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Fibrous dysplasia of bone is a connatal but not hereditary disease with monostotic or polyostotic manifestations and may be associated either with the extraskeletal disease McCune-Albright syndrome or with myxoma of the skeletal muscle, termed Mazabraud syndrome.The confirmation of recurrent chromosomal aberrations may lead to the conclusion that fibrous dysplasia is a neoplasia rather than a dysplastic skeletal disease.The primary cause of all forms of the described diseases is the activating GNAS mutation, which is detectable in almost all lesions. Research into the impact of this mutation has increased the understanding of these up to now solely descriptively defined diseases and also allowed easier discrimination of various fibro-osseous skeletal lesions. Current insights suggest that this mutation may also play a pivotal role in other extraskeletal neoplasias.

The intramuscular myxoma is a rare benign soft tissue tumor characterized by bland spindle-shaped and stellate cells embedded in hypovascular myxoid stroma. We report the isolated case of a 44-year-old female patient with an intramuscular myxoma in the anterior tibial muscle and report the clinical and radiographic findings. We performed an analysis of the GNAS gene mutation status with a positive finding. In difficult cases, recurrent tumors or small biopsies detection of a GNAS mutation can be useful to confirm the diagnosis of an intramuscular myxoma.

Sex cord markers comprise proteins and hormones that are produced in sex cord-derivatives in normal ovaries and testes as well as in gonadal sex cord-stromal tumors. Sex cord markers (e.g. inhibin-alpha) are used clinically as serum tumor markers. Immunohistochemical staining of sex cord markers may be helpful in the differential diagnosis of ovarian sex cord-stromal tumors versus surface epithelial-stromal tumors, germ cell tumors, other ovarian tumors, and ovarian metastases. Inhibin-alpha has been shown to be the most specific marker of sex cord differentiation. In comparison, calretinin is a somewhat more sensitive albeit less specific marker. Currently, an immunohistochemical panel including inhibin-alpha and calretinin is considered most helpful in the differential diagnosis of ovarian sex cord-stromal tumors. CD99, Müllerian inhibiting substance (MIS), melan A and CD10, being sex cord markers of limited sensitivity and specificity, should only be used as part of an antibody panel in specific diagnostic settings. EMA, CK7 and chromogranin are considered additional markers that may be useful in the differential diagnosis of ovarian sex cord-stromal tumors.

Albright hereditary osteodystrophy (AHO) is characterized by a symptom complex including short stature, brachymetacarpia, obesity, round facies, cutaneous osteomas, and mental retardation. AHO is caused by mutations in the GNAS-gene localized on chromosome 20 encoding for Gsalpha protein, a signal transducer of endocrine pathways. Therefore, AHO is often associated with endocrinopathy such as pseudohypoparathyroidism or hypothyroidism. A nine-month-old boy presented with typical features of this syndrome. The diagnosis was confirmed by biochemical and molecular analyses. An unusual feature was calcinosis cutis at such an early age, which led to extensive differential diagnostic procedures.

We report on a case of paraganglioma of the cauda equina in a 48-year-old man. These slow-growing, mostly benign and encapsulated intradural-extramedullar tumours are clinically characterized by lumbago, paraesthesia and motor deficits as well as occasionally by incontinence. Paragangliomas of the cauda equina show monomorphous (main) cells arranged in a typical cell cluster pattern, demonstrating a lobular architecture and a fine net of connective tissue formed by so-called sustentacular cells; some tumours show focal ganglionic differentiation. Because of their morphological similarity to the more common ependymomas, paragangliomas of the cauda equina are sometimes misdiagnosed so that their incidence is likely to be higher than previously estimated. Immunohistochemistry findings are positive for neuron-specific enolase, chromogranin and other neuronal markers as well as neuropeptides (main cells) and S-100 protein (sustentacular cells) while widely lacking reactivity for GFAP. Paragangliomas of the cauda equina represent a rare entity, of which only 80 cases have been described in the literature. Because they only occur sporadically, they are often not included in the differential diagnosis of mass lesions of the region of the cauda equina.

