Thigh Mass in a 73-Year-Old Woman

Abstract

LEARNING OBJECTIVES On completion of this activity, the reader should be able to: identify radiographic features that suggest the presence of an adipose neoplasm; describe the histologic differences between adipose neoplasms; and select the appropriate treatment for the adipose lesion. HISTORY AND PHYSICAL EXAMINATION A 73-year-old female was referred to the orthopaedic service with a history of a large right thigh mass first noticed 2 months previously. The mass was nonpainful, but was associated with a feeling of heaviness and pressure, especially with standing for long periods of time. The patient denied numbness, parasthesias, and weakness of the right lower extremity. There was no history of trauma and no history suggestive of infection. The patient did not report other masses. The patient’s medical history included a small, possibly benign soft tissue mass excised from the same area 3 years previously. No further information concerning this mass was available. Other past medical history and family history were noncontributory. On physical examination, the patient had a normal gait pattern. A 20 × 10 cm deep, soft, nontender mass was palpated on the proximal ⅔ of the anterolateral right thigh. There was no warmth, erythema, or surrounding edema. A 3-cm linear scar that had healed by primary intention was observed superficial to the mass. Range of motion, strength, and neurovascular examination were normal for both lower extremities. No other masses were palpated on general exam, and there was no considerable lymphadenopathy. The rest of the physical examination was normal. Anteroposterior and lateral plain radiographs, a CT scan, and MR imaging scans of the right leg obtained 2 weeks before referral to the authors’ institution are shown in Figures 1, 2, and 3. Based on the history, physical examination, and imaging studies, what is the differential diagnosis?Fig 1.: An AP plain radiograph of the right thigh shows a large, well-defined soft tissue mass.Fig 2.: An unenhanced axial CT scan of the right thigh shows a well-defined hypodense mass containing an area with a slightly increased density (arrow).Fig 3.: A-B. (A) An unenhanced T1-weighted coronal MR scan shows a hyperintense mass with a small foci of hypointensity superiorly. (B) A STIR coronal MR scan shows suppression of the areas of the mass that are hyperintense on T1-weighted images and hyperintensity of the small foci that are hypointense on T1-weighted images.IMAGING INTERPERETATION Plain radiographs (Fig 1) of the right thigh showed a large, lucent lesion in the soft tissue of the right thigh laterally. No bony abnormalities were observed. An unenhanced CT image (Fig 2) of the right thigh showed a well-defined hypodense mass in the vastus lateralis muscle measuring −100 to −127 Hounsfield Units (HU). The mass contained an ill-defined area with a slightly increased density laterally (Fig 2, arrow). A T1-weighted (TR=600/TE=10) unenhanced coronal MR image (Fig 3A) and a STIR (TR=5866/TR=32.6/TI=150) coronal MR scan (Fig 3B) showed a 20 cm × 8.5 cm × 5.3 cm mass that was hyperintense on the T1-weighted images and suppressed on the STIR sequences almost entirely, with small foci of hypointensity in the mass superiorly on the T1-weighted scans (Fig 3, arrow), which became hyperintense on the STIR images (Fig 3, arrow). DIFFERENTIAL DIAGNOSIS Lipoma Atypical lipoma Liposarcoma Hibernoma Intramuscular myxoma The mass was completely excised without complications and was sent for routine histologic analysis. Based on the history, physical examination, imaging studies, and histologic picture, what is the diagnosis and how should the patient be treated? See page 269 for diagnosis and treatment. Continuation of ORP conference from page 268. HISTOLOGY INTERPRETATION The gross specimen consisted of multiple fragments of soft, yellow, lobulated tissue with admixed white fibrous tissue measuring 19.0 × 8.0 × 4.8 cm in aggregate. A low-power histologic section (Fig 4) showed that the lesion consisted of predominantly mature-appearing, uniloculated adipose tissue. A well-defined area of increased cellularity, mild atypia, and nuclear hyperchromasia was observed within the section. A high-power image (Fig 5) showed details of the lipoblast (Fig 5, arrow), including a multiloculated cytoplasm with locules causing scalloping of the nucleus (Fig 5, arrowhead). Undifferentiated fusiform cells and primitive round cells were not identified within the lesion.Fig 4.: A photomicrograph of a low-power histologic section (Stain, hematoxylin and eosin; original magnification ×100) shows that the