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Myolipoma of Soft Tissue Clinicopathologic Analysis of 34 Cases

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Myolipoma of Soft Tissue Clinicopathologic Analysis of 34 Cases ORIGINAL ARTICLE Myolipoma of Soft Tissue Clinicopathologic Analysis of 34 Cases Mana Fukushima, MD, Inga-Marie Schaefer, MD, and Christopher D.M. Fletcher, MD, FRCPath Key Words: myolipoma, soft tissue, HMGA2, benign tumor Abstract: Myolipoma of soft tissue, which was first described by Meis and Enzinger (1991), is a rare benign neoplasm char- (Am J Surg Pathol 2017;41:153–160) acterized by the admixture of mature adipocytes and well-differentiated smooth muscle cells. Recently, cytogenetic alteration of the HMGA2 gene has been reported in 2 my- yolipoma of soft tissue is a rare benign neoplasm olipomas. We present the clinicopathologic features of 34 cases Mcharacterized by the admixture of mature adipo- of myolipoma of soft tissue, study immunoreactivity for cytes and well-differentiated smooth muscle cells. It is HMGA2, and review the previous literature. In our series, there classified as a variant of lipoma of extrauterine sites in the were 32 women and 2 men, with age at presentation ranging World Health Organization classification,1 thereby being from 35 to 94 years (median, 55 y). The most frequently affected distinguished from uterine “lipoleiomyoma.” Myolipoma site was retroperitoneum (47%), followed by pelvis (15%), ab- of soft tissue more often occurs in adults with a female dominal wall (12%), and intra-abdominal sites (9%). Follow-up predominance, tends to be large, and arises in deep-seated information was available for 17 patients (50%), ranging from 1 locations. This distinct entity was first fully described by to 202 months (mean, 41 mo). None has developed local re- Meis and Enzinger in 1991,2 in which they reported 9 currence or metastasis. Grossly, tumors were well circumscribed, cases of myolipoma of soft tissue. To date, <50 cases and the cut surface showed an admixture of yellowish adipose have been reported. tissue and tan-whitish nodules. The size ranged from 2.4 to Cytogenetic alteration of the high-mobility group 60 cm (median 10.5 cm). Histologically, the tumors were com- AT-hook 2 (HMGA2) gene has been reported in 2 cases of posed of an intimate admixture of mature fat cells and bland myolipoma.3,4 HMGA2 is an architectural transcription spindle-shaped cells with brightly eosinophilic cytoplasm, ar- factor located at 12q14-15, usually expressed only in early ranged in fascicles. Some cases showed the following unusual development, and plays an important role in the tumori- features focally: hypercellular fascicular pattern (N = 2), de- genesis of various epithelial and mesenchymal tumors. generative nuclear atypia (N = 1), round cell morphology Rearrangement of HMGA2 is well recognized in both (N = 1), hemosiderin deposition (N = 1), metaplastic cartilage adipocytic and smooth muscle tumors,3,5–10 including (N = 1), metaplastic bone (N = 1), and eosinophil infiltrates conventional lipoma, atypical lipomatous tumor (ALT)/ (N = 1). Immunohistochemically, spindle cells showed strong well-differentiated liposarcoma (WDLPS), leiomyoma, and and diffuse positivity for desmin (26/26 cases), SMA (20/21), leiomyosarcoma (LMS). In these tumors, overexpression of and ER (13/15). Nuclear positivity for HMGA2 was identified HMGA2 can be detected by immunohistochemistry,5,9–11 in 15 of 25 cases (60%). MDM2 and CDK4 were usually neg- but data regarding HMGA2 immunoexpression in my- ative (14/15, 8/9, respectively). In summary, myolipoma of soft olipoma are still limited. To date, only 1 case has been tissue is a distinctive benign tumor composed of mature fat cells published, which was negative for HMGA2.11 In this study, and smooth muscle cells and arises most commonly in deep- we present the clinicopathologic features of 34 cases of seated locations of middle-aged women. In our study, 60% of myolipoma of soft tissue, study their immunoreactivity for cases showed nuclear staining for HMGA2 by im- HMGA2, and review the previous literature. munohistochemistry, which supports the possibility that these tumors harbor aberration of the HMGA2 gene, as seen in lip- MATERIALS AND METHODS omas and leiomyomas elsewhere. Thirty-four cases diagnosed as myolipoma between 1992 and 2015 were retrieved from the consultation file of From the Department of Pathology, Brigham and Women’s Hospital, 1 of the authors (C.D.M.F.). One additional case was Harvard Medical School, Boston, MA. excluded when follow-up data revealed origin from fe- Current address: Mana Fukushima, Department of Molecular Pathol- male gynecologic organs. Hematoxylin and eosin–stained ogy, Shinshu University, Graduate School of Medicine, Nagano, Japan. sections were reviewed when available, and pathologic Conflicts