Papillary and follicular thyroid carcinomas with an insular component.
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Publications and source records attributed to M Papotti.
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Recent evidence suggests that anti-androgen therapy may be useful in patients with androgen receptor (AR)-positive hepatocellular carcinomas (HCC), as determined by a steroid binding assay. To evaluate the AR expression of HCC, in both histological and cytological material, we developed a non-radioisotopic in situ hybridisation (NISH) assay specific for the human AR mRNA. A synthetic oligonucleotide complementary to positions 661-695 of the human AR coding sequence was end-labelled with digoxigenin-dUTP and revealed by an alkaline phosphatase-conjugated anti-digoxigenin antibody. We analysed 22 formalin-fixed, paraffin-embedded HCC, obtained at surgery, together with the corresponding non-neoplastic liver tissues (19 cases). In six cases, cell blocks obtained by fine-needle aspiration (FNA) prior to surgery were also available. Positive controls included seminal vesicles and prostate tissues. Sixteen HCCs (73%) expressed a variable amount of AR mRNA, with the proportion of positive cells ranging from very few to more than 90%. Normal hepatocytes were stained weakly and focally in eight cases (42%). Appropriate controls, inclusive of immunohistochemical detection of the AR protein in selected cases, established the specificity of the assay. Data obtained on FNA specimens were predictive of the results on histologic material. However, in two cases the NISH assay was negative on the cytological specimen but stained rare hepatocytes within the surgically resected tumor. In conclusion, NISH is a novel procedure for rapid and specific assessment of the expression of AR in HCC tissue. Its clinical significance, in terms of predictivity of response to anti-androgen treatment, needs to be assessed in large correlative studies.
Immature newborn rabbits delivered at a gestational age of 27 days were tracheotomized and treated, via the tracheal cannula, with clinically recommended doses of natural or synthetic surfactant (Curosurf and Exosurf, respectively). Littermates received 0.1% tyloxapol, 5% Tween 20, or saline. The dose volume of Curosurf was 2.5 ml/kg, that of the other materials 5 ml/kg. Animals were kept in a multiplethysmograph system and ventilated for 30 min with a standardized sequence of insufflation pressures. End-expiratory lung gas volume was calculated at the end of the experiment from measurements of lung weight and total lung volume. Tidal volumes were significantly improved in all groups of animals receiving surfactant or detergents. However, expiratory time constant (determined from the tidal volume tracing) was significantly longer, and end-expiratory gas volume significantly larger, in animals treated with Curosurf than in those receiving Exosurf or detergents. These differences were confirmed by semiquantitative evaluation of alveolar air expansion in histological sections. In addition, airway epithelial necrosis was reduced in animals receiving Curosurf, Exosurf, or Tween 20, but not in animals treated with tyloxapol. The discrepancy between improvements in tidal volume, expiratory time constant, and end-expiratory gas volume reflects failure of lung stabilization in animals treated with Exosurf or detergents, probably due to absence of specific hydrophobic proteins in the synthetic products.
The authors report their personal experience in 160 patients affected with thyroid conditions examined with US and fine needle aspiration (FNA). Benign nodular hyperplasia, cystic-colloid nodular hyperplasia, colloid cyst, hemorrhagic cyst, adenoma, thyroiditis, follicular and malignant lesions were studied. The latter consisted of 5 papillary carcinomas, 6 follicular carcinomas, 1 medullary carcinoma, 1 Hürthle cell carcinoma, 1 lymphoma and 1 metastatic lesion. The following US patterns were observed: 69.2% of the malignant lesions were hypoechoic, 15.4% were hyperechoic and 7.7% isoechoic. Most of the malignant lesions (84.6%) had inhomogeneous echo texture; 46.1% of them exhibited peripheral microcalcifications. US diagnoses were compared with cytologic and/or histologic findings to assess US accuracy. In the surgical patients US accuracy reached 78.6% in benign lesions and 61.5% in malignant lesions. Since US alone fails to yield enough pieces of information for an accurate diagnosis to be made, especially when malignant lesions are concerned, FNA should be used, while trying to define the actual role of color-Doppler US.
Pulmonary lymphangioleiomyomatosis, a disease largely confined to women in their reproductive years, is reported in two postmenopausal patients. Nine similar cases in the literature are reviewed. In older women, the disease appears to be similar to that described in younger women, with the possible exception that the clinical course may be longer and more benign after the menopause. It would appear that hormonal factors play a role in the development of the disease both before and after the menopause, and that hormonal treatment may be beneficial in the older women.
