Tumorlike Lesions of Soft Tissue

Nicholas S. Tedesco, DO, FAAOS

Dr. Tedesco or an immediate family member has stock or stock options held in Doctorpedia and RomTech, Inc. and serves as a board member, owner, officer, or committee member of American Academy of Orthopaedic Surgeons and Musculoskeletal Tumor Society.

ABSTRACT

Definitive management of nonneoplastic, tumorlike masses of soft tissue will require careful assessment of clinical, radiographic, and histopathologic features where necessary, as well as an appropriate clinical approach to abscesses, myonecrosis, rheumatoid nodules, periprosthetic pseudotumors, hematomas, seromas, heterotopic ossification, tumoral calcinosis, and gouty tophi. It is important to provide an up-to-date, evidence-based reference to aid in the recognition, diagnosis, and management of these common tumor-mimicking conditions.

INTRODUCTION

Tumorlike lesions of soft tissue comprise a heterogeneous group of nonneoplastic masses that mimic many benign and malignant tumors. These lesions are not true neoplasms, or growth of aberrant, new tissue. Rather, they comprise masslike swelling or enlargement of tissue caused by various pathologic processes including fluid or blood extravasation, reactive or infiltrative processes of the immune system, sequelae of long-standing inflammation or injury, processes of mineral deposition, or metaplastic syndromes with conversion of one tissue type to another. Many of these tumorlike lesions can enlarge over time, can be either painful or painless, and can occur spontaneously or from a causal event. They can be confused for each other and for many other lesions. Depending on the location and nature of this group of masses, the differential diagnosis on presentation can include infection, crystalline tophi, deep vein thrombosis (DVT), benign soft-tissue neoplasms, lymphadenopathy (reactive or neoplastic), metastatic soft-tissue nodules, and soft-tissue sarcomas. Therefore, care should be taken in the diagnosis and management of these tumorlike lesions with diligent use of oncologic principles to avoid mistaking a soft-tissue malignancy such as lymphoma, sarcoma, or metastatic soft-tissue deposits for one of these mimickers. This also highlights the importance of obtaining a thorough history and performing a diligent physical examination with appropriate testing when needed to elucidate potential risk factors or underlying causes for many of these lesions.

INFECTIOUS AND REACTIVE LESIONS

Abscess

An abscess is a collection of necrotic debris, predominantly composed of dead neutrophils that have been recruited to a site of active infection within a current (ie, surgical bed) or potential (ie, dermal-subdermal junction) space with no outlet for drainage such as an open wound or fistula tract. Abscess is often a clinical diagnosis, but in atypical presentations, such as nonreactive, asymptomatic lesions in severely immunosuppressed patients (patients who underwent organ transplantation or those on marrow-suppressive chemotherapy) or in deep locations that are neither overtly visible nor palpable, imaging may be indicated to aid in diagnosis. Advanced cross-sectional imaging should be considered, because a lack of specificity has made ultrasonography a poor choice for diagnosis and it may only be useful to rule out the presence of a mass.¹

MRI will demonstrate some homogeneity of the lesion with purulence within the abscess cavity brighter than skeletal muscle on T1 spin echo imaging because of its cellular and protein content (Figure 1). The lesion will also have very bright signal intensity on T2 fast spin echo images because of its fluid content. A thin peripheral rim of enhancement will be present at the reactive interface of the surrounding tissue because, with purulence representing dead neutrophils, there are no intralesional capillaries that could allow extravasation of the contrast dye. Extensive edema, seen as a feathery, infiltrative bright signal on T2 fast spin echo imaging involving multiple tissue planes, is often present. This reactive zone will enhance with gadolinium contrast.

FIGURE 1 Magnetic resonance images showing an enlarging, painless abscess in the forearm of an immunocompromised patient after organ transplant. A, Axial T1-weighted image. B, T2-weighted fast spin echo image. C, Contrast-enhanced T1-weighted fast spin echo image. Note the bright signal intensity compared with skeletal muscle indicative of purulence on both the T1 and T2 images, and thin rim of peripheral enhancement postcontrast that suggest a fluid-filled cavity. The lack of reactive edema surrounding the lesion and lack of pain demonstrates the immunosuppression of this patient and can result in the clinical picture easily being confused for a hemorrhagic mass.

Treatment typically involves surgical or percutaneous drainage, irrigation, and débridement of exudate and necrotic tissue (Table 1). As discussed in a 2022 study, surgical packing for lesions larger than 5 cm may decrease the risk of recurrence.² In addition, in a 2022 study, posttreatment ultrasonographic confirmation that the entire cavity has been evacuated can decrease the risk of treatment failure.³ The choice of additional antibiosis with oral or intravenous antibiotics depends on patient morbidities and/or presence of immunosuppression. However, routine antibiotics for all cases is not currently recommended.²^,⁴ The antibiotics should be tapered in accordance with cultures and bacterial sensitivities for appropriate antibiotic stewardship.

