V Ninfo

University of Padova, Padua, Veneto, Italy

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Publications (86)232.72 Total impact

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    ABSTRACT: Undifferentiated sarcomas are primitive mesenchymal tumors that cannot be classified among standardized histopathologic entities. Whether they represent a homogeneous group with common histogenesis and clinical behavior or comprise a variety of tumors able to differentiate along specific maturative lineages is still debated. To identify prognostic and histogenetic markers, we analyzed 7 undifferentiated sarcomas (4 in the trunk and 3 in the extremities). Mean patient age was 7.5 years, and mean follow-up was 18 months. Two clinicopathologic subtypes emerged from this study. Four primitive mesenchymal undifferentiated sarcomas arose mainly on the trunk and very proximal extremities, had an aggressive clinical course with poor outcome (3 deaths from disease, 1 with persistent disease), and displayed sheets of oval cells, with bland nuclei. Three spindle cell undifferentiated sarcomas arose on the extremities, had a favorable outcome, and showed elongated spindle cells with areas of primitive fibrosarcoma. All were negative for epithelial membrane antigen, cytokeratins, CD34, smooth muscle actin, desmin,Myf4, and HMB45 and showed nuclear staining for INI. Focal staining for S100 and CD99 was found in 3 and 4, respectively. Among stem cell markers, CD117 was positive in 3 cases (1 primitive, 2 spindle), nestin in 5 cases (4 primitive, 1 spindle), and CD105-stained tumor cells lining newly formed vascular spaces in 4 cases (1 primitive, 3 spindle). Survivin was weakly expressed in 6 cases and reflected low levels of mRNA (median survivin/GAPDH ratio, 1.096). Cytogenetic analysis revealed nonspecific translocations in 3 tumors. No translocations associated with Ewing sarcoma, synovial sarcoma, or alveolar rhabdomyosarcoma were found. In summary, primitive undifferentiated sarcomas occur in the trunk, behave aggressively, and express nestin. Spindle cell undifferentiated sarcomas occur in extremities, have a favorable outcome, resemble fibrosarcomas, and have similarly low survivin levels and display CD105-positive vascular spaces, which may represent an early hemangiopericytomatous pattern.
    No preview · Article · Aug 2009 · Human pathology

  • No preview · Article · May 2009 · Human pathology
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    ABSTRACT: Hepatoblastoma (HB) is the most frequent malignant liver tumor in infancy, and both its biological features and its prognostic behavior are still under investigation. DNA content and proliferative activity of the tumor have been considered as biological parameters related to the tumor's aggressiveness. The present study attempts to investigate the possible association between histologic subtype, DNA content, and proliferative indices in HB. DNA content and the proportion of cells in the S-phase were assessed by flow cytometry in 34 cases of HB (14 prior to chemotherapy, 20 after chemotherapy), using formalin-fixed, paraffin-embedded archival samples. The proliferative cell nuclear antigen (PCNA) labeling index was also evaluated by immunohistochemistry, and both the flow cytometry (FC) and the immunohistochemical data were correlated with tumor pathology. A significant association was found between histological type, DNA content and the percentage of cells in the S-phase, with aneuploidy and the highest proportions of S-phase cells significantly associated with embryonal tumors. The PCNA labeling index was found to be significantly higher in embryonal than in fetal phenotype. The biological heterogeneity of HB is confirmed by the different nuclear content of the fetal (diploid) and embryonal (aneuploid) epithelial components of the tumor, also ruling out the likelihood of fetal (diploid) clones deriving from the embryonal (aneuploid) neoplastic cells. Since the highly proliferative neoplastic clones (i.e., embryonal) are thought to be more sensitive to antimitotic drugs, further studies are indicated to determine the relationship between ploidy, proliferative indices and chemoresponsiveness.
