Laparoscopic resection of an adrenal hydatid cyst.
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Adrenal Gland Diseases↗
Biomedical subjects
C De Micco
Publications and source records attributed to C De Micco.
In situ hybridization and immunohistochemistry study of thyroid peroxidase expression in thyroid tumors.
Malignant thyroid tumors reportedly exhibit an anomaly in thyroid peroxidase (TPO) resulting in a lower affinity for monoclonal antibody 47 (mAb 47) in immunohistochemistry studies. The purpose of the present study was to compare TPO immunostaining in normal, benign, and malignant thyroid tissue with expression of mRNA sequences in four exons of the molecule including the epitope of mAb 47. TPO immunostaining was performed using mAb 47 and a polyclonal antibody (pAb). Messenger RNA expression was investigated by in situ hybridization using probes specific for mRNA sequences in exons 2, 12 (epitope of mAb), 15, and 17. As expected, pAb immunostaining was significantly positive on all benign tumors and 50% of carcinomas. With mAb 47, little or no immunostaining was observed in 16 of 17 carcinomas while significantly positive immunostaining was found in normal tissue and benign tumors. In situ hybridization showed a decrease and heterogeneity in the expression of all mRNA sequences in carcinomas as compared to normal tissue and benign tumors. Unlike the other three probes, the probe specific for exon 12 hybridized strongly with benign tumors but poorly with most carcinomas. Poor hybridization was usually correlated with defective mAb 47 immunostaining. These results confirm that TPO is expressed in thyroid carcinomas but in smaller amounts than in normal tissue and benign tumors. In malignant tumors, qualitative changes in TPO may also impede mAb 47 immunostaining. In situ hybridization showed a concomitant decrease in the corresponding TPO mRNA sequence. These changes could be due to abnormalities in the maturation of TPO mRNA leading to a different splicing variant.
Adenocarcinoma, Follicular↗
The value of thyroid peroxidase immunohistochemistry for preoperative fine-needle aspiration diagnosis of the follicular variant of papillary thyroid cancer.
BACKGROUND: With the use of May-Grunwald-Giemsa staining, cytologic features of the follicular variant of papillary thyroid cancers (FVPTCs) on thyroid fine-needle aspiration (FNA) often resemble those of hyperplastic and adenomatous nodules. Detection of reduced staining after thyroid peroxidase (TPO) immunohistochemistry with monoclonal antibody MoAb47 has been shown to be a helpful diagnostic marker. The purpose of this study was to assess the value of TPO immunohistochemistry for the diagnosis of FVPTC. METHODS: Of 3505 patients with adequate FNA samples, 1576 patients underwent surgical procedures. Histologic examination of the surgical specimen demonstrated papillary thyroid cancer in 227 cases, including 42 FVPTCs (18%). The diagnostic accuracy of standard thyroid FNA and TPO immunohistochemistry, which we use routinely, was compared in these 42 FVPTCs. RESULTS: Standard FNA allowed accurate diagnosis of malignancy in 32 of the 42 FVPTCs and in 170 of the 185 typical papillary thyroid cancers. TPO-immunohistochemistry staining was accurate in all 42 FVPTCs and in 182 of 185 typical PTCs. CONCLUSIONS: FVPTC is a frequent source of false-negative results on standard thyroid FNA. This study shows that TPO immunostaining accurately demonstrates malignancy in these tumors.
Adolescent↗
Latent subclinical medullary thyroid carcinoma: diagnosis and treatment.
