[The activating GNAS mutation : A survey of fibrous dysplasia, its associated syndromes, and other skeletal and extraskeletal lesions]. / Die aktivierende GNAS-Mutation : Eine Bestandsaufnahme bei der Fibrösen Dysplasie, der ihr assoziierten Syndrome sowie weiterer skelettaler und extraskelettaler Läsionen.

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.

[Ewing's sarcoma, fibrogenic tumors, giant cell tumor, hemangioma of bone : Radiology and pathology]. / Ewing-Sarkom, fibrogene Tumoren, Riesenzelltumor, Hämangiom des Skeletts : Radiologie und Pathologie.

Radiological imaging only reflects the anatomy and its pathological abnormalities. Therefore, the radiologist should be able to recognize the basic features of the pathological anatomy of bone tumors. This can only be learned working closely with a pathologist who is experienced in this field. On the other hand, the pathologist needs from the radiologist their diagnostic assessment with information on size, location, aggressiveness and the existence of a bone tumor's matrix, of the whole lesion, because he usually only receives a small part for examination in the form of a biopsy. In this article, the features and fundamentals (standards) of radiological-pathological cooperation as the mainstay for a precise diagnosis in bone tumors are outlined. The radiological appearance and the histopathological features behind it are presented for Ewing's sarcoma, fibrogenic tumors, giant cell tumor, and hemangioma of the bone.

Immunohistochemical expression of receptor tyrosine kinase PDGFR-α, c-Met, and EGFR in skull base chordoma.

Chordomas are rare, locally aggressive malignancies that often exhibit an insidious natural history and are difficult to eradicate. Surgery and radiotherapy are the treatment mainstays of chordoma, but the chance of local recurrence remains high. Reports of receptor tyrosine kinase (RTK) expression in chordoma suggest that these tumors may respond to kinase inhibitor therapy. Currently, there are no effective chemotherapeutic protocols for chordoma. A tissue microarray containing 74 tumor specimens from primary chordoma patients and 71 from their recurrent tumors for a total of 145 tumor specimens was immunohistochemically analyzed for expression of a number of proteins involved in signal transduction from RTKs. Platelet-derived growth factor receptor-α (PDGFR-α), epidermal growth factor receptor (EGFR), c-Met, and CD-34 were detected in 100, 92, 100, and 59% of cases, respectively. PDGFR-α and c-Met staining was of moderate to strong intensity in all cases. In contrast, total EGFR staining was variable; weak staining was detected in 10 cases. Our results contribute to the understanding of the expression of RTKs in skull base chordomas and support the development of targeted therapies that inhibit RTKs, which may have a synergistic effect for chemotherapy in patients. There were statistically significant correlations between the expression of PDGFR-α, c-Met, and EGFR and disease-free survival. The results nonetheless suggest that chordomas may respond to RTK inhibitors or modulators of other downstream signaling.

Expression of vascular endothelial growth factor receptor 2 (VEGFR-2), inducible nitric oxide synthase (iNOS), and Ki-M1P in skull base chordoma: a series of 145 tumors.

Chordomas are locally invasive tumors that have a tendency to relapse despite optimal treatment. Specific biological markers might be used to describe their behavior. There is currently no agreement regarding the best way to manage intracranial chordomas. We studied the expression of vascular endothelial growth factor receptor 2 (VEGFR-2), inducible nitric oxide synthase (iNOS), and Ki-M1P in 145 paraffin-embedded tumors. The purpose of our study was to determine: (a) the role of potent angiogenic factors VEGFR-2 and iNOS and their relationship to each other in skull base chordoma and (b) the role of monocytes/macrophages as a potential iNOS source in the angiogenic process. A series of 74 chordoma patients for a total of 145 lesions (including 71 recurrent lesions) and 10 specimens from embryonic notochord were investigated for the expression of iNOS, VEGFR-2, Ki-M1P, and CD-34 using immunohistochemistry. In the majority of the chordomas, correlations were found between iNOS and the immunoreactivity of Ki-M1P (r = 0.5303, P < 0.0001). Furthermore, the expressions of Ki-M1P was correlated with VEGFR-2 (r = 0.4181, P < 0.0001). Our results indicate that chordomas may respond to receptor tyrosine kinase inhibitors such as VEGFR-2 or modulators of other downstream signaling molecules. The future of VEGFR-2 and iNOS inhibitors as therapeutic agents in the treatment of chordoma will be clearer over the next years as results of the current clinical trials become available and as the factors regulating angiogenesis and the interactions between these factors are elucidated. However, appropriate functional experiments remain to be conducted to prove such a hypothesis.

