Rosette-forming glioneuronal tumor of the fourth ventricle: Report of two cases with a differential diagnostic overview

We report on clinicopathological findings in two cases of rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) occurring in females aged 16 years (Case 1) and 30 years (Case 2). Symptoms included vertigo, nausea, cerebellar ataxia, as well as headaches, and had been present for 4-months and 1 week, respectively. Magnetic resonance imaging (MRI) indicated a cerebellar-based tumor of 1.8cm (Case 1) and 5cm (Case 2) diameter each, bulging into the fourth ventricle. Case 2 involved a cyst-mural-nodule configuration. In both instances, the solid component appeared isointense on T(1) sequences, hyperintense in the T(2) mode, and enhanced moderately. Gross total resection was achieved via suboccipital craniotomy. However, functional recovery was disappointing in Case 1. On microscopy, both tumors comprised an admixture of low-grade astrocytoma interspersed with circular aggregates of synaptophysin-expressing round cells harboring oligodendrocyte-like nuclei. The astrocytic moiety in Case 1 was nondescript, and overtly pilocytic in Case 2. The architecture of neuronal elements variously consisted of neurocytic rosettes, of pseudorosettes centered on a capillary core, as well as of concentric ribbons along irregular lumina. Gangliocytic maturation, especially "floating neurons", or a corresponding immunoreactivity for neurofilament protein was absent. Neither of these populations exhibited atypia, mitotic activity, or a significant labeling for MIB-1. Cerebellar parenchyma included in the surgical specimen did not reveal any preexisting malformative anomaly. Despite sharing some overlapping histologic traits with dysembryoplastic neuroepithelial tumor (DNT), the presentation of RGNT with respect to both patient age and location is consistent enough for this lesion to be singled out as an autonomous entity.

Astroblastoma with rhabdoid features and favorable long-term outcome: report of a case with a 12-year follow-up

Astroblastoma is a historically traded microscopic diagnosis to denote a rare neuroepithelial tumor of uncertain nosology, involving a distinctive pattern of pseudorosette arrangement of neoplastic cells. While displaying some glial properties, the latter shall not - by definition - be either reducible to or part of any conventional glioma type. We report on clinicopathologic correlations in a case of astroblastoma involving an extensive rhabdoid phenotype of tumor cells. The male patient was operated on at the age of 53 and 59 years for a left parietal tumor measuring 5.8 cm in diameter at the first presentation. On magnetic resonance imaging and angiography, both the primary and its recurrence were discrete, highly vascularized, and contrast-enhancing. The second surgery was complemented with radiotherapy of 66 Gy, followed by chemotherapy with Temozolomide. Twelve years into clinical history, the patient has stable minimal residual disease at the age of 65. A review of pathology samples from both surgeries showed well-differentiated astroblastoma according to current standards, with an MIB-1 labeling index of 1% and 4%, respectively. Neither of the specimens involved cellular anaplasia, overt mitotic activity, microvascular proliferation, or palisading necrosis. Most tumor cells harbored paranuclear filamentous rhabdoid inclusions that were immunostained for vimentin and, in part, also for GFAP. No polyantigenic reactivity was observed. This example contributes another facet to the spectrum of the so-called composite rhabdoid tumors. Involving a low-grade parent neoplasm, it also further substantiates the incipient perception that the rhabdoid phenotype neither is a peculiar but nonspecific convergence point of anaplastic evolution, nor are such lesions indiscriminately bound for a relentless course.

"Exterritorial" lymphocytic hypophysitis within an ovarian teratoma during pregnancy: a possible sentinel lesion?

