Kyphomelic dysplasia (KD) is a rare autosomal recessive entity characterized by disproportionate ... more Kyphomelic dysplasia (KD) is a rare autosomal recessive entity characterized by disproportionate dwarfism with shortening and bowing of the limbs, narrow chest, 11 ribs and metaphyseal flaring. Mental development is generally normal. We report the in utero ultrasound appearances and post-mortem radiographic findings of a 22-week-old male fetus suggestive of KD. A review of 19 previously reported patients with KD is also presented.
Virchows Archiv A Pathological Anatomy and Histology, 1982
A case of juvenile secretory carcinoma of the breast is reported. The tumor occured in a 19 yr-ol... more A case of juvenile secretory carcinoma of the breast is reported. The tumor occured in a 19 yr-old nulliparous woman and was treated by local resection; it recurred 7 years later. Slight infiltration of the pectoral muscle, metastatic involvement of one lymph node and multifocal areas of carcinoma were found at radical mastectomy. No further recurrence has been detected after 1 year. This case confirms the slow evolution of this neoplasm but stresses that its behaviour is not always as indolent as previously believed. We have used histochemical techniques for mucins (PAS, Alcian Blue) and immunoperoxidase methods for milk proteins (MFGM, fl-Casein, c~-lactalbumin), for myoepithelial cells (actin) and for oncofetal antigens (CEA). Our results suggest that: Immunoperoxidase methods for milk proteins are a more specific and reliable marker than PAS staining in characterizing the secretory activity of juvenile carcinoma. The absence of myoepithelial cells in infiltrative areas detected by immunoperoxidase methods for actin confirms the low degree of organization in this well differentiated carcinoma of limited aggressiveness which secretes milk proteins.
Arteriovenous fistulas of the placenta rarely occur in singleton pregnancies. This report describ... more Arteriovenous fistulas of the placenta rarely occur in singleton pregnancies. This report describes the fetal and neonatal hemodynamic pattern in a singleton gestation in which multiple placental artery-to-vein anastomoses were associated with a large atrial septal defect and a single umbilical artery with an anomalous connection of the persistent right and left umbilical veins. Possible links between the extracardiac vascular malformation and the congenital heart defect are discussed.
... Correspondence. Increased nuchal translucency in the first trimester as a sign of osteogenesi... more ... Correspondence. Increased nuchal translucency in the first trimester as a sign of osteogenesis imperfecta. Elsa Viora 1,* ,; Andrea Sciarrone 1 ,; Simona Bastonero 1 ,; Giuseppe Errante 1 ,; Mario Campogrande 1 ,; Giovanni Botta 2 ,; Piergiorgio Franceschini 3. ...
The RAF1:p.Ser257Leu variant is associated with severe Noonan syndrome (NS), progressive hypertro... more The RAF1:p.Ser257Leu variant is associated with severe Noonan syndrome (NS), progressive hypertrophic cardiomyopathy (HCM), and pulmonary hypertension. Trametinib, a MEK-inhibitor approved for treatment of RAS/MAPK-mutated cancers, is an emerging treatment option for HCM in NS. We report a patient with NS and HCM, treated with Trametinib and documented by global RNA sequencing before and during treatment to define transcriptional effects of MEK-inhibition. A preterm infant with HCM carrying the RAF1:p.Ser257Leu variant, rapidly developed severe congestive heart failure (CHF) unresponsive to standard treatments. Trametinib was introduced (0.022 mg/kg/day) with prompt clinical improvement and subsequent amelioration of HCM at ultrasound. The appearance of pulmonary artery aneurysm and pulmonary hypertension contributed to a rapid worsening after ventriculoperitoneal shunt device placement for posthemorrhagic hydrocephalus: she deceased for untreatable CHF at 3 months of age. Autopsy s...
