The many faces of osteosarcoma

Osteosarcoma is the most common primary malignant tumor of bone in adolescents and young adults. It accounts for approximately 15% of all primary bone tumors confirmed at biopsy. There are numerous types of primary osteosarcoma, including intramedullary (high grade, telangiectatic, low grade, small cell, osteosarcomatosis, and gnathic), surface (intracortical, parosteal, periosteal, and high-grade surface), and extraskeletal. Osteosarcoma may also occur as a secondary lesion in association with underlying benign conditions. The identification of osteoid matrix formation and aggressive characteristics usually allows prospective radiologic diagnosis of osteosarcoma. As with all bone tumors, differential diagnosis is best assessed with radiographs, whereas staging is performed with computed tomography or magnetic resonance imaging. Understanding and recognition of the variable appearances of the different varieties of osteosarcoma allow improved patient assessment and are vital for optimal clinical management including diagnosis, biopsy, staging, treatment, and follow-up.     

Osteocalcin and osteonectin immunoreactivity in the diagnosis of osteosarcoma

Osteosarcomas (OSAs) can be difficult to distinguish histologically from tumors with significantly different biologic potentials and treatment protocols. The correct diagnosis of OSA relies on identification of malignant osteoblasts that are capable of producing neoplastic bone. To determine the use of immunohistochemistry for the diagnosis of OSA, 106 tumors from the Massachusetts General Hospital and the University of Vermont were immunostained with monoclonal antiosteocalcin (OC) and antiosteonectin (ON) antibodies. They included 42 OSAs, 25 non-bone-forming sarcomas, 24 other malignant tumors including lymphomas, carcinomas, and melanomas, and 15 benign bone tumors. Cytoplasmic staining with OC showed 70% sensitivity and 100% specificity, while staining with ON showed 90% sensitivity and 54% specificity for bone-forming tumors, consistently staining cell types other than osteoblasts. Of the OSAs, 83% demonstrated matrix staining with one or both antibodies, whereas dense collagen was negative for both antibodies in all tumors. We conclude that tumor cell cytoplasmic staining with monoclonal OC may be helpful in distinguishing OSAs from other malignancies, and staining of extracellular matrix for OC and ON antibodies concurrently may help distinguish bone matrix from dense collagen.     

Accuracy of frozen section in the evaluation of salivary tumors

The records of 333 patients who underwent surgery were reviewed to document the accuracy of frozen section in the evaluation of salivary gland tumors. Frozen sections were obtained in 310 patients. The final pathologic diagnoses included 210 benign tumors and 45 malignancies. The sensitivity for the detection of malignancy was 69%, and the specificity was 96%. The specific accuracy to correctly identify the type of malignancy present was only 51%. In four patients, a false-positive diagnosis of malignancy was made. Frozen section was much more accurate in the evaluation of benign salivary tumors. Forty-three of 45 Warthin's tumors were correctly identified by frozen section. Two tumors thought to be Warthin's tumors on frozen section proved to be low-grade mucoepidermoid carcinomas. One tumor reported to be a benign mixed tumor was actually a malignant mixed tumor. In this series of patients, frozen section proved to be no more accurate in the evaluation of salivary tumors than what has been reported in the literature for fine-needle aspiration biopsy.     

Clinical utility of autoantibodies in Guillain-Barre syndrome and its variants

In children and adolescents, primary neoplasms of the tracheobronchial tree and lungs are rare, with most tumors involving the respiratory system being metastatic, small, blue cell tumors of childhood. Of the primary pulmonary neoplasms, most are malignant with mucoepidermoid carcinoma representing about 10% of these malignant tumors. We present an 8-year-old Hispanic male with hemoptysis and several episodes of pneumonia which initially was thought to be infectious upon biopsy during bronchoscopy, but proved to be mucoepidermoid carcinoma of the tracheobronchial tree by microscopic examination during an open lung biopsy. This rare tumor is more common in adults than in children, and infrequently presents with hemoptysis. Mucoepidermoid tumors of the tracheobronchial tree carry a more favorable prognosis in children than adults. In the adult population, the overall mortality is slightly less than 30%. In contrast, of the 31 reported cases of tracheobronchial mucoepidermoid carcinoma in pediatrics, all children are free of tumor involvement with a mean follow-up period of 5.8 years (range, 0.7-21 years). Based upon the available clinical outcome and survival data, it would appear that tracheobronchial mucoepidermoid carcinoma may be successfully managed by surgical intervention alone in children and adolescents.     

