Undifferentiated Intimal Sarcoma Research Articles

A RARE CASE OF MYOCARDIAL INFARCTION DUE TO INTIMAL SARCOMA OF THE AORTIC ARCH

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Intimial sarcoma (IS) of the large systemic arteries are an extremely rare class of tumors with only 81 reported cases in literature, most commonly arising in the abdominal aorta (1). Due to its nonspecific clinical presentation, IS is frequently diagnosed late in the disease process when metastasis has already developed, specifically to the lungs, abdominal organs, vertebral bone, and skin (2). Accurate diagnosis is made with immunohistochemical (IHC) staining positive for CD31, Fli-1, and ERG1. We present a case of an IS of the aortic arch resulting in a fatal tumor embolism to the left coronary artery (LCA), as diagnosed on autopsy. CASE PRESENTATION: A healthy 51-year-old male presented with severe sharp pain in the thoracic spine. Physical exam was positive for tenderness to palpation in the mid-thoracic spine with bilateral lower extremity (LE) neurological deficits. Magnetic resonance imaging (MRI) of the spine revealed bone lytic lesions in the thoracic spine from T5 to T7 with a T6 compression fracture. A computed tomography (CT) scan of the chest, abdomen, and pelvis showed no evidence of the primary tumor site. Biopsy revealed metastatic bone sarcoma of unknown origin. The patient underwent palliative radiation therapy for two weeks. One month after completion of treatment, the patient was re-admitted with worsening back pain. Repeat CT scan showed worsening compression fractures and extraosseous tumor extension into the prevertebral space. Subsequently, the patient underwent spinal cord decompression surgery. On post-operative day 4, he developed severe chest pain with refractory ventricular fibrillation leading to his death. Autopsy revealed an IS extending from the aortic arch to the aortic valve with metastasis to the thoracic vertebrae and thyroid gland. Ultimately, the cause of death was due to a tumor embolus that occluded his LCA. DISCUSSION: Aortic IS is an extremely rare neoplasm that typically presents late in the disease process. The initial manifestation of aortic IS in our case was metastatic vertebral bone lesions with no other evidence of the primary site on radiologic modalities, despite retrospective imaging analysis. It is important that aortic IS be included on the differential diagnosis for sarcoma of unknown origin in order to better understand the disease course. To our knowledge, this is the first reported case of aortic IS that presented as a sarcoma of unknown origin with bone metastases and resulted in a myocardial infarction with findings of metastasis to the thyroid gland. CONCLUSIONS: Aortic IS can be classified as: Angiosarcoma, expressing endothelial-specific antigens, and Myofibroblast, expressing mesenchymal-specific antigens. Diagnosis is tricky as IS are easily missed on CT and MRI. Definitive diagnosis requires IHC analysis. Prognosis for aortic IS is quite poor, with a mean survival period of one year. REFERENCE #1: Sebenik, M., et al. (2005). Undifferentiated Intimal Sarcoma of Large Systemic Blood Vessels. American Journal of Surgical Pathology, 29(9), 1184-1193. REFERENCE #2: Staats, P., et al. (2014). Intimal sarcomas of the aorta and iliofemoral arteries: A clinicopathological study of 26 cases. Pathology,46(7), 596-603 DISCLOSURES: No relevant relationships by Daniel Rushing, source=Web Response No relevant relationships by Amjed Zidan, source=Web Response

Activating mutation of PDGFRB gene in a rare cardiac undifferentiated intimal sarcoma of the left atrium: a case report.

Cardiac sarcoma is a rare malignant tumor with undefined genetic mutations and no targeted therapy. Here in one rare case of undifferentiated cardiac intimal sarcoma (IS), a next-generation sequencing based assay, MSK-IMPACT (Memorial Sloan Kettering - Integrated Mutation Profiling of Actionable Cancer Targets), identified a somatic, activating mutation in PDGFRB, along with amplification of PDGFRA. This E472D mutation of PDGFRB was discovered for the first time in IS. These findings suggest that concurrent aberrant PDGFRA and PDGFRB signaling may be a diagnostic biomarker and molecular therapeutic target of IS of the heart.