Sporadic medullary thyroid carcinoma (SMTC) is usually diagnosed at a clinical stage often associated with lymph node involvement. Hence surgical treatment does not result in definitive cure in many patients. Studies have demonstrated that routine measurement of serum basal calcitonin (CT) in patients with nodular thyroid disease allows preoperative, early diagnosis of unsuspected SMTC. The aim of this work was to assess the results of surgery in patients operated on for subclinical SMTC detected preoperatively by measurement of serum CT. Results were compared with those obtained in patients with SMTCs diagnosed at a clinical stage and operated on during the same period. During a 4-year period (1993-1996) 24 SMTCs were diagnosed and treated in our department. They were diagnosed at a clinical stage in 13 patients (group 1): palpable thyroid tumor (n = 11), palpable metastatic lymph node (n = 6), distant metastases (n = 4). In nine cases the diagnosis was made by both fine-needle aspiration cytology and serum CT measurement. In the four other cases the initial cytology was incorrect, but the diagnosis was revised on the basis of elevated basal CT values. In 11 patients (group 2) presenting with nodular thyroid disease, SMTC was not clinically detectable. SMTC was preoperatively suspected by elevated CT levels: basal CT > 10 pg/ml and pentagastrin-stimulated CT peak > 100 pg/ml. One patient in group 1 with distant metastases was not operated on. All of the other 12 patients underwent total thyroidectomy and extensive lymph node dissection. The mean size of the tumors was 27 mm. Lymph node involvement was found in nine patients. After surgery, CT levels returned to normal in five patients but remained elevated in five others; the two remaining patients died of distant metastases. All 11 patients in group 2 underwent total thyroidectomy and central neck dissection. None of the 11 patients had nodal extension. All 11 patients are biochemically cured. It was concluded that routine measurement of basal serum CT in those with nodular thyroid disease allows early, preoperative diagnosis of subclinical SMTC and improves the results of surgery.
Adult↗
Comparison of thyroid peroxidase expression with cellular proliferation in thyroid follicular tumors.
Thyroid cancer is associated with abnormal thyroid peroxidase (TPO) expression as shown by abolition of immunodetection by monoclonal antibody 47 (Mab 47). The purpose of this study was to determine the relation of this abnormality with differentiation and proliferative potential of follicular tumors evaluated by analyzing thyroglobulin (TG) expression and proliferative cell nuclear antigen (PCNA) index. TPO, TG, and PCNA immunostaining were performed in a series of 30 thyroid follicular tumors ranging from adenoma to invasive carcinoma. Our findings confirmed that TPO abnormalities and PCNA index were correlated with malignancy, and that PCNA as well as TPO could be used to determine the growth potential of follicular proliferations in fine-needle aspirates. The most discriminant parameter was the ratio between the percentage of Mab-47 and PCNA positive cells. Ratios under 0.6 were correlated with malignancy in 90% of the cases, with only 3 cases of atypical adenomas being misdiagnosed as carcinomas. An inverse correlation was found between TPO and PCNA expression, but TG, which persisted at high levels in several actively growing follicular carcinomas, did not appear directly linked to cellular proliferation. These findings confirm that, unlike a decrease in TG synthesis that merely reflects the progressive loss of differentiation occurring in high-grade proliferations, alteration of TPO is an early marker of thyroid follicular tumors, closely related to acceleration of tumor growth in the first stages of malignant transformation.
Adenocarcinoma, Follicular↗
Immunoexpression of E-cadherin and beta-catenin correlates to survival of patients with hepatocellular carcinomas.
Expression of E-cadherin (E-cad) and -catenin ( -cat) was investigated immunohistologically in 91 cases of excised hepatocellular carcinomas. Immunodectection was altered in 56% of tumours for E-cad and in 30.8% for -cat. Downregulation of E-cad and -cat correlated with the size of tumours, and high nuclear grade, but only E-cad alteration correlated with the mitotic index. Alterations of E-cad and -cat expression correlated with survival. Although E-cad and -cat immunodetections were independent prognostic factors, their prognostic value was lower than that of current clinicopathological parameters.
Adult↗
[Polycystic disease of the salivary glands: report of an attack of the submaxillary glands].
Bilateral dysgenetic polycystic disease of parotid glands is an extremely rare pathologic condition in which salivary parenchyma is partially replaced by multiple epithelial-lined cysts arising from intercalated ducts. Review of the fourteen cases published in literature shows that it affects nearly exclusively women with an history of asymptomatic progressive enlargement of almost always both parotid glands. We report here the first case, to our knowledge, of a polycystic disease involving both submandibular salivary gland in a man.
