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Chest wall tumors

Oncology
Surgery

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Ju Ae Park, MD
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Kei Suzuki, MD MS FACS
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Introduction

Chest wall tumors are a small but important subset of thoracic neoplasms, with primary tumors of the chest wall accounting for approximately 1-2% of all thoracic tumors. These tumors can be subcategorized by tissue of origin into soft tissue or bone/cartilage tumors[1].
Slightly over half of these tumors are malignant[1, 2] and can arise from any portion of the thoracic cavity or can arise as a metastatic lesion with direct invasion into the chest wall from a separate primary cancer. Secondary tumors are most commonly from breast, lung, or skin primaries[3].
Primary and metastatic chest wall neoplasms can arise from or involve any portion of the thoracic skeleton, including the ribs, sternum, scapulae, and clavicles. Wide surgical resection remains the primary management strategy for most chest wall tumors and the involvement of a multi-disciplinary team with tailored treatment regimens for individual cases and patients is highly recommended for diagnosis, treatment, and reconstruction.
In this chapter, we will focus mainly on primary tumors of the chest wall.

Presentation

Approximately 20% of chest wall masses are discovered incidentally on imaging obtained for different medical reasons[2]. The remaining 80% present with symptoms consisting of pain, dyspnea, or neurologic and/or vascular involvement[4].
Some patients present with nonspecific generalized symptoms such as fever, night sweats, muscle aches, and fatigue. Many times, soft tissue masses are found to be painless whereas bony lesions are associated with pain due to periosteal invasion[5].
Almost all malignant lesions are painful while only two-thirds of benign lesions produce pain. Despite this, pain is not a reliable predictor of malignancy. There are no consistent signs and symptoms associated with chest wall tumors that can distinguish between benign and malignant tumor development[6].
As chest wall tumors are rare and make up approximately 0.04% of all new cancer diagnoses[7], there are no formal recommendations for screening.

Diagnostic Workup

Work up begins with complete history and physical examination with attention to history of past malignancies, radiation exposure, and presence of family history. Plain radiographs are often obtained; however, they are usually not enough to elucidate the extent of invasion and disease process. A CT scan or MRI (magnetic resonance imaging) can be helpful in formulating a treatment plan. MRIs are especially useful in evaluation of posterior or apical lesions to assess for involvement of the spinal cord or neurovascular structures[8].
PET (positron emission tomography) imaging can be an adjunctive study to plan tissue sampling, assess staging, response to treatment, or diagnose recurrent disease[9]. While some chest wall lesions have characteristic imaging findings which can ascertain an accurate diagnosis of benign or malignant process through imaging alone, other entities are difficult to distinguish on imaging due to a significant overlap of features[10].
Chest wall lesions can be classified according to their predominant composition: fat, calcification and ossification, soft tissue, or fluid. The identification of this composition through imaging, together with patient age, clinical history, and lesion location, can aid in the appropriate diagnostic and treatment plan[10].
Ultimately, a definitive diagnosis can only be made with a biopsy. Core needle biopsy utilizing image guidance is the initial preferred method of tissue diagnosis. If this results in non-diagnostic findings or for tumors necessitating larger tissue samples, an excisional vs incisional biopsy can be performed.
Excisional biopsies can be considered for smaller lesions (less than 2cm). If incisional biopsy is planned, all biopsy tracts and/or incision sites should be made within the planned final excision site of the tumor in order to complete definitive excision[11].
For any suspected secondary metastases, fine needle aspiration is usually a sufficient method of diagnosis.

Differential Diagnoses

A number of differentials are considered in working up a chest wall tumor. The most common benign primary tumors consist of osteochondromas, chondromas, fibrous dysplasia and/or desmoid tumors (Table 1).
The most common malignant primary tumors consist of soft tissue sarcomas, chondrosarcomas, and Ewing sarcoma[11] (Table 2).

