A clinical finding of groin swelling or palpable lump within the inguinal region may generate multiple differential diagnoses which need to be cleverly examined in order to recognize the correct one among a wide range of possibilities. Inguinal or crural hernias, reactive or neoplastic lymphadenopathies, hydrocele or varicocele are the most likely entities responsible for the arising of a groin or scrotal mass.

Patient medical history and a careful clinical examination may address the physician toward the most probable diagnosis, although misdiagnosing sometimes occurs leading to subsequent inappropriate treatments [102, 103].

Primary tumors, in fact, may affect the groin, but given their rarity (incidental tumors may be discovered in less than 0.1% patients treated for inguinal hernia repair) and the lack of clinical peculiar findings or laboratory abnormalities, identifying them usually represents a real challenge also for expert clinicians [71].

As already discussed and largely reported, the majority of STSs arising within the inguinal region are considered to originate from the spermatic cord [103, 105–108]. Interestingly, to date an increasing number of cases regarding primary and recurrent retroperitoneal sarcoma herniating through the deep inguinal ring and mimicking an inguinal hernia or a generic groin swelling have been recently described. According to this particular disease presentation, the clinical aspects and the pattern of symptoms tend to be more specific, showing during patient physical examination a firm and irreducible solid mass in the context of the inguinal canal or just below the inguinal ligament. The retroperitoneal cavity, in fact, communicates with the pelvic and the inguinal region following the gonadal vessels, and hence retroperitoneal STSs can occasionally extend through the inguinal canal into the scrotum. This possibility is further increased by the deep inguinal ring, which is a defect in the fascia transversalis through which cord structures enter the inguinal canal. This peculiar anatomical situation provides a favorable pathway of spread through which retroperitoneal sarcomas may invade the groin presenting as an indirect inguinal hernia or less frequently through the femoral and obturator foramen herniating into the thigh. The largest part of retroperitoneal STS usually shows an indolent pattern of growth, but due to the absence of anatomical barriers within the retroperitoneal cavity, they might grow indefinitely, becoming symptomatic only after the tumor has reached a remarkable size. Diffuse and a specific abdominal pain is the most common symptom, affecting approximately 50% of patients; less frequent symptoms may include general discomfort, fatigue, early satiety, nausea, vomiting, weight loss, lower extremity swelling, and GI hemorrhage or obstruction.

In the clinical scenario of discovering a groin lump, a retroperitoneal or pelvic tumor with inguinal or scrotal extension should be considered and preoperatively excluded. MRI and CT scan may be helpful either in the staging or diagnostic process and to define the most appropriate therapeutic strategy also including and planning the proper intervention.

In contrast, if the diagnosis of sarcoma was incidentally made in the operating room during the initial operation for an inguinal hernia or a lipoma removal, the suspicious of facing a retroperitoneal sarcoma should always be taken into consideration and surgery therefore suspended after collecting enough tissue sample to achieve the correct diagnosis. The patient would need to be evaluated and fully staged for retroperitoneal sarcoma and surgery rescheduled referring the patient to a sarcoma reference center [116–121].

Undoubtedly, surgery remains the cornerstone of treatment also in these locally advanced pelvic and retroperitoneal sarcomas. In order to improve the tumor resectability, an abdomino-inguinal incision is often preferred. It involves a lower midline incision, which is extended from 2 cm below the umbilicus transversely to the mid-inguinal point on the affected side and then vertically for few centimeters in the femoral triangle. The ipsilateral rectus abdominis and the anterior sheath are divided, as well as the obliquus externus, internus, and transversus muscles; the inguinal ligament is divided off the pubic tubercle, the inferior epigastric vessels are ligated and divided near their origin from the femoral vessels, which are exposed, and the lateral third of the inguinal ligament is detached from the iliac fascia. This approach provides better surgical exposure in one continuous field from the lower abdomen to the groin area on the side affected by the tumor, allowing safer proximal and distal control of the iliac-femoral vessels, easier identification of the femoral nerve lateral to the femoral artery, and easier disconnection of the iliac-psoas muscle from the lesser trochanter if required to achieve a wider resection.

