Risk of malignancy in follicular thyroid neoplasm: predictive value of thyrotropin.

UNLABELLED: The cytological diagnosis of follicular neoplasm is a common finding in fine needle aspiration cytology (FNAC) of thyroid nodules and includes benign disease as well as differentiated thyroid cancer. The aim of the study is to determine if thyrotropin is a predictive factor for a malignant nature of follicular neoplasm. PATIENTS, METHODS: The records of 119 patients with follicular neoplasm on FNAC, who underwent surgery for final diagnosis, were reviewed retrospectively. The predictive value of serum parameters including thyrotropin, thyroglobulin, and anti-thyroid antibodies, ultrasonographic criteria and clinical variables was evaluated by univariate analysis and logistic regression analysis. RESULTS, DISCUSSION: Patients with malignant nodules showed a higher thyrotropin concentration compared to patients with benign nodules (median 1.6 mU/l, interquartile range 1.4-3.0 mU/l vs. median 1.2 mU/l, interquartile range 0.8-1.6 mU/l, p < 0.01). ROC-analysis of thyrotropin revealed an optimal cut off value to differentiate benign and malignant nodules of 1.34 mU/l. The incidence of malignancy was 30.3% for a thyrotropin concentration higher than 1.34 mU/l compared to 6.4% for a thyrotropin concentration lower than or equal to 1.34 mU/l. On univariate analysis thyroglobulin higher than 300 ng/ml, positive anti-thyroid antibodies, hypoechogenicity, and ill-defined margins, respectively, were also significantly associated with malignancy. On logistic regression analysis higher thyrotropin concentrations, ill-defined margins, and thyroglobulin higher than 300 ng/ml, respectively, were independent predictive factors for malignancy (OR 20.0, 10.7, and 22.7, respectively). CONCLUSION: Higher thyrotropin concentrations are predictive for a malignant nature of follicular neoplasm.

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.

A rare case of Salmonella osteomyelitis in the humerus as a differential diagnosis to a malignant bone tumor.

Salmonella osteomyelitis without predisposing factors is seldom seen and thus difficult to diagnose. We report on a 14-year-old healthy boy with Salmonella osteomyelitis which occurred 2 years after trauma. Radical operative debridement is recommended. Intravenous ciprofloxacin has proved to be effective because of good tissue penetration and sensitivity towards Salmonella.

Periosteal chondroma: MR characteristics.

PURPOSE: The purpose of this study was to describe the MR characteristics of periosteal chondroma. METHOD: MR images of 12 proven cases of periosteal chondroma were analyzed with reference to tumor morphology and size. MR features were correlated with radiographic and pathologic findings. RESULTS: Tumor size ranged from 1 to 7 cm in maximum diameter with a mean value of 2.6 cm. On MR images, a soft tissue mass at the bone surface with pressure erosion of adjacent cortical bone could be identified in all cases. All lesions were bordered by a hypointense rim (100%) and frequently showed a lobulated configuration (75%). Edema of medullary bone or soft tissues was not observed in any of the cases. Signal intensity of cartilaginous tumor tissue was typically hypo-or isointense relative to muscle on T1-weighted (100%) and hyperintense relative to fat on T2-weighted (92%) and T2*-weighted (100%) MR images. Radiographically significant calcifications of the tumor matrix, present in half of the cases, caused focal signal loss on MR images of all pulse sequences. Contrast enhancement was observed predominantly at the periphery of the lesions (100%), which on pathologic examinations typically contained fibrovascular bundles, surrounding the cartilage lobules. CONCLUSION: Periosteal chondroma appears to have a relatively typical MR appearance, which reflects the histologic composition of the lesion. In addition to radiography, MRI therefore can substantially aid in the preoperative diagnosis of this rare bone lesion.

[MR morphology of primary aneurysmal bone cysts: a retrospective analysis of 38 cases]. / MR-Morphologie der primären aneurysmatischen Knochenzyste: Retrospektive Analyse von 38 Fällen.

