Radiogenic fracture of the proximal humerus of a 11-year old male patient. After complete surgical removal (R0) of a recurrent Desmoid-type fibromatosis local radiotherapy with 60 Gy was administered after repeated recurrence. Six month after completion of radiotherapy, pathologic fracture of the proxial humerus occured while swimming (left picture). Bony consolidation is noticed 5 month after intramedullary nailig (right picture)
Enchondroma of the proximal humeral metaphysis in a 49-year old female patient (left picture) and status after intralesional curettage and grafting with bone substitute (second picture from left). Pathological humerus fracture, originating from the caudal border of the bone window. The fracture occured 14 days after initial surgery, when the patient tried to open a water bottle (third picture from left). The right picture shows status after open anatomic reduction and stable fixation with a locking plate
The so-called insufficiency fracture is a sub-type of the pathologic fracture and is characterized by a break of the diseased bone under physiological loading.
In general this term is exclusively used for osteoporotic fractures . Accordingly insufficiency fractures are most often found at load bearing parts of the skeleton, particularly the pelvis and sacrum, the proximal femur and also the thoraco-lumbar transition of the spine. In contrast the so-called stress fracture is defined as a break of healthy bones due to unphysiological loading (e.g. marching fracture) and is considered as chronic incident.
Epidemiology and Etiology
Compared to the total number of fractures excluding osteoporotic and insufficiency fractures pathological fractures are of rare occurence. In the current literature. Incidences between 0.5 and 5 % are given depending on author [3, 8]. Metastases are the most common malignant bone tumors and the most common cause of pathological fractures.
In contrast to the weight-bearing skeletal portions load-related pain, a common symptom of bone metastases, does usually not occur at the humerus. Thus quite often pathological fractures of the humerus are the first manifestation of a previously unknown underlying malignant disease .
Since the year 2000 in our University hospital, a total of 487 bone tumors of the upper extremity were treated surgically. Pathological fractures of the humerus occurred in 65 patients (13.3 %) whereas the most common benign cause of fractures was an enchondroma (n = 9), followed by juvenile bone cysts (n = 8). For metastases the renal cell carcinoma (n = 10) and lung cancer (n = 7) and in the primary malignant bone tumors, Ewing’s sarcoma (n = 5) followed by osteosarcoma (n = 3) was present.
An elaborate anamnesjs including fracture mechanism (traumatic vs. atraumatic), history (tumor history, endocrinological diseases, previous spontaneous fractures) and pre-existing complaints in the fractured area can help in diagnosing pathological fractures. After anamnesis the diagnosis of suspected pathological fractures relies primarily on performing radiographs in two planes so that the morphology of osseous lesions in general can be assessed. Lodwick et al. developed a classification system, which is helpful in correlating growth rate and radiographical morphology of a lesion 
The problem in definitely diagnosing pathological fractures is that the radiographichal morphology of tumorous lesions is often changed by fractures or tumor osteoid (e.g. in case of an osteosarcoma) might be misinterpreted as fracture callus .
For more detailed diagnostics both cross sectional imaging techniques in terms of Magnetic resonance imaging (MRI) and computed tomography (CT) are useful. MRI is usually performed to assess intra- and extraosseous tumor portions, the exact anatomical location of the tumor and its relation to other surrounding anatomical structures. CT allows for a three-dimensional visualization of the fracture and the extent of osseous destruction as well as the precise growth pattern of the lesion.
CT of thorax and abdomen using i.v. iodinated contrast media is recommended to search for primary tumors when osseous metastases have been found (e.g, carcinoma of the gastrointestinal tract) as well as to exclude or detect organ metastases.
Three-phase bone scintigraphy shows however information about the local bone metabolism of the lesion (osteoblastic activity) and also helps in detecting further metastases in the entire skeleton. However, it should be noted that scintigraphy might be disturbed by fractures as well as certain tumors, such as eosinophilic granuloma, simple bone cyst, multiple myeloma or aggressive osteolytic bone metastases may be silent on scintigrams (Fig. 19.3).
Pathological proximal humerus fracture based on a osteolytic metastasis of a renal cell carcinoma in a 65-year old female patient
The diagnostic algorithm until the histo-pathological diagnosis is reached should always follow a strict pattern also in case of a pathological fracture: open or percutaneous image-guided biopsy of the suspicious lesion should thus be followed by immobilizing the injured limb by cast, occasionally even using external fixation. In order to avoid complication, biopsy should be performed at the same institution, which will be responsible for the final treatment. The technical performance of the biopsy should not limit the options of the definitive local treatment and should therefore be well planned in advance. The biopsy approach should be chosen in a way so that a tumor en bloc resection ultimately including the scar is still possibly achievable .
Benign bone tumors occur much more frequently than malignant ones. While the exact number of malignant bone disease is well documented in numerous national cancer indices, the majority of benign bone lesions remains undetected due to a lack of symptoms or are detected as incidental findings . According to the classification of Enneking et al. benign tumors and so-called tumor-like lesions are divided in inactive, active and aggressive lesions .
Depending on the author and tumor center, the five most common benign bone tumors differ in their order of incidence. Cartilaginous exostosis (35 %) presents the most common benign bone tumor. However, the multiple manifestations forms in terms of pedunculated, sessile, solitary or multiple occurence does not predispose to pathological fractures.