Benign Tumors

Osteochondroma
Osteochondroma is the most common type of benign bone tumor, accounting for approximately 30% of all benign bone tumors[12]. By location, osteochondromas are more commonly found at the costochondral junction[13].
Demographically, osteochondromas have a peak incidence in the second decade of life, mostly occurring in males[14, 15]. Imaging is characterized by punctate calcifications with a mineralized hyaline cartilage cap best visualized on CT imaging. The risk of malignant degeneration to chondrosarcoma is rare, occurring in approximately 1% of cases, and is related to the thickness of the cartilaginous cap, with caps greater than 2 cm in thickness being suspicious for carcinoma[16, 17].
In order to decrease the risk of malignant transformation and to provide symptomatic relief, the recommended treatment is surgical resection[14]. Recurrence has rarely been reported[18].
Chondroma
Chondromas are common, benign cartilaginous tumors, which make up 15 to 20% of benign chest wall lesions. By location, they are found in the anterior portion of the rib and are usually painless and slow growing[19].
Demographically, chondromas typically present between the second and third decade of life. Imaging is characterized by well-circumscribed lesions with punctate calcifications of the matrix and scalloping of the cortex often seen on CT and MRI[16, 20].
Histologically, they are characterized by nodules of hyaline cartilage with chondrocytes containing small, condensed nuclei. Clinically, the distinction between chondroma and low-grade malignant chondrosarcoma is difficult to ascertain unless there are imaging features demonstrating extensive destruction of the cortex or soft tissue infiltration which indicates evidence of malignancy[20].
Due to this difficulty in distinguishing between the two entities, chondromas are assumed to be malignant lesions until pathological diagnosis confirms otherwise, and wide excision with 2-cm margin is recommended[2].
Fibrous dysplasia
Fibrous dysplasia is a benign lesion, typically located in the lateral or posterior ribs[19] and is discovered most commonly in the second and third decades. Most cases (70-80%) only involve one rib[21]. It can be associated with Albright’s syndrome, in which multiple bone cysts, skin pigmentation, and precocious sexual maturity in females are seen.
The appearance of a lytic lesion on chest radiograph with a ground-glass appearance, well-circumscribed margins, and no soft tissue component are characteristic findings. On MRI, lesions are patchy with low to intermediate signaling on T1 and T2-weighted images[22]. These lesions are also referred to as Chinese characters due to their irregular appearing spicules[23].
Malignant degeneration is unusual, and these lesions do not require resection unless symptomatic or if diagnosis is in question. Antiresorptive agents may be used, and recent research into anti-IL6 antibodies shows this may also be efficacious in the treatment of this disorder[24].
Eosinophilic granuloma
Eosinophilic granuloma, or Langerhans cell histiocytosis, is a less common benign tumor which can be present in the anterior chest wall, accounting for less than 1% of all bone tumors[25].
It is a subset of the disorder histiocytosis X, including Letterer–Siwe disease (infants) and Hans–Schüller–Christian disease (children). These masses can present with systemic signs and symptoms such as fever, malaise, weight loss, and lymphadenopathy, as well as local symptoms of chest pain and an isolated tender mass.
Laboratory findings are typically unremarkable, except for an occasional moderate elevation in the erythrocyte sedimentation rate or a mild leukocytosis[25].
The radiographic appearance includes a lytic bone lesion without reactive sclerosis, and in most cases, a hypervascularized soft-tissue mass surrounding affected bone. Diagnosis is made by identification of Birbeck granules on electron microscopy. Treatment options are varied and include methylprednisolone injections, radiofrequency ablation, surgical excision and curettage, chemotherapy and irradiation.
Utilization and results of treatment are varied and depend on extent of disease and symptomatology[25].
Benign soft tissue tumors