This peculiar surgical approach, though very effective in the intraoperative management of locally advanced retroperitoneal and pelvic sarcomas, leaves the abdominal wall extremely weak. The integrity of the anterior abdominal wall could be difficult to restore by primary sutures, and for this purpose the use of a synthetic mesh is often required. The use of a nonadsorbable polypropylene or polyester prosthesis is preferable, which is more suitable to reinforce the iliac fossa anterior wall and to reconstruct the inguinal canal into the lacuna vasorum and lacuna musculorum. In case of sporadic larger soft tissue defect with a consequent harmful exposure of major vessels and nerves, a solid plastic reconstruction is often recommended. The more common alternatives may be the transposition of the ipsilateral sartorius muscle and the rotation of the contralateral rectus abdominis myocutaneous flap [122, 123] (Fig. 10.3).

Ultimately the incidental finding of STSs herniating through the deep inguinal ring to the inguinal canal may be an uncommon presentation of primary retroperitoneal STSs (most commonly liposarcoma). Given the rarity of this scenario, the diagnosis is not always immediate and may be incidentally detected during the repair of a suspected inguinal hernia or lipoma removal. Of course, it represents an important diagnostic challenge for a surgeon, due both to the surgical and oncological implications.

Any patient with the suspicion of a retroperitoneal sarcoma should be referred to a tertiary center to be properly staged and treated. In fact, although surgery represents the formal approach for retroperitoneal STS, the extension of the surgical resection or the potential administration of complementary treatments has to be assessed and eventually performed only in a high-volume sarcoma center.

The management of STSs is generally a crucial problem when the tumor develops in constrained anatomical areas adjacent to noble or vital structures. The goal of R0 resection in these peculiar regions often results in complex defects including soft tissue layers with the overlying skin and major vessels and nerves.

Indeed, sarcomas usually respect anatomical boundaries, with local anatomy able to influence tumor growth by setting natural barriers to their extension, and in general, sarcomas follow the path of least anatomical resistance, initially growing within the anatomical compartment in which they arise. However, major vessels and nerves may sometimes be involved or even give rise to STSs, and their resection becomes mandatory in roughly 5% of all STSs. Undoubtedly, whether STSs arise from arterial or venous blood vessels or infiltrate or encase the vascular tree, the vessels must be resected in order to achieve adequate surgical margins. In contrast, STSs surrounded by a plane of normal tissue can be dissected from major blood vessels. By longitudinally splitting the adventitia opposite the tumor, a rim of normal tissue is preserved in the vessel-tumor interface. This thin layer of tissue, while not infiltrated by the tumor, is usually sufficient to provide microscopic negative margins without requiring any type of vascular resection and reconstruction (Fig. 10.4).

Recently, the continuous development of reconstructive techniques including flap coverage, limb revascularization, and nerve grafting has improved the surgical outcome for major defects and vascular involvement [124–128].

However, albeit resection of major vessels is feasible and has potentially facilitated local control, it cannot offset the high biological risk of these tumors. Therefore, although technically manageable, involvement of major vessels may be regarded as an added negative prognostic factor and possibly addressed by means of an effective systemic therapy, when the malignancy grade of the tumor is high [125, 126, 129].

Limb preservation is then possible, although given the high complexity of these surgical procedures the rate of postoperative complications may be substantial: disabling lymphedema, vascular graft thrombosis, wound dehiscence especially when flap coverage is required, and ultimately amputation are frequent complications of limb salvage with vascular reconstruction [124–126, 130].

