Diab_10_Tumors : simplebooklet.com

199CHAPTER 10TUMORSEvaluation .........................................................................199History ..........................................................................199Physical Examination .....................................................200Imaging .........................................................................200Laboratory Analysis .......................................................202Staging .........................................................................202Biopsy ...........................................................................203Differential Diagnosis ....................................................203Bone Cyst .........................................................................204Unicameral Bone Cyst ...................................................204Aneurysmal Bone Cyst ...................................................205Benign Fibrous Tumors ......................................................206Nonosteogenic Fibroma .................................................206Fibrous Dysplasia ...........................................................206Desmoid Tumor .............................................................207Focal Fibrocartilaginous Dysplasia ..................................208Benign Cartilage Tumors ...................................................208Osteochondroma ..........................................................208Enchondroma ................................................................209Chondromyxoid Fibroma ...............................................209Chondroblastoma .........................................................209Benign Bone Tumors .........................................................210Osteoid Osteoma and Osteoblastoma ............................210Eosinophilic Granuloma .................................................211Giant Cell Tumors ..........................................................211Other Benign Tumors ........................................................212Hæmangioma ...............................................................212Pigmented Villonodular Synovitis ...................................212Malignant Soft Tissue Tumors ...........................................213Rhabdomyosarcoma ......................................................213Synovial Sarcoma ..........................................................213Malignant Bone Tumors ....................................................214Osteosarcoma ...............................................................214Ewing Sarcoma .............................................................214Leukæmia .....................................................................215Metastasis .....................................................................215Malignant tumors of the musculoskeletal system constitute 10% of new cancers in children, numbering approximately 1,000 cases in the United States per annum. Benign tumors are 10 times the rate. We are presently on an exponential curve for advancement in oncol-ogy, for example, overall 5-year survival has risen from 10% to 20% in 1970 to better than 70% today. The most common pædiatric tumor is the benign ﬁbrous cortical defect. The most common malignant tumor is osteosarcoma of bone and rhabdomyosarcoma of soft tissue; Ewing sarcoma traverses tissue types. This chapter focuses on common diag-noses.EVALUATIONBecause the word “tumor” may have sinister connotations, consider clas-sifying tumors in simple terms for patients [A]. Most tumors are not life threatening. They may threaten local tissues, for example, risk of mor-bid fracture, and thus require surgical management. They may be stable, amenable to conservative measures, or incidental ﬁndings, which are left alone.HistoryDuration may be difﬁcult to determine. The tumor requires time to grow sufﬁciently to disturb function or to be physically apparent or visible. Hence the poorer prognosis for axial tumors compared with appendicular lesions. Age is the universal discriminator of disease, for example, 2/3 of rhabdomyosarcomas occur in the ﬁrst decade, while osteosarcoma peaks at puberty [B]. Reﬁne the presentation of pain [C]. Abrupt pain may indi-cate morbid fracture. Beware of being distracted by a sporting or other benign injury. Not all malignant or aggressive tumors elicit pain: rhabdo-myosarcoma typically does not hurt. Race may be helpful, for example, Ewing sarcoma is less common in blacks than whites.TUMORbadbad-goodOncologist:medical managementgoglobally threatening:malignant“cancer”good-goodOrthopædic surgerylocally aggressiveobserveodincidentalbenignA Classification of tumors This simple approach provides clarity and perspective for patients.Diab_Chap10.indd 199 9/23/2015 3:24:17 PM

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Physical ExaminationTake the temperature. Ewing sarcoma may be mistaken for osteomyelitis at ﬁrst. Observe gait for alteration due to pain or other interference with function. Does the child look ill, as if overcome by pain or a generalized process? Are the complaints focal or diffuse? Are there “hard” objective signs? Are the soft tissues reactive, as evidenced by swelling, redness, induration, and adhesion? Is there articular stiffness to suggest guarding? Is there atrophy of disuse or other asymmetry? If a mass is detectable, is it tender? Is it soft, ﬁrm, or hard? How large is it? Greater than 5 cm is ominous for soft tissue sarcoma.ImagingDevelop a method that is clear, standard, efﬁcient, and reproducible.Röntgenogrammes The acronym ALLMDS facilitates communication [D]: • A: Age.• L: “Looks like.” This admits descriptives such as “sunburst,” “moth eaten,” scalloped,” and “expansile” [E].• L: Location. Where within the bone, for example, metaphysis, diaph-ysis, or epiphysis [F], or what bone, for example, long bone such as the femur, irregular bone such as the spine, or ﬂat bone such as the pelvis [G].• M: Margins. These are divided into distinct, called “geographic,” or nondistinct, called “nongeographic.” The latter is more ominous, as it is a sign of rapid tumor growth and failure of bone to react and delimit this growth.• D: Density. Lesions may be lytic, which are radiolucent; blastic, which are radiodense; or mixed, which are heterogeneous. This aids local assessment of bone but is not prognostic. Lytic lesions erode the integrity of bone and risk morbid fracture, inﬂuenc-ing decision on internal ﬁxation. On the other hand, while blas-tic lesions may be more stable, they may represent a high-grade osteosarcoma. • S: Soft tissue. This may be reactive, such as elevation of periosteum, or a mass, for example, Ewing sarcoma.200 Tumors / EvaluationB Age distribution of some tumors NB, neuroblastoma; EG, eosinophilic granuloma; NOF, nonossifying fibroma; OO, osteoid osteoma; OB, osteoblastoma.0 5 10 20yearsEwingrhabdomyosarcomaosteosarcomaEGcystNOFNBWilmOO/OBleukæmiaosteochondromaPAINLow HighTypeMechanical ConstantNocturnalDelays sleepAwakens from sleepFunctionalSymptomSign: stops sports, limpTimingGradual Abrupt onset: fracture?C Pain Characteristics of pain may be of low or high concern.Diab_Chap10.indd 200 9/23/2015 3:24:18 PM