Undifferentiated Intimal Sarcoma of the Inferior Vena Cava with Extension to the Right Atrium and Renal Vasculature

Primary sarcomas of the great vessels (aorta, pulmonary artery, and inferior vena cava (IVC)) are exceedingly rare. We report a rare case of an undifferentiated intimal sarcoma of the IVC with extension to the right atrium, adrenal, and renal veins. The patient underwent extensive resection, reconstruction of the IVC, and subsequent adjuvant chemotherapy. Patient has tolerated chemotherapy and, at 17 months after resection, the patient remains free of tumor recurrence. Undifferentiated intimal sarcomas remain a rare entity with only five cases of venous undifferentiated intimal sarcomas reported in the literature, two of which occurred in the IVC. Intimal sarcomas tend to carry a poor prognosis with the limited literature available on treatment approaches. Our objective is to highlight this rare entity and possible treatment approach which we utilized. Primary sarcomas of IVC need to be included as part of a complete differential diagnosis in patients with atrial masses or recurrent pulmonary emboli.

Uncommon case of brain metastasis in a patient with a history of heavy smoking.

Primary sarcomas of the aorta are extremely uncommon. Depending on histomorphology and immunohistochemical pattern, intimal sarcomas can show angiosarcomatous differentiation. Here, we describe the case of a 60-year-old woman with a primary intimal sarcoma of the aortic arch and signs of cerebral metastatic disease as the initial manifestation. After the patient experienced the onset of severe headaches, ataxia, and left-sided weakness, magnetic resonance imaging showed several brain lesions. Histologic assessment of a brain biopsy specimen revealed a malignant tumour composed of large pleomorphic cells that were positive for pancytokeratin and CD10. Radiation to the brain did not significantly improve the patient's symptoms, and cranial computed tomography (ct) imaging revealed several metastases, indicating lack of response. Because of the patient's smoking history, the presence of central nervous system and skeletal metastases on combined positron-emission tomography and ct imaging, and the focal pan-cytokeratin positivity of the tumour, carcinoma of the lung was favoured as the primary tumour. Despite chemotherapy with cisplatin and etoposide, the patient's neurologic symptoms and general condition deteriorated rapidly, and she died within a few days. At autopsy, an undifferentiated intimal sarcoma of the aortic arch was diagnosed. The primary tumour in the aorta consisted of large pleomorphic cells. Immunohistochemical analysis of the aortic tumour and brain metastases demonstrated diffuse positivity for vimentin and p53 and focal S-100 staining. In summary, we report a challenging case of advanced intimal sarcoma of the aortic arch with brain and bone metastases at initial presentation. Our report demonstrates the difficulties in diagnosing and treating this disease, and the need for multicentre studies to accrue more patients for investigations of optimal therapy.

Undifferentiated Intimal Sarcoma Masquerading As a Contained Abdominal Aortic

Undifferentiated Intimal Sarcoma Masquerading As a Contained Abdominal Aortic

RUNX‐1 and CD44 as markers of resident stem cell derivation in undifferentiated intimal sarcoma of pulmonary artery

To report a rare case of undifferentiated intimal sarcoma (UIS) of the pulmonary artery in a 44-year-old woman, and to study it by electron microscopy and a novel immunohistochemical (IHC) panel that recognizes markers of endothelial and haematopoietic stemness, in order to extend current knowledge about the histogenesis of this rare neoplasm. Immunohistochemical reactions for CD31, CD34, α-smooth muscle actin (α-SMA), caldesmon, calponin, actin, desmin, epithelial membrane antigen, WT1, CD117, Ki67, nestin, RUNX-1, platelet-derived growth factor, NG2, CD44, CD90 and CD105 were performed manually or automatically. Neoplastic cells were negative for CD31 and CD34, but positive for calponin, nestin, WT1, CD44, and RUNX-1. Electron microscopy was performed after osmium tetroxide fixation and staining with lead citrate and uranyl acetate. Ultrastructurally, tumour cells had slightly irregular nuclei, cisternae of rough endoplasmic reticulum, and punctate intercellular junctions. We report a case of pulmonary artery UIS expressing previously unreported markers, i.e. RUNX-1, nestin, WT1, and CD44, that are commonly seen in different stages of the vascular differentiation hierarchy. These findings, together with the negativity for mature endothelial and smooth muscle markers, raise the question of whether this neoplasm may derive from a vessel wall-resident stem cell, such as the haemangioblast or an embryonic-like stem cell.

