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Biomedical subjects

S Lanzafame

Publications and source records attributed to S Lanzafame.

At least 19 recordsLinked to original sources

Thyroid transcription factor 1 (TTF-1) and p63 expression in two primary thyroid papillary carcinomas of branchial cleft cysts.

Malignant lateral cervical cysts can be related to metastatic tumors or rarely to primary thyroid carcinoma arising in branchial cleft cysts. This study evaluates the expression of thyroid-associated transcription factor-1 (TTF-1) and p63 in three branchial cleft cysts and in two primary thyroid papillary carcinoma of branchial cleft cysts. TTF-1 was negative in the nuclei of the lining epithelia of branchial cleft cysts, but positive in the adjacent normal thyroid tissue, while TTF-1 was positive in the nuclei of the lining epithelia and in the nuclei of the papillae and follicles in branchial cleft cysts with ectopic thyroid carcinoma. P63 was positive in the nuclei of the lining epithelia of branchial cleft cysts, but negative in the adjacent normal thyroid tissue. Papillary thyroid carcinoma of branchial cleft cysts displayed p63-positive foci. In conclusion, our results demonstrate that TTF-1 cannot distinguish between primary and metastatic tumors of branchial cleft cysts. The detection of p63 in papillary thyroid carcinomas of branchial cleft cysts could suggest that p63 contributes to the onset of this tumor. It is really important to evaluate if the case has a metastatic derivation or represents papillary thyroid carcinoma arising in ectopic thyroid tissue in a branchial cleft cyst.

Adenocarcinoma, Papillary↗

About a case of GIST occurring during pregnancy with immunohistochemical expression of epidermal growth factor receptor and progesterone receptor.

The coexistence of gastrointestinal stromal tumors (GISTs) and pregnancy is very rare. We are the first to add to the literature a case report of GIST occurring during pregnancy with immunohistochemical staining for epidermal growth factor receptor (EGFR) and progesterone receptor (PgR). A role of PgR and EGFR in tumor growth should not be excluded, and these findings indicate that the expression of these receptors could provide pertinent biological information required to determine adequate therapeutic regimens. In conclusion, considering that GIST occurring during pregnancy is a rare event, with frequent delay in diagnosis, it is important to consider this diagnosis for early recognition, correct diagnosis, and a better outcome.

Adult↗

p63 expression in odontogenic cysts.

A total of 123 cases of odontogenic cysts, distributed as follows: 30 follicular (FC), 35 radicular (RC), 53 keratocysts, 1 glandular odontogenic and 4 calcifying odontogenic cysts, were analysed by immunohistochemistry for expression of p63, a component of p53 protein family. In RCs p63 positivity was not only in basal and parabasal layers but also in the intermediate layer and about 1/3 of cases displayed a percentage of stained cells comprised between 0 and <5%, and about 2/3 between >5% and <50%. In FCs positivity was confined to basal and parabasal layers of the epithelium and in the majority of FCs the stained cells were comprised between 0 and <5%. OKCs displayed the most intense and diffuse p63 labeling. In conclusion, these data suggest that p63 expression may be useful to identify cysts type with more aggressive and invasive phenotype supporting the hypothesis of a suprabasal proliferative compartment in OKCs.

DNA-Binding Proteins↗

[Solitary ganglioneuroma of the ileo-cecal valve].

Ganglioneuromas may occur in the small and large intestine as either solitary lesions or, more commonly, as multiple lesions (ganglioneuromatosis). The former are very rare, whereas ganglioneuromatosis may be associated with von Recklinghausen's disease and multiple endocrine neoplasia (MEN) type II B. We described the clinicopathologic features of a case of solitary polypoid ganglioneuroma of the ileocecal valve. The lesion was endoscopically diagnosed in a 27 year old man, with a history of abdominal pain. No association with von Reckling-hausen's disease or MEN was identified. Mutational analysis for RET was negative. Microscopically, the tumor consisted of a proliferation of well differentiated Schwann cells and ganglion cells in the lamina propria. The solitary polipoid ganglioneuroma is invariably benign. It shows no evidence of recurrence after total excision.

Adult↗

Spinal meningeal mesenchymal chondrosarcoma. Report of a new case and review of the literature.