    No preview · Article · Dec 2008 · Liver International
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    ABSTRACT: We report on a previously unrecognized fibro-myofibroblastic tumor in the oral cavity of a 15-year-old girl. Morphologically, the tumor mimicked a rhabdomyosarcoma, botryoid variant. It was composed of mitotically active small- to medium-sized, vimentin+/desmin+, round- to oval- to epithelioid-shaped cells embedded in an alternating fibrous to myxoid/edematous stroma. These cells were separated from the overlying squamous epithelium by a rim of fibrous stroma. The tumor contained abundant small- to medium-sized, thin-walled blood vessels without hyalinization. Frequently, neoplastic cells condensed around these vessels. An unusual and striking feature was the presence of numerous hyalinized collagen mats, including "amianthoid-like fibers", similar to those observed in myofibroblastomas. The presence of these collagen mats and the expression of desmin, in association with no immunoreactivity to myogenin and MyoD1, were in keeping with the fibro-myofibroblastic nature of the tumor, excluding the diagnosis of embryonal rhabdomyosarcoma. Regarding fibro-myofibroblastic tumors, we believe that the present case falls within the wide spectrum of benign stromal tumors, originally described in the lower female genital tract, but potentially occurring also at extragenital sites. As morphological and immunohistochemical features were reminiscent of, but not identical with, angiomyofibroblastoma, the term "polypoid angiomyofibroblastoma-like tumor" is proposed. Awareness and recognition of this tumor is crucial to avoid a diagnosis of malignancy.
    No preview · Article · Nov 2008 · Pathology - Research and Practice
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    ABSTRACT: Recently, jawbone osteonecrosis has been reported as a potential adverse effect of bisphosphonates administration. This paper considers and highlights histopathologic and radiologic features of this condition. Eleven patients, owing to unresponsiveness to conservative treatment and uncontrollable pain, underwent surgical resection of diseased jawbone after extensive hyperbaric oxygen therapy. A thorough clinical, laboratory, and imaging study was performed. Surgical specimens underwent histopathologic and immunohistochemical evaluation. Computerized tomography (CT) scans showed increased bone density, periosteal reaction, and bone sequestration in advanced stages. With magnetic resonance imaging (MRI), exposed areas showed a low signal in T1- and T2-weighted and inversion recovery images, which suggests low water content and is histopathologically correlated with paucity in cells and vessels (osteonecrotic pattern). Unexposed diseased bone was characterized by T1 hypointensity and T2 and IR hyperintensity, which suggests high water content and inflammation, associated with hypercellularity, osteogenesis, and hypervascularity (osteomyelitic pattern). Diseased bone extends beyond the limits of the bone exposed in the oral cavity. Histopathologic examination correlated well with CT and MRI, which are the choice for the evaluation of bisphosphonate-associated jawbone osteonecrosis.
    Full-text · Article · Apr 2008 · Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology
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    ABSTRACT: The aim of the present study was to evaluate maspin expression in bladder urothelial papillary neoplasms and test the results for correlation with clinicopathological parameters. A total of 111 urothelial neoplasms from 66 patients were evaluated: pathological examination of primary tumours disclosed 48 pTa and 18pT1. Fourteen additional biopsies, negative for neoplasm, were collected as control biopsies. For each of the 111 neoplastic samples and for the 14 control cases maspin and MIB1 immunoreactivity was evaluated. The immunohistochemical reactions of the 66 primary neoplasms were used for statistical analysis when the disease-free interval, presence and number of relapses, and progression of the disease were tested, whereas all of the 111 tumors were used when the association between the maspin pattern and histological grade and/or pT were evaluated. Thirty-three patients with primary pTa papillary neoplasms (68.7%) and 11 out of eighteen with pT1 (61%), had subsequent relapses of disease. For maspin immunoreactivity the presence/absence of nuclear staining and the pattern of staining were considered. Four patterns of reactivity were recognized and were used for statistical analyses. A statistical association was found between the maspin pattern and pT, histological grade and nuclear staining. In papillary urothelial neoplasms, maspin has a pattern of distribution that is associated with the histological grade and pathological stage, and this probably reflects its different activities in the neoplastic process.
