Other Rare Sinonasal Malignant Tumours Involving the Anterior Skull Base.

Sinonasal tumours are rare, and among these there exist a small number of histologic subtypes that are infrequently encountered and rarely mentioned in the literature. These have been presented as either case reports or small case series, and their very low incidence makes prospective studies practically impossible. This review analyses the available literature, including our own experience and endeavours to outline management strategies, which involve a high index of suspicion and counselling of patients. In most instances, these tumours require aggressive multimodal treatment to improve survival outcomes. The overall prognosis remains dismal.

Prenatal diagnosis and outcomes of fetal teratomas.

PURPOSE: Our aim was to evaluate the diagnostic performance of ultrasonography (US) in the prenatal identification of teratomas and the perinatal outcome of the fetuses with those teratomas. METHODS: In this retrospective case series study, we searched the archives using the keywords "fetal mass" or "fetal tumor" or "fetal teratoma" and "sacrococcygeal teratoma," diagnosed between 2009 and 2014, within the US database of our center. RESULTS: One hundred seven fetuses were prenatally diagnosed as having a cystic or solid mass, tumor, or teratoma. Nineteen of those cases were diagnosed prenatally as having fetal teratoma, but that diagnosis could not be verified in three cases. In one fetus, the prenatal diagnosis could not be confirmed. The sensitivity of US in identifying fetal teratoma was 100% and the false-positive rate, 3.3%. Six pregnancies complicated by a fetal teratoma were terminated. A normal karyotype was identified in all fetuses that underwent karyotyping. Among the nine women who continued their pregnancy, polyhydramnios was identified in four fetuses; although high-output heart failure was also identified in two of those fetuses during prenatal follow-up, none developed hydrops. On delivery, nine infants were born alive, but three (33.3%) of them died within the early neonatal period. CONCLUSIONS: US has very high sensitivity and low false-positive rates in identifying fetal teratoma prenatally. The risk of chromosomal abnormalities is very low in fetuses with teratoma, and their prognosis depends on the location and size of the tumor and any associated perinatal complications.

Craniospinal dissemination in teratocarcinosarcoma.

There have been fewer than 60 cases of malignant teratocarcinosarcoma (TCS) described in the literature, usually arising in the nose and paranasal sinuses. The authors report on a patient who presented with neurological symptoms caused by a frontal lobe TCS, and in whom widespread spinal tumor dissemination developed. In rare cases, TCSs can occur with a predominantly cranial and neurological presentation and spread to the spinal canal.

[Sinonasal teratocarcinosarcoma: a clinical, radiologic and pathologic study of 5 cases].

OBJECTIVE: To study the clinical, radiologic and pathologic features, as well as differential diagnosis of teratocarcinosarcoma in nasal cavity and paranasal sinuses. METHODS: Light microscopic examination and immunohistochemical study was performed in 5 cases of sinonasal teratocarcinosarcoma. The clinical, radiologic and pathologic features were analyzed and the literature was reviewed. RESULTS: All 5 patients were males and their age ranged from 34 to 43 years (mean age = 39 years). The clinical presentation was nasal obstruction, epistaxis and headache. Physical examination often revealed a polypoid mass with contact bleeding. Computed tomography showed a homogeneous nasal mass with obturation of sinuses. Cystic changes, calcification or ossification was not observed. Histologically, the tumor showed a heterogeneous admixture of components from the 3 germ cell layers, exhibiting various degrees of maturation. Squamous epithelium, smooth muscle cells, chondro-osseous tissue, intestinal or respiratory type epithelium, "fetal-type" clear cells and immature neuroepithelium were commonly seen. Immunohistochemical study demonstrated that the epithelial component expressed cytokeratin and epithelial membrane antigen, while the mesenchymal component variably expressed vimentin, smooth muscle actin and S-100 protein. On the other hand, the neuroepithelial component expressed neuron-specific enolase, synaptophysin and chromogranin, and the primitive component expressed CD99. The initial biopsy diagnosis included capillary hemangioma, olfactory neuroblastoma, craniopharyngioma and malignant mixed tumor. Follow-up information was available in all patients. Two of which had local recurrence and 1 had cervical lymph node metastasis. CONCLUSIONS: Sinonasal teratocarcinosarcoma is a rare and highly malignant tumor occurring in sinonasal tract. It manifests mainly in adult males and is characterized by a complex admixture of teratomatous and carcinosarcomatous components. "Fetal-type" clear cells, squamous epithelium and immature neuroepithelium represent important histologic characteristics useful in diagnosis.

Evaluation of anti-VEGFR-3 specific scFv antibodies as potential therapeutic and diagnostic tools for tumor lymph-angiogenesis.