Pituitary tissue is rarely to be found among the constituents of ovarian teratomas (dermoid cysts). In some exceptional cases, however, such ectopic pituitary anlagen may even give rise to secondary organ-specific pathologies. Akin to those of the pituitary in its natural location, these tend to be adenomas. We describe a unique example of lymphocytic hypophysitis incidentally encountered in a mature left ovarian teratoma from a 30-year-old woman in the 19th week of pregnancy. Amidst various fully differentiated derivatives of all three embryonic layers, the cyst wall also included a miniature replica of the anterior pituitary lobe 0.5 cm in diameter. While a full set of adenohypophyseal hormone-producing cell types could be identified, there was characteristic pregnancy-related hyperplasia of lactotrophs. This was further overlaid by prominent mononuclear inflammation, including infiltration by T lymphocytes, follicular aggregates of B cells, and attendant destruction of parenchyma. There was no significant inflammatory reaction elsewhere. Discounting the non-standard location, the ensemble of the clinical setting and histology were felt to be indistinguishable from the classical paradigm of lymphocytic hypophysitis complicating pregnancy. To date, lymphocytic thyroiditis is the sole form of organ-specific inflammatory process within an ovarian teratoma on record. By analogy, we hypothesize that this ectopic manifestation of immune-mediated inflammation of pituitary parenchyma may possibly be read as a preclinical sentinel lesion of lymphocytic hypophysitis.

Effect of platelet-rich plasma on the healing of intrabony defects treated with an anorganic bovine bone mineral: a pilot study

BACKGROUND: Periodontal therapy using the combination of platelet-rich plasma (PRP) and different grafting materials has been suggested as a modality to enhance the outcome of regenerative surgery. In most clinical studies, a barrier membrane was used to cover the defects, and thus, the effects of PRP may have been masked by the effects of the barrier. The data from controlled clinical studies evaluating the effect of regenerative therapy using various grafting materials with or without PRP are still limited. The purpose of this study was to clinically compare the healing of intrabony defects treated with either a combination of an anorganic bovine bone mineral (ABBM) and PRP to those obtained with ABBM alone. METHODS: Thirty patients with advanced chronic periodontal disease and displaying one intrabony defect were randomly treated with PRP + ABBM or ABBM alone. The following clinical parameters were evaluated at baseline and 1 year after treatment: plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), gingival recession (GR), and clinical attachment level (CAL). The primary outcome variable was CAL. RESULTS: No statistical significant differences in any of the investigated parameters between the two groups were observed at baseline. Healing was uneventful in all patients. In the PRP + ABBM group, mean PD decreased from 8.6 +/- 1.8 mm to 3.4 +/- 1.4 mm (P <0.001) and mean CAL changed from 9.9 +/- 1.7 mm to 5.3 +/- 1.8 mm (P <0.001). In the ABBM group, mean PD decreased from 8.5 +/- 2.0 mm to 3.2 +/- 1.3 mm (P <0.001) and mean CAL changed from 9.6 +/- 1.9 mm to 4.9 +/- 1.5 mm (P <0.001). CAL gains >or=3 mm were measured in 80% (12 of 15 defects) of cases treated with PRP + ABBM and in 87% (13 of 15 defects) of cases treated with ABBM alone. No statistically significant differences in any of the investigated parameters were observed between the two groups at the 1-year reevaluation. CONCLUSIONS: Within the limits of the present study, it can be concluded that 1) at 1 year after regenerative surgery with PRP + ABBM and ABBM alone, significant PD reductions and CAL gains were found, and 2) the use of PRP failed to improve the results obtained with ABBM alone.

Five-year results evaluating the effects of platelet-rich plasma on the healing of intrabony defects treated with enamel matrix derivative and natural bone mineral

BACKGROUND Regenerative periodontal surgery using the combination of enamel matrix derivative (EMD) and natural bone mineral (NBM) with and without addition of platelet-rich plasma (PRP) has been shown to result in substantial clinical improvements, but the long-term effects of this combination are unknown. METHODS The goal of this study was to evaluate the long-term (5-year) outcomes after regenerative surgery of deep intrabony defects with either EMD + NBM + PRP or EMD + NBM. Twenty-four patients were included. In each patient, one intrabony defect was randomly treated with either EMD + NBM + PRP or EMD + NBM. Clinical parameters were evaluated at baseline and 1 and 5 years after treatment. The primary outcome variable was clinical attachment level (CAL). RESULTS The sites treated with EMD + NBM + PRP demonstrated a mean CAL change from 10.5 ± 1.6 to 6.0 ± 1.7 mm (P <0.001) at 1 year and 6.2 ± 1.5 mm (P <0.001) at 5 years. EMD + NBM-treated defects showed a mean CAL change from 10.6 ± 1.7 to 6.1 ± 1.5 mm (P <0.001) at 1 year and 6.3 ± 1.4 mm (P <0.001) at 5 years. At 1 year, a CAL gain of ≥4 mm was measured in 83% (10 of 12) of the defects treated with EMD + NBM + PRP and in 100% (all 12) of the defects treated with EMD + NBM. Compared to baseline, in both groups at 5 years, a CAL gain of ≥4 mm was measured in 75% (nine of 12 in each group) of the defects. Four sites in the EMD + PRP + NBM group lost 1 mm of the CAL gained at 1 year. In the EMD + NBM group, one defect lost 2 mm and four other defects lost 1 mm of the CAL gained at 1 year. No statistically significant differences in any of the investigated parameters were observed between the two groups. CONCLUSIONS Within their limits, the present results indicate that: 1) the clinical outcomes obtained with both treatments can be maintained up to a period of 5 years; and 2) the use of PRP does not appear to improve the results obtained with EMD + NBM.