    Full-text · Article · Jan 2008 · Anticancer research
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    ABSTRACT: The aim of the present study was to evaluate the tissue expression of squamous cell carcinoma antigen (SCCA) in oesophageal dysplasia and squamous cell carcinoma (SCC) with reference to its clinico-pathologic and prognostic significance. Immunohistochemistry using SCCA polyclonal antibody was performed on SCCs from 61 surgical oesophagectomies. Fifteen cases of low-grade dysplasia (LGD) and 37 non-coexistent high-grade dysplasia (HGD) were also sampled from these materials, together with sixteen chronic cases of oesophagitis. SCCA immunoreactivity was present in the maturative compartments of all normal epithelia and oesophagitis. LGDs showed no SCCA immunoreactivity in the dysplastic proliferative component but only in the superficial normal layers. In 94.6% of HGDs, no SCCA immunoreactivity was detected throughout the thickness of the epithelium. In SCCs, SCCA expression higher than 25% was found in 54% of cases. SCCA positivity showed an inverse correlation with histological grade, whereas no statistically significant correlation was found with TNM classifications, stage, or survival. SCCA is not expressed in early oesophageal carcinogenesis but, in SCC, it represents an indicator of histologic differentiation. In differentiated SCC, SCCA may represent a negative factor for cancer invasiveness, through inhibition of proteases.
    Full-text · Article · Oct 2007 · Histology and histopathology
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    ABSTRACT: To report three cases of serous cystadenoma and endocrine tumour in the same pancreas, to review the literature and to evaluate the clinicopathological features of the tumours. Cases: Three women (71, 57 and 31 years old) were admitted to hospital, two for diseases unrelated to the pancreas and the third for increasing obstructive jaundice in von Hippel-Lindau disease. Preoperative examination showed two distinct lesions in the first patient and only cystic lesions in the other two. Histological examination of the pancreas showed one serous oligocystic adenoma associated with a benign, well-differentiated endocrine tumour, one serous oligocystic adenoma associated with an endocrine microadenoma, and a von Hippel-Lindau-related cystic neoplasm with a well-differentiated endocrine carcinoma. Serous cystadenoma associated with endocrine tumour shows some clinicopathological differences with respect to the two tumours considered separately, and with respect to von Hippel-Lindau-related cases, although there is no convincing evidence at present to justify considering this association as a separate entity.
    Full-text · Article · Apr 2007 · Journal of Clinical Pathology
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    ABSTRACT: We report 2 intra-abdominal tumors originally diagnosed as leiomyosarcomas, occurring in adolescents, one as a second malignancy after a Hodgkin lymphoma. Both tumors exhibited unusual morphologic features characterized by spindle cells arranged in sheets or in fascicles, devoid of the typical desmoplastic stroma. Cytokeratins and mesenchymal markers, including smooth muscle actin, desmin, and muscle specific actin, were coexpressed in the tumor cells, whereas EMA was negative. Reverse transcription-polymerase chain reaction analysis showed an EWS-WT1 fusion transcript. Both patients are alive and in complete remission at 3 and 13 years after diagnosis, respectively. These tumors raise a variety of diagnostic possibilities. They could represent intra-abdominal desmoplastic small round cell tumor, with histologic features of epithelioid leiomyosarcoma or an unusual subtype of leiomyosarcoma with an EWS-WT1 transcript. Alternatively, they could represent an unrecognized subgroup of tumors with spindle cell morphology, bearing the same translocation as desmoplastic small round cell tumor, but characterized by a more favorable clinical course.
    No preview · Article · Apr 2007 · American Journal of Surgical Pathology
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    ABSTRACT: Maspin is a unique serine proteinase inhibitor which has tumor suppressor activity. The aim of the present study was to investigate the role of maspin in ampullary adenocarcinomas, its correlation with apoptosis and its value as a prognostic marker. Twenty-three cases of ampulla of Vater adenocarcinoma were collected from archival material. For each sample, maspin, M30, p53 and Mib1 immunohistochemical reactivity were evaluated and results compared with clinicopathological parameters. A statistical relation was found between nuclear maspin and M30 (Spearman's Q = 0.46, p = 0.02), and p53 (Kruskal-Wallis = 0.03); a trend was found between nuclear maspin and pT (Kruskal-Wallis = 0.09), and pM (Mann-Whitney = 0.08) and pN status (Fisher's mid-point test: p = 0.070). The present study evaluated the role of maspin in ampullary adenocarcinomas and for the first time demonstrated its association with apoptosis, tumor growth and metastasis.
