Many miscellaneous benign soft-tissue tumors are brought to clinical attention because of a palpable mass. Pain is a symptom of some of these tumors. Most are true neoplasms, but others are considered reactive.

Elastofibroma is a reactive benign soft-tissue pseudotumor with an excellent prognosis. It comprises 2% of all primary tumors localized on the chest wall¹ and was first described in 1961.² It has a peak incidence in the sixth and seventh decades of life and is more prevalent in women than in men. Most patients have a history of involvement in heavy manual labor or sports that require extensive use of the upper extremities. Autopsy studies have shown that elastofibromas occur in up to 24% of females and 11% of males older than 55 years, with elastofibromalike changes seen in as many as 81% of these patients, suggesting aging as a cause.^3,4 Elastofibromas have been found incidentally in approximately 0.8% to 3% of chest CT scans.^5,6 The lesion is an ill-defined mass that almost always occurs between the inferior angle of the scapula and the chest wall (beneath the latissimus dorsi and rhomboid muscles and the chest wall) and is firmly attached to the chest wall in the area of the seventh and eighth ribs posteriorly. Some authors consider this location pathognomonic.⁷ Elastofibromas can occur in other rare locations such as ischial tuberosity, olecranon, deltoid muscle, axilla, interspinal space, and omentum.⁸ They often present with unilateral disease, but up to 60% are bilateral.⁹ Clinically, elastofibromas are rarely painful, and patients most often report the symptom of a snapping sensation in the lower portion of the scapula. Pathogenesis is unclear but is thought to be a proliferative response to mechanical stresses due to repetitive trauma and manual labor. However, a genetic predisposition is suspected in those with a high familial incidence and in the rare occasion when the lesion occurs in the gastrointestinal tract.⁹ As discussed in a 2020 study, familial occurrence has been reported in Europe and Japan with the largest series of lesions, noting
32% of cases occurring within the same family lines.¹⁰ Immunohistochemical studies have pointed to possible overexpression of transforming growth factor beta 1 and basic fibroblast growth factor. Genomic analysis has shown recurrent gains in Xq12-q22 and losses in 1p, 13q, 19p, and 22q.^11,12

Grossly, the lesion is firm with an appearance similar to a desmoid tumor and can contain mature fat (Figure 1). Histologically, elastofibromas are composed of intertwining eosinophilic collagen fibers and abnormal thick elastin fibers. Abnormal thick elastin fibers have a degenerated, beaded appearance, or are fragmented into small globules or droplets that are visualized with antibodies or Verhoeff stain (specific for elastin fiber). CT reveals an inhomogeneous soft-tissue mass with densities approximating muscle and with poorly defined margins. CT shows the highest correlation with actual pathologic size.¹⁰ MRI shows a mass with intermediate signal intensity on T1-weighted and T2-weighted images with interlaced areas of fat. There is heterogeneous enhancement with gadolinium. Ultrasonography can also show these masses.¹³ Imaging with positron emission tomography-CT has shown mild diffuse increased uptake, with a mean standardized uptake value of 2.24.¹⁴ As discussed
in a 2020 study, diffusion-weighted magnetic resonance images have been used to confirm the benign character of these lesions, with restricted diffusion noted.¹⁵ Simple excision is usually curative, with a low recurrence rate (0.06% to 4.5%).⁹ Excision is recommended for symptomatic lesions larger than 5 cm. However, postoperative complications including hematoma and seroma formation have been reported and can occur in 17% to 40% of cases. Antiplatelet drugs and body mass index less than 25 kg/m² were risk factors for complications, as discussed in recent studies.^10,16 Scapulothoracic joint arthroscopic excision has been performed in selected cases.¹⁷ There are also reports of curative treatment with radiation therapy alone without surgery.¹⁸ There are no reports of malignant transformation or metastatic potential.

Tenosynovial giant cell tumor (TGCT) is the preferred term in contemporary World Health Organization nomenclature¹⁹ for what was previously called giant cell tumor of tendon sheath, nodular tenosynovitis, or localized pigmented villonodular synovitis. It is a slow-growing, benign soft-tissue tumor that typically occurs as a solitary lesion in the hand. It is the second most common tumor of the hand (after ganglions) and also can occur in other areas, such as the foot, knee, elbow, and wrist.^20,21 It is the most common proliferative lesion in the upper extremity. Typical location is the volar aspect of the hand with propensity for the radial three digits and the distal interphalangeal joints. These tumors are more common in adults (fourth and fifth decades) and are more common in females than in males.²² The lesion is rare in children, but when it is found in children, its presentation and treatment are similar to that for adults.²³ Lesions typically appear as a painless mass that has existed for several years. Pain can be a sign of neurovascular bundle involvement.²⁴ Radiographs can reveal cortical erosion or remodeling of adjacent bone or degenerative changes in an adjacent joint.