A case of T12-L2 intraspinal extradural meningeal mesenchymal chondrosarcoma is described in a patient presenting with a clinical history of low-back pain and weakness of the lower limbs. Magnetic resonance T1-weighted Gadolinium enhanced imaging, showed an intraspinal extradural mass, extending from T12 to L2, located anterolaterally into the spinal canal and pushing posteriorly the conus medullaris. The mass was completely removed and postoperative histological diagnosis was of mesenchymal chondrosarcoma. The patient was completely symptoms-free after surgery. Intraspinal meningeal mesenchymal chondrosarcoma and treatment options are reviewed.

Adult↗

[Fibromatosis of the breast: a clinical, radiological and pathological study of 6 cases].

We describe the clinical, radiological and pathological features of a series of six cases of primary fibromatosis of the breast. Most patients (5 of 6) were women of 22-58 years of age; one case occurred in a 47-year-old man. The fibromatosis of the breast in all cases presented as a monolateral solid nodule, clinically suspicious for malignancy and in three cases was also associated with cutaneous and/or nipple retraction. None of the patients was affected by any genetic disorder characterized by fibromatoses involving multiple sites, including breast. Both echographic and mammographic examinations revealed solid masses with irregular margins but without calcifications, mimicking scirrhous carcinoma. All cases were surgically treated by lumpectomy (4 of 6) or quadrantectomy (2 of 6), and after a follow-up period ranging from 5 months to 13 years all patients are well and disease-free. Histological examination revealed finger-like infiltrating margins entrapping adjacent breast parenchyma and adipose tissue in all cases. The hallmark of the lesion was the presence of bland-looking spindle cells, with a low mitotic index, organized in long sweeping and intersecting fascicles. Three different morphological phases (i.e. proliferative, involutional and residual), identical to those observed in Dupuytren's superficial fibromatosis, variably coexisted in each case. At immunohistochemistry the cells which comprised the lesion exhibited a diffuse expression of vimentin and a heterogeneous immunoreactivity to a-smooth muscle actin, thus confirming their fibro-myofibroblastic nature. No expression of estrogen, progesterone or androgen receptors or of pS2 correlated-estrogen protein was observed. We discuss both the pathogenesis of the mammary fibromatosis, pointing to the fibroblastic cells of the mammary stroma as the putative precursors, and the differential diagnosis versus the bland-looking, monomorphic spindle cell tumor-like or tumorous lesions of the breast.

Adult↗

Correlation between histological grade, MIB-1, p53, and recurrence in 69 completely resected primary intracranial meningiomas with a 6 year mean follow-up.

Sixty-nine intracranial, totally excised meningiomas were immunostained for MIB-1 and p53 protein expression. According to the 1993 WHO criteria, revised by Perry et al., the 69 meningiomas were classified into: grade I = 54 benign meningiomas, grade II = 10 atypical meningiomas, grade III = 5 malignant meningiomas. The patients were followed until death or for an average of 6.7 years. The 69 meningiomas were divided into two groups, according to the absence (n = 42) or presence (n = 27) of recurrences. In the last group we included 3 patients who died of meningioma recurrence. According to the percentage of MIB-1 positively stained cells, meningiomas were divided into three groups: <1% (n = 36), 1-10% (n = 28), >10% (n = 5). We found the MIB-1 labeling index (LI) <1% in 33 grade I (61%) and in 3 grade II (30%) meningiomas. On the other hand, 7 grade II (70%) and all grade III (100%) meningiomas presented a MIB-1 LI >1%. Correlation between histological grade and MIB-1 LI was statistically significant (p = 0.0006). The correlation between MIB-1 LI and follow-up was also highly significant (p < 0.001): the majority of meningiomas which did not recur (32/42 equal to 76%) were characterized by a low (<1%) MIB-1 LI. In the recurrence group MIB-1 LI was significantly higher than in the disease-free patients' group. Moreover, MIB-1 appeared to be a prognostic parameter not strongly related to the histological grade. In fact, it was significantly higher in recurrent histologically benign meningiomas, as compared with benign meningiomas without recurrence (p = 0.0006). Positive p53 protein expression (>1%) was shown in 26/45 meningiomas (57%), with an LI of 1-10% in 18 (40%) and an LI of >10% in 8 (17%) meningiomas. Although the p53 LI tended to be higher in atypical and malignant meningiomas, no significant correlation was found between the p53 expression and the recurrence (p = 0.05). The authors conclude that quantitative MIB-1 labeling is a useful technique in the routine diagnostic assessment of meningiomas, and helpful in obtaining more information about prognosis and thereby in planning the most suitable treatment.

