Papers by Francesca Garbini
Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, characterized by comp... more Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, characterized by complex pathophysiology, heterogeneous morphology, and variable clinical manifestations over time. Besides cardiac hypertrophy, the HCM phenotype is characterized by a host of manifestations, including mitral valve and subvalvar abnormalities, subaortic and mid-ventricular left ventricular (LV) obstruction, microvascular dysfunction, myocardial fibrosis, disarray, atrial remodeling, myocardial bridging of epicardial coronary arteries, LV apical aneurysms, and autonomic nervous system abnormalities. Such heterogeneous phenotype still lacks a comprehensive explanation, which cannot be accounted solely by genetic heterogeneity, despite the large number of genes and mutations involved. It is likely that pre-natal and acquired features deriving from the primary genetic defect interact with the environment to produce the final result evident in each patient. Based on novel insights provided by cardiac developmental biology, a common lineage ancestry of several HCM manifestations might be traced back to the pluripotent epicardium-derived cells, which early during heart development differentiate into interstitial fibroblasts, coronary smooth muscle cells, and atrio-ventricular endocardial cushions as mesenchymal cells. To date, the different faces of HCM have not been sufficiently liked or explained. We here attempt to address these issues by describing the various components of the disease, their origin, interaction, and clinical significance.
The Journal of Thoracic and Cardiovascular Surgery, 2010
Objectives: The relevance of iatrogenic left coronary artery fistulas complicating surgical myect... more Objectives: The relevance of iatrogenic left coronary artery fistulas complicating surgical myectomy in patients with hypertrophic cardiomyopathy is not known. We prospectively defined the echocardiographic features, prevalence, and clinical significance of left coronary artery fistulas in 40 consecutive patients with hypertrophic cardiomyopathy undergoing extended septal myectomy. Methods: Echocardiographic analysis was performed preoperatively and 1 and 6 months after surgical intervention. Diagnosis of left coronary artery fistulas required evidence of diastolic flow draining from the left ventricular wall into the left ventricular cavity according to prespecified criteria. Results: Left coronary artery fistulas were detected in 9 (23%) of the 40 study patients as a single occurrence in all except 1 patient, who had multiple fistulas. At 6 months, left coronary artery fistulas could still be detected in only 2 of the 9 patients. Of these, 1 patient remained asymptomatic but continued to show left coronary artery fistula persistence at 37 months postoperatively. The other, a woman with prior alcohol septal ablation, had progressive severe symptoms that required percutaneous closure of the fistula with a covered stent after angiographic identification of a large first septal branch fistula associated with distal left anterior descending coronary artery steal. Conclusions: In patients with hypertrophic cardiomyopathy, left coronary artery fistulas are common in the early period after surgical myectomy, although their echocardiographic prevalence is dependent on operator awareness. Most left coronary artery fistulas heal spontaneously. Occasionally, however, fistulas can persist and cause symptoms requiring therapeutic intervention.
Clinical and experimental rheumatology
To diagnose a probable case of rheumatoid arthritis in a mummified female body from the 16th cent... more To diagnose a probable case of rheumatoid arthritis in a mummified female body from the 16th century and to backdate the first clinical diagnosis, entering the diatribe regarding the ancientness of the disease. Image techniques such as normal X-ray, X-ray by mammography, total body CT and high resolution CT were used. Microscopic examination by stereomicroscopy was performed. Samples of tissue were submitted to histology. These data and the review of past literary references, of artistic representations and of paleopathological cases provided an interesting contribution to reconstruct the history of the disease. The body of the "Braids Lady" showed all the "stigmata" of the disease. The left hand revealed large erosions of the metacarpophalangeal joints of both the third and the fourth fingers, volar metacarpophalangeal subluxation of both the third and the fourth fingers and lateral deviation of all the fingers. The carpus showed some minute and marginal erosion...