Benign soft tissue tumors are relatively uncommon and typically present as painless and slow growing masses. The predominant benign tumors involving the chest wall include: lipomas, neurogenic tumors, vascular tumors (hemangiomas), and connective tissue tumors. Benign peripheral nerve sheath tumors consist of neurofibromas and schwannomas.
Malignant degeneration of these lesions are uncommon and in many cases, imaging findings are consistent with benign characteristics[42].
However, as the percentage of malignant soft tissue lesions is high and preoperative differentiation between the various neoplasms can be difficult, if there is any doubt in regards to the malignancy of the tumor, wide surgical resection instead of local excision is the recommended treatment.
Desmoid
Desmoid tumors arise from musculo-aponeurotic structures and are considered myofibroblastic or fibroblastic in origin. Desmoid tumors are most common in the extremities, with only 10 to 28% arising in the chest wall[43].
Their histology is benign, but due to their often aggressive growth rates and tendency for local invasion, they can be treated similar to malignant masses. These tumors are usually found in populations younger than 40 years, have a higher prevalence in women, and can occur in sites of previous trauma, scar, or radiation. Desmoid tumors can be found in patients with familial adenomatous polyposis, where they are related to a mutation in the APC gene[42].
On CT, desmoid tumors have a variable nondescript appearance depending on the amount of collagen content, but generally have similar enhancement to muscle. On MRI, lesions typically have homogenous signal intensity on T1 weighted images as opposed to heterogenous, high signal intensity on T2 weighted images[44].
Histologically, there is a sheet-like pattern of uniform, well-differentiated fibroblasts without mitoses or necrosis. Finger-like projections of tumor infiltration are frequently observed pathologically. Recurrence rates for desmoid tumors are high. Abbas et al. reported a 37% local recurrence rate in 5 years with the rate significantly increasing to 89% in patients who had positive margins at the time of resection[45].
Chemotherapy with a doxorubicin-based regimen may be of benefit in the adjuvant setting. Intraoperative brachytherapy has been used when resection was limited by the tumor’s proximity to vital structures[44].
Due to the high recurrence rates and consideration of the more commonly seen indolent growth patterns of these tumors, recommendation for active surveillance rather than immediate resection has been more prevalent in the recent years especially in those who demonstrate very little growth after presentation and/or the resection may result in significant functional deficits[48].
Radiation therapy is reserved for unresectable disease, locally recurrent disease, or post-surgical positive margins[44].
Table 1 – Benign Chest Wall Tumors
Tissue CompositionTypical PresentationStandard TreatmentRecommended surveillance/Recurrence ratePrevalence
OsteochondromaBonePainless, M>F; Most common in long bones, followed by ilium and scapulaResectionUnlikely to recur30% of all benign bone tumors; 50% of benign rib tumors
ChondromaCartilagePainless, slow-growing; typically incidentalResectionImaging every 3-6 mo for the first year; then annually for at least three years15 – 20% of benign chest wall lesions
Fibrous dysplasiaBone+/- painSurveillance; resection if symptomaticbased on symptomatology~5% of benign bone lesions
Eosinophilic granulomaBonePainful mass, fever, malaise, weight loss, lymphadenopathysteroids, radiofrequency ablation, surgical excision/curettage, chemo and RTDepends on extent of disease<1 % of all bone tumors
Solitary plasmacytomaMonoclonal plasma cellsbone pain, anemia, neurological symptoms, pathological fractureRadiation ± resectionCan progress to multiple myeloma at a rate of approximately 40% to 50% over 5 years3% of all plasma cell neoplasms, 15% have lesions in the bones of the chest
DesmoidConnective tissue mass +/- painSurveillance; resection if symptomatic followed by chemotherapy or RT, especially at recurrenceHigh recurrence rate; as many as 50 % of patients experiencing a recurrence within 5 years< 3% of all soft-tissue tumors
Abbreviations: RT, radiation therapy; M, males; F, female