Adult↗

Localized fibrosis of the corpus cavernosum: an example of fibrosis arising from the vascular smooth muscle cells. Report of a case with histogenetic considerations.

We report a rare case of a localized fibrosis of the corpus cavernosum (CC) presenting as a nodular mass in the dorsal region of the penis without abnormal curvature of the organ. Histological and immunohistochemical examination revealed a fibrotic process, involving CC but not tunica albuginea, arising from the smooth muscle cells of the vascular channels. Two different morphological phases were identified in these vascular lesions: proliferative and residual phase. The proliferative phase was characterized by hyperplasia and moderate fibrous thickness of the smooth muscle layer of the vascular channels of CC, resulting with the formation of concentric perivascular cuffs and nodules. The residual phase was characterized by a progressive nodular fibrotic transformation with narrowing of the original vascular channels and replacement of the normal CC structures. The cells of this phase exhibited an immunophenotype of both fibroblasts (vimentin+; alpha-smooth muscle actin-) and myofibroblasts (vimentin+; alpha-smooth muscle actin+). The clinicopathological features of the lesion and histogenetic considerations are discussed.

Fibrosis↗

Lhermitte duclos disease and Cowden disease: clinical, pathological and neuroimaging study of a case.

The authors report the case of a 26-year-old female patient affected by Lhermitte Duclos disease and Cowden disease. Preoperative MRI allowed a correct diagnosis which was confirmed by pathological examination. The authors stress the possibility that Lhermitte Duclos and Cowden disease be a single phakomatosis; for this reason all the patients affected by Lhermitte-Duclos should be screened for the presence of multiple hamartomas or malignant neoplastic lesions typical of Cowden disease.

Adult↗

Myofibroblastoma of the breast with hemangiopericytoma-like pattern and pleomorphic lipoma-like areas. Report of a case with diagnostic and histogenetic considerations.

Myofibroblastoma (MFB) of the breast is an uncommon benign spindle cell tumor which may exhibit a wide spectrum of histological features. We report an unusual case of MFB of the male breast, showing cellular areas with a hemangiopericytoma-like pattern similar to that observed in solitary fibrous tumor (SFT) and extensive fibromyxoid areas containing numerous atypical stromal cells. The association of these atypical cells with mature adipocytes and microcystic and/or myxoid degenerative changes resembled pleomorphic lipoma-like and myxoid liposarcoma-like features, respectively. To our knowledge, these peculiar morphological findings have not been previously reported in MFB of the breast. They should be recognized to avoid confusion with other mesenchymal tumors, especially with hemangiopericytoma, pleomorphic lipoma (PL), spindle-cell lipoma (SCL) and myxoid liposarcoma. A case of MFB of the breast showing morphological features also commonly seen in SFT and PL/SCL is further morphological evidence in support of the speculation that the mesenchymal tumors of the breast, also known under the terms benign spindle cell tumors, fibromas, SFTs, SCLs and MFBs, are histogenetically related lesions.

Biomarkers, Tumor↗

Correlated expression of BCL-2 protein, estrogen receptor, cathepsin D and low growth fraction (PCNA) in intracystic papillary breast carcinoma.

The expression of BCL-2 protein was evaluated immunohistochemically in 23 intracystic papillary carcinomas (IPCs) of the breast. Twenty-two patients were female and one male, aged 49-90 years (median 72). Twenty-one cases had a benign behaviour, while two cases developed local recurrence. Of the 23 tumours, 19 (82%) were immunoreactive for BCL-2, the majority of positive carcinomas showing intense cytoplasmic staining of more than 50% neoplastic cells. The intensity of BCL-2 expression was significantly correlated with prognostic markers such as estrogen receptor (ER) positivity (p = 0.001), cathepsin D (CD) reactivity in the neoplastic cells (p = 0.001) and low growth fraction, evaluated by proliferating cell nuclear antigen (PCNA) immunostaining (p = 0.008). An inverse relationship was also found between BCL-2 and p53 protein (p = 0.001). Three cases of high grade (G3) IPC expressed p53, high PCNA index, and CD (the latter only in the stromal cells), but no immunostaining for BCL-2 and ER. Thus, absence of BCL-2 expression in high grade IPC was associated with ER-negative, rapidly proliferating and p53-positive immunophenotype. All high grade tumours showed invasion of the cystic wall. Local recurrence developed in one of these. The authors conclude that BCL-2 immunoreactivity in IPC is related with tumour grade and with a range of molecular markers of favourable prognosis such as ER positive status, CD expression in the neoplastic cells, and low PCNA index. These findings are consistent with the indolent clinical course and the very favourable prognosis of IPC of the breast.