Cysts↗
[Prognostic value of E-cadherin expression in hepatocellular carcinoma].
Expression of E-cadherin (E-cad) was investigated immunohistologically in 91 cases of operated hepatocellular carcinomas. An alteration of E-cad immunodetection was found in 56% of tumours. These alterations were correlated with histopathologic features of prognostic value including tumour size (> 3 cm), high nuclear grade and mitotic index. Patients with down-regulated E-cad expression had statistically significant shorter survival than the others. Although E-cad immunodetection was an independent prognostic factor, the Cox multivariate analysis showed that its prognostic value was low when compared to other prognostic factors.
Adult↗
Immunohistochemical study of 100 pancreatic tumors in 28 patients with multiple endocrine neoplasia, type I.
One hundred pancreatic tumors ranging in size from 0.3 to 7 cm were studied in 28 patients (17 male and 11 female patients; mean age 35 years) with multiple endocrine neoplasia, type I. An immunohistochemical study was performed on deparaffinized sections using the following antibodies: neuron-specific enolase, chromogranin A or synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), gastrin, adrenocorticotropic hormone, alpha-subunit of human chorionic gonadotropin, gonadotropin-releasing factor, serotonin, and calcitonin. Among the 100 tumors (all multiple), seven were unclassified, 10 were plurihormonal, and 83 produced a predominant hormonal secretion (with 50-90% of the same cell type), including 37 "A-cell tumors" (glucagon), 27 "B-cell tumors" (insulin), 11 PP-cell tumors, one G-cell tumor (gastrin) and one vasoactive intestinal peptide (VIP)-cell tumor. These multiple tumors had a different predominant hormonal secretion in the same patient in 23 of the 28 cases. There was a preferential association of A-cell tumor and B-cell tumor. Hyperplasia of the islets of Langerhans was not detected in adjacent pancreas. Nesidioblastosis was observed in 30% of cases.
Adolescent↗
[Tumor markers in the cytodiagnosis of thyroid nodules. Detection of dipeptidyl aminopeptidase IV (DAP IV) activity].
Dipeptidyl-aminopeptidase IV (DAP IV), an exopeptidase involved in T-cell activation is absent from normal thyroid tissue but highly expressed by malignant thyroid cells. It has been suggested to be a useful adjunct for the diagnosis of malignant thyroid tumors on fine needle aspirates (FNA). To assess this assumption DAP IV activity was demonstrated by histochemical staining on FNA performed on 102 thyroid nodules at the time of surgery (60 macrofollicular adenomas, 15 microfollicular adenomas. 7 Hashimoto's thyroïditis, 3 Graves' disease. 13 papillary carcinomas and 4 follicular carcinomas). A staining score based on the percentage of positive epithelial cells and staining intensity was established for each case and results were compared to histological diagnosis. Most cells in malignant tumors were deeply stained except in one case of papillary carcinoma. Null or very low scores resulting from light or medium staining of less than 40% of the cells were obtained in 78/85 benign nodules. In 6 macrofollicular adenomas and in 1 case of thyroiditis staining score was as as high as in carcinomas. DAP IV staining was correlated to malignancy in all follicular tumours (4 malignant tumours were positive and 15 benign were negative). The sensitivity for diagnosis of malignancy was 94.1% and the specificity 91.7%. This study brings confirmation that DAP IV activity detection could be an useful adjunct to cytological examination for the distinction between benign and malignant thyroid nodules, especially in cases of follicular tumors.
Biomarkers, Tumor↗
Thyroid peroxidase immunodetection as a tool to assist diagnosis of thyroid nodules on fine-needle aspiration biopsy.