Malignant Tumors

Chondrosarcoma
Chondrosarcomas represent the most common primary malignant neoplasm of the chest wall. By location, they are most commonly found on the anterior chest wall, usually at the costochondral junction[26].
Demographically, they present between the fourth to seventh decades of life with a slight male predominance[9]. Most chondrosarcomas are believed to develop de novo; however, these tumors may also represent a malignant degeneration of benign chondromas[27].
Imaging is characterized by a lobulated soft tissue mass with dense calcifications[21]. Contrast administration can demonstrate a characteristic pattern of peripheral and septal enhancement of the mass[44].
Resection is the backbone of therapy, with radiation therapy only administered to patients with unresectable lesions and cytotoxic chemotherapy only recommended for younger patients with good tolerance; however, the efficacy is disputed[28].
For malignancies that cannot be controlled with conventional treatment, targeted, anti-angiogenic agents (e.g., pazopanib) can be attempted as rescue therapy[29].
Grade 1 tumors are treated by extensive intra-lesional curettage with local adjuvant chemical treatment or cryotherapy/cementation, or resection with disease free margins[28, 30].
Grade 2 and 3 chondrosarcomas, as well as local recurrence of an M0 condition are treated by radical resection with the goal of R0 resection. The minimum required resection margin is 4 cm for any chest lesion. Factors associated with prolonged survival are lack of metastases, lack of recurrence, younger age, size of soft tissue component, and tumor grade[28].
Osteosarcoma
Osteosarcomas are the most common type of bone sarcomas and second most common primary malignant neoplasm of the chest wall, often occurring in the rib, scapula, and clavicles[2]. The peak incidence is between the first to third decade of life, during the period of most active skeletal growth, and presents with localized pain and swelling[31].
Possible risk factors include environmental triggers such as high fluoride exposure and residency on a farm, as well as genetic predisposition for other musculoskeletal abnormalities and malignancies[32]. Certain syndromes associated with an increased risk in osteosarcoma include Retinoblastoma, Li-Fraumeni, Rothmund Thompson, and Werner syndromes[53].
Imaging findings are characterized by a large, heterogeneous mass with areas of bony destruction. The most characteristic finding is a sunburst appearance due to the pattern of calcification occurring at right angles to the bony cortex. MRI is useful in determining tumor size and invasion into nearby structures which would assist in resection planning.
Due to poor outcomes of single modality therapy, these tumors are typically treated with neoadjuvant chemotherapy followed by surgical resection[31].
Consistent with the mainstay of sarcoma treatment, R0 resections are associated with improved survival. It must be emphasized that even with reduction of disease burden with neoadjuvant therapy, the originally measured tumor circumference including the recessed bed must be completely resected[34].
Osteosarcomas are not very radiosensitive, but radiation therapy, sometimes in conjunction with radio-sensitizing agents, has been used for tumors with inadequate resection. Immunotherapy has not proven to be beneficial in this patient population, however gene therapy studies have shown promise in the preclinical setting.
Ewing sarcoma
Ewing sarcoma, along with PNETs (primitive neuroectodermal tumors, also known as Askin tumors), represent a highly malignant, small, round cell-type tumors sharing a common (t11;22) (q24;q12) translocation[35]. Approximately 15% of Ewing sarcomas[37] and 50% of PNETs arise in the chest wall[38]. Demographically, they frequently occur in the second to third decade of life with a twofold increased prevalence in males compared to females[44].
Radiographically, Ewing sarcoma usually presents as an osteolytic lesion with heterogenous appearance representing hemorrhage and necrosis or cystic degeneration. On MRI, the lesion is typically found to have high signal density on T2-weighted images[35].
Incisional biopsy demonstrating small round blue cells with clear cytoplasm positively staining on period acid-Schiff stains with FISH-based detection of EWSR1 rearrangements is diagnostic for Ewing sarcoma. Distinguishing PNETS from Ewing sarcoma are oval nuclei with neurofibrillary cores[35].