Albumin is a specific product of normal and transformed hepatocytes, but unfortunately its immunohistochemical demonstration proves unreliable because of diffusion artifacts. An in situ hybridization procedure to reveal albumin mRNA was applied to fine needle aspiration specimens of liver nodes with the aim of testing the usefulness of this marker in the cytological diagnosis of hepatocellular carcinomas (HCC). A 51-base pair oligonucleotide probe was labeled with digoxigenin and used on paraffin sections of alcohol-fixed cell blocks. A series of 97 cases originally interpreted, on the basis of cytology alone, as "hepatocellular carcinoma" (62 cases), as "carcinoma cells, not otherwise specified" (15 cases), as "adeno-carcinoma" (16 cases), and as "non-epithelial neoplastic cells" (4 cases), was studied. In all cases, clinical and follow-up information was obtained; a diagnosis of HCC was reached with certainty in 44 cases and suspected in 22. Thirty-one other cases were proven to be bile duct adenocarcinomas or metastatic tumors. Taking into account proven cases only, albumin mRNA was found in 42/44 HCC and in none of the control cases (sensitivity, 95.5%; specificity, 100%). Of 22 cytologically suspected HCC, albumin mRNA was positive in 19 cases. Also, high grade pleomorphic HCCs expressed albumin gene, and this finding is of value in the differential diagnosis with liver metastases of anaplastic tumors from lung, adrenal, pancreas, etc. The diagnosis of HCC on a cytological basis is becoming increasingly important because most cases are unresectable and have to be included in different therapeutic protocols.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Apocrine carcinomas of the skin are rare and incompletely studied neoplasms. METHODS: An immunohistochemical and ultrastructural study is reported of specimens from six patients with apocrine skin carcinoma in various body sites. Three tumors were in the axilla; one, the eyelid; one, the ear; and one, the scalp. There were three local recurrences and three regional lymph node metastases, but no patient died of cancer (follow-up, 2-10 years). RESULTS: The most reliable histopathologic criteria for identifying apocrine skin carcinoma appear to be decapitation secretion, periodic acid-Schiff-positive diastase-resistant material in the cells or lumen, and immunoreactivity with gross cystic disease fluid protein 15. All specimens expressed common epithelial antigens (cytokeratins, carcinoembryonic antigen, and epithelial membrane antigen) and histiocytic-secretive antigens (Leu-M1, lysozyme, LN5, alpha-1-antitrypsin, and alpha-1-antichymotrypsin). S-100 protein was found in the three nonaxillary tumors. Ultrastructurally, the primary tumors, and especially the secondary lesions, were dedifferentiated compared with normal apocrine glands. CONCLUSIONS: Apocrine differentiation in skin tumors does not indicate an exclusive origin from the apocrine sweat glands; these neoplasms usually have an indolent clinical course.
Estrogen receptor mRNA was detected by a non-radioactive in situ hybridization assay in tumor and non-neoplastic liver tissues. A synthetic oligonucleotide complementary to the human estrogen receptor mRNA was 3'-labeled with digoxigenin-deoxyuridine triphosphate (dUTP). Hybrids were revealed by an alkaline phosphatase-conjugated anti-digoxigenin antibody. Fourteen primary hepatocellular carcinoma tissues (and one metastatic) were obtained at surgery from 15 patients. The corresponding non-neoplastic liver tissues were available in 13 cases. The estrogen receptor mRNA was detected in 11 tumorous and 7 non-tumorous liver specimens. The staining was cytoplasmic and involved the majority of transformed hepatocytes, whereas a less widespread and weaker signal was found in normal hepatocytes. Within non-neoplastic tissue, bile duct epithelial cells could also be occasionally stained, whereas other cell types, such as vasal endothelial cells, were negative. Appropriate controls established the specificity of the reaction. Detection of the estrogen receptor protein by immunohistochemistry in these same specimens was invariably negative. This in situ hybridization assay can therefore be used as a complementary tool to evaluate the estrogen receptor expression within liver cancer.
Poorly differentiated carcinomas of the thyroid share insular, trabecular, and solid histological patterns that are different from those of papillary, follicular, medullary, and anaplastic varieties. We have collected 63 cases of poorly differentiated thyroid carcinomas. Thirty-one tumors (Group A) corresponded to the so-called insular carcinomas, and 32 tumors (Group B) had predominant trabecular and solid or focally follicular patterns in the presence of a minor insular component. The cells characterizing these lesions were relatively small and globoid, with uniform nuclei and intracytoplasmic deposits of thyroglobulin. They were in every respect similar to primordial cells present in the early stages of fetal thyroid development. None of the tumors proved fatal within 6 months, and most responded to radioiodine therapy. Although no differences in survival between the two groups were found, a significantly (p < 0.01) higher percentage of recurrences or distant metastases was observed with Group A tumors. The term primordial cell carcinoma appears appropriate for this type of tumor, which displays characteristic histocytological features and production of thyroglobulin. Clinically, these tumors are aggressive but generally show a slow course and good response to radioiodine therapy.