In a previous work we have reported the presence in 96.9% of malignant and 4.2% of benign thyroid tumors of an immunological abnormality of the enzyme thyroid peroxidase, impeding the fixation of the anti-thyroid peroxidase monoclonal antibody termed "MoAb47". The present study has been designed to establish the ability of thyroid peroxidase immunodetection to assist the diagnosis of malignancy in fine-needle aspiration of thyroid nodules. The fixation of anti-thyroid peroxidase monoclonal antibody was investigated by immunohistochemistry on fine-needle aspirates of 150 surgically removed thyroid nodules (20 papillary carcinomas, five follicular carcinomas, 90 colloid adenomas, nine fetal adenoma, 13 atypical adenomas, five oncocytic adenomas, six Hashimoto's thyroiditis and two Graves' disease). The percentage of positive cells has been compared to the final histological diagnosis. In samples from 113/125 benign nodules 80-100% cells presented a positive immunoreaction, whereas all samples from malignant tumors yielded less than 80% positive cells. Benign nodules exhibiting less than 80% positive cells corresponded to three degenerative colloid nodules, five atypical follicular adenomas, two oncocytomas and two thyroiditis. According to results obtained in this series, with the value of 80% as the limit for discrimination between benign and high-risk nodules, the sensitivity of thyroid peroxidase staining for diagnosis of malignancy would be 100%, its specificity 90% and its overall accuracy 92%. Thyroid peroxidase staining with monoclonal antibody MoAb47 on fine-needle aspirates is a useful adjunct to conventional cytology for the investigation of patients with thyroid nodules.
Biopsy, Needle↗
Fine-needle aspiration of thyroid follicular neoplasm: diagnostic use of thyroid peroxidase immunocytochemistry with monoclonal antibody 47.
BACKGROUND: We previously demonstrated that thyroid peroxidase (TPO) immunocytochemistry with monoclonal antibody 47 can help to differentiate benign (staining score, 80% or more) from malignant (staining score, less than 80%) thyroid nodules on fine-needle aspiration (FNA) samples. In the present study we assessed the use of TPO immunocytochemistry in the cytologic diagnosis of thyroid follicular neoplasms. METHODS: A total of 109 histologically proven follicular tumors were studied. There were 60 microfollicular adenomas, 23 atypical adenomas, 17 oncocytic adenomas, and 9 follicular carcinomas. Adequate preoperative FNA samples were available in all cases. TPO immunocytochemistry was performed on one half of the slides. RESULTS: The staining score was less than 80% in all follicular carcinomas, whereas it was 80% or more in 68 of 100 benign tumors. There was no false negative and 32 false positives for diagnosis of malignancy. The false positives were 10 microfollicular adenomas, 13 atypical adenomas, and 9 oncocytic adenomas. TPO immunocytochemistry has a sensitivity of 100% and a specificity of 68% for screening of follicular cancer. CONCLUSIONS: TPO immunocytochemistry with monoclonal antibody 47 on FNA samples is a highly sensitive and fairly specific method to distinguish benign from malignant follicular neoplasms. This technique can help to reduce the number of surgical procedures for benign thyroid nodules without increased risk of overlooking malignancy.
Antibodies, Monoclonal↗
[Thyroid cancers. Pathological anatomy].
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Adenocarcinoma, Follicular↗
Significance of thyroglobulin antibodies cross-reactive with thyroperoxidase (TGPO antibodies) in individual patients and immunized mice.