A DNA microspectrofluorimetric study on smears from cells detached from paraffin embedded tissue ... more A DNA microspectrofluorimetric study on smears from cells detached from paraffin embedded tissue is presented. The cellular DNA values of these smears were compared with the cellular DNA values of fresh imprints and paraffin embedded sections obtained from the same tissue. The histograms were similar for fresh imprints and paraffin embedded smears while the DNA values in the sections were notably different. This method appears very suitable for retrospective studies of DNA using microspectrofluorimetry in routine histopathology.
Objectives To evaluate the accuracy of ultrasound in the diagnosis of placenta accreta and its va... more Objectives To evaluate the accuracy of ultrasound in the diagnosis of placenta accreta and its variants, and to assess the impact of prenatal diagnosis in our population. Methods A total of 314 women with placenta previa were enrolled prospectively and underwent transabdominal and transvaginal ultrasound examinations. An ultrasound diagnosis (grayscale and color/power Doppler) of placental attachment disorder (PAD) was based on the detection of at least two of the following ('two-criteria system'): loss/irregularity of the retroplacental clear zone, thinning/interruption of the uterine serosa-bladder wall interface, turbulent placental lacunae with high velocity flow, myometrial thickness < 1 mm, increased vascularity of the uterine serosa-bladder wall interface, loss of vascular arch parallel to the basal plate and/or irregular intraplacental vascularization. Definitive diagnosis was made at delivery by Cesarean section. Maternal outcome in cases diagnosed antenatally was compared with that in cases diagnosed at delivery. Results There were 37/314 cases of PAD (29 anterior and eight posterior). The two-criteria system identified 30 cases of placenta accreta, providing a sensitivity of 81.1% and specificity of 98.9%. When anterior and posterior placentae were considered separately, the detection rates of PAD were 89.7 and 50.0%, respectively. Maternal outcome was better in women with prenatal diagnosis of PAD, as seen by less blood loss and shorter hospitalization.
Lobular Neoplasia of the breast, a term which we prefer to that of Lobular Carcinoma in Situ, is ... more Lobular Neoplasia of the breast, a term which we prefer to that of Lobular Carcinoma in Situ, is a multifocal microscopic entity of uncertain and controversial clinical significance. Lobular Neoplasia is a incidental histological finding among otherwise benign breast biopsies (0.5%-3.5%) depending mainly upon the diagnostic intensity. Its extent is rarely so massive that it makes up a palpable tumor. Although this lesion may be demonstrated at all ages after puberty it occurs most often in premenopausal women. The multicentricity is not below 70% and bilateral occurrence not below 30-35%. Demonstration of Lobular Carcinoma in situ means a 7-12 times greater risk of later developing invasive breast carcinoma as compared with an age corrected general population. Both breast are at risk and about one half of these subsequent carcinomas will develop in the controlateral breast. Attempts at correlating the histological appearances in Lobular Neoplasia with the subsequent occurrence of in...
Virchows Archiv. B, Cell pathology including molecular pathology, 1980
The distribution of the myoepithelial cells in 32 cases of ductal carcinoma-in-situ (DCIS) of the... more The distribution of the myoepithelial cells in 32 cases of ductal carcinoma-in-situ (DCIS) of the breast (11 not associated, 21 associated with invasive carcinoma) was investigated with a recently developed immunoperoxidase method for actin. Actin-rich myoepithelial cells were detected at the periphery of some ducts, however, their presence was neither constant nor continuous. Large areas of DCIS were devoid of a myoepithelial cell layer and the neoplastic cells were directly in contact with the stroma. No differences related to the histological pattern of DCIS or the presence and absence of invasive carcinoma were noted. The behaviour of the myoepithelial cells in ductal carcinoma appears different from that observed in cases of lobular carcinoma (Bussolati 1980) and of cystic disease, and may thus be of diagnostic interest. The selective destruction of myoepithelial cells in cases of DCIS might result in a focal disruption of the basement membrane, thus faciliatating invasion.
