Intimal sarcoma is a rare aggressive malignant neoplasm that arises from the heart or large blood vessels. 

Intimal sarcoma is a rare mesenchymal neoplasm with a mean age at diagnosis of approximately 40-65 years. ^1-3 It most commonly occurs in the proximal pulmonary circulatory system, aorta, and heart, where it is the most common primary cardiac sarcoma,^4,5

Intimal sarcoma of the aorta or its proximal branches frequently gives rise to tumor emboli that can occlude large vessels, leading to ischemia of somatic soft tissue or visceral sites.⁶For primary intimal sarcoma of the right heart or pulmonary arteries, tumor instead embolizes to the lung, leading to non-specific symptoms such as fatigue or shortness of breath.⁷

Intimal sarcoma can exhibit a wide range of morphologies.^1,2 It is most frequently a high-grade, pleomorphic spindle cell sarcoma, and some examples are myxoid or epithelioid. ¹ Rarely, tumors contain cartilage or bone, and some cases show rhabdomyoblastic differentiation. ^1,5,8 Given the non-specific and wide-ranging morphologic findings, the most important clue to the diagnosis is the tumor location and clinical context.

In most cases, intimal sarcoma expresses MDM2 and CDK4, which are diagnostically helpful if positive. ^9-11 It also commonly express SMA and can express other non-specific markers such as CD34 and desmin.¹⁰

Intimal sarcoma is an aggressive malignancy, with a mean survival of roughly 6-18 months depending on primary site.^2,3,9 Intimal sarcoma of the pulmonary artery commonly involves the lung, either via direct extension or metastasis; in general, about 25% of tumors metastasize to extrathoracic sites.¹ Treatment strategies for intimal sarcoma are evolving; a recent multi-institutional study demonstrated that anthracycline-based chemotherapy regimens increased progression-free survival, while pazopanib- and gemcitabine-based regimens had more limited benefit.⁴

• 12q12-q15 amplification, including MDM2, CDK4, and GLI1 loci, has been demonstrated in most cases (Fig. 1). ^9,12 A recent study using FISH, quantitative PCR, and array CGH demonstrated MDM2 amplification in all 42 examined cardiac intimal sarcomas. ⁵

• 4q12 amplification, (containing KIT and PDGFRA) is detected in about 70-80% of cases.^5,13

• Amplification or polysomy of 7p12 (containing EGFR) is detected in about 50-80% of cases. ^5,14

• Amplification or polysomy of PDGFRB is detected in about 70-80% of cases. ¹⁴

• Intimal sarcoma also exhibits complex chromosomal copy number gains and losses.⁹

Figure 1. Intimal sarcoma harbors MDM2 amplification in most cases.