In recent years, significant insights regarding the biology and therapy of giant cell tumor of bone (GCTB) have been published. Crucial for diagnostics was the discovery of the highly characteristic mutation in the H3F3A gene, which leads to a G34W amino acid exchange in histone H3. In addition, the treatment of inoperable GCTB with the anti-RANKL antibody denosumab has become established in therapy. Reports of malignant transformation of GCTB in association with denosumab therapy have been published, however the concrete influence of denosumab is not clearly clarified. The Arbeitsge-meinschaft Knochentumoren (AGKT e. V.) has initiated a multi-institutional study to establish a clinically well-defined cohort of GCTB with the aim of a) a detailed description of morphological changes caused by denosumab; b) identification of possible risk factors regarding a potential malignant transformation into sarcoma for establishment of a histological risk stratification; c) comparison of these data to recurrent GCTB for identification of potential risk factors of recurrency in GCTB. For this purpose, 26 GCTB before and after denosumab therapy and 14 recurrent GCTB compared to the primary tumor without denosumab were included in this study in pairs. Techniques used area detailed histological assessment of morphological changes during denosumab therapy and in recurrent GCTB including a broad panel of markers for immunohistochemical analysis. This clinically well-defined cohort will serve as a basis for a database and tissue bank for further molecular pathologic analysis.

ZusammenfassungIn den letzten Jahren wurden bedeutsame Daten zur Biologie und Therapie des Riesenzelltumor des Knochens (RZTK) veröffentlicht. Ein entscheidender Durchbruch für die Diagnostik von RZTK war die Entdeckung der hoch tumorcharakteristischen Mutation im H3F3A-Gen, die zum Aminosäureaustausch G34W im Histon H3 führt. Zudem konnte sich in der Therapie die Behandlung von inoperablen RZTK mit dem anti-RANKL Antikörper Denosumab etablieren. Im Zusammenhang mit einer Denosumab-Therapie gibt es allerdings auch Berichte einer malignen Transformation des Tumors, wobei der konkrete Einfluss von Denosumab nicht eindeutig geklärt ist. Die Arbeitsgemeinschaft Knochentumoren (AGKT e. V.) hat daher eine multi-institutionelle Studie initiiert, um ein Kollektiv von RZTK zu etablieren mit dem Ziel a) morphologische Veränderungen unter Denosumab-Therapie detailliert zu beschreiben; b) Faktoren hinsichtlich einer potentiellen Malignisierung in ein Sarkom im Sinne einer Risikostratifizierung zu identifizieren; c) im direkten Vergleich RZTK im Rezidiv zu analysieren und mögliche Risikofaktoren hinsichtlich eines Rezidivs zu erarbeiten. Dafür wurden 26 RZTK vor und nach Denosumab-Therapie und 14 RZTK im Vergleich Primarius zu Rezidiv ohne Denosumab-Behandlung paarweise in die Studie eingeschlossen. Eingesetzte Techniken sind zunächst die histologische Beurteilung der morphologischen Veränderungen und die immunhistologische Analyse mittels eines breiten Panels an Markern. Das klinisch gut definierte Kollektiv soll im weiteren als Grundlage für eine Daten- und Gewebebank für zusätzliche molekularpathologische Analysen dienen.

Das Basler Knochen Tumor Referenzzentrum wurde 1972 auf Initiative von Prof. Dr. Hans-Ulrich Zollinger, dem damaligen Vorsteher des Instituts für Pathologie des Universitätsspitals Basel, gegründet. Anlass dafür war eine Studienreise in die USA mit Besuch des American College of Surgeons und seiner Register. Von diesem Besuch nahm Zollinger die Erkenntnis mit, dass seltene Tumoren nur an einem Ort gesammelt und bearbeitet werden sollten, da nur so eine ausreichende diagnostische Expertise zu gewinnen ist.

