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Soft Tissue Sarcoma. Orthopedic oncological surgery covers  the treatment of musculoskeletal injuries, including benign and malignant bone neoplasms, pseudotumor lesions and benign and malignant neoplasms of soft tissues.

Soft Tissue Sarcoma

    Soft tissue sarcoma is a malignant neoplasm, derived from the  mesenchyme  that occurs in soft tissues, such as muscles, fascia, tendons, etc. It is not called carcinoma because this name refers to malignant neoplasms that have their embryonic origin in the ectoderm, such as the skin, nerves, viscera or glands.

            This neoplasm arises from a mesenchymal cell that undergoes mutation and begins to have an anomalous cellular reproduction, producing polymorphic cells, with varying sizes, hyperchromatic, resulting in an atypical tissue, therefore malignant.

            Their nomenclature is given by their similarity to the tissue they try to reproduce. Thus, for example, when atypical neoformed tissue presents an appearance similar to fatty tissue, it is called liposarcoma.

Etiology:

           Most soft tissue sarcomas do not have a defined etiology, but some risk factors are well described, such as previous radiotherapy, lymphedema, Li-Fraumeni syndrome, type I neurofibromatosis, individual genetic propensity and HIV infection.

Incidence:

            It is a rare tumor, as the group of all these sarcomas comprises approximately 12 percent of pediatric neoplasms, with the “small round cell” pattern predominating, such as embryonal rhabdomyosarcoma and primitive peripheral neuroectodermal tumor, and only one percent of all adult malignant tumors  1,2 , Table 1.

            It is estimated that there are 12 thousand new cases of soft tissue sarcomas per year in the USA, causing around 4700 deaths  1 .

            About 60 percent of soft tissue sarcomas arise in the limbs, with the majority of them occurring in the thigh. It also occurs in the chest wall and retroperitoneum. In order of frequency, soft tissue sarcomas appear in the lower limb (46%), back (18%), upper limb (13%), retroperitoneum (13%) and head and neck (9%) 1 .

Quadro 1: Sarcomas de tecidos moles mais frequentes na população adulta e pediátrica
Table 1: Most common soft tissue sarcomas in the adult and pediatric population

Classification:

           The World Health Organization (WHO) classifies soft tissue sarcoma according to the histological subtype that the neoplasm resembles, such as liposarcoma, synovial sarcoma, rhabdomyosarcoma, etc. 1

            In some cases, the histology is uncertain and the morphological aspect is used to classify them as alveolar sarcoma or clear cell sarcoma.

          The most common soft tissue sarcomas in adults are: undifferentiated, liposarcoma, synovial sarcoma, leiomyosarcoma and malignant tumor of the peripheral nerve sheath, which is included in this chapter, despite originating in the ectoderm, as it presents biological behavior , treatment and prognosis similar to soft tissue sarcomas  1,2 .

            Histological grade is also used to classify soft tissue sarcomas, being classically divided into  Grade 1 ,  well differentiated  with a low degree of histological malignancy;  Grade 2 ,  moderately differentiated  and  Grade 3 ,  poorly differentiated  with a high degree of malignancy  1 .

 Clinical condition:

           The initial clinical picture is palpable tumor bulging, often painless, with progressive growth that can reach considerable size, especially in the thigh.

            Some patients may eventually experience pain and paresthesia due to the compressive effect of the tumor. They are clinically eutrophic in most cases, with fever or weight loss being exceptional symptoms.

          Soft tissue sarcomas tend to grow between adjacent muscles, pushing and compressing the surrounding structures, rarely extending beyond the anatomical compartments. Growth speed varies between histological subtypes.

          There are no absolute clinical criteria to differentiate benign from malignant soft tissue tumors. However, all deep tumors, that is, below the plane of the muscular fascia, and superficial tumors greater than 5 cm, have a high probability of being malignant  2 .

Staging:

           At the time of diagnosis, soft tissue sarcoma rarely metastasizes, not exceeding 10 percent of cases. This occurs more frequently in large volume tumors, deep to the muscular fascia and of high grade  2 .

            The dissemination pattern for most sarcomas is hematogenous and the main site of metastasis is the lung. For this reason, all patients with soft tissue sarcoma must undergo chest staging. Chest tomography to search for lung metastasis should always be indicated, especially for high-risk patients, such as superficial lesions larger than 5 cm, deep tumors and those with a high degree of malignancy.

            Regional lymph nodes are the site of metastases in 2.6% of cases, however, in some histological subtypes these may be more frequent and should be investigated, such as rhabdomyosarcoma, synovial sarcoma, epithelioid sarcoma, clear cell sarcoma and angiosarcoma  2 .