Regulated secretory vesicles of neuroendocrine cells encompass two distinct types, i.e. hormone-storing large dense core vesicles (LDCV) and neuron-like small synaptic vesicles (SSVs). The membranes of the vesicles and the acceptor organelles contain proteins which are essential for targeted membrane fusion and protein transport (SNARE hypothesis). Membrane proteins of SSV analogues such as synaptophysin, synaptobrevin (v-SNARE) and synaptotagmin are key proteins of neurosecretion. The plasma membrane proteins syntaxin and SNAP25 (t-SNARE) are indispensible for this locking/fusion process. This study was done to identify the molecular components of LDCVs, SSV analogues and the SNARE-complex in neuroendocrine tumors. Immunohistochemical analysis using a panel of antibodies was done on file material from benign or low-grade malignant neuroendocrine tumors (n = 20) and high-grade malignant intermediate or small cell carcinomas (n = 27) of the gut, pancreas and lung. The statistical evaluation of our results indicate that the expression of all marker molecules of the regulated secretory pathway is significantly reduced in high-grade malignant carcinomas when compared to benign or low-grade malignant tumors. The reduction of the LDCV matrix protein chromogranin A and of the SSV membrane protein synaptobrevin is highly significant in high-grade malignant carcinomas, which may even loose these proteins. In contrast, the synthesis of synaptophysin and the t-SNARE-protein SNAP25 appears to be better maintained even in small cell carcinomas. We conclude that the immunohistochemical diagnosis of high-grade malignant neuroendocrine tumors should mainly be based on the identification of SSV- and SNARE-proteins, especially synaptophysin and SNAP25. These marker molecules of the regulated secretory pathway are valuable tools for the diagnosis and classification of neuroendocrine tumors and contribute to the understanding of cellular differentiation pathways.

Secretogranin II (chromogranin C) has been demonstrated in normal and hyperplastic C cells of the thyroid as well as in medullary thyroid carcinoma. Both by immunohistochemistry and immunoblotting it was found that C cells and medullary thyroid carcinomas contain substantially less secretogranin II when compared to chromogranins A and B. Secretoneurin, a biologically active protein endoproteolytically processed from secretogranin II, has been found to have a potent chemotactic activity towards monocytes. This and the finding that histamine specifically induces secretogranin II mRNA in cultured bovine chromaffin cells may indicate a possible role of this peptide in inflammatory conditions. The aim of the present study was to investigate secretogranin II both on the mRNA and protein level on routinely processed tissues from 18 cases with Hashimoto's thyroiditis. In contrast to normal, hyperplastic, and neoplastic C cells, the C cells in cases with Hashimoto's thyroiditis showed increased secretogranin II mRNA as well as protein (secretogranin II and secretoneurin) expression. Our results support the concept that secretogranin II/secretoneurin may be involved in inflammatory conditions. Further studies are necessary to elucidate whether secretogranin II is of biological relevance in Hashimoto's thyroiditis.

Ultrasound-guided, laser-induced thermocoagulation with Nd:YAG laser (1064 nm) was performed in a child with metastatic gastrinoma disease. The emitted laser energy to coagulate a radius of 15-20 mm of metastatic liver tissue was 4 W with a duration time of 300 s. Marked reduction of gastrin was observed after interstitial laser hyperthermia.

Merkel cell tumors represent a rare subepidermal tumor of the skin. Despite the high tumor-mitosis-rate, the survival rate is rather high. This characterizes the biologic behavior of these tumors. We report on a 104-year-old female patient who presented with a histologically proven Merkel cell tumor of the finger existing over a period of more than 15 years. Based on our case report, the specific behavior of these tumors is documented. The pertinent literature is discussed.

A 40-year old male patient presented with a history of subtotal strumectomy, excision of multiple cutaneous lesions at the upper trunk and gastrointestinal polyposis of unknown origin. The patient was admitted for weight loss and intermittent diarrhea. Physical examination revealed craniomegaly, papillomatosis of the oral mucosa and epigastric tenderness. Endoscopically, multiple polyps were seen in the stomach, the duodenum, the terminal ileum, the distal colon and the rectum. Histologically, these lesions were classified as hamartomatous and hyperplastic polyps. In the punctate of the relapsed nodular goitre, neoplastic follicular cells were found. These findings led to the diagnosis of Cowden's disease. A complete thyroidectomy was performed. The histology verified a follicular thyroid carcinoma and showed a combined expression of thyroglobulin and of the neuroendocrine marker synaptophysin (appr. 50% of all tumor cells). Chromogranin A (a neuroendocrine tumor marker) was also elevated in the serum of the patient. Postoperatively, a radioiodine therapy was performed and the clinical condition of the patient has improved ever since. The presented case of Cowden's disease is the first male patient with thyroid carcinoma. Early consideration of Cowden's disease is substantial as multiple malignant neoplasms may occur in this disorder in increased incidence.

A 41-year-old woman with a chronic atrophic gastritis after endoscopic investigation diagnosed a carcinoid at the corpus of the stomach. There were more lesions in the mucosa of the stomach in the form of dysplasias. The labor investigation indicated an hypergastrinaemia. We performed a resection of the basis of the carcinoid. It has shown to be histologically tumor-free as the rest of the stomach. A gastrectomy was not necessary. After resection the patient was under therapy with vitamin B-12. The level of gastrin in blood was normal under this treatment. Two years later the patient remained symptom-free. Regular endoscopic investigations show a stagnation of the growth of the dysplastic lesions of the mucosa of the stomach.

