According to the current classification of musculoskeletal tumors of the World Health Organisation (WHO) giant cell tumors present as local aggressively growing benign tumors, also considered as tumors of intermediate malignancy by virtue of its biological behavior [18]. The relapse rate accounts for up to 25 % and lung metastases probably occur in 2 % of the cases. Pathological fractures occur in 5–10 % of all giant cell tumors. The radiograph shows an origin of the lesion at the bony epiphysis presenting as an eccentric osteolytic lesion characteristically with a destructive pattern type Lodwick 1c. MRI usually presents a low to intermediate signal intensity on T1-w images and intermediate to high signal intensity on T2-weighted images in contrast.

Open biopsy with subsequent immobilization of the limb is necessary to differentiate benign from malignant dedifferentiated giant cell tumors (<1). Only after the distinct diagnosis of a giant cell tumor is met and a malignancy is excluded a definitive surgical therapy with intralesional curettage, cement filling and osteosynthesis is to be performed. The initial reconstruction with autologous bone material is not indicated because of the high likelihood of recurrence. High primary stability, thermal adjuvant effects, the bone-saving approach and a good delineation of possible recurrence in imaging follow-up is in contrast to a revision including cement removal and biological reconstruction as well as a statistically increased risk of required endoprosthetical treatment of the adjacent joint [20, 21]. In very rare cases, it may be necessary in severe defect situations to use a primary endoprosthesis. Drug therapy with denosumab, an osteoclast-modifying human monoclonal antibody, shows promising results in several studies and becomes increasingly important in the treatment of unresectable or recurrent giant cell tumors [22–24] (Fig. 19.4).

The juvenile bone cyst is a unilocular cavity lined with varying thick membrane filled with clear or sanguinary liquid [19]. In contrast to the aneurysmatic bone cyst (Abc), juvenile bone cysts do not present with any symptoms until a pathological fracture occurs due to its less aggressive behavior. On radiographs this type of cyst is usually located in the meta-diaphyseal junction, presents as a well-defined centric lesion with homogeneously decreased radioopacity (Fig. 19.6). In the location of the cyst the cortex is often thinned, on MR imaging a septation is either not or only sparsely present and the cyst appears to be filled with fluid isointense content without air-fluid levels. In general, there exists a grand variety of therapeutic options, including minimal invasive intralesional procedures [26], curettage with autologous bone grafting, implantation of cannulated screws or injection of autologous bone marrow aspirate or cortisone [27, 28]. In the presence of a pathological fracture the surgical treatment usually consists of an osteosynthetic stabilization by implanting an elastic stable intramedullary nail (ESIN), which also allows for an internal decompression of the cyst. In comparison to other therapeutical options if ESIN is performed there is no possibility to resect the cyst wall which can potentially increase the risk of recurrence (Fig. 19.7). However, in case a pathological fracture induces a decompression of the cyst so-called self-healing processes are initiated and thus, surgical treatment is in case of adequate immobilization not obligatory.

The “conventional” osteosarcoma can appear with a great variety on radiographs, but usually a mixed osteoblastic/osteolytic, eccentric-growing lesion is found in the metaphysis of the bone with concomitant cortical destruction, periosteal reaction and invasion of the surrounding soft tissue. If the osteosarcoma occurs in the diaphysis of the bone an increased risk for pathological fractures is present, but also in case of an osteolytic growth pattern and telangiectatic as well as fibroblastic osteosarcoma variants [30]. Compared to other anatomical locations, the osteosarcoma of the proximal humerus presents with a statistically higher incidence of pathological fractures (Fig. 19.8a, b) [31].

In case of manifestation of Ewing’s sarcoma in long bones it is typically found in a diaphyseal location and characterized by a poorly definable, permeative or moth-damage like osteolytic osteodestruction along with onion peel-like periosteal reaction. Pathological fractures usually occur in association with neoadjuvant radiotherapy [30], but can also represent the first symptoms of a previously unknown tumor. While in osteosarcoma also low-malignant subtypes exist (e.g. paraosseal osteosarcoma G1) and local therapy may differ from a vast continuity interrupting resection, however, Ewing sarcoma, presents by definition always a low-differentiated, highly malignant tumor. After the diagnosis is confirmed by histology neoadjuvant therapy in terms of chemo- and/or radiotherapy should be initiated as soon as possible [16]. The definitive tumor resection and, if possible limb-preserving surgical reconstruction should consecutively be performed. Pathologic fractures due to underlying primary malignant bone tumors is not necessarily followed by ablative procedures along with amputation or exarticulation. In the current literature the risk of local recurrence is not described as increased if limb-preserving procedures are performed keeping tumor-free surgical margins and for pathological fractures including resection of the fracture hematoma [10, 12, 29, 32].