            Tomography of the abdomen and pelvis is recommended, especially in the staging of round cell soft tissue sarcoma and myxoid liposarcoma, due to the high rate of extrapulmonary metastasis to the abdomen and retroperitoneum. In the case of angiosarcoma, evaluation of the central nervous system, through skull tomography, is necessary due to the propensity for metastasis to the brain.

 Imaging exams:

 a)  Radiography:

            Radiography is the cheapest and most accessible imaging test. It can be used as the first line of tumor evaluation, to differentiate a tumor of skeletal origin from a soft tissue sarcoma. Furthermore, it may show calcifications inside.

b) Magnetic resonance imaging:

          Magnetic resonance imaging is still the test of choice to evaluate soft tissue sarcomas when there are no metallic elements, such as an orthopedic prosthesis. It can detail the limits of the tumor and its relationship with neighboring structures. The use of contrast can also differentiate solid lesions from lesions filled with liquid, and the examination using contrast should be requested.

c) Tomography:

          Tomography is the exam of choice in retroperitoneal tumors and in the search for pulmonary metastasis, as resonance is not adequate due to respiratory movement and intestinal peristalsis. In the study of MTS of extremities, resonance is superior in delineating neoplastic extension  2 .

d) Pet-Cet:

          Fluorine deoxyglucose positron emission tomography (FDG-PET/CT) allows, with high sensitivity, to differentiate high-grade soft tissue sarcoma from benign soft tissue tumors. However, it loses value in differentiating between low-grade and low-grade tumors. intermediaries  2 .

            FDG-PET/CET should not be used routinely in the initial evaluation of a patient with tissue tumor, however its use is indicated in determining prognosis and response to chemotherapy treatment  , 3 .

            The  standaruptakevalue  (SUV) is a quantification of fluorine-labeled glucose consumed by the tumor and demonstrates tumor metabolism. Soft tissue sarcoma with SUV equal to or greater than 6, which after chemotherapy shows a reduction in this value of less than 40 percent, presents a higher risk of systemic recurrence of the disease  2 .

e) Scintigraphy:

            Bone scintigraphy is not always performed in the initial staging of soft tissue sarcoma, as bone metastases in adults are infrequent in the initial stage of the disease. The exception is round cell tumors and myxoid liposarcoma, but skeletal mapping can be false negative and evaluation using magnetic resonance imaging is recommended  2 .  

Biopsy:

           Biopsy is indicated for the histological diagnosis of MTS, since imaging tests do not present characteristics suggestive of the histological subtype, as we can infer in some bone neoplasms, such as osteosarcoma.

            A biopsy is not always necessary for treatment, as the treatment of MTS is still primarily surgical and, in some cases, the biopsy can be replaced by excisional resection or also called excisional biopsy.

            Superficial tumors, above the muscular fascia, smaller than 5 cm, have a low probability of being malignant. In these cases, they can be resected without histological diagnosis if they are subject to oncological surgery  (wide resection with an oncological margin, without compromising surrounding noble structures) , as this would be the correct treatment in the event that we are dealing with a high-quality soft tissue sarcoma. degree.

            The biopsy must be performed by the surgeon who will carry out the definitive treatment or be guided by him. The biopsy path must be in line with the incision that will be used for resection and this entire biopsy path must be removed en bloc, along with the tumor.

            Incisional biopsy, performed through a surgical incision, exposing part of the tumor, was the most used for the diagnosis of soft tissue sarcoma. Currently, percutaneous biopsies have gained ground with the development of appropriate needles, such as the Trucut®, and imaging methods such as ultrasound and tomography to guide them.

Pathology:

            The pathologist must always be present to perform the frozen section examination, in order to confirm and ensure that the material collected is representative of the lesion, avoiding the need to repeat the procedure. The definitive histological result must await paraffin histology and possibly immunohistochemistry.

            Percutaneous needle biopsy, performed with these precautions, generally makes it possible to differentiate malignant tumors from benign ones and experienced pathologists are able to correctly determine the histological grade of the tumors in 97.6 and 86.3 percent respectively, in addition to this technique causing less local dissemination of the tumor. injury during the procedure  3 .

Soft tissue sarcoma – Treatment:

           The treatment of soft tissue tumors is generally surgical, however, as with most neoplasms, monitoring of cancer patients must always be multidisciplinary.

            From diagnosis to staging and treatment, a team of several professionals interacts in managing the case, such as the orthopedist who will perform the  oncological surgery , the pathologist, the radiologist, the clinical oncologist, the radiotherapist, the psychologist, the social worker, etc.

          The objective of treatment is to preserve the patient’s life, avoiding local recurrence, maximizing the function of the affected limb and minimizing treatment morbidity.