Neoadjuvant chemotherapy typically precedes local therapy with surgery and/or radiation. Current standards of treatment for local control involve surgical resection in resectable cases with or without postoperative radiation or radiation alone when resection would impede critical bodily functions. Regardless of the form of local control, the treatment course is completed with a course of adjuvant chemotherapy[33].
The optimal margin to qualify as a R0 resection is >2mm which is consistent with most sarcomas[35].
Solitary plasmacytoma
Solitary plasmacytoma is a rare, localized tumor consisting of monoclonal plasma cells in a discrete mass without diffuse spread. It is more commonly found in the axial skeleton, especially the vertebra[34]. Approximately 15% of these patients have lesions in the bones of the chest[41].
Most patients are older males, with a median age of diagnosis of 65 years, and present with pathologic fracture, anemia and have an elevated erythrocyte sedimentation rate[41]. Histologic examination demonstrates a vascular lesion consisting of sheets of plasma cells of varying degrees of differentiation. Immunohistochemical confirmation of the diagnosis can be made by identifying a kappa or lambda light chain-restricted population of cells[34].
As radiation therapy is the mainstay of treatment, it is administered to all patients, regardless of extent of surgical resection. Five-year survival has increased to over 60% in recent decades and overall survival is dependent on multiple factors including age, sex, and development of multiple myeloma[2, 41].
The added benefit of surgical resection is debated as approximately 35% of patients who receive any modality of therapy will eventually develop multiple myeloma[34].
Malignant fibrous histiocytoma
Malignant fibrous histiocytoma (MFH) mostly occurs in patients between the sixth and eighth decade of life but has a bimodal distribution, with the first peak occurring between the second and third decade of life. These tumors are usually not painful and are commonly found in elderly men with a history of previous chest wall radiation[42].
On CT imaging, these lesions have a heterogenous appearance which can be enhancing or calcified. There are four histologic subtypes: pleomorphic, giant cell, myxoid, and inflammatory, with myxoid subtype recorded to have the best prognosis. Treatment is wide excision, as radiation and chemotherapy have not proven effective[46].
Rhabdomyosarcoma
Rhabdomyosarcoma is the most common soft tissue sarcoma and second most common malignant chest wall tumor in children. There are three major subtypes: alveolar, embryonal, and pleomorphic[49]. A slight male predominance exists, and it is also known to be more frequently occurring in patients with neurofibromatosis, Li-Fraumeni, and Beckwith-Wiedemann syndromes[48].
Treatment entails neoadjuvant chemotherapy, wide resection, if possible, followed by radiation and/or chemotherapy depending on tumor response[38, 42]. Approximately 20% of patients present with metastatic disease at diagnosis[50].
Liposarcoma
Liposarcomas are common malignant soft tissue tumors, however they are rare in the chest wall[42]. These tumors are most common in men in the fifth to seventh decade of life. Standard treatment is wide local excision with negative margins[46].
Local recurrence rates are high, and risk can be reduced by treatment with radiation in high-grade lesions. Chemotherapy is not beneficial in all subtypes, however with improved understanding of the genomic landscape of the disease, targeted therapies are under development[51].
Tumor location, grade, histology, and most importantly margin status, have all been shown to be associated with survival rates[52].
Table 2 – Malignant Chest Wall Tumors
Tissue CompositionTypical PresentationStandard TreatmentRecommended surveillance/Recurrence ratePrevalence
ChondrosarcomaCartilagePainful, hard, slow growing massResection, RT and chemotherapy in select patients, antiangiogenic agentsDepends on grade and extent of disease; low grade tumors  unlikely to recur30% of all primary malignant bone tumors
OsteosarcomaBone between 10-14 yo, localized pain and swellingNeoadjuvant chemotherapy, resectionRecurrence in 30-50% of patients with initial localized disease; 80% of patients presenting with metastatic disease20% of all cases of primary malignant bone tumors; 10 – 15% of malignant chest wall tumors
Ewing sarcomaBonesecond decade of life, localized pain and swellingNeoadjuvant chemotherapy, resection ± RT, adjuvant chemoapprox 30% of patients with recurrence within the first 5 years5-10% of malignant chest wall tumors
LiposarcomaFatPainful mass, swellingResection, RT for high-grade lesionsHigh rates of local recurrence20% of adult mesenchymal tumors; rare in chest wall
Abbreviations: RT, radiation therapy