Adenomatous tumors of the middle ear and temporal bone: clinical, morphological and tumor biological characteristics of challenging neoplastic lesions.

Adenomatous tumors of the middle ear and temporal bone are rare tumors. In this retrospective study, we examined nine patients who underwent surgery for an adenomatous tumor of the middle ear, mastoid cavity or eustachian tube. In seven patients, a middle ear adenoma (MEA) and in two patients an aggressive papillary tumor (APT) was diagnosed. We report the clinical, radiologic, morphologic, immunohistochemical and DNA image cytometrical characteristics that can help to correctly classify these tumors. Therapy consisted of surgical excision of the tumors in eight cases. In one elderly patient, only a large biopsy was taken, because this patient suffered from cardial and kidney disorders and was not suitable for an extended surgical approach. This patient received stereotactic radiotherapy. Seven patients underwent planned second look operation. Recurrences occurred in three patients (one with APT, two with MEA), whereas in two of these cases rather a residual tumor due to initial incomplete tumor resection occurred. By image analysis, DNA cytometry MEA were considered benign, whereas the appearance of aneuploid tumor cells in APT confirmed these tumors as low grade malignant lesions. The proliferation rates were equally low in both entities. APT and MEA are tumor entities which can only be correctly classified by a synopsis of histopathology, immunohistochemistry and DNA image cytometry. The recommended therapy is the complete tumor excision. In cases of APT, von Hippel-Lindau syndrome has to be excluded.

Protracted disseminated skeletal metastases from angiosarcoma of the spleen.

Angiosarcomas are high-grade vascular tumors associated with poor prognosis due to their aggressive nature. Occasional skeletal manifestations present commonly as osteolytic destruction. The 55-years-old patient presented in this case report had a disease-free 4 years interval between splenectomy after primary angiosarcoma of the spleen and an unusual skeletal metastatic pattern mimicking benign angiomatosis. Despite lacking radiographic evidence for a highly aggressive osseous process, the histopathological resemblance of the bone biopsy with the primary tumor manifestation and the fulminant course of disease after onset of disseminated osseous spread confirmed the malignant character of the vascular tumor. The case demonstrates the highly variable radiographic pattern and particular pathobiological behavior of vascular malignancies.

Brain abscess formation within an endodermal cyst of the frontal lobe: case report.

A 38-year-old man with a right frontal lobe cyst was treated by endoscopic cystoventriculostomy in 1998. Cyst capsule histology revealed surprisingly an endodermal cyst. The patient was reoperated for cyst expansion by endoscopic re-cystoventriculostomy in 2005. In 2007, the patient suffered from brain abscess formation within the cyst which was punctured. The history was positive for a dental infection. In 2008, a recurrent brain abscess in the cyst occurred. The cyst was completely resected. There was no history of trauma or sinusitis. In all, endodermal cysts may mimic a paraxial arachnoid cyst. It may predispose for recurrent brain abscess formation - especially due to bacteraemia. This report confirms earlier presentations that endodermal cysts should be resected, and endoscopic cyst opening is not sufficient.

Analysis of c-KIT expression and KIT gene mutation in human mucosal melanomas.

Recent data suggested an increased frequency of KIT aberrations in mucosal melanomas, whereas c-KIT in most types of cutaneous melanomas does not appear to be of pathogenetic importance. However, studies investigating the status of the KIT gene in larger, well-characterised groups of patients with mucosal melanomas are lacking. We analysed 44 archival specimens of 39 well-characterised patients with mucosal melanomas of different locations. c-KIT protein expression was determined by immunhistochemistry, KIT gene mutations were analysed by PCR amplification and DNA sequencing of exons 9, 11, 13, 17 and 18. c-KIT protein expression could be shown in 40 out of 44 (91%) tumours in at least 10% of tumour cells. DNA sequence analysis of the KIT was successfully performed in 37 patients. In 6 out of 37 patients (16%) KIT mutations were found, five in exon 11 and one in exon 18. The presence of mutations in exon 11 correlated with a significant stronger immunohistochemical expression of c-KIT protein (P=0.015). Among the six patients with mutations, in two patients the primary tumour was located in the head/neck region, in three patients in the genitourinary tract and in one patient in the anal/rectal area. In conclusion, KIT mutations can be found in a subset of patients with mucosal melanomas irrespective of the location of the primary tumour. Our data encourage therapeutic attempts with tyrosine kinase inhibitors blocking c-KIT in these patients.