Tumori Journal, 2008
Aims and Background Colorectal cancer is the second most common cause of cancer-related death in ... more Aims and Background Colorectal cancer is the second most common cause of cancer-related death in Europe and the United States. Several studies have evaluated the immune response to colorectal cancer, with contradictory results. Some studies showed that lymphocyte infiltration in colorectal cancer seemed to be an important prognostic parameter, a finding not confirmed by other studies. Several studies showed the gamma-delta T-cell receptor repertoire of intestinal adenocarcinoma. In this study, we hypothesize that the presence of T cells with the T-cell receptor gamma complex may play a particular role in carcinogenesis and tumor progression. Methods A total of 58 patients with colon adenocarcinoma was included in the analysis. We used the TNM staging system to grade colon cancer. Results Thirty samples (52.6%) revealed a polyclonal rearrangement of T-cell receptor gamma. In the N0 cases, only 5 samples revealed a T-cell receptor gamma molecular assessment; in N1/N2 cases, 25 reveale...
Tumori Journal, 2008
Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tr... more Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract. Until today, there have been few markers specific for the tumor. This has complicated the differential diagnosis of the neoplasm from tumors of smooth muscle origin. Recently, the proto-oncogene c-kit has been shown to be a very relevant marker as it almost invariably is expressed in gastrointestinal stromal tumors. Radiation exposure, hormonal and genetic factors, particularly neurofibromatosis 2, have been implicated in their development and growth. GIST initiation, either in NF2-associated or in sporadic cases, is linked to inactivation of members of the proteins 4.1 superfamily. The majority of the mutations identified in the NF2 gene result in a truncated protein and are clinically associated with a severe phenotype. Occasionally, missense mutations associated with a mild phenotype may occur. We compared NF2 gene expression in 5 cases with gastrointestinal stromal tumors by qua...
Pathologica, 2009
Gestational diabetes insipidus (GDI) refers to the state of excessive water intake and hypotonic ... more Gestational diabetes insipidus (GDI) refers to the state of excessive water intake and hypotonic polyuria. Those cases manifesting in pregnancy and referred to as GDI may persist thereafter or may be a transient latent form that resolves after delivery. Microscopic examination of affected subjects has not been previously reported. In the literature, there are various case reports and case series on diabetes insipidus in pregnancy. In this study, we present a case that had transient diabetes insipidus during pregnancy in which the placenta was examined.
Case reports in medicine, 2009
A 42-year-old man with a cardiac tamponade underwent an urgent pericardiotomy that showed tumoral... more A 42-year-old man with a cardiac tamponade underwent an urgent pericardiotomy that showed tumoral tissue, covering the surface of the right atrium. The tumor was then partially excised, and the histological examination revealed the presence of a moderately-differentiated angiosarcoma. The patient was then referred to the oncology unit and scheduled for a chemotherapy schedule including Epirubicin (60 mg/m(2), on days 1 and 2) plus Ifosfamide (2000 mg/m(2), on days 1 to 3) and Uromitexan (2000 mg/m(2) at hours 0, 4, 8 after IFO). All drugs were administered every three weeks. After two cycles, a restaging work-up revealed a partial remission. The treatment was continued for another two cycles. A new evaluation by cardiac MRI evidenced a local and distant (lung) progression of disease. The patient died after three months. This paper confirms that cardiac angiosarcoma is a fatal disease, and the prognosis is usually 6-11 months from time of diagnosis.
Pathologica, 2008
Acute renal failure occurring in pregnancy or postpartum is often associated with preeclampsia, H... more Acute renal failure occurring in pregnancy or postpartum is often associated with preeclampsia, HELLP syndrome or haemolytic uremic syndrome: differential diagnosis may be difficult due to the overlapping symptoms of these syndromes. We report our experience on diagnosis, management and outcome of women with pregnancy associated haemolytic uremic syndrome, focusing on placental features.
Neuropathology, 2010
Lipoastrocytoma is an extremely rare tumor, with only six cases described. We report the case of ... more Lipoastrocytoma is an extremely rare tumor, with only six cases described. We report the case of an astrocytoma involving the upper part of the cerebellar-pontine angle and the right portion of the clivus starting from the brainstem with a diffuse lipomatous component in a 39 year-old man. The patient was admitted with headache of 1 year's duration and diplopia over the previous 3 months. MRI revealed a ponto-cerebellar lesion that showed irregular enhancement after contrast administration. Subtotal excision of the tumor was accomplished. Adjuvant chemotherapy and radiation therapy were not administered. Histologically the tumor showed the classical histology of low-grade astrocytoma and a portion of the lesion was composed of lipid-laden cells. Immunohistochemistry for glial fibrillary acid and S-100 proteins clearly demonstrated the glial nature of these cells. Ki-67/Mib-1 labeling index was low (2%). The patient remains in good neurological conditions after 10 months. Our case has a benign postoperative behavior, also after subtotal excision, with restrictions due to the short follow-up. It is important to record each new case of this rare tumor to produce a better characterization of this lesion.