"Leiomyomatoid angiomatous neuroendocrine tumor" (LANT) of the pituitary reflects idiosyncratic angiogenesis in adenomas of the gonadotroph cell lineage.

Based on a single-case observation, the descriptive label "leiomyomatoid angiomatous neuroendocrine tumor" (LANT) has been tentatively applied to what was perceived as a possible novel type of dual-lineage pituitary neoplasm with biphasic architecture. We report on two additional examples of an analogous phenomenon encountered in male patients, aged 59 years (Case 1) and 91 years (Case 2). Both tumors were intra- and suprasellar masses, measuring 5.6 cm × 4.4 cm × 3.4 cm, and 2.7 cm × 2 cm × 1.7 cm, respectively. Histologically, Case 1 was an FSH-cell adenoma interwoven by vascularized connective tissue septa that tended to exhibit incremental stages of adventitial overgrowth. The epithelial component of Case 2 corresponded to an LH-cell adenoma, and lay partitioned by a maze of paucicellular to hyalinized vascular axes. Irrespective of architectural variations, perivascular spindle cells exhibited immunopositivity for vimentin, muscular actin, and smooth muscle actin. Conversely, negative results were obtained for CD34, EMA, S100 protein, GFAP, and TTF-1. Ultrastructural study failed to reveal metaplastic cell forms involving transitional features between adenohypophyseal-epithelial and mesenchymal-contractile phenotype. We propose that LANT be regarded as a peculiar reflection of maladaptive angiogenesis in some pituitary adenomas, rather than a genuine hybrid neoplasm. While no mechanistic clue is forthcoming to account for this distinctive pattern, hemodynamic strain through direct arterial - rather than portal - supply of the adenoma's capillary bed may be one such explanatory factor. The apparent predilection of the LANT pattern for macroadenomas of the gonadotroph cell lineage remains unexplained.

Platelet-rich concentrates differentially release growth factors and induce cell migration in vitro

