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G Pasquinelli

Publications and source records attributed to G Pasquinelli.

At least 19 recordsLinked to original sources

The "in situ" expression of human leukocyte antigen class I antigens is not altered by cryopreservation in human arterial allografts.

This study was aimed to establish whether the cryopreservation procedure we currently use in clinics can modify arterial homograft antigenicity. To this purpose, we performed an immunohistochemical study on fresh and cryopreserved human arterial homografts to visualize the expression of HLA class I heavy and light chains "in situ" by using the HC-10 and Namb-1 monoclonal antibodies. Human femoral arteries and thoracic aortas were harvested from 18 heart-beating donors and sampled before and after cryopreservation. Arterial segments were frozen in liquid nitrogen vapors in a controlled rate freezing system. After thawing, samples were processed for routine immunohistochemistry. To standardize immunostaining, flow-cytometry indirect immunofluorescence analysis was performed on HUVEC; immunohistochemistry of human ovarian cortical vessels was performed as an additional positive control. Negative controls were performed by omitting tissue incubation with primary antibodies. HLA-class I antigens were markedly expressed by endothelial cells lining surface intima and adventitial vasa vasorum; a moderate expression was found in medial smooth muscle cells. Except for the surface unreactivity caused by loss of endothelium, results from cryopreserved arterial allografts were strictly comparable to those observed in fresh, unfrozen tissues. These results support the view that cryopreserved arterial allografts are immunogenic as their fresh counterparts; apart from smooth muscle cells which retained a moderate expression of HLA class I antigens following cryopreservation, our study suggests that the highly HC-10 positive endothelial cells we found to line the rich adventitial network of vasa vasorum are expected to be one of the major targets of the serological response in the recipient.

Adult↗

Smooth muscle cell injury after cryopreservation of human thoracic aortas.

The cryopreservation protocol we use for arterial reconstructive surgery has been studied to evaluate smooth muscle cell (SMC) structural integrity and viability before implantation. Samples of human thoracic aortas (HTA) were harvested from five multi-organ donors. Sampling included unfrozen and cryopreserved specimens. Cryopreservation was performed using RPMI with human albumin and 10% Me(2)SO in a controlled-rate freezing apparatus. Thawing was accomplished by submerging bags in a water bath (39 degrees C) followed by washings in cooled saline. In situ cell preservation as investigated by light and transmission electron microscopy showed that SMCs from cryopreserved HTA had nuclear and cytoplasmic changes. A TUNEL assay, performed to detect DNA fragmentation in situ, showed increased SMC nuclear positivity in cryopreserved HTA when compared to unfrozen samples. 7-AAD flow cytometry assay of cells derived from cryopreserved HTA showed that an average of 49+/-16% cells were unlabeled after cryopreservation. Organ cultures aimed to study cell ability to recover cryopreservation damage showed a decreasing number of SMCs from day 4 to day 15 in cryopreserved HTA. In conclusion, the cryopreservation protocol applied in this study induces irreversible damage of a significant fraction of arterial SMCs.

Aorta, Thoracic↗

An Italian case of CADASIL with mutation CGC-TCG in codon 1006, exon 19 Notch3 gene.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is commonly overlooked or misdiagnosed owing to its recent identification. It is characterized clinically by recurrent cerebral infarcts, usually appearing between the ages of 30 and 50 years, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in approximately one-third of patients. The pathological hallmark of angiopathy is the presence of characteristic granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells. The defective gene in CADASIL is Notch3, which encodes a large transmembrane receptor, and 70% of missense mutations are in exons 3 and 4. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular N-terminal domain of the molecule. We report the case of a 53-year-old woman admitted to the hospital for transient ischemic attack and stroke-like episodes recurrent since age 43 years. The patient had pseudobulbar palsy, pyramidal signs, and cognitive impairment but not frank dementia. Cerebral MRI showed periventricular diffuse and confluent ischemic lesions. Ultrastructural study revealed an abnormal deposition of granular osmiophilic material (GOM) within the basal lamina in skin capillaries. Direct sequence analysis of the Notch3 gene was performed. Since no mutation was detected in exons 3 and 4, the remaining exons were sequenced and a missense mutation, CGC-TGC in codon 1006 of exon 19 was found. The mutation led to a gain of a cysteine residue. This is the first missense mutation in codon 1006 of exon 19 of the Notch3 gene to be described in Italy and the second reported in the literature.