Tumoral Carcino Embryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) expression was inves... more Tumoral Carcino Embryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) expression was investigated by immunoperoxidase technique on paraffin embedded tissues of 191 patients with infiltrating breast cancer and negative axillary nodes. TPA was almost always detected at high levels. CEA staining was evenly distributed, but high CEA positivity was associated with higher TPA expression. Lower levels of both markers were found in medullar carcinomas as well as in cancers larger than 1 cm. Higher estrogen and progesterone receptor content was associated with higher expression of tissue CEA and TPA. After a median follow-up of 9 years, neither tissue CEA nor tissue TPA show any prognostic value.
Between 1978 and 1986 we treated 318 consecutive patients with stage I breast cancer. Median foll... more Between 1978 and 1986 we treated 318 consecutive patients with stage I breast cancer. Median follow-up time is 8.5 years. In all cases the invasion of peritumoral lymphatic (LVI) and blood vessels (BVI) was studied by the hematoxylin-eosin staining method. Different ten-year survival (86% vs 67%) and disease-free survival (82% vs 61%) probabilities were found in patients with or without LVI. BVI showed low sensitivity and specificity, therefore vessel invasion was reassessed on 190 specimens with the immunoperoxidase technique using the Ulex Europeus Type 1 lectine. A significant correlation between the vessel staining intensity and the presence of intraluminal metastases was found. With this method a better sensitivity was obtained, but it was associated with a loss of specificity and prognostic significance.
To describe the cytogenetic and FISH characterization of a prenatally diagnosed de novo complex c... more To describe the cytogenetic and FISH characterization of a prenatally diagnosed de novo complex chromosome rearrangement (CCR), showing the involvement of four chromosomes and six breakpoints, and review the literature concerning prenatally detected CCRs in order to obtain insights into addressing karyotype-phenotype correlations in prenatal genetic counseling. Conventional protocols were used to set up cultures and chromosome preparations. Commercial and homemade probes were used for the FISH analyses. An apparently balanced de novo t(4;10;20) was prenatally identified by means of cytogenetic analysis. FISH revealed a rearrangement mediated by six breakpoints and the insertion of chromosome 8 material within the 4q region. The pregnancy was interrupted. The fetus showed malformations and anomalous cortical neuron migration. The assembled list of 20 prenatally detected CCRs points to the preferential involvement of chromosomes 4, 6 and 14. The involvement of chromosome 20 is described here for the first time. FISH analysis is essential for the accurate definition of a complex rearrangement. Phenotype description of fetuses carrying CCRs investigated by means of molecular cytogenetic techniques may contribute to improving and personalizing genetic counseling in prenatal diagnosis.
Prevalence of congenital heart disease increases with nuchal translucency (NT) thickness. First-t... more Prevalence of congenital heart disease increases with nuchal translucency (NT) thickness. First-trimester fetal bradycardia may result from heart block associated with complex congenital heart disease. We report two cases detected in the first trimester of pregnancy, in which both fetuses showed an increased nuchal translucency and bradycardia. Fetal karyotype was normal in both fetuses. First-trimester fetal echocardiography was performed and, in both cases, complex congenital heart disease was diagnosed. We discuss the added role of fetal heart rate in first-trimester ultrasound screening, in fetuses with increased nuchal translucency and normal karyotype. We stress, as well, the importance of echocardiography performed in the first trimester as a potential tool for early diagnosis in selected cases.