Chemotherapy:

          Soft tissue sarcomas, in the pediatric population, respond to systemic chemotherapy by presenting a greater response to drugs, providing an improvement in survival, as the child is able to withstand the doses of chemotherapy necessary to control the disease, unlike adults.

            In children, the most common soft tissue sarcomas are rhabdomyosarcoma, the extraosseous form of osteosarcoma, and the extraosseous form of Ewing’s sarcoma. All of these with neoadjuvant and adjuvant chemotherapy protocols.

            In the rare cases of these neoplasms occurring in adults, the pediatric chemotherapy protocol is chosen, at doses supported for adults and their possible comorbidities.

          In adult soft tissue sarcomas, there is great controversy regarding the use of chemotherapy. The meta-analysis published in 1997 by the  Sarcoma Meta-analysiscollaboration  showed that the use of doxorubicin in these patients increased the time free from local recurrence and distant metastasis, but there was no statistically significant benefit in the patients’ overall survival  3 .

            A new updated meta-analysis was published in 2008 demonstrating that the use of doxorubicin associated with ifosfamide promoted an improvement in patient survival  3 . However, chemotherapy is extremely toxic, especially in the adult population where the presence of clinical comorbidities can make effective treatment unfeasible. The current recommendation is to individualize each case, remembering that systemic treatment does not correct an inadequate surgical resection.

            In general, adult MTS are poor responders to chemotherapy. Treatment, therefore, relies on surgical resection.

Oncological surgery:

 Soft tissue sarcoma resection surgery must be performed with wide margins, so that the entire tumor is removed en bloc and covered by healthy tissue, aiming to ensure that there are no residual neoplastic cells after resection.

          Soft tissue sarcomas have a surrounding pseudocapsule. This structure is represented by an inflammatory process produced by tumor aggression and is not always a sufficient barrier for neoplastic cells, which permeate the surrounding tissues. Adjuvant radiotherapy may be indicated to act on the margins when they need to be small, due to the need to preserve noble structures, such as vessels and nerves.

            Tumor resection through the pseudocapsule can leave microscopic neoplastic tissue in the patient and may be a risk factor for local recurrence and worse prognosis.

          Soft tissue sarcomas tend to grow by expanding and pushing against surrounding tissue, but rarely by infiltrating it. Therefore, invasion of bone or adjacent muscle tissues is uncommon.

            Most of the time when the tumor approaches the bone, it is possible to dissect it by removing the periosteum that surrounds the bone in question, along with the tumor. This deperiostization associated with radiotherapy, which is generally used as adjuvant, increases the risk of fracture, especially in the femur  4 .

Recurrence:

          The thickness of the wide margins around the tumor is questionable, with 1 cm being recommended, but this rarely happens homogeneously throughout its circumference.

            To preserve noble tissues, such as large nerves or vessels, the surgeon eventually reduces this margin to avoid resection of such a structure, which can put both the patient and the limb itself at risk in order to preserve the best function.

            On the other hand, anatomical tissue planes represent different barriers to the tumor, such as muscular fascia where 1 to 2 millimeter margins may be adequate for safe resection.

            Other tissues such as fat or muscle belly require wider margins.

          Large nerves can be preserved by dissecting and removing the outer nerve sheath as a margin, since soft tissue sarcomas do not usually infiltrate nerves. When the tumor surrounds the nerve, there is greater technical difficulty and this nerve may need to be sectioned and reconstructed with microsurgical sutures.

          Nerve grafts for reconstruction are rarely useful in the lower limbs of adults, especially in a site that will need to be irradiated. Children, however, may have better results.

            Ablative surgery is generally avoided, as even limited function of the lower limb may be viable, even in cases requiring complete resection of the sciatic nerve.

Radiotherapy:

          The use of  adjuvant radiotherapy  promotes the destruction of tumor cells around the main lesion. When associated with limb-preserving surgical resection, it promotes increased local control, minimizing recurrence to 10 to 15%  4 . However, the association of this therapeutic modality does not increase overall survival.

          Radiotherapy is indicated for almost all cases of soft tissue sarcoma.

            Exclusive surgical resection may be sufficient for cases of low-grade superficial tumors or small-volume, totally intramuscular tumors, as long as wide margins are guaranteed in the  oncological surgery  performed.

          With the improvement in local control, radiotherapy as an adjuvant in soft tissue sarcomas has reduced the rate of amputation of extremities from 50% in the 1970s to 1% today, without compromising survival  5 .

          The indication for amputation in the presence of MTS may be necessary in excessively extensive tumors, such that the residual limb has no function.

            An example is the need to resect a main nerve trunk, such as the brachial plexus, with the impossibility of obtaining wide margins. In this case, the loss of sensation results in a non-viable remaining limb.