When looking at the different histology subtypes growing within the inguino-femoral region, it was no surprise that leiomyosarcoma was identified as one of the most frequent tumor types given that leiomyosarcomas are the most common malignancy affecting the vascular system, directly arising from the smooth muscle cells of the major vessel wall. Indeed leiomyosarcomas of intravascular origin are extremely rare, presenting only 0.001% of all malignancies, which arise five times more commonly from the venous than from the arterial system, with a strong predilection for the larger veins. The inferior vena cava, in fact, is the most commonly involved vein, being the site of origin in over 50% of cases, while most of the reported sarcomas arising in the extremities affect the femoral bundle.

A direct infiltration of the vascular bundle is not a unique prerogative of vascular leiomyosarcoma. Any STS subtypes would be theoretically able to invade or encase the vascular tree. According to this peculiar anatomical location, synovial sarcoma and liposarcoma are the two most common histologies responsible for secondary vascular involvement.

Synovial sarcoma often affects girdles and the proximal aspect of upper and lower limbs. It may even arise within the proximal thigh close to the neurovascular bundle; synovial sarcoma, in fact, is the second most common histotype after malignant peripheral nerve sheath tumor originating from the peripheral nerves and in this context from the femoral nerve, then invading the nearby vascular axis.

Liposarcoma typically arises from the retroperitoneum/pelvis, and its usual massive extension may lead the tumor to herniate through the deep inguinal ring down to the inguinal or femoral canal, often encasing the iliac-femoral artery and vein.

Conversely, vascular involvement is exceedingly rare for myxofibrosarcoma aside from its typical infiltrative pattern of growth. This may be explained by the predilection for different sites which these tumors originate from; myxofibrosarcomas, in fact, are more common in superficial tissues or distal extremities and only occasionally approach the deep location close to the major vessels [125, 131–133].

Several methods for vascular reconstruction have been reported. Conduit selection, whether autologous venous graft or synthetic graft, is the most controversial aspect of complex groin reconstruction. While the need for arterial reconstruction is obvious, veins are reconstructed predominantly only if they were patent at the time of surgery and had no clinical or radiological evidence of collateralization. The need for vein replacement is controversial, mainly due to its related risk of developing graft thrombosis and subsequent pulmonary embolism. Indeed it is debatable whether it is worth considering reconstructing veins which are already occluded by the tumor, especially in the presence of collaterals. In contrast, when the vein is patent, it is beneficial to replace it in order to improve the short-to-medium-term functional outcome avoiding or delaying the onset of limb edema.

Autologous venous grafts are the ideal conduit because of their long-term superior patency rate without requiring any anticoagulation therapy. Among the wide range of possibilities, the most preferred autologous graft is the contralateral superficial femoral vein. Alternatively, when the diameter of the resected vascular stump is smaller, the contralateral greater saphenous vein is also a valid conduit (Fig. 10.5). Of course in any case of arterial replacement, the autologous venous graft needs to be reversed (to allow normal blood circulation avoiding the opposition of the vein valves), while it has to be kept straight in case of vein replacement.

A suitable option instead of autologous venous grafting is the use of a banked cadaver graft, which possesses all the advantages of the autologous graft, limiting any additional incision on the patient.

Unfortunately, the availability of homologous graft is generally limited, especially when surgery is not performed in a transplant center where tissue banking is usually available allowing the selection of the most appropriate cadaver graft for the receiving patient.

In contrast, when any kind of homologous vein graft is available, the most suitable choice is a PTFE graft with or without integrated rings. PTFE grafts are resistant to kinking and compression; in addition, their diameter can be properly selected to match the diameter of the arterial or venous stump.

The major drawbacks of PTFE grafts are the requirement for lifelong anticoagulation therapy, a higher risk of postoperative infection, and a less favorable long-term patency rate [125–128, 134, 135].