Frozen section diagnosis (FSD) given in 4436 consecutive breast biopsies performed in 5 years in ... more Frozen section diagnosis (FSD) given in 4436 consecutive breast biopsies performed in 5 years in a single pathology laboratory were checked against the final pathological report. In 4284 cases (96.57%) there was no difference between the FSD and the definitive diagnosis. There were 74 (1.66%) false negative reports and no false positive diagnoses. The diagnosis was deferred to paraffin sections in 78 cases (1.75% of biopsies). The predictive value for positive results was 100% and for negative results 97.5%; the specificity was 100%, the sensitivity 94.6% and the accuracy 98.3%. Minimal breast cancer, in situ (CIS) especially, was the main source of false negative reports. In non minimal invasive cancers (NMIC) FSD was correct in 99.42%. In minimal invasive cancers (MIC) FSD was correct in 80.21%, false negatives and deferred diagnosis increased to 8.79% and 10.98%. In CIS false negatives increased to 76.82% and deferred diagnoses to 12.19%. The sensitivity of fine needle aspiration, performed before biopsy in a portion of the patients, was lower than FSD in NMIC (71.39% versus 99.21%) and in MIC (41.66% versus 80.55%), identical to FSD in CIS (7.40% versus 7.40%). The value of cytodiagnosis in addressing surgery is discussed.
To evaluate the role of histology in diagnosis and management of biologically benign heart tumors... more To evaluate the role of histology in diagnosis and management of biologically benign heart tumors causing life-threatening symptoms and even death in children and fetuses. The clinical impact of a multidisciplinary approach including 2-D echocardiography, histology, genetics, and cardiac surgery has not yet been fully elucidated. Forty-one consecutive antenatal (n = 17) or postnatal (n = 24) detected cardiac masses were evaluated by 2-D echocardiography (in alive patients) or at autopsy, and 12/41 cases with definite histologic diagnosis of primary and benign cardiac tumor were entered in this study. Rhabdomyomas (n = 6), hemangiomas (n = 3), central fibrous body chondroma (n = 1), fibroma (n = 1), or left atrial myxoma (n = 1) were histologically diagnosed in 4 fetuses and in 8 children. Death occurred in 6 patients showing diffuse or infiltrative tumors, 2/6 experiencing intrauterine death or sudden and unexpected infant death. Seven patients underwent surgery, 4/7 are alive and well at &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5 years follow-up, whereas 3 deaths followed partial tumor resection. Two fetuses with extensive tumor/s were aborted. Tuberous sclerosis complex gene mutations were seen in patients with rhabdomyomas. Histology represents the best diagnostic approach in life-threatening pediatric cardiac tumors allowing definite diagnosis in cases other than rhabdomyoma and in sudden deaths, influencing clinical management and counselling. 2-D echocardiography remains the main tool for early clinical diagnosis and follow-up. A multidisciplinary approach is advisable because of rarity, difficult management, and possible associations with inheritable diseases.
The value of immunocytochemical methods for detecting seven tumour-associated antigens was assess... more The value of immunocytochemical methods for detecting seven tumour-associated antigens was assessed in ten cases of bone metastases from carcinoma of the breast. In order to obtain the optimal preservation of both their structure and antigenicity, the biopsies were fixed-decalcified in Bouin's fluid by means of an apparatus based on ion-exchange resins recently developed in this laboratory. Of the different tumour markers, milk fat globule membrane antigen and carcino-embryonic antigen were found to be present in the majority of the cases of neoplastic cells. These two markers appear, therefore, to be the most useful for the immunocytochemical identification of metastatic neoplastic cells in the bone marrow originating from carcinoma of the breast.
Advances in ultrasound technology and sonographer&amp;amp;#39;s experience lead to the descri... more Advances in ultrasound technology and sonographer&amp;amp;#39;s experience lead to the description of many rare syndromes and malformations through prenatal diagnosis. Diaphragmatic hernia is a rather common malformation but can be an indicator of different syndromes. We report the prenatal diagnosis of lethal multiple pterygium syndrome type II which has been established in the 34th week of pregnancy. The sonographically detectable symptoms consisted of polyhydramnios, hygroma colli, diaphragmatic hernia, scoliosis, short forearms, hypokinesia of the fetus and pterygia over the large joints. Labour was induced in the 34th week of pregnancy; the neonate died shortly after vaginal delivery as a result of the pulmonary hypoplasia. A multidisciplinary approach in prenatal assessment may help to clarify difficult diagnostic problems and may be of direct benefit for the pregnant patient.