Metastatic seminoma simulating malignant lymphoma in an HIV infected hemophiliac

Although most common, malignant lymphoma and Kaposi's sarcoma are not the only malignancies encountered in lymph nodes from HIV-infected patients. An increased frequency of testicular germ cell tumors in HIV-infected individuals has been reported. We report here the first case, to our knowledge, of a metastatic seminoma in an HIV-infected hemophiliac. The atypical clinical presentation, cervical and axillary adenopathy, simulated malignant lymphoma. The diagnosis was first suspected when a fine needle aspiration biopsy from an enlarged cervical node revealed a mixture of benign appearing lymphocytes and loosely cohesive large tumor cells in a "tigroid" background. Immunocytochemistry and a subsequent excisional biopsy confirmed the cytologic diagnosis. Metastatic germ cell tumors should be considered in the differential diagnosis of HIV-related lymphadenopathy.     

Staphylococcal enterotoxin-A directly stimulates signal transduction and interferon-gamma production in psoriatic T-cell lines

MRI has gained an undisputed place in the evaluation of malignant bone tumors, not only for verifying results of conventional radiographs and clarifying differential diagnoses; it has also become increasingly important for the assessment of the malignant/benign nature of the tumor, its growth rate, definition of adequate sites for biopsy, local preoperative staging, and evaluation of the response to chemotherapy. However, several pitfalls have to be observed regarding choice of technical parameters (coils, sequences, imaging planes), tissue differentiation, and tumor staging. When staging malignant tumors, critical aspects which have to be observed are tumor extension, integrity of the cortical bone, soft tissue components, infiltration of a joint or neurovascular bundle. The use of contrast agents provides important additional information but can also give rise to misinterpretations. Thus, all features of a tumor have to be observed in order to establish a final diagnosis. Particular difficulties can occur with the interpretation of MR images of osteomyelitis, osteoid osteoma, stress and insufficiency fractures, bone infarcts, myositis ossificans, hemangiomas, and aneurysmal bone cysts.     

Neoadjuvant chemotherapy in malignant fibrous histiocytoma of bone and in osteosarcoma located in the extremities: analogies and differences between the two tumors

BACKGROUND: Malignant fibrous histiocytoma (MFH) is a rare bone tumor usually treated like osteosarcoma. Studies on analogies and differences between the two tumors have seldom been reported. PATIENTS AND METHODS: Between March 1982 and December 1994, 51 patients with high-grade MFH of bone and 390 with high-grade osteosarcoma were treated with the same regimen of neoadjuvant chemotherapy. All of the tumors in both groups were located in the limbs. Preoperative chemotherapy was performed according to three different, successively activated, regimens consisting of MTX/CDP intraarterially, MTX/CDP/ADM, and MTX/CDP/ADM//IFO. RESULTS: The rate of limb salvage was the same in both the MFH (92%) and osteosarcoma (85%) patients. MFH showed a statistically significantly lower rate of good histologic response, 90% or more tumor necrosis (27% vs. 67%, P = 0.00001) for all three regimens. Despite this low chemosensitivity, the disease-free survivals of the two neoplasms were similar (67% vs. 65%). CONCLUSIONS: In terms of histologic response to primary chemotherapy, MFH has a lower chemosensitivity than osteosarcoma. Nevertheless, the two tumors have similar prognoses when treated with chemotherapy regimens based on MTX, CDP, ADM and IFO.     

Expression of P-glycoprotein in high grade osteosarcomas with special emphasis on chondroblastic subtype

The development of chemoresistance is one of the major clinical problems in the therapy of malignant bone tumors in childhood. The expression of membrane-bound P-glycoprotein turned out to be an essential factor in the evidence of resistant tumor cells. To investigate the significance of multidrug resistance in the prognosis of highly malignant osteosarcomas, the immunohistologic expression of P-glycoprotein was investigated in the tumor tissue of 52 patients under special consideration of the histologic subtype. The data were compared with the histologic regression grade in the resection specimen and correlated with clinical data. Formalin-fixed, paraffin-embedded tissue and, additionally, fresh frozen material taken from the primary biopsy were stained using monoclonal antibody JSB1. 29 (55%) of the tumors investigated were P-glycoprotein positive. Considering the response to chemotherapy, no conclusion could be drawn regarding P-glycoprotein expression, regression grade in the resection specimens, and the clinical follow-up. P-glycoprotein was detected in only 52% of the non-responders. A positive reaction was also evidenced in 59% of the patients with high chemosensitivity. A comparison of the histologic subtypes yielded a significant result in the chondroblastic osteosarcomas. 11 of 12 cases showed a strong expression of P-glycoprotein. Most of the cases were non-responders, and using Kaplan-Meier live tables, an unfavorable clinical outcome could be demonstrated. Possibly, chondroblastic tumors have a special position among osteosarcomas because of their differentiation.     