lesion consists of predominantly mature adipose tissue, with well-defined areas of increased cellularity, mild atypia, and nuclear hyperchromasia.Fig 5.: A photomicrograph (Stain, hematoxylin and eosin; original magnification ×400) of a high-power histologic section shows features of a lipoblast (arrow) including scalloping of the nucleus (arrowhead).DIAGNOSIS Atypical lipoma DISCUSSION AND TREATMENT The lesion was treated surgically. A longitudinal incision was made on the lateral aspect of the right thigh, which was then dissected to the level of the mass. The tumor was then easily excised, as it was well-demarcated from the surrounding tissue and was not in close proximity to main neurovascular structures. The wound was closed in layers and the patient’s postoperative course was uneventful. The clinical features, imaging, and histology of the mass led to its categorization as a lipomatous tumor. Differentiating among the variety of lipomatous tumors requires a careful consideration of the history, physical examination, imaging, and histologic evidence. The large size of the mass and thick fibrous septa, evident radiographically on CT and MR imaging, make the diagnosis of a classic lipoma unlikely.17 Although radiographic evidence alone is inadequate for differentiating atypical lipomas from liposarcomas,4,5 analysis of the histologic evidence made this distinction clear. Features of high-grade liposarcomas, including undifferentiated fusiform cells, small lipoblasts in a myxoid matrix, and primitive round cells with hyperchromic nuclei, were histologically absent in this case. Although intramuscular myxomas can mimic atypical lipomas on clinical presentation and imaging, the diagnosis was excluded based on histology. Intramuscular myxomas typically appear as paucicellular and hypovascular lesions with an abundant myxoid matrix, containing bland spindle-shaped or stellate cells and rare muciphages.19 These tumors lack an abundance of the mature fat cells seen in histology images of the lesion presented in this case. The diagnosis of hibernoma was excluded based on its rare occurrence in muscle and the lack of brown fat on histology.18 The histologic appearance of the patient’s specimen was most consistent with that of an atypical lipoma. There has been some debate in the literature about the terminology used to describe atypical lipomas. Previously, the term well-differentiated liposarcoma was used to define a group of lipomatous tumors found in the retroperitoneum, groin, and extremities, which tend to have a more benign course than other liposarcomas, but show a greater degree of atypia and tendency for recurrence than benign lipomas. Most authors now use the term atypical lipoma to describe more appropriately the subset of well-differentiated liposarcomas occurring in the extremities, which generally have a more benign nature and favorable prognosis than those found in the retroperitoneum.9,17 Other authors argue for maintaining the term well-differentiated liposarcoma for such masses occurring deep in the extremities because of their greater tendency for recurrence and dedifferentiation than masses that are superficial.20 Although both terms, atypical lipoma and well-differentiated liposarcoma, continue to be used in the literature by different authors to describe similar entities in different circumstances, they can be considered synonyms. Atypical lipomas traditionally have been divided into three histologic subtypes, although the classification is rarely used in the clinical setting.17 The most common is the lipoma-like type of atypical lipoma, presented in this case. Histologically, this type appears as clusters of mature adipose cells of variable shape and size divided by fibrous septa composed of scattered, atypical, irregularly shaped lipoblast cells as well as clusters of multivacuolated cells intermixed with spindle cells. The inflammatory type of atypical lipoma is much less common and occurs most often in the retroperitoneum. Histologically, it appears as mature adipose cells interspersed with scattered lipoblasts and an inflammatory infiltrate composed of lymphocytes and plasma cells. Because lipoblasts tend to be rare in these lesions, they are easily mistaken for lipomas or inflammatory processes involving fatty tissue. Lastly, the uncommon sclerosing type appears histologically as scattered lipoblasts and atypical cells within adipose tissue intermixed with areas of dense fibrosis. Although some authors advocate the inclusion of spindle cell and pleomorphic lipomas with atypical lipomas because of their similarly benign nature,2,6 most classify them as separate