[Eccrine porocarcinoma of the cheek skin with parotid gland infiltration]. / Ekkrines Porokarzinom der Wangenhaut mit dem klinischen Bild eines primären Gl. parotis-Tumors.

BACKGROUND: Eccrine porocarcinoma is a rare malignant tumor, arising from the intraepithelial ductal parts of the sweat glands. Although the clinical appearance is variable, some tumors present with a diameter of 10 cm or more. In most cases the tumor presents as a slowly growing painless mass. PATIENTS AND METHODS: A case of a 61 year old male patient is presented, who was admitted because of a peripheral facial nerve palsy. The patient reported about a sting in this area some ten years ago with a persistent swelling. Four years ago this lesion began to grow slowly. RESULTS: Clinically a huge mass in the left cheek extended to the parotid gland was obvious. The patient underwent radical tumor excision with histologically clear margins. The defect was reconstructed by a microvascular forearmflap, the facial nerve was reconstructed using either a graft from the suralis nerve (for the upper part of the facial nerve) along with a hypoglossal facial nerve anastomosis for the lower part of the facial nerve. Postoperative radiation therapy was added. Histologically an eccrine porocarcinoma was confirmed with an infiltration of the facial nerve and the parotid gland. Lymph nodes in the neck were negative. DNA image cytometry achieved a DNA malignancy grade of 0.73, the immunohistochemical assessment using a monoclonal antibody against the proliferation antigen MIB-1 achieved a proliferation rate of < 10 %. CONCLUSIONS: Although very rare eccrine porocarcinoma should be considered in the differential diagnosis of slowly growing skin masses in the face. Therapeutically a radical resection with histological clear margins is recommended, in case of lymph node metastases with additional postoperative radiotherapy.

[Intratesticular metastasis of renal cancer]. / Intratestikuläre Metastasierung eines Nierenzellkarzinoms.

We report on a 66-year-old man after nephrectomy of the right kidney because of renal cell carcinoma. One year after diagnosis, an osseous metastasis of the right femur occurred and was resected. The following investigations, including positron emission tomography/computed tomography, showed no relapse. Three and a half years after diagnosis, the patient developed a testicular tumor of the right hemiscrotum, which was treated by testicular ablation. The histological investigation showed a testicular metastasis of renal cancer. This case represents one of the unusual forms of metastatic invasion of renal cell cancer.

[Osteochondrosis dissecans of the hip in adults--differential diagnosis of free joint bodies--case report]. / Osteochondrosis dissecans der Hüfte beim Erwachsenen -- Differenzialdiagnostik freier Gelenkkörper -- Fallbeschreibung.

The causes of hip pain in adults can vary greatly. We present the case of a 44-year-old woman with recurrent hip pain over a period of years. Medical history and clinical examination did not provide any decisive information. The X-rays revealed a loose body in the cavity of the hip joint. The MRI scan made the following differential diagnosis plausible: osteochondrosis dissecans coxae, osteochondroma and chondromatosis. The final diagnosis of osteochondrosis dissecans coxae was confirmed by surgical dislocation of the hip as modified by Ganz and histological examination of the loose body. This case supports the importance of including rare lesions in the differential diagnostic work-up of joint pain. The advantages of the offset operation as modified by Ganz versus arthroscopy of the hip are outlined.

[A rare case of isolated prostate metastasis from primary pancreatic cancer]. / Seltener Fall der Metastase eines Pankreaskarzinoms in die Prostata.

An otherwise healthy 66 year old male presented with a suspicious intraprostatic lesion detected by digito-rectal examination. Serum PSA levels were normal. A CT scan of the abdomen revealed a nondistinctive mass within the pancreatic head. A transrectal biopsy confirmed the intraprostatic lesion as a metastatic lesion from pancreatic cancer. Therefore, we report this unusual case of a primary pancreatic carcinoma, clinical stage IV, which led to metastases in the liver and prostate.

Surgical removal of primary central nervous system lymphomas (PCNSL) presenting as space occupying lesions: a series of 33 cases.

AIMS: In this study we present a series of 33 patients with primary CNS lymphomas (PCNSL), many presenting with acute signs of increased intracranial pressure due to large space occupying lesions. METHODS: A series of 32 PCNSL patients for a total of 33 tumours treated from 1986 to 2000 in the Neurosurgical Department were reviewed. RESULTS: Radiotherapy and chemotherapy improved survival. No benefit could be demonstrated for the role of surgery. CONCLUSIONS: Our data confirm previous reports about the role of radiation and chemotherapy in the treatment of PCNSL's. Surgery might have a role in a selected subset of patients presenting with large single space occupying lesions and deteriorating neurological status.

