Absence of allelic imbalance involving EMSY, CAPN5, and PAK1 genes in papillary thyroid carcinoma.

Papillary thyroid cancer (PTC) accounts for 80% of all thyroid malignancies, and genetic alterations associated to its etiology remain largely unknown. Chromosomal band 11q13 seems to be one of the most frequently amplified regions in human cancer, providing several candidate genes that need detailed characterization. The aim of our study was to investigate the existence of allelic imbalance at EMSY, CAPN5, and PAK1, as candidate genes within 11q13.5-q14 region using a single nucleotide polymorphism-based analysis. We selected a panel of 9 polymorphisms that were analyzed in 41 thyroid carcinoma samples, their contralateral non-pathological tissue and 178 controls from the general population. We did not detect allelic imbalance at these loci in our series. However, we observed a difference in the EMSY-haplotype distribution among PTC patients when compared to controls (odds ratio=2.00; p=0.02). We conclude that 11q13.5-q14 is not imbalanced in PTC, but there is evidence suggesting that EMSY might be of relevance in PTC etiology.

Detection of high mobility group I HMGI(Y) protein in the diagnosis of thyroid tumors: HMGI(Y) expression represents a potential diagnostic indicator of carcinoma.

Hyperplastic or neoplastic proliferative lesions of thyroid follicular epithelium consist of a spectrum, ranging from nodular hyperplasia to undifferentiated (anaplastic) carcinoma, and usually present as palpable thyroid nodules. Thyroid nodules are a common occurrence in the general population, but only a small proportion of them are eventually diagnosed as carcinoma. The difficulty in objectively identifying those thyroid nodules that are malignant to avoid unnecessary surgery, combined with the range and effectiveness of the available therapeutic options in those patients who do, indeed, have thyroid carcinoma, has prompted the search for tumor markers and prognostic indicators. The high mobility group I (HMGI) proteins represent a class of nuclear proteins involved in the regulation of chromatin structure and function. HMGI(Y), one of the members of this class, is expressed at high levels during embryogenesis and in malignant tumors but at generally low levels in normal adult human tissues. Previous work on a limited number of thyroid samples suggested that the detection of the HMGI(Y) proteins may provide a clinically useful diagnostic tool. To verify this assumption, we analyzed HMGI(Y) expression by a combination of immunohistochemistry and reverse transcription-PCR in 358 thyroid tissue samples that were representative of the spectrum of thyroid tumor pathology. HMGI(Y) was detectable in 18 of 19 follicular carcinomas, 92 of 96 papillary carcinomas, and 11 of 11 undifferentiated (anaplastic) carcinomas but in only 1 of 20 hyperplastic nodules, 44 of 200 follicular adenomas, and 0 of 12 normal tissue samples. The correlation between HMGI(Y) expression and a diagnosis of carcinoma was highly significant (P < 0.0001). We also prospectively collected and analyzed for HMGI(Y) expression by immunohistochemistry and reverse transcription-PCR in 12 fine needle aspiration biopsies from 10 patients who subsequently underwent surgical removal of a solitary thyroid nodule. HMGI(Y) was detectable only in the four fine needle aspiration biopsies, corresponding to the thyroid nodules that were definitively diagnosed as carcinomas after surgery (two follicular carcinomas and two papillary carcinomas). The remaining eight samples (six follicular adenomas and two samples consisting of normal follicular cells) were negative. The findings of this study confirm the differential expression of HMGI(Y) in thyroid neoplasia and indicate the HMGI(Y) protein as a potential marker for thyroid carcinoma.

The expression of the high mobility group HMGI (Y) proteins correlates with the malignant phenotype of human thyroid neoplasias.

High Mobility Group I (HMGI) proteins are nuclear proteins involved in the regulation of chromatin structure and function. Elevated expression of the HMGI proteins (HMGI, HMGY and HMGI-C) has been correlated with the presence of a highly malignant phenotype in epithelial and fibroblastic rat thyroid cells, and in several experimental carcinomas. Here, we demonstrate that HMGI and HMGY proteins are expressed in human thyroid carcinomas and thyroid carcinoma cell lines, but not in adenomas, goiters, normal thyroid tissues and cells. These results indicate a correlation between HMGI and HMGY expression and the malignant phenotype of thyroid neoplasias, suggesting that these proteins may be used as markers in thyroid cancer.

RET/PTC oncogene activation is an early event in thyroid carcinogenesis.

RET/PTC oncogene activation occurs in about 20% of human thyroid papillary carcinomas. However, it is not known yet whether it is an early or late event in the process of thyroid carcinogenesis. Here we demonstrate, by using a combined immunohistochemical and reverse transcriptase-polymerase chain reaction based approach, that RET/PTC activation is present in 11 out of 26 occult thyroid papillary carcinomas analysed. Therefore, we conclude that it represents an early event in the process of thyroid cell transformation.