Pathogenesis of TGCT is thought to be due to a balanced translocation breakpoint localized to 1p13, leading to an overproduction of macrophage colony-stimulating factor (colony stimulating factor 1 [CSF-1]). This occurs in both diffuse and localized forms of TGCT as well as pigmented villonodular synovitis within joints. This results in a tumor landscaping phenomenon in which only a small portion of the cells are truly neoplastic (2% to 16%), producing CSF-1 in an autocrine and paracrine manner.^25,26

Histologically, TGCT is composed of multinucleated giant cells, round to polygonal mononuclear cells, collagen fibers, and hemosiderin deposits. Mitotic figures, which occur in more than 50% of patients, can lead to a misdiagnosis of malignancy.²²

TGCT has a reported recurrence rate of up to 45%.²⁰ Recurrence typically is within 2 to 4 years following excision, but recurrence after more than 10 years has been reported.²⁷ Risk factors for recurrence have included the presence of adjacent degenerative joint disease, location at the distal interphalangeal joint of the finger or interphalangeal joint of the thumb, the presence of osseous pressure erosions or indentation, incomplete tumor excision, location near the neurovascular bundle, and increased mitotic activity on histologic assessment.^27,28

MRI of TGCT is distinctive and sometimes diagnostic, showing the characteristic low or intermediate signal intensity on both T1-weighted and T2-weighted images (Figure 2). There is postcontrast enhancement. Management of TGCT consists of complete surgical excision under loupe magnification to reduce local recurrence. Adjuvant therapy and bone grafting are recommended for areas with cortical erosion or cortical penetration and osseous invasion, as discussed in recent studies.^28,29 Recurrent or infiltrative tumors can be managed with radiation therapy, with acceptable results.³⁰ Locally advanced or metastatic TGCT has been managed with imatinib (Gleevec), with 19% of patients having a partial or complete response and 74% with stabilization of the disease. Mechanism of action of imatinib is inhibition of the CSF-1 receptor’s tyrosine kinase activity.³¹ Pexidartinib, a CSF-1 receptor inhibitor, has been FDA approved as well for TGCT.³² Other small-molecule CSF-1 receptor inhibitors that have been developed recently include vemseltinib (DCC-3014) and pimicotinib (ABSK021), as well as monoclonal antibodies such as emactuzumab (RG-7155), cabiralizumab (FPA008), and AMB-5X (intra-articular injection).³³ All of these agents can lead to similar adverse effects (liver enzyme elevation or toxicity, periorbital edema, etc) but have shown improved clinical efficacy (pain, swelling, stiffness) and radiographic response. A 2023 phase 1B clinical trial of pimicotinib in patients with TGCT who are not amenable to surgery demonstrated significant antitumor activity with favorable pharmacokinetic profiles. There was no apparent hepatotoxicity.³⁴ Because liver toxicity is a concern with most of these drugs, regular monitoring should be considered mandatory. Because these drugs block the CSF-1 receptor and not the neoplastic cells producing CSF-1, patients must continue taking them for an extended period.

Glomus tumor is a benign neoplastic process named for the identification of cells that resemble the modified smooth muscle cells of the normal glomus body under light microscopy.³⁵ These tumors arise from a neuromyoarterial structure called the glomus body (Sucquet-Hoyer canal) that provides a thermoregulatory function and is likely unrelated to these tumors. These uncommon tumors represent less than 2% of soft-tissue tumors and 1% to 5% of tumors of the upper extremity. They occur in the third through fifth decades, and although there is no sex predilection, females usually present with tumors in the subungual region of the hand, whereas males often experience tumors in other body parts.³⁶ They appear as small, blue-red nodules in the deep dermis or subcutaneous area of the upper or lower extremity. The most common site is the subungual region of the finger, where the tumor occurs more frequently in females (3:1 ratio). Other common locations include the palm, wrist, forearm, and foot.³⁷ However, glomus tumors can occur in less common locations such as the gastrointestinal tract, female reproductive tract, mesentery, trachea, and bone.³⁸ The lesions are usually solitary, but multiple lesions have been reported in 10% of patients. In the multifocal form, they occur more frequently in children, are usually not in a subungual location, and are less likely to be painful. Multiple glomus tumors are typically associated with a mutation in the glomulin gene, located at chromosome band 1p21-22, which codes for synthesis of the glomulin protein. This mutation is inherited in an autosomal dominant pattern.³⁹ Multiple glomus tumors have also been associated with neurofibromatosis type 1 because of biallelic loss of the NF-1 gene.

Glomus tumors produce the characteristic symptom of paroxysms of lancinating pain that is out of proportion to the size of the lesion. The pain is usually elicited by changes in temperature or touch/pressure to the area of the lesion.⁴⁰ Subungual glomus tumors can cause nail changes and pressure erosion into the underlying distal phalanx (visible on radiographs). The mechanism of pain is thought to be mediated by the release of substance P from nerve fibers contained in glomus tumors.

Recommended imaging modalities include ultrasonography and MRI, as discussed in a 2022 study.⁴¹ MRI is useful in imaging tumors larger than 2 mm. A characteristic high-signal central dot with a surrounding zone of lower signal is seen. There is low signal intensity on T1-weighted images, high signal intensity on T2-weighted images, and postcontrast enhancement.⁴²

Histologically, glomus tumors can have varying proportions of glomus cells, vascular structures, and smooth muscle tissue. They are categorized into three groups on the basis of these proportions and include glomus tumor proper (75%), glomangioma (20%), and glomangiomyoma. Management of glomus tumors involves simple excision.³⁶ Recurrence rates of 4% to 50% are usually associated with incomplete excision, as discussed in a 2021 study.⁴³