The malignancy of gastro-intestinal carcinoids is dependent on localisation and size of the tumor. Tumors of the small bowel seem to have a tissue infiltration depth and extension independent of the primary tumor size. We give a case report of a patient with a carcinoid tumor in the terminal ileum with a diameter of 5 mm and a tissue infiltration depth to submucosa. Based on the immunohistochemical investigation of lymphnode metastases for little, accidentally found carcinoids in the ileum a hemicolectomy with wide mesenteric lymph resection is necessary.

Clinical characteristics, echocardiographic and Doppler echocardiographic findings, as well as serum levels of chromogranin A were recorded on 62 patients (27 women, 35 men; mean age 55 [11-83] years) with histologically confirmed tumours of the gastroenteropancreatic (GEP) system. Changes in the right heart were found in 14 patients (22%), club-like thickening of tricuspid leaflets in 13, tricuspid regurgitation in 14, stenosis in 2 and right atrial or right ventricular dilatation in 11 and 5, respectively. There was no difference between the patients with or without right-heart changes in regard to age, presence of carcinoid syndrome, duration of symptoms, primary tumour site, pattern of metastases, treatment or chromogranin A level. Two patients with nonfunctioning tumours had right-heart changes. While clinical and biochemical parameters did not identify patients with right-heart changes, echocardiography demonstrated all haemodynamically significant endocardial changes. Even patients with nonfunctioning GEP tumours should be regularly monitored by echocardiography.

Medullary thyroid carcinoma, a tumour derived from the calcitonin-producing C cells, is a rare tumour. Nevertheless it has evoked considerable interest in the past two decades amongst pathologists, clinicians, and human geneticists. Medullary thyroid carcinoma occurs either sporadically or as part of the inherited MEN II syndromes. The introduction of sensitive biochemical screening tests for the detection of early, clinically occult disease, and the advent of specific immunohistochemical staining methods have proved ideally for the study of this tumour. Immunohistochemical confirmation of the diagnosis of medullary thyroid carcinoma and the demonstration or exclusion of concomitant C cell hyperplasia (which precedes medullary thyroid carcinoma) are regarded as mandatory. Immunohistochemical markers used in routine histopathology and/or research of medullary thyroid carcinoma are reviewed and briefly discussed in the present paper.

A glomus jugulare tumor arises from the glomus bodies located in the adventitia of the dome of the jugular bulb. A glomus tumor has the same microscopic appearance as a carotid body tumor. The present report includes the extraordinary clinical and morphological features of a catecholamine-secreting glomus tumor (paraganglioma) in a 41-year-old woman. The patient presented with uncontrollable hypertension und pulsatile tinnitus. The diagnostic and therapeutic management is reported, including MIBG scintigraphy, computed tomography, magnetic resonance imaging, embolization, angiography, selective venous sampling studies and control of hypertension. After cardiovascular stabilization and tumor embolization, the tumor was removed surgically, with subsequent resolution of hypertension. While light microscopical analysis showed a classical glomus tumor, ultrastructural analysis revealed particular details of the tumor cells.

102 unselected and untreated prostate carcinomas were immunohistochemically analysed with regard to neuroendocrine (ne) differentiation using a monoclonal antibody against Chromogranin A. Density of ne-tumor cells/mm2 tumor area and arrangement of ne-tumor cells (single cells; small groups and large groups) were determined. We found ne-tumor cells in 90% of all carcinomas (n = 92). 70% had a low density of ne-tumor cells (or = 1 cell/mm2). 67% of carcinomas with ne-differentiation showed only single ne-tumor cells, there were small groups in 19% and large groups in 14%. There was an association between higher densities of ne-tumor cells and arrangement in groups. In high malignancy carcinomas we found a higher density of ne-tumor cells and more often an arrangement in groups than in low grade tumors. Our results support reports in literature that ne-differentiation is of prognostic significance.

A primary carcinoid tumour of the testicle without carcinoid syndrome was recorded from a patient aged 48 years. The tumour was made up of solid and acinar structures which exhibited strongly pronounced argyrophilia. Teratogenic structures were not established. Neuron-specific enolase (NSE) and chromogranin were immunohistologically recorded from tumour cells. The carcinoid had not spread metastases. Semi-castration was chosen as therapeutic approach. Orchidectomy was not followed by complications.

The histologic features and morphometric data of the endocrine pancreas (surgical specimens) of 12 infants suffering from persistent hyperinsulinemic hypoglycemia are reported. In 3 cases, a focal nesidioblastosis, in another 3 cases, a diffuse nesidioblastosis were observed. 2 infants demonstrate B-cell adenomata and 4 adenomata combined with a diffuse nesidioblastosis. In respect to volume density of the endocrine pancreas and diameter of the islets, there are no differences between cases with diffuse nesidioblastosis and age-matched controls. Structural changes of the endocrine pancreas in cases with nesidioblastosis are detectable by their chromogranin-A-immunoreactivity. Further investigations are necessary to clarify if there are disturbances in the relationships between chromogranin A and peptide hormones additionally to structural changes in the pancreas.