Early Pleomorphic Hyalinizing Angiectatic Tumor: Precursor or Distinct Lesion?

Abstract

Case Reports Free Vincent M. Moretti, MD; Michael de la Cruz, MD; John S.J. Brooks, MD; Richard D. Lackman, MD Early pleomorphic hyalinizing angiectatic tumor is a rare and recently described soft tissue lesion. Originally believed to be a precursor lesion to neoplastic pleomorphic hyalinizing angiectatic tumor, and possibly identical to hemosiderotic fibrohistiocytic lipomatous lesion/tumor, there have been recent suggestions that it is distinct from pleomorphic hyalinizing angiectatic tumor and is instead a reactive process. This article reports a case of a mass in the foot of a 45-year-old woman, which is 1 of only 15 published cases of early pleomorphic hyalinizing angiectatic tumor and is the first case to describe its radiographic appearance. Early pleomorphic hyalinizing angiectatic tumor predominantly develops in the fourth to sixth decades (average age, 45 years, range, 10-67 years). Females predominate 4 to 1. The foot/ankle is the most common site (67%). On magnetic resonance imaging (MRI), the mass appeared inhomogeneously dark on T1-weighted sequences and inhomogeneously bright on fat-suppressed T2-weighted sequences. Forty-four percent of resected lesions recur locally, but no early pleomorphic hyalinizing angiectatic tumor lesion has ever metastasized. These clinical characteristics of early pleomorphic hyalinizing angiectatic tumors closely mirror those of hemosiderotic fibrohistiocytic lipomatous lesions/tumors and are dissimilar to those for classic pleomorphic hyalinizing angiectatic tumors. Therefore, although the 3 entities share several histologic features, we believe early pleomorphic hyalinizing angiectatic tumor is equivalent to hemosiderotic fibrohistiocytic lipomatous lesion/tumor and is not a true precursor to classic pleomorphic hyalinizing angiectatic tumor. Pleomorphic hyalinizing angiectatic tumor is a rare benign soft tissue neoplasm. Smith et al¹ first described these tumors in 1996 after recognizing their consistent histologic pattern in the masses of 14 patients. Folpe and Weiss² later published a larger series on pleomorphic hyalinizing angiectatic tumor in 2004, in which they proposed an evolution of these tumors from a new precursor lesion they named early pleomorphic hyalinizing angiectatic tumor. Folpe and Weiss² also recognized the histologic similarities between early pleomorphic hyalinizing angiectatic tumor and hemosiderotic fibrohistiocytic lipomatous lesion/tumor, a rare and presumably benign fibrolipomatous entity that was first described by Marshall-Taylor and Fanburg-Smith³ in 2000. This prompted Folpe and Weiss² to further propose that the 2 lesions were identical in addition to being neoplastic precursors of pleomorphic hyalinizing angiectatic tumor.² Subsequent authors have questioned this precursor relationship, however.^3-6 Including this article, only 15 cases of isolated early pleomorphic hyalinizing angiectatic tumor have been published in the scientific literature, primarily in pathology journals.^2,7 There are no prior reports of these lesions in any of the orthopedic or oncologic literature. This article presents a case of a rare lesion arising in the foot of a 45-year-old woman, including the first radiographic description of an early-pleomorphic hyalinizing angiectatic tumor lesion. A 45-year-old woman presented with a left foot mass of indeterminate duration. The mass caused mild pain during activity, but none at rest. She reported no fever/chills, night sweats, or weight loss. Her medical history was notable for schizophrenia and paraplegia. Examination revealed bilateral equinus and a large soft tissue mass in her dorsal left foot. The mass was soft, minimally tender, and purple. Vascular examination was normal, but strength, range of motion, and neurologic examination were limited by the patient’s other medical conditions. Magnetic resonance imaging revealed a 7.7×7.0×9.1-cm well-defined mass in her left foot (Figure 1). It appeared inhomogeneously dark on T1-weighted sequences and inhomogeneously bright on fat-suppressed T2-weighted sequences (Figure 1). The mass enhanced avidly and heterogeneously with contrast (Figure 1C). Figure 1: A T1-weighted sagittal MRI demonstrates an inhomogeneously low-signal mass in the dorsum of the left foot (A). A T2-weighted fat-suppressed axial MRI demonstrates an inhomogeneously high-signal mass (B). A T1-weighted fat-suppressed sagittal MRI demonstrates avid and heterogeneous contrast enhancement (C).