Kyphomelic dysplasia (KD) is a rare autosomal recessive entity characterized by disproportionate ... more Kyphomelic dysplasia (KD) is a rare autosomal recessive entity characterized by disproportionate dwarfism with shortening and bowing of the limbs, narrow chest, 11 ribs and metaphyseal flaring. Mental development is generally normal. We report the in utero ultrasound appearances and post-mortem radiographic findings of a 22-week-old male fetus suggestive of KD. A review of 19 previously reported patients with KD is also presented.
Virchows Archiv A Pathological Anatomy and Histology, 1982
A case of juvenile secretory carcinoma of the breast is reported. The tumor occured in a 19 yr-ol... more A case of juvenile secretory carcinoma of the breast is reported. The tumor occured in a 19 yr-old nulliparous woman and was treated by local resection; it recurred 7 years later. Slight infiltration of the pectoral muscle, metastatic involvement of one lymph node and multifocal areas of carcinoma were found at radical mastectomy. No further recurrence has been detected after 1 year. This case confirms the slow evolution of this neoplasm but stresses that its behaviour is not always as indolent as previously believed. We have used histochemical techniques for mucins (PAS, Alcian Blue) and immunoperoxidase methods for milk proteins (MFGM, fl-Casein, c~-lactalbumin), for myoepithelial cells (actin) and for oncofetal antigens (CEA). Our results suggest that: Immunoperoxidase methods for milk proteins are a more specific and reliable marker than PAS staining in characterizing the secretory activity of juvenile carcinoma. The absence of myoepithelial cells in infiltrative areas detected by immunoperoxidase methods for actin confirms the low degree of organization in this well differentiated carcinoma of limited aggressiveness which secretes milk proteins.
Arteriovenous fistulas of the placenta rarely occur in singleton pregnancies. This report describ... more Arteriovenous fistulas of the placenta rarely occur in singleton pregnancies. This report describes the fetal and neonatal hemodynamic pattern in a singleton gestation in which multiple placental artery-to-vein anastomoses were associated with a large atrial septal defect and a single umbilical artery with an anomalous connection of the persistent right and left umbilical veins. Possible links between the extracardiac vascular malformation and the congenital heart defect are discussed.
... Correspondence. Increased nuchal translucency in the first trimester as a sign of osteogenesi... more ... Correspondence. Increased nuchal translucency in the first trimester as a sign of osteogenesis imperfecta. Elsa Viora 1,* ,; Andrea Sciarrone 1 ,; Simona Bastonero 1 ,; Giuseppe Errante 1 ,; Mario Campogrande 1 ,; Giovanni Botta 2 ,; Piergiorgio Franceschini 3. ...
The RAF1:p.Ser257Leu variant is associated with severe Noonan syndrome (NS), progressive hypertro... more The RAF1:p.Ser257Leu variant is associated with severe Noonan syndrome (NS), progressive hypertrophic cardiomyopathy (HCM), and pulmonary hypertension. Trametinib, a MEK-inhibitor approved for treatment of RAS/MAPK-mutated cancers, is an emerging treatment option for HCM in NS. We report a patient with NS and HCM, treated with Trametinib and documented by global RNA sequencing before and during treatment to define transcriptional effects of MEK-inhibition. A preterm infant with HCM carrying the RAF1:p.Ser257Leu variant, rapidly developed severe congestive heart failure (CHF) unresponsive to standard treatments. Trametinib was introduced (0.022 mg/kg/day) with prompt clinical improvement and subsequent amelioration of HCM at ultrasound. The appearance of pulmonary artery aneurysm and pulmonary hypertension contributed to a rapid worsening after ventriculoperitoneal shunt device placement for posthemorrhagic hydrocephalus: she deceased for untreatable CHF at 3 months of age. Autopsy s...
