Primary Leiomyosarcoma of the Great Saphenous Vein: Case Report and Review of the Literature.

Soft tissue sarcomas are very rare tumors, representing less than 1% of all cancers. Leiomyosarcomas are a rare group of them representing about 6% of soft tissue sarcomas and they involve smooth muscles. Less than 2% of all leiomyosarcomas involves large blood vessels. Leiomyosarcomas of vein tunica media are very rare (1/100,000 malignant cancers) and only 10% of these originate from the great saphenous vein. In this article, we report a clinical case that occurred in our institution and review all the literature available at now.

Putative Intravascular Myofibroma Mimicking a Vascular Malformation With Phleboliths.

Myofibroma is a rare, benign myofibroblastic tumor that commonly presents at birth or in early infancy, usually as a painless, slow-growing, solitary, nodular mass. We present a case of a 40-year-old woman with a painful, solitary, myofibroma on the right elbow. The unique features of this case include age and gender of the patient, site, pain on presentation, tumor morphology, and putative intravascular nature of the tumor.

Intravascular Myopericytoma of the Plantar Region: Case Report and Discussion of the Probable Origin From a Cutaneous Vascular Malformation.

Myopericytoma is a perivascular myoid neoplasm of skin and soft tissues characterized by numerous thin-walled blood vessels surrounded concentrically by round to spindle myoid tumor cells, which shows α-smooth muscle actin and h-caldesmon coexpression and commonly negativity for desmin. These tumors arise predominantly in extremities of adult patients with benign clinical course. Based on the architectural pattern, there are various histologic variants as classical-solid myopericytoma, hemangiopericytoma-like myopericytoma, angioleiomyoma-like myopericytoma, myofibroma-like myopericytoma, hipocelular fibroma-like myopericytoma, intravascular myopericytoma, cellular immature myopericytoma, and malignant myopericytoma. The authors report a case that fully satisfies the morphological and immunohistochemical criteria for intravascular myopericytoma, which plantar location is not previously described in the literature. In addition, the authors discuss about its possible development from a preexistent cutaneous vascular malformation.

[Pulmonary epithelioid hemangioendothelioma: a clinicopathologic analysis of six cases].

OBJECTIVE: To investigate the clinicopathologic characteristics, differential diagnosis and prognosis of pulmonary epithelioid hemangioendotheliomas (PEHs). METHODS: The clinical symptoms and imaging findings of 6 cases of PEHs were investigated and pathologic analyses including histomorphologic and immunohistochemical studies were performed. RESULTS: Clinical symptoms of the patients were nonspecific and insidious. The typical radiological manifestation was characterized by multiple small pulmonary nodules. The pathological findings were well-demarcated hypocellular hyalinized nodules with more cellularity at the periphery of the nodule. The neoplastic cells showed mild nuclear atypia and prominent eosinophilic cytoplasm with vacuoles, attempting to form primitive vasculature. Immunohistochemically, tumor cells were positive to CD31, CD34 and ERG. Follow-up data from 8 months to 5 years showed no tumor progression, except for the development of bone metastases in one case at 6 months. CONCLUSIONS: PEHs are uncommon vascular tumors with low-intermediate malignancy. Using H&E and immunohistochemistry, the final pathological diagnosis can be made and misdiagnosed as a benign fibrotic nodule or other malignant tumors can be avoided. The most effective treatment is surgical resection, if necessary, combined with chemotherapy or radiotherapy.

A Case of Mesenchymal Chondrosarcoma Arising from the Femoral Vein with 8 Years of Follow-up.

Mesenchymal chondrosarcoma (MCS) is an infrequent malignancy of bone and soft tissue that is characterized by a peculiar bimorphic histologic pattern with areas of undifferentiated malignant small cells surrounding well-differentiated cartilaginous islands. Involvement of the large vessels is a rare occurrence. Here, we report a case of MCS arising from the femoral vein that was treated by wide-margin resection combined with autogenous vein revascularization and then followed up for 8 years. The long-term postoperative results showed distant metastasis to the pancreas and both lobes of the lung, without recurrence at the primary site. This case indicates that for MCS arising from the femoral vein, although wide-margin resection combined with autogenous vein revascularization may avoid recurrence at the primary site, this treatment strategy has no obvious benefit for controlling long-term distant metastases.

A Primary Primitive Neuroectodermal Tumor Arising from Left Subclavian Vein and Extending along Left Brachiocephalic Vein and Superior Vena Cava into Right Atrium.