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202 Tumors / EvaluationUltrasonography This is indicated for a soft tissue mass when there is a low index of suspicion for malignancy. It may be used as a guide to aspi-ration or needle biopsy. It is simple to perform in an awake child without a special facility or medication.Scintigraphy This is a measure of bone turnover and activity of a lesion. It may discern between a benign lesion that is incidental and not the explanation for regional pain and one that has a microfracture, thereby guiding treatment. It surveys the skeleton for other sites of disease. It has a high negative predictive value for malignant disease. Overlap between benign and malignant disease reduces the positive predictive value.CT This is essential to staging as a survey of the chest and abdomen. Its ﬁne bone detail aids operative decision making.MRI Like CT, MRI is essential to staging. It is indicated for soft tis-sue tumors and bone tumors with a signiﬁcant soft tissue component. It is supplanting CT for bone, for example, osteoid osteoma of a long bone. It has high sensitivity but speciﬁcity declines in differentiation of tumor from infection. The principal disadvantage is the requirement for seda-tion in the young child.PET Detects gamma rays from the positron-emitting radioactive iso-tope ﬂuorine-18 substituted for a hydroxyl group on glucose (ﬂuorode-oxyglucose). The glucose analogue is taken up by actively dividing cells, where it is trapped but not metabolized, resulting in concentration of radioactive signal in tissue with high glucose uptake. This modality may enhance CT and surveys for metastases and is useful to follow response to treatment.Laboratory AnalysisA peripheral blood smear is useful in leukæmia. White blood cell count may be difﬁcult to interpret, for example, it may be reduced due to chronic disease. Inﬂammatory markers may be increased in tumor, for example, Ewing sarcoma, or in infection. Elevation of alkaline phos-phatase may be sensitive though nonspeciﬁc, for example, in the active phase of ﬁbrous dysplasia. It may serve as a marker of response to med-ical treatment, such as with bisphosphonates. Blood cultures distinguish infection. Special tests may be indicated, such as urinary catecholamines and metabolites, which are elevated in neuroblastoma.StagingThere are three stages of benign tumor. • Latent. These may be asymptomatic and incidentally found. They show little or no growth and do not disturb or escape the compartment.• Active. There is growth of tumor, as well as destruction, remodeling, and possible fracture of bone, limited to the conﬁnes of the compartment.• Aggressive. Tumor grows rapidly; destroys, distorts, and fractures bone; and escapes the compartment into surrounding soft tissue, including rare metastasis (e.g., giant cell tumor).G Tumor types by skeletal site Common location of benign tumors in green. Malignant tumors in red, and common sites indicated in bold.Eosinophilic granulomaOsteoblastomaAneurysmal cystHæmangiomaEwing sarcomaMetastasisEosinophilic granulomaAneurysmal cystOsteochondromaFibrous dysplasiaEwing sarcomaOsteochondromaEnchondromaFibrous dysplasiaEosinophilic granulomaEwing sarcomaCystOsteochondromaChondroblastomaOsteosarcomaEwing sarcomaEosinophilic granulomaEwing sarcomaOsteosarcomaOsteochondromaEosinophilic granulomaAneurysmal cystFibrous dysplasiaEwing sarcomaOsteosarcomaFibrous dysplasiaOsteochondromaCystOsteoid osteomaChondroblastomaEwing sarcomaNonosteogenic fibromaOsteochondromaGiant cell tumorOsteosarcomaNonosteogenic fibromaOsteochondromaChondromyxoid fibromaFocal fibrocartilaginous defectOsteosarcomaEosinophilic granulomaOsteoid osteomaEwing sarcomaOsteoid osteomaEosinophilic granulomaFibrous dysplasiaAdamantinomaOsteosarcomaEwing sarcomaEpiphysisChondroblastomaGiant cell tumorEnchondromaDesmoidCystOsteoid osteomaEwing sarcomaMalignant vascular tumorsEnchondromaCystDesmoidOsteoid osteomaSynovial cell sarcomaEwing sarcomaMalignant vascular tumorsCystOsteoblastomaChondroblastomaEosinophilic granulomaGiant cell tumorEwing sarcomaNonosteogenic fibromaCystDiab_Chap10.indd 202 9/23/2015 3:24:20 PM

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Tumors / Evaluation 203Staging of malignant tumors is complex and disease speciﬁc. It is essential to management and prognosis of malignant tumors. Several factors contribute to stage [H]. Surgical staging (Enneking) emphasizes pathologic grade and the compartmental nature of a lesion: fascia, joint, and bone deﬁne a compartment [I]. Broadly, stage 0 may be considered precancerous. For stage I, surgical treatment is sufﬁcient. Surgery for stage IV is prophylactic or palliative, for example, for impending or actual mor-bid fracture. Stages II and III combine medical and surgical management.BiopsyThis may be percutaneous or open. Percutaneous may be of bone marrow from the iliac crest, for example, in leukæmia or Ewing sarcoma, or with image guidance when open access is morbid, for example, in the spine, or when there remains uncertainty about the diagnosis of tumor. Plan a large and wide enough specimen from multiple locations to be deﬁni-tive. Biopsy may be incisional for diagnosis, excisional when geographic and localized, or compartmental when margins are indistinct but there is no regional or distant spread [J]. The principles of open biopsy are well established, founded on the spirit that this must be undertaken with the same level of preparation as the deﬁnitive procedure. • Plan for future reconstruction when selecting incision, which should be as small as possible and extensile.• Perform a transmuscular approach to limit contamination within that compartment.• Avoid major neurovascular structures. Unlike muscle, these are not expendable in the event of future resection.• Include the margin of a lesion, where growth and atypia tend to be greatest.• Strict hæmostasis reduces contamination.• Intraoperative frozen section conﬁrms that enough tissue has been obtained to establish diagnosis or that a lesion is benign before pro-ceeding with deﬁnitive care.• Consider referral before biopsy if the surgeon, pathologist, and insti-tution are not equipped to manage the case regardless of diagnosis.Differential DiagnosisThe adage “culture tumor, biopsy infection” was conceived in the diagnostic dilemma each can pose the other. Consider fever, systemic signs, age, location, and elevation of inﬂammatory markers. Presence or absence of a mass and appearance on imaging sharpen the diagnosis [K]. Biopsy may be necessary for certainty.Distinguish osteosarcoma from myositis ossiﬁcans by zone reversal. The latter is characterized by central proliferating cells surrounded by a margin of ossiﬁcation. In osteosarcoma, the rapidly growing periphery has not yet ossiﬁed.Differentiate fractures by history, for example, trauma or repetitive stress, and empirically by treating with rest and immobilization. Distinguish anxiety time from biologic time: 4 to 6 weeks will not alter tumor progno-sis. Laboratory analysis is normal. Advanced imaging may be necessary, such as MRI showing no soft tissue extension or mass. Resist biopsy.Factor CommentTumor 1: confined to site of origin2: outside the site of originNodal involvement0: none1: local2: regional3: distantMetastasis0: absent1: presentGrade 1: low4: highSerum markers ElevationResection Measure of free or contaminated marginsVascular Invasion of vasculatureLymphatic Invasion of lymphatic systemResponse To chemotherapy, based upon % necrosis in surgical specimenImaginge.g., MRI H Some factors considered for staging of tumors These may vary according to disease type.Reactive zone PseudocapsuleTumor1AIntracompartmentalLow grade2AIntracompartmentalHigh grade1BExtracompartmentalLow grade2BExtracompartmentalHigh grade3Any metastasisHigh or low gradeI Staging of musculoskeletal tumors Surgical staging is determined by grade and physical extent of lesion.J Biopsy of tumor This may be incisional, within the tumor (red), excisional (white dots), or compartmental (green dots).K Infection, not tumor Atypical features of infection include periosteal reaction and diaphysial location (red) and extension from metaphysis transphysis to epiphysis (yellow).Diab_Chap10.indd 203 9/23/2015 3:24:22 PM