Brain↗

Clear-cell proliferation of the lung with lymphangioleiomyomatosis-like change.

AIMS: To describe two cases of a peculiar pulmonary lesion, which expand both the morphological and the immunophenotypic spectrum of perivascular epithelioid cell (PEC)-related disorders. METHODS AND RESULTS: One man and one female, with and without the tuberous sclerosis complex (TSC), respectively, showed pulmonary cysts and small nodules on computed tomography scan. In the former, lymphangioleiomyomatosis (LAM) was suspected. In both cases, an open lung biopsy was performed, whose cut surface displayed numerous cysts lined by thin/thick septa. Microscopically, the septa were associated with micronodular or interstitial proliferation of medium/large-sized elements with abundant clear (periodic acid-Schiff-positive/diastase-sensitive) cytoplasm and distinct cell borders, embedded in fibrous tissue. The elements were CD34+, vimentin-positive and, to a lesser extent, HMB-45+ and MART-1+. The stains for specific muscle actin, desmin, S100 protein, CD31, FVIIIRAg, cytokeratins, CD45, CD68, oestrogen and progesterone receptors were all negative. Ki67 labelling was <1%. Electron microscopy displayed cytoplasmic vacuoles containing glycogen particles. The TSC1 and TSC2 gene status could not be assessed because of poor DNA preservation. In the man with TSC, a focus of micronodular pneumocyte hyperplasia was also found. CONCLUSIONS: Because of the coexpression of CD34 and melanoma-associated antigens and the occurrence of TSC in one patient, the cases described here add a new piece to the puzzle of PEC lesions and contribute to the open discussion on the origin of LAM and LAM-like proliferations.

Adult↗

[Pulmonary hyalinizing granuloma. Clinicopathologic study of 2 cases, with some original ultrastructural observations and review of the literature].

AIM: To report the clinical, histological, immunohistochemical and ultrastructural features of 2 new cases of pulmonary hyalinizing granuloma. RESULTS: Both patients were males: one, 72-year-old with retroperitoneal fibrosis, was asymptomatic, while the other, 67-year-old, presented with non productive cough. In both cases, a chest x-ray showed a solitary pulmonary nodule. Microscopically, the nodules were well circumscribed and composed of lamellae of hyalinized collagen. At the periphery, a more cellular rim consisting of lymphocytes, plasma cells and myofibroblasts was present. Immunohistochemical and ultrastructural examinations revealed myofibroblastic elements actively synthesizing collagen fibrils.

Aged↗

Smooth muscle cell differentiation in mammary stromo-epithelial lesions with evidence of a dual origin: stromal myofibroblasts and myoepithelial cells.

AIMS: We investigated the origin of myoid cells in benign stromo-epithelial lesions of the breast in order to ascertain their myoepithelial or myofibroblastic origin. METHODS AND RESULTS: We selected 22 stromo-epithelial lesions of the breast and reviewed their morphological features at haematoxylin-eosin (H&E) level. The lesions were classified as fibrous stromo-epithelial lesions (without evidence of myoid differentiation at H&E level) (13 cases), type 1 myoid stromo-epithelial lesions (myoid cells directly merging with the myoepithelial layer) (three cases), type 2 myoid stromo-epithelial lesions (bundles of myoid cells unrelated to the glands) (six cases). All cases were studied immunohistochemically and myoid stromo-epithelial lesions were also studied with electron microscopy. The myoid component in two out of three cases of type 1 myoid lesions showed immunohistochemically co-expression of smooth muscle and myoepithelial markers. In contrast, the remainder showed immunohistochemical results identical to those found in type 2 myoid lesions (positivity with SMA, desmin, calponin, CD34 and bcl2 and negativity with cytokeratin 14 and p63). Ultrastructural study confirmed the presence of cells with myoepithelial features in type 1 myoid lesions and of cells with myofibroblastic features in type 2 myoid lesions. CONCLUSIONS: Myoid cell differentiation is common in stromo-epithelial lesions of the breast, and is evident in H&E sections in up to 40% of cases. In addition, the origin of myoid cells is myofibroblastic in most cases, but in some cases, cells present immunohistochemical and ultrastructural evidence of myoepithelial origin.