A DNA microspectrofluorimetric study on smears from cells detached from paraffin embedded tissue ... more A DNA microspectrofluorimetric study on smears from cells detached from paraffin embedded tissue is presented. The cellular DNA values of these smears were compared with the cellular DNA values of fresh imprints and paraffin embedded sections obtained from the same tissue. The histograms were similar for fresh imprints and paraffin embedded smears while the DNA values in the sections were notably different. This method appears very suitable for retrospective studies of DNA using microspectrofluorimetry in routine histopathology.
Objectives To evaluate the accuracy of ultrasound in the diagnosis of placenta accreta and its va... more Objectives To evaluate the accuracy of ultrasound in the diagnosis of placenta accreta and its variants, and to assess the impact of prenatal diagnosis in our population. Methods A total of 314 women with placenta previa were enrolled prospectively and underwent transabdominal and transvaginal ultrasound examinations. An ultrasound diagnosis (grayscale and color/power Doppler) of placental attachment disorder (PAD) was based on the detection of at least two of the following ('two-criteria system'): loss/irregularity of the retroplacental clear zone, thinning/interruption of the uterine serosa-bladder wall interface, turbulent placental lacunae with high velocity flow, myometrial thickness < 1 mm, increased vascularity of the uterine serosa-bladder wall interface, loss of vascular arch parallel to the basal plate and/or irregular intraplacental vascularization. Definitive diagnosis was made at delivery by Cesarean section. Maternal outcome in cases diagnosed antenatally was compared with that in cases diagnosed at delivery. Results There were 37/314 cases of PAD (29 anterior and eight posterior). The two-criteria system identified 30 cases of placenta accreta, providing a sensitivity of 81.1% and specificity of 98.9%. When anterior and posterior placentae were considered separately, the detection rates of PAD were 89.7 and 50.0%, respectively. Maternal outcome was better in women with prenatal diagnosis of PAD, as seen by less blood loss and shorter hospitalization.
Lobular Neoplasia of the breast, a term which we prefer to that of Lobular Carcinoma in Situ, is ... more Lobular Neoplasia of the breast, a term which we prefer to that of Lobular Carcinoma in Situ, is a multifocal microscopic entity of uncertain and controversial clinical significance. Lobular Neoplasia is a incidental histological finding among otherwise benign breast biopsies (0.5%-3.5%) depending mainly upon the diagnostic intensity. Its extent is rarely so massive that it makes up a palpable tumor. Although this lesion may be demonstrated at all ages after puberty it occurs most often in premenopausal women. The multicentricity is not below 70% and bilateral occurrence not below 30-35%. Demonstration of Lobular Carcinoma in situ means a 7-12 times greater risk of later developing invasive breast carcinoma as compared with an age corrected general population. Both breast are at risk and about one half of these subsequent carcinomas will develop in the controlateral breast. Attempts at correlating the histological appearances in Lobular Neoplasia with the subsequent occurrence of in...
Virchows Archiv. B, Cell pathology including molecular pathology, 1980
The distribution of the myoepithelial cells in 32 cases of ductal carcinoma-in-situ (DCIS) of the... more The distribution of the myoepithelial cells in 32 cases of ductal carcinoma-in-situ (DCIS) of the breast (11 not associated, 21 associated with invasive carcinoma) was investigated with a recently developed immunoperoxidase method for actin. Actin-rich myoepithelial cells were detected at the periphery of some ducts, however, their presence was neither constant nor continuous. Large areas of DCIS were devoid of a myoepithelial cell layer and the neoplastic cells were directly in contact with the stroma. No differences related to the histological pattern of DCIS or the presence and absence of invasive carcinoma were noted. The behaviour of the myoepithelial cells in ductal carcinoma appears different from that observed in cases of lobular carcinoma (Bussolati 1980) and of cystic disease, and may thus be of diagnostic interest. The selective destruction of myoepithelial cells in cases of DCIS might result in a focal disruption of the basement membrane, thus faciliatating invasion.