Aged↗

Myofibroblasts of palmar fibromatosis co-express transforming growth factor-alpha and epidermal growth factor receptor.

Several studies have shown that different growth factors are involved in the pathogenesis of palmar fibromatosis. The aim of the present study was to investigate whether transforming growth factor alpha (TGF-alpha) and its cellular receptor, epidermal growth factor receptor (EGF-R), are expressed in palmar fibromatosis. Nodules from 20 patients with palmar fibromatosis and control normal palmar fascias were studied by the reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR followed by Southern blotting demonstrated that palmar fibromatosis nodules contained high levels of TGF-alpha and EGF-R messenger RNA (mRNA) transcripts, while normal fascias showed only low levels. Depending on the degree of cellularity and fibrosis, the three following histological phases were recognized in palmar fibromatosis nodules: proliferative, involutional, and residual. Immunohistochemistry, using alpha-smooth muscle actin as a cellular marker for myofibroblasts, revealed that TGF-alpha and EGF-R are co-expressed by myofibroblasts in the highly cellular areas of both proliferative and involutional phases, while they are absent or only focally detectable in the fibroblasts of normal fascia and in hypocellular and fibrotic areas of both involutional and residual phases. The restricted co-expression of TGF-alpha and EGF-R to myofibroblasts, the proliferating cellular component of nodules, suggests that an autocrine and/or juxtacrine growth stimulation by TGF-alpha via the EGF-R may be involved in the pathogenesis of palmar fibromatosis.

Actins↗

Myofibroblasts and extracellular matrix glycoproteins in palmar fibromatosis.

We investigated immunohistochemically the presence of myofibroblasts and their surrounding extracellular matrix (ECM) in palmar fibromatosis nodules, obtained from 30 patients. Histologically, the three following phases were identified in palmar fibromatosis nodules: proliferative, involutional, and residual. A variable association of these phases was simultaneously detected within the same nodule. In most cases (20/30), we found that involutional and residual phases coexisted, while the association of proliferative/involutional/residual and proliferative/involutional phases was observed in 8 and 2 cases, respectively. Alpha-smooth muscle actin, a reliable marker for myofibroblastic cellular phenotype, revealed that most spindle-shaped cells of cellular areas of both proliferative and involutional phases were myofibroblasts. Regardless of the predominant association of histologic phases, these findings demonstrate that a myofibroblastic cellular component is constantly found in palmar fibromatosis nodules, although its degree is variable. Immunohistochemical study of ECM showed that collagen types IV, VI, laminin, and fibronectin were strongly expressed and restricted to cellular areas of involutional and residual phases. A combined study of cellular phenotype and ECM, using consecutive sections, demonstrated that the distritubion of collagen types IV, VI, laminin, and fibronectin followed the distribution of myofibroblasts, while they were not expressed in the areas devoid of these cells. These findings suggest that interactions between myofibroblasts and these surrounding ECM glycoproteins may be involved in the pathophysiology of palmar fibromatosis.

Actins↗

Immunohistochemical expression and distribution of alpha2beta1, alpha6beta1, alpha5beta1 integrins and their extracellular ligands, type IV collagen, laminin and fibronectin in palmar fibromatosis.