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204 Tumors / Bone CystBONE CYSTUnicameral Bone CystThe name implies a “single chamber” (Latin camera = Greek καµαρα: “vaulted chamber”) without loculation, although some have septæ. This most commonly occurs in the humerus and femur. Cause is unknown. The cysts are ﬁlled with yellow ﬂuid and lined with a ﬁbrous capsule.Evaluation These may be incidental or may present with pain. They are metaphysial and travel toward the diaphysis with growth. Incidental ﬁndings are assessed for fracture risk [A]. Pain indicates bending under load or fracture and may be severe enough to interfere with function. Lesions in the proximal femur are high risk because of concentration of the force of weight bearing and the grave anatomic consequences of fracture in this region.RÖNTGENOGRAMME The lesion is central, nonexpansile, geographic with a sclerotic margin, and lytic. It may have septæ and an osseous fragment may ﬂoat in its midst, known as “fallen leaf sign.”Management The natural history is spontaneous resolution of cysts by maturity in most cases. Latent cysts may be observed. Active cysts, which abut the physis, grow inexorably, and may fracture, tend to be treated surgically. Age, location, and fracture risk and consequences guide treatment.LOW RISK EXCEPT FEMUR Observe. A humeral cyst that is small, asymptomatic, or acceptably painful may be managed conservatively, such as activity modiﬁcation and nonnarcotic analgesics, and may resolve with maturity.LOW RISK PROXIMAL FEMUR Observe or treat surgically because of concerns regarding load at, and fracture of, the hip.HIGH RISK Observe if patient is very young and humerus is involved, or treat surgically. The proximal femur trumps age: consider ﬁxation even in the very young.FRACTURE EXCEPT FEMUR Treat by closed methods as long as align-ment is acceptable. Healing of the fracture may partially heal cyst, poten-tially converting a cyst that is high risk by size into one that is low risk due to ﬁlling in with new bone.FRACTURE FEMUR Treat surgically. Immobilization, for example, in hip spica cast, is associated with residual deformity, in particular coxa vara, due to intrinsic instability of the fracture and incomplete healing. For the proximal femur, improved alignment with surgical ﬁxation may reduce complications of fracture such as malunion and osteonecrosis.Surgical treatment may be divided into cases.PERCUTANEOUS WITHOUT FIXATION This began as injection of steroid (Scaglietti), for its angiostatic and ﬁbroblastic inhibitory effects. The method has evolved in multiple directions such that there is no consensus on best practice. It is preferred for the upper limb and lower risk lower limb lesions. • The cyst is drained. If it is solid, reconsider diagnosis and perform an incisional biopsy.• A cystogramme determines whether the cyst is uni- or multilocular. If the former, inject with steroid or other adjuvant. Bone marrow aspirate may bring mesenchymal stem cells that will promote bone ingrowth and healing. Calcitonin inhibits osteoclasts. Calcium sulfate cement is osteoconductive. Proprietary ﬁbrosing agents have been promoted.• If the latter, break up septæ to form a unilocular cyst. In the process, perforate the cyst to create channels of communication with the medulla, based upon the rationale that altered hæmodynamics with venous obstruction may be a causative factor, and to allow access to the cyst by bone stem cells.• Repeat for recurrence.12 3Pain Mild Moderate FunctionalLocation Upper limb Lower limb Proximal femurSize < 1/31/3-2/3 > 2/3Density BlasticMixedLyticA Assessing risk for morbid fracture of hole in bone 3 points are given for pain that is sufficiently severe to disturb function. A critical value is 9, which represents the beginning of the exponential part of the fracture curve (>1/3 will fracture). This system is a guide: it was developed for bone metastases in adults (Mirels).B Active unicameral bone cyst There is a fracture fragment floating inside the cyst like a “fallen leaf” (yellow). The fracture takes up the entire width of the bone and has eroded the cortex to the point of fracture (red).C Aspiration and injection of a bone cyst Injection may be of steroid, bone marrow aspirate, or other adjuvant.BiopsyBreak up septæInject No fluidInjectCystogramme:multilocularDrainageDiagnosisCystogramme:unilocularDiab_Chap10.indd 204 9/23/2015 3:24:23 PM

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Tumors / Bone Cyst 205OPEN WITH FIXATION This is indicated for high-risk lesions, such as proximal femur [D], or where open access is simple, for example, calcaneus. • Create an ovoid window to avoid stress concentration at an angle. The cyst may dictate location of this at the eroded cortex.• Débride the wall to remove all cells, manually or with power.• Consider adjuvant intralesional therapy to kill residual cells, for exam-ple, liquid nitrogen (freezing), phenol (chemical), argon laser (coag-ulation), or hydrogen peroxide. For liquid nitrogen, leave in cavity until it evaporates; for other chemicals, let sit for 2 to 3 minutes. Cycle thrice. Reduce application hazard by controlling the agent within the osseous cavity in order to minimize injury to surrounding soft tissue. These augment but do not substitute for complete débridement.• Pack the cyst with graft, allogenous or autogenous, or with a substi-tute. There are no robust data suggesting anything is better than bone, and allogenous bone avoids the morbidity of harvesting bone, in par-ticular because much may be needed to fully ﬁll a large cyst.• If the bone is stable, apply a cast. If internal ﬁxation is indicated, for example, proximal femur, medullary implants will load share and thereby be more durable in the event of recurrence. In the immature child, elastic medullary nails may be inserted antegradely or retro-gradely. They provide stability even in proximal lesions because they may be anchored in the unaffected and hard proximal epiphysis: no physial arrest will occur given their smooth surface and small frac-tional cross-sectional area [E].Complications While bone cyst is a benign or “good” tumor, it is a “bad–good” tumor because outcomes can be vexing. • Recurrence. Some factors cannot be controlled, such as abutment against a physis. The principal factor that is controllable is débride-ment; hence the recommendation to use a burr, to be methodical, to proceed until healthy bleeding bone, and to leave only periosteum in places (so long as the bone is not unreasonably destabilized or resected).• Growth disturbance. This may be iatrogenic or related to activity of cyst. The former may be minimized by avoiding physis during oper-ation. The latter is a reﬂection of duration and aggressiveness of cyst.• Malunion. This is most common in the proximal femur. Likelihood increases with closed management.Aneurysmal Bone CystAs the name implies, this is vascular and expansile. Cause is unknown, although vascular malformation is most subject to speculation. Evalua-tion and management principles overlap with unicameral cyst, with key distinctions. Aneurysmal cyst is more aggressive: • Location. 1/4 arise in the axial skeleton, including posterior elements of the spine and the periacetabular region of the pelvis [F]. Conse-quences are greater morbidity of disease, for example, neural compro-mise, and of treatment, including more invasive dissection and more complex reconstruction.• Recurrence. Correct surgical technique has reduced a formerly uni-versal rate. Recurrence occurs within 2 years of operation, although children must be followed until maturity.• Association with other tumors, including giant cell and osteosarcoma, in which it may represent the cystic component of a primary tumor.Proximal femurCurettageBurringBone graftInternal fixationD Open treatment of bone cyst The cyst is débrided and bone grafted (green), after which the femur is stabilized with elastic medullary nails (red).E Open treatment of bone cyst This cyst fractured (red). Retrograde elastic nailing was stable by purchase in the hard, unaffected proximal epiphysis (orange).F Distribution of aneurysmal cyst The axial skeleton, including the spine (red) and the pelvis (white), makes advanced imaging and open treatment more typical.1 2 3DecadeDiab_Chap10.indd 205 9/23/2015 3:24:26 PM

