bromochloroacetic-acid and Tuberous-Sclerosis

A rare case of pancreatic neuroendocrine neoplasm in a patient with tuberous sclerosis complex is described. The patient was a 31-year-old man who had multiple congenital subependymal nodules, bilateral cortical tubers, and seizures of difficult control. A 2.3 cm × 2 cm well-delimitated solid tumor in the tail of the pancreas was discovered during a monitoring abdominal computed tomography. A distal pancreatectomy was performed. Histologically, the tumor was formed by uniform cells with moderated cytoplasm arranged in a combined trabecular and nested pattern. The nuclear features were bland, and mitosis was infrequent. There was no vascular invasion. Immunoreactivity for cytokeratine AE1/AE3, chromogranin A, and synaptophysin confirmed the neuroendocrine nature of this neoplasia. Pancreatic hormones were negatives. One of the 5 lymph nodes isolated from the peripancreatic adipose tissue was positive for metastases. Small series and case reports have documented that in tuberous sclerosis many endocrine system alterations might occur, affecting the function of the pituitary, parathyroid, and other neuroendocrine tissue, including islet cells of the pancreas. However, the true association of these pathological conditions remains uncertain. As far as we know, there are 10 cases reported of pancreatic neuroendocrine tumors in a setting of tuberous sclerosis complex, in which 2 cases resulted in malignant, nonfunctioning pancreatic neuroendocrine tumors.

Topics: Adult; Biomarkers, Tumor; Chromogranin A; Humans; Keratins; Lymphatic Metastasis; Male; Neuroendocrine Tumors; Pancreatectomy; Pancreatic Neoplasms; Synaptophysin; Tuberous Sclerosis

The association between renal carcinoma and angiomyolipoma is rare. Only 14 cases have been reported in the literature. The purpose of this paper is to present an additional case and review the literature on this association.. A healthy 42 year old woman was found to have a left flank mass incidentally when she presented for a Papanicolaou smear. The computerised tomography scan revealed a left lower pole renal mass consistent with a renal cell carcinoma. A nephrectomy was performed and the patient recovered uneventfully. The nephrectomy specimen was processed routinely. In addition to haematoxylin and eosin staining, immunohistochemistry for CAM 5.2, vimentin, CD34, antismooth muscle actin, and HMB45 was carried out. Transmission electron microscopy was also performed.. Macroscopically, the lower pole of the kidney contained a well circumscribed, non-encapsulated, tan coloured tumour with a large area of central haemorrhage measuring 10.5 cm. In addition, there was a 0.4 cm poorly circumscribed unencapsulated yellow nodule adjacent to the tumour. Microscopically, the larger tumour showed characteristic features of an oncocytoma. Numerous mitochondria were seen on electron microscopy. The smaller yellow nodule was an angiomyolipoma.. This paper presents an additional case of oncocytoma associated with angiomyolipoma. Of the 15 cases described in the literature, three were associated with the tuberous sclerosis complex, all from a single study. In tuberous sclerosis, angiomyolipomas are more commonly associated with renal cell carcinoma. If angiomyolipomas are found incidentally in nephrectomy specimens together with other tumours, it is important to exclude tuberous sclerosis retrospectively.

Topics: Actins; Adenoma, Oxyphilic; Adult; Angiomyolipoma; Antigens, CD34; Autoradiography; Biomarkers; Female; Humans; Keratins; Kidney Neoplasms; Microscopy, Electron; Neoplasms, Multiple Primary; Nephrectomy; Tomography, X-Ray Computed; Tuberous Sclerosis

Topics: Acrodermatitis; Amino Acid Metabolism, Inborn Errors; Basal Cell Nevus Syndrome; Epidermolysis Bullosa; Hair Diseases; Humans; Ichthyosis; Keratins; Keratosis; Neurofibromatosis 1; Psoriasis; Refsum Disease; Skin; Skin Diseases; Skin Neoplasms; Tuberous Sclerosis; Tyrosine; Warts; Xeroderma Pigmentosum

Tuberous sclerosis complex results from mutations in 1 of 2 interacting gene products, hamartin or tuberin. The syndrome is characterized by hamartomas and neoplastic lesions, including angiomyolipomas of the kidney and other organs. Renal cell carcinoma (RCC) in tuberous sclerosis remains relatively poorly characterized because historical studies were confounded by the inclusion of epithelioid angiomyolipomas. The authors present a patient with tuberous sclerosis and bilateral renal lesions, including multiple minute angiomyolipomas, cortical cysts, and 4 separate RCCs of unclassified type. The carcinomas shared distinctive morphological features, including sheet-like, glandular, trabecular, or cystic architecture and abundant granular eosinophilic cytoplasm. By definition, the carcinomas were keratin positive and negative for HMB-45 and Melan-A. Detailed immunohistochemical analysis revealed heterogeneity among the cortical cysts and carcinomas. The histopathological features of these carcinomas illustrate characteristics of renal carcinoma that are probably related to genetic alterations of tuberous sclerosis.