Neuropathology, 2007
One of the most common regions involved in the meningiomas tumorigenesis is chromosome 22q where ... more One of the most common regions involved in the meningiomas tumorigenesis is chromosome 22q where the NF2 gene resides. The deficiency or loss of the NF2 gene product, merlin/schwannomin, plays a role in tumor development and metastatization. Conflicting results have been reported on the prognostic value of merlin in meningiomas. Several studies have indicated NF2 gene inactivation as an early tumorigenic event unrelated to the histological grade or clinical behavior. On the contrary, the NF2 gene alteration rate differs between the different histotypes. A pathogenesis independent from the NF2 gene has been suggested in meningothelial meningiomas. In the present work, we studied the NF2 gene expression through real time-PCR (RT-PCR) in 30 meningiomas. The average of the NF2 gene expression of all meningiomas was considered as reference value. The average of expression of WHO grade I and II meningiomas was higher than the average of all meningiomas, whereas that of WHO grade III meningiomas was lower. When we compared the NF2 gene expression in the different meningioma grades we did not note a significant difference (P = 0.698) despite the tendency to decrease from grade I to grade III. The average expression of meningothelial meningiomas was higher than the reference value, and that of non-meningothelial meningiomas was lower. The difference in NF2 gene expression between meningothelial and non-meningothelial meningiomas was statistically significant (P = 0.013). Our data supports the finding that alterations in NF2 gene alteration are histotype related but not grade related.
Journal of Pediatric Hematology/Oncology, 2011
Herein, we describe an intracerebral primary low-grade myxofibrosarcoma occurring in a 9-year-old... more Herein, we describe an intracerebral primary low-grade myxofibrosarcoma occurring in a 9-year-old boy. The lesion measured 7 cm and occupied the left parieto-occipital region. A gross-total removal of the tumor was performed. Nine months later, radiologic follow-up revealed a local recurrence which was again surgically removed. The patient then underwent radiotherapy and chemotherapy. He was well and disease-free at 6 months follow-up. The tumor was composed of spindle, stellated, and multinucleated cells embedded in a myxoid background. Foci of increased cellularity, pleomorphism, and high mitotic rate were present. The tumor borders were sharply demarcated from the non-neoplastic nervous parenchyma. Immunohistochemical staining showed that the neoplastic cells were vimentine and CD34 positive. Fluorescence in-situ hybridization analyses did not show FUS and EWSR1 gene rearrangements. Primary intracranial myxofibrosarcomas are very rare (to the best of our knowledge, less than 10 published cases in the international literature). We believe each new case should be recorded to produce a better clinical, pathologic, molecular, prognostic, and therapeutic characterization of this lesion.
Journal of Chemotherapy, 2008
Ependymomas are the third most common brain tumor in children. The post surgical management is co... more Ependymomas are the third most common brain tumor in children. The post surgical management is controversial. There are no convincing data on an effective role for chemotherapy. O(6)-Methylguanine-DNA-Methyltransferase (MGMT) is a DNA repair protein considered to be a chemosensitivity predictor. Hypermethylation of the MGMT gene promoter is an important cause of MGMT inactivation. We evaluated the MGMT gene promoter methylation and the immunohistochemical MGMT protein expression in 12 recurrent anaplastic ependymomas affecting children. Our purpose was to investigate the molecular rationale of the administration of alkylating agents to children affected by recurrent anaplastic ependymomas. All ependymomas lacked MGMT promoter hypermethylation and 9 (75%) showed high MGMT protein expression (>50% tumoral cells). Differences between different recurrences in the same patient were not observed. These results may indicate MGMT as a factor of chemoresistance to alkylating drugs in anaplastic ependymomas and support the uncertainties regarding the actual benefit of chemotherapy for patients with anaplastic ependymomas.