Vascular endothelial growth factor receptor-3 (VEGFR-3) plays a major role in lymph-angiogenesis, tumor growth and metastatic tumor cell dissemination. The receptor is over-expressed on lymphatic vessels in the vicinity of tumors and on the tumor vasculature and therefore may be an excellent target for an effective cancer intervention. We generated and characterized single chain antibody fragments (scFv) recognizing VEGFR-3 by phage display technology and expression in P. pastoris and analyzed selected antibodies in vitro and in vivo. The scFvs were functionalized by the introduction of cysteines at the C-terminal end of the proteins. The scFvs are species cross-specific and bind to recombinant human and mouse VEGFR-3. ScFv AFC5 showed specific tumor accumulation in an hVEGFR-3 expressing F9 terato-carcinoma mouse model, which was also used for tumor visualization by combined single proton emission computed tomography (SPECT/CT) and immunohistochemical analysis. This antibody also inhibited binding of hVEGF-C to its receptor and reduced proliferation of human lymphatic endothelial cells. Thus, the generated VEGFR-3 specific scFv antibodies represent a valuable tool for novel cancer therapies and diagnostic applications.

[Seminoma and teratocarcinoma: synchronic unitesticular presentation as independent nodules with different histologies? Ultrasound characteristics]. / Seminoma y teratocarcinoma: presentación sincrónica monotesticular como nódulos independientes con distintas histologías? Caracteres ecográficos.

OBJECTIVE: To describe the ultrasound characteristics, vascularization pattern (colour Doppler ultrasound) and possible histogenesis of one case of synchronic untesticular seminoma and teratocarcinoma as independent tumor nodules, histologically different, in a 19-year-old patient with testicular mass for eight months. METHODS: Conventional ultrasound, colour Doppler ultrasound, and high resolution Doppler angiogram were performed, analyzing vascular flows. After resection of the tumor, macroscopic and histological sections were related with ultrasound images. RESULTS: The patient showed three independent, well limited, tumoral nodules in the right testicle: two of them heterogeneous, 20 and 33 mm in diameter, with cystic areas and calcifications. The third nodule was solid, hypoechoic and homogeneous, 26 mm in diameter. All nodules presented an increase in vascularization with low resistance arterial flows. Histologically the first two nodules were teratocarcinomas (predominantly mature teratoma and embryonal carcinoma) and the third classic seminoma. CONCLUSIONS: Although seminoma and mixed germ cell tumors are common, "their presentation in the some testicle as independent nodules with different histologies is a rarely referred case in the literature, which allows us to apply a histogenetic and ultrasound-pathologic correlation model in seminomatous and nonseminomatous tumors. The presence of cystic cavities and gross calcifications is highly correlated with teratoma. In our case there are not significant differences in the vascularization pattern with Doppler ultrasound.

Fat-containing lesions of the chest.

Although most lesions that occur in the chest have a nonspecific soft-tissue appearance, fat-containing lesions are occasionally encountered at cross-sectional computed tomography (CT) or magnetic resonance imaging. The various fat-containing lesions of the chest include parenchymal and endobronchial lesions such as hamartoma, lipoid pneumonia, and lipoma. Endobronchial hamartoma usually appears at CT as a lesion with a smooth edge, focal collections of fat, or fat collections that alternate with foci of calcification. Mediastinal fat-containing lesions include germ cell neoplasms, thymolipomas, lipomas, and liposarcomas. The most frequent CT manifestation of the germ cell neoplasm teratoma is a heterogeneous mass with soft-tissue, fluid, fat, and calcium attenuation. Cardiac lesions with fat content include lipomatous hypertrophy of the interatrial septum and arrhythmogenic right ventricular dysplasia. Diagnosis of the former is made with CT when a smooth, nonenhancing, well-marginated fat-containing lesion is identified in the interatrial septum. Finally, fat may herniate into the chest at several characteristic locations. When such a lesion is identified, the time required for differential diagnosis is significantly reduced, often allowing a definitive radiologic diagnosis. Sagittal and coronal reformatted images can add valuable information by showing diaphragmatic defects and hernia contents.

Selective targeting of tumoral vasculature: comparison of different formats of an antibody (L19) to the ED-B domain of fibronectin.

We recently demonstrated that a human recombinant scFv, L19, reacting with the ED-B domain of fibronectin, a marker of angiogenesis, selectively targets tumoral vasculature in vivo. Using the variable regions of L19, we constructed and expressed a human "small immunoprotein" (SIP) and a complete human IgG1 and performed biodistribution studies in tumor-bearing mice to compare the blood clearance rate, in vivo stability and performance in tumor targeting of the 3 L19 formats [dimeric scFv (scFv)(2), SIP and IgG1]. The accumulation of the different antibody formats in the tumors studied was a consequence of the clearance rate and in vivo stability of the molecules. Using the SIP, the %ID/g in tumors was 2-5 times higher than that of the (scFv)(2), reaching a maximum 4-6 hr after injection. By contrast, the accumulation of IgG1 in tumors constantly rose during the experiments. However, due to its slow clearance, the tumor-blood ratio of the %ID/g after 144 hr was only about 3 compared to a ratio of 10 for the (scFv)(2) and 70 for the SIP after the same period of time. The different in vivo behavior of these 3 completely human L19 formats could be exploited for different diagnostic and/or therapeutic purposes, depending on clinical needs and disease. Furthermore, the fact that ED-B is 100% homologous in human and mouse, which ensures that L19 reacts equally well with the human and the murine antigen, should expedite the transfer of these reagents to clinical trials.