Adult↗

[Cellular fibroma of the ovary: description of a case].

Cellular fibromas of the ovary are rare neoplasms belonging to the group of sex-cord stromal tumours. They have been described to show from 1 to 3 mitotic figures per 10 high power fields (HPF) and they generally behave in a benign fashion. Herein we describe the clinicopathological features of a case of ovarian cellular fibroma. The patient, a 22-year-old woman, presented with acute abdominal pain. Laparotomy revealed a large ovarian mass. Histologically the lesion was composed of spindle cells showing slight or moderate pleomorphism and 3 mitoses per 10 HPF. The spindle cells were immunoreactive for vimentin, smooth muscle actin and inhibin alpha-subunit. The differential diagnoses that we considered included the mitotically active leiomyoma because of the strong positivity for smooth muscle actin, but positive immunoreaction with anti alpha-inhibin antibody helped in confirming a sex-cord stromal tumour. Electron microscopy did not show any evidence of smooth muscle differentiation.

Actins↗

[Pulmonary carcinoma with myoepithelial differentiation, analogous to basal cell adenocarcionma of the salivary glands: description of a case].

We describe a case of pulmonary carcinoma with myoepithelial differentiation, analogous to basal cell adenocarcinoma of salivary glands. The patient, a 60 year-old man, smoker, presented with three peripheral nodules of the left lung. Preoperative staging was negative for metastatic disease and the patient underwent a surgical resection of the nodules. After 22 months, the patient is alive with no evidence of disease. Microscopically, the tumours were composed of atypical cells arranged in lobules, separated by basal membrane-like material. Immunohistochemically, tumour cells were positive for cytokeratin AE1/AE3, cytokeratin 14, vimentin, calponin, S-100 protein and gliofibrillary acid protein (GFAP). Electron microscopy showed features of epithelial and myoid differentiation and confirmed the myoepithelial nature of the tumour. Pulmonary tumours with myoepithelial differentiation are rare, but they have a wide and distinctive morphological spectrum.

Basement Membrane↗

Merkel cell carcinoma of the parotid gland associated with Warthin tumour: report of two cases.

AIMS: Two cases of Merkel cell carcinoma occurring simultaneously and in close association with a Warthin tumour of the parotid gland are reported. METHODS AND RESULTS: The patients were a 65-year-old man and a 70-year-old man, respectively. The Merkel cell carcinoma component was immunoreactive for chromogranin and keratin 20 and contained neuroendocrine-type granules at the ultrastructural level. CONCLUSIONS: The histogenesis of this heretofore undescribed combination is discussed.

Adenolymphoma↗

[Benign unclassified tumor of the gonadal stroma: importance of alpha-inhibin expression].

We present a begin unclassified gonadal stroma tumor in a 62 year-old menopausal woman. We discuss the differential diagnosis with the most frequent fibromas and thecomas and with the rarer sclerosing stromal tumor of the ovary. The immunohistochemical staining for alpha-inhibin was important to confirm the origin of the spindle-cell proliferation from undifferentiated (unclassified) ovarian gonadal stroma.

Actins↗

[Glycogen-rich clear-cell breast carcinoma with neuroendocrine differentiation features].

