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Intimal Sarcoma

Intimal sarcomas are malignant mesenchymal tumors arising in large blood vessels of the systemic and pulmonary circulation and also in the heart. The defining feature is predominantly intraluminal growth with obstruction of the lumen of the vessel of origin and seeding of emboli to peripheral organs.

Symptoms & Causes

Introduction

Intimal sarcoma is a rare malignant tumor of blood vessels, characterized by intraluminal growth that can obstruct vessels and send emboli to distant sites.

Reference
WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2020 [cited 2024 09 11]. (WHO classification of tumours series, 5th ed.; vol. 3). Available from: https://tumourclassification.iarc.who.int/chapters/33.

Related Terminology
None

Subtype(s)
None

Symptoms

Clinical presentation is nonspecific and often related to tumor emboli, with recurrent pulmonary embolic disease being the most common primary diagnosis. Proper diagnosis is often delayed or made after death. Imaging is nonspecific, but the neoplastic nature of the tissue occluding the lumen can be suspected on the basis of some diagnostic procedures (CT, MRI, PET).

Localization

Intimal sarcomas of the pulmonary circulation mainly involve the proximal vessels: the pulmonary trunk, the right or left pulmonary arteries, or both. Some tumors involve cardiac structures: the left heart, pulmonary valve, or right ventricular outflow. Direct infiltration or lung metastases are observed in 40% of cases, and extrathoracic spread occurs at presentation in 20% (brain, skin, lymph nodes). Aortic intimal sarcomas mostly arise in the abdominal aorta between the celiac artery and the iliac bifurcation, and 30% are located in the thoracic aorta.

Epidemiology

Intimal sarcomas are very rare tumors, with major pulmonary vessel sarcomas being twice as common as aortic tumors. Intracardiac intimal sarcomas are rare, although this is the most common type of heart sarcoma. Pulmonary and heart intimal sarcomas are slightly more common in females (M:F ratio: ~0.7:1), whereas aortic tumors may be more common in males. The mean age at diagnosis is 48 years for pulmonary, 50 years for heart, and 62 years for aortic intimal sarcomas.

Etiology

Unknown

Diagnosis & Treatment

Staging

Not clinically relevant

Pathogenesis

By comparative genomic hybridization (CGH) and array comparative genomic hybridization (aCGH), gains/amplifications of 12q12-q15 (CDK4, TSPAN31, MDM2, GLI1) and 4q12 were reported as the most consistent aberrations. Interphase FISH revealed amplification of PDGFRA and KIT (CD117) and amplification/polysomy of EGFR in all and in 6 of 8 tumors, respectively. In a recent aCGH study, 6 of 8 tumors showed 4q12 amplification, with the common region containing only PDGFRA. Other, less consistent alterations were gains/amplifications in 7p14-p22, 8q11-q23, 12p11, and 12q13-q15 (GLI1, CDK4, DDIT3, HMGA2, BEST3, MDM2) and losses in 3q12-q21, 9p21, 10q22, 12q12, and 12q23. Frequent high-level (co)amplifications/gains of PDGFRA (81%), EGFR (76%), and/or MDM2 (65%) were confirmed in 21 tumors by FISH. Recently, based on molecular analysis, intimal sarcoma was identified as the most frequent sarcoma histotype (42%) in a series of 100 cardiac sarcomas. With the use of FISH, quantitative PCR, and aCGH, MDM2 amplification was detected in 100% of cardiac intimal sarcomas. aCGH showed a complex profile, with recurrent 12q13-q14 amplicons containing MDM2, 7p12 gain involving EGFR, 9p21 deletion targeting CDKN2A in all cases, and KIT and PDGFRA amplification in 2 of 5 cases.

Macroscopic Appearance

By definition, intimal sarcomas are mostly intravascular masses attached to the vessel wall, grossly resembling thrombi and extending distally along the branches of the involved vessels. Occasionally, a mucoid lumen cast can be recovered intraoperatively, or harder, bony areas corresponding to osteosarcomatous differentiation are found. Some of the aortic tumors may cause thinning and aneurysmal dilatation with adherent thrombus, suggesting atherosclerosis.

Histopathology

Intimal sarcomas are morphologically non-distinctive, poorly differentiated malignant mesenchymal tumors, consisting of mildly to severely atypical spindle cells with varying degrees of mitotic activity, necrosis, and nuclear polymorphism. Some tumors show myxoid areas or epithelioid morphology. Prominent spindling and bundling may resemble leiomyosarcoma. Rare cases may contain neoplastic cartilage or tumor osteoid, or show focal rhabdomyosarcomatous or angiosarcomatous features. Immunohistochemically, variable positivity for SMA is found, and some tumors exhibit positivity for desmin. Rhabdomyosarcomatous differentiation is accompanied by the expression of myogenin and MYOD1. Nuclear expression of MDM2 can be observed in at least 70% of cases.

Cytology

FNA specimens of intraluminal sarcomas contain obviously malignant, spindled and pleomorphic mesenchymal tumor cells.

Prognosis and Prediction

The prognosis for patients with intimal sarcomas is poor, with a mean survival time of 5–9 months in patients with aortic sarcomas and 13–18 months in patients with pulmonary sarcomas.

Clinical Features

Diagnostic Molecular Pathology

Demonstration of MDM2 amplification can be helpful.

Essential and Desirable Diagnostic Criteria

Essential: occurrence within the lumen of a large vessel of the pulmonary or systemic circulation or within the heart cavities; primary high-grade sarcoma, with or without heterologous elements.

Desirable: MDM2 amplification (in selected cases).

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