Table 1 Highlights of the Different Tumorlike Lesions of Soft Tissue

Lesion	Presentation	Diagnosis	Imaging Highlights	Common Mimics	Treatment	Recurrence Risk
Abscess	Pain, swelling, erythema, warmth	Clinical versus advanced imaging if deep	Brighter than skeletal muscle on T1 MRI	Hematoma, DVT, myositis, acute HO	I&D ± antibiotics	Low
Calcific myonecrosis	Painless growth	Clinical	Amorphous peripheral calcification	HO, tumoral calcinosis, OGS, chondrosarcoma	Observation	N/A
Diabetic myonecrosis	Painful spontaneous swelling	Clinical	Necrotic muscle with large reactive zone on MRI	Acute HO, hematoma, DVT, hemorrhagic soft-tissue sarcoma, abscess	Symptomatic	N/A
Rheumatoid nodule	Painful or painless asymmetric swelling	Clinical	N/A	Gouty tophus, bursitis	Modify DMARDs, steroid injection, resection	High
Periprosthetic pseudotumor	Painful swelling around artificial joint	MRI	Heterogenous periprosthetic mass with tissue destruction on MRI	Soft-tissue sarcoma, periprosthetic infection	Resection with revision arthroplasty	Low
Hematoma	Painful spontaneous or traumatic swelling	Clinical ± MRI	Heterogeneous, infiltrative mass brighter than skeletal muscle on T1 with large reactive zone on MRI	Abscess, DVT, myositis, acute HO	Observation, I&D	Low
Ancient hematoma	Painless or painful enlarging mass	Clinical ± MRI	Heterogeneous, circumscribed mass with little to no reactive zone and contrast dye uptake	Soft-tissue sarcoma, pseudoaneurysm	Resection	Low
Seroma	Painless mass with history of remote trauma or surgery	Clinical ± MRI	Single fluid-fluid level with thin peripheral rim of enhancement on MRI	Soft-tissue sarcoma, pseudoaneurysm, ganglion, cyst	Resection	High
HO	Painless or painful mass, ± stiffness with history of remote trauma, TBI, or SCI	Radiograph	Zonation phenomenon of peripheral dense calcification and central trabecular bone on radiograph	Abscess, DVT, myositis, hematoma (acute) or soft-tissue sarcoma, tumoral calcinosis (chronic)	Observation vs. resection at maturity if symptomatic	High
Fibrodysplasia ossificans progressiva	Pain, stiffness, neurologic symptoms, eventually fatal	ACVR1 genetic testing	Zonation phenomenon of peripheral dense calcification and central trabecular bone on radiograph	Benign HO	Genetic counseling, symptomatic, medical trials ongoing	High
Tumoral calcinosis	Painless or painful periarticular mass	Radiograph	Amorphous, dense, cloudlike calcification on radiograph	HO, calcific myonecrosis,	Observation vs. resection if symptomatic	Moderate
Gouty tophus	Pain, swelling, erythema, warmth	Clinical versus calcium urate crystals on histopathology	N/A	Rheumatoid nodule, abscess, bursitis	Pegloticase, steroid injection, resection	Low
ACVR1 = activin A receptor type 1, DMARDs = disease-modifying antirheumatic drugs, DVT = deep vein thrombosis, HO = heterotopic ossification, I&D = irrigation and débridement, N/A = not applicable, OGS = osteogenic sarcoma, SCI = spinal cord injury, TBI = traumatic brain injury

Myonecrosis

Muscle death can occur as a result of multiple underlying causes. As a result, it can be either acute or insidious, either painful or painless, and can cause calcification or for the muscle to be surrounded by extensive reactive change. The most common types of myonecrosis occur as the result of severe localized trauma, downstream effects of vascular occlusion, long-standing poorly controlled diabetes with microvascular damage, long-standing reactive change to severe nerve damage, or sequelae from an ischemic limb injury.

Among the more commonly encountered conditions, diabetic myonecrosis (Table 1) occurs as a result of microvascular disease in the setting of chronic and uncontrolled diabetes mellitus. It can often mimic infection or DVT because of its appearance, symptoms, elevated serum inflammatory markers, and acuity; thus, infection or DVT must first be ruled out.⁵ Another common presentation of myonecrosis, calcific myonecrosis (Table 1), is almost exclusively seen in the anterolateral compartments of the lower leg and often manifests years to decades after a lower extremity trauma, leading to vascular injury or compartment syndrome.⁶

Plain radiographic imaging is typically normal in posttraumatic or diabetic myonecrosis. However, in calcific myonecrosis, plain radiographs and CT scans will show the characteristic amorphous, lobular calcifications (Figure 2) that can be confused for tumoral calcinosis or malignant matrix production. On MRI, calcific myonecrosis will show pressure-related erosion of the adjacent tibia as well as the scattered calcific debris, whereas posttraumatic, ischemic, or diabetic-induced myonecrosis will show a lack of calcification and will have extensive reactive change from the acuity (Figure 3).