Epididymal tumors (author's transl)

Six cases of benign primary epididymal tumor have been investigated in our patients. The tumor size fluctuated between 3 and 35 mm in diameter. Frequency, histology and medical development are described. The majority of epididymal tumors (53%) is comprised of so-called adenomatoid tumors of benign nature and their histogenesis is being discussed. The difficulties of differential diagnosis are pointed out. Since malignity exists in 26% of the cases, the surgical exposure and diagnosis by frozen section is being postulated, when suspicion of epididymal tumor becomes evident.     

Technetium-99m-MIBI in primary and recurrent head and neck tumors: contribution of bone SPECT image fusion

We prospectively investigated 200 patients with the clinical suspicion for head and neck tumors. The final diagnoses were 94 primary and 56 (37 confirmed, 19 excluded) recurrent squamous cell carcinomas (SCCs), 3 primary and 7 (4 confirmed, 3 excluded) recurrent adenoid cystic carcinomas (ACCs), 6 non-Hodgkin's lymphomas, 10 distant metastases, 6 other malignancies, 10 inflammatory and 8 other nonmalignant conditions. METHODS: Bone (600 MBq 99mTc-3,3-diphosphono-1,2-propane dicarboxylic acid tetrasodium salt) and hexakis-2-methoxyisobutyl isonitrile (MIBI) (600 MBq 99mTc-MIBI) SPECT were both performed under identical conditions (triple-head gamma camera; ultra-high-resolution, parallel-hole collimators; three-dimensional postfiltering) and judged independently and after superimposition. The results were compared to the results of biopsy, surgery and CT. RESULTS: The overall sensitivity/specificity of MIBI was 90%/78% for tumor detection and 90%/95% for the identification of malignant lymph node involvement (CT: 79%/66%, respectively 90%/79%). In the subgroup of recurrent SCC and ACC the sensitivity/specificity for tumor detection was 95%/71% for MIBI versus 78%/68% for CT. The isolated assessment of bone SPECT had a sensitivity/specificity of 100%/17% for osseous tumor spread. Image fusion of MIBI and bone SPECT differentiated between regio-local bone involvement and inflammatory changes and increased the specificity of bone SPECT to 100% in primary staging. Tumor size, stage, histology and pretreatment had no statistically significant effect on tracer uptake or diagnostic utility of scintigraphy. CONCLUSION: We propose the combined 99mTc-MIBI and bone ultra-high resolution SPECT as a highly useful imaging approach in the primary and secondary staging in patients with suspected malignancies in the head and neck region. The high specificity for malignancies in the head and neck region may be used in the differential diagnosis between head and neck malignancies and inflammatory disease in patients with the accidental finding of enlarged lymph nodes and no clinical signs of a primary tumor. Image fusion with bone scanning is mandatory for the topographical orientation and increases the specificity of bone scanning to differentiate between inflammatory or malignant causes of increased bone metabolism.     

Benign fibrous mesothelioma: report of 8 cases

Benign fibrous mesothelioma (BFM) is a primary, isolated tumor of the pleura. In 80% of patients the tumor originates in the visceral pleura. BFM is rare and localized malignant mesothelioma, whose prognosis and treatment is significantly different, must be considered as a differential diagnosis. We report 8 cases of BFM excised by thoracotomy. In 6 asymptomatic patients, diagnosis was based on radiological images. One patient with a large tumor suffered dyspnea, acropachia and hypertrophic osteoarthropathy. The last patient experienced long-lasting chest pain even though the tumor was small (3 x 3 x 1 cm). Diagnosis was before thoracotomy in 3 cases, 2 by punch biopsy (tru-cut) and the other by thoracoscopy. The results of pleural fluid analysis were nonspecific in 2 of the 3 cases in which pleural effusion was present. Thoracotomy allowed removal of the entire tumor in all patients.     

Malignant fibrous histiocytoma of the mesentery--a rare cause of abdominal pain. Case report with a review of literature

Malignant fibrous histiocytoma (MFH) is a tumor most frequently occurring in lower and upper extremities and in retroperitoneum. This paper presents the extremely rare case of a 55-year-old male patient with a MFH of storiform pleomorphic subtype originating from the mesentery. Sonography, computed tomography as well as endoscopy and ERCP did not reveal the diagnosis. Finally the tumor was diagnosed by laparoscopy with biopsy and histological examination. Two months after diagnosis of the tumor the patient died of bronchopneumony and heart failure contracted during a generalisation of MFH.     

Analysis of case-control studies of the efficacy of screening for cancer: How should we deal with tests done in persons with symptoms?