Palmar fibromatosis is characterized by changes in the expression of extracellular matrix (ECM) proteins and re-organization of the interactions between cellular and extracellular compartments. We compared the expression and distribution of alpha2beta1, alpha6beta1, alpha5beta1 integrins and their corresponding extracellular ligands, type IV collagen, laminin and fibronectin in palmar fibromatosis nodules from 24 patients. Depending on the degree of cellularity and fibrosis, three different histologic phases were identified: proliferative, involutional, and residual. Immunohistochemistry revealed that only stromal cells of the highly cellular areas of both proliferative and involutional phases were myofibroblasts, as demonstrated by their cytoplasmic positivity for alpha-smooth-muscle actin. The ECM, surrounding these cells, was strongly and diffusely positive to type IV collagen, laminin and fibronectin, whereas no immunoreactivity was found in the ECM of the fibrotic and hypocellular areas of both involutional and residual phases. Immunostaining for alpha2beta1, alpha6beta1 and alpha5beta1 integrins revealed that alpha5beta1 integrin was expressed and restricted to the myofibroblast-rich cellular areas, whereas no expression was detected for alpha2beta1 and alpha6beta1 integrins. By examining serial sections, a co-localization of alpha5beta1 integrin and fibronectin was observed in the myofibroblast-rich cellular areas, indicating that, in palmar fibromatosis, a co-ordinate expression between cellular and extracellular ligand is detected only for the alpha5beta1 integrin/fibronectin complex. These findings suggest that the alpha5beta1 integrin/fibronectin complex may be involved in regulating the interactions between myofibroblasts and ECM in palmar fibromatosis.

Actins↗

Correlation of alpha 2 beta 1 integrin expression with histological type and hormonal receptor status in breast carcinomas.

Interactions between cells and extracellular matrix are mediated in part by a family of alpha beta heterodimeric molecules known as integrins. Immunohistochemical studies have shown that benign hyperplastic/neoplastic mammary epithelium expressed high levels of alpha 2 beta 1 collagen/laminin receptor. In contrast, malignant cells of breast carcinoma exhibited marked diminuition or loss of the alpha 2 beta 1 integrin. A correlation has been suggested between the loss of the alpha 2 beta 1 expression and the increased invasiveness of neoplastic cells. This study investigated the expression of alpha 2 beta 1 integrin and its extracellular ligand collagen TV by using monoclonal antibodies on the cryostat section of 124 invasive mammary carcinomas. Two patterns of alpha 2 beta 1 immunoreactivity, i.e. pericellular and basolateral, were identified in breast carcinomas and correlated with their histological type. In most invasive ductal carcinomas of no special type (NOS), integrin staining tended to decrease in both pericellular and basolateral aspects. Loss of basolateral staining for alpha 2 beta 1 integrin corresponded closely to the loss of immunoreactivity for collagen IV. Mucinous and medullary carcinomas showed strongly alpha 2 beta 1 pericellular staining, but no basolateral reactivity or collagen IV expression. Only two of the infiltrating lobular carcinomas expressed strong pericellular reactivity. In 82 ductal carcinomas NOS, the abnormally low expression/absence of alpha 2 beta 1 integrin correlated with estrogen and progesterone receptor negativity (p < 0.04 and p < 0.002, respectively). No correlation between integrin expression, histological grade, nodal involvement and proliferative activity was found. The results of the present study suggest that changes in alpha 2 beta 1 expression correlate with the histological type and hormonal receptor status in breast carcinomas. The clinical implications of these findings remain to be elucidated.

Adenocarcinoma↗

Co-ordinate expression of alpha 5 beta 1 integrin and fibronectin in Dupuytren's disease.

The expression of alpha 5 beta 1 (alpha 5 beta 1) integrin and its extracellular ligand fibronectin was studied immunohistochemically in 23 cases of Dupuytren's disease using an immunoperoxidase method for light microscopic visualization. All cases consisted of multiple nodules showing a variable degree of cellularity and fibrosis. Depending on the histological appearance of these nodules, each case was assigned to the three following phases: proliferative, involutional and residual. Alpha 5 beta 1 integrin was detected in the highly cellular areas of both proliferative and involutional phases where fibronectin was simultaneously expressed in the extracellular matrix (ECM). Diversely alpha 5 beta 1 and fibronectin disappeared from the hypocellular areas of involutional phase, undergoing fibrotic transformation, and from the fibrotic connective tissue of residual phases. These findings indicate that the expression pattern of alpha 5 beta 1 integrin correlates with the presence in the ECM of the corresponding ligand fibronectin during the different phases of Dupuytren's disease. We suggest that alpha 5 beta 1 integrin, linking fibronectin to stromal cells of both proliferative and involutional phases, may be involved in the contractile processes occurring in Dupuytren's disease.

Dupuytren Contracture↗