Andrea Amorosi

A unique three-dimensional SCID-polymeric scaffold (SCID-synth-hu) model for in vivo expansion of human primary multiple myeloma cells.

Multiple myeloma (MM) cells home to the bone marrow (BM) and adhere to extracellular matrix (ECM) proteins and to bone marrow stromal cells (BMSCs). The close cross talk between MM cells and cells of the non-tumor compartment within the BM has a key role in supporting tumor growth, survival and development of drug resistance. This biological scenario has led to a growing interest in novel drugs, targeting MM cells and/or interfering with their human BM milieu (HuBMM).1, 2 Based on this, appropriate in vivo models that recapitulate the complex interactions occurring between MM and its HuBMM are required for preclinical evaluation of new anti-MM agents. To date, the in vivo study of MM pathobiology and the validation of therapeutic anti-MM agents has been carried out using a variety of models of murine MM or human MM xenografts in immunocompromised mice.3 These models, however, do not replicate the HuBMM. The development of the SCID (severe combined immunodeficiency)-hu model has been an important advance, as it was the first model to recapitulate a HuBMM in mice.4, 5, 6 However, although the SCID-hu system remains a highly relevant model for preclinical investigation, it does have important limitations: (i) restricted availability of human fetal bone chips; (ii) the allogeneic nature of the fetal BM milieu versus MM cells; and (iii) the significant heterogeneity of implanted human bone chips, collected from different individuals at different gestational age, that may produce experimental variability.

New evidence for a critical role of elastin in calcification of native heart valves: immunohistochemical and ultrastructural study with literature review.

Perrotta I, Russo E, Camastra C, Filice G, Di Mizio G, Colosimo F, Ricci P, Tripepi S, Amorosi A, Triumbari F & Donato G
(2011) Histopathology59, 504–513

Pathological findings in subsynovial connective tissue in idiopathic carpal tunnel syndrome.

Recent studies suggest that in patients with carpal tunnel syndrome, pathological changes occur in the subsynovial connective tissue. Such changes are non-inflammatory synovial fibrosis and vascular proliferation. Thickening of the tendon sheet may cause an increase of canal pressure and damages to the median nerve in the wrist; however, the causes of such events still remain to be clarified. We examined synovial specimens from 26 patients operated on for idiopathic carpal tunnel syndrome. Analysis included histological, ultrastructural and immunohistochemical examination in order to establish a pathological underlying pattern. An explanation for the pathogenesis of the found changes suggested. Our data confirm the presence of a non-inflammatory fibrosis with irregular bundles of collagen. De novo blood vessel formation was also noted. Interestingly the neo-angiogenesis consists of anomalous vessels and may be triggered from various cell types secreting vascular endothelial growth factor (VEGF), including macrophage-like elements similar to endothelial progenitor cells. Therefore, we believe that in the future a non-surgical management of carpal tunnel syndrome might be conjecturable via anti-VEGF drugs.

Chordoid Meningioma: Case Report and Literature Review

Chordoid meningioma (CM) is a meningioma containing regions that are histologically similar to chordoma, with trabeculae of eosinophilic, vacuolated cells in a myxoid background and corresponds to ...

Analysis of UbcH10 expression represents a useful tool for the diagnosis and therapy of astrocytic tumors.

Previous studies suggest the expression of UbcH10 gene, that codes for a protein belonging to the ubiquitin-conjugating enzyme family, as a valid indicator of the proliferative and aggressive status of tumors of different origin. Therefore, to look for possible tools to be used as diagnostic markers in astrocytic neoplasias, we investigated UbcH10 expression in normal brain, gliosis and low-grade and high-grade astrocytic tumors by immunohistochemistry. UbcH10 expression was observed in low-grade astrocytoma and in glioblastoma. Our data indicate a clear correlation between UbcH10 expression and the histological grade of the astrocytic tumors. Moreover, the analysis of UbcH10 expression allows the differentiation between gliotic and malignant tissues. Finally, since proteasome inhibitors have recently been considered as possible drugs in the chemotherapy of various tumors, our results would suggest new perspectives for the treatment of brain malignancies based on the suppression of the UbcH10 function.

Tryptase-positive mast cells and angiogenesis in keloids: a new possible post-surgical target for prevention

Literature data indicate that mast cells (MCs) are involved in angiogenesis through the release of several pro-angiogenetic factors among which tryptase, a serine protease stored in MC granules, is one of the most active. However, no data are available concerning the role of MCs during keloids’ angiogenesis. In this study, we evaluated the correlations of the number of MCs positive to tryptase (MCDPT) and microvascular density (MVD) within a series of 15 keloids and 10 normotrophic scars, by means of immunohistochemistry and image analysis methods. Data demonstrated a significant difference of MVD and MCDPT between keloids and normotrophic scars and a significant correlation between MVD and MCDPT in keloids. Our results suggest that tryptase-positive MCs might play a key role in keloids’ angiogenesis. In this context, several tryptase inhibitors might be clinically evaluated as a possible new anti-angiogenetic approach to prevent keloid formation after surgery.