OBJECTIVE: The congenital occurrence of malignant rhabdoid tumor (MRT) is rare. Initial presentation of congenital MRT as a skin tumor is even more rare. We report 2 cases in which a cutaneous nodule appeared prior to the discovery of the primary tumor. METHODS: Histologic, ultrastructural, and immunohistochemical studies were performed on skin nodules from 2 neonates. Other congenital examples of MRT in the literature were reviewed. RESULTS: Both neonates were male and both were fullterm. Skin nodules were noted at birth. The tumors were located on the right neck in case 1 and on the right back in case 2. The primary tumors were later found in the kidney and the right chest wall, respectively. The skin biopsy of the first case had been interpreted as undifferentiated sarcoma, and MRT was diagnosed after the renal tumor was examined. In the second case, a correct diagnosis was promptly made based on the skin biopsy owing to experience with the first case. CONCLUSIONS: Congenital MRT is very uncommon and may present as a skin tumor at birth. Since MRT exhibits various histologic patterns, the diagnosis should be made by a complete pathologic study with proper clinical correlation. To our knowledge, the unique mode of manifestation in these 2 cases is described for the first time. We suggest that MRT should be considered when making the differential diagnosis in such a clinical setting.     

The stepchild of intestinal diagnosis. Evaluation of radiologic methods in the diagnosis of leiomyoma of the small intestine

PURPOSE: Various radiological methods to diagnose small bowel neoplasms and problems of differential diagnosis specially considering leiomyomas are discussed. PATIENTS AND METHODS: Two patients with leiomyoma of the ileum underwent enteroclysis, computed tomography of the abdomen, intra-arterial DSA and colour Doppler sonography. Another patient with leiomyosarcoma just underwent CT of the abdomen with CT-guided biopsy. RESULTS: Due to the homogenous density and the smooth surface of the tumors in computed tomography and respectively enteroclysis and the presentation of the tumor vascularisation in the angiography and Colour Doppler sonography in both patients a leiomyoma of the small bowel was diagnosed. Postoperatively this diagnosis was histologically confirmed. The CT-findings of the patient with leiomyosarcoma were not suspicious of a malignant tumor. CONCLUSION: Radiologically it is not possible to determine the dignity of smooth muscle cell tumors safely. That is the reason why the diagnosis has to be achieved operatively. But the histopathological diagnosis based on the mitotic rate may be difficult. Therefore the after care has to be carried out thoroughly.     

Structure of the glycosylphosphatidylinositol membrane anchor glycan of a class-2 variant surface glycoprotein from Trypanosoma brucei

Neoplasms of the small bowel are rare lesions that account for less than 5% of all gastrointestinal tumors. Although the differential diagnosis for a small bowel tumor is extensive, various small bowel neoplasms have characteristic features at computed tomography (CT) that may aid in making a diagnosis. Small bowel adenocarcinoma may appear at CT as an annular lesion, a discrete nodular mass, or an ulcerative lesion. Non-Hodgkin lymphoma may appear as a segmental bulky mass that gradually merges into the normal bowel wall. Lymphoma is characteristically associated with marked luminal dilatation. Carcinoid tumor may appear as an ill-defined homogeneous mass that displaces bowel loops. Calcification and desmoplastic reaction in a mesenteric mass suggest the diagnosis of carcinoid tumor. Gastrointestinal stromal tumors (GISTs), both benign and malignant, may be submucosal, subserosal, or intraluminal. The CT appearance of a GIST may include a sharply defined mass with homogeneous attenuation, sometimes with calcification. Lipoma appears at CT as a well-circumscribed, intraluminal homogeneous mass with fat attenuation. Most malignant small bowel tumors are actually metastases that have spread intraperitoneally, hematogenously, or by local extension. Intraperitoneal seeding usually manifests at CT as multiple small nodular metastases along the small bowel serosa, mesentery, and omentum. In patients with Peutz-Jeghers syndrome, nonneoplastic lesions may mimic small bowel neoplasms.     

Primary bone and metastatic tumors of the cervical spine

Cervical spine tumors, whether primary bone tumors or metastatic tumors, are rare. The possibility of tumors existing must be considered in the differential diagnosis of patients with persistent neck pain, with or without neurologic symptoms, particularly in those with significant pain at night. The clinical presentation is extremely variable, though a history of malignancy should always raise the concern for recurrence. The evaluation and diagnostic assessment includes a thorough physical examination. Radiographic imaging is usually initiated with plain radiographs and additional advanced imaging obtained as indicated. Using appropriate biopsy principles and techniques, tissue is obtained for histologic determination of the suspected lesion before surgical intervention. Treatment options are extremely variable and depend on many factors, including tumor type, location, and patient preference. Treatment warrants a multidisciplinary approach from experienced physicians and is most successfully accomplished in referral centers. Oncologic staging using the Enneking staging system, followed by surgical staging using the Weinstein, Boriani, Biagini system, will aid in the accurate characterization of the tumor load, maximize surgical goals, assure use of appropriate terminology, and provide optimal communication among treatment centers regarding tumor characteristics, treatment efforts, and results.     