Primary STS originating from neural structures such as MPNST and synovial sarcoma or locally advanced tumors directly invading the femoral nerve may require its sacrifice when identifying a safe plane of dissection beneath the perineurium is not feasible. Perineurium nerves such as the adventitia of major vessels generally represent an acceptable margin which is seldom surmountable by neoplastic cells. Indeed, when the tumor breaks that anatomical barrier, the transection of the nerve with clear margins is mandatory. Although nerve reconstruction is not a lifesaving procedure and patients’ quality of life may be acceptable even after the resection of the major peripheral nerve, the attempt to restore the neuromotor unit should be pursued especially in young patients with a short, possibly less than 10 cm, neural gap. Classically, the sural nerve has been the predominant source of nerve autograft, as sural donor site morbidity is minimal resulting in diminished sensation at the lateral foot and minimal, often invisible, scars [136–141].

In case of extensive groin resections, soft tissue and skin defect may also be challenging to reconstruct. Transferring a soft tissue flap into the surgical defect fills the dead space; incorporates healthy, well-vascularized tissue into the wound; and facilitates tension-free closure. Various flap coverage techniques are available, and flap selection is potentially a critical component for these complex defects, because multiple vital anatomical structures should be reconstructed simultaneously. Given its reliable vascularization, the large skin surface, and the considerable amount of tissue, pedicled vertical rectus abdominis myocutaneous (VRAM) flap is usually the preferred choice especially for remarkable defects of the inguinal region.

An ipsilateral VRAM would always be the ideal option, but it is seldom practicable since the ipsilateral deep inferior epigastric vessels are necessarily transected during the tumor removal. A contralateral VRAM flap is then a valid alternative as it can reach the contralateral distal thigh without excessive tension. The disadvantages of using contralateral VRAM flap depend on the consequent weakness of the anterior abdominal wall, although fixed by a synthetic mesh, which can lead to donor site bulging or herniation.

For patients with smaller groin soft tissue defects, pedicled anterolateral thigh (ALT) flap may be an appropriate reconstruction as long as the source vessel is not sacrificed proximally at the tumor ablation.

When local flaps are not available or adequate to cover the whole surgical defect, the transfer of a free flap remains the last option. The choice of which free flap depends on the size of the groin defect. For patients with small to moderate defects, an ALT free flap is normally indicated, while for wider defects, a latissimus dorsi free flap is usually more appropriate. The major obstacle to free flap transfer for complex groin defects is the availability of suitable recipient vessels when the external iliac or femoral vessels are transected [124, 142–144].

In conclusion, we confirm that locally advanced groin sarcoma can be removed with negative microscopic resection margins by a limb salvage approach. Involvement or infiltration of noble or vital structures does not represent a contraindication to perform or attempt surgery since major peripheral vessels, motor nerves, and soft tissue defects may be well reconstructed. However, this category of patients is at high risk of developing metastatic disease due to the underlying nature of their disease. This should be carefully considered when planning the treatment strategy; for example, the perioperative risks/postoperative functional impact should be adequately assessed against the limited benefit in overall survival. This is a rare indication for a rare tumor, and patients should definitely be treated only in STS reference centers where all the medical and surgical specialties are available in order to deliver the best standard of care.

About 25–30% of extremity soft tissue sarcoma (ESTS) patients develop metastatic disease, mainly disseminating through the bloodstream, with the lungs being the primary site in 80% of patients with distant metastases.

In contrast, lymph node metastases have been identified in less than 5% of cases, although some series report overall rates of lymphatic spread in up to 10% of ESTS patients [145–147].

In specific histotypes, there is a strong propensity toward lymph node metastasis. Between 2000 and 2009, from the National Cancer Data Base of the United States, 27,536 patients with extremity STS were identified; 1924 (7.0%) underwent nodal evaluation and 25,612 (93.0%) did not have any nodes examined at surgery. Of 1924 patients with extremity STS who underwent nodal evaluation, 290 (15.1%) had nodal metastases. Assessment by histologic subtype revealed higher rates of lymph node metastases in patients with rhabdomyosarcoma (32.1%), angiosarcoma (24.1%), clear cell sarcoma (27.7%), and epithelioid sarcoma (31.8%). Lower rates of nodal metastases were seen in patients with fibrosarcoma (9.5%), leiomyosarcoma (7.5%), synovial sarcoma (6.0%), and liposarcoma (3.5%). Nodal metastasis rates were higher in patients with tumors 5–10 cm in size (18.6%) than in patients with tumors <5 cm in size (12.4%). Patients with high-grade tumors (18.4%) also had higher rates of nodal metastases than patients with low-grade tumors (5.3%) [148].