             The involvement of large vessels by the tumor was already an indication for amputation in the past, however with the vascular reconstruction technique it became possible to resect the tumor en bloc with the vessels and reconstruct them with a vascular graft, allowing a viable limb.

Surgical margins:

          The main variable in local control of the disease is the surgical margins of tumor resection  5 .

            The presence of margins coinciding with the tumor increases the risk of local recurrence and recurrence increases the risk of distant metastasis, which can lead to shorter survival.

          The presence of compromised margins, however, does not represent certainty of local recurrence, since only 30 percent of cases undergoing incomplete resection and undergoing adjuvant radiotherapy suffered recurrence.

            Wide margins, on the other hand, are also no guarantee of local control, since, even when associated with radiotherapy, recurrence in this situation is around 5 to 10 percent.

          The presence of positive margins in the resection may require a new approach to the surgical bed, seeking to expand the previously obtained margins.

            This new approach will depend on the analysis of which anatomical structure will need to be resected for this expansion.

            In reference centers for oncological surgery, the presence of compromised margins is usually related to a possible residual tumor in large nerve bundles that would require amputation for resection. If this is the case, a higher dose of radiotherapy (66-68 Gy) can be used or amputation can be chosen as a last resort.

Benign soft tissue tumors:

            Benign soft tissue tumors are one hundred times more common than malignant tumors. Among them, subcutaneous lipoma is among the most diagnosed in clinical practice. 

            These lesions do not cause pain and are diagnosed when they are superficial and protrude into the skin or when they are deep and reach a large volume. The exception is schwannoma that arises from a peripheral nerve and can present pain, paresthesia and, less frequently, motor changes.

            Despite being benign, as these tumors grow, compression of adjacent structures may occur and only then will symptoms appear.

            The treatment of most benign soft tissue tumors depends on the symptoms they eventually produce. As most of them are asymptomatic, surgical resection is indicated when they increase in size, causing discomfort or aesthetic changes.

            In superficial, small-sized, asymptomatic tumors without signs suggestive of malignancy on imaging exams, it is possible to choose to observe the clinical evolution.

            Desmoid tumor, despite being benign, is a locally aggressive soft tissue neoplasm, which produces symptoms by attacking neighboring tissues.

            Unlike most benign soft tissue neoplasms, desmoid resection should be indicated with wide margins, an oncological surgery similar to the treatment for malignant tumors.

            Desmoid tumor is highly recurrent, even after adequate resection. In some cases, the patient may require amputation of the limb due to numerous recurrences, or when experiencing intractable pain or dysfunction and a new resection becomes impossible.

Discussion:

  • One consideration is to perform a  prior biopsy  or  excisional biopsy  ( biopsy resection ) in cases of small, superficial soft tissue sarcomas, or in places where oncological surgery is possible, with wide margins around the entire circumference of the tumor?
  • Another consideration is regarding adult soft tissue sarcomas, in which neoadjuvant chemotherapy does not improve locally nor interfere with survival. There is controversy regarding the use of neoadjuvant radiotherapy:
  1. A) Radiotherapy + surgery + radiotherapy or
  2. B) Surgery + radiotherapy?

Table 2 below summarizes parameters that we must consider.

Quadro 2: Os tumores de tecidos moles são raros, representam 5 % das neoplasias, ocorrendo em todas as idades e localizações, sendo 50 % nos membros inferiores. Representam a quinta neoplasia maligna na infância e sua disseminação é hematogênica. A biópsia é apenas uma amostra da lesão!
Table 2: Soft tissue tumors are rare, representing 5% of neoplasms, occurring at all ages and locations, 50% in the lower limbs. They represent the fifth malignant neoplasm in childhood and their dissemination is hematogenous. The biopsy is just a sample of the lesion!

 To define  oncological surgery , we must analyze the relationship between the tumor and the skin, aponeuroses, vessels and nerves. It is also necessary to define whether or not a prior biopsy is necessary or the possibility of performing a biopsy resection, excising the lesion in a single step, as long as it is possible to operate on it with an oncological margin without compromising function.

            For this purpose, imaging studies will define this possibility in tumors that are sufficiently distant from noble structures.

            The possibility of resection without biopsy is advantageous as it facilitates surgery and avoids the need to repeat biopsies with inappropriate tumor samples and review surgeries performed with inadequate diagnoses. 

            Many soft tissue sarcomas are initially operated on as benign tumors ( including after an anatomopathological study of the biopsy, which is just a sample of the lesion ), but in reality they were malignant neoplasms, which were later diagnosed with a complete study of the surgical material that was resected. .

            We will discuss the definition of treatment by discussing the following cases:

Case 1 – Soft tissue tumor of the shoulder , figure 1.