Poorly differentiated "insular" thyroid carcinoma is a rare, aggressive and often lethal variant of thyroid cancer. Thirty-one cases of this entity were encountered over a 18-yr period. In most of them surgical therapy consisted of total or near-total thyroidectomy. Six patients had distant metastases and/or mediastinal or tracheal infiltration at presentation. Fifteen out of 25 apparently cured after surgery (60%) developed recurrence in the neck and/or distant sites. Radioiodine was employed to destroy thyroid remnants (22 cases) and subsequently to treat persistent/recurrent disease (17 cases). Thirteen patients showed radioiodine uptake in neoplastic lesions and in 3 cases complete resolution was observed. After a mean follow-up of 4.5 years (range 1-16) 6 patients had died of their tumor, 12 are alive with persistent/recurrent disease, 13 do not show any evidence of disease. This experience confirms that "insular" carcinoma tends to have an aggressive behavior, but therapy can be effective. Recognition of this entity is therefore important for planning adequate surgical approach and subsequent patient management.
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An uncommon case of gastric neurofibroma is described: it was an incidental finding during assessment for abdominal pain, possibly due to pancreatitis, in a 58 year old man, with no sign of von Recklinghausen's disease. The generic diagnosis of gastric wall neoplasia was made by CT scanning; the neoplasm was resected with wedge resection of gastric wall. Histological and ultrastructural examination revealed a neurofibroma. Gastrointestinal stromal tumors are rare occurrence and usually are of smooth muscle derivation: a small percentage arises from nerve sheet, but such a distinction is never sharp. Neurogenic gastric tumors are usually benign and only 10% of von Recklinghausen associated neurofibromas can undergo malignant transformation. Wide excision of the tumor appears therefore the treatment of choice.
Epithelial and myoepithelial cells coexist in the rat R3230AC mammary tumor. To test the hypothesis that these two cell types constitute interactive but independent neoplastic populations, we obtained in vitro cell lines with epithelial or myoepithelial patterns and transplanted them in syngeneic animals. One stabilized line (EPI) and four cloned lines (A, C, D, E) with epithelial characteristics, confirmed by positive reactions for keratins in immunocytochemical and immunoblot tests, constantly gave rise in vivo to carcinomas, which, however, lacked structural and functional patterns typical of the original tumor. A fusiform shape and immunocytochemical characteristics of myoepithelial cells were observed in three clones (H, I, L), which in vivo gave rise to sarcomatous and mixed carcinosarcomatous neoplasms. These data are consistent with the above hypothesis and indicate that breast carcinomas derive from epithelial cells, while sarcomatous and carcinosarcomatous neoplasms can originate from myoepithelial cell proliferation. This study provides data suggesting myoepithelial cell involvement in the development of pathological entities occurring in the human breast and displaying mixed epithelial and stromal neoplastic components, i.e., cystosarcoma phylloides and sarcomatous metaplasia in carcinomas.
We have studied the binding of 125I-labeled human prolactin (PRL) to membranes from various regions of the human brain (hypothalamus, cerebral cortex, cerebellum and choroid plexus) derived from autopsy specimens. Among the various regions studied, the choroid plexus of both male and female subjects showed the highest specific binding and a clearly detectable specific binding was also observed in the hypothalamus of both sexes, whereas it was very low in other brain regions. No significant sex differences in PRL binding to various brain regions were observed except for the hypothalamus where a higher binding was seen in female subjects. The binding did not vary with the age of the subjects. Moreover, the cause of death and the time elapsed from death to autopsy in this study did not affect the binding significantly. The binding of 125I-labeled human PRL to hypothalamus and choroid plexus membranes from female specimens was inhibited in a dose-dependent manner by both unlabeled human and ovine PRL and by human growth hormone (GH), but not by other polypeptide hormones. Scatchard analysis of the binding revealed the presence of saturable binding sites with low capacity and high affinity for human PRL ligand. These results provide strong preliminary evidence for the presence of PRL binding sites in the human brain.