Tumoral Carcino Embryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) expression was inves... more Tumoral Carcino Embryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) expression was investigated by immunoperoxidase technique on paraffin embedded tissues of 191 patients with infiltrating breast cancer and negative axillary nodes. TPA was almost always detected at high levels. CEA staining was evenly distributed, but high CEA positivity was associated with higher TPA expression. Lower levels of both markers were found in medullar carcinomas as well as in cancers larger than 1 cm. Higher estrogen and progesterone receptor content was associated with higher expression of tissue CEA and TPA. After a median follow-up of 9 years, neither tissue CEA nor tissue TPA show any prognostic value.
Between 1978 and 1986 we treated 318 consecutive patients with stage I breast cancer. Median foll... more Between 1978 and 1986 we treated 318 consecutive patients with stage I breast cancer. Median follow-up time is 8.5 years. In all cases the invasion of peritumoral lymphatic (LVI) and blood vessels (BVI) was studied by the hematoxylin-eosin staining method. Different ten-year survival (86% vs 67%) and disease-free survival (82% vs 61%) probabilities were found in patients with or without LVI. BVI showed low sensitivity and specificity, therefore vessel invasion was reassessed on 190 specimens with the immunoperoxidase technique using the Ulex Europeus Type 1 lectine. A significant correlation between the vessel staining intensity and the presence of intraluminal metastases was found. With this method a better sensitivity was obtained, but it was associated with a loss of specificity and prognostic significance.
To describe the cytogenetic and FISH characterization of a prenatally diagnosed de novo complex c... more To describe the cytogenetic and FISH characterization of a prenatally diagnosed de novo complex chromosome rearrangement (CCR), showing the involvement of four chromosomes and six breakpoints, and review the literature concerning prenatally detected CCRs in order to obtain insights into addressing karyotype-phenotype correlations in prenatal genetic counseling. Conventional protocols were used to set up cultures and chromosome preparations. Commercial and homemade probes were used for the FISH analyses. An apparently balanced de novo t(4;10;20) was prenatally identified by means of cytogenetic analysis. FISH revealed a rearrangement mediated by six breakpoints and the insertion of chromosome 8 material within the 4q region. The pregnancy was interrupted. The fetus showed malformations and anomalous cortical neuron migration. The assembled list of 20 prenatally detected CCRs points to the preferential involvement of chromosomes 4, 6 and 14. The involvement of chromosome 20 is described here for the first time. FISH analysis is essential for the accurate definition of a complex rearrangement. Phenotype description of fetuses carrying CCRs investigated by means of molecular cytogenetic techniques may contribute to improving and personalizing genetic counseling in prenatal diagnosis.
Prevalence of congenital heart disease increases with nuchal translucency (NT) thickness. First-t... more Prevalence of congenital heart disease increases with nuchal translucency (NT) thickness. First-trimester fetal bradycardia may result from heart block associated with complex congenital heart disease. We report two cases detected in the first trimester of pregnancy, in which both fetuses showed an increased nuchal translucency and bradycardia. Fetal karyotype was normal in both fetuses. First-trimester fetal echocardiography was performed and, in both cases, complex congenital heart disease was diagnosed. We discuss the added role of fetal heart rate in first-trimester ultrasound screening, in fetuses with increased nuchal translucency and normal karyotype. We stress, as well, the importance of echocardiography performed in the first trimester as a potential tool for early diagnosis in selected cases.