Extracardiac vascular and neural lesions in the toxic oil syndrome.

The toxic oil syndrome is a multisystemic disease caused by the ingestion of adulterated rapeseed oil. The basic lesion is a peculiar vasculitis that affects mainly the intima, showing the features of an endovasculitis. Vessels of every type and size are involved, affecting practically every organ. The vascular lesions begins with endothelial damage that varies from cellular swelling to cellular necrosis. It then progresses by mixed cellular inflammatory infiltration of the intima and, in some cases, of the media and adventitia. In some cases the infiltrate is rich in eosinophils and a few show foamy histiocytes. Proliferation of myointimal cells and in advanced stages fibroblastic proliferation causes narrowing or obliteration of the vascular lumen. Thromboembolic complications perpetuate the vascular lesion and compound the ischemia and parenchymal atrophy of several organs. The peripheral nerve lesions begin with an inflammatory neuropathy with lymphocytic perineuritis and progress to perineural fibrosis with secondary axonal degeneration. Skeletal muscle lesions exhibit an interstitial inflammatory myopathy at first, followed by a neurogenic muscular atrophy. A direct effect of unidentified toxic substances, possibly free radicals, may cause the endothelial lesion. Other factors, such as immunopathologic mechanisms of delayed hypersensitivity, may contribute to the progression of the vascular lesions.

Clinical and pathologic manifestations of pulmonary vascular disease in the toxic oil syndrome.

The toxic oil syndrome in Spain affected greater than 20,000 people. In the initial stages, it was characterized by a respiratory distress syndrome with myalgias and eosinophilia. Pulmonary hypertension developed in 20% of the patients and in many, it has spontaneously regressed. Nevertheless, in a small subgroup, it has progressed to a malignant course of cor pulmonale, leading rapidly to death. Clinical and pathologic features of 40 patients with severe pulmonary hypertension due to the toxic oil syndrome are presented (32 female and 8 male patients; mean age 26 +/- 13 years). The study began in June 1981, which was near the onset of the toxic oil epidemic, and ended in December 1987, greater than 6 years later. The pulmonary hypertension is clinically and pathologically indistinguishable from primary pulmonary hypertension. Direct endothelial injury by the toxic agent is proposed as the initial trigger of this type of pulmonary hypertension, but an interaction between the toxic agent and specific individual susceptibility is probably required in its pathogenesis.

Cardiac abnormalities in the toxic oil syndrome, with comparative observations on the eosinophilia-myalgia syndrome.

Early in the course of studies of the Spanish toxic oil syndrome it was recognized that vascular lesions were a major problem, most logically attributable to endothelial damage by the toxic oil. However, most clinical attention has been directed to the pulmonary complications and the evolution into a scleroderma-like illness later. In this study of 11 victims of the toxic oil syndrome careful postmortem studies of the coronary arteries and conduction system and neural structures of the heart demonstrated major injury to all those components of the heart. Obliterative fibrosis of the sinus node in four cases resembled findings in fatal scleroderma heart disease, and in eight the cardiac lesions resembled those of lupus erythematosus. The more impressive pathologic features involved the coronary arteries and neural structures, which were abnormal in every heart. The arterial disease included widespread focal fibromuscular dysplasia, but there was also an unusual myointimal proliferative degeneration of both small and large coronary arteries in five patients, four of whom were young women. In two hearts, portions of the inner wall of the sinus node artery had actually detached and embolized downstream. Coronary arteritis was rarely found. Inflammatory and noninflammatory degeneration of cardiac nerves was widespread. Fatty infiltration, fibrosis and degeneration were present in the coronary chemoreceptor. In most respects these cardiac abnormalities resemble those described in the eosinophilia-myalgia syndrome caused by an altered form of L-tryptophan. In both diseases there is good reason to anticipate more clinical cardiac difficulties than have so far been reported, and even more basis for future concern, especially relative to coronary disease and cardiac electrical instability.

Pulmonary hypertension due to toxic oil syndrome. A clinicopathologic study.

Clinical and pathologic findings in seven patients who died of severe pulmonary artery hypertension due to toxic oil syndrome are assessed. These cases correspond to a late stage of evolution of the disease characterized by progressive deterioration in clinical features--increasing dyspnea, chest pain, syncope, and death (in low-output heart failure). The main pathologic pulmonary vascular findings consisted of plexiform lesions, thromboses, and venous lesions. Endothelial damage induced by the toxic agents is suggested as an initial causative mechanism, perpetuated by intimal proliferation and in situ thrombosis. Plexiform lesions appear late and active histologically. This new cause of pulmonary artery hypertension, with pathologic findings similar to those found in primary pulmonary hypertension, may help in understanding the pathophysiology of this unknown disease.

