Aortic intimal sarcoma with acute myocardial infarction

An autopsy case of aortic sarcoma who died of acute myocardial infarction caused by coronary involvement is reported. The patient was a 54 year old woman who was admitted because of an undiagnosed fever and general fatigue of 6 months duration. Magnetic resonance imaging (MRI) showed a tumor in the aortic arch. Total aortic arch replacement was performed, it was diagnosed as a malignant mesenchymal tumor of the aorta. The patient died of acute myocardial infarction 10 months after the operation. At autopsy, the tumor had invaded the luminal surface and intima of the proximal anastomosis (the remnant ascending aorta and the graft), the aortic valves, the distal anastomosis (surgical line of the thoracic aorta plus the graft), and the coronary arteries. The left main coronary artery showed complete obstruction by fibrin thrombus with tumor invasion in the intima, which was responsible for acute myocardial infarction. Primitive and bizarre tumor cells proliferated with many slit-like tissue spaces. Most of the tumor except for its luminal surface showed necrosis. Ultrastructurally, there were spaces between tumor cells, suggesting lumen formation, and some of them had microvilli. This sarcoma was considered to be the so-called aortic intimal sarcoma.     

外周原始神经外胚肿瘤／尤因肉瘤临床病理学

目的：研究原始神经外胚叶瘤（PNET）／尤因肉瘤的（EWS）的诊断,鉴别诊断。方法：41例病人按传统病理学分为3类,并用免疫组织化学两步法检测CD99,NSE,S－100蛋白,Syn,VIm,LCA,Des,Myo抗体的表达。结果：（1）41例病人有27例PNET,8例EWS和6例Askin瘤。（2）免疫表型,CD99有87．8％强阳性表达,NSE53．7％,S－100蛋白22％,Syn4.9%,vim41.5%,统计结果显示CD99强阳性表达与NSE,S-100蛋白,Syn,Vim强阳性表达差异有显著性（P＜0．01）。（3）,PNET,EWS,Askin瘤对各种抗体的阳性表达差异无显著性（P＞0．05）,结论：（1）PNET,EWS,Askin瘤属同一肿瘤家族,（2）用组织学,免疫组织化学可与其他小圆细胞肿瘤进行鉴别诊断。     

Cytohistological correlation,immunohistochemistry and Murine Double Minute Clone 2 amplification of pulmonary artery intimal sarcoma: A case report with review of literature

Pulmonary artery intimal sarcoma is a rare aggressive intraluminal tumor often misdiagnosed as acute or chronic pulmonary thromboembolism due to its clinical presentation and radiological findings. Thus early diagnosis is very crucial and may improve patient outcome. There is limited literature on diagnosis of pulmonary artery sarcoma by endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA). Herein, we report a case of mass‐like lesion in the PA diagnosed on cytological material obtained by EBUS‐TBNA with rapid on‐site evaluation (ROSE). The aspirate showed pleomorphic malignant spindled cells arranged in loosely cohesive clusters. The intraluminal origin of PAIS was supported by radiographic findings. Subsequently, the patient received preoperative chemotherapy and underwent tumor resection with reconstruction. This report describes the cytomorphologic features of this rare intravascular tumor and demonstrates how limited cytological sample obtained from EBUS‐TBNA with ROSE can be triaged efficiently for ancillary studies like immunohistochemistry and MDM2 amplification, thus expediting the management.     

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

Vasuri F, Resta L, Fittipaldi S, Malvi D & Pasquinelli G
(2012) Histopathology  61, 737–743 RUNX‐1 and CD44 as markers of resident stem cell derivation in undifferentiated intimal sarcoma of pulmonary artery Aims: 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. Methods and results: 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. Conclusions: 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.     