International Journal of Gynecological Cancer, 2006
Surgery is the treatment of choice for uterine carcinosarcomas; nevertheless, the poor effect of ... more Surgery is the treatment of choice for uterine carcinosarcomas; nevertheless, the poor effect of chemotherapy and radiotherapy represents an insidious problem for patients with metastatic or unresectable disease, and indeed, new therapeutic approaches are clearly required to improve survival of uterine carcinosarcoma patients. The HER-2 oncogene, located on chromosome 17, encodes for a tyrosine kinase growth factor receptor. We analyzed HER-2/neu overexpression by immunohistochemistry in 28 uterine carcinosarcomas. HER-2/neu amplification with fluorescence in situ hybridization (FISH) was tested in positive cases. The expression of HER-2/neu was correlated with disease-free interval and survival (Kaplan-Meier estimates). We observed HER-2/neu overexpression in nine cases (32.1%) and HER-2/neu amplification in all the four HER-2/neu 31 score positive cases tested by FISH. HER-2/neu expression was not correlated with clinical outcome. Patients with disease limited to the uterus (stages I-II) displayed a significantly better diseasefree survival (P ¼ 0.004) and actuarial survival (P ¼ 0.01). Demonstration of HER-2/neu overexpression and amplification in uterine carcinosarcoma may represent the first rationale step for further investigations. Hence, the results of this analysis may support the challenge of a new therapeutic approach, which could test the role of anti-HER-2 (trastuzumab) in patients with advanced or metastatic uterine carcinosarcoma.
Gynecologic and Obstetric Investigation, 2008
Aims: The aim of this study was to evaluate the utility of liquid-based cytology for endometrial ... more Aims: The aim of this study was to evaluate the utility of liquid-based cytology for endometrial surveillance in patients receiving tamoxifen. Methods: One hundred and sixty-eight women scheduled for hysteroscopy were enrolled in the study. The women sequentially underwent hysteroscopy, endometrial cytology and biopsy. Results: Endometrial biopsy only was inadequate in 112 (67%) patients, both endometrial biopsy and cytology were inadequate in 19 (11%) patients, endometrial cytology only was inadequate in 4 (2%) patients, and both endometrial biopsy and cytology were adequate in 33 (20%) patients. Overall, endometrial biopsy was inadequate in 131 (78%) patients and endometrial cytology in 23 (14%) patients. Endometrial cytology provided sufficient material for diagnosis more often than endometrial biopsy (p < 0.05). In the series of 33 patients (20%) in whom both endometrial cytology and biopsy were adequate, there was a 100% correlation between the endometrial cytology and biops...
Diagnostic Molecular Pathology, 2008
Diagnostic Cytopathology, 2008
... Francesca Garbini MD 1,* ,; Anna Maria Buccoliero MD 1 ,; Francesca Castiglione MD 1 ,; Chiar... more ... Francesca Garbini MD 1,* ,; Anna Maria Buccoliero MD 1 ,; Francesca Castiglione MD 1 ,; Chiara Francesca Gheri MD 1 ,; Daniela Moncini MD 1 ,; Duccio Rossi Degl'Innocenti B.Sc. 1 ,; Alfredo Barbetti B.Sc. 1 ,; Alessandro Villanucci MD 2 ,; Gian Luigi Taddei MD 1. ...
Diagnostic Cytopathology, 2007
Liquid-based cytology represents an opportunity to re-evaluate endometrial cytology. We evaluated... more Liquid-based cytology represents an opportunity to re-evaluate endometrial cytology. We evaluated the accuracy of liquid-based endometrial cytology as compared to biopsy in 670 women scheduled for histeroscopy because of thickened endometrium (>4 mm), as evaluated by transvaginal sonography. Endometrial biopsy detected pathology in 41 (6%) of cases (21 of which were adenocarcinomas). Cytologic study found pathology in 62 (9%) cases (19 of which were adenocarcinomas). Two hundred ninety-one biopsies (43%) and 28 (4%) cytologies were inadequate. The sensitivity and the specificity were estimated, respectively, at 95% and 98%; the positive and negative predictive values were estimated, respectively, at 83% and 99%. Cytology provided sufficient material more often than biopsy (P < 0.01). We consider endometrial cytology an efficacious diagnostic opportunity. It could be usefully applied in association with transvaginal sonography. The combination of these procedures might reduce more invasive and expensive diagnostic procedures.
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Papers by Francesca Garbini