    Preview · Article · Mar 2007 · Anticancer research
  • S Blandamura · L Giacomelli · G Leo · P Segato · V Ninfo
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    ABSTRACT: To investigate the presence of maspin in renal tumours in an attempt to improve our understanding of the underlying mechanism of renal carcinogenesis and for diagnostic purposes. We examined 122 renal neoplasms of varying histological types and immunohistochemically investigated maspin and p53 expression. All clear cell carcinomas (CC) were negative for maspin, whereas oncocytomas (OC), papillary renal cell carcinomas (PC), chromophobe carcinomas (CPC) and, at least focally, collecting duct carcinomas (CDC) stained positively. We found that p53 positivity had a statistically significant correlation with metastasis (P=0.009) in CC and maspin showed a significant inverse correlation with the presence of metastasis in PC and CDC (P=0.02). The detection of maspin may be useful for differential diagnostic purposes and suggests a different underlying mechanism in the development of the various histological types of renal carcinomas.
    No preview · Article · Oct 2006 · Histopathology
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    ABSTRACT: Pilocytic astrocytoma is a central nervous system neoplasia that arises during pediatric age. Only few cases have been documented in patients older than 50 years old. It is a low-grade lesion that can rarely undergo malignant changes presenting the histologic features of a high-grade glioma. We report a case of a pilocytic astrocytoma arising in the eyeball of a 53-year-old man affected by glaucoma that underwent malignant evolution.
    No preview · Article · Sep 2006 · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
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    ABSTRACT: Soft tissue sarcomas in the first year of life are rare, and the most common sarcomas in infancy are embryonal rhabdomyosarcoma, Ewing sarcoma/primitive neuroectodermal tumor, congenital infantile fibrosarcoma, and primitive sarcomas such as undifferentiated sarcoma. In this study, we report 6 cases of a primitive myxoid mesenchymal tumor of infancy (PMMTI), which previously may have been included under the diagnostic categories of congenital-infantile fibrosarcoma or infantile fibromatosis. PMMTI occurred in 6 infants, 3 of whom had a congenital presentation of a soft tissue mass. All patients were otherwise healthy. The tumors occurred on the trunk, extremities, and head and neck. Grossly, the tumors were nonencapsulated and had a multinodular appearance with focal infiltrative growth, a white fleshy cut surface, and a tumor diameter ranging from 2 to 15 cm. Histologically, a diffuse growth of primitive spindle, polygonal, and round cells occurred in a myxoid background. The tumor cells were arranged in a vaguely nodular pattern with peripheral collagenized stroma, higher cellularity at the periphery, and a delicate vascular network in the background. Immunohistochemically, the tumors displayed diffuse reactivity for vimentin and no reactivity for smooth muscle actin, muscle specific actin, desmin, S-100 protein, or myogenin. Electron microscopy documented a poorly differentiated fibroblastic proliferation. Four cases tested negative for the ETV6-NTRK3 gene fusion by RT-PCR. One tumor had a complex karyotypic abnormality with rearrangements involving chromosomes Y, 9, and 3. Three patients had recurrences or metastasis treated with a combination of surgery and chemotherapy. One patient is alive with persistent locally aggressive disease, 2 are alive with no evidence of recurrence, 1 had a recurrence treated surgically without further follow-up information, 1 patient died with persistent tumor and sepsis 6 weeks after diagnosis, and 1 patient was lost to follow-up. The morphologic appearance combined with the ultrastructural features and absence of the typical gene rearrangement of congenital-infantile fibrosarcoma are unique, and we propose that PMMTI represents a new category of pediatric fibroblastic-myofibroblastic tumor.
