Loss of succinate dehydrogenase B immunohistochemical expression distinguishes pulmonary chondromas from hamartomas.

AIMS: Pulmonary chondromas, which are rare cartilaginous neoplasms that often arise in the setting of Carney triad, are morphologically similar to pulmonary hamartomas, which are much more common. There is evidence that succinate dehydrogenase (SDH) deficiency drives neoplasia in patients with Carney triad, and SDHB immunohistochemistry can be used as a surrogate marker to detect SDH deficiency. The aim of this study was to investigate the utility of SDHB immunohistochemistry in distinguishing pulmonary chondromas from hamartomas. METHODS AND RESULTS: Immunohistochemistry for SDHB (clone 21A11AE7) was performed on histological sections from six cases of pulmonary chondroma and 33 cases of pulmonary hamartoma. SDHB expression was retained in all 33 pulmonary hamartomas, and lost in the majority of evaluable chondromas (five of six). Of the five patients with chondromas showing SDHB loss, four had definitive Carney triad. Most patients with pulmonary hamartomas were older males with small solitary masses, whereas chondromas often presented as multiple masses in young females. CONCLUSION: Loss of SDHB immunohistochemical expression can be useful for differentiating pulmonary chondromas from hamartomas, and potentially identifying patients with Carney triad.

[Benign tumours and tumour-like lesions of the bone : General treatment principles]. / Benigne Tumoren und tumorähnliche Läsionen des Knochens : Allgemeine Behandlungsprinzipien.

BACKGROUND: Benign bone lesions are much more common than malignant lesions. Some benign bone tumors have a characteristic and typical radiographic appearance, while others are more challenging. Therapy of benign bone tumors differs greatly. While the majority of benign bone tumors do not require surgical therapy, other specific lesions, e. g. aneurysmal bone cysts or giant cell tumors (GCT) of the bone require surgery due to their locally aggressive behavior. DIAGNOSTICS: The major challenge for the radiologist and/or pathologist is the differentiation between a benign and low-grade malignant lesion (e. g. enchondroma versus low-grade chondrosarcoma) for which all available clinical and radiographic information is mandatory. Therefore, surgical therapy is rather more often performed than necessary due to uncertainty in many cases. THERAPY: Novel systemic therapies are available for fibrous dysplasia and GCT of the bone: Fibrous dysplasia can be treated with bisphosphonates, and GCT responds to denosumab. In fact, denosumab has been approved for the treatment of irresectable GCT. Osteoid osteoma is fairly easy to recognize and also to treat given the characteristic clinical presentation and rapid and effective response to local therapy (possible as percutaneous thermo-/laser ablation). In summary, several therapeutic options exist for benign bone tumors, and the choice depends upon the tendency/risk of local recurrence, the rate of surgical complications, options for defect reconstruction, postoperative functional deficits, and specific patient characteristics.

[Gastrointestinal stromal tumor (GIST): advances in 2013]. / Gastrointestinální stromální tumor (GIST): pokroky do roku 2013.

Gastrointestinal stromal tumors (GIST) are currently regarded as a heterogenous group of tumors sharing common histological appearance, KIT immunopositivity and supposed origin from tissue progenitor cells capable of differentiation into the phenotype of Cajal interstitial cells. GISTs can be divided according to immunoexpression of the beta subunit of mitochondrial enzyme succinate dehydrogenase (SDHB) to SDHB-positive (encompassing KIT, PDGFRA and NF1 mutated GISTs), and SDHB-deficient GISTs (including Carney-Stratakis syndrome, Carney triad, sporadic pediatric GISTs, and a small subset of sporadic adult GISTs). The individual molecular subtypes differ in biological behavior and in their response to systemic targeted therapy, which is indicated in metastatic GISTs or in tumors with high risk of recurrence. Although several risk-stratification classifications have been developed, strictly defined criteria to identify patients at risk are still lacking. Pharmacogenomics have been successful in designing drugs to overcome not only the primary resistance of GISTs to the action of imatinib (e.g. GISTs with a substitution of Asp842Val in exon 18 PDGFRA or SDHB-deficient GISTs), but also the secondary resistance caused by secondary mutation of a gene encoding either the receptor tyrosine kinase or other molecules involved in the respective signalling cascade. Future directions concentrate on rational molecular targeting for systemic therapy based on complex genetic investigation of the tumor. Peripheral blood is planned to be used as a source of information for genetic events responsible for the secondary resistance of metastatic tumors.

Assessment of interobserver variability and histologic parameters to improve reliability in classification and grading of central cartilaginous tumors.