肺动脉内膜肉瘤1例并文献复习

目的探讨血管内膜肉瘤的临床及病理特点。方法对1例肺动脉内膜肉瘤进行光镜、电镜观察和免疫组化检测并复习文献。结果肿瘤位于肺动脉血管腔内,阻塞管腔,并延伸至周围小血管。光镜下肿瘤细胞主要为梭形细胞,散在分布上皮样细胞和多核巨细胞,核分裂象约46／50HPF。电镜观察见细胞内含有丰富的粗面内质网、线粒体,无向特殊细胞分化的特征。免疫组化染色vimentin呈弥漫阳性、α—SMA灶性阳性、HMB-45散在弱阳性,CKpan、CD34、CD31和S-100蛋白等均阴性。结论内膜肉瘤是一种罕见的发生于大血管壁的恶性肿瘤,预后差,免疫表型无特异性,了解该肿瘤发病部位、临床及病理特点有助于做出正确诊断。     

乳腺上皮样型管周间质肉瘤病理特征及与叶状肿瘤比较观察

目的 探讨乳腺上皮样型管周间质肉瘤的临床病理特点及与叶状肿瘤的关系。方法 采用HE、特殊染色、免疫组化染色(CK，EMA，S-100蛋白，SMA，Vim，Des，MG，CD34，CD99，CD117，PR，HMB45)对1例乳腺上皮样型管周间质肉瘤与5例叶状肿瘤(良性、交界性各1例，恶性3例)做比较性观察。结果 乳腺管周间质肉瘤(上皮样型)有独特的镜下图像：①显著的多角形(上皮样)细胞绕导管或小管的上皮肌上皮层呈间质性增生，无叶状结构；②组织学模式有袖套状、花冠状、菊形团状、结节状、融合结节状和片状浸润；③瘤细胞形态有：多角形(大、小)、柱状和梭形。多角形细胞呈上皮样形态，异型明显，核分裂象多见(10～30个／10HPF，个别区域达6个／1HPF)，病理性核分裂象易见，在浸润灶内见肿瘤性坏死；④瘤细胞Vim弥漫阳性、EMA灶性阳性、CD99和CD117灶性弱阳性、CD34少数阳性，CK、SMA、S-100蛋白、Des、MG、PR、HMB45均阴性。5例叶状肿瘤均具备叶状结构、间质过度增生、细胞密集(异质性分布)、核分裂象2～10个／10HPF等诊断要素。在3例恶性叶状肿瘤中，2例有极少的上皮样袖套状病灶，2例有梭形细胞袖套状病灶。结论 乳腺上皮样型管周间质肉瘤是一种极罕见的恶性纤维上皮肿瘤亚型，它可能是恶性叶状肿瘤的最早期病变，也可能是一种独特的类型。     

Expression of intercellular adhesion molecules in epithelioid sarcoma and malignant rhabdoid tumor

We clinicopathologically evaluated 31 cases of epithelioid sarcoma (ES; 25 'classical' type and six 'proximal variant' type) and six cases of malignant rhabdoid tumor (MRT; three extrarenal and three renal). We also did immunohistochemical studies on 12 classical and three proximal variant cases of ES, and six cases of MRT, to clarify the differences in biological behavior in these tumors. E-cadherin, beta-catenin and CD34 expression was evaluated. We also carried out mutational analysis of exon 3 of the beta-catenin gene by polymerase chain reaction-single-strand conformation polymorphism analysis. In ES, the 5- and 10-year survival rates were 71.1 and 55.3%, respectively. A high mitotic rate (>15/10 high-power fields) was significantly correlated with a poor overall survival rate in ES (P = 0.0248). E-cadherin expression was observed in nine cases (69.2%) of ES and in four cases (66.7%) of MRT. Most of these tumors showed aberrant E-cadherin expression. Seven cases (46.7%) of ES were positive for CD34, although none of the cases of MRT were CD34 positive. Eleven cases (73.3%) of ES were positive for beta-catenin, which was localized to the cellular membrane, whereas all of the cases of MRT were beta-catenin negative. Mutational analysis for the beta-catenin gene was done in nine cases of ES and six cases of MRT, however, genetic alteration was not found. From our results, we conclude that beta-catenin membranous expression could be a useful marker for distinguishing ES, including the proximal variant, from MRT.     