    No preview · Article · Apr 2006 · American Journal of Surgical Pathology
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    ABSTRACT: The regulation of apoptosis, as a distinctive form of programmed cell death, in multistep Barrett's esophagus (BE) carcinogenesis is poorly understood. The aim of this study was to investigate, in the intestinal metaplasia-dysplasia-carcinoma sequence, the role of survivin, an inhibitor of apoptosis; the p53 protein, a tumor suppressor gene involved in cell cycle control; and caspase 3, a protease-inducing apoptosis and inhibited by survivin. Immunohistochemical expression was tested in 40 cases of BE, including 11 low-grade and 19 high-grade dysplasias (HGD), and samples were obtained from 40 surgical specimens of esophagectomy performed for HGD or Barrett's adenocarcinoma. To define the deregulation time of the proteins, overexpression was evaluated in relation to the proliferative and/or maturative compartment. In BE, cytoplasmic expression of survivin and caspase 3 (100% of cases) was significantly higher than expression of p53 (25%). The latter increased with increasing grade of dysplasia. In BE, the expression of survivin, p53, and caspase 3 mainly involved the proliferative compartment, whereas in LGD and HGD, the 3 proteins were coexpressed in both proliferative and maturative compartments. These results indicate that survivin overexpression is an early event in the proliferative compartment of BE, preceding both p53 accumulation and dysplastic changes. Cytoplasmic survivin location may indicate an initial antiapoptotic, more than proliferative, role in the early phases of Barrett carcinogenesis. Expression of caspase 3 in BE and dysplasia may be ascribed to accumulation of the nonactivated form, as the antibody used detects both cleaved and uncleaved caspase 3.
    No preview · Article · Feb 2006 · Human Pathlogy
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    ABSTRACT: Infantile myofibromatosis (IM) is a distinctive mesenchymal disorder with different clinical forms, including solitary, multicentric, and generalized with visceral involvement. A wide morphologic spectrum is encountered, with the extremes resembling congenital infantile fibrosarcoma (CIFS) and infantile hemangiopericytoma. We report a series of lesions with mixed features of CIFS and IM and compare them in order to further define their clinicopathologic features and the significance of the so-called composite fibromatosis. Seven lesions with unusual overlapping morphologic "composite" features of both IM and CIFS were selected from a series of 106 myofibroblastic lesions. Three cases classified as composite infantile myofibromatoses (COIM) were highly cellular tumors with a diffuse growth of primitive mesenchymal cells and focal features of IM combined with areas resembling infantile fibrosarcoma (IF). Four cases were classified as IF. Three of these exhibited a biphasic pattern with foci resembling IM, including whorls of primitive and spindle cells and perivascular and intravascular projections of myofibroblastic nodules, and the 4th had a close histologic resemblance to a primitive, immature IM. With reverse transcriptase polymerase chain reaction, the ETV6-NTRK3 transcript was absent in 3 COIM and was detected in 3 CIFS; the other CIFS had typical cytogenetic aberrations. On the basis of currently available information, COIM represents a morphologic variant of IM that can mimic IF. Careful histologic evaluation to detect the typical features of IM is essential to avoid classification as IF. Molecular analysis for the ETV6-NTRK3 gene fusion is an important diagnostic tool in this group of lesions.