Neoplastic lymph node involvement has also been described in myxofibrosarcoma. In this last subtype, the tumor cells may spread into the lymph node parenchyma or peculiarly give rise to soft tissue metastases invading only the perilymph node stroma [12, 149].

Metastatic lymph node involvement is usually suspected when regional nodes are enlarged on clinical examination or have an abnormal appearance on ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI). However, both clinical and radiographic assessments may overestimate the presence of metastatic disease in the case of normal reactive nodes or underestimate tumor involvement if the nodes are not pathologically enlarged. One cooperative group study reported that 17% of clinically and radiologically normal lymph nodes were found to contain neoplastic cells at the time of biopsy [150].

Various approaches have been proposed in order to try to identify the presence of metastatic lymph nodes in extremity STS patients.

Historically, random sampling of the anatomic regional lymph node basin has been performed, but this can lead to excessive dissection with a high morbidity rate such as infection, nerve and vascular damage, and chronic lymphedema. Sentinel lymph node biopsy (SLNB) was designed as a reasonable alternative to random sampling, hypothesizing that the first (sentinel) node receiving lymphatic drainage from a tumor site would be the most likely one to contain metastatic cells. The methylene blue and the gamma probe guide the surgeons to the identification of the sentinel lymph nodes, which are subsequently excised. It has quickly become the standard of care in selected types of cancer. Several studies, in fact, have supported this procedure in both melanoma and breast cancer.

Due to the potential advantages of SLNB, many physicians have explored, with mixed success, the use of lymphatic mapping for malignancies other than breast cancer or melanoma. These included lung cancer, colon cancer, head and neck squamous cell carcinoma, gynecologic cancers, thyroid cancer, Merkel cell carcinoma, upper gastrointestinal cancers, and non-small cell lung cancer.

Unfortunately, until date, SLNB has not been formally investigated in the management of sarcoma. This is not particularly surprising given that the majority of sarcomas spread by local extension or hematogenously. Regional lymph node metastases seldom occur, developing in less than 10% of patients with localized disease. In addition, recurrence within the locoregional nodal basin is rare, representing 4–10% of local recurrences [151–153].

Functional imaging using [18F]fludeoxyglucose positron emission tomography/computed tomography (FDG-PET-CT) represents a valid and noninvasive alternative to SLNB to assess the regional lymphatic basin for the presence of metastatic disease. It uses not just the size but also the metabolic characteristics of tissue to determine whether a metastatic tumor may be present. Although PET/CT scans have been found to be less reliable than SLNB in melanoma and breast cancer, it has proved to be superior to any other radiological method for staging of locoregional lymph nodes and the detection of skeletal metastases in sarcoma patients. However, what emerged from recent studies is that PET-CT cannot be considered specific enough for nodal metastases such that biopsy can be avoided. The positive predictive value of PET-CT was reported to be 29%, while the negative predictive value of PET-CT was 79%. These findings imply poor predictive power for PET to identify small-volume metastatic nodal disease in STSs.

Therefore, when clinical examination and imaging are not conclusive, fine-needle aspiration biopsy (FNAB) should be performed preoperatively to assess whether tumoral cells within the lymph node are present. It is, in fact, absolutely crucial to distinguish between metastatic and reactive enlarged lymph nodes before defining any patient treatment plan [150–153].