Jaw Osteonecrosis in Patients Treated with Bisphosphonates: An Ultrastructural Study

Osteonecrosis of the jaw is a severe bone disorder traditionally associated with periodontal disease, local malignancy, chemotherapy, glucocorticoid therapy, or trauma. Recently a growing number of publications reported the occurrence of osteonecrosis of the jaw in patients undergoing treatment with bisphosphonates. The mechanism by which bisphosphonates might contribute to the development of osteonecrosis of the jaw is far from being fully elucidated. Suppression of bone turnover, infection, tissue hypoxia and cellular toxicity were proposed as possible mechanisms by which bisphosphonates may exert adverse effects on bone metabolism. Here, we studied 25 consecutive patients treated with bisphosphonates for osteoporosis or tumoral pathologies. We provide good evidence of hyperactive osteoclastic bone resorption and suggest a direct cytotoxic effect of bisphosphonates on bone tissue through induction of osteocyte cell death. We also demonstrate that bisphosphonates only have limited adverse effects on bone vascular network.

Expression of tenascin-c and CD44 receptors in cardiac myxomas

BACKGROUND Myxomas are the most frequent primary cardiac neoplasms. They have an abundant extracellular matrix rich in proteoglycans. Interactions between cells and matrix are very important in the development of tumors, but data about myxomas in this setting are scarce because of the rarity of such neoplasms. The expression of tenascin-c and hyaluran receptors in cardiac myxoma has never been investigated. Moreover, it is now well recognized that cells of cardiac myxoma differentiate along endothelial lines. METHODS We have analyzed left atrial myxomas from 13 consecutive patients (six male and seven female, surgically treated), via immunohistochemical methods for the expression of molecules also implicated in angiogenesis in normal and pathological conditions, like tenascin-c and hyaluran receptors CD44s, CD44v5 and CD44v6. RESULTS Our data suggest that tenascin-c and CD44s play a synergic and perhaps complementary role in development of cardiac myxomas. In particular, tenascin-c seems to promote aggregation of cells and differentiation in vascular structures, whereas CD44s receptors might be important for cellular motility. Cell proliferation rate in such tumors was very low (MIB-1 labeling index <1%) and uniform in all the areas of the neoplasms regardless of the presence of characteristic structures such as cords and rings of multinucleated cells or the expression of tenascin-c and CD44 receptors. CONCLUSIONS This study shows that cardiac myxomas express in the extracellular matrix tenascin-c and on the cellular membranes of neoplastic cells the hyaluran receptor CD44s. Such molecules take part in the mechanism of development of the myxomas and might be in the future the target of nonsurgical treatments.

Glomangioma of the Sural Nerve

nasal cavity, trachea, and sacrococcygeal region. Glomus tumor of peripheral nerves is uncommon but has been recorded in the upper limbs and once in the lower limb. A glomus tumor located in or near a peripheral nerve may compress it and mimic a peripheral Glomangioma is a benign neoplasm originating from the specialized smooth muscle cells of the vascular glomus. The classic location of glomus tumor is the subungual region, but it can also occur in the skin, soft tissues, peripheral nerves, stomach, International Journal of Surgical Pathology Volume 14 Number 4 October 2006 332-333

Neurocutaneous Melanosis in a Woman with Multiple Brain Melanocytomas, Cutaneous Melanocytosis and Oral Involvement

A 34-year-old female was referred to us for a consultation of her dermatological lesions (pigmented lesions present in her oral cavity and on her right shoulder) in May 2007. These lesions had been present since childhood. Recently, the patient had developed seizures and a headache. An MRI of the brain showed the presence of two intracranial masses. The intracranial tumours were surgically removed whereas skin and mucosal lesions were biopsied. Histological findings of brain tumours were consistent with a diagnosis of “melanocytoma” while cutaneous lesions presented “benign dermal melanocytic infiltrations”. Whole brain irradiation was performed. After 3 months a new melanocytic skin lesion appeared on the scalp with histological picture similar to the other cutaneous ones. At the 5-year follow-up examination no recurrence of intracranial tumour or other skin or mucosal lesions were registered. According to the clinical and histological findings, we classify our case as a form of neurocutaneous melanosis in a young adult patient and we present it for the rarity of this syndrome, for the difficulty of the diagnosis, for the potential aggressive behaviour of intracranial lesions that necessitates a constant attentive follow-up and for the unusual feature of new developing skin lesion during the course of the disease.