            What surgical approach will be recommended? Previous biopsy? Surgical resection only? In this case, a biopsy was performed prior to surgery.

            The first diagnosis of this biopsy sample was indeterminate spindle cell sarcoma.

            The pathology review carried out by other pathologists from Brazil and the USA reported: “…  unclassified spindle cell sarcoma, of intermediate grade, with some possibility that it could be dedifferentiated liposarcoma  …”

            Oncological surgery needs to be performed with a safety margin. This case must be operated on as a malignant neoplasm, as it is a heterogeneous lesion.

Figura 1: Neste exemplo era possível que tivéssemos realizado de imediato a ressecção biópsia com margem oncológica, removendo a neoplasia com bom resultado estético e funcional, pois a biópsia não foi suficiente para definir o diagnóstico nem para sugerir terapia adjuvante.
Figure 1: In this example, it was possible that we would have immediately performed the biopsy resection with oncological margin, removing the neoplasm with good aesthetic and functional results, as the biopsy was not sufficient to define the diagnosis nor to suggest adjuvant therapy.

Case 2 – High-grade soft tissue sarcoma of the lower limb , figures 2 to 4.

What is the treatment for this injury in the anterior thigh region?

Figura 2: Neoplasia sólida, de grande volume, profunda, heterogênea, intensa captação de contraste, intimamente relacionada aos feixes vasculares e nervosos e ainda em contato com mais da metade circunferencial do fêmur?
Figure 2: Solid, large-volume, deep, heterogeneous neoplasm, intense contrast uptake, closely related to the vascular and nervous bundles and still in contact with more than the circumferential half of the femur?

 This lesion is certainly a malignant soft tissue neoplasm.

            Even if the biopsy infers that it is a benign lesion, the surgical approach must necessarily be performed with the technique indicated for malignant neoplasms, an oncological surgery, due to the heterogeneity of the lesion.

            The biopsy is just a sample of the tumor and can obtain material from a benign area and not help at all. The procedure in these cases must be performed by an orthopedist specialized in oncosurgery, to perform the biopsy during the future surgery. A biopsy was performed, figure 3.

Figura 3: Sarcoma indiferenciado de alto grau. … ?
Figure 3: High-grade undifferentiated sarcoma. …?

This type of lesion should be resected with as much margin as possible. In this case we know that the limits will be tight.

            However, there is no indication for ablative surgery, since amputation does not improve survival.

  • Neoadjuvant chemotherapy ? Low probability of response. It delays surgery and, as the injury increases, the possibility of preserving the limb decreases.
  • Neoadjuvant radiotherapy ? Intense fibrosis with greater difficulty releasing vessels and nerves and complications with the surgical wound.

            As both neoadjuvant chemotherapy and/or radiotherapy do not change the survival prognosis, we do not recommend neoadjuvant treatment in these cases and perform the surgery first, using a dual approach.

            First medial access, for safe isolation of the vascular and nerve bundle, medial release of the periosteum and later lateral access, complementing local control with adjuvant radiotherapy, figure 4.

Figura 4: Para uma adequada ressecção com segurança realizamos dois acessos cirúrgicos. Primeiramente o acesso medial da coxa, para isolamento do feixe femoral vascular e nervoso e descolamento periosteal medial, complementando com a via lateral, para a dissecção e descolamento periosteal lateral e anterior.
Figure 4: For an adequate and safe resection, we perform two surgical approaches. Firstly, the medial approach to the thigh, for isolation of the femoral vascular and nerve bundle and medial periosteal detachment, complementing with the lateral approach, for dissection and lateral and anterior periosteal detachment.

 Case 3 – High-grade STM of the popliteal cavity , figures 5 to 11 and video 1.

             What is the recommended approach for this case?

Figura 5: Tumor do cavo poplíteo, de evolução rápida, com íntima relação com o feixe vascular, envolvendo, dividindo e afastando os ramos do nervo ciático. Qual será o diagnóstico?
Figure 5: Tumor of the popliteal cavus, of rapid evolution, with an intimate relationship with the vascular bundle, involving, dividing and separating the branches of the sciatic nerve. What will be the diagnosis?

  The choice of biopsy route must be determined by  oncology orthopedics . The point of greatest heterogeneity should be chosen, outside the area of ​​possible necrosis and along the path of the future surgical incision.