Analysis of potential receptor tyrosine kinase targets in intimal and mural sarcomas

Primary sarcomas of the great vessels are very rare neoplasms and only a few cases have been reported. They are divided into the two broad categories of intimal or luminal and mural sarcomas. We analysed eight advanced high-grade sarcomas originating from major vessels (seven intimal and one mural sarcoma) by means of immunohistochemistry and FISH analysis for PDGFRA, PDGFRB, EGFR and KIT receptor tyrosine kinases (RTKs), together with immunoprecipitation/western blotting, sequencing of the corresponding genes, and the search for cognate ligands. The intimal sarcomas showed a wide spectrum of morphologies and immunophenotypes, whereas the mural sarcoma had common leiomyosarcomatous features. Regardless of their category, all of the cases had a PDGFRA-deregulated cytogenetic profile mainly consisting of an amplification cluster; five were also polysomic for PDGFRB, whereas three showed disomy. Six cases had a deregulated EGFR gene, and c-Kit gene status was similar to that of PDGFRA. In one case, biochemical analysis revealed the presence of activated and highly expressed PDGFRA, PDGFRB and EGFR, whereas KIT was expressed at reference level. Sequencing of the corresponding genes revealed no activating mutations in any of the analysed receptors. The cognate ligands were detected in all cases. In predictive terms, the evidence of gene amplification/high polysomy of several RTKs, together with PDGFRA, PDGFRB and EGFR expression and phosphorylation, suggests that these tumours may be sensitive to RTK-inhibiting treatments.     

Aortic intimal sarcoma: an unusual case with pulmonary vasculature involvement

A disseminated intravascular tumour, presenting initially with splenic and small bowel infarction, caused both clinical and histological diagnostic difficulty. At subsequent autopsy the main tumour mass was identified within the aorta. Dissemination of this tumour was confirmed histologically and lectin and immunohistochemical staining performed. On the basis of the clinical and pathological features, we believe this represents a further case of aortic intimal sarcoma.     

Autopsy case of primary myelofibrosis in which myeloid sarcoma was the initial manifestation of tumor progression

Myeloid sarcoma (MyS) is defined as an extramedullary tumor-forming neoplasm consisting of immature myeloid cells with/without maturation. We experienced a case involving a 68-year-old Japanese male patient who had been followed-up for four years with a diagnosis of chronic idiopathic myelofibrosis/primary myelofibrosis (PMF) and noticed a painful mass in his left axilla. A wedge biopsy characterized the lesion as MyS that displayed megakaryoblastic/megakaryocytic differentiation. As his complete blood count included a few myeloid blasts (1% of WBC) and a bone marrow biopsy detected fibrosis without evidence of acute myelogenous leukemia (AML), a diagnosis of extramedullary blastic transformation of PMF was made, which was confirmed later by V617F mutation in Janus kinase-2 in both initial bone marrow biopsy and axillary tumor biopsy specimens. The patient died of pneumonia eight months after developing the axillary tumor. At autopsy, multiple MyS masses were detected in his soft tissue, but his bone marrow only contained fibrosis. Although MyS rarely develops before the leukemic transformation of PMF, no evidence of AML could be found in the patient's bone marrow at any point during the course of his disease. Thus, it is possible that the blasts in his peripheral blood were derived from the remaining MyS. Furthermore, the present case indicates that extramedullary blastic transformation, which is occasionally seen in CML, can also occur in PMF. Therefore, it is important to recognize that there is a wide variation in the pathogeneses of MyS and PMF.     

Morphometric and immunohistochemical characterization of the intimal layer throughout the arterial system of elderly humans

The purpose of the present study was to obtain insight into the natural development of adaptive intimal thickening and atherosclerosis in the arterial tree of human species. The morphometry and composition of the intimal layer were studied in the arterial system of elderly individuals. Post mortem, a total of 703 arterial segments were dissected from 24 subjects (age 81.9 ± 9.9 years). From each subject, segments were dissected from 31 different arteries. Area stenosis [(plaque area/vessel area) × 100%] was determined in each segment. By (immuno)histochemistry, lipid content and the presence of inflammatory cells (macrophages) were assessed in the coronary, common carotid, brachial, radial and internal iliac arteries. Adaptive intimal thickening or advanced atherosclerosis was observed in all studied artery types. Area stenosis was highest in the coronary arteries (median, 30%) and lowest in the arteries supplying the brain (median, ≤ 7%). Plaques hiding a lipid‐rich core and plaques with macrophage infiltration were observed in all five selected artery types. In summary, the present observation demonstrates that intimal thickening is a systemic process involving most artery types. Within elderly humans, features of advanced atherosclerotic disease, a lipid‐rich core and macrophages, can be observed in the intimal layer of artery types that are recognised for their relation with clinical syndroms as well as artery types that remain clinically silent.     