Topics: Adult; Angiolipoma; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Neoplasms, Multiple Primary; Treatment Outcome; Tuberous Sclerosis

This study investigated the clinical and pathological findings of lung disease in tuberous sclerosis complex (TSC) as previously reported in Japan.. The clinical and pathological findings in 15 patients diagnosed as having multifocal micronodular pneumocyte hyperplasia (MMPH) with TSC were analysed.. The majority of patients (80%) were women and the mean age was 37 years. Three patients had a family history of TSC. The radiological findings were small multiple nodular shadows with ground-glass opacity randomly distributed in the bilateral whole-lung fields in most patients. Differentiation from multiple atypical adenomatous hyperplasia or metastatic lung cancer was necessary in most patients. In 11 patients, the diagnostic method used to identify pulmonary lesions of MMPH with TSC was VAT. Among the complications of MMPH with TSC, lymphangioleiomyomatosis was recognized in 53% of patients. The prognosis was comparatively good because only one patient died of respiratory failure. The histological findings were papillary or tubular proliferation of type II pneumocytes without nuclear atypia lining the thickened alveolar septa and lymphocyte infiltration. Immunohistochemical staining for cytokeratin, and surfactant proteins A and B was positive in alveolar lining cells of all MMPH lesions. However, staining for HMB-45, alpha-smooth muscle actin, p53, carcinoembryonic antigen and hormonal receptor was negative in most patients.. Surgical investigation and immunohistochemical staining for pathological markers are useful for diagnosing MMPH when the radiological findings indicate multiple micronodules with ground-glass opacity in patients with TSC.

Topics: Adult; Diagnosis, Differential; Disease Progression; Female; Humans; Hyperplasia; Immunohistochemistry; Incidence; Japan; Keratins; Lung; Male; Middle Aged; Multiple Pulmonary Nodules; Retrospective Studies; Tuberous Sclerosis; Young Adult

Topics: Actins; Antigens, Neoplasm; Desmin; Diagnosis, Differential; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; Lung; Lung Neoplasms; Lymphangioleiomyomatosis; Melanoma-Specific Antigens; Middle Aged; Muscle, Smooth; Neoplasm Proteins; Nuclear Proteins; Receptors, Estrogen; Receptors, Progesterone; Thyroid Nuclear Factor 1; Transcription Factors; Tuberous Sclerosis

Tuberous sclerosis complex (TSC) is a tumor suppressor gene disorder characterized by mutations in the TSC1 or TSC2 genes. These mutations lead to the development of benign tumors involving smooth muscle cells, causing life-threatening lymphangioleiomyomatosis. We isolated and characterized two types of cells bearing a mutation in TSC2 exon 18 from a renal angiomyolipoma of a TSC patient: one population of alpha-actin-positive smooth muscle-like cells with loss of heterozygosity for the TSC2 gene (A(+) cells) and another of nonloss of heterozygosity keratin 8/18-positive epithelial-like cells (R(+) cells). Unlike control aortic vascular smooth muscle cells, A(+) cells required epidermal growth factor (EGF) to grow and substituting EGF with insulin-like growth factor (IGF)-1 failed to increase the cell number; however, omission of EGF did not cause cell loss. The A(+) cells constantly released IGF-1 into the culture medium and constitutively showed a high degree of S6K phosphorylation even when grown in serum-free medium. Exposure to antibodies against EGF and IGF-1 receptors caused a rapid loss of A(+) cells: 50% by 5 days and 100% by 12 days. Signal transduction mediated by EGF and IGF-I receptors is therefore involved in A(+) cell survival. These results may offer a novel therapeutic perspective for the treatment of TSC complications and lymphangioleiomyomatosis.