In the current literature risk factors for tumor-free survival are heterogeneously discussed. However, some authors do not see a negative influence of pathological fractures on the prognosis of Ewing’s sarcoma, regardless of the time point when the fracture (before or during irradiation) occurs [10, 29]. However, in case of osteosarcoma the localization in the humerus as well as the presence of a pathological fracture seems to worsen the prognosis significantly [31, 33–35]. It needs to be stated that prognosis can not be improved by a more radical surgical therapy in terms of amputation. The reason why for Ewing’s sarcoma the prognosis is not changing following a pathological fracture compared to osteosarcoma can be explained by the higher chemo-sensitivity of the tumor [29, 36].

In case of a pathological fracture due to underlying chondrosarcoma it stresses some exceptions regarding diagnosis and treatment of fractures. On the one hand the transition between enchondroma and low-grade chondrosarcoma is ambigous so that the histopathological analysis of a biopsy often does not allow for a definitive conclusion regarding dignity of the lesion. On the other hand no useful adjuvant therapy options exist since chondrosarcoma present as rather insensitive towards chemo- and radiotherapy. Chondrosarcoma in the humerus is found to be associated with a higher risk of pathologic fractures and of local recurrence respectively [37]. Pathological fractures, however, are not necessarily afflicted with higher rate of recurrence.

Pathological fractures due to chondrosarcoma seem also to negatively effect the mean survival rate as described for osteosarcoma but in contrast to Ewing’s sarcoma [29]. In the literature some authors recommend more generous indications for ablative procedures [32, 37] due to the lack of chemo sensitivity of the tumor but sufficient studies of evidence are missing. The treatment recommendations should be based ultimately on the grading and the resectability of the tumor, since the prognosis of the primary (conventional) chondrosarcoma is directly correlated with the histological grade (Fig. 19.9). In case of low-grade chondrosarcoma (well differentiated, G1) of the extremities, followed by a pathological fracture, indication for intralesional currettage using chemical or thermal adjuvants has not changed. The difficulty is to distinguish well from a moderately or poorly differentiated tumors. Neither guide biopsy nor instantaneous section diagnostics can sometimes provide a clear graduation in case of insufficient representative tissue of a heterogeneous tumor. However, radiological criteria can help in decision making. As radiological criteria of aggressiveness an increase of the bony circumference and cortical thinning are considered as well as a deep scalloping (enosteal “nibbling” of the cortex) of the affected bone [38]. If these radiological criteria are present intralesional therapy should be refrained. Intramedullary tumor dimensions with a critical size of four to five cm as well as the presence, type and distribution of matrix calcification (“rings and arcs”) are not any more considered as hard evidence of malignancy [38–42]. Permeative or moth-damage-related cortical destruction, perifocal edema and soft tissue component of the tumor are further suspicious changes suggesting a poor differentiated tumor presenting as argument against a primary surgical management of the pathological fracture with intralesional resection and also expressing the need of an extended biopsy or en bloc resection including tumor-free margins.

Multiple myeloma (MM) is different from all other tumors of the musculoskeletal system, since it presents a systemic disease with neoplastic proliferation of B lymphocytes [43]. Osteolytic lesions, which may result in pathological fractures, only represent a local osseous MM-manifestation and are caused by increased cytokine production of malignant plasma cells and the associated increased osteoclastic activity [44]. Therefore, diagnosistics and treatment of this disease also differs from the other previously described musculoskeletal tumors. Often MM- patients present with pain in the musculoskeletal system as initial symptom of a pathological fracture. On radiographs typically an increased radiolucency of the bone with focal lucency and enosseal cortical destruction is found [45] (Fig. 19.10). Further diagnostics consist of an extensive laboratory diagnostics. Serum- and 24-h urine electrophoresis are usually performed to detect the typically present monoclonal immunoglobulins. To confirm the diagnosis, however, a bone marrow biopsy is mandatory. The treatment of multiple myeloma primarily consists of systemic chemotherapy along with or without autologous stem cell transplantation (ASCT). However, in general multiple myeloma represents an incurable disease, which can be brought into remission. In the case of solitary focal plasmacytoma, radiation therapy can be performed as stand- alone therapy or as adjuvant therapy following surgery [44]. Osteolysis at risk for fracture or pathologic fractures, however, should always initially be treated surgically performing an intralesional resection and consecutive stabilization using osteosynthesis. At non-load-bearing bones such as the humerus a compound osteosynthesis is recommended by plate fixation and bone cement, since a high initial stability can be achieved with good function [46, 47]. In rare cases of severe bone destruction endoprothetic replacement may be indicated with additional adjuvant radiotherapy or combined radio/chemotherapy.