PURPOSE: To define MR imaging characteristics of primary aneurysmal bone cyst. MATERIALS AND METHODS: MR imaging studies of 38 patients with histologically proven primary aneurysmal bone cyst were reviewed with reference to morphological features, signal characteristics, and patterns of contrast-enhancement. RESULT: Most lesions were well marginated towards bone and soft tissues (95%), either surrounded by a complete (84%) or incomplete (16%) rim of low signal intensity on images of all pulse sequences. Frequent features were polycyclic margins (84%), cortical expansion (87%), cystic spaces (100%), contrast-enhancing cyst walls (100%), internal septations (89%), fluid levels (71%) and diverticula-like projections of cyst walls (68%). Solid tissue components could be identified by MR imaging in all lesions which, on pathological examination, contained larger portions of solid material (18%). Edema of surrounding soft-tissues was observed in 29% of the cases. CONCLUSIONS: Primary aneurysmal bone cysts demonstrate a relatively uniform MR imaging appearance, which reflects the patho-anatomic composition of the lesion.

Pulmonary manifestation of systemic mast cell disease.

Systemic mast cell disease is a rare disease of unknown aetiology. Systemic infiltration and proliferation of mast cells in skin, bone marrow, gastrointestinum and lymph nodes is the central pathological feature. This study reports a patient with mastocytosis of the skin (urticaria pigmentosa) for 10 yrs. The patient was referred to hospital for dyspnoea. Chest radiograph showed moderate reticular infiltration of both lungs, computerized tomography revealed multiple lymph nodes of the mediastinum and faint nodular lesions of middle and upper areas of lungs. Transbronchial biopsy demonstrated mast cell infiltration of the lung with formation of mast cell granuloma. According to the current literature, systemic mast cell disease with pulmonary involvement is a very rare entity. After a treatment with interferon alpha-2a over 6 months, the patient's condition and particularly dyspnoea showed improvement in parallel with an amelioration of the lesions as demonstrated by thorax computed tomography.

Aneurysmal bone cysts of the spine.

Thirteen patients with aneurysmal bone cyst of the spine (excluding sacral lesions) were retrospectively reviewed. Treatment for aneurysmal bone cysts remains controversial, but surgical resection, irradiation, and embolization are common treatment modalities for those involving the spine. Of 102 patients with aneurysmal bone cysts, 15 had a lesion of the spine, including 2 sacral cases. Of the 13 patients with a lesion of the thoracic or lumbar spine, 9 underwent resection of the lesion, 2 curettage and cementation, and 2 only currettage. Eleven patients underwent segmental arthrodesis with instrumentation after treatment of the primary or recurrent lesion, while 2 patients underwent segmental arthrodesis using autogeneic bone. Nine patients did not develop a local recurrence after resection of the lesion. However, the 2 patients who underwent curettage alone developed local recurrences. None of 4 patients developed recurrences after curettage and cementation. After recurrence, 1 patient underwent additional resection with irradiation, and 1 patient underwent resection alone. At the final follow-up, all lesions were under control. In one patient, lumbar kyphosis developed after segmental arthrodesis with instrumentation, and arthrodesis was performed again. Radical resection of aneurysmal bone cysts of the spine with instrumentation is the optimal method of acquiring a high degree of local control and preventing spinal deformity.

[Nasal T-cell lymphoma as a differential diagnosis of the midline granuloma syndrome]. / Das hochmaligne nasale T-Zell-Lymphom als Differentialdiagnose des Midline-Granuloma-Syndroms (Granuloma gangraenescens).

BACKGROUND: The lethal midline granuloma is a heterogeneous disorder and the pathogenesis is likely to be complex. Advances in immunocytochemical phenotyping and molecular genetics suggest that in several cases the origin have been proven to be malignant lymphomas, especially of T-cell lineage. PATIENT: The present clinical and pathological cases of a 35-year-old woman shows how difficult it is to establish the precise diagnosis of lethal midline granuloma (LMG). The patient presented with recurrent infections of the paranasal sinuses. Later she developed infiltrates and ulcerous lesions of the nose, paranasal sinuses, and the base of the skull clinically consistent with a LMG. Immunohistologic studies using monoclonal antibodies led to the positive diagnosis of peripheral lymphoma of T-cells. RESULTS: Several surgical interventions and explorations revealed a diffuse infiltration and partly necrotic lesions of the tissue. After identification of a T-cell lymphoma by histological examination, the patient received megavoltage irradiation of 45 Gy. Additional chemotherapy with alkylating agents was given. Two years after treatment the patient achieved and remained in remission. CONCLUSION: The midline granuloma syndrome is a mutilating process produced by a number of diseases that progressively destroy the nose, paranasal sinuses and other regions of the midface. Infectious, neoplastic and idiopathic forms have been described. The specific diagnosis must be ascertained, as the treatment is different depending of the etiology of the disease. Sinonasal lymphomas constitute a important distinct clinicopathologic entity which may present as lethal midline granuloma. They seems to be strongly associated with Epstein-Barr virus. Aggressive therapy with radiotherapy and chemotherapy can stop the progress of the midfacial destruction. The correct treatment is still discussed controversially.