Given the unlikely event of nodal spread in ESTS patients and consequently the relatively limited experience in this area, data are lacking, and comprehensive recommendations on lymph node evaluation (SLNB-FNAB-PET/CT scan) or treatment when involved are not available in the National Comprehensive Cancer Network’s guidelines for sarcoma. There is a formal consensus regarding the uselessness of performing prophylactic locoregional lymph node dissection as part of the initial treatment of these patients, at least in the absence of macroscopic lymphatic disease.

The confirmation of metastases in regional nodes is a clinical expression of the biological aggressiveness of the sarcoma, with 5-year survival rates between 10 and 23%, while 10-year survival rates have been reported to be approximately 3% [147, 154].

For STSs, isolated lymph node metastasis has been thought to carry a prognosis similar to distant metastatic disease, and, in fact, the 2002 American Joint Committee on Cancer staging guidelines classify lymph node metastasis as stage IV disease [147]. Nevertheless, according to this classification, patients with lymph node-positive sarcomas had worse overall survival when compared to patients with localized disease, but showed improved survival rates if compared to patients with distant metastases. Localized disease, regional lymph node metastatic disease, and distant metastatic disease had 5-year survival rates of 81%, 51%, and 22%, respectively [145]. Besides, as recently underlined in a large ESTS patients series, the outcome of patients presenting with simultaneous locoregional lymphatic disease and distant metastasis definitely had a worse long-term prognosis when compared to patients only presenting with nodal spread. The 1- and 2-year survival for patients with isolated regional lymph node metastasis (RLNM) was 77% and 47%, respectively. The 1- and 2-year survival for patients with distant metastases present at the time of presentation of RLNM was 36% and 21%, respectively. The 5-year survival for patients with isolated RLNM was 24%, while it was 0% for patients who presented with RLNM and distant metastasis.

There is a general agreement that lymph node metastasis detected at the time of diagnosis indicates a poorer outcome. The 1-year survival for metachronous and synchronous RLNM was 94% and 68%, respectively, and the 2-year survival was 56% and 42%, respectively. Metachronous RLNM then has a better outcome than synchronous RLNM at the time of diagnosis of primary STSs [147]. In contrast to this tendency, recent studies have supported the view of better survival for patients with lymph node metastases at the time of diagnosis. Post regional lymphadenectomy, disease-free survival was significantly longer in patients with regional lymph node metastases at the time of diagnosis than in patients with lymph node recurrence after prior curative surgery. Significantly, patients with initial and recurrent regional lymph node metastases showed longer disease-free survival than patients with distant metastases [146].

The surgical treatment of radical lymph node dissection is generally considered a palliative procedure, because it invariably indicates distant micrometastatic disease [145]. However, several studies demonstrated that aggressive treatment could bring about long-term survivors. It was, in fact, demonstrated that primary surgical treatment of lymph nodes gives a better survival if compared to patients treated by chemotherapy and RT [41, 146]. To date, the question about the extension of the lymphatic dissection is controversial, and the role of radical lymphadenectomy among node-positive patients remains to be defined. Although it is widely known that the presence of lymph node metastasis directly impacts overall survival, it has been recently reported that neither the degree of lymph node burden nor the extent of resected lymph nodes influenced survival, calling into question the role of radical lymphadenectomy in patients with isolated regional lymph node metastasis. In further case series of ESTS patients with limited nodal disease, any survival benefit was proved for those patients who underwent radical lymphadenectomy compared to patients who had a limited lymph node dissection consisting in the resection of the only macroscopically detectable tumor [145, 155, 156].

In contrast with these results, evidence in favor of extended lymph node dissection in sarcoma patients with isolated regional lymph node metastasis is primarily based on previous retrospective investigations and studies supporting the advantage of radical lymphadenectomy, such as axillary dissection including level I to III lymph nodes and ilioinguinal dissection, in order to improve the local control rate and prolong the overall survival in ESTS patients. In addition, when there is recurrence in the regional lymph node basin, performing radical lymphadenectomy would further increase survival [40, 41, 147, 157, 158].