Metastatic Pulmonary Intimal Sarcoma Presenting as Cauda Equina Syndrome

Case report and clinical discussion. To describe a rare case of metastatic pulmonary intimal sarcoma presenting as cauda equine syndrome. Pulmonary artery sarcoma is a rare tumor, frequently misdiagnosed as pulmonary embolism, and although it is highly aggressive, metastasis to bone is very rare. In our case, the tumor metastasised to the vertebral column, which lead the patient to present with cauda equine-type symptoms. We report the clinical and imaging features in a 38-year-old female presenting with back pain and weakness of the legs. Although initially misdiagnosed as a primary bone tumor of the vertebral column and a concurrent pulmonary embolism, the final diagnosis of pulmonary artery sarcoma with spinal metastasis, presenting as cauda equina syndrome was made. At surgery, the mass was excised with the pulmonary valve and replaced with a homograft. The histology demonstrated an undifferentiated intimal sarcoma of the pulmonary artery. When stable enough the patient underwent a posterior L4-S1 decompression laminectomy after which she regained the power in the legs. The histology also showed a metastatic undifferentiated intimal sarcoma likely to have come from the pulmonary artery. The patient went on to receive a more formal vertebrectomy, front and back repair, and radiotherapy. Her 1-year follow-up computed tomography (CT) chest showed evidence of further metastases. To our knowledge, this is the first case of metastatic pulmonary intimal sarcoma presenting as cauda equine syndrome described in the literature.

Primary aortic intimal sarcoma

Aortic intimal angiosarcoma is extremely rare, and the prognosis of patients with a tumor is unfavorable even if they have undergone surgery. We treated a patient with primary intimal angiosarcoma of the aortic arch who underwent an operation. The tumor originated from the inner wall of the aortic arch on the lesser curve. In order to remove the tumor completely, the entire aortic arch from the ascending to the middle of descending aorta was resected through an L-shape skin incision. On histologic examination, an undifferentiated intimal sarcoma was diagnosed. It grew into the aortic lumen while spreading along the aortic intima, focally infiltrating the media. The postoperative course was uneventful. Postoperative CT performed at 6, 12 and 18 months after surgery showed no local recurrence or metastasis. According to some reports endoarterectomy has been performed to treat this type of tumor, since the malignant cells are thought to be limited to the luminal surface. However, we favor aortic resections and graft interpositions rather than an endoarterectomy because the tumor could have invaded the media.

Undifferentiated Intimal Sarcoma of Large Systemic Blood Vessels

Intimal sarcoma (IS) is defined as a malignant tumor arising in the tunica intima of large blood vessels. In systemic circulation, the majority of IS develop in the aorta, where close to three fourths of published cases lack specific differentiation and are called undifferentiated intimal sarcomas (UIS). The remaining cases are intima-associated sarcomas of recognized types, also called differentiated intimal sarcomas (DIS). In this report, we further characterize UIS, including its immunohistochemical profile and results of comparative genomic hybridization. A total of 14 cases of UIS were collected from 17 medical institutions, including slides, blocks, electron photomicrographs, clinical abstracts, and reports of surgical pathology specimens and autopsies. The patients, 7 women and 7 men, were 41 to 85 years of age (median, 65.6 years). Twelve tumors arose from the aorta, one from the left external iliac and femoral arteries, and one in a large systemic vein (the venous tumor was included due to histologic similarity with the arterial lesions). Tumors ranged from 1 cm to over 10 cm in diameter. Histopathology was that of a largely necrotic, poorly differentiated epithelioid and pleomorphic malignant neoplasm relating to the tunica intima. Usually there was only a thin layer of viable tumor cells overlying a large thrombus. All tumors stained at least focally with the endothelial markers CD31 and Fli-1; however, there was otherwise considerable variability in immunophenotype. The distinctive histopathologic appearance of the primary luminal lesion was lost whenever tumor invaded outside the vessel wall (into adventitia and beyond) or in metastatic sites. Such extravascular tumors assumed a variety of patterns reminiscent of undifferentiated pleomorphic sarcoma (UPS; in older literature also known as pleomorphic malignant fibrous histiocytoma, MFH) or other distinct types of sarcomas, including osteosarcoma, angiosarcoma, and rhabdomyosarcoma. The results of comparative genomic hybridization were nonspecific. Eleven patients died of the disease, in an average of 11 months after diagnosis. Three patients are still alive and free of disease at 4, 16, and 27 years. UIS of large systemic vessels represents a distinct clinical entity where intraluminal sarcoma presents with thrombosis and occlusion of large vessels. It is associated with a highly characteristic, although not entirely specific, histology and immunohistochemical phenotype. The histogenesis of UIS is not certain; however, it seems that the cell of origin must leave the confines of the vessel wall to show altered morphology. Although there are rare long-term survivors, UIS behaves as a fully malignant neoplasm that is almost uniformly associated with metastases and tumor-related death.