    No preview · Article · Jan 2006 · Pediatric and Developmental Pathology

  • No preview · Article · Jun 2005 · Histopathology
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    ABSTRACT: FLI-1 nuclear transcription factor has been proposed as a useful tool in the differential diagnosis of small round cell sarcomas. Recently, FLI-1 has been reported as the first nuclear marker of endothelial differentiation. However, its clinical use has been hampered by major interpretation problems, due to the presence of background staining as well as staining variation between different lots of the same antiserum. In this study, a novel monoclonal antibody raised against the carboxyl terminal of the FLI-1 protein (clone GI146-222, BD Pharmingen) was tested in a series of small round cell and vascular neoplasms. Furthermore, in order to assess FLI-1 specificity, we analyzed its expression in a series of common epithelial and nonepithelial malignancies. In total, 15 Ewing's sarcomas, 10 rhabdomyosarcomas, 5 desmoplastic small round cell tumors, 10 synovial sarcomas, 10 high-grade pleomorphic sarcomas, 10 malignant melanomas, 5 Merkel's carcinomas, 10 colonic adenocarcinomas, 10 breast carcinomas, 10 lung adenocarcinomas, 20 angiosarcomas, 5 epithelioid hemangioendotheliomas, 10 Kaposi's sarcomas and 10 benign hemangiomas, were stained. A strong FLI-1 immunoreactivity was detected in all Ewing's sarcomas and vascular neoplasms, highlighting the high sensitivity of FLI-1 monoclonal antibody. However, 2/5 Merkel's carcinomas and 1/10 malignant melanomas showed a strong nuclear immunostaining, suggesting that FLI-1 may not be so helpful in the differential diagnosis of cutaneous Ewing's sarcoma. In addition, a weak immunoreactivity was found in 3/5 Merkel cell carcinomas, 3/10 synovial sarcomas, 5/10 malignant melanomas, 6/10 lung adenocarcinomas and in 1/10 breast carcinomas. In contrast, all the rhabdomyosarcomas, desmoplastic small round cell tumors, high-grade pleomorphic sarcomas and colonic adenocarcinomas tested were negative. Importantly, in contrast with previous studies, no background staining was observed. Our results indicate that FLI-1 monoclonal antibody can be reliably applied to the differential diagnosis of small round cell neoplasms of soft tissue, and confirm its important role as nuclear marker of endothelial differentiation, mainly helpful in those cases in which technical artifacts are seen by using the traditional membranous and cytoplasmic endothelial markers.
    Full-text · Article · Jun 2004 · Modern Pathology
  • M C Montesco · R Alaggio · Vito Ninfo
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    ABSTRACT: Sarcomas included in the broad group of small round-cell tumors (SRCT) and some non-SRCT lesions that typically are seen in pediatric-age patients can rarely occur in adults. However, there are differences in the anatomic sites that are involved and the prognosis in these two patient groups. The diagnosis of pediatric-type sarcomas in adults is often challenging because of the unusual contextual clinical setting and morphologic features. Immunohistochemical studies have greatly facilitated this process. Moreover, limited biomolecular studies that have been conducted have demonstrated comparable cytogenetic alterations in adults and children with pediatric-type tumors. They also have raised interesting questions concerning possible biological bases for differences in clinical behavior in the two cohorts. This review focuses on the morphological, immunohistochemical, and molecular characteristics of childhood-type sarcomas that affect adults, with emphasis on possible pitfalls in differential diagnosis.
    No preview · Article · Dec 2003 · Seminars in Diagnostic Pathology
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    ABSTRACT: Aggressive angiomyxoma is a rare tumor that predominates in the female genital tract. Multiple relapses may occur in adjacent organs and tissues, but metastases have not been reported. We present a case of aggressive angiomyxoma in a young woman with multiple local recurrences that metastasized to the lungs, killing the patient. We document this case and report a similar one, found in the literature, of a postmenopausal woman with pulmonary and mediastinic metastases. These cases may expand the current concepts of potential behavior of aggressive angiomyxoma.
    No preview · Article · Nov 2003 · Human Pathlogy
  • V Ninfo · R Alaggio

    No preview · Article · Nov 2003 · Pathologica

Publication Stats

2k Citations
232.72 Total Impact Points


  • 1976-2008
    • University of Padova
      • • Department of Surgery, Oncology and Gastroenterology DISCOG
      • • Department of Pediatrics
      • • Dipartimento di Scienze Mediche e Chirurgiche
      Padua, Veneto, Italy
  • 2002-2005
    • University-Hospital of Padova
      • UOC di Oncoematologia Pediatrica
      Padua, Veneto, Italy
  • 1992-2000
    • It-Robotics
      Vicenza, Veneto, Italy