Primitive neuroectodermal tumor (PNET) is an extremely rare malignancy thought to be derived from fetal neuroectodermal precursor cells. It usually occurs in central and peripheral nervous system or soft tissue and bone, while intravenous or intracavitary PNET is considered as an extremely rare tumor. We reported a case of a 44-year-old woman who presented with the left unilateral facial and neck swelling. Magnetic resonance imaging revealed a tape-shaped solid mass within left subclavian vein, left brachiocephalic vein, superior vena cava, and right atrium; the proximal end proportion occupied almost the entire right atrium with a pedicle flip protruded into the right ventricle. Ultrasonography revealed an irregular hypoechnoic mass arising from the left subclavian vein, which extended along the left brachiocephalic vein and superior vena cava into the right atrium and up to the right ventricle. Positron emission tomography-computed tomography revealed several hypermetabolic thyroid nodules with no evidence of intravenous hyperactive lesion. The patient underwent tumor resection under cardiopulmonary bypass. At 15 days postoperatively, total thyroidectomy and resection of the left subclavian vein were simultaneously performed. The patient received chemotherapy and radiotherapy later. Histologically, the neoplasm displayed small, round, blue cells with hyperchromatic nuclei and scant cytoplasm. The neoplastic cells showed a strong immunopositivity for CD99, synaptophysin, CD56, CD57, and friend leukemia integration 1, thus confirming a diagnosis of the PNET. Histopathological examination of the thyroid showed papillary carcinoma. Thus, this PNET had no definitive organ or tissue of origin, which primarily originated from the left subclavian vein with tumor extension along the superior vena cava to the right ventricle.

Insulin-like Growth Factor II mRNA-binding Protein 3 is a Highly Sensitive Marker for Intravascular Large B-cell Lymphoma: Immunohistochemical Analysis of 152 Pathology Specimens From 88 Patients.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of blood vessels, particularly capillaries. IVLBCL lacks mass formation, and its diagnosis can be challenging. We analyzed the utility of insulin-like growth factor II mRNA-binding protein 3 (IMP3) immunohistochemistry for IVLBCL diagnosis in various organs. Double staining with paired box 5 (PAX5) was performed for validation. Overall, 152 pathological specimens (111 positive and 41 negative for IVLBCL) obtained from 88 patients with a diagnosis of IVLBCL were stained for IMP3 and IMP3/PAX5. As negative controls, 40 pathology specimens from 38 patients with no history of IVLBCL or other B-cell lymphomas were stained for IMP3, which comprised 31 benign pathological specimens from 29 patients in whom malignancy was suspected, 7 cases of appendicitis with intravascular and/or intralymphatic lymphoid proliferations, and 2 cases of intravascular natural killer/T-cell lymphoma. All mononuclear cells with cytoplasmic staining were considered positive for IMP3 expression, but expression restricted to germinal center B cells was excluded from evaluation. All 111 IVLBCL pathological specimens were positive for IMP3 and IMP3/PAX5. In addition, 11 of the 41 specimens originally diagnosed as IVLBCL-negative showed IMP3/PAX5 double-positive cells, raising the suspicion of IVLBCL. However, of the 40 negative control samples, IMP3-positive non-germinal center B cells were detected in only 2 samples ( P = 0.0131) and no intravascular IMP3-positive B cells suspicious for IVLBCL were identified. Altogether, IMP3 immunohistochemistry is a highly sensitive marker of IVLBCL and can be a helpful adjunct for IVLBCL diagnosis.

The miR-17-92 cluster and its target THBS1 are differentially expressed in angiosarcomas dependent on MYC amplification.

Angiosarcomas (ASs) represent a heterogeneous group of malignant vascular tumors that may occur spontaneously as primary tumors or secondarily after radiation therapy or in the context of chronic lymphedema. Most secondary ASs have been associated with MYC oncogene amplification, whereas the role of MYC abnormalities in primary AS is not well defined. Twenty-two primary and secondary ASs were analyzed by array-comparative genomic hybridization (aCGH) and by deep sequencing of small RNA libraries. By aCGH and subsequently confirmed by fluorescence in situ hybridization, MYC amplification was identified in three out of six primary tumors and in 8 out of 12 secondary AS. We have also found MAML1 as a new potential oncogene in MYC-amplified AS. Significant upregulation of the miR-17-92 cluster was observed in MYC-amplified AS compared to AS lacking MYC amplification and the control group (other vascular tumors, nonvascular sarcomas). Moreover, MYC-amplified ASs were associated with a significantly lower expression of thrombospondin-1 (THBS1) than AS without MYC amplification or controls. Altogether, our study implicates MYC amplification not only in the pathogenesis of secondary AS but also in a subset of primary AS. Thus, MYC amplification may play a crucial role in the angiogenic phenotype of AS through upregulation of the miR-17-92 cluster, which subsequently downregulates THBS1, a potent endogenous inhibitor of angiogenesis.

Cutaneous apocrine mixed tumor with intravascular tumor deposits: a diagnostic pitfall.