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206 Tumors / Benign Fibrous TumorsEvaluation On röntgenogramme, it is eccentrically expansile, lytic, and multiloculated, giving a “soap-bubble” appearance. The thin mar-gin has been likened to an “eggshell.” The radiographic appearance may raise concern and prompt further imaging. Scintigramme may show a “halo” of increased uptake surrounding a central cold region. MRI will show blood–ﬂuid levels [G] and deﬁne soft tissue extension.Management This tends to be open and has the additional consider-ations: • Preoperative angiography and selective embolization before surgical treatment of large lesions, in particular in the pelvis, will decrease hæmorrhage and may shrink the lesion to decrease recurrence where complete resection is unrealistic.• Entry into a cyst will return blood. Include soft tissue within, or the lining of, the cyst for biopsy, which will show proliferative ﬁbro-blasts, spindle cells, osteoid, and multinucleated giant cells.• Break up all septæ to deﬁne the entire cyst wall, which may be inter-rupted.• Consider an en bloc resection with reconstruction where feasible to reduce recurrence.• In the spine, excision may result in instability necessitating recon-struction, including bone grafting, fusion, and internal ﬁxation.BENIGN FIBROUS TUMORSNonosteogenic FibromaOriginally reported as a cyst of bone (Phemister), this was named sep-arately as nonosteogenic (Jaffe) and nonossifying ﬁbroma. The appella-tion ﬁbrous cortical defect is reserved for small lesions conﬁned to the cortex without medullary extension.This is the most common benign lesion of bone in children, peaking in adolescence [A]. Cause in unknown, although it has been related to physis and traction by tendon or ligament, for example, at origin of the gastrocnemius from the distal femur.Evaluation Most are incidental ﬁndings on röntgenogrammes obtained for injury followed by pain.RÖNTGENOGRAMME The lesion is metaphysial, eccentric, geograph-ic with a “scalloped” margin, and lytic with one or more loculations [A]. A large lesion may show a cortical breach.SCINTIGRAMME This is indicated when there is uncertainty whether the lesion is a source of pain, suggesting structural failure, or when the lesion risks morbid fracture, such as in the proximal femur or >50% diameter of the bone. Fracture will demonstrate increased signal.Management The natural history is spontaneous resolution by matu-rity. Observe incidental ﬁndings and follow clinically based upon symp-toms. For fracture through a lesion, immobilize and observe for (partial) healing. If the fracture cannot be immobilized effectively, or for lesions with signiﬁcant risk of morbid fracture, treat like a unicameral cyst (q.v.).Fibrous DysplasiaNeoplastic ﬁbrosis replaces and weakens bone, causing microfractures that hurt and lead to progressive deformity. It may arise in any bone, though the ribs and the proximal femur [B], as well as maxilla, are dis-tinctive sites. Two types are distinguished: monostotic (80%) or polyos-totic. The latter subtype is more severe and occurs in conjunction with café au lait spots and precocious puberty as part of McCune-Albright syn-drome (cf. Syndromes chapter) and in conjunction with soft tissue myx-omata in Mazabraud syndrome. Polyostotic ﬁbrous dysplasia is caused by an activating gain of function mutation in the GNAS1 gene located on chromosome 20q13.2. This results in abnormal synthesis of both organic and inorganic components of the extracellular matrix, thereby compro-mising the structural integrity of bone.Evaluation Pain is the most common presentation. Other signs include deformity and limb length discrepancy. 1 2 3 4+DecadeA Nonosteogenic fibroma It peaks in adolescence and commonly affects the tibia. It is eccentric, loculated with a scalloped margin (yellow). 1 2 3 4+DecadeB Fibrous dysplasia The femur is distorted to resemble a “shepherd’s crook” (red). Note the thick periosteal healing response. Appearance may be so varied, including provoking concern (green), that further imaging often is necessary.G Aneurysmal cyst of the pelvis The expansile and otherwise aggressive appearance on röntgenogramme led to MRI, which shows a characteristic blood–fluid level (yellow).Diab_Chap10.indd 206 9/23/2015 3:24:28 PM

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Tumors / Benign Fibrous Tumors 207IMAGING This tumor is one of the grand mimics. The classic appearance on röntgenogramme is the “shepherd’s crook” deformity of the femur, which is slowly eroded and deformed progressively by sub-clinical microfractures. At the other extreme is the simple geographic lucent lesion, surrounded by a “rind” of sclerotic bone and producing no deformity. Opacity, resembling “ground glass,” correlates with woven bone, with ﬁbrous tissue being the principal tissue in lucent lesions.The radiographic range is so broad that it often prompts further imag-ing. Scintigramme surveys the skeleton and may expose a fracture. CT is useful for complex lesions, in particular in the spine and craniofacial skeleton. MRI distinguishes this from malignancy and deﬁnes the extent of disease in bone and soft tissue.ManagementMEDICAL Bisphosphonates alleviate pain in polyostotic disease.SURGICAL At biopsy, there is yellow-gray, gritty ﬁbrous tissue with occasional cartilage foci forming a circumscribed mass that readily falls away from surrounding bone. Microscopically, a ﬁbrous stroma is punctuated by “Chinese characters” or an “alphabet soup” of immature woven bone populated by some osteoblasts but many osteoclasts.Indications for operation follow general principles, including pain, which is evidence of bone instability from microfracture, deformity interfering with function, or clinical fracture. Educate parents that oper-ation may be the ﬁrst stage before deﬁnitive management at maturity, when lesions stabilize. Medullary ﬁxation is preferable because lesions progress during childhood and because recurrence is high. Follow meticulous technique for the cavity remaining after removal of the mass (cf. Cyst). Allograft bone will be resorbed partially by the neoplastic process.Desmoid TumorGreek δεσµος = Latin ﬁbra, which describes a tumor of ﬁbrous tissue. It also is known as ﬁbromatosis, reﬂecting an inﬁltrative and locally aggressive nature. This is a broad spectrum that encompasses Dupuytren contracture of the hand and Ledderhose disease of the foot.Evaluation Firm smooth mass anchored to deep fascia but sparing overlying skin. In the limbs, 1/4 of cases are bilateral. An extraintesti-nal abdominal form of the disease affects 10% of patients with familial adenomatous polyposis (Gardner syndrome): both disorders are caused by mutation in the adenomatous polyposis coli gene on 5q22.2. Desmoid tumor may represent an error in response to injury, including a surgi-cal incision. MRI demonstrates the nongeographic nature of the tumor and aids determination of extent of soft tissue inﬁltration. Biopsy shows a dense collagen matrix populated by myoﬁbroblasts expressing plate-let-derived growth factor-β proto-oncogene, which encodes the mito-genic β-chain of PDGF-B.Management Because it is inﬁltrative and recurrence is high, nonop-erative management is preferable. Because the injury of surgery may aggravate the tumor, plan to perform a wide excisional biopsy and con-ﬁrm clear margins by intraoperative frozen section. Recurrence is high, and secondary operation is difﬁcult in the setting of iatrogenic scarring. Collagenase, cryotherapy, and steroid injection may be helpful adjuncts. Radiation therapy for a benign condition raises concerns of physial arrest and tumorigenesis in a child.C Plantar fibromatosis Firm smooth mass associated with plantar aponeurosis.D Focal fibrocartilagenous dysplasia A lucent corticometaphysial lesion (yellow) adjacent to the insertion of pes anserinus or hip adductors is interposed between proximal physis and a region of sclerotic reactive bone (green).Diab_Chap10.indd 207 9/23/2015 3:24:29 PM

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208 Tumors / Benign Cartilage TumorsFocal Fibrocartilaginous DysplasiaThe name (Bell) reﬂects the tissue of which the tumor is composed. Cause is unknown. Trauma, including abnormal periosteal traction, for example, by pes anserinus at the proximal tibia or hip adductors at the distal femur, has been proposed.Evaluation Onset is infancy in the lower limb and later in childhood for upper limb lesions. The most affected is the tibia [D]. It may be mis-taken for pseudarthrosis of the tibia, which is bowed with a region of lucency, representing the lesion, adjacent to sclerosis produced by the osseous reaction [D].Management Spontaneous resolution is possible, representing perhaps rupture of the periosteal tether. The rarity of the condition makes nonop-erative guidelines, for example, bracing, impossible. Tibial lesions cor-rect most predictably, in particular if deformity is <25 degrees. Persistent signiﬁcant deformity, for example, genu varum, is treated with osteotomy and lengthening as indicated.In the forearm, deformity and growth retardation may have deleteri-ous effects on the uninvolved bone, such as ulnar tethering of the radius with radiocapitular instability. Early excision may allow restoration of growth and mitigate dysfunction.BENIGN CARTILAGE TUMORSOsteochondromaThe name describes a stem of “bone” capped by “cartilage.” This also is known as exostosis, after the appearance of bone growing “away” from the main body. It is distinguished as such under the nail (cf. Foot chapter). It may arise from any bone [A]. Like ﬁbrous dysplasia, osteochondroma may be solitary or multiple. The latter is a skeletal dysplasia having a genetic basis that is deforming [B] and associated with considerable mor-bidity, including malignant potential (cf. Syndromes chapter). Injury to the peripheral physis, followed by slow growth away with retention of physial cartilage as a cap, may explain the pathogenesis.Evaluation Pain and a mass are typical of the presentation. Promi-nence may take the mass vulnerable to physical trauma. The mass may hurt or limit motion if it interferes with muscle movement. In a critical location, or if sufﬁciently large, an osteochondroma may produce neuro-vascular compromise [C].IMAGING Röntgenogrammes usually sufﬁce. Solitary osteochon-droma may be sessile, characterized by a smooth rounded lesion with a wide “base,” or pedunculated, which is narrow and elongated like a “stalk” or ﬁnger [B]. It arises juxtaphysial out of the metaphysis, from which it is directed and grows away. Medullary and cortical continuity between the main bone and osteochondroma gives rise to the description “aclasis” (Greek κλαω: “to break, interrupt”). For complex lesions in complex locations, MRI will show the structure of the lesion and the sur-rounding structures impacted by it to aid operative planning. Integrated PET/CT aids in identifying conversion of osteochondroma to chondro-sarcoma in the multiple form of the disease.Management Observe osteochondromata unless they signiﬁcantly disturb a patient: there is no rôle for prophylactic removal. The natural history is unpredictable growth during childhood and stabilization after maturity. Follow clinically for unacceptable symptoms or signs. Indica-tions for operation are pain; signiﬁcant prominence, for example, at the medial condyle of the tibia, which is exposed during sports and where there is thin soft tissue coverage; dysfunction such as of joint or muscle; and neurovascular compromise.A Distribution of solitary osteochondroma The knee and proximal arm are most commonly affected. Multiple hereditary exostosis, which is more akin to a skeletal dysplasia, may affect the entire skeleton, except for relative sparing of the spine.B Röntgenogramme of osteochondroma In multiple hereditary exostosis, the lesions deform affected bones and do not stand out alone (red). The presentation of solitary osteochondromata is classic, either sessile or pedunculated (yellow).C Complicated osteochondroma Proximal fibula lesion may impinge upon the common fibular nerve, held by a silastic loop (white). A lesion arising from the posterior proximal tibia may obstruct the popliteal artery, before it bifurcates (red).Diab_Chap10.indd 208 9/23/2015 3:24:31 PM