Topics: Actins; Adult; Angiomyolipoma; Aorta; Cell Culture Techniques; Cell Proliferation; Cell Survival; DNA Mutational Analysis; Epidermal Growth Factor; Exons; Female; Fluorescein-5-isothiocyanate; Fluorescent Antibody Technique, Indirect; Fluorescent Dyes; Genes, Tumor Suppressor; Genetic Markers; Humans; Immunohistochemistry; Insulin-Like Growth Factor I; Keratins; Loss of Heterozygosity; Microsatellite Repeats; Muscle, Smooth; Muscle, Smooth, Vascular; Mutation; Phosphorylation; Rhodamines; Ribosomal Protein S6 Kinases, 70-kDa; Tuberous Sclerosis; Tuberous Sclerosis Complex 1 Protein; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by mental retardation, seizures, and central nervous system and visceral hamartomas. Pulmonary involvement manifesting as lymphangioleiomyomatosis (LAM) occurs in 1% of patients (all women) with TSC. Micronodular pneumocyte hyperplasia also has been described as a rare pulmonary manifestation of TSC. We report 14 patients with micronodular pneumocyte hyperplasia (MNPH). The patients ranged in age from 23 to 57 years (mean 37.5). There were 12 women and 2 men. Nine of the patients (one man and eight women) had documented clinical manifestations of TSC: seven with LAM, two without LAM (including one man). Of the five patients who did not have TSC, three had LAM and two did not (including one man). Histologically, all 14 cases demonstrated multiple well-demarcated nodules usually measuring up to 8 mm in size, but most were 1-3 mm. The nodules were produced by a proliferation of enlarged cytologically benign type II pneumocytes, with an associated increase in alveolar macrophages and interstitial reticulin. Immunoperoxidase studies showed the type II pneumocytes within lesions to be reactive with antibodies to cytokeratin (four of four), epithelial membrane antigen (EMA) (five of five), and surfactant apoprotein B (8 of 10). HMB-45 was negative in the MNPH lesions in all nine cases studied. Follow-up was available in 9 of 10 living patients and ranged from 1 to 14 years (mean 6 years). Nine patients are alive; six are clinically stable and three have repeated pneumothoraces related to LAM. Four patients have died. None of the deaths were attributable to MNPH. MNPH appears to be a hamartomatous proliferation occurring most frequently in patients with tuberous sclerosis, is separable from and not a manifestation of LAM, has been observed to occur in men, and, like other hamartomas of tuberous sclerosis, does not appear to possess malignant potential.

Topics: Adult; Biomarkers; Female; Humans; Hyperplasia; Immunohistochemistry; In Situ Hybridization; Keratins; Lung; Lymphangioleiomyomatosis; Male; Middle Aged; Repressor Proteins; RNA, Messenger; Tomography, X-Ray Computed; Tuberous Sclerosis; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins

Tuberous sclerosis (Bourneville-Pringle phacomatosis) has been known to be associated with cardiac rhabdomyoma, but apparently never previously with primary pericardial mesothelioma. We present an autopsy case of this condition in a 59-year-old man, who had been diagnosed as having tuberous sclerosis in view of the presence of facial sebaceous adenoma, mental retardation, intracranial calcification, cerebral ventricular dilatation and renal tumor. During the clinical course, characterized by heart failure due to cardiac tamponade, cardiac sarcoma was diagnosed by imaging techniques. Autopsy revealed biphasic-type primary pericardial mesothelioma. As to the tuberous sclerosis, atypical giant cells in the tubers of the cerebral cortex and the lateral ventricular wall were found, which were considered to be derived from neurons rather than glial cells on the basis of staining with Bodian, Holzer, and antibodies against NSE, GFA and S-100 protein. In old tubers protruding into the lateral ventricles, fibrous glias were present with dense calcospherite deposits, coinciding with the CT findings. The renal tumors were angiomyolipomas, which were present bilaterally and showed partially infiltrative growth, but seemed to have a benign nature because of the lack of metastasis and atypism of the leiomyocytes.

Topics: Autopsy; Cerebellum; Glial Fibrillary Acidic Protein; Heart Neoplasms; Hemangioma; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Kidney; Kidney Neoplasms; Lipoma; Male; Membrane Glycoproteins; Mesothelioma; Middle Aged; Mucin-1; Pericardium; Phosphopyruvate Hydratase; S100 Proteins; Tuberous Sclerosis

Subcellular defects of hypomelanosis in tuberous sclerosis (TS) (28 subjects) were compared by light and electron microscopy with oThere forms of congenital circumscribed hypomelanosis that occur in nevus depigmentosus (ND) (8 subjects) and in piebaldism (PB) (4 subjects), respectively. On the light microscopic level in both TS and ND, the population density of functioning melanocytes was normal but each perikaryon was small, and dopa activity was decreased. On the ultrastructural level, the hypomelanotic skin and hair of TS were associated with a decrease in the synthesis, melanization, and size of melanosomes; the decrease in the size of melanosomes resulted in the aggregation of melanosomes (i.e., a melanosome complex) in the keratinocytes in all the specimens examined. In ND, ther were no obvious changes in the size and melanocytes. the hypomelanosis of ND is related to the decreased synthesis and also, perhaps, abnormal transfer of melanosomes. In PB the hypomelanosis of the skin and hair results from the absence of functional melanocytes. The hypermelanotic areas of PB, however, characteristically contain melanocytes that synthesize abnormal (sperical and granular) as well as normal (ellipsoidal and lamellar) melanosomes.

Topics: Adolescent; Adult; Albinism; Black People; Child; Child, Preschool; Dihydroxyphenylalanine; Female; Hair; Humans; Infant; Keratins; Male; Melanins; Melanocytes; Microscopy, Electron; Nevus; Organoids; Pigmentation Disorders; Skin; Skin Neoplasms; Tuberous Sclerosis; White People

Topics: Alexander Disease; Brain Diseases; Diffuse Cerebral Sclerosis of Schilder; Histocytochemistry; Humans; Hydrocephalus; Infant; Intellectual Disability; Keratins; Nerve Tissue Proteins; Pathology; Seizures; Tuberous Sclerosis