Osteoblastoma and osteoid osteoma. Clinical and morphological features of 162 cases.

A study of 46 osteoblastomas and 91 osteoid osteomas, selected from a total of 162 cases proceeding from 15 Spanish Hospitals was done to establish epidemiological data on clinico-pathological parameters and to compare them with the findings of other authors. A comparative study between both tumors is done and emphasis is put on the discussion of aggressive osteoblastoma.

Malignant fibrous histiocytoma of bone. A clinico-pathological and electronmicroscopical study.

The clinicopathological and ultrastructural features of seven Malignant Fibrous Histiocytomas reported to the Spanish Registry of Bone Tumors were studied. Two patients were females (20 and 60 years old) and the other five males (15, 37, 67, 38 and 17 years old). The tumors were located in the lower femur (3 cases), upper tibia, upper humerus, rib and iliac bone. The past medical history revealed previous fracture in one patient and previous radiation of the affected bone in another; in a third patient the tumor associated to a bone infarct. Microscopically all tumors presented a storiform pattern composed of neoplastic fibroblasts, histiocytes, and malignant multinucleated giant cells. There was no evidence of osteoid or bone tissue formation by the tumor cells. Five cases were studied with electronmicroscopy; the tumor cells had features of fibroblasts, myofibroblasts, histiocytes and multinucleated histiocytes. Primary and secondary lysosomes, along with lipid vacuoles were common findings in the tumor cells. The value of the electron-microscopy in the differential diagnosis of this tumor is emphasized.

Hepatocellular carcinoma. A study of 50 autopsy cases with detection of hepatitis B surface antigen in fixed tissues.

Fifty patients who died of hepatocellular carcinoma (HCC) were autopsied at the Ciudad Sanitaria "1 degree de Octubre" and the Hospital de la Cruz Roja (Madrid) from 1974 to 1980. Formalin fixed paraffin-embedded autopsy tissue of liver and tumor from the 50 HCC and liver tissue from 50 liver cirrhosis (LC) and from 50 autopsy of non cirrhotic control cases were examined for the presence of cytoplasmic hepatitis B surface antigen (HBsAg). The study was carried out using orcein staining, immunoperoxidase technique (IP) and indirect immunofluorescence (IF). In livers with HCC the HBsAg was detected in the cytoplasm of the hepatocytes in 10 cases (20%) with the orcein staining and in 11 (22%) with the IP and IF techniques. In one case (2%) HBsAg was found in the cytoplasm of tumor cells with the three methods--In four cases (8%) of LC and 2 (4%) control cases cytoplasmic positive cells were found. In 41 patients with HCC HBsAg was studied in the serum by radio-immunoassay (RIA) (13 cases) and immunodiffussion (28 cases). 5 patients (12,1%) were positive and 36 (72%) were negative. In the 5 serum positive HBsAg HCC the staining methods for cytoplasmic HBsAg were positive (100%). In 36 serum negative HBsAg HCC the staining method were positive in 2 cases. The results let us to conclude that HBV is a probable important etiologic factor of HCC in our milieu. 54% of the patients with HCC had a previous history of alcohol abuse; however, histologic features compatible with an alcoholic etiology were found in only 5 cases. Nevertheless we consider that the described histopathologic findings do not exclude excess alcohol consumption as a possible etiologic factor for HCC in our series.

Chest wall hamartoma. Report of two cases with secondary aneurysmal bone cysts.

Chest wall hamartoma is a rare non-neoplastic benign lesion occurring in the neonatal period with particular clinical, radiological and pathological features. Histologically, it is composed of a mixture of bone trabeculae with spindle-cell stroma, chondroblast-like cells, and mature and immature hyaline cartilage. Aneurysmal bone cyst is a benign lesion that may arise secondary to several bone processes, such as giant cell tumor, chondrosarcoma, non-ossifying fibroma or osteosarcoma. We present two new cases of chest wall hamartoma with secondary aneurysmatic bone cyst formation studied with histological and immunocytochemical methods.

Nasolabial cyst: report of a case with extensive apocrine change.

The nasolabial cyst is a rare condition of the midline with an uncertain pathogenesis. This case report describes a 44-year-old woman in which the clinicopathologic findings were consistent with nasolabial cyst. On histologic examination, extensive apocrine change was noticed. To our knowledge, this feature has not been mentioned in previous papers. In addition, cases reported during the last decade are summarized.

Primary adenocarcinoma of the vagina. A case report with light and electron microscopic study.

A case of primary adenocarcinoma of the vagina in a 46 year old woman is reported. The light and electron microscopic studies are highly suggestive of a Müllerian origin. The ultrastructural features are discussed in relation to clear cell adenocarcinoma of the vagina, establishing the differences between them.

Salivary gland heterotopia in the lower neck: a report of five cases.