… Early pleomorphic hyalinizing angiectatic tumor is a rare and recently described soft tissue lesion. Originally believed to be a precursor lesion to neoplastic pleomorphic hyalinizing angiectatic tumor, and possibly identical to hemosiderotic fibrohistiocytic lipomatous lesion/tumor, there have been recent suggestions that it is distinct from pleomorphic hyalinizing angiectatic tumor and is instead a reactive process. This article reports a case of a mass in the foot of a 45-year-old woman, which is 1 of only 15 published cases of early pleomorphic hyalinizing angiectatic tumor and is the first case to describe its radiographic appearance. Early pleomorphic hyalinizing angiectatic tumor predominantly develops in the fourth to sixth decades (average age, 45 years, range, 10-67 years). Females predominate 4 to 1. The foot/ankle is the most common site (67%). On magnetic resonance imaging (MRI), the mass appeared inhomogeneously dark on T1-weighted sequences and inhomogeneously bright on fat-suppressed T2-weighted sequences. Forty-four percent of resected lesions recur locally, but no early pleomorphic hyalinizing angiectatic tumor lesion has ever metastasized. These clinical characteristics of early pleomorphic hyalinizing angiectatic tumors closely mirror those of hemosiderotic fibrohistiocytic lipomatous lesions/tumors and are dissimilar to those for classic pleomorphic hyalinizing angiectatic tumors. Therefore, although the 3 entities share several histologic features, we believe early pleomorphic hyalinizing angiectatic tumor is equivalent to hemosiderotic fibrohistiocytic lipomatous lesion/tumor and is not a true precursor to classic pleomorphic hyalinizing angiectatic tumor. Pleomorphic hyalinizing angiectatic tumor is a rare benign soft tissue neoplasm. Smith et al¹ first described these tumors in 1996 after recognizing their consistent histologic pattern in the masses of 14 patients. Folpe and Weiss² later published a larger series on pleomorphic hyalinizing angiectatic tumor in 2004, in which they proposed an evolution of these tumors from a new precursor lesion they named early pleomorphic hyalinizing angiectatic tumor. Folpe and Weiss² also recognized the histologic similarities between early pleomorphic hyalinizing angiectatic tumor and hemosiderotic fibrohistiocytic lipomatous lesion/tumor, a rare and presumably benign fibrolipomatous entity that was first described by Marshall-Taylor and Fanburg-Smith³ in 2000. This prompted Folpe and Weiss² to further propose that the 2 lesions were identical in addition to being neoplastic precursors of pleomorphic hyalinizing angiectatic tumor.² Subsequent authors have questioned this precursor relationship, however.^3-6 Including this article, only 15 cases of isolated early pleomorphic hyalinizing angiectatic tumor have been published in the scientific literature, primarily in pathology journals.^2,7 There are no prior reports of these lesions in any of the orthopedic or oncologic literature. This article presents a case of a rare lesion arising in the foot of a 45-year-old woman, including the first radiographic description of an early-pleomorphic hyalinizing angiectatic tumor lesion. A 45-year-old woman presented with a left foot mass of indeterminate duration. The mass caused mild pain during activity, but none at rest. She reported no fever/chills, night sweats, or weight loss. Her medical history was notable for schizophrenia and paraplegia. Examination revealed bilateral equinus and a large soft tissue mass in her dorsal left foot. The mass was soft, minimally tender, and purple. Vascular examination was normal, but strength, range of motion, and neurologic examination were limited by the patient’s other medical conditions. Magnetic resonance imaging revealed a 7.7×7.0×9.1-cm well-defined mass in her left foot (Figure 1). It appeared inhomogeneously dark on T1-weighted sequences and inhomogeneously bright on fat-suppressed T2-weighted sequences (Figure 1). The mass enhanced avidly and heterogeneously with contrast (Figure 1C). Figure 1: A T1-weighted sagittal MRI demonstrates an inhomogeneously low-signal mass in the dorsum of the left foot (A). A T2-weighted fat-suppressed axial MRI demonstrates an inhomogeneously high-signal mass (B). A T1-weighted fat-suppressed sagittal MRI demonstrates avid and heterogeneous contrast enhancement (C). An open biopsy was subsequently performed. Intraoperatively the mass lacked a pseudocapsule and was adherent to the overlying skin, with no normal subcutaneous tissue in the area. Several small specimens were removed by biopsy and sent to pathology for review. Histology revealed variable cellularity, a myxoid matrix, and an inflammatory infiltrate comprising primarily mast cells (Figure 2). Lesional cells contained occasional intranuclear pseudoinclusions and hemosiderin deposition (Figure 2). Small thin-walled vessels and entrapped adipose tissue were also present (Figure 2). A diagnosis of early pleomorphic hyalinizing angiectatic tumor was made. Figure 2: At high power, a cellular area containing lesional cells with intracytoplasmic hemosiderin is seen (A). Intermixed mast cells can also be visualized. At high power, a myxoid area is apparent (B). At high power, large multinucleated cells with hemosiderin and intranuclear inclusions are seen (C). At low power, entrapped mature adipose tissue is visible (D). The mass was subsequently followed clinically with routine observation. At recent follow-up, 50 months after biopsy, the patient was found to be doing well. Her caretakers reported no appreciable change in the mass’s size or asymptomatic nature. Pleomorphic hyalinizing angiectatic tumor is a rare soft tissue neoplasm.