Frozen section diagnosis (FSD) given in 4436 consecutive breast biopsies performed in 5 years in ... more Frozen section diagnosis (FSD) given in 4436 consecutive breast biopsies performed in 5 years in a single pathology laboratory were checked against the final pathological report. In 4284 cases (96.57%) there was no difference between the FSD and the definitive diagnosis. There were 74 (1.66%) false negative reports and no false positive diagnoses. The diagnosis was deferred to paraffin sections in 78 cases (1.75% of biopsies). The predictive value for positive results was 100% and for negative results 97.5%; the specificity was 100%, the sensitivity 94.6% and the accuracy 98.3%. Minimal breast cancer, in situ (CIS) especially, was the main source of false negative reports. In non minimal invasive cancers (NMIC) FSD was correct in 99.42%. In minimal invasive cancers (MIC) FSD was correct in 80.21%, false negatives and deferred diagnosis increased to 8.79% and 10.98%. In CIS false negatives increased to 76.82% and deferred diagnoses to 12.19%. The sensitivity of fine needle aspiration, performed before biopsy in a portion of the patients, was lower than FSD in NMIC (71.39% versus 99.21%) and in MIC (41.66% versus 80.55%), identical to FSD in CIS (7.40% versus 7.40%). The value of cytodiagnosis in addressing surgery is discussed.
To evaluate the role of histology in diagnosis and management of biologically benign heart tumors... more To evaluate the role of histology in diagnosis and management of biologically benign heart tumors causing life-threatening symptoms and even death in children and fetuses. The clinical impact of a multidisciplinary approach including 2-D echocardiography, histology, genetics, and cardiac surgery has not yet been fully elucidated. Forty-one consecutive antenatal (n = 17) or postnatal (n = 24) detected cardiac masses were evaluated by 2-D echocardiography (in alive patients) or at autopsy, and 12/41 cases with definite histologic diagnosis of primary and benign cardiac tumor were entered in this study. Rhabdomyomas (n = 6), hemangiomas (n = 3), central fibrous body chondroma (n = 1), fibroma (n = 1), or left atrial myxoma (n = 1) were histologically diagnosed in 4 fetuses and in 8 children. Death occurred in 6 patients showing diffuse or infiltrative tumors, 2/6 experiencing intrauterine death or sudden and unexpected infant death. Seven patients underwent surgery, 4/7 are alive and well at &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5 years follow-up, whereas 3 deaths followed partial tumor resection. Two fetuses with extensive tumor/s were aborted. Tuberous sclerosis complex gene mutations were seen in patients with rhabdomyomas. Histology represents the best diagnostic approach in life-threatening pediatric cardiac tumors allowing definite diagnosis in cases other than rhabdomyoma and in sudden deaths, influencing clinical management and counselling. 2-D echocardiography remains the main tool for early clinical diagnosis and follow-up. A multidisciplinary approach is advisable because of rarity, difficult management, and possible associations with inheritable diseases.
The value of immunocytochemical methods for detecting seven tumour-associated antigens was assess... more The value of immunocytochemical methods for detecting seven tumour-associated antigens was assessed in ten cases of bone metastases from carcinoma of the breast. In order to obtain the optimal preservation of both their structure and antigenicity, the biopsies were fixed-decalcified in Bouin's fluid by means of an apparatus based on ion-exchange resins recently developed in this laboratory. Of the different tumour markers, milk fat globule membrane antigen and carcino-embryonic antigen were found to be present in the majority of the cases of neoplastic cells. These two markers appear, therefore, to be the most useful for the immunocytochemical identification of metastatic neoplastic cells in the bone marrow originating from carcinoma of the breast.
Advances in ultrasound technology and sonographer&amp;amp;#39;s experience lead to the descri... more Advances in ultrasound technology and sonographer&amp;amp;#39;s experience lead to the description of many rare syndromes and malformations through prenatal diagnosis. Diaphragmatic hernia is a rather common malformation but can be an indicator of different syndromes. We report the prenatal diagnosis of lethal multiple pterygium syndrome type II which has been established in the 34th week of pregnancy. The sonographically detectable symptoms consisted of polyhydramnios, hygroma colli, diaphragmatic hernia, scoliosis, short forearms, hypokinesia of the fetus and pterygia over the large joints. Labour was induced in the 34th week of pregnancy; the neonate died shortly after vaginal delivery as a result of the pulmonary hypoplasia. A multidisciplinary approach in prenatal assessment may help to clarify difficult diagnostic problems and may be of direct benefit for the pregnant patient.
Uploads
Papers by G. Botta