Aims Giant cell tumour of bone (GCTB) is histologically defined as a lesion containing reactive giant cells and a neoplastic mononuclear cell population; in up to 92% of cases, GCTB is characterised by a specific mutation of the histone gene H3F3A. The cellular composition ranges from giant-cell-rich to giant-cell-poor. The diagnosis of GCTB can be challenging, and several other lesions need to be excluded, e.g. aneurysmal bone cysts, non-ossifying fibromas, chondroblastomas, brown tumours, and giant-cell-rich osteosarcomas. Our aim was to analyse the clinical history, imaging, molecular pathology and histology of three H3F3A-mutated bone tumours without detectable giant cells. None of the patients received denosumab therapy. Methods and results Diagnostic material was obtained by curettage or resection and/or biopsy. Common histomorphological features of all three reported lesions were fibrocytic, oval cells in a background of osteoid and an absence of multinuclear giant cells as confirmed with CD68 immunohistochemistry. We used immunohistochemistry and Sanger sequencing to demonstrate positivity for the H3.3 p.G34W mutation. Differential diagnoses were systematically excluded on the basis of histomorphology, immunohistochemistry, and fluorescence in-situ hybridisation. The imaging (radiography, computed tomography, and magnetic resonance imaging) for all three cases is presented and discussed. Conclusions We believe that these GCTBs without giant cells expand one end of the heterogeneous range of GCTB. Because of the lack of giant cells, correct diagnosis of GCTB is challenging or even impossible on histological grounds alone. In these cases, detection of the characteristic H3F3A mutation (G34W-specific antibody RM263 or sequencing) is extremely helpful for diagnosing those lesions without giant cells as giant cell tumours of bone.

Mit der fünften Auflage der WHO Knochentumor-Klassifikation, die zusammen mit der Klassifikation der Weichteiltumoren im Jahr 2020 erschienen ist, haben sich einige Änderungen ergeben, die auch für die tägliche Arbeit von Bedeutung sind [1].

IntroductionWe describe the use of telepathology in countries with restricted resources using two diagnosis assistance systems (Isabel and Memem7) in addition to the diagnoses made by experts in pathology via the iPath-Network.MethodsA total of 156 cases, largely from Afghanistan, were analysed; 18 cases had to be excluded because of poor image quality.ResultsOf the remaining 138 cases (100%), a responsible physician provided a tentative diagnosis for 61.6% of them. With a diagnosis from a consultant pathologist, it was then possible to make a definite diagnosis in 84.8% of cases on the basis of images taken from hematoxylin and eosin staining sections alone. The use of the diagnosis assistance systems resulted in an ordered list of differential diagnoses in 82.6% (IsabelHealth) and in 74.6% (Memem7) of cases, respectively. Adding morphological terminology reduced the list of possible diagnoses to 52.2% (72 cases, Memem7), but improved their quality.DiscussionIn summary, diagnosis assistance systems are promising approaches to provide physicians in countries with restricted resources with lists of probable differential diagnoses, thus increasing the plausibility of the diagnosis of the consultant pathologist.

Vaskuläre Läsionen sind häufig und treten z. B. in Form vorwiegend oberflächlicher infantiler Hämangiome bei ca. 4 % aller Neugeborenen auf. Auch in der orthopädischen Praxis sind Gefäßanomalien präsent: Skelettale vaskuläre Läsionen werden bei ca. 10 % aller Menschen beschrieben, und betreffen meist das Achsenskelett in Form von venösen Malformationen (früher sogenanntes „Hämangiom“ des Knochens).

Epuliden sind fokale reaktive Hyperplasien der Gingiva. Nach ihrer Histologie werden das teleangiektatische Granulom (Epulis granulomatosa), die fokale fibröse Hyperplasie (Epulis fibromatosa), das periphere ossifizierende Fibrom (ossifizierende fibroide Epulis) und das periphere Riesenzellgranulom (Riesenzellepulis) unterschieden. Epuliden gehen vom periodontalen Ligament aus und entwickeln sich aus dem Sulcus gingivalis, infiltrieren aber den darunterliegenden Knochen nicht. Als Therapie genügt eine konservative Abtragung, auch wenn Rezidive nicht selten vorkommen können (bis zu 17,5 % beim peripheren Riesenzellgranulom). Da eine eindeutige klinische Diagnose nicht möglich ist und zahlreiche gutartige, aber auch maligne Tumoren differenzialdiagnostisch in Betracht kommen, sollten die Läsionen immer histologisch untersucht werden.