of Interest and Source of Funding: The authors have disclosed features were reevaluated. Immunostains were performed that they have no significant relationships with, or financial interest on 4-mm-thick formalin-fixed paraffin-embedded tissue in, any commercial companies pertaining to this article. sections, using the following antibodies and conditions: Correspondence: Christopher D.M. Fletcher, MD, FRCPath, Depart- ment of Pathology, Brigham and Women’s Hospital, 75 Francis desmin (Sigma-Aldrich, St Louis, MO, DE-U-10, 1:5000, Street, Boston, MA 02115 (e-mail: cfl[email protected]). citrate buffer pressure cooker), SMA (Sigma-Aldrich, Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved. 1A4, 1:20,000, no pretreatment), h-Caldesmon (Dako, Am J Surg Pathol Volume 41, Number 2, February 2017 www.ajsp.com | 153 Copyright r 2017 Wolters Kluwer Health, Inc. All rights reserved. Fukushima et al Am J Surg Pathol Volume 41, Number 2, February 2017 Carpinteria, CA, h-CD, 1:300, citrate buffer pressure All tumors presented in deep-seated locations, most fre- cooker), MDM2 (EMD Millipore, Billerica, MA, 1F2, quently occurring in retroperitoneum, including pelvic ret- 1:15, citrate buffer pressure cooker), CDK4 (Cell Sig- roperitoneum (16 cases, 47%), followed by pelvic cavity/ naling, Danvers, MA, D9G3E, 1:400, citrate buffer pelvis not otherwise specified (5 cases, 15%), abdominal wall pressure cooker), estrogen receptor (ER) (Dako, ER-1D5, (4 cases, 12%), intra-abdominal sites (including stomach) (3 1:100, citrate buffer pressure cooker) and HMGA2 (Bi- cases, 9%), inguinal/vulval/groin region (3 cases), lower ex- oCheck, Foster City, CA, HMGA2-P1, 1:1000, citrate tremity (2 cases), and buttock (1 case). Patients had either no buffer pressure cooker). Immunostained sections that had symptoms, pain, or abdominal distension. Some patients been performed at the time of diagnosis were reviewed, noticed an enlarging mass. The tumors were occasionally except ER and HMGA2, which were added for this study found incidentally by computed tomography imaging or in all cases with available unstained slides. Appropriate during abdominal surgery for another disease. controls were used throughout. Clinical course and Follow-up information was available for 17 of 34 follow-up data, when available, were kindly provided by patients (50%), ranging from 1 to 202 months (mean the referring pathologists and clinicians (see the follow-up, 41 mo). None has developed local recurrence Acknowledgements section). This study was performed or metastasis, emphasizing the benign clinical behavior of with the approval of the Institutional Review Board at myolipoma. Fifteen of 17 patients (88%) were alive the Brigham and Women’s Hospital. without evidence of disease after 1 to 115 months (mean, 32 mo), and 2 patients had died from other causes after 20 RESULTS and 202 months, respectively. For many patients there were no follow-up data, as patients were often discharged Clinical Findings from care after the benign diagnosis. The clinical data for the 34 patients are summarized in Table 1. There were 32 women and 2 men (F:M = 16:1). Pathologic Findings Patient age at diagnosis ranged from 35 to 94 years (median, The tumor size ranged from 2.4 to 60 cm (median, 55 y); two thirds of patients were in the fifth or sixth decades. 10.5 cm). Grossly, tumors were nodular or lobulated, well TABLE 1. Clinicopathologic Characteristics of 34 Cases of Myolipoma of Soft Tissue Case No. Age Sex Site (Side) Size (cm) Resection Margins SMA Desmin Caldesmon 1 42 F Retroperitoneum 3 R0 Positive Positive NA 2 60 F Retroperitoneum (R) 13 R1 Positive Positive NA 3 75 F Retroperitoneum 10.5 NA Negative Positive NA 4 66 F Abdominal wall 6.5 NA NA Positive NA 5 61 F Pelvic cavity 6.9 NA Positive Positive NA 6 68 F Abdomen/pelvis NA NA NA NA NA 7 70 F Pelvis (L) (Extraperitoneal) 8 R0 Positive Positive NA 8 51 F Retroperitoneum NA NA Positive Positive NA 9 54 F Retroperitoneum (R) 9 NA NA NA NA 10 57 F Retroperitoneum (R) 24 R0 Positive Positive NA 11 35 F Retroperitoneum/Pelvis 5.2 NA NA Positive NA 12 49 F Pelvic cavity (L) 15.2 R0 NA Positive NA 13 64 F Abdominal wall NA NA Positive Positive NA 14 79 F Abdominal wall 6 R0 Positive Positive Positive 15 50 F Retroperitoneum/Pelvis 18 R0 NA Positive NA 16 67 F Retroperitoneum NA NA Positive Positive Positive 17 53 F Retroperitoneum/pelvis 28 R0 NA NA NA 18 60 F Stomach 2.4 NA Positive Positive Positive 19 64 M Thigh (R) 13 R0 Positive Positive NA 20 54 F Abdominal wall 8.5 NA NA Positive NA 21 50 F Retroperitoneum 15 NA Positive Positive Positive 22 45 F Retroperitoneum/pelvis 12.5 NA Positive Positive Positive 23 65 F Retroperitoneum 12 NA NA NA NA 24 52 F Inguinal region (L) 16 R0 NA NA NA 25 54 F Vulva/inguinal canal (R) 10.5 NA NA NA NA 26 94 F Pelvis NOS 9 NA Positive Positive NA 27 59 F Omentum 3.5 NA Positive Positive NA 28 