Chest Wall Reconstruction

As a result of oncologically sound resection, patients are often left with sizable chest wall defects. In reconstructing the chest wall, one must achieve skeletal rigidity, prevention of lung herniation and scapula impaction, and protection of underlying organs, all while maintaining cosmesis.
In planning the chest wall reconstruction, it helps to think of the chest wall as skeletal and soft tissue components. For the approach in skeletal reconstruction, two main factors to consider are size and location. For skeletal defects less than 5cm or posterior defects under the scapula above the 4th rib, soft tissue coverage only may be adequate. For large chest wall defects (≥5 cm) or defects more than 3 ribs, skeletal reconstruction is recommended. For defects anteriorly, rigid reconstruction is recommended for protection of underlying organs[55].
In choosing the material for skeletal reconstruction, factors to consider are rigidity, in-growth of tissues, infection rate, and malleability. Meshes are easy to handle and allow in-growth of regenerative tissues. They do not provide much strength, and as such are not ideal when rigid reconstruction is necessary to protect the underlying organs. Among the different meshes, Vicryl (polyglactin-910) mesh (Ethicon, Inc, Somerville, NJ, USA) is a commonly used mesh. It is inert, biocompatible, and slowly absorbing, and is a good option in patients at risk of infection[58].
Polytetrafluoroethylene (PTFE) patch (Gore-Tex & Gore-Dualmesh, W.L. Gore & Associates, Inc, Flagstaff, AZ, USA) is another commonly used option that has the advantage of preventing fluid and air movement across the reconstructed chest wall[56].
When a rigid reconstruction is necessary, a couple techniques can be utilized. One is the methyl methacrylate sandwich technique in which methyl methacrylate (bone cement) is sandwiched between two layers of Marlex mesh. This is then allowed to cool and harden as it is conformed to the shape/contour of the defect, which is then secured to the chest wall with Prolene sutures[57,59].
Other options for rigid reconstructions include osteosththesis systems such as Stratos (MedXpert, Heitersheim, Germany)[60] and Synthes Titanium Sternal Fixation System (Synthes, Solothurn, Switzerland) as well as titanium[61,62].
After the skeletal structure is reconstructed, one needs to assess if there is adequate soft tissue coverage. In situations where soft tissue coverage is needed, local muscle flaps are utilized as the tissue of choice. Local muscle flaps are generally safe, require less operative time when compared to free flaps, can be taken as muscle only or with an overlying skin paddle, and can be combined to create larger flaps when needed.
Muscles that can be utilized locally include: latissimus dorsi – which is good for most of anterior, lateral, and posterior coverage, pectoralis major – which is useful for sternal defects, serratus anterior – which is useful for intrathoracic coverage, and rectus abdominis -which is good for sternal and anterior coverage. Omental flaps are reserved for partial-thickness coverage or as an alternative in situations where local muscle flaps have failed or are not available[56].

Summary

  • Primary chest wall tumors are uncommon and incredibly varied
  • Particularly for benign tumors, disease is often identified incidentally
  • Imaging alone is not typically a reliable diagnostic method due to significant overlap in differentials; biopsy to confirm diagnosis is often required
  • Surgical resection is the mainstay for many chest wall tumors, efficacy of radiation and chemotherapy are varied and depend on histology
  • If tumors are chemo-sensitive, preoperative chemotherapy should be administered to reduce tumor burden
  • Metastatic disease is difficult to treat and has poor outcomes
  • Research into novel, alternative treatment methodologies have uncovered some strategies, such as targeted therapy, to be efficacious. There is little data to support the use of immunotherapy in these tumors.

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