BACKGROUND Platelet-rich concentrates are used as a source of growth factors to improve the healing process. The diverse preparation protocols and the gaps in knowledge of their biological properties complicate the interpretation of clinical results. QUESTIONS/PURPOSES In this study we aimed to (1) analyze the concentration and kinetics of growth factors released from leukocyte- and platelet-rich fibrin (L-PRF), leukocyte- and platelet-rich plasma (L-PRP), and natural blood clot during in vitro culture; (2) investigate the migration of mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs) as a functional response to the factors released; and (3) uncover correlations between individual growth factors with the initial platelet/leukocyte counts or the induced cell migration. METHODS L-PRF, L-PRP, and natural blood clot prepared from 11 donors were cultured in vitro for 28 days and media supernatants collected after 8 hours and 1, 3, 7, 14, and 28 days. Released transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), insulin growth factor (IGF-1), platelet-derived growth factor AB (PDGF-AB), and interleukin-1β (IL-1β) were measured in the supernatants with enzyme-linked immunosorbent assay. Migration of MSC and HUVEC induced by the supernatants was evaluated in Boyden chambers. RESULTS More TGF-ß1 was released (mean ± SD in pg/mL of blood) from L-PRF (37,796 ± 5492) compared with L-PRP (23,738 ± 6848; p < 0.001) and blood clot (3739 ± 4690; p < 0.001), whereas more VEGF and IL-1ß were released from blood clot (1933 ± 704 and 2053 ± 908, respectively) compared with both L-PRP (642 ± 208; p < 0.001 and 273 ± 386; p < 0.001, respectively) and L-PRF (852 ± 376; p < 0.001 and 65 ± 56, p < 0.001, respectively). No differences were observed in IGF-1 and PDGF-AB released from any of the concentrates. TGF-β1 release peaked at Day 7 in L-PRF and at 8 hours and Day 7 in L-PRP and 8 hours and Day 14 in blood clot. In all concentrates, main release of VEGF occurred between 3 and 7 days and of IL-1β between Days 1 and 7. IGF-1 and PDGF-AB were released until Day 1 in L-PRP and blood clot, in contrast to sustained release over the first 3 days in L-PRF. The strongest migration of MSC occurred in response to L-PRF, and more HUVEC migration was seen in L-PRF and blood clot compared with L-PRP. TGF-β1 correlated with initial platelet counts in L-PRF (Pearson r = 0.66, p = 0.0273) and initial leukocyte counts in L-PRP (Pearson r = 0.83, p = 0.0016). A positive correlation of IL-1β on migration of MSC and HUVEC was revealed (Pearson r = 0.16, p = 0.0208; Pearson r = 0.31, p < 0.001). CONCLUSIONS In comparison to L-PRP, L-PRF had higher amounts of released TGF-β1, a long-term release of growth factors, and stronger induction of cell migration. Future preclinical studies should confirm these data in a defined injury model. CLINICAL RELEVANCE By characterizing the biologic properties of different platelet concentrates in vitro, we may gain a better understanding of their clinical effects and develop guidelines for specific future applications.

Impact of platelet rich plasma and adipose stem cells on lymphangiogenesis in a murine tail lymphedema model.

BACKGROUND Lymphedema is an underdiagnosed pathology which in industrialized countries mainly affects cancer patients that underwent lymph node dissection and/or radiation. Currently no effective therapy is available so that patients' life quality is compromised by swellings of the concerned body region. This unfortunate condition is associated with body imbalance and subsequent osteochondral deformations and impaired function as well as with an increased risk of potentially life threatening soft tissue infections. METHODS The effects of PRP and ASC on angiogenesis (anti-CD31 staining), microcirculation (Laser Doppler Imaging), lymphangiogenesis (anti-LYVE1 staining), microvascular architecture (corrosion casting) and wound healing (digital planimetry) are studied in a murine tail lymphedema model. RESULTS Wounds treated by PRP and ASC healed faster and showed a significantly increased epithelialization mainly from the proximal wound margin. The application of PRP induced a significantly increased lymphangiogenesis while the application of ASC did not induce any significant change in this regard. CONCLUSIONS PRP and ASC affect lymphangiogenesis and lymphedema development and might represent a promising approach to improve regeneration of lymphatic vessels, restore disrupted lymphatic circulation and treat or prevent lymphedema alone or in combination with currently available lymphedema therapies.

Intelligence and the psychological refractory period: A lateralized readiness potential study

The psychological refractory period (PRP) refers to a delay of response times (RT) to the second of two stimuli when these stimuli are presented in rapid succession. If this limitation of rapidly processing the second stimulus contributes to the well-known differences in speed of information processing between individuals with higher and lower mental ability, individuals with lower mental ability should exhibit a more pronounced PRP effect than individuals with higher mental ability. Previous studies on this question, however, yielded inconsistent results. In the present study, we assessed mental ability-related differences in the PRP by measuring lateralized readiness potentials (LRPs) to separate premotor and motor aspects of speed of information processing in 95 individuals with higher and 95 individuals with lower mental ability. Although individuals with higher mental ability processed information faster than individuals with lower mental ability as indicated by shorter RTs and shorter premotor LRP latencies, the PRP effect was equally pronounced in both groups. These findings suggest that the processes underlying the PRP effect do not contribute to mental ability-related differences in speed of information processing. Rather, these differences seem to occur at an earlier stage of information processing such as stimulus encoding, stimulus analysis, or stimulus evaluation.