Figura 6: A Ressonância revela neoplasia profunda, de grande volume, heterogênea e com intensa captação de contraste. Todas as características clínicas e de imagem indicam tratar-se de lesão agressiva e de natureza maligna. O procedimento cirúrgico deverá ser de ressecção com a maior margem possível, independentemente do que revelar a biópsia. Esta pode ser realizada, para atender aspectos legais e acadêmicos, mas a cirurgia deverá ser sempre uma cirurgia oncológica.
Figure 6: The MRI reveals a deep, large-volume, heterogeneous neoplasm with intense contrast uptake. All clinical and imaging characteristics indicate that it is an aggressive and malignant lesion. The surgical procedure should involve resection with the largest possible margin, regardless of what the biopsy reveals. This can be performed to meet legal and academic aspects, but the surgery must always be an oncological surgery.
Figura 7: Se optarmos por realizar a biópsia, ela deverá estar no trajeto da futura ressecção cirúrgica e o seu trajeto deverá ser removido, juntamente com a lesão. Neste caso a biópsia foi realizada no trajeto medial, com agulha fina e auxílio da ultrassonografia, realizada no ponto de maior heterogeneidade, visando objetivar o diagnóstico preciso.
Figure 7: If we choose to perform the biopsy, it must be in the path of the future surgical resection and its path must be removed, along with the lesion. In this case, the biopsy was performed in the medial path, with a fine needle and the aid of ultrasound, carried out at the point of greatest heterogeneity, aiming to obtain an accurate diagnosis.
Figura 8: Incisão ampla póstero medial e curvando-se sobre a prega poplítea, com exérese do trajeto da biópsia. Operamos sem garrotear o membro, realizando cuidadosa hemostasia e expondo os ramos do nervo ciático deslocados pelo tumor.
Figure 8: Wide posteromedial incision curving over the popliteal fold, with excision of the biopsy path. We operated without garroting the limb, performing careful hemostasis and exposing the branches of the sciatic nerve displaced by the tumor.
Figura 9: Liberação cuidadosa dos ramos nervosos, o que poderia não ser viável com a realização de radioterapia neoadjuvante.
Figure 9: Careful release of the nerve branches, which might not be feasible with neoadjuvant radiotherapy.
Figura 10: Cirurgia oncológica com total preservação da função. Tumor ressecado com margens exíguas. Realizamos radioterapia adjuvante.
Figure 10: Oncological surgery with total preservation of function. Resected tumor with small margins. We perform adjuvant radiotherapy.
Figura 11: Função normal, após a cirurgia oncológica, possível neste paciente e radioterapia pós-operatória (adjuvante).
Figure 11: Normal function, after cancer surgery, possible in this patient and postoperative radiotherapy (adjuvant).

      In these three cases presented, we verified that a biopsy was performed. Surgical management, in all of them, was performed without neoadjuvant therapy.

            Therefore, in the majority of cases of neoplasms in which the clinic and imaging tests suggest malignancy and which are subject to resection with an oncological margin, preserving both aesthetics and function, we prefer to opt for a frozen section biopsy, performed during surgery. , with the presence of the pathologist, who confirmed that it was a malignant neoplasm and we performed the biopsy resection ( excisional biopsy )  first, as was performed in case 4, described below.

Case 4 – TMS of the thigh with metastasis to the sternum bone , figures 12 to 20.

            Patient seen in 1997, with pain and a rapidly growing tumor on the medial aspect of the right thigh, affecting the soft tissues.

            The best imaging test to evaluate soft tissue injuries is magnetic resonance imaging (MRI). This examination revealed the presence of a solid lesion measuring approximately 5.5 cm by 7.0 cm, within the adductor muscles of the thigh, figure 12.

Figura 12: a- Rm axial T1, com lesão de baixo sinal, heterogênea, junto ao plano da musculatura adutora da coxa. b- Rm axial, captação de contraste, heterogênea, vascularizada e com aparente delimitação por pseudocapsula. c- RM axial T1 com saturação de gordura, evidencia o vaso nutrício da lesão. d- Rm sagital com captação de contraste e evidente vascularização.
Figure 12: a- Axial T1 MRI, with low-signal, heterogeneous lesion, close to the plane of the adductor muscles of the thigh. b- Axial MRI, contrast uptake, heterogeneous, vascularized and with apparent delimitation by a pseudocapsule. c- Axial T1 MRI with fat saturation, showing the nutrient vessel of the lesion. d- Sagittal MRI with contrast uptake and evident vascularization.

   With this clinical and imaging picture we have to answer the following question:

               1- Perform a biopsy, or biopsy resection, since in this case it is possible to excise the lesion with an oncological margin, without changing its function?

               2- If the biopsy result reports a lesion without atypia, fibroxanthoma for example, would the surgical resection be changed? Would a resection be more economical? Even with the characteristics of these images, since the biopsy is just a small sample of the lesion?

            In our guidance, surgical management cannot change. Resection must be performed with an oncological margin in this case. The biopsy must be performed with the purpose of guiding the indication or not of neoadjuvant therapy, if it is confirmed that it is a malignant neoplasm that responds, such as embryonal rhabdomyosarcoma, in the child.

