis, facial pain or deformity, sinus-
itis, or sometimes asymptomatically. On some occasions,
there is a delay between symptom onset and diagnosis. The
treatment of almost all osseous orbital tumors is surgical. We
provide here a review of osseous tumors originating from the
orbit. Osteoma, osteoid osteoma, osteoblastoma, ossifying
fibroma, fibrous dysplasia, and aneurysmal bone cyst are all
benign primary bone tumors found in the orbit. Malignant
primary bone tumors of the orbit include mainly osteosar-
coma, Ewing sarcoma and mesenchymal chondrosarcoma.
We will review the clinicopathologic and radiologic features
as well as molecular characteristics, treatment options, and
recurrence risk of each of these lesions.
Osteoma
Osteomas of the orbit are benign, slow growing, and com-
monly asymptomatic lesions that are incidentally found on
imaging studies secondary to their indolent growth and small
size (< 2cm). When symptomatic they may cause facial
deformity, facial pain, sinusitis, and headache [1]. On imag-
ing, osteomas are uniformly dense, well-marginated lesions
with a broad base of attachment to underlying cortex without
any evidence of cortical invasion [2] (Fig.1A). Osteomas
predominantly affect bones formed by membranous ossifi-
cation and commonly present in the skull bones. They tend
to localize to the surface of craniofacial bones most often
in the fourth through sixth decades of life, equally in males
and females. They are well-circumscribed tumors composed
of mature compact, spongiotic/trabecular or mixed compact
and spongiotic bone with usually inconspicuous osteoblas-
tic and osteoclastic activity and set in a loose fibrovascular
stroma (Fig.1B). Sino-orbital osteomas may have zones
indistinguishable from an osteoblastoma with characteristic
conspicuous osteoblastic and osteoclastic activity mimicking
osteoblastoma (Fig.1C), thus labeling them as osteoblas-
toma-like osteomas [3]. However, this diagnosis may be sub-
jective and varies among institutions as some would refer to
such lesions with a predominant osteoblastoma-like pattern
as osteoblastomas or osteoblastomas with areas of sclerosis.
Although most are considered hamartomas, a subset of
osteomas is associated with APC gene mutations [4, 5] or
* Rana Naous
naousr@upmc.edu
Mariel Bedell
bedellml@upmc.edu
1 Department ofPathology, University ofPittsburgh Medical
Center (UPMC), Shadyside Hospital, 5230 Centre Avenue,
WG02.6, Pittsburgh, PA15232, USA
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
ResearchGate has not been able to resolve any citations for this publication.
Article
Full-text available
The fifth edition of the World Health Organization classification of soft tissue and bone tumors redefined Ewing sarcoma by fusions between EWSR1/FUS and ETS family of transcription factors, and recognized three tumor groups among Ewing-like sarcoma: CIC-rearranged sarcoma, sarcoma with BCOR genetic alterations, and round cell sarcoma with EWSR1::non-ETS fusions. Although this classification underscores the critical role of molecular genetics in the diagnosis of small round cell sarcoma, each entry is recognized as a specific entity not only because they have different genetics but because their phenotypes are distinct and reasonably robust to support the diagnosis. This review focuses on the morphological aspects of Ewing sarcoma and a subset of Ewing-like sarcomas (CIC-rearranged sarcoma, BCOR-associated sarcoma, and EWSR1::NFATC2 sarcoma) for which phenotypic characteristics have been well established. Classic histological findings, uncommon variations, and recurrent diagnostic pitfalls are addressed, along with the utility of recently developed immunohistochemical markers (NKX2.2, PAX7, ETV4, BCOR, CCNB3, and NKX3.1). Phenotypic expertise would significantly expedite the diagnostic process and complement (or sometimes outperform) genetic testing, even in well-resourced settings. Morphological knowledge plays an even more substantial role in facilities that do not have easy access to molecular testing.
Article
Full-text available
Osteoma is a benign bone forming tumor predominantly arising on the surface of craniofacial bones. While the vast majority of osteomas develops sporadically, a small subset of cases is associated with Gardner syndrome, a phenotypic variant of familial adenomatous polyposis caused by mutations in the APC gene resulting in aberrant activation of WNT/β-catenin signaling. In a sequencing analysis on a cohort of sporadic, non-syndromal osteomas, we identified hotspot mutations in the CTNNB1 gene (encoding β-catenin) in 22 of 36 cases (61.1%), harbouring allelic frequencies ranging from 0.04 to 0.53, with the known S45P variant representing the most frequent alteration. Based on NanoString multiplex expression profiling performed in a subset of cases, CTNNB1-mutated osteomas segregated in a defined “WNT-cluster”, substantiating functionality of CTNNB1 mutations which are associated with β-catenin stabilization. Our findings for the first time convincingly show that osteomas represent genetically-driven neoplasms and provide evidence that aberrant WNT/β-catenin signaling plays a fundamental role in their pathogenesis, in line with the well-known function of WNT/β-catenin in osteogenesis. Our study contributes to a better understanding of the molecular pathogenesis underlying osteoma development and establishes a helpful diagnostic molecular marker for morphologically challenging cases.