Rare differential diagnosis of breast tumor. Giant cell tumor of the ribs

We report a case of a breast tumor. As carcinoma of the breast was suspected, a biopsy was taken and a very rare osteoclastoma originating in the rib was identified. Semimalignant bone tumors tend to recur locally. The symptoms are nonspecific; the initial diagnosis is often made late. To differentiate the diagnosis, one should think about primary and secondary bone diseases and tumors of the organs of the thorax. In our case, the tumor was completely resected, including the ribs, and the defect was covered with a corium plasty. In this way, we are able to save the breast. We discuss different methods for covering chest wall defects.     

Positron emission tomography (PET) methodology for small animals and its application in radiopharmaceutical preclinical investigation

Among the more uncommon tumors that may sometimes be encountered in the laryngeal region is the recently described giant cell tumor of the larynx. This lesion is a true neoplasm, presumably of the fibrohistiocytic series. Histologically, it closely resembles the more familiar true giant cell tumor of long bone. The laryngeal giant cell tumors appear, to date, to be nonmetastasizing lesions; it is possible that they may recur locally if incompletely excised (although this remains to be demonstrated). In view of the rarity of these tumors, a tentative diagnosis of such a neoplasm should always prompt consideration of other (more frequently encountered) differential diagnostic possibilities, including cytologically malignant giant cell-rich tumors such as malignant fibrous histiocytoma and sarcomatoid carcinoma.     

Histology, immunohistochemistry, and electron microscopy of small round cell tumors of bone

Small round cell tumors (SRCTs) of the bone make up a family of primary bone sarcomas with morphologically, biologically, and clinically specific features. Among them, Ewing's sarcoma (ES) is the most common entity, but several varieties such as atypical ES, large cell ES, and ES with neuroectodermal differentiation (peripheral primitive neuroectodermal tumor of the bone or neuroepithelioma of the bone) have been identified recently. Histology and electron microscopy together with the variable expression of several epitopes (as shown by immunohistochemistry, mainly HBA/71 [Mic2 antigen]) provide the basis for characterizing the group within the context of neuroectodermal-derived neoplasms. A number of other ES-like tumors with small round cells, mimicking those previously described, have been characterized; Askin's tumor of the thoracopulmonary region will be considered as an ES similar to those already described, but within a particularly anatomic location. On the other hand, the presence of an endothelial appearance within a poorly differentiated neoplasm may be present in some ES-like SRCTs (atypical ES with endothelial features). The differential diagnosis with other sarcomas defined by small round to spindle cell contours might prove difficult. Particular attention must be paid to small cell osteosarcoma and mesenchymal chondrosarcoma. Likewise, "primitive sarcoma of bone" is considered in this study because it is a very rare neoplasm differing from the formerly discussed types; its pluripotentiality provides this tumor a blastemic character and a multiphenotypic expression. Malignant non-Hodgkin's lymphoma is an unusual presentation when primary to the bone, previous to any other anatomic location. Several subtypes have been considered within a histology that encompasses that seen in lymph nodes.     

Genetic instability in osteoblastic tumors of the skeletal system

At the histological level, the differential diagnosis of osteoblastic bone tumors is characterized by several problems that cannot be solved by conventional histological methods including immunohistology. Differentiating aneurysmal bone cyst from telangiectatic osteosarcoma or giant cell tumor from giant cell-containing highly malignant osteosarcoma are only two examples reflecting the complexity of this field. To develop a new approach to these diagnostic problems, we analyzed the genetic instability in a large number of bone-forming tumor-like lesions as well as in benign and malignant osteoblastic tumors. Our research concentrated on genetic alterations in cell cycle regulator genes: mutations in the p53 gene and ras gene, loss of heterozygosity at the p53, p16 and Rb-locus, and amplification of the mdm2-gene and the c-myc-gene. In addition to cell cycle regulators, the telomerase activity has also been analyzed. The results show that the number of genetic alterations increases with the malignancy of the tumors. The highest number of genetic alterations could thus be found in conventional intraosseous osteosarcoma. In tumor-like lesions, genetic alterations have rarely been observed. The results of this study show that analyzing the genetic instability probably contributes to an improvement in the differential diagnosis of osteoblastic tumors.