                3- What type of biopsy to perform? With a tru-cut needle? Incisional? With frozen section diagnosis and oncological surgery at the same time?

Guidance:

            It is best to always perform a biopsy of soft tissue lesions with a tru-cut needle, guided by ultrasound and pathological frozen section anatomy, to validate the material collected.

            The resection procedure will depend on each case and can be performed in cases where the oncological margin is possible, without functional loss.

            Otherwise, you must wait for the results of the anatomopathological examination in paraffin and even immunohistochemistry, when necessary.

            In this case, the diagnosis was high-grade sarcoma, on frozen section and as resection with a margin was possible, the surgery was performed using the same anesthetic procedure, figure 14, where we can observe the anaplastic histological aspect of this tumor.

            Adjuvant radiotherapy was initiated in this surgery, with the placement of catheters for brachytherapy, which was still a highly recommended procedure at that time.

            These catheters are passed through a needle with sufficient tubular diameter for subsequent placement of the iridium wires. The catheters are passed and fixed with a plastic clip, figures 14  a  and  b .

            Subsequently, the catheters are removed and supplemented with external radiotherapy. Figure 14  c  shows the local appearance after adjuvant radiotherapy treatment. 

Figura 14: a- Cateteres para a braquiterapia, posicionados no leito operatório onde se encontrava o tecido tumoral. b- Pele suturada e cateteres posicionados paralelamente, distantes 1,3 cm entre si e fixados por presilha plástica. c- Aspecto da cicatrização da ferida operatória, após a cirurgia e o tratamento radioterápico adjuvante.
Figure 14: a- Catheters for brachytherapy, positioned in the operating bed where the tumor tissue was located. b- Skin sutured and catheters positioned parallel, 1.3 cm apart and fixed with a plastic clip. c- Aspect of surgical wound healing after surgery and adjuvant radiotherapy treatment.

The case was discussed in a multidisciplinary team that chose not to perform adjuvant chemotherapy, as the relationship between possible benefits and side effects was not favorable, taking into account the fact that this chemotherapy does not increase overall survival, Lancet 1997 20 .

Evolution:

            In the control evaluation, after four years and three months, the patient reported bulging and pain in the sternum. The x-ray highlights the presence of a lesion in the distal portion of the sternum. Figures 15  a  and  b . Bone scintigraphy performed for skeletal staging revealed a single lesion, with intense uptake in this region.

Figura 15: a- Radiografia de tórax, em perfil, evidencia lesão expansiva no esterno. b- A cintilografia apresenta intensa captação na metade inferior do esterno.
Figure 15: a- Chest X-ray, in profile, shows an expansive lesion in the sternum. b- The scintigraphy shows intense uptake in the lower half of the sternum.

Figure 15 :  a – Chest X-ray, in profile, shows an expansive lesion in the sternum. b- The scintigraphy shows intense uptake in the lower half of the sternum.

            The MRI study showed the presence of a solid, heterogeneous lesion, with cortical erosion and destruction of the bone tissue of the sternum, with intense contrast uptake, characterizing an aggressive tumor, in a patient with a history of high-grade pleomorphic sarcoma, figures 16  a  and  b .

Figura 16: a- Ressonância magnética sagital T1, evidenciando a erosão e abaulamento da região. b- Ressonância magnética sagital T1 com contraste mostrando uma lesão heterogenia de alto e baixo sinal.
Figure 16: a- T1 sagittal magnetic resonance imaging, showing erosion and bulging of the region. b- Sagittal T1 magnetic resonance imaging with contrast showing a heterogeneous lesion of high and low signal.

With this patient’s past clinical history and these images, we asked the following questions:

1- Perform a biopsy of this lesion?

2- What should we do if we receive a diagnosis of a benign tumor, such as fibrohistiocytoma for example? Or an aneurysmal bone cyst? What would be the surgical approach given the history of this patient who had already undergone surgery for high-grade sarcoma? Curettage? Biopsy repeats?

              We must remember that the biopsy is just a sample, therefore it is questionable to repeat biopsies until we obtain a diagnosis of a malignant lesion for this patient.

              We must assume the need for resection with a margin of this lesion, since oncological surgery is indicated and resection of the sternum does not cause aesthetic or functional damage.

              We still have to consider that neoadjuvant chemotherapy would not add any advantage to the case nor would prior radiotherapy change the need for resection of the compromised area.

Conduct:

            If we are going to resect the sternum, what access route should we use? What is the incision that allows the widest and most aesthetic resection?

            We chose the infra-mammary, horizontal access route, figure 18.