The prognostic value of progesterone receptor status in meningiomas.

BACKGROUND: Meningiomas are known to recur frequently, and their longterm management remains controversial. Previous studies indicate that progesterone and its receptors can play a role in the recurrence of meningiomas, but the correlation between the presence of these receptors and patients' outcome is unclear. AIM: To conduct a retrospective analysis to investigate the prognostic relevance of progesterone receptor (PR) expression in meningiomas. METHODS: Five hundred and eighty eight meningiomas operated on over a period of 10 years were examined immunohistochemically to determine the PR status using monoclonal antibodies. Several factors including recurrence (mean follow up of 65 month), sex, tumour tissue consistency, location, vascularity, and en plaque appearance were analysed. RESULTS: PR status showed comparable values for men and women. World Health Organisation (WHO) grade II and III tumours had significantly fewer receptors than benign meningiomas. There was no significant correlation between PR status and recurrence rates in WHO grade I totally removed meningiomas. However, a combination of PR status and proliferation indices was shown to predict recurrence reliably. CONCLUSIONS: Together with routine histological evaluation, PR status can help to describe the biological behaviour of meningiomas. Only a combination of clinical and biological features can describe the behaviour of meningiomas, predict their recurrence, and help to devise more effective follow up strategies.

Chondroid tumors arising from the meninges--report of 2 cases and review of the literature.

Chondroid tumors are rare intracranial tumors usually arising from the base of the skull. We present 2 cases of intracranial cartilaginous tumors with unusual location. In case 1, a 19-year-old woman, a chondroma of the falx cerebri with extensive secondary ossification was diagnosed. In case 2, a 30-year-old woman, a low-grade chondrosarcoma was resected from the right frontal lobe. Both patients showed an uneventful clinical course without evidence of disease 4.5 and 6 years after total extirpation. Our cases show that chondromas and low-grade chondrosarcomas of the dura and meninges usually occur in young adults with a good prognosis after complete extirpation.

[Sentinel node biopsy in breast cancer]. / Wächterlymphknotenbiopsie beim Mammakarzinom.

The international consensus conference from St. Gallen concerning the treatment of early breast cancer concluded in 2003, that sentinel node biopsy was now accepted as method allowing axillary staging in breast cancer. This procedure may avoid complete lymph node dissection in appropriate cases. Since numerous questions associated with the technique are still not defined and the procedure itself is not yet standardized, the German Society of Senology defined the conditions for the routine clinical use of sentinel node biopsy in an interdisciplinary consensus meeting.

The Ki-67 proliferation antigen in meningiomas. Experience in 600 cases.

BACKGROUND: Meningiomas are mostly benign tumours that can be cured by surgical resection. Because meningiomas tend to recur, long term management in patients with subtotal tumour resection remains controversial. Previous studies have shown that the proliferation potential of meningiomas by Ki-67 labelling indices (LI) might predict their natural history. The purpose of this study was to analyse the reliability of Ki-67-labelling index in predicting the behaviour of meningiomas, and to help the neurosurgeon in establishing better follow up criteria and long term management strategies for these patients. METHOD: From 1990 to 2000 1328 meningiomas have been operated in our Neurosurgical Department. A total of 600 tumours were examined immunohistochemically using the Mib-1 monoclonal antibody. Clinical charts of the patients including surgical, histological and follow up records, as well as imaging studies were analysed retrospectively. Ki-67 LI were correlated with neuroradiological findings, 3D volumetric studies, histological subtype, recurrence-free survival, grade of resection, consistency of tumour tissue, location, osseous involvement, en plaque appearance, vascularity and progesterone-receptor status. FINDINGS: Among the 600 patients analysed, there were 66% females (mean LI 3.8%) and 34% males (mean LI 5.7%), including 20 neurofibromatosis-type-2 (NF-II) patients with a mean LI of 5.2%. Histological grading revealed 91% WHO degrees I meningiomas (mean LI 3.28%), 7% WHO degrees II (mean LI 9.95%) and 2% WHO degrees III (mean LI 12.18%). Labelling indices in recurrent meningiomas increased from initial resection to a fourth local resection. A significant correlation between negative progesteron-receptor status and high tumour vascularity with high Ki-67 LI was seen. Ki67 was not a statistically significant predictor of survival time in totally excised WHO degrees I meningiomas. INTERPRETATION: Mib-1 is one important tool in addition to routine histological evaluation, but a combination of clinical factors and particularly the extent of surgical resection, along with the biological features of the tumour, should influence the decision of the neurosurgeon to the patient follow up.