Pilot assessment of a human extracellular matrix-based vascular graft in a rabbit model.

BACKGROUND: Herein we describe a small-diameter vascular graft constructed from rolled human amniotic membrane (hAM), with in vitro evaluation and subsequent in vivo assessment of its mechanical and initial biologic viability in the early postimplantation period. This approach for graft construction allows customization of graft dimensions, with wide-ranging potential clinical applicability as a nonautologous, allogeneic, cell-free graft material. METHODS: Acellular hAMs were rolled into layered conduits (3.2-mm diameter) that were bound with fibrin and lyophilized. Constructs were seeded with human smooth muscle cells and cultured under controlled arterial hemodynamic conditions in vitro. Additionally, the acellular hAM conduits were surgically implanted as arterial interposition grafts into the carotid arteries of immunocompetent rabbits. RESULTS: On in vitro analysis, smooth muscle cells were shown to adhere to, proliferate within, and remodel the scaffold during a 4-week culture period. At the end of the culture period, there was histologic and biomechanical evidence of graft wall layer coalescence. In vivo analysis demonstrated graft patency after 4 weeks (n = 3), with no hyperacute rejection or thrombotic occlusion. Explants displayed histologic evidence of active cellular remodeling, with endogenous cell repopulation of the graft wall concurrent with degradation of initial graft material. Cells were shown to align circumferentially to resemble a vascular medial layer. CONCLUSIONS: The vascular grafts were shown to provide a supportive scaffold allowing cellular infiltration and remodeling by host cell populations in vivo. By use of this approach, "off-the-shelf" vascular grafts can be created with specified diameters and wall thicknesses to satisfy specific anatomic requirements in diverse populations of patients.

p16INK4a immunohistochemical and histopathologic study of Pap test cases interpreted as HSIL without CIN2-3 identification in subsequent cervical specimens.

Tissue biopsy following a pap test diagnosis of high grade squamous intraepithelial lesion (HSIL) sometimes fails to confirm the presence of a corresponding high grade cervical intraepithelial lesion (CIN 2-3), leading to confusion as to how best to manage the patient. It has been shown that these patients are still at higher risk for future detection of CIN 2-3 even if the initial biopsy fails to detect it. It has also been shown that immunohistochemical staining for p16INK4a can be reliably used as a surrogate marker for infection with high risk human papillomavirus in cervical samples, and that it can be used to enhance detection of CIN2-3 in cases where suspicion is high. To evaluate the use of p16INK4a staining in cases of HSIL which were not confirmed on initial biopsy, two pathologists rereviewed Pap and hematoxylin and eosin preparations from all such cases seen within the preceding 3 years. Immunohistochemical study for p16INK4a was performed and graded on representative sections. The results were tabulated and analyzed. Of the identified 596 HSIL Pap cases, 82% had HSIL on initial cervical specimens. Table 1 shows the 56 cases included in the study with graded and stratified p16INK4a results. On review of the p16INK4a slides, only 2 cases could be upgraded to HSIL/CIN2-3 from the original diagnosis. p16INK4a 2-3+ was expressed more frequently in cases initially interpreted on Pap as low-grade cervical lesion as compared with benign (24 of 35 cases). In the younger than 24-yr-old group p16 2-3+ reactivity was more frequent in benign and low-grade cervical lesion/CIN1 groups (benign: 3 of 5 cases, and CIN1: 6 of 8), and p16 negative reactivity was not seen. p16INK4a was graded 0-1+ more frequently in specimens interpreted as benign in the older than 25 yr olds (10 of 16 cases). The study suggests some diagnostic benefit from the use of p16INK4a immunohistochemical study on cervical specimens from women with a HSIL Pap test without HSIL/CIN2-3 on original hematoxylin and eosin review.

Xp11.2 translocation renal carcinoma with placental metastasis: a case report.

Renal cell carcinomas with sporadic Xp11.2 translocations are uncommon malignancies in children and young adults associated with several different reciprocal translocations involving the TFE3 gene located on chromosome Xp11.2. Placental metastases are extremely rare, with only a handful of cases reported. This study reports the case of a 20-year-old woman with an Xp11.2 translocation renal carcinoma that metastasized to the placenta. This is the first reported case of a renal cell carcinoma metastatic to the placenta and highlights the aggressive behavior of Xp11 translocation renal cell carcinomas.

Endometrial stromal sarcomas with unusual histologic features: a report of 24 primary and metastatic tumors emphasizing fibroblastic and smooth muscle differentiation.

We report the clinicopathologic features of 24 uterine primary and metastatic endometrial stromal sarcomas with fibromyxoid features (ESS-F) and smooth muscle differentiation (ESS-SM) (endometrial stromal sarcoma variants). Two groups of tumors were retrieved from the surgical pathology files at Memorial Sloan-Kettering Cancer Center: 1) gynecologic mesenchymal neoplasms with striking smooth muscle or fibroblastic differentiation that did not meet the clinical or histologic criteria for leiomyosarcoma or other established neoplasms containing smooth muscle; and 2) metastatic lesions showing ovoid and spindle cell morphology, involving lung, originally diagnosed as low-grade leiomyosarcoma, low-grade smooth muscle neoplasm, intravenous leiomyomatosis, fibrous hamartoma, and benign metastasizing leiomyoma. We identified 12 patients with 30 tumors; 24 were available for review. The mean age was 51 years (range 21-74 years). Follow-up >1 year was available for eight patients, with a mean time of 8.5 years. Each patient had a uterine primary and 10 experienced metastases. Mean time to recurrence was 6.8 years. Sites of metastasis included lung, retroperitoneum, right atrium/inferior vena cava, colon, and ovaries. No patient died of disease, but in many cases the follow-up period ended with the discovery of a metastasis. Four patients were originally diagnosed with endometrial stromal sarcoma, but other presenting diagnoses included benign metastasizing leiomyoma, fibroleiomyomatous tumor of lung, smooth muscle tumor of uncertain or low malignant potential, and intravascular leiomyomatosis. On review each patient had at least one tumor (primary and/or metastasis) that was determined to be an endometrial stromal sarcoma variant. Review diagnoses were as follows: endometrial stromal sarcoma (nonvariant), ESS-F, and ESS-SM. Eight of 10 primary tumors with available slides were endometrial stomal sarcoma variants (six ESS-F and two ESS-SM). When these variant features were present, they comprised between 50% and 100% of the neoplasm. The variant histology tumors exhibited prominent spiral arterioles, perivascular edema, and stromal cell condensation around blood vessels. All metastases but one were variant tumors; eight were ESS-F and five were ESS-SM. Four metastases did not resemble the uterine primary. Desmin marked smooth muscle mostly but not specifically. h-Caldesmon marked smooth muscle exclusively. Endometrial stromal cells as well as some fibroblasts and smooth muscle cells expressed CD10. We conclude that the presence of even focal endometrial stromal differentiation in an invasive uterine mesenchymal lesion with a predominant low-grade smooth muscle, fibroblastic, and/or myxoid phenotype should permit classification as low-grade sarcoma-they should be considered endometrial stromal sarcomas.