[Malignant teratocarcinosarcoma of the nose and paranasal sinuses].

Malignant teratocarcinosarcoma of the nasal cavity and the paranasal sinuses is a rare and invasive tumor. It is characterized by a mixture of mesenchymal and epithelial components, with cellular elements of a fetal nature. We describe in detail the first and only case in Israel of a patient with such a tumor. Only 40-50 such cases have been described in the medical literature. We have also reviewed the existing literature dealing with malignant teratocarcinosarcoma.

Nasopharyngeal teratocarcinosarcoma.

Congenital germ cell tumors are uncommon. The most common site of origin is in the saccrococygeal region. Teratomas arising from the head and neck comprise a small proportion of this entity, and of these, nasopharyngeal lesions are rare. Also known by various synonyms such as hamartoma and hairy polyp, the teratoma is a well-recognized, and generally benign, clinical and histopathological entity. We present a case of a nasopharyngeal teratocarcinosarcoma associated with a cleft palate and the congenital replacement or absence of the ipsilateral Eustachian tube.

[Surgical treatment of intrathoracic compression of respiratory ways caused by mediastinal teratocarcinoma in children]. / Khirurgicheskoe lechenie vnutrigrudnoi kompressii dykhatel'nykh putei, obuslovlennoi teratodermoidnoi opukhol'iu sredosteniia, u detei.

Twelve children with mediastinal teratodermoid tumor, causing intrathoracic compression of respiratory ways (ITCRW) in 8 of them, were treated in clinic. In 75% of children with ITCRW the conduction of special preoperative preparation was necessary. All the patients were operated on. Tumor was removed en bloc or using the fragmentation method. In secondary tracheomalacia the anterior aortopexy for the tracheal lumen preservation was done simultaneously.

Increased binding affinity and valence of recombinant antibody fragments lead to improved targeting of tumoral angiogenesis.

The formation of new blood vessels (angiogenesis) is an important step in tumor progression. Molecules capable of selectively targeting markers of angiogenesis may offer opportunities for the in vivo imaging of aggressive tumors and for the delivery of toxic agents to the tumoral vasculature. Using antibody phage display libraries and combinatorial mutagenesis, we isolated single-chain Fv antibody fragments, which recognize with different affinities the same epitope of the ED-B domain of fibronectin, a marker of angiogenesis. Two single-chain Fv fragments, E1 and L19, with dissociation constants of 41 nM and 0.054 nM, respectively, were investigated for their ability to target F9 murine teratocarcinoma grafted s.c. in nude mice when injected i.v. in either monomeric or homodimeric form (Mr 27,000 and 54,000, respectively). Biodistribution studies, performed at two time points (4 h and 24 h) with radiolabeled samples, showed that the higher affinity antibody targets the tumor significantly better than the lower affinity one, in terms both of tumor:organ ratios and of the amounts of antibody delivered to the tumor. In particular, more than 20% of the injected dose of dimeric L19 accumulated per gram of tumor at 4 h; the tumor:organ ratios at 4 h and 24 h were in the (2.1-8.6):1 and (10.3-29.4):1 range, respectively. This study demonstrates that, although vasculature represents only a small fraction of the total tumor mass, anti-ED-B antibodies can selectively target tumors in vivo and that this process is particularly efficient if very high-affinity binders are used.

A xenograft line of human teratocarcinoma established by serial transplantation in severe combined immunodeficient (SCID) mice.

We established a xenograft line of human teratocarcinoma (TC-1) and characterized the pluripotency of differentiation of the neoplastic cells. A teratocarcinoma specimen obtained from a primary mediastinal lesion (22-year-old male patient) was inoculated subcutaneously into severe combined immunodeficient (SCID) mice. The carcinoma formed tumors in the mice. We established a xenograft line by serial passage of the tumor in vivo. The primary tumor was composed of papillary and pseudoglandular nests of highly atypical epithelial cells with foci of glomeruloid structures. The metastatic cells showed apparent production of mucin and differentiation to striated muscle. The xenograft line TC-1 retained the basic histopathological features seen in the primary and metastatic cells. The xenograft line showed focal differentiation to cartilage through serial passages. Immunohistochemical studies with anti-alpha-fetoprotein (AFP) demonstrated positive immunoreactivity on the TC-1 cells. Serum AFP levels were also elevated in the TC-1-bearing SCID mice. The human teratocarcinoma xenograft line TC-1 will be useful for studying the differentiation mechanism in human totipotent stem cells.