The distinction between benign and malignant cartilaginous tumors of bone is one of the most difficult subjects in surgical pathology. The grading of chondrosarcoma also seems to vary considerably among pathologists. However, clinical management differs. The purpose of this study was (1) to investigate interobserver variability in histological diagnosis and grading of central cartilaginous tumors and (2) to assess the diagnostic value of defined histologic parameters in differentiating enchondroma and central grade I chondrosarcoma. The interobserver variability was assessed using a set of 16 cases evaluated by 18 specialized pathologists. Subsequently, 20 enchondromas and 37 central grade I chondrosarcomas diagnosed in a multidisciplinary team with full clinical, radiologic, and pathologic data available with 10 years of follow-up were collected. Cytologic and tissue-architectural features were assessed to find an optimal set of parameters to differentiate enchondroma from central grade I chondrosarcoma. We demonstrate considerable variation in the histologic assessment of cartilaginous tumors (weighted kappa=0.78). The distinction between enchondroma and grade I chondrosarcoma was shown to be the most disconcordant (kappa coefficient=0.54), and also the differentiation between grade I and grade II chondrosarcoma was subjected to variation (kappa coefficient=0.80). The application of a combination of 5 parameters (high cellularity, presence of host bone entrapment, open chromatin, mucoid matrix quality, and age above 45 y) allowed optimal differentiation between enchondromas and central grade I chondrosarcomas. With a classification tree based on 2 parameters (mucoid matrix degeneration more than 20% and/or host bone entrapment present), 54 of the 57 (94.7%) cases were assessed correctly (sensitivity 95% and specificity 95%). Our study confirms the low reliability of the diagnosis and grading of central chondrosarcoma. However, these classifications guide therapeutic decision making in daily practice. Therefore, we propose a classification model that, combined with a tailored radiologic assessment, may improve reliability of the diagnosis of cartilaginous tumors.

[Cartilage tumors of the skeleton]. / Chondrogene Tumoren des Skeletts.

Although the spectrum of benign and malignant cartilaginous bone tumors is extremely wide, a distinct diagnosis, even from small biopsy specimens, is almost always possible if radiological findings, age, clinical data, and localization within the skeleton as well as within the bone are considered. With limitations, this also holds true for distinguishing enchondromas from low-grade chondrosarcomas; however, extensive experience in multidisciplinary bone tumor diagnosis is required. In single cases, immunohistochemical findings may be helpful in the differential diagnosis if they are integrated into the context of all other findings. Because of treatment-related or prognosis-related consequences, collaboration with a reference center is recommended.

A reproducible and simple grading system for classical chondrosarcomas. Analysis of 35 chondrosarcomas and 16 enchondromas with emphasis on recurrence rate and radiological and clinical data.

In the past, six histological grading systems for classical chondrosarcoma have been published. Due to the inhomogeneity and complexity of these classifications, the comparison of clinical data, survival rates and local failures has to be considered critically. In 1996, the author published a grading system that was simple to use and easily reproduced. This system was based on a few nuclear features. The main intention of the current study was to verify whether the histological grade, which was defined by the author's classification, correlates with the recurrence rate. In a retrospective study, clinical data, X-rays and histological material from 35 patients with classical chondrosarcoma and 16 patients with enchondroma were analysed. Statistical analysis was done using the chi-squared test and the Fisher exact test. Local recurrence occurred in 25.7% of all patients. The difference in recurrence rate among grades 1-3 was statistically significant ( P=0.002). The frequency of grades 1-3 varied up to 54%, when published grading systems were compared. No significant difference between the histological grade and features such as double nuclei and mitosis were observed. The frequency of cellularity, double nuclei and mitoses was similar between enchondromas and low-grade chondrosarcomas. Of chondrosarcoma patients, 90.6% of total patients and 87.5% of those with grade-1 lesions reported pain, whereas only 43.8% of the enchondroma patients did. Even in patients with grade-1 chondrosarcomas, radiological findings were much more aggressive in comparison with enchondromas. The histological grade, defined on the basis of the author's simple and reproducible grading system, indicates the risk of local recurrence, especially in cases that are inadequately treated. Grade-3 chondrosarcomas and lesions located in regions where the removal of the tumour would be difficult have to be given special attention.

Simple curettage without bone grafting for enchondromata of the hand: with special reference to replacement of the cortical window.

We studied 23 patients (25 bones) with enchondromata of the hand which were treated with simple curettage without bone grafting. The cortical window was replaced in 18 bones (group A), whereas it was not replaced in six bones (group B). In one bone, only half of the cortical window was replaced. Local recurrence was not seen in any patient. Although bone grafting was not performed, new bone formation was observed in all the patients. Radiographic and functional results were excellent in most bones. Restoration of the continuity of the cortex was seen at 3 (range, 1.5-4) months in group A and 8 (range, 6-12) months in group B. This restoration is important for the recovery of mechanical strength and we therefore consider that the cortical window should be replaced, unless this is impractical.