Apocrine mixed tumor of the skin is a benign adnexal neoplasm usually posing no diagnostic problem for a histopathologist. The purpose of our investigation is to present a small series of 4 benign cutaneous apocrine mixed tumors of the skin that contained small foci of intravascular tumor deposits, a feature not previously described, to the best of our knowledge. The 4 lesions were identified retrospectively after a review of 312 apocrine mixed tumors and 51 eccrine mixed tumors in the collective files of the authors. In all cases, this feature was originally overlooked. The patients were 3 men and 1 woman, ranging in age at diagnosis from 29 to 66 years. Locations included nose (2), forehead (1), and the fifth toe (1). Histopathologically, all 4 neoplasms demonstrated typical features of a benign apocrine mixed tumor; 2 cases were classified as hyaline cell-rich tumors. In all cases, there were either blood or lymphatic vessels containing small intraluminal collections of neoplastic cells, which had the appearances of hyaline cells and immunohistochemically expressed cytokeratins and were partly immunoreactive for S-100 protein and calponin, thus indicating the myoepithelial phenotype. The intravascular location of the neoplastic cells was confirmed by CD31 staining. The nature of the vessels (lymphatics vs. blood vessels) was supported by staining for alpha smooth muscle actin, which stained pericytes in blood vessels. Lymphatic vessels were also stained for D2-40. No eccrine mixed tumor manifested intravascular tumor deposits. Follow-up of the patients revealed no recurrences or metastasis (range: 2-21 years). It is concluded that occurrence of intravascular involvement in benign apocrine mixed tumor of the skin is rare (approximately 1%-2%). This feature is discrete and is easy to overlook. At present, its significance is not completely clear. Until proved otherwise in future, we suggest to consider intravascular deposits in cutaneous apocrine mixed tumors as an innocuous phenomenon.

Intravascular schwannoma.

Schwannoma is defined as a benign nerve sheath neoplasm of Schwann cell origin. Cutaneous schwannoma typically manifests along the course of peripheral nerves as a solitary, well-defined, skin-colored nodule within the deep dermis or subcutis of the flexor aspects of the extremities. Schwannoma enlarges slowly and typically follows a benign course, with local recurrence and malignant transformation being exceedingly rare. Although involvement of the vasculature by neurofibroma has been rarely reported, intravascular schwannoma has not been documented to date. We present a unique case of cutaneous schwannoma, as confirmed by histological morphology and immunohistochemistry, within the dermal venous system. Presentation of this case is followed by a discussion of the differential diagnoses of schwannoma, the possible etiologies of the extension of this lesion into the vasculature, and the significance of such a phenomenon.

A case of intravenous leiomyomatosis with high levels of hyaluronan.

Intravenous leiomyomatosis (IVL) is a rare benign tumor. The clinical behavior can be life-threatening due to extension through the pelvic veins. A 70-year-old woman was referred to our hospital with IVL originating from a uterine leiomyoma and extending to the inferior vena cava. The patient was diagnosed on the basis of the results of various studies, and the tumor was resected completely through a single-stage approach. The intravascular tumor was 20 cm long, multinodular and rubbery. Microscopic findings showed benign smooth muscle that was partly hyalinized and fibrous. Immunohistochemical studies revealed that hyaluronan was expressed more prominently in IVL than in uterine leiomyomas. IVL has viscoelastic properties and contains a large amount of hyaluronan, which may promote invasion during pathogenesis.

Intravascular lymphoma presenting as an orbital mass lesion: a case report.

We describe a case of intravascular lymphoma that presented as an orbital mass lesion. A 77-year-old female presented with longstanding fatigue and one-month of diplopia. Magnetic resonance imaging (MRI) revealed a frontal lobe brain lesion and a right orbital mass. Brain biopsy was interpreted as anaplastic oligodendroglioma. Orbital biopsy revealed intravascular lymphoma. On review of brain histopathology, the diagnosis was revised to CNS intravascular lymphoma. To the best of our knowledge, this case represents the first report of intravascular lymphoma presenting as an orbital mass lesion.

MED12 exon 2 mutation is uncommon in intravenous leiomyomatosis: clinicopathologic features and molecular study.