entities.3 The usual clinical presentation of an atypical lipoma is that of a middle-aged patient with a slow growing, painless mass that reaches a large size before recognition. Pain, tenderness, and functional disability are rare and usually associated with larger tumors. Superficial atypical lipomas occur most often in the posterior neck and upper back, whereas those that are deep most often occur in the thigh, arm, and buttock.6 Atypical lipomas tend to occur in patients of a slightly older age than patients affected by liposarcomas.7 Unlike retroperitoneal liposarcomas, which affect a slightly higher proportion of women, lipomas occurring in the extremities are more often found in men.7,10,13 Racial or geographic associations with atypical lipomas have not been reported in the literature.17 Although MRI and CT scans can be used preoperatively to help delineate lipomatous masses, the radiologic diagnosis of atypical lipomas may be difficult. On fat-suppressed, T1-weighted MR images, lipomas tend to show thin septa, which only enhance slightly, while atypical lipomas and liposarcomas have thick septa that enhance to a greater degree.8 Furthermore, lipomas usually show a uniform fat density, whereas liposarcomas are characterized by a paucity to absence of fat density on MRI.5 However, because atypical lipomas can mimic liposarcomas on CT and MRI,4,5 this clinical distinction is more difficult to establish radiologically, making a histologic diagnosis necessary. Because of the heterogeneous nature of these masses, a needle biopsy would be an unreliable source of tissue, therefore making excisional biopsy the preferred modality of diagnosis and management. Few reports describing the natural history and outcomes of treatment of atypical lipomas exist in the orthopaedic literature. Whereas local recurrence and dedifferentiation can occur, it is clear that these tumors have little tendency for distant metastasis.20 Recurrence rates for superficial atypical lipomas have been reported between 0 and 50%.1,6,15 Reports of recurrence rates for deep atypical lipomas have been more consistent, ranging from 43 to 69%.6,15,16 The identified risk factors for recurrence include occurrence of a deep lesion and positive margins at the time of excision.11,15 Most recurrences are known to occur within 6 years of the original diagnosis.15 It is possible that the atypical lipoma of the patient described in this report represents a recurrence of the mass excised 3 years previously. Dedifferentiation of atypical lipomas to more aggressive tumors with a potential for metastasis is rare for lipomas of the extremities, occurring in up to 6% of these masses at an average of 10 years after diagnosis.15,16 These data suggest that the treatment of choice for deep atypical lipomas is wide excision to prevent recurrence and the appropriate follow-up should be at 6-month intervals during the first 6 years to monitor for recurrence clinically, after which annual clinical followup should be continued.15 Considerable progress has been made in research aimed at discovering genetic abnormalities associated with atypical lipomas. Karyotype analysis has shown that supranumerary ring and giant marker chromosomes often are found in low-grade soft tissue tumors, including atypical lipomas. Fluorescent in situ hybridization (FISH) studies have been used to show that the ring and marker structures consist of amplified material from specific chromosome segments, including the 12q15-12q21 region. This segment is known to contain several tumorigenic genes, including MDM2, HMGIC, CDK4, GLI, and SAS.12 These genes encode a cell surface protein (SAS), a protein kinase (CDK4), a tumor suppressor regulator (MDM2), and transcription factors (GLI and HMGIC) involved in cell activation and proliferation. It is possible that amplification of these genes leads to abnormal cellular activity and subsequent tumor growth. Evidence has shown a considerable association among atypical lipomas and supranumerary ring and giant marker chromosomes and that these structures are associated with potential for local recurrence and tumor progression among atypical lipomas.14 These findings support the potential clinical role of genetic analysis in the delineation of atypical lipomas from other histologically similar tumors and in the prediction of the malignant behavior of a given atypical lipoma. In the current case, subsequent to tumor excision, the wound healed uneventfully and at 9-month followup, the patient continued to do well and had maintained full function of her right leg. The patient will be followed clinically to monitor for recurrence.