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Tumors / Benign Cartilage Tumors 209EnchondromaThe name suggests a tumor of cartilage “inside” a long bone (medulla). However, it may occur in or on the cortex. It shows a predilection for the appendicular skeleton, where half occur in the hands and feet [D]. The tumor may be solitary or multiple (cf. Syndromes chapter), without (Ollier) or with hæmangiomata (Maffucci). Pathogenesis is an ectopic remnant of physial cartilage. Macroscopically, lobules give the blue-gray hue of cartilage punctuated by yellow-white mineralized foci. Immuno-histochemistry shows S100-positive chondrocytes.Evaluation Solitary lesions typically are incidental ﬁndings. Pain may be a presenting sign of fracture. Lower limb length discrepancy may result, in particular for lesions about the knee.RÖNTGENOGRAMME Lytic, lobulated lesion with scalloped margins and speckled mineralization is a manifestation of endochondral ossiﬁca-tion that accompanies these tumors.Management For intractable pain, débride the cavity and bone graft. Add ﬁxation as indicated. Lengthen a short limb, with deformity correc-tion as indicated. Recurrence is rare (<5%).Chondromyxoid FibromaThe tumor is composed of lobular myxoid and chondroid tissue with occasional multinucleated giant cells and foci of calciﬁcation. It has been linked to mutation on 6q, in the region that includes the gene encoding the α-1 chain of collagen type XII.Evaluation The majority (>80%) occur in long bones in the lower limb, most commonly about the knee. The tumor is associated with sec-ondary aneurysmal bone cyst.RÖNTGENOGRAMME The eccentric, geographic, lytic, ovoid metaphy-sial lesion looks like a “bite” out of the cortex [E]. It may extend to, but never is solely in, the epiphysis.Management Manage according to general principles for hole in bone. En bloc resection, feasible for an eccentric lesion, reduces recurrence (25%). Reports of malignant transformation probably represent misdiag-nosis of chondrosarcoma.ChondroblastomaThis tumor is distinguished by the epiphysis or apophysis as the primary site [F]. It also is known as Codman tumor, after the original report of “chondromatous giant cell tumors” in the proximal humerus.Evaluation Pain may be associated with joint swelling for epiphysial lesions. Absence of systemic involvement excludes other disease. Micro-scopically, chondroblastoma resembles giant cell tumor of the tendon sheath and pigmented villonodular synovitis. Chondroblastoma is S100 and vimentin positive. Metastasis has been reported, calling into question the appellation “benign” or the initial diagnosis.RÖNTGENOGRAMME The lesion is geographic, lytic, solely epiph-ysial, or apophysial, with erosion into metaphysis.Management Percutaneous radiofrequency ablation may be effective for small lesions and avoids articular dissection. Large lesions are at risk for articular collapse, which is an indication for open débridement and bone grafting. For the epiphysis, intralesional adjuvant risks injury to the physis and articular surface, which additionally limits surgical access on either side of the tumor. Epiphysial lesions have poorer outcomes due to incomplete excision, which leads to a high recurrence rate (30%), as well as to physial and articular injury, which may be due to disease or iatrogenicity. 1 2 3 4+DecadeD Enchondroma The hands and feet are most affected. In the distal femur, growth disturbance may result in shortening and deformity (red).E Chondromyxoid fibroma A “bite” out of the cortex (white).F Chondroblastoma The original report was in the proximal humerus. The lesion may be apophysial, for example, trochanter major (orange), in addition to being epiphysial (red). Epiphysial lesions undermine the articular surface and may erode through the physis into the metaphysis. 1 2 3 4+DecadeDiab_Chap10.indd 209 9/23/2015 3:24:33 PM