A series of 3 tumourlets (TLs), 81 typical carcinoids (TCs), 14 atypical carcinoids (ACs) (well-differentiated neuroendocrine carcinomas, WDNCs) and 24 small cell-intermediate cell carcinomas (SCC-ICCs) of the lung were studied. Histopathological features were correlated with amine and peptide hormone immunoreactivity and with clinical data. All types of tumours expressed general neuroendocrine (NE) markers: Grimelius positivity and chromogranins were detected more frequently in well-differentiated (TLs, TCs) than in less well differentiated tumours [ACs (WDNCs) and SCC-ICCs] whereas neuron specific enolase (NSE) was prominent in the latter tumours. TLs and peripheral TCs were benign, often showing a paraganglioid pattern and frequently expressing gastrin-releasing peptide (GRP), which is present in the peripheral airways of normal lung. Central TCs were associated with lymph node metastases in 8.5% of the cases, frequently had a trabecular architecture, often associated with human milk fat globule 2 (HMFG2)-positive acinar and rosette-like structures, and were mainly immunostained for the alpha-subunit of human chorionic gonadotrophin (alpha-hCG) and serotonin. ACs (WDNCs) were associated with intrathoracic and/or extrathoracic metastases in 57.1% of the cases with a mortality rate of 35.7%. Their histological and cytological features were intermediate between those of TCs and SCC-ICCs. ACs (WDNCs) expressed serotonin and alpha-hCG less frequently than TCs. All SCC-ICCs were surgically treated and displayed a mortality rate of 91.6% with a mean survival of 10.2 months after operation. These tumours were characterized by high expression of HMFG2 and NSE, while the expression of both orthotopic (serotonin, GRP) and ectopic (ACTH) specific NE substances was very low. Since all TCs (either central or peripheral) had a favourable outcome, while about 36% of ACs (WDNCs) were fatal, the latter seem more appropriately designated "well-differentiated NE carcinomas". The differential diagnosis between different NE tumours of the lung is important and is mainly based on morphology. Both panendocrine and specific immunohistochemical markers are helpful in distinguishing the less aggressive, mostly benign varieties from the more malignant varieties.
Four cases of oat cell (neuroendocrine) carcinoma of the breast are reported. Three patients died within 15 months of the diagnosis and the fourth patient is alive after 44 months. Histochemical, ultrastructural and mRNA markers of endocrine differentiation were present in three cases. These tumours show histological similarities to breast metastases of bronchial oat cell carcinoma, but a distinguishing feature is the presence of in situ ductal lesions. It appears that the breast is a further site which has to be added to the long list of extrapulmonary oat cell carcinomas.
The Dunning tumor, originally described as a carcinoma of the rat dorsal prostate, has for long been used as an experimental model of prostatic cancer. We have recently presented a number of morphological findings that are incompatible with the prostatic origin of the H-subline of the Dunning tumor. In this paper, biochemical and immunohistochemical markers of rat prostate and mammary gland are studied in the R-3327 Dunning H tumor. Pieces of the H tumor were inoculated in male or lactating female rats. The electrophoretic protein pattern of Dunning tumor extracts was more similar to that of the mammary gland than the dorsolateral prostate. Proteins selectively appearing after metabolic labeling in Dunning tumors grown in lactating rats corresponded to labeled proteins in mammary glands from the same animals. Secretory proteins typical of the lateral prostate (SVS II) and dorsal prostate (transglutaminase) could not be detected immunohistochemically in the Dunning tumor. Western blot studies of tumor extracts and slot blot analysis of RNA preparations from the tumor confirmed the absence of SVS II and prostate specific transglutaminase from the Dunning tumor. On the other hand, the presence of mammary gland proteins such as milk fat globule membrane proteins, lactoperoxidase and lactalbumin were detected in the Dunning tumor by immunohistochemistry and Western blotting, but were absent from the dorsolateral prostate. Transferrin-mRNA, expressed in the male urogenital tract and also in the liver and other tissues, was detected in the mammary gland and Dunning tumor, but not in the dorsolateral prostate. The absence of mammary gland secretory beta-casein in the Dunning tumor was related to the elevated Ha-ras oncogene expression in the tumor, previously reported to suppress casein expression. The findings clearly demonstrate that the prostate cannot be the origin of the Dunning tumor, presently being used in prostatic cancer research. The designation prostatic adenocarcinoma for this tumor is therefore invalid. Furthermore, the data support our view that mammary gland might be the origin of the Dunning tumor, although the derivation from the bulbourethral or the parotid glands cannot strictly be excluded.
Expression of the members of the chromogranin family [i.e., chromogranin A (CgA), chromogranin B, and secretogranin II (SgII)], the acidic proteins of the matrix of the chromaffin granules presently regarded as specific neuroendocrine markers, was investigated at gene and protein levels in a series of 14 cases of primary untreated neuroblastomas. Oligonucleotides and cRNA probes were employed for hybridization analysis of specific mRNAs (both by Northern blots and nonradioactive in situ hybridization); proteins were localized by immunocytochemistry. Expression of different amounts of each type of chromogranin was determined in all tumors. Cases found immunocytochemically negative were all positive by Northern blot and in situ hybridization. A better prognosis was associated with a higher relative expression of SgII; on the contrary, a worse outcome was observed in cases with a higher expression of CgA. These findings are consistent with the hypothesis that SgII is preferentially expressed in neuroblastomas undergoing neuronal differentiation. In cases of neuroblastomas, determination of expression levels of the different chromogranins in the tissues (and in the serum) can provide parameters of high diagnostic and prognostic value.