Intimal sarcoma of the abdominal aorta with platelet‐derived growth factor receptor α overexpression and amplification in mural invasive cells and pulmonary metastatic cells but not in intimal spreading cells

Intimal sarcoma (IS) is the most common sarcoma of the aorta. The platelet‐derived growth factor receptor α (PDGFRA), murine double minute 2 (MDM2), and cyclin‐dependent kinase 4 (CDK4) genes are often simultaneously amplified in IS. While immunohistochemical analysis of IS tissue has demonstrated frequent overexpression of the MDM2 and CDK4 proteins, the expression pattern of PDGFRA has not been well characterized, particularly in terms of intratumoral heterogeneity. Here, we present the case of a 46‐year‐old man who presented with a backache and was subsequently diagnosed with IS. Intratumoral heterogeneity of PDGFRA gene amplification was observed using fluorescence in situ hybridization and was positively correlated with PDGFRA protein expression using immunohistochemistry (IHC). The expression of PDGFRA was also correlated with cytological atypia: PDGFRA was not overexpressed in intimal spreading cells that displayed the lowest degree of atypia while PDGFRA overexpression and amplification were observed in invasive cells of progressive areas such as the aortic wall and a pulmonary metastatic site, which showed increased cytological atypia. Although PDGFRA has not been well examined on IHC, IHC of PDGFRA could be useful to diagnose IS. However, the areas within the tumor from which specimens are derived are important given potential intratumoral heterogeneity.     

Extensive endothelial replacement by tumor cells in the portal system: An autopsy case of intrahepatic cholangiocarcinoma

An autopsy case of intrahepatic cholangiocarcinoma (ICC) with a peculiar form of extensive portal invasion is reported here. A 76‐year‐old woman presented with anorexia and abdominal discomfort. A high level of serum carbohydrate antigen 19‐9 and endoscopically detected esophageal varices were found. Obvious mass lesion was not identified on CT scan and no portal blood flow was found. The patient died 6 months after admission. At autopsy multiple irregular shaped tumors in the liver were found. The size of the largest one was 3 × 2 cm. These tumors were well‐differentiated adenocarcinomas with partial mucinous carcinoma morphology. Surprisingly, portal veins contained mucinous fluid and the inner surface was lined with a single layer of tumor cells but not endothelial cells. Invasion of carcinoma into the tissue outside the blood vessels was hardly observed in organs other than the liver. This form of extensive invasion of the tumor, termed intimal carcinoma spreading, caused complete obstruction of the portal system. To our knowledge there has been no report on this type of portal invasion of ICC.     

Low-grade periductal stromal sarcoma of the breast with myxoid features: Immunohistochemistry

A 52-year-old woman was admitted with a painful right breast tumor measuring more than 20 cm in largest diameter, which ulcerated the overlying skin. The lesion had appeared 4 years previously but the patient hesitated to seek medical care due to 'fear of cancer'. Microscopically, the tumor was composed of spindle cells that formed cuffs around multiple open tubules and ducts set in an abundant, myxoid stroma. The spindle cells had significant atypia with nuclear pleomorphism, occasional cytoplasmic vacuolation and moderate mitotic activity. The ducts and lobules surrounded by the proliferating tumor cells had minimal distortion, with a pericanalicular growth pattern devoid of the phyllodes pattern. The tumor had a multinodular growth pattern with coalesced and individual tumor nodules, the latter being found mostly at the periphery of the lesion. On immunohistochemistry the tumor cells were positive for smooth muscle actin, CD34, and vimentin, and focally positive for CD10. A diagnosis of low-grade periductal stromal sarcoma (PDSS) with myxoid features was established. PDSS is a distinct low-grade breast sarcoma, the appropriate diagnosis of which requires extensive tumor sampling and additional broad immunohistochemistry. PDSS should not be confused with other spindle cell breast tumors because they require different treatment.     