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210 Tumors / Benign Bone TumorsBENIGN BONE TUMORSOsteoid Osteoma and OsteoblastomaOsteoid osteoma is a benign, bone-producing, highly vascular tumor that induces an intense reaction and a characteristic pain pattern. Several fea-tures distinguish this from osteoblastoma [A].Evaluation The clinical course of osteoid osteoma consists of an acute phase lasting 1 to 3 years followed by a recovery phase characterized by healing of the lesion with maturity. Pain is intense, focal, and worst at night. Pain results from secretion by the central nidus (Latin “nest”) of prostaglandins (in particular E2 and I2 or prostacyclin), inﬂammatory mediators that elicit a hypervascular response similar to that of injury. Pain is relieved by nonsteroidal anti-inﬂammatory agents, which block prostaglandin synthesis and are used as diagnostic and therapeutic tools. Osteoblastoma in the thoracolumbar spine presents with pain often asso-ciated with scoliosis (75%). In the cervical spine, it is one cause of tor-ticollis.IMAGING Röntgenogrammes show dense eccentric sclerosis with-out or with a radiolucent center. There may be surrounding osteopenia as a sign of disuse. Scintigramme shows focal increased uptake with 100% sensitivity, including early in cases when röntgenogrammes are negative, thereby accelerating diagnosis. CT reveals that the sclerosis forms an envelope surrounding a central nidus, likened to a “target.” In the spine, osteoblastoma affects the posterior elements, with sparing of the vertebral bodies. CT is essential to operative treatment, localizing lesions for complete resection and demonstrating extent of disease for planning of reconstruction. MRI tracks CT, but the inﬂammatory nature of the tumor reduces accuracy.DIFFERENTIAL DIAGNOSIS Signs such as swelling in a subcutaneous bone, for example, tibia, as well as the nidus surrounded by a sclerotic rim, raise the specter of infection. The periosteal reaction may be mis-taken for stress fracture. Increased uptake in posterior elements of the spine on scintigramme raises the question of spondylolysis. The two may be distinguished by the fact that osteoblastoma will show uptake in the immediate or ﬂow phase (seconds) when increased signal in spondyloly-sis is delayed until the second or blood pool phase (minutes). A herniated intervertebral disc may be suspected in an adolescent with sudden-onset back pain and deformity. The length and breadth of the differential list account for a characteristic delay in diagnosis (1 to 3 years).Management The natural history is resolution with maturity in most children.MEDICAL Nonsteroidal anti-inﬂammatory agents help but rarely are sufﬁcient due to the intensity and duration of pain.PERCUTANEOUS The rationale is limitation of morbidity, including dissection and bone compromise, which ease convalescence and reduce complications such as fracture. CT guides localization. Options include radiofrequency or laser coagulative (50°C to 90°C) necrosis. Repeat cycles for lesions >1 cm. The principal disadvantage is lack of immedi-ate conﬁrmation of tumor removal. A hybrid approach is percutaneous cannulated drilling with CT guidance until complete resection. The dis-advantages are drill control and fracture risk.OPEN EXCISION This may be intralesional débridement, with identi-ﬁcation of the nidus, without or with bone grafting, or en bloc excision for noncritical bone to reduce recurrence. The nidus appears deep red, reﬂecting a microscopic architecture of osteoid within a highly vascular stroma. Intraoperative CT with navigation aids localization and resec-tion and conﬁrms completeness. Add ﬁxation as indicated for stability. Advantages of open treatment are direct visualization to ensure sufﬁ-cient resection, no size limitation, and ability to stabilize a critical site. Recurrence correlates inversely with aggressiveness of resection.Spontaneous resolution of spine deformity after excision is more likely in younger patients with short duration of disease (<1 year).Overall recurrence or persistence of pain regardless of percutaneous or open method is 10%.Osteoid Osteoma OsteoblastomaSize 2 cmLocation 90% long bone 1/3 spine:1/3 cervical1/3 thoracic1/3 lumbarSymptoms Intense, night painLess painLess responsive to NSAIASign Swelling DeformityA Differences between osteoid osteoma and osteoblastoma NSAIA: nonsteroidal anti-inflammatory agent.B Osteoid osteoma and osteoblastoma Osteoid osteoma most frequently occurs in the femur (red). The posterior elements of the vertebrae are the exclusive domain of osteoblastoma (yellow). 1 2 3 4+DecadeC Forms of Langerhans cell histiocytosis.Letterer-Siwe Hand–Schüller–ChristianEosinophilic granulomaMultifocal multisystem Multifocal unisystem UnifocalInfantDiffuse diseaseLow survival1st decadeTriad:ExophthalmosDiabetes insipidusOsteolysis (skull)Skeletal onlyMonostoticPolyostoticDiab_Chap10.indd 210 9/23/2015 3:24:34 PM

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Tumors / Benign Bone Tumors 211Eosinophilic GranulomaThis is the most benign form of Langerhans cell histiocytosis [A], lim-ited to the skeleton, most often as a solitary lesion. Langerhans cells are antigen-presenting immune cells, distinguished by Birbeck granules and populating skin and mucosa. Like ﬁbrous dysplasia, eosinophilic granu-loma imitates other disease. The two tumors also share a predilection for the craniofacial skeleton and ribs [B].Evaluation Onset peaks in infancy. Pain may be associated with low-grade fever, which, together with elevated inﬂammatory markers and the radiographic appearance, makes differentiation from infection difﬁcult. Skull lesions may resemble disorders of the central nervous system, such as arachnoid granulation (Pacchioni).One-sixth of cases involve the spine, of which 1/2 have multilevel disease, 1/3 affect the cervical spine, and 1/6 will be deforming. Back pain is a universal ﬁnding. Deformity and soft tissue mass may encroach upon vertebral canal and intervertebral foramina to compromise the neu-ral elements.RÖNTGENOGRAMME Expansile, lytic lesions without or with peri-osteal reaction suggest aggressive destruction and simulate malignancy. Skull lesions may show “hole in hole” due to asymmetric erosion of the inner and outer tables. Vertebra plana (Calvé disease) describes “ﬂatten-ing” of the body, which collapses from a rectangle to a wedge or a line in anteroposterior and lateral projections. Image the entire spine.OTHER IMAGING Scintigramme, which surveys the skeleton for polyostotic disease, may be cold in 1/3 of cases. CT provides best osseous detail, which is of particular importance for skull and spine lesions. MRI, enhanced with gadolinium, shows an associated soft tissue component.Management While skull involvement and vertebra plana focus the differential, biopsy often is necessary for conﬁdence in the diagnosis. Long bone lesions are treated according to principles of hole in bone (cf. Cyst). Operative indications for spine lesions are neural compromise and evidence of instability, including progressive deformity. Otherwise, support with a spinal orthotic primarily to control pain, with the second-ary goal to protect alignment. The majority of cases (>90%) reconstitute without signiﬁcant residual deformity. There is no consensus on chemo-therapy. Do not irradiate children for this condition.Giant Cell TumorsWhile it peaks around the age of 30, 10% occur in children. 50% occur in the knee; it also has a predilection for the sacrum [F]. Measures of the aggressiveness of this benign tumor include the following: • It traverses the physis between metaphysis and epiphysis, eroding to the articular surface.• 3% metastasize to the lungs.• 25% fracture.• 25% recur.It is more often solitary than polyostotic, which behaves more aggres-sively. It is characterized by giant cells with multiple central nuclei as opposed to the peripheral nuclei of Langerhans cells.Evaluation Patients present with pain and swelling.RÖNTGENOGRAMME Expansile and lytic lesion, erosive of bone yet eliciting little reaction, with soft tissue component. MRI aids determina-tion of the extent of bone involvement and soft tissue extension.Management Treat according to principles of hole in bone (cf. Cyst). Complications relate to involvement of the physis and erosion of sub-chondral bone, which lead to growth disturbance and arthritis. As for aneurysmal cyst and other high recurrence benign tumors, en bloc resec-tion is preferable; however, this may not be feasible given proximity to joint. Like chondroblastoma, intralesional adjuvant risks iatrogenic injury to the physis and articular surface. 1 2 3 4+DecadeD Eosinophilic granuloma Vertebra plana may be seen on lateral projection in the cervical spine (red) and anteroposterior projection in the thoracic spine (yellow). Despite collapse, there is neither kyphosis nor scoliosis.E Eosinophilic granuloma of the spine This lesion has eroded the vertebral body (yellow) and is associated with a large soft tissue mass (red), which occupies most of the spinal canal (red). The neural elements are outlined in white dots.F Giant cell tumor It may extend between metaphysis and epiphysis, eroding the physis and subchondral bone (yellow). 1 2 3 4DecadeDiab_Chap10.indd 211 9/23/2015 3:24:35 PM