Classification of bone tumors.

The classification of bone tumors relies on the cytologic features and products of tumor cells. This classification is reproducible and accepted by pathologists, oncologic surgeons and oncologists. Chondrogenic tumors are the second largest group of bone tumors. Their histologic pattern suggests a relationship to hyaline cartilage. Exostoses, or osteochondromas, represent about 1/3 of chondrogenic lesions. Chondromas are hyaline cartilage tumors which can be found centrally or subperiosteally; they may contain some calcifications and/or ossifications. Chondroblastomas are tumors whose cells produce, at least focally, a matrix similar to hyaline cartilage. Histology of chondromyxoid fibromas shows large or small areas where proliferating cells produce a matrix resembling the hyaline cartilage. Chondosarcomas are tumors whose malignant cells produce a cartilaginous matrix. Most of them occur in previously normal bones; they are classified as conventional or primary chondrosarcomas. Secondary chondrosarcomas result from the malignant transformation of a benign cartilaginous lesion less commonly enchondromas and most commonly osteocartilaginous exostoses, or osteochondromas. Less common variants include dedifferentiated, mesenchymal and clear cell chondrosarcomas. Osteogenic tumors are the third largest group of bone tumors, with osteosarcomas being the most frequent type. The most important criterion for a tumor to be considered an osteosarcoma is that the malignant tumor cells must produce a recognizable osteoid matrix, at least focally. Osteosarcomas are divided into three groups: osteoblastic, chondroblastic and fibroblastic, according to the dominant histologic feature. Osteosarcomas can be multifocal, synchronous or metachronous; they are also classified by the histologic grade of malignancy. Pathologically low grade lesions, which are clinically indolent, are generally known as low grade central and parosteal osteosarcomas.

Magnetic resonance imaging of cartilaginous tumors: a retrospective study of 79 patients.

OBJECTIVE: Hyaline cartilaginous tumors are characterized by extremely high signal intensity on T2-weighted images. Recently, some distinctive MR features of cartilaginous bone tumors were reported in small series. Low signal intensity septa surrounding high signal intensity cartilage lobules were seen on T2-weighted images in low-grade chondrosarcomas. On spin-echo T1-weighted images after Gd contrast injection, marked 'septal' or 'ring-and-arc' enhancement was observed in low-grade chondrosarcomas and enchondromas. The purpose of this study was to determine sensitivity and specificity of these MR findings in diagnosis of cartilaginous tumors, and to assess the value of MR in diagnostic workup of these lesions. MATERIALS AND METHODS: Retrospective evaluation of MR findings in 79 cartilaginous tumors and in 79 non-cartilaginous tumors. All lesions were biopsy proven. Each MR examination was independently reviewed by two experienced radiologists without knowledge of clinical data, radiographic and/or CT findings, or histological diagnosis. All lesions were evaluated for morphology (lobular or non-lobular), presence of a high signal intensity mass on T2-weighted images, presence of low signal intensity septa separating high signal intensity lobules on T2-weighted images, and evidence of septal ('ring-and-arc') enhancement. RESULTS: None of the reviewed parameters is useful in diagnosing osteochondromas. Since osteochondromas have a characteristic appearance on plain radiography, the value of MR imaging in the workup of these lesions remains limited. MR findings in enchondromas have a low specificity and a low sensitivity. Low-grade chondrosarcomas, often hard to diagnose on plain radiography and difficult to differentiate from enchondromas, are characterized by the MR tandem of 'low signal intensity septa on T2-weighted images' together with 'septal or ring-and-arc enhancement' (sensitivity 92.3%, specificity 76.5%). High-grade chondrosarcomas are easily recognized on plain radiography. CONCLUSIONS: In differentiating cartilaginous from non-cartilaginous tumors, MR features are highly specific but lack sensitivity. Grading potentials of MR parameters are promising due to the high accuracy in diagnosing low-grade chondrosarcomas.

Genochondromatosis.

We report a new disorder that we have called genochondromatosis. Four patients from the same family with the characteristic localisation of chondromatosis (clavicle, upper end of humerus, and lower end of femur) were investigated. The favourable course, the dominant transmission, and previous publication of similar cases confirm the uniqueness of this new entity. The chondrodysplasias with disorganised development of cartilage are far from being completely understood. Recently, several disorders within this group have been well defined, including metachondromatosis and spondyloenchondroplasia, but there still remain numerous clinical subgroups that are very difficult to classify.

Rare sacral space-occupying lesions, their surgical management and reconstructive measures involved.