Biomechanical characterization of ascending aortic aneurysm with concomitant bicuspid aortic valve and bovine aortic arch

Studies have shown that patients harboring bicuspid aortic valve (BAV) or bovine aortic arch (BAA) are more likely than the general population to develop ascending aortic aneurysm (AsAA). A thorough quantification of the AsAA tissue properties for these patient groups may offer insights into the underlying mechanisms of AsAA development. Thus, the objective of this study was to investigate and compare the mechanical and microstructural properties of aortic tissues from AsAA patients with and without concomitant BAV or BAA. AsAA (n = 20), BAV (n = 20) and BAA (n = 15) human tissues were obtained from patients who underwent elective AsAA surgery. Planar biaxial and uniaxial failure tests were used to characterize the mechanical and failure properties of the tissues, respectively. Histological analysis was performed to detect medial degenerative characteristics of aortic aneurysm. Individual layer thickness and composition were quantified for each patient group. The circumferential stress–strain response of the BAV samples was stiffer than both AsAA (p = 0.473) and BAA (p = 0.152) tissues at a low load. The BAV samples were nearly isotropic, while AsAA and BAA samples were anisotropic. The areal strain of BAV samples was significantly less than that of AsAA (p = 0.041) and BAA (p = 0.004) samples at a low load. The BAA samples were similar to the AsAA samples in both mechanical and failure properties. On the microstructural level, all samples displayed moderate medial degeneration, characterized by elastin fragmentation, cell loss, mucoid accumulation and fibrosis. The ultimate tensile strength of BAV and BAA sampleswere also found to decrease with age. Overall, the BAV samples were stiffer than both AsAA and BAA samples, and the BAA samples were similar to the AsAA samples. The BAV samples were thinnest, with less elastin than AsAA and BAA samples, which may be attributed to the loss of extensibility of these tissues at a low load. No apparent difference in failure mechanics among the tissue groups suggests that each of the patient groups may have a similar risk of rupture.     

羊水栓塞的病理诊断

目的探讨羊水栓塞病人病理诊断的有关问题。方法通过HE染色、胆色素和黏液组织化学染色以及CD34、cytokeratin(H)、HCG-β免疫组化染色，对死于围产期的13例尸检资料及1例抢救成功的外检资料进行回顾性分析。结果尸检中明确诊断为羊水栓塞的5例，在其HE染色的肺组织切片中小血管及毛细血管内都看到了长梭形，三五成团或散在分布的鳞状上皮，其中4例观察到胎粪小体的存在，经胆色素染色证实，3例观察到黏液，2例经黏液染色证实。1例外检诊断为羊水栓塞抢救成功的病例在子宫小血管及毛细血管内也看到了鳞状上皮，并经免疫组化标记证实。其他8例病例，无1例观察到明确羊水成分，其中6例在肺小血管内发现红染、丝状细胞团，但量少且无其他羊水成分证据，cytokeratin(H)全部阴性，CD34染色有3例阳性，3例在肺血管或子宫血管内看到了大细胞，HCG染色均为阴性。结论羊水栓塞的病理诊断应该以HE切片结合病史及临床表现为主，特殊染色及免疫组化染色可以辅助诊断，但不应完全依赖于特殊染色及免疫组化染色。     

Prostatic stromal sarcoma with rhabdoid features

Rhabdoid tumors have been reported in many different anatomic sites as an aggressive tumor and usually present with a rhabdoid tumor component (a composite tumor) rather than a pure rhabdoid tumor. Rhabdoid tumor in the prostate has been described only once in the prostatic region as a possible epithelial origin. Rhabdoid features in prostatic stromal sarcomas (PSSs) have never been described in the literature. Here, we report a case of a PSS with rhabdoid features. A 31-year-old man presented with a 4-month history of voiding difficulty and anal pain. Computed tomography of the abdomen revealed an ovoid mass in the prostate invading rectum and urinary bladder. A needle biopsy was diagnosed as an unclassified spindle cell sarcoma, and 2 cycles of adriamycin-based neoadjuvant chemotherapy were given, followed by radical prostatectomy. The prostatectomy specimen revealed a high-grade sarcoma with fascicles of highly cellular spindle cells and numerous mitoses with hemorrhage and necrosis. In areas, the tumor also contained sheets of loosely cohesive epithelioid cells with rhabdoid tumor component. Both spindle and rhabdoid tumor cells were positive for vimentin, CD34, and progesterone receptor and negative for desmin and cytokeratin immunostainings. The rhabdoid tumor cells retained INI1 expression. The tumor recurred in the bladder, and the patient died of sepsis. To the best of our knowledge, this is the first case of PSS with rhabdoid features. The tumor showed an aggressive clinical behavior with a short-term survival (7 months after diagnosis).