Glycogen-rich, clear cell carcinoma of the breast (GCC) is a rare type of breast cancer. Histological features are usually those of ductal carcinoma, but cases featuring lobular, tubular, and mixed ductal-tubular carcinoma have been reported. The presence of "numerous cells with clear cytoplasm" has been reported in some cases of primary neuro-endocrine tumors of the breast. Moreover, no case of GCC of the breast with neuro-endocrine features has been described. We report a case of 33-year-old woman with a palpable lump of the right breast. Fresh tissue obtained from the operating theatre was fixed in 10% formalin and routinely processed to paraffin. Serial sections were stained with haematoxylin and eosin (H&E), periodic acid Schiff (PAS) and PAS following diastase digestion (PASd); other sections were processed for immunohistological detection of chromogranin, synaptophysin, vimentin and smooth muscle actin. For electron microscopy, the tissue was fixed in 2.5% glutaraldehyde in cacodylate buffer. The samples were post-fixed in osmium, dehydrated in ethanol and embedded in araldite. Thin sections, counterstained in uranyl acetate and lead citrate, were studied under a Philips 400T electron microscope. The lump at histological examination was entirely composed of optically clear, neoplastic cells. The cytoplasm was filled with numerous PAS-positive granules which did not stain after the diastase digestion, leading to a diagnosis of GCC of the breast. Some histological (i.e. pattern of growth, blunt edges of neoplastic glands and numerous vessels) and cytological features (i.e. nuclear monomorphism and fine chromatin) prompted us to investigate the possible neuro-endocrine differentiation of the lesion. Immunohistochemical and ultrastructural studies strongly support such hypothesis. To the best of our knowledge, we report the first case of GCC of the breast with neuro-endocrine features.

Actins↗

Acinic cell carcinoma of the breast: an immunohistochemical and ultrastructural study.

The clinicopathological features of six cases of breast carcinomas showing features of acinic cell differentiation, which are similar to those seen in homologous tumors of salivary glands, are presented. The patients, all women, were 35-80 years of age. One case recurred after 4 years, and in two cases axillary lymph node metastases were found at the time of surgery. Histologically the tumors showed a microglandular pattern merging with solid areas. Cytologically, immunohistochemically, and ultrastructurally the tumors were very similar to cases of acinic cell carcinoma of the parotid gland. The differential diagnostic criteria with microglandular adenosis and carcinomas showing granular cytoplasm are discussed. It seems that acinic cell carcinomas of the breast have to be added to the long list of tumors that affect the salivary glands and can also arise in the breast.

Adult↗

Primary neuroendocrine carcinoma with ganglion cell differentiation in a crural lymph node.

A primary neuroendocrine carcinoma with ganglion cell differentiation is described in a crural lymph node. The patient, a 48-year-old woman, presented a palpable lymph node of the crural region in March 1994. Histologically, the lesion was composed mostly of small cells immunoreactive for cytokeratins, neuron specific enolase and synaptophysin. The small cells merged gradually with areas containing ganglion cells immersed in a fibrillar matrix resembling neuropil. Ganglion cells expressed neuron-specific enolase, synaptophysin, neurofilament proteins and S-100 protein. Moreover, a minority of them featured cytokeratin expression. Electron microscopy was performed in the small cell component. These cells featured attenuated desmosomes and electron dense granules with an average size of 120 nm within bundles of intermediate filaments. Clinically, no tumour was found elsewhere despite extensive work-up over the 76-month follow-up period. Although similarities with previous cases of primary neuroendocrine carcinoma of lymph node, ganglion cell differentiation has never been described.

Carcinoma, Neuroendocrine↗

Small cell neuroendocrine carcinoma with skeletal muscle differentiation: report of three cases.

Three cases of neuroendocrine carcinoma showing skeletal muscle differentiation are presented. The tumors were located in the skin and subcutaneous tissue, the urinary bladder, and the nasal cavity respectively, and were composed by two cell types admixed intimately with each other. One cell type had features identical to those seen in conventional small cell neuroendocrine carcinoma, including scanty cytoplasm, round nuclei with fine granular chromatin, immunohistochemical reactivity for neuron-specific enolase, chromogranin and cytokeratins, and electron-dense granules on ultrastructural examination. The second cell type was either plasmacytoid or elongated and straplike, with abundant eosinophilic cytoplasm and irregular nuclei with prominent nucleoli. These cells showed immunohistochemical positivity for desmin, sarcomeric actin, myoglobin, and myogenin. They also exhibited ultrastructural evidence of rhabdomyoblastic differentiation in the form of contractile filaments with abortive Z-band formation. An origin from a cell capable of dual differentiation toward neuroendocrine and rhabdomyoblastic elements is postulated for these tumors.

Aged↗