Monitoring radiation-induced changes in bone marrow histopathology with ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI.

The purpose of this study was to monitor radiation-induced alterations of the blood-bone marrow barrier (BMB) and the reticuloendothelial system (RES) with AMI-227-enhanced magnetic resonance imaging (MRI). Twenty New Zealand white rabbits (n = 10 following total body irradiation and n = 10 controls) underwent AMI-227-enhanced MRI. Pulse sequences included dynamic fast low-angle shot (FLASH; TR/TE 50/4 msec, flip angle 60 degrees) MRI and static T1- and T2-weighted spin-echo (SE) and turbo-SE sequences of the lumbar spine and sacrum. Bone marrow enhancement was quantified as delta signal intensity (SI) (%) =|[(SIpost - SIpre)/SIpre] x 100%| and compared with histopathology, including iron stains and electron microscopy. Dynamic bone marrow deltaSI (%) data steadily increased up to 10-15 minutes after AMI-227 administration, while blood deltaSI (%) data stayed nearly constant, histologically corresponding to iron oxide leakage into the bone marrow interstitium. This bone marrow contrast enhancement increased significantly following irradiation, corresponding to alterations of the endothelial lining of the bone marrow sinusoids. Late postcontrast images exhibited a significant positive T1 enhancement and negative T2 enhancement of the normal bone marrow, which further increased with irradiation due to increased RES activity. Irradiation-induced changes in bone marrow physiology could be reliably assessed with AMI-227-enhanced MRI.

Malignant fibrous histiocytoma of bone: conventional X-ray and MR imaging features.

OBJECTIVE: To evaluate the conventional X-ray and MR imaging features of malignant fibrous histiocytoma (MFH) of bone. DESIGN: MRI examinations and conventional radiographs were reviewed in 39 patients with biopsy-proven MFH. Imaging characteristics were analyzed and the differential diagnoses assessed in a masked fashion by two experienced radiologists. RESULTS: Typical X-ray features included aggressive, destructive tumor growth centrally located in the metaphysis of long bones. Periosteal reactions and expansive growth were rarely seen. On MR images extraosseous tumor spread was frequently noted. On T2-weighted images and contrast-enhanced T1-weighted images most of the tumors displayed an inhomogeneous, nodular signal pattern with peripheral Gd-DTPA enhancement. CONCLUSIONS: Although several MR imaging criteria were typical for MFH none of them was specific. X-ray diagnosis of MFH may also prove difficult, with the main differential diagnosis being metastasis in the older and osteosarcoma in the younger population.

Melanotic progonoma of the brain: a case report and review.

So far, only 25 melanotic progonomas have been found in the central nervous system (male/female ratio 3.5), mostly located in the cerebellum. The average age is 8 years (range 3.5 months to 69 years) with 85% becoming clinically apparent in the first decade of life; 73.7% of the patients reported succumbed to their disease at a mean age of 2.8 years, with a postoperative survival time of just 9 months. Systemic metastases were reported in 9 cases and had mostly spread via cerebrospinal fluid. In contrast to peripheral melanotic progonomas usually found in the maxilla, cerebral progonomas have a much worse outcome and have to be regarded as malignant. We present the case of a 1-year-old boy suffering from a melanotic progonoma of the pineal gland, who died at the age of 22 months with extensive spinal and abdominal metastases 10 months after partial removal of the tumor.

Metastatic retroperitoneal paraganglioma in a 16-year-old girl. Case report, molecular pathological and cytogenetic findings.

Retroperitoneal paraganglioma is a rare tumor, especially occurring in childhood and adolescence, with a marked tendency to become biologically malignant. It has not been possible to predict the clinical outcome of paraganglioma patients by conventional histology, hence malignancy can only be demonstrated by the occurrence of metastatic lesions. Currently, only limited information on the genetics of this tumor is available. We report on a 16-year-old girl with a large retroperitoneal paraganglioma and an osseous metastasis to the first lumbar vertebra. In addition to morphological and immunohistochemical examinations, a molecular cytogenetic analysis was performed. Comparative genomic hybridization (CGH) revealed imbalanced chromosomal aberrations with a loss of chromosome 1p and a gain of 1q, indicating isochromosome 1q. A loss of chromosome 3 as well as low-level gains of chromosomes 4, 5, 6q, 11q and 13q were detected. A PCR-based microsatellite analysis of 1p confirmed the loss of heterozygosity, including NB1 and NB2 putative tumor-suppressor gene regions. Telomerase activity, which is found in the majority of malignant tumors, could not be detected. The case presented here is the first more comprehensive molecular genetic analysis of a sporadic malignant paraganglioma.