Giant cell tumors (20 %) as well as enchondroma (10–25 %) and tumor-like lesions (current name: “Tumours of undefined neoplastic nature” ) such as juvenile bone cysts or aneurysmal bone cyst range among the most frequent benign bone lesions and regularly occur within the humerus. Since the biological behavior of these lesions ranges from active to aggressive it might be responsible for the occurence of pathological fractures.
Giant Cell Tumor
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 . 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).
Non-displaced, pathological humerus fracture in a 11-year old girl with histologically confirmed giant cell tumor. Surgical therapy was postponed due to initial eggshell-like, thinned-out cortex and fear of loss of the proximal humerus. Within four month of s.c. therapy with Denosumab (Prolia©) bony concolidation is clearly visible
Due to its biological behavior the enchondroma, the second most common benign bone tumor, presents in several variants. All degrees reaching from asymptomatic incidental findings to sarcomatous degenerations including pathological fracture are possible. The proximal humerus presents the most commonly affected location following the small tubular bones of hands and feet (Fig. 19.5). Due to possible enossal erosion of the cortex (scalloping) and the resulting reduced stability of the bone, pathologic fractures are also possible despite its benign dignity, but compared to metacarpals and phalanges of the hand of very rare occurence. A pathological fracture of the humerus in the presence of a chondromatous tumor should always remind the treating surgeon of a chondrosarcoma. A biopsy may not always lead the way despite a clinical and radiological suspected malignancy. The reason for this is that in practically all cases of low malignant highly differentiated chondrosarcoma histological malignancy criteria such as cellular atypia, pleomorphic stroma, increased mitotic activity are only focally and in many places the histological picture can not be distinguished from an enchondroma . The reason for this is that in practically all cases of low grade, highly differentiated chondrosarcoma histological malignancy (cellular atypia, pleomorphic stroma, increased mitotic activity) are only focally and in many spots the histological picture can not be distinguished from an enchondroma . Therefore, the diagnosis of low malignant chondrosarcoma G1 often derives besides the histopathological analysis from the combination of possible symptoms and findings and specific radiological criteria (see, chondrosarcoma).
Proximal humerus fracture based on an enchondroma in a 41-year old female patient. Conventional radiography, which was obtained after a fall on the right shoulder, clearly shows matrix mineralization, typically found in chondromatous bone tumours. Histopathological work-up of open biopsy confirmed diagnosis of enchondroma and allowed for a joint-preserving tumor resection. (a) Plain radiography pre- and postop; (b) preoperative coronal and axial CT-scans
Juvenile Bone Cyst
The juvenile bone cyst is a unilocular cavity lined with varying thick membrane filled with clear or sanguinary liquid . 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 , 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.
Non-dispaced pathological humerus fracture in a 11-year old male patient with extensive unicameral bone cyst. Arrow shows the typical “fallen-leaf”-sign, representing a fragment of the thinned-out cortex in the cyst cavity
Diaphyseal pathological humerus fracture based on a recurrent unicameral bone cyst in a 13-year old male patient (left picture), osteosynthesis with ESIN/Elastic Stable Intramedullary Nailing (picture in the middle) and bony consolidation of the fracture next to another recurrence/residuum with expansive cortical widening 7 month postop
Primary Malignant Tumors
The 3 most common primary malignant tumors of the bone in terms of osteosarcoma, chondrosarcoma and Ewing’s sarcoma show an annual incidence of approximately 10 per 1 million inhabitants. Whereas patients with osteo- and Ewing’s sarcoma are mostly younger than 20 years old, the peak incidence of the primary (conventional) chondrosarcoma is in the fifth to seventh decade of life [16, 19]. Pathological fractures occur in patients suffering from osteo- and Ewing’s sarcoma in 5–10 % of cases [10, 12, 29] and in patients with chondrosarcoma, depending on the degree of differentiation, in 2–25 % of the cases [37.1].
Diagnosis and treatment of osteo-, Ewing’s sarcoma and chondrosarcoma may differ significantly, so that the major differences will be highlighted as follows:
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 . Compared to other anatomical locations, the osteosarcoma of the proximal humerus presents with a statistically higher incidence of pathological fractures (Fig. 19.8a, b) .
(a) High-grade, giant-cell-rich osteosarcoma with pathological fracture of the left humerus in a 50-year old male patient (left picture). The picture in the middle shows preoperative planning including the level of resection and endoprosthetic reconstruction. Postoperative x-rays after wide tumor resection and implantation of a modular megaprosthesis (Orthodynamics, MML) in combination with a trevira tube for soft tissue reconstruction. (b) Local recurrence despite complete initial resection (R0) of the poorly differentiated giant-cell-rich osteosarcoma (G3) 27 month postop (left picture) and status after gleno-humeral disarticulation due to tumor-infiltration to the neuro-vascular bundle
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 , 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 . 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 . 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 . 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 . 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.
Plain radiography and MRI with coronal T1- and T2- weighted cross sectional imaging of a dedifferentiated chondrosarcoma with pathological fracture in a 47-year old patient. Limb salvage was not viable and forquater amputation had to be performed
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 . 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 . 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  (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 . 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.
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