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212 Tumors / Other Benign TumorsOTHER BENIGN TUMORSHæmangiomaHæmangioma may be isolated, when it is regarded as a tumor, or part of a systemic condition, where it is an anomaly [A]. The tumors may be capillary, involving small vessels, or cavernous, involving large vessels. They may be distinguished according to tissue distribution.Muscular Most tumors occur in the lower limb, the majority in the thigh. Unlike vascular anomaly syndromes, skin is unaffected. Presen-tation includes pain without or with swelling, which may increase with dependent position of the limb or with activity. Röntgenogrammes show soft tissue swelling. MRI with gadolinium enhancement shows serpen-tine inﬁltration of muscle in early disease.The natural history is spontaneous involution. Indications for surgical removal are unacceptable pain or dysfunction. Preoperative embolization may reduce hæmorrhage. Recurrence is associated with lesions having less deﬁned margins and those that are in critical locations, for example, forearm, where wide margins may impair function.Synovial This may affect joint (mostly knee) or tendon sheath. Artic-ular involvement is characterized by pain, hæmarthrosis, stiffness, and mechanical symptoms. Effusion should serve as an alert for further workup. Mechanical symptoms have been attributed to more innocent causes of internal derangement, thereby delaying diagnosis.Treat arthroscopically for central lesions, or open for a peripheral lesion, where any capsule may be identiﬁed for a complete extralesional excision.Osseous Two-thirds occur in the craniofacial skeleton and spine [B], where the tumor affects the anterior column. Hæmangioma is the most common benign tumor of the vertebrae (10% of autopsies). Tumor may involve a single bone, adjacent bones, or separate sites. Osseous hæman-gioma also includes massive osteolytic hæmangiomatosis (Gorham), where increased blood supply is stimulatory of osteoclasts more than osteoblasts, tipping the normal state toward resorption.Most are asymptomatic. Consider embolization for pain that is not alleviated by conservative methods. Vertebroplasty alleviates pain and stabilizes deformity. Spinal canal decompression and reconstruction are indicated for neural compromise.Pigmented Villonodular SynovitisThis disorder affects synovial joints, most frequently the knee, and ten-don sheaths, most frequently in the hand, where it is known as giant cell tumor of the tendon sheath. Fusion transcripts of the gene encoding α-1 chain of collagen type VI and colony-stimulating factor-1 have been found, although causation has not been established.Evaluation Patients present with pain, swelling, and stiffness. There are two types: diffuse and focal. Röntgenogrammes show shadow of soft tissue swelling and may show saucerized erosions on both sides of the joint in advanced disease. MRI with gadolinium enhancement reveals hyperplastic and hypervascular synovial membrane, hæmosiderin depo-sition, and hæmorrhagic effusion. Histologic analysis shows synovial cell proliferation and multinucleated giant cells.Management Deﬁnitive treatment consists of complete synovectomy, arthroscopically or open, and with radiation if necessary. The articular location and inﬁltrative nature of this tumor raises recurrence.A Hæmangioma This may represent an isolated tumor (yellow) or a vascular anomaly, such as in Klippel-Trénaunay-Weber syndrome (red).B Hæmangioma of bone Radiodense longitudinal stripes reflecting osseous deposition along vascular channels give the appearance of a “jailhouse” or “corduroy” (orange) and appear as “polka dots” in transverse plane on CT (green). These findings contrast with thicker transverse striations parallel to end plates, as seen in the rachitic spine, which are likened to a “rugger jersey.”Diab_Chap10.indd 212 9/23/2015 3:24:36 PM

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Tumors / Malignant Soft Tissue Tumors 213MALIGNANT SOFT TISSUE TUMORSThese tumors account for about 7% of malignant tumors of childhood. They may be divided into ﬁve general categories [A].RhabdomyosarcomaThis is a sarcoma of the skeletal muscle and constitutes more than half of malignant soft tissue tumors in children. It is the most common pædiatric soft tissue sarcoma [B].Evaluation Two-thirds occur in the ﬁrst decade. Blacks and Asians are affected less commonly than Whites. Rhabdomyosarcoma may occur anywhere, and presentation varies accordingly [C]. One-quarter occur in the head and neck and 1/4 in the limbs. In a limb, it typically manifests as a ﬁrm, painless mass, without or with nodal involvement. Nodal exten-sion is predictive of metastasis. By contrast with muscle, osseous lesions are painful. In the orbit, it produces proptosis. In the bladder or prostate, it produces urinary tract obstruction or hæmaturia, which may be gross or detected by urinalysis. In the chest, abdomen, or pelvis, it may grow large before manifestation.There are 2 principal histologic types of rhabdomyosarcoma: embry-onal (80%) and alveolar (20%), which have 2/3 the survival rate. Tumors arising in sites other than the limbs typically are embryonal, whereas limb tumors are alveolar, hence the poorer prognosis.Embryonal rhabdomyosarcoma may be caused by somatic mutation in the SLC22A18 gene on chromosome 11p15.5, resulting in loss of het-erozygosity of a tumor suppressor gene. Alveolar rhabdomyosarcoma results from fusion of the PAX3 gene on chromosome 2 with the FKHR gene on chromosome 13 as a result of a translocation t(2;13), or from fusion of the PAX7 gene on chromosome 1 with the FKHR gene as a result of a translocation t(1;13). Such translocations produce hybrid mol-ecules that serve as potent transcription activators, deinhibiting myoblast proliferation. These mutations may be detected by ﬂuorescent in situ hybridization (FISH) and reverse transcriptase–polymerase chain reac-tion (RT-PCR) testing of a biopsy specimen.Management Survival for solitary lesions is >70%, which declines to the historical level <30% for metastatic disease. Operative treatment includes resection with a wide margin (>2 cm) and sampling of local lymph nodes.Synovial SarcomaThis occurs most frequently in the lower limbs, around the knee. It is the most common malignant soft tissue tumor of the foot. It is caused by the chromosomal translocation t(X;18)(p11;q11), leading to fusion of the SYT gene (18) with the SSX gene (X). The fusion proteins may func-tion as aberrant transcriptional regulators to activate proto-oncogenes or inhibit tumor suppressor genes.Evaluation Delay in diagnosis is characteristic, often >12 months. This is due to varied presentation, including latency, which gives the impression of benignity but which may be followed by rapid growth. The tumor is associated with deep fascia, manifesting as a deep, tender mass. Intralesional calciﬁcation (“snowstorm”) on röntgenogramme is pathog-nomonic though infrequent. MRI is the imaging modality of choice for diagnosis and surgical staging. Cytogenic analysis (FISH, RT-PCR) con-ﬁrms diagnosis.Several factors inﬂuence survival [C].Management Adjuvant monoclonal antibody against a cell surface receptor (FZD10) unique to synovial cell sarcoma cells may improve outcomes, including need for amputation and survival.Wide resection (2-cm margin) limits recurrence. Location in the knee may involve popliteal artery and tibial nerve, which may preclude limb salvage.0% 25% 50% RhabdomyosarcomasRound blue cell tumorsMalignant fibrous tumorsSynovial sarcomasMiscellaneous sarcomasA Types of soft tissue sarcomas. 1 5 10 15 20Age (years)B Rhabdomyosarcoma age distribution 2/3 occur in the first decade.C Prognosis for synovial cell sarcoma For good prognostic factors (green), survival rate is >80%. This declines to <20% for poor prognostic factors. Distal limb signifies hand and foot. Central location is the trunk, head, and neck.Size Histology Location< 5cmBiphasic:synovial cells in glandular architectureDistal limb5-10 cm Monophasic:spindle + round cellsProximal limb> 10 cmPoorly differentiated CentralDiab_Chap10.indd 213 9/23/2015 3:24:37 PM