FIGURE 2 Plain AP radiograph (A) and axial CT scan (B) from a patient with calcific myonecrosis that began almost 40 years after a knee dislocation injury requiring popliteal vessel bypass with chronic occlusion of the bypass graft and peroneal nerve palsy. Note the fusiform, amorphous calcification on the radiograph, with CT confirming peripheral calcification of the necrotic tissue as well as the tibial invasion commonly seen as a pressure-related erosive phenomenon.

FIGURE 3 Calcific myonecrosis.

A and B, Axial T1-weighted and T2-weighted fast spin echo magnetic resonance images from the patient described in Figure 2 demonstrating the characteristic heterogeneity of the lesion with scattered calcifications as well as focal regions of tibial cortical effacement without substantial reactive zone. However, in diabetic myonecrosis, the axial T1, postcontrast T1-weighted FSE, and T2 fast spin echo magnetic resonance images (C through E) show the necrotic muscles surrounded by extensive reactive change and peripheral reactive enhancement of the necrotic center.

Treatment of these lesions is often limited to observation alone and symptomatic management⁵ with or without serial imaging, versus surgical marginal resection in the case of calcific myonecrosis if symptomatic and refractory. However, local or free flap coupled with split-thickness skin grafting is often needed because of the amount of skin blood supply compromised requiring concomitant resection. Biopsy should be avoided because of the characteristic appearance and history these patients generally have, because it often leads to a chronic, draining fistula that can become infected and even lead to amputation as a result of the poor blood flow and compromised healing environment.⁶^,⁷

Rheumatoid Nodule

A rheumatoid nodule is an extra-articular soft-tissue mass-like manifestation of rheumatoid arthritis, characterized histopathologically by leukocytoclastic vasculitis and central necrobiosis with surrounding palisading histiocytes and fibrin deposition.⁸ Paradoxically, treatments for rheumatoid arthritis including methotrexate or tumor necrosis factor inhibition can actually increase their size and number. Rheumatoid nodules are found most commonly in the hand and upper extremities, but can occur anywhere in the body, including solid organs.⁹

Imaging is often not warranted, given the characteristic clinical appearance of these lesions and association with long-standing rheumatoid arthritis (Figure 4). Occasionally, imaging is performed if the lesion is isolated, in an abnormal location, or clinical concern exists for another soft-tissue mass. Treatment of these lesions is often limited to observation alone with or without adjustments in the medical management of the underlying systemic rheumatoid syndrome. Percutaneous steroid injections can be beneficial, but according to a 2022 study there is an increased risk of infection with this approach in lesions larger than 2 cm.¹⁰ Therefore, marginal surgical resection can be considered if symptomatic and refractory or for larger lesions (Table 1). However, as discussed in a 2023 study, patients should be counseled on the significantly higher risk of recurrence compared with other benign tumor resections.¹¹

FIGURE 4 Clinical photograph of multiple subcutaneous rheumatoid nodules on bilateral elbows of a patient with long-standing rheumatoid arthritis.

Note the abnormal contour of the nodules and lack of rubor or visible subcutaneous pearly white fluid, helping to rule out tophaceous gout or bursitis.

Periprosthetic Pseudotumor

Workup for persistent or new-onset pain in a previously painless artificial joint often includes metal artifact reduction sequence MRI to assess for subtle soft-tissue or bony pathology surrounding an endoprosthesis that may otherwise appear well fixed and well aligned on plain radiographs. In the presence of metal debris in the soft tissues, principally cobalt, the body can have a very robust and massive inflammatory reaction that can appear clinically and radiographically as a large, heterogeneous mass, often confused for infection or soft-tissue sarcoma (Figure 5). However, these masses are a polyclonal, immune-mediated, reactive process surrounding the offending prosthesis, histologically represented by necrotic debris, granulomatous foreign body reaction, and heavy lymphoid infiltrate that includes lymphocytes, plasma cells, and perivascular lymphoid aggregates¹² (Figure 6). These lesions are known as aseptic lymphocytic vasculitis-associated lesions as opposed to true neoplasia. Because of this confusion, they have been colloquially referred to as a pseudotumor. However, the only reliable parameter short of MRI in predicting the presence of an aseptic lymphocytic vasculitis-associated lesion in painful arthroplasty is a synovial aspiration monocyte percentage greater than 39%.¹³

FIGURE 5 Images showing a large periprosthetic pseudotumor. A, AP radiograph. B, Axial fat-sensitive proton density magnetic resonance image. C, Coronal short tau inversion recovery magnetic resonance image. Note the masslike formation of the inflammatory debris and fluid as well as destruction and resorption of the adjacent bone and soft tissues.