Nine cases of space-occupying lesions of the sacral bone are presented. The problems of the clinical diagnosis, which in many cases comes too late, are discussed together with the indications for surgical treatment in this special group of tumours. The main clues are provided by the changes in the X-rays as well as the more modern imaging techniques (CT and MRI). The surgical technique aims at a most radical tumour removal with preservation of the sacral nerve roots, after which stabilisation of the sometimes weakened pelvic girdle may be necessary. The good prospects of complete removal of these tumours of the sacrum with satisfactory results seem to be very little known and justifies further dissemination of this information.

[Classification of primary bone tumors]. / Zur Klassifikation primär ossärer Geschwülste.

An expanded classification for bone tumors is presented based on the well known international classification as well as earlier systems. The current status and future trends in this area are discussed.

Histopathology and ultrastructure of tumours and tumour-like lesions of bone.

The monograph summarizes the most important data and experience based on the clinicopathological analysis, histological and histoenzymatic examinations of more than 1000 primary tumours and 400 tumour-like lesions of bones. The diagnosis of them has been based on the WHO classification of bone tumours which appeared to be the best in meeting the needs of diagnostic practice. However, in our collection of cases also occurred such cases which did not fit into the WHO diagnostic scheme. They included lesions the separate existence of which could be proved only recently or has remained the matter of discussion, such as periosteal osteosarcoma, clear-cell and dedifferentiated chondrosarcoma, malignant fibrous histiocytoma, the so-called parachordoma, resorptive giant-cell granuloma, reactive periostitis of tubular bones of hands and feet, and the tibial lesion reminiscent of cementifying fibroma. In the majority of types of the tumours and tumour-like lesions of bones electron microscopical examination was carried out (203 cases), the results of which are presented here in a considerable extent. On the one hand, electron microscopy facilitated the diagnosis in some cases, and, on the other hand, it proved as extremely important in solving the problems of histogenesis of some of the lesions.

[Classification of benign tumors and cysts of the jaws]. / Classification des tumeurs bénignes et kystes des maxillaires.

On the basis of 324 cases of maxillary tumours, the authors review the classification of these neoplasms. The most frequent tumours are benign epithelial odontogenic tumours, which represent 55% of all tumours. The most common of these tumours is the ameloblastoma, followed by the odontomas. Most of the tumours of non-dental origin are benign (72% of this group). Amongst the malignant tumours, osteosarcomas are much more common than chondrosarcomas. The authors also discuss the various types of cyst and their respective relative frequency.

[Cytological classification of bone tumors]. / Tsitologicheskaia klassifikatsiia opukholei kostei.

The creation of a classification is a first need for the improvement of the cytological diagnosis. The cytologic classification of bone tumours is worked out on the basis of the International Histological Classification. The possibilities and limitations of the cytologic method are taken into consideration. A brief description of all nosological entities mentioned in the classification is given.

[Bronchopulmonary hamartomas, chondromas, fibromas and myxomas]. / Bronchopulmonale Hamartome, Chondrome, Fibrome und Myxome.

The observation of 23 bronchopulmonary hamartomas, 9 chondromas, one fibroma and one myxoma has provided insight into the particularities of these tumors. The group of hamartomas, tumors of "erroneous mixture of tissue", included 20 cases which can be considered a malformation of the entodermal bronchial anlage, and 3 cases which can be regarded as a malformation of the mesenchymal anlage. The first type consists of multiple cleft-like spaces surrounded by ciliated and cuboidal epithelium. There are no alveolar cells. Cartilaginous, fibrous, myxomatous and lipomatous tissue and lymphocytes are also found. The second type consists mainly of undifferentiated mesenchymal cells with tubules, lined by cuboidal epithelial cells or an intestinal type of mucus-secreting epithelium. There may be some immature alveoli, but no ciliated epithelium is found. In contrast to the hamartomas, the chondromas are not derived from a dysontogenetic malformation of the bronchopulmonary tissue but are tumors which develop directly from the bronchial cartilage and are for this reason mainly localized in the endobronchial region. A special form seen in one case is association of pulmonary chondromas, gastric leiomyomas or leiosarcomas and extra-adrenal paraganglioma, though the latter is not always present.

[Cartilaginous tumors of the skeleton]. / Die Knorpelgeschwülste des Skelets

Chondrogenic tumors of the skeleton are divided into 6 separate groups: 1. chondroblastomas 2. chondromyxoidfibromas, 3. osteochondromas (cartilaginous exostoses), 4. enchondromas, 5. periostal chondromas, and 6. chondrosarcomas. The presentation of the different types of tumors demonstrates the pathogenesis, pathology, clinical findings, treatment, and prognosis. States of tumors before and after operative treatment are illustrated.