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214 Tumors / Malignant Bone TumorsMALIGNANT BONE TUMORSOsteosarcomaOsteosarcoma is third in frequency to blood and brain cancers in child-hood. It is the most common malignant tumor of bone. It is related to rapid growth, as evidenced by geographic distribution in the knee (more than half of cases) and the proximal humerus, as well as peak incidence during adolescence [A].Loss of heterozygosity and tumor suppressor allelic inactivation at chromosome 3q13.31 have been found in osteosarcoma. A genetic pre-disposition is suggested by association of osteosarcoma with retino-blastoma (mutation in the RB1 gene on 13q14), Paget disease of bone (mutation in the TNFRSF11A gene on 18q22), Li-Fraumeni syndrome-1 (mutation in the TP53 gene on 17p13), Li-Fraumeni syndrome-2 (muta-tion in the CHEK2 gene on 22q12), and Rothmund-Thomson syndrome.Evaluation Pain, limp, stiffness, inﬂammatory swelling, and focal mass are characteristic. Systemic presentation is uncharacteristic, except in metastasis. There is no gender or race predilection. Several factors are critical to prognosis [B].LABORATORY Alkaline phosphatase elevation correlates with risk of metastasis. Elevation of lactate dehydrogenase bears a worse prognosis. Histologic analysis shows osteoid and cells that may be distinguished as osteoblastic, ﬁbroblastic, chondroblastic, and telangiectatic, which contain loculi of blood. The tissue distinctions do not correlate with prognosis. Two clinical subtypes, parosteal, which is intracortical, and periosteal, which is low grade and encircles (Greek περι: “around”) the bone, have a favorable prognosis.RÖNTGENOGRAMME One-half of cases are blastic, including osteo-genesis in a radiating “sunburst” or “cotton wool” pattern [C], 1/3 are lytic, and others are mixed. Repeated periosteal elevation and reaction results in lamellar bone deposition likened to “onion skin.” The telangi-ectatic type may resemble aneurysmal bone cyst.SCINTIGRAMME Survey the skeleton for metastasis, within both the same osseous compartment and extracompartmental.CT CT of the chest is essential to staging. Of the site, it is essential to operative planning.MRI This best visualizes medullary disease and soft tissue involvement.PET This may detect disease missed by other modalities, predict response to chemotherapy, and aid in determination of response after treatment.Management Neoadjuvant chemotherapy aids prognostication and improves surgical outcomes, including limb salvage, by shrinking the tumor. Osteosarcoma is radioresistant, leaving surgical as the only treat-ment for local control.Operation for cure may include wide margins (> 5 cm); radical mar-gins, deﬁned as the entire osseous compartment from joint to joint; or amputation. Limb salvage is the ﬁrst goal in a child, but is not always feasible [D]. For every patient, balance the functional beneﬁts, including appearance, and the morbidity, physical and psychic, of limb salvage and reconstruction against early amputation and prosthetic ﬁtting: there is no universal approach.Ewing SarcomaEwing sarcoma is part of a family of small, round, blue cell tumors that includes peripheral primitive neuroectodermal tumor and neuroepithe-lioma. The family shares the same reciprocal translocation of the EWS gene on chromosome 22q12 with various members of the ETS family of transcription factors on 11q24. The fusion protein is a target of cur-rent molecular treatment modalities (e.g., YK-4-279). Ewing sarcoma is the second most common malignant bone tumor of childhood. It may be osseous, medullary, or soft tissue.0% 25% 50%FemurTibiaHumerusPelvisSkull 1 2 3 4+DecadeA Geographic and age distributions of osteosarcoma Growth influences distribution, both geographic (knee) and temporal (adolescence).Factor PrognosisGradeLow: favorableLocation Distal limb (best) - proximal limb - axial skeleton (worst)Metastasis Absence better than presenceResponse to neo-adjuvant chemotherapyIncreasing tumor cell kill improves prognosisResectability Complete primary resection improves prognosisAlkaline phosphataseLactate dehydrogenaseElevation unfavorableClinical subtype Parosteal and peri-osteal favorableRelapse Poor prognosisB Prognostic factors.C Radiographic appearance of osteosarcoma Osteogenesis look like a “sunburst” (red) or resemble “cotton wool” (yellow).D Contraindications to limb salvage.Estimated lower limb length discrepancy >8 cm in immature childPoor response to neo-adjuvant chemotherapyTumor contamination beyond compartment, e.g., after biopsy or due tohæmatoma after morbid fracture Major infectionUnresectable lesion, e.g., due to extensive soft tissue involvement, suchas penetration of neurovascular structures. Diab_Chap10.indd 214 9/23/2015 3:24:38 PM

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Tumors / Malignant Bone Tumors 215Evaluation It peaks in the second decade [E]. In contrast with osteo-sarcoma, Ewing sarcoma occurs with equal frequency in ﬂat bones, such as the pelvis, and long bones, where it may arise in the diaphysis. It also may arise in soft tissues. Whites are affected onefold more than blacks. Focal osseous symptoms and signs include pain, limp, stiffness, inﬂam-matory swelling, and mass, while petechiae and other signs of blood dyscrasia are medullary manifestations and fever is systemic. Back pain may be spinal, retroperitoneal, or pelvic in origin. Most important deter-minants of prognosis are metastasis [F], followed by location (cf. Osteo-sarcoma).LABORATORY Findings include abnormal blood cell count such as thrombocytopenia, and elevated inﬂammatory markers, including CRP and ESR. Histology shows characteristic small, round cells of which the glycogen-rich cytoplasm stains blue with hematoxylin and eosin. Immunohistochemical marker MIC2 antigen (CD99) stains the cell membrane. Cytogenetic studies of tissue specimen conﬁrm the t(11;22) translocation.RÖNTGENOGRAMME This is one of the diaphysial lesions. It is per-meative (wide zone of transition between disease and normal), destruc-tive of bone, and eliciting a periosteal reaction.MRI This tumor is characterized by a soft tissue mass, which is best visualized by MRI. MRI also reveals medullary extent.PET This is sensitive for metastasis, though scintigramme and whole-body MRI may substitute.Management Principles resemble those for osteosarcoma. A difference is the use of radiation therapy to augment surgery for local control of disease. A cost is radiation-induced sarcoma, in particular leukæmia.LeukæmiaThis is the most common cancer of childhood. The most common sub-type is acute lymphoblastic.Evaluation This peaks early in the ﬁrst decade. Patients with chromo-somal anomalies (e.g., trisomy 21) are at increased risk for leukæmia. 20% of children with leukæmia present with bone pain, of which the characteristic is a migratory pattern, and 10% present with a limp. An orthopædic surgeon or rheumatologist may be the ﬁrst medical consul-tant. Keys to the diagnosis include physical evidence of systemic disease, such as fever, malaise, lymphadenopathy, hepatosplenomegaly, and signs of myelophthisis, such easy bruising and bleeding, infection, and pallor of mucous membranes.LABORATORY Abnormal blood counts and peripheral smear, for example, leukocytosis (hence the name of the disease by Virchow), are diagnostic.RÖNTGENOGRAMME “Leukæmic lines,” transverse radiolucent metaphysial bands, are rare though pathognomonic. More common is periosteal new bone formation in a background of disuse osteopenia and, in severe cases, geographic osteolysis.Management The essential component for the surgeon is recognition. Bone marrow aspiration establishes the diagnosis.MetastasisThe spine is third in frequency after the lung and liver as a destination for metastasis [G]. Most patients are symptomatic and half have multi-ple level involvement, hence the importance of survey imaging such as scintigramme or PET. Greater than 90% of lesions are vertebral or epi-dural, with <10% intradural. Most metastasis represents vascular seed-ing, including via Batson plexus, a network of valveless veins that drain the body cavities to the vertebral veins.The tumor that most frequently metastasizes to bone is neuroblas-toma [H]. This small, round, blue cell tumor has onset in infancy, is of sympathetic neural origin, may spontaneously regress to benign gan-glioneuroma, and in more than half of cases presents with metastasis. 2/3 originate in the abdomen and pelvis; in the spine, 10% reach into the vertebral canal to encroach upon the neural elements. 1 2 3 4+DecadeE Ewing sarcoma Half are axial and half are appendicular. Subtle radiographic change (yellow) despite a large soft tissue component (red).MetastasisLung - 50% Bone - 50%Lung - 90% Bone - 10%OsteosarcomaEwing sarcomaF Metastasis of osteosarcoma and Ewing sarcoma Metastasis at diagnosis halves the 5-year relapse-free survival.0% 20% 40% 60% 80%SpineRibsSkullFemurPelvisHumerusTibiaRadiusScapulaFibulaHandFootClavicleSacrumUlnaG Distribution of skeletal metastasis.H Tumors metastasizing to bone.0% 25% 50%NeuroblastomaRhabdomyosarcomaTeratomaWilms tumorRetinoblastomaCraniofacialOtherDiab_Chap10.indd 215 9/23/2015 3:24:40 PM

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