Thyroglobulin (TG) and thyroperoxidase (TPO), both involved in thyroid hormone synthesis, represent major autoantigens in thyroid autoimmune disease. Despite numerous studies, the emergence, pathophysiological significance and role of autoantibodies to TG and TPO remain elusive. The recent identification of a new category of thyroid-specific autoantibody interacting with both TG and TPO (TGPO autoantibodies) offers a new opportunity in the study of thyroid autoimmunity. To gain a better insight into the significance of these TGPO autoantibodies, measurement in individual samples appeared necessary. The unique property of TGPO autoantibodies, simultaneous binding to TG and TPO, was used to set up a sandwich method which combined coated TG and radio-iodinated TPO. This method was found to be strictly specific for TGPO autoantibodies and sensitive enough to assay TGPO autoantibodies in serum. In humans, TGPO autoantibodies were found in most of the sera with high TG and TPO autoantibody titres, but not in sera negative for TG autoantibodies, whatever the TPO autoantibody titre. Furthermore, high TGPO autoantibody titres were found in sera strongly cytotoxic for cultured porcine thyroid cells. However, significant correlation of TGPO autoantibody titre was observed neither with TG and TPO autoantibody titres (n = 48) nor with complement-dependent cytotoxicity (n = 50). TGPO antibody assay was also performed in individual plasma of CBA/J mice immunized with either human TG (n = 6) or human TPO (n = 6). Immunization with TG induced high levels of not only TG but also TGPO antibodies, which exhibited a strong reactivity for TPO and whose binding to TG and TPO was fully inhibited by TG. In contrast, immunization with TPO induced high levels of only specific TPO antibodies accompanied by low levels of specific TG antibodies. In this case TGPO antibodies were not detected. Of note, TG- and TPO-immunized mice mounted an immune response against their own TG, but did not exhibit histological signs of thyroiditis. Large panels of TG and TPO MoAbs were also investigated with this method: 18/25 TG MoAbs and only 1/13 TPO MoAbs were found cross-reactive. Taken together, these data provide evidence that TGPO antibodies are effectively present in individual patients and TG-immunized mice, are different from specific TG and TPO antibodies, and may derive from natural B cell repertoire by autoimmune processes involving TG and not TPO.
Animals↗
Immunohistochemical study of thyroid peroxidase in normal, hyperplastic, and neoplastic human thyroid tissues.
An immunohistochemical study using two monoclonal antibodies (MoAb 30 and MoAb 47) against thyroid peroxidase (TPO) was performed on surgical specimens of human thyroid carcinoma (n = 65), adenoma (n = 70) and Graves' disease (n = 10). Normal adjacent thyroid tissue was used as positive control. Monoclonal antibody 30 reacted significantly with all adenoma and most carcinoma, whereas MoAb 47 reacted with 66 adenoma but only two carcinoma. Of the four adenomas that did not react with MoAb 47, three were of the fetal type. Both carcinoma reacting with MoAb 47 were of the well-differentiated follicular type. These findings further confirm the hypothesis that thyroid carcinoma is associated with changes in the quantity and antigenic properties of TPO. Although the alterations in antigenic behavior revealed by MoAb 47 are not 100% specific, they may allow more accurate diagnosis of malignancy in thyroid tumors.
Adenocarcinoma↗
[Anatomo-pathology of cholesteatoma].
The authors, from their own histopathological studies and from an overview of otological literature focus the controversial problems about the so-called disease cholesteatoma. The history of cholesteatoma has been marked out by pathologic data which, initially caused the cholesteatoma to be identified as a keratinized squamous tumor. This misnomer will however be retained because of it long-established usage. "Skin in the wrong place" in the middle ear summarizes this clinical entity. Electron microscopic observations provide arguments in favour of the migratory theory and the invasion of the epidermis from the bottom of the external ear canal into the middle ear cavity (identical fine morphology between skin and cholesteatoma, presence of Langerhans and Merkel cells, sharp junction between the advancing front of the cholesteatoma and the middle ear mucosa). Recent immunohistological techniques allow consideration of cholesteatoma as a self-induced inflammatory process in response to tissular and cellular conflicts. A cholesteatoma could be merely a non-healing wound process and a disease of epidermal growth control occurring in the middle ear space. The logical principles governing cholesteatoma surgery, suggested by these biological considerations, are: total removal of cholesteatoma matrix, prevention of cholesteatoma recurrence by a careful respect of the barrier separating the middle ear mucosa from the skin-lined bony external ear canal, maintenance of good healing conditions for both mucosa in a closed well-ventilated middle ear and epidermis in a harmonious anatomical external canal.
Cell Movement↗
[Immunohistochemistry of thyroid cancers. II. Medullary carcinomas (CMT) and "mixed" or "intermediate" tumors].
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Biomarkers, Tumor↗