BACKGROUND:Guidelines recommend both histological analysis and culture for definite diagnosis of osteomyelitis. It is not clear if histological and culture criteria can be used interchangeably in the clinical scenario of toe amputation. We therefore prospectively compared the results of intraoperative culture and those of histological examination in this setting. METHODS:Consecutive patients requiring toe or forefoot amputation at the University Hospital Basel during a 2-year period were included in the study. Biopsy specimens from the residual bone were cultured according to microbiological standards. Histological analysis was performed using standardized criteria for osteomyelitis. Clinical outcomes were assessed retrospectively via chart review. RESULTS:Of 51 patients included in the study, 33 (65%) had a positive culture of residual bone and 14 (27%) showed histological signs of osteomyelitis. A negative histological result but a positive culture was found for 21 (41%) of the patients, suggesting that culture has a high false-positive rate if histological analysis is used as the reference to rule out osteomyelitis. The recommended criteria of both positive histological findings and positive culture were fulfilled by 12 (24%) of the 51 patients. CONCLUSIONS:Positive cultures of residual bone after forefoot or toe amputation overestimate the true rate of osteomyelitis as defined by histological analysis, presumably because of contamination from soft tissue at the time of surgery. Additional studies are needed to evaluate the indications for, and the duration of, antibiotic treatment according to these findings. CLINICAL RELEVANCE:Our results cast doubt on the strategy of relying solely on culture of bone biopsy specimens when deciding whether antibiotic treatment for osteomyelitis is necessary after toe or forefoot amputation.

We report a patient with tuberous sclerosis (TSC) who shows a firm swelling of the right mandibula (29 × 56 × 45 mm) at the age of 2.6 years. The histologic evaluation demonstrated a desmoplastic fibroma, a benign yet aggressive and infiltrative growing bone tumor with high recurrence rates. The swelling led to a loosening of the teeth and an impairment of the mouth function.

Die 2013 erschienene 4. Auflage der WHO-Klassifikation der Weichteil- und Knochentumoren baut den seit der 3. Auflage verfolgten Weg weiter aus, Genetik und Pathologie dieser Tumoren zusammen mit Epidemiologie, Klinik und Bildgebung darzustellen. Hinzugekommen sind wenige neue Entitäten, außerdem erfolgten Umbenennungen und Umgruppierungen. Als wichtigster, klinisch relevanter Punkt mit therapeutischen Konsequenzen wurde in Analogie zu den Weichteiltumoren die Einteilung nach dem biologischen Verhalten in 3 Gruppen (gutartig – intermediär – bösartig) auch für die Knochentumoren übernommen.

Historically, tumor-like lesions of bone were defined as non-neoplastic bone lesions. Today, however, some of them are considered real neoplasms. They are among the most frequent bone lesions. They usually grow slowly, but occasionally they grow rapidly. Many of them can be diagnosed by plain films alone; in others, CT and MRI yield additional features for a correct diagnosis. Some lesions do not need treatment; others should be resected, and some may even recur. Non-ossifying fibroma, juvenile and aneurysmal bone cysts, fibrous and osteofibrous dysplasia and eosinophilic granuloma are presented.

The correlation between BRAF mutation and the aggressiveness of ameloblastoma remains controversial. The aim of this study was to investigate the association of BRAF V600E expression with clinicopathological features and disease-free survival (DFS) in patients with ameloblastoma. Seventy-four conventional ameloblastoma samples were collected. Immunohistochemistry using anti-BRAF V600E antibody was performed on formalin-fixed, paraffin-embedded tissue sections. Clinicopathological characteristics and treatment outcomes were retrieved from the patient medical records. BRAF V600E immunoreactivity was detected in 50/74 cases (67.6%); 39 were strongly positive and 11 weakly. There was a significant difference in BRAF V600E expression between ameloblastoma and dental follicle (P = 0.034). However, there was no significant association of BRAF V600E expression with any clinicopathological features, including sex, age, location, duration, tumour size, radiographic appearance, cortical perforation, recurrence, and histological subtype. DFS analysis revealed that patients with BRAF-mutated ameloblastoma had a shorter median survival time (84 months vs 168 months) and lower 5-year survival rate (59% vs 67%) compared to the BRAF wild-type group; however, this was not statistically significant (P = 0.169). Moreover, logistic regression analysis revealed that treatment with enucleation was an independent risk factor for tumour recurrence (odds ratio 9.236; P = 0.028). This study demonstrated that the BRAF V600E mutation was not associated with any clinicopathological features of ameloblastoma. A trend towards earlier recurrence in tumours with BRAF mutation was observed, but this requires further investigation. Furthermore, the findings suggest that the treatment modality is an important factor in determining recurrence in ameloblastoma despite genetic alterations.