Article
Full-text available
Gardner syndrome is a neoplasic disease that associates intestinal polyposis and colorectal adenocarcinoma with osteomas and soft tissue tumors determined by germline mutations in the APC gene. The early diagnosis and identification of high-risk individuals are important because patients have a 100% risk of colon cancer. We present the case of a family with Gardner syndrome. Cephalometric, panoramic X-rays and CBCT of the proband and her brother showed multiple osteomas affecting the skull bones, mandible and paranasal sinuses. The detailed family history showed an autosomal dominant transmission with the presence of the disease in the mother and maternal grandfather of the proband. Both had the typical signs of disease and died in the fourth decade of life. Based on these aspects the clinical diagnosis was Gardner syndrome. By gene sequencing, a novel pathogenic variant c.4609dup (p.Thr1537Asnfs*7) in heterozygous status was identified in the APC gene in both siblings. We reviewed literature data concerning the correlation between the localization of mutations in the APC gene and the extracolonic manifestations of familial adenomatous polyposis as well as their importance in early diagnosis and adequate oncological survey of patients and families based on abnormal genomic variants.
Article
Full-text available
Cemento-ossifying fibroma is a benign fibro-osseous lesion of the jaws. Cemento-ossifying fibroma develops from the periodontal ligament and contains multipotent stem cells that can form cementum, lamellar bone, and/or fibrous tissue. These tumours occur in the third and fourth decades of life with higher predilection of occurrence in the female population and seldom attain a large size. We report a rare case of cemento-ossifying fibroma in a 45-year-old man involving the body of the mandible and extending into the para-pharyngeal and infratemporal region. This article describes the clinical, radiographic, and histological features of a large cemento-ossifying fibroma of the mandible.
Article
Full-text available
Osteosarcoma is the most common primary malignant bone tumor in children and young adults. The standard-of-care curative treatment for osteosarcoma utilizes doxorubicin, cisplatin, and high-dose methotrexate, a standard that has not changed in more than 40 years. The development of patient-specific therapies requires an in-depth understanding of the unique genetics and biology of the tumor. Here, we discuss the role of normal bone biology in osteosarcomagenesis, highlighting the factors that drive normal osteoblast production, as well as abnormal osteosarcoma development. We then describe the pathology and current standard of care of osteosarcoma. Given the complex heterogeneity of osteosarcoma tumors, we explore the development of novel therapeutics for osteosarcoma that encompass a series of molecular targets. This analysis of pathogenic mechanisms will shed light on promising avenues for future therapeutic research in osteosarcoma.
Article
Osteoblastoma is a rare benign bone tumor. Although the histologic features in most cases are distinctive, there are various permutations that make the diagnosis challenging. It can mimic a variety of other benign bone tumors, but more importantly, distinguishing it from osteoblastoma-like osteosarcoma can be difficult. In this case report, I describe the clinicopathologic findings for a 13-year-old adolescent boy with T7 spinal osteoblastoma and review salient clinical, radiographic, and pathologic features of osteoblastoma, as well as the differential diagnoses.
Article
An 11-year-old boy presented with a lesion of the right orbit that was thought to be a hemophilic pseudotumor. Excisional biopsy revealed an unexpected diagnosis of mesenchymal chondrosarcoma. Both mesenchymal chondrosarcoma and hemophilic pseudotumor of the orbit are exceedingly rare. To the best of our knowledge, this is the first reported case of orbital mesenchymal chondrosarcoma masquerading as hemophilic pseudotumor.
Article
Aims Mesenchymal chondrosarcoma (MC) is characterized typically by a bimorphic microscopic appearance of islands of a well‐differentiated cartilaginous component, admixed with a primitive small cell component, which commonly expresses CD99 and NKX2.2. Given the variable relative abundance of each component and histological overlap with other small round cell tumors, the diagnosis can be challenging, especially in a limited sample. A distinctive gene fusion between HEY1 (located in 8q21) and NCOA2 (located in 8q13) was identified in MC, but the downstream molecular events are unknown. NKX3.1 (coding gene located in 8p21.1) recently was reported to be expressed in a small number of MC cases. The purpose of this study was to evaluate the potential diagnostic utility of NKX3.1 immunohistochemistry in MC. Methods and results We evaluated sections from 25 cases of MC, including 20 extraskeletal and 5 osseous. The tumor affected 9 females and 16 males, with a median age of 34 yrs. (age range = 7‐82 yrs.). Two different rabbit antibodies against NKX3.1 (monoclonal and polyclonal) were used for immunohistochemistry. However, no immunoreactivity was observed with either in all 25 (100%) MC. Conclusions NKX3.1 immunoreactivity was not identified in our cohort. Clonality of the antibody could not explain the negativity.