^1,2,8 Smith et al¹ first described these tumors in 1996 and distinguished them histologically by their sheet-like proliferations of mitotically inactive spindled and pleomorphic cells, scattered clusters of ectatic vessels with circumferential hyalinization, intranuclear inclusions, and intracytoplasmic hemosiderin deposits. Folpe and Weiss² later published a larger series on pleomorphic hyalinizing angiectatic tumor in 2004, in which they proposed an evolution of these tumors from a new precursor lesion they named early pleomorphic hyalinizing angiectatic tumor. They defined early pleomorphic hyalinizing angiectatic tumor as a hypocellular proliferation of bland spindled cells that infiltrated fat amongst a variably myxoid background.² Their evolutionary claim was based on the observation of this pattern in association with 70% of their classic pleomorphic hyalinizing angiectatic tumor lesions.² They also saw these same low-grade spindle-cell lesions in isolation in 13 of their cases, completely absent from any area of classic pleomorphic hyalinizing angiectatic tumor, and reported 1 isolated early pleomorphic hyalinizing angiectatic tumor case that recurred as a mixed early pleomorphic hyalinizing angiectatic tumor and classic pleomorphic hyalinizing angiectatic tumor lesion.² Folpe and Weiss² further supported their claim by describing several histologic features frequently seen in early pleomorphic hyalinizing angiectatic tumor that mirror those of classic pleomorphic hyalinizing angiectatic tumor: abundant intracytoplasmic hemosiderin pigment, tiny ectatic vessels, and rare pleomorphic cells with intranuclear pseudoinclusions.² These histologic similarities were subsequently reported by other authors as well.^9,10 Folpe and Weiss² were also the first to recognize the histologic similarities between early pleomorphic hyalinizing angiectatic tumor and hemosiderotic fibrohistiocytic lipomatous lesion/tumor, a rare and presumably benign fibrolipomatous entity that was first described in 2000.³ This prompted them to propose that the 2 lesions were identical, in addition to being neoplastic precursors of pleomorphic hyalinizing angiectatic tumor.² Several subsequent authors acknowledged the histologic overlap between early pleomorphic hyalinizing angiectatic tumor and hemosiderotic fibrohistiocytic lipomatous lesion/tumor: an admixture of mature adipocytes arranged in lobules, fibrous septa composed of spindle cells and inflammatory cells, hemosiderin deposition, nuclear pseudoinclusions, and foci of myxoid stroma.^2,4,6,7 However, some authors questioned the precursor relationship for early pleomorphic hyalinizing angiectatic tumor or hemosiderotic fibrohistiocytic lipomatous lesion/tumor.^3-6 Michal and Kazakov⁶ instead proposed that the early pleomorphic hyalinizing angiectatic tumor or hemosiderotic fibrohistiocytic lipomatous lesion/tumor seen in association with classic pleomorphic hyalinizing angiectatic tumor may simply be reactive changes secondary to vascular damage from the neoplastic pleomorphic hyalinizing angiectatic tumor. Although there is histologic overlap between all 3 entities, differences arise when early pleomorphic hyalinizing angiectatic tumor’s clinical patterns is compared to those for hemosiderotic fibrohistiocytic lipomatous lesion/tumor and classic pleomorphic hyalinizing angiectatic tumor. Our review of all 15 cases of isolated early pleomorphic hyalinizing angiectatic tumor (Table ) suggests that it predominately occurs in the fourth to sixth decades, with a mean age of 45 years (range, 10-67 years) at diagnosis.^2,7 In comparison, the mean age from all cases in the literature for hemosiderotic fibrohistiocytic lipomatous lesion/tumor and classic pleomorphic hyalinizing angiectatic tumor is 50 years (range, 0.67-74 years)^3-5,11-15 and 57 years (range, 19-89 years), respectively.^{1,2,9,10,16-31} Early pleomorphic hyalinizing angiectatic tumor shows a strong female predilection of 4:1,^2,7 similar to hemosiderotic fibrohistiocytic lipomatous lesion/tumor’s strong female predilection of 22:9.^3-5,11-15 Classic pleomorphic hyalinizing angiectatic tumor, in contrast, only shows a minimal female predilection of 12:11.