Multicentric malignant transformation of multiple exostoses.

We treated a patient with large multiple chondrosarcomas derived from multiple cartilaginous exostoses. One sarcoma originated in the left pubic bone and the other sarcoma in the posterior aspect of the greater trochanter of the left femur. Thirty months after hindquarter amputation, the patient is alive without relapse. This is the first report of a patient with synchronous multiple malignant transformation of multiple cartilaginous exostoses.

Possible relationship between heat shock protein 70, cardiac hemodynamics, and survival in the early period after heart transplantation.

BACKGROUND: Heat shock proteins (HSPs) are produced by cells in response to a wide variety of stresses. To determine a possible relationship between hemodynamic parameters and HSP 70 in the early postoperative period after heart transplantation, we examined immunohistochemically the inducible HSP 70 (anti-HSP 72) response in human heart biopsies, as well as the effect of myocardial rejection on HSP. METHODS: A total of 105 routinely processed endomyocardial biopsies from 15 consecutive patients who underwent heart transplantation were examined. Analysis of hemodynamic and echocardiographic parameters were performed within 30 min and 12 hr after the biopsies. RESULTS: Immunohistochemically detected inducible HSP 70 was mainly located in the cytoplasm and nucleus/nucleolus of cardiomyocytes. Two specimens additionally showed HSP 70-positive interstitial cells and smooth muscle cells of arteries, whereas lymphocytes were consistently negative. There was a significant relation between the echocardiographically determined increased relaxation time and positive HSP 70 staining (P < 0.011). Patients with elevated right atrial pressure (P < 0.098), as well as those with increased left ventricular end systolic diameter (P < 0.06), showed a trend to higher HSP expression. Three patients who died of sepsis or multiorgan failure showed significantly higher cytoplasmic HSP 70 expression compared with 12 patients with stable clinical course. In case of rejection, significantly more patients showed no HSP expression. CONCLUSION: Although only five patients showed organ rejection, our results suggest an inverse relationship between HSP expression and rejection with the possibility of a role for HSP 70 as a graft marker to assess graft function.

[Comparative genomic hybridization (CGH) for detecting a heretofore undescribed amplified chromosomal segment in high-grade medullary osteosarcoma]. / Komparative Genomische Hybridisierung (CGH) detektiert bisher nicht beschriebene amplifizierte chromosomale Abschnitte bei medullären High-Grade Osteosarkomen.

Osteosarcoma is one of the most commonly biopsied primary tumor of bone. High-grade osteosarcomas in particular exhibit a wide spectrum of cytogenetic changes. Molecular cytogenetic studies on osteosarcomas have shown that genomic amplification, especially of both the TP53-binding MDM2 gene and the flanking SAS gene, plays an important role in the biology of these tumors. We applied CGH in order to obtain a global view of DNA-sequence losses and gains in osteosarcoma. CGH was performed on 20 high-grade medullary osteosarcomas (13 primary tumors prior to chemotherapy, 5 tumors after chemotherapy, 2 established cell lines [MB63, HOS58]) using genomic DNA of snap-frozen tumor specimens. CGH revealed DNA copy number aberrations, mostly gains, in all the tumors studied with an average of 18.5 aberrations/tumor (range 8-32). High-level amplifications were observed in all cases (average 4.1 amplifications/tumor [range 1-10]). Amplicons affecting at least five tumors were mapped to 1p21-31 (9/20 cases), 3q25-qter (6/20), 6p12-21 (6/20), 8q12-qter (10/20), 12p11-12 (9/20), 12q12-15 (enclosing MDM2 and SAS loci, 7/20). Losses were most frequently seen at 3p, 10q, 11p and 13 (all 10/20). In conclusion, our CGH data indicated that genomic amplification plays an important role in the biology of osteosarcoma. CGH demonstrated the complexity of genetic aberrations in osteosarcomas. The detection of novel non-random DNA amplifications in our study has defined regions for further targeted molecular genetic research aimed at identifying those oncogenes that are characteristic of osteosarcoma development.