Heterotopic salivary gland tissue (HSGT) represents an uncommon lesion, usually presenting as a discharging sinus in the base of the neck. Diagnostic criteria and embryogenesis of this entity still remain unclear. For the purpose of clarifying both subjects, all lateral cervical anomalies undergoing surgery during a 12-year period were examined. Histological study showed salivary tissue in 10 out of 119 patients. However, only 5 of them accomplished HSGT criteria. This study presents the second largest series to date of undisputed HSGT in the lower neck. Both accessory glands and branchial cleft anomalies should be distinguished from this lesion. Neoplastic transformation in HSGT, although extremely rare, should also be considered.

Immunoreactivity in granular cell tumours of the larynx.

OBJECTIVE: To elucidate histogenesis and behaviour of laryngeal granular cell tumours (GCT) and to determine the role of p53 protein expression in these lesions. METHODS: The clinical, pathological and immunohistochemical findings of three cases of laryngeal GCTs are described. RESULTS: All tumours were surgically excised and appeared histologically benign. Pseudoepitheliomatous hyperplasia, mitosis and nuclear pleomorphism were not found in any of the three cases. All lesions were negative for keratin 8, desmin and actin. Only one case stained for collagen IV. Positive staining was found for S-100 protein and CD68 in all tumours. Ki-67 and Bcl-2 staining was confined to occasional cells. p53 reactivity was seen in all tumours; positivity ranged from 35 to 42%. The three patients have remained free of disease without complications up to 10 years after treatment. CONCLUSION: Immunohistochemical findings support benign behaviour and a Schwann cell origin for laryngeal GCT. The expression of p53 by granular cells is unclear but appears to be unrelated to behaviour.

[Clinico-pathologic study of renal cell carcinoma]. / Estudio clínico-patológico del carcinoma de células renales.

Renal cell carcinoma (RCC) is an uncommon tumour with high mortality mainly due to late diagnosis. The various morphological variables and the clinico-pathological stage, however, induce highly different evolutions. Awareness of these characteristics would be a significant part of deciding the most appropriate therapy for each case. The pathological anatomy of 130 renal cell carcinomas obtained through nephrectomy was reviewed. A follow-up of at least 5 years was done in 121 patients. Also, a survival study related to the various clinical and pathological parameters was carried out. A significantly lower survival rate was observed for solid tumours with spindle or giant cells and nuclear degrees superior to 2, over 10 mitosis in 10 fields and staging higher than II. A significant correlation was also found between number of mitosis and staging, presence of metastatic disease, survival interval, degree of tumoral necrosis, histological type, cell type and nuclear grade. Our results indicate that staging, histological type, cell type, microscopic vascular infiltration, nuclear grade and number of mitosis can be highly predictive of the evolution and prognosis of RCC patients.

[An analysis of the prognostic factors in renal-cell carcinoma]. / Analisis de factores pronósticos en el carcinoma de células renales.

OBJECTIVES: The study proposes the analysis of the influence of gross, microscopical and clinical pathoanatomical prognostic factors in the survival of patients with RCC through univariance and multivariance statistical analysis, and its global evaluation as a predictive model. PATIENTS AND METHOD: The study involved 218 RCC cases operated on over 20 years, with a mean follow-up of 60 months. RESULTS AND CONCLUSIONS: All prognostic factors studied have a significant influence on the survival. When studied jointly, they include separately and in order of significance the metastatic involvement, mitotic index, cava vein involvement, nuclear grade and sarcomatoid histologic pattern. Also, we confirm that considered jointly they conform a valid predictive model.

[Branchial cysts with heterotopic salivary tissue in the upper third of the neck]. / Quistes branquiales con tejido salival heterotópico en el tercio superior del cuello.

The presence of heterotopic salivary gland tissue (HSGT) in rather uncommon in the neck. Usually it has been located in its lower third. HSGT in the upper neck is believed to be a rare entity. Two cases of HSGT in the upper neck are presented, with a review of their clinical and histopathological characteristics. The embryologic derivation of salivary tissue and close association with the branchial apparatus are discussed. The possibility of neoplastic transformation must always be considered in these uncommon lesions.

[Granular cell tumor: an infrequent cause of dysphonia in childhood]. / Tumor de células granulares: una causa poco frecuente de disfonía en la infancia.

Granular cell tumors (GCT) are rare and usually benign tumors whose histogenesis is debated. The skin, subcutaneous tissues, and mucosae of the head and neck are areas of predilection for GCT. Laryngeal involvement is uncommon, but may create diagnostic and therapeutic problems when it occurs. Laryngeal GCT are decidedly uncommon in children, only 17 cases having been reported in the literature. A case of GCT of the larynx in an 11-year-old girl is reported. The presenting symptom was hoarseness. The macroscopic tumor and hoarseness disappeared after chemotherapy (EVAIA) for Ewing sarcoma of the knee.