Intravenous leiomyomatosis (IVL) is a rare neoplasm that is characterized by smooth muscle cell proliferation within venous vessels. The aim of this study is to investigate the clinicopathological features, immunophenotypes, and MED12 gene mutations in IVL. Nine cases of IVL from the Affiliated Hospital of Qingdao University were collected, and the clinicopathological features were reviewed. The immunohistochemical expressions of p16, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), alpha thalassemia/mental retardation syndrome X-linked (ATRX), retinoblastoma 1 (RB1), fumarate hydratase (FH), and p53, were evaluated. The mutation status of MED12 gene exon 2 was detected by Sanger sequencing. All the 9 patients were women ranging from 32 to 58 years, and uterine leiomyomas were identified in 5 patients. Immunohistochemical staining showed that all IVL and leiomyoma samples were positive for estrogen receptor and progesterone receptor, but negative for CD34. IVL displayed similar immunostaining patterns with their uterine counterparts with focal p16 immunostaining. FH, PTEN, ATRX, and RB1 were variably positive, and p53 and Ki-67 positive rates were less than 5% in all cases. Two novel genetic variations at MED12 exon 2, a synonymous mutation c.141C>T (p.Asn47=), and an in-frame deletion mutation c.133_147del15 (p.Phe45_Pro49del) were identified in two IVL cases. One missense mutation c.131G>A (p.Gly44Asp) was identified in one uterine leiomyoma. The remaining 11 tumor samples (7 IVL cases and 4 uterine leiomyomas) showed no mutations at MED12 exon 2. Our results showed two novel MED12 mutations in IVL. The MED12 mutations are different between IVL and uterine leiomyoma. These findings indicate that IVL is a unique entity and different from uterine leiomyoma.

Primary leiomyoma of the inferior vena cava mimicking a cystic neoplasm of the pancreas: a case report.

Benign smooth muscle tumors of the inferior vena cava (IVC) are unusual, but mostly consist of intravenous leiomyomatosis, which arises from the uterus. Primary leiomyoma of the IVC is extremely rare. Here, we report a primary leiomyoma of the IVC, misleadingly reported as a cystic neoplasm of the pancreas in images. Immunohistochemical analysis was positive for (estrogen receptor) ER and (progesterone receptor) PR, indicating gynecologic leiomyomas. The use of ER and PR immunostaining is recommended to help distinguish between somatic and gynecologic leiomyomas, whose criteria of malignancy differ.

An autopsy case of pulmonary artery intimal sarcoma: detailed observation of tumor and its related lesions in pulmonary arteries.

We report an autopsy-proven case of a 33-year-old man who died of intimal sarcoma of the pulmonary artery. A large mass (5×4 cm) occluded the main and bilateral pulmonary arteries. Tumor cell morphology was consistent with that of undifferentiated pleomorphic sarcoma. Comprehensive histological observation of 18 pulmonary arteries from proximal to distal revealed continuous extension of the tumor from the main to the subsegmental arteries along the intima, forming an arteriosclerosis-like intimal thickening. Distal small arteries were also affected by eccentric intimal thickening or recanalization. Lung parenchyma was not involved, although there were two wedge-shaped small pulmonary infarctions caused by tumorous obstruction of the associated arteries. Histological results indicated that the intimal sarcoma in the pulmonary artery, which appeared occlusive with growth limited to the proximal artery, had in fact already spread more peripherally than expected. Both the proximal lesions and the distal small arteries were affected by peripheral tumor emboli or by pulmonary hypertension induced by the proximal tumor. However, as seen in this case, most of the occlusive tumor was located locally and intraluminally, in the proximal artery, and removing the proximal tumor by pulmonary endarterectomy was considered effective for symptomatic improvement.

Primary angiosarcoma of the femoral artery in patient with kidney and liver polycystosis and multiple arterial aneurysms: report of the case and review of the literature.

The association between kidney and liver polycystosis and arterial aneurysms is well documented. However, it remains unclear whether these patients are at increased risk of malignant transformation. In this article, we describe a case of a primary angiosarcoma of the femoral artery with metastatic spread into the lungs and hilar lymph node arising in a 74-year-old man with kidney and liver polycystosis and multiple arterial aneurysms.

Annexin 2 and hemorrhagic disorder in vascular intimal carcinomatosis.

Vascular intimal carcinomatosis refers to a characteristic tumor proliferation on vascular intima that replaces normal endothelium. This pathological event of unknown cause is quite different from tumor thrombotic microangiopathy due to the absence of thrombi on the tumor cell surfaces. We analyzed renal transitional cell carcinoma cases with metastasis to the main pulmonary arteries and marked hyperfibrino(geno)lysis. The fibrinogen-derived products from patients' plasma were identified as D1A/gamma, D1/gamma, and D1/beta by immunoblotting with the NH2-terminus of the fragment D specific antibody JIF-23. In all cases, the neoplastic cells with vascular intimal carcinomatosis were stained positive for anti-human annexin 2, which is a unique cell surface co-receptor for plasminogen and tissue-type plasminogen activator. In contrast, normal renal pelvic mucosa or renal transitional cell carcinoma without vascular intimal carcinomatosis did not express any annexin 2. The isolated transitional cell carcinoma cells contained annexin 2 mRNA and expressed its protein. Anti-annexin 2 antibody and transfection of annexin 2 small interfering RNA into these carcinoma cells significantly inhibited tissue-type plasminogen activator dependent plasmin generation. These findings suggest that annexin 2 mediated fibrinolysis on the transitional cell carcinoma cells may play a role in inducing hemorrhagic disorder in vascular intimal carcinomatosis.