Figura 17: a- Radiografia evidenciando a lesão. b- Incisão realizada na região infra mamária. c- Ressecção do esterno. d- Imagem do local onde foi ressecado o esterno.
Figure 17: a- Radiograph showing the injury. b- Incision made in the infra-mammary region. c- Resection of the sternum. d- Image of the place where the sternum was resected.

Figure 17 :   a – Radiograph showing the injury.   b – Incision made in the infra-mammary region.  c – Resection of the sternum.  d – Image of the place where the sternum was resected.

We can observe the good hemostasis achieved, which must be careful to eliminate the need for drain placement and allow for better aesthetics.

4- How to reconstruct this resection? In this case, there is no need for a sternum prosthesis or the placement of a rigid cement plate, which, with respiratory mobility, can cause deformity and pain. No need for rigid structure, no sagging chest occurs

The aesthetic appearance of the scar can be observed three years and five months after the sternum operation, figure 18  d .

Figura 18: a- Visualização da peça ressecada. b- Radiografia da peça evidenciando a lesão. c- Reconstrução da cavidade com Tela de Marlex. d- Aspecto estético da cicatriz operatória, após 3 anos.
Figure 18: a- Visualization of the dried piece. b- Radiograph of the piece showing the injury. c- Reconstruction of the cavity with Marlex Mesh. d- Aesthetic appearance of the surgical scar, after 3 years.

 This case was discussed again in a multidisciplinary meeting.

            Postoperative radiotherapy was not indicated after the type of en bloc resection in this case, in this location.

            The literature review at the time did not indicate the benefit of chemotherapy versus toxicity and the evidence of overall survival was equal, Cancer 2008 10 . The patient did not receive adjuvant treatment.

            After seven years and eight months of treatment for the thigh tumor and another four years and two months of resection of the sternum, the patient presented metastasis in the thoracic vertebra, T11, figure 19.

Figura 19: a- Pet-Cet. com imagem evidenciando a lesão na vértebra torácica T11. b- Tomografia com a lesão na vértebra torácica T11.
Figure 19: a- Pet-Cet. with an image showing the injury to the T11 thoracic vertebra. b- Tomography with the lesion in the T11 thoracic vertebra.
The patient underwent adjuvant palliative chemotherapy and after two years the lesion spread, dying due to lung metastases, figure 20.
Figura 20: Tomografia de tórax, com inúmeras metástases, em ambos os pulmões, em 2011, quatorze anos após a primeira cirurgia, sendo doze deles em boa saúde e sem desconfortos.
Figure 20: Chest tomography, with numerous metastases, in both lungs, in 2011, fourteen years after the first surgery, twelve of which were in good health and without discomfort.

Video 1 : Walking with full support on the operated limb, single-leg load with good balance, good hip and knee flexion function with load. Excellent functional result for a total internal hemipelvectomy, without reconstruction, 12 years and three months after surgery.

Comments:

            A randomized study in 2012 of adjuvant chemotherapy with doxorubicin and ifosfamide did not show any benefit in relapse-free survival or overall survival, Lancet 28 .

In the literature in 2013, UpToDate 29             still reported the benefits of neoadjuvant and adjuvant chemotherapy as uncertain  .

            Chemotherapy for soft tissue sarcoma still needs to evolve a lot. It is necessary to individualize drug therapy for each particular histology.

            It is not possible to place all histological diagnoses of “Soft Tissue Sarcoma” in the same package and treat with the same protocol and, on top of that, carry out “scientific work” with prognostic conclusions, without particularizing each diagnosis.

            The vast majority of MTS treatments are not individualized. We know that chemotherapy for Ewing sarcoma is different from chemotherapy for osteosarcoma, which is why we have favorable results in the treatment of these conditions.

            Therefore, the large pool of sarcomas cannot be placed in the same treatment protocol, just as work on the results of treatment for this pool of tumors does not allow conclusions.

            Cases that respond are mixed with the majority that do not respond and the oncologist is left without parameters.

            In adults, toxicity is further aggravated by comorbidities and the cost/benefit ratio to date has been unfavorable.

            Surgery is still the primary treatment for soft tissue sarcomas.

            Radiotherapy has its role in controlling high-grade sarcomas, but it does not rescue an inadequate resection. Neoadjuvant radiotherapy has fewer complications for the surgical wound than brachytherapy. Adjuvant radiotherapy is recommended in practically all cases, with occasional exceptions being made for superficial lesions, resectable tumors smaller than five centimeters and lesions of low histological grade.

______________________________

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Author: Prof. Dr. Pedro Péricles Ribeiro Baptista

 Orthopedic Oncosurgery at the Dr. Arnaldo Vieira de Carvalho Cancer Institute

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