^{1,2,9,10,16-31} All 3 entities typically present as a slow-growing painless mass in the subcutaneous tissue. Early pleomorphic hyalinizing angiectatic tumor most frequently occurs in the lower extremity (11 cases, 73%), particularly in the foot/ankle (10 cases, 67%). Hemosiderotic fibrohistiocytic lipomatous lesion/tumor similarly predominates in the foot/ankle (84%),^3-5,11-15 while classic pleomorphic hyalinizing angiectatic tumor has only developed in the foot/ankle 19% of the time.^{1,2,9,10,16-31} Early-pleomorphic hyalinizing angiectatic tumor’s average size at diagnosis is 5.7 cm, with values ranging from 2 to 10.2 cm.^2,7 Both hemosiderotic fibrohistiocytic lipomatous lesion/tumor and classic pleomorphic hyalinizing angiectatic tumor are similarly sized at diagnosis, with means of 7.7 cm (range, 0.1-19 cm)^3-5,11-15 and 5.4 cm (range, 0.3-19.7 cm), respectively.^{1,2,9,10,17-31} Imaging studies have not previously been reported for early pleomorphic hyalinizing angiectatic tumor, and they are rarely reported in the literature for hemosiderotic fibrohistiocytic lipomatous lesion/tumor or classic pleomorphic hyalinizing angiectatic tumor. The early pleomorphic hyalinizing angiectatic tumor in our patient appeared inhomogeneously dark on T1, inhomogeneously bright on T2, and heterogeneous-enhanced after contrast. Somewhat similarly, classic pleomorphic hyalinizing angiectatic tumor appears as a soft tissue mass with low signal on T1, high signal with scattered areas of low signal on T2, and homogenous contrast enhancement.^27,29,31 Hemosiderotic fibrohistiocytic lipomatous lesion/tumor, however, appears as a fatty tumor with ill-defined borders on MRI.^11,15 It is typically isointense to fat on T1- and T2-weighted sequences, and has variable responses to contrast.^11,15 More radiographic examples of early pleomorphic hyalinizing angiectatic tumor are needed before comparisons can be made based on its imaging appearance. Although the small number of published cases of these 3 entities makes it difficult to establish any consensus, the prognosis for each is generally considered good due to their slow growth and benign histologic appearance. The lack of any metastases to date with early pleomorphic hyalinizing angiectatic tumor,^2,7 classic pleomorphic hyalinizing angiectatic tumor,^{1,2,9,10,16-31} or hemosiderotic fibrohistiocytic lipomatous lesion/tumor^3-5,11-15 further supports these benign presumptions. All 3 have been associated with relatively high local recurrence rates after surgical excision. Our review of early pleomorphic hyalinizing angiectatic tumor revealed that 4 patients (44%) had local recurrences out of the 9 with documented follow-up.^2,7 Similarly, the 2 largest studies on hemosiderotic fibrohistiocytic lipomatous lesion/tumor, by Marshall-Taylor and Fanburg-Smith³ and Browne and Fletcher,¹³ revealed local recurrence rates of 38% and 33%, respectively. The 2 largest studies on classic pleomorphic hyalinizing angiectatic tumor, by Smith et al¹ and Folpe and Weiss,² revealed local recurrence rates of 50% and 17%, respectively. Early pleomorphic hyalinizing angiectatic tumor is a rare soft tissue lesion defined histologically by hypocellular proliferation of bland spindled cells that infiltrate fat in a variably myxoid background. Early pleomorphic hyalinizing angiectatic tumor typically presents as a slow-growing soft tissue mass in the foot/ankle of middle-aged women. On MRI it can appear inhomogeneously dark on T1 and inhomogeneously bright on T2, with avid heterogeneous enhancement. Early pleomorphic hyalinizing angiectatic tumor has shown a propensity for local recurrence after surgical excision, but no metastases have ever been reported. The clinical characteristics of early pleomorphic hyalinizing angiectatic tumor closely mirror those of hemosiderotic fibrohistiocytic lipomatous lesion/tumor and are dissimilar to those for classic pleomorphic hyalinizing angiectatic tumor. Drs Moretti and Lackman are from the Department of Orthopedic Surgery, University of Pennsylvania, and Drs de la Cruz and Brooks are from the Department of Pathology, Pennsylvania Hospital of the University of Pennsylvania Health System, Philadelphia, Pennsylvania. Dr Moretti received support (research fellowship) from Stryker Orthopaedics, Mahwah, New Jersey. Dr Lackman is a consultant for Stryker Orthopaedics, Mahwah, New Jersey. Drs de la Cruz and Brooks have no relevant financial relationships to disclose. The authors thank Carol A. Dolinskas, MD, for assistance with the magnetic resonance imaging interpretation of this case. Correspondence should be addressed to: Vincent M. Moretti, MD, 301 S 8th St, Ste 2C, Philadelphia, PA 19106-6192 (vincent.moretti@uphs.upenn.edu). doi: 10.3928/01477447-20100526-23 10.3928/01477447-20100526-23 Early pleomorphic hyalinizing angiectatic tumor is a rare and recently described soft tissue lesion. Originally believed to be a...