Inducible heat shock protein 70 in rat cardiac allograft and its immunohistochemical localization in cardiac myocytes.

BACKGROUND: Heat shock proteins (HSP) are induced by a variety of stress and are presumed to play an important role in protecting cells from the effects of stress. Some evidence exists that HSP is involved in allograft rejection. Recently, an increase of inducible HSP 70 in heterotopic rat heart allografts was shown by quantitative Western blotting. To determine a possible mRNA induction and the localization of inducible HSP 70, we examined 19 heart transplants in rats. METHODS: Fisher F344 rat hearts were heterotopically transplanted into Lewis recipients (n=10), and nine cardiac isografts (Fisher to Fisher) were performed. The 19 native hearts of the recipients served as controls. Animals were killed on posttransplantation days 1, 3, and 5. The hearts were examined immunohistologically for inducible HSP and analyzed by a semiquantitative polymerase chain reaction for inducible mRNA. RESULTS: The level of HSP 70 mRNA in the allograft increased from day 1 to 3 and day 3 to 5 after transplantation and was significantly higher than that of time-matched isografts (0.92+/-0.49 vs. 0.49+/-0.05 and 1.14+/-0.53 vs. 0.53+/-0.15; P<0.05). The native hearts showed no elevated HSP 70 expression compared with isografts. Immunohistochemically, the majority of inducible HSP was located in cardiomyocytes adjacent to infiltrating lymphocytes, which where consistently negative. CONCLUSIONS: These results demonstrate that HSP mRNA expression in cardiac allografts is time-dependent, and its protein is expressed in cardiomyocytes.

Assessment of molecular genetic detection of chromosome translocations in the differential diagnosis of pediatric sarcomas.

BACKGROUND: Recent studies have shown that many types of soft-tissue sarcomas are characterized by specific chromosomal translocations, which are likely to be of etiologic significance. In order to evaluate their diagnostic impact, a panel of 129 sarcomas comprising 78 Ewing's tumors (ET), 19 rhabdomyosarcomas (RMS), 20 neuroblastomas (NB), 9 synovialsarcomas, 2 esthesioneuroblastomas, and 1 desmoplastic small-round-cell tumor (DSRCT) were analysed for the occurrence of the major recurrent translocations, such as t(11;22)(q24;q12), t(21;22)(q22;q12), t(11;22)(p13;q12), t(2;13)(q35;q14), t(1;13)(p36;q14), and t(X;18)(p11;q11). METHODS: Nitrogen-frozen tissue material was analysed by means of Reverse Transcription followed by PCR (Polymerase-Chain Reaction) and nested PCR (RT-PCR). Specificity of the PCR products obtained was confirmed by non-isotopic Southern-Blot analysis with gene-specific probes and/or automated direct sequence analysis. RESULTS: 75 ETs have been shown to carry either a t(11;22) or t(21;22) translocation by identification of chimeric EWS-FLI-1 or EWS-ERG gene-fusion transcripts respectively. 3 ETs were lacking EWS/FLI-1 or EWS-ERG fusion products. 2 of these tumors were shown on review to have unusual morphological features for ETs. 8/19 RMS were initially diagnosed as alveolar RMS. These tumours were shown to carry either a t(2;13) translocation exhibiting chimeric PAX3-FKHR fusion transcripts or a t(1;13) translocation with PAX7-FKHR chimeric gene products. One RMS of the embryonal group also carried a t(1;13) translocation. Reevaluation demonstrated a partly alveolar morphology. In 8/9 synovial sarcomas a t(X;18) translocation was identified. Expression of a EWS-WTI gene-fusion product associated with a t(11;22) translocation was found in the DSRCT. None of these rearrangements were detected in the NBs and 2 esthesioneuroblastomas. CONCLUSIONS: Our results support the concept that the major recurrent translocations are histogenetically specific for a subset of sarcomas. Thus, the detection of tumor type-specific translocations represents an extremely useful diagnostic modality as an adjunct to surgical pathology.

[Angiosarcoma of the hand. Case report]. / Angiosarkom der Hand. Falldarstellung.

Angiosarcoma is a very rare malignant bone tumour. The case of a 45-year-old man is presented with a primary epithelioid hemangioendothelioma in the fourth metacarpus. After radical extirpation of the tumour radiation followed. The function of the hand was fully preserved. Five years after operation the patient is free of disease.