Non-neoplastic soft tissue masses may mimic soft tissue sarcoma in a wide variety of clinical settings. Systematic and thorough review of patient history, physical examination, imaging, laboratory results, and biopsy will allow the clinician to differentiate between the two in most cases. We describe several common non-neoplastic entities that may mimic soft tissue sarcoma in case presentation format along with the characteristics that help distinguish them.
Key points
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Atypical features of soft tissue sarcoma that may be more common in benign imitators include small size, superficial location, soft consistency, painful character, inflammatory or homogeneous signal on axial imaging, or irregular shape.
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Heterogeneous cystic necrosis of a soft tissue mass is an ominous sign and may indicate a malignant neoplastic process.
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Plain radiographs are a valuable adjunct to the evaluation of any soft tissue mass.
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When other diagnostic modalities fail, core needle biopsy at the treating institution is the gold standard for diagnosis.
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The diagnosis should be pursued with repeat needle or open biopsy if initial needle biopsy is unsuccessful.
Introduction
Soft tissue masses that arise in the extremities can be diagnostically challenging because of the breadth of the differential diagnosis and the nonspecificity of current imaging technology. Although benign tumors are overall much more common than their malignant counterparts, the clinician must be aware of and often entertain the possibility of a malignant diagnosis at some stage in the diagnostic pathway.
Fortunately, some masses can be quickly and readily identified before any invasive maneuver because of their characteristic imaging findings. For example, the magnetic resonance imaging (MRI) characteristics of benign lipomatous tumors, hemangiomas, or giant-cell tumor of tendon sheath are often conclusive enough to allow the clinician to proceed with a treatment algorithm. In other cases in which the diagnosis is not as clear based on imaging, small size (<5 cm) and location superficial to the fascia make the lesion likely enough to be benign such that it can be either observed or excised with little risk to the patient.
In most other instances, the mass in question should be presumed sarcomatous until proven otherwise. The goal of this review is to provide additional tools to the clinician to help distinguish common non-neoplastic entities from true sarcomatous tumors. In particular, we review several lesions that have a propensity to mimic sarcoma, and discuss the diagnostic and treatment approaches that allow safe navigation of a broad differential landscape.
Introduction
Soft tissue masses that arise in the extremities can be diagnostically challenging because of the breadth of the differential diagnosis and the nonspecificity of current imaging technology. Although benign tumors are overall much more common than their malignant counterparts, the clinician must be aware of and often entertain the possibility of a malignant diagnosis at some stage in the diagnostic pathway.
Fortunately, some masses can be quickly and readily identified before any invasive maneuver because of their characteristic imaging findings. For example, the magnetic resonance imaging (MRI) characteristics of benign lipomatous tumors, hemangiomas, or giant-cell tumor of tendon sheath are often conclusive enough to allow the clinician to proceed with a treatment algorithm. In other cases in which the diagnosis is not as clear based on imaging, small size (<5 cm) and location superficial to the fascia make the lesion likely enough to be benign such that it can be either observed or excised with little risk to the patient.
In most other instances, the mass in question should be presumed sarcomatous until proven otherwise. The goal of this review is to provide additional tools to the clinician to help distinguish common non-neoplastic entities from true sarcomatous tumors. In particular, we review several lesions that have a propensity to mimic sarcoma, and discuss the diagnostic and treatment approaches that allow safe navigation of a broad differential landscape.
History and physical
A detailed history and physical examination should be taken, although most factors discovered during this component of the encounter are merely clues and are not pathognomonic for any one condition. Patients may attribute the onset of a mass to a trivial traumatic event, when in fact the two are unrelated, and this should as much as possible be distinguished from conditions that can arise from true traumatic events, such as intramuscular hematoma or mysositis ossificans. The patient should be questioned in detail about the symptoms related to the soft tissue mass, as a painful mass is more consistent with traumatic or inflammatory etiologies than soft tissue sarcoma. Rate of growth of the mass also is important to discover, as progressive growth usually indicates a more aggressive process. This said, certain soft tissue malignancies, such as synovial sarcoma, have been widely reported to remain indolent for long periods. Recent weight loss may give the impression of mass growth when in fact the tissues around the mass have diminished.
The mass itself should be carefully examined. Immobility under the skin indicates a lesion deep to the fascia. A well-defined, firm mass is more typical with sarcoma than other benign conditions, such as vascular malformations that may be less well defined or lipoma, which may be softer. Skin changes, such as cellulitis or puncture wounds, may indicate a deep abscess; telangiectatic vascular changes of the skin are more concerning for malignant neovascularization. Transillumination or a fluid wave may indicate a ganglion or other fluid-filled lesion.
Laboratory results
Although most patients with sarcoma have normal laboratory values, a complete blood count (CBC), coagulation studies, and electrolytes may be helpful for the patient being considered for a malignant process. These may uncover hematologic problems, such as lymphoma, hemophilia, or other coagulopathies that can lead to a soft tissue mass. Other laboratory tests, such as inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) can indicate infection or another inflammatory process, but specificity of these studies is low. Creatinine kinase can indicate muscle breakdown, such as with myositis-spectrum conditions. If the index of suspicion is high, Bartonella henselae , Francisella tularensis , or Borrelia burgdorferi serologies may be sent and can explain multifocal lymphadenopathy.
Imaging
Plain radiographs should initiate most imaging workups, even when a mass is clearly confined to the soft tissues. Centrifugally progressive or diffuse radiodensity may represent either calcific necrosis of malignancy or true osteoid production of the rare soft tissue osteosarcoma. Conversely, a centripetal ossification pattern progressing from the periphery to the center of the mass over a much faster time course (2–8 weeks) is nearly pathognomonic for myositis ossificans. Phleboliths in the case of vascular malformation may be visualized. Bony reaction or destruction in response to an aggressive soft tissue sarcoma also may be demonstrated.
Ultrasound is a cost-effective, noninvasive imaging modality that may give better insight into the composition of the soft tissue mass. In addition to delineating the size and depth of the lesion, it may effectively demonstrate fluid or blood-product density, and may demonstrate vascular flow through the lesion. These are nonspecific findings, as certain sarcomas also may have large, necrotic, fluid-filled areas or large vessels within the tumor.
Axial imaging is mandatory when the diagnosis cannot be made based on history, examination, and other imaging. MRI with contrast is the gold standard for imaging examination of soft tissue tumors. Content that may be bright on T1-weighted imaging includes fat, gadolinium, melanin, proteinaceous fluid, and old blood products, such as with chronic hematoma. Fat suppression images in comparison with standard T1 sequences are particularly helpful when characterizing T1-bright material. Another helpful finding is peripheral or so-called “rim” enhancement, which indicates uniform fluid content and an absence of central vascularization. Masses with T1 hypointensity/T2 hyperintensity signal profiles that diffusely enhance on postcontrast imaging may represent benign solid tumors or sarcoma. On the other hand, masses that have these characteristics and additionally display central areas of nonenhancement or other heterogeneity due to necrosis are much more worrisome for a malignant process because this indicates either growth-related exhaustion of blood supply to the central parts of the tumor or genetic instability of the oldest malignant tumor cells undergoing apoptosis and necrosis. Finally, one should consider the inflammatory characteristics of the mass along with how well defined the borders are. Although sarcoma can demonstrate perilesional edema, this is an atypical finding and lesions with extensive edema in the surrounding tissues are more likely to represent benign processes, such as myositis, myonecrosis, or abscess. Further, sarcomatous tumors are typically round, ovoid, or occasionally slightly lobular in shape. On the other hand, slow-growing benign tumors, such as lipoma or atypical lipomatous tumor, may be irregularly shaped. Other benign entities, such as fibromatosis (extra-abdominal desmoid tumor), may demonstrate infiltration into surrounding tissues, consistent with its benign but locally aggressive nature.
Other local imaging, such as computed tomography (CT) scans, may be helpful in delineating ossification or calcification patterns, as well as detecting subtle changes in surrounding bony architecture. Systemic imaging, such as pulmonary radiographs, pulmonary CT, bone scan, or positron emission spectroscopy, also may be required in certain cases, such as with suspected sarcoma, tuberculosis, lymphoma, or in other condition-specific cases.
Biopsy
When all other modalities fail to narrow the differential to a specific or definitively benign diagnosis, tissue sampling is required. Although fine-needle aspiration may answer the question of whether or not malignant cells are present and is the standard of care for entities such as pathologic lymph nodes, core needle biopsy is typically preferred for its increased accuracy because of its ability to preserve tissue architecture. This can be done with or without image guidance, and should be targeted ideally to enhancing areas of the mass based on MRI for the highest yield. Open biopsy is also an option, either initially or after failed needle biopsy. Dissection through tissue planes should be avoided, hemostasis should be maintained, incisions should be longitudinal, and should be placed in the distribution of extensile exposures in anticipation of subsequent biopsy tract excision. Open biopsy performed at the presenting as opposed to the treating tertiary center is discouraged. Although false negatives routinely occur given the sampling error involved with biopsy of a heterogeneous mass, the clinician should be aware that false positives can also occur. Diagnostic accuracy and safety is enhanced when all members of the treating team, from surgeon to pathologist, are experienced and routinely treat sarcoma or potentially sarcomatous masses.
Infection
Soft tissue abscess and other forms of infection can be confused with sarcoma. An acute soft tissue infection may present with clinical characteristics that make the diagnosis straightforward, such as pain, cellulitis, a precipitating puncture wound, or fevers. In addition, edema and inflammatory signal in the surrounding tissues on MRI frequently point toward an infectious or other inflammatory process. Laboratory studies, such as CRP, ESR, or serum white blood cell count may be elevated. However, there are rare cases of sarcoma with inflammatory imaging characteristics, such as inflammatory undifferentiated pleomorphic sarcoma (formerly malignant fibrous histiocytoma or MFH). In addition, a chronic soft tissue abscess may become “walled off” and lose many of its inflammatory imaging characteristics. For these reasons, the entire clinical picture should be considered, and tissue diagnosis via biopsy obtained when there is uncertainty. It is helpful practice to routinely send any biopsy specimen for both permanent pathologic analysis as well as microbiological analysis because of the overlap in appearance between some infectious and neoplastic processes.
One particular infectious process that is commonly mistaken for sarcoma is infectious involvement of lymphoid structures with B henselae , otherwise known as “cat scratch disease.” This condition presents with unilateral lymphadenopathy that can be mistaken for soft tissue neoplasm. Nearly half the patients presenting with this condition have lymphadenopathy of the unilateral upper extremity, most commonly in the epitrochlear nodal chain. Most report an exposure to the bite or scratch of the common housecat, as this is the longitudinal vector for Bartonella species. The definitive diagnosis may be made noninvasively in the appropriate setting with serum Bartonella titer measurement. Most patients experience self-limited disease over 4 to 8 weeks and do not require antibiotics. For prolonged or severe involvement, especially in immunocompromised patients, azithromycin is the antibiotic treatment of choice.
Fig. 1 demonstrates the T1 fat-suppressed postgadolinium axial and coronal MR images of a 52-year-old woman who presented with a 2-week history of a distal and medial right arm mass. She had mild tenderness but no systemic signs of illness. Her CBC, ESR, and CRP were within normal limits. An ultrasound-guided core needle biopsy demonstrated necrotizing granulomatous lymphadenitis, and follow-up serologies after biopsy demonstrated B henselae titers of 1:512 (normal <1:64). She was treated with warm compresses, antipyretics, and analgesics, with spontaneous resolution of symptoms over the next 2 months.
Ganglion cyst
Ganglion cyst is the most common mass of the hand, and when present at the dorsum of the wrist around the scapholunate interval, there is little doubt of the diagnosis. When this mass occurs in other locations or is multiloculated, the diagnosis may be less obvious. Generically, ganglion cysts arise from joints, tendons, bursae, or ligaments. This may be due to degenerative or posttraumatic attenuation of a joint capsule or tendon sheath causing expansion of a fluid-filled capsular sac. However, the pathogenesis is controversial and there may be other mechanisms. The diagnosis is made by a history of fluctuating size, positive transillumination test, ultrasound demonstrating a homogeneous fluid-filled sac originating from a joint, or MRI demonstrating a uniloculated or multiloculated, rim-enhancing fluid-filled sac. Surgical treatment is aimed at marginal excision of the ganglion sac at the base of the stalk from which it emanates.
Fig. 2 demonstrates the axial and sagittal T1 fat-suppressed postgadolinium MRIs of a 67-year-old man who presented with an enlarging proximal lateral leg mass and a dense peroneal nerve palsy. There was a concern for sarcoma from the referring institution, but MRI scans demonstrated the classic appearance of a uniloculated, homogeneous, fluid-filled cyst emanating from the tibia-fibular joint with peripheral rim enhancement. The diagnosis of ganglion cyst was made and the patient underwent open excision of the mass, with resolution of his nerve palsy. The cyst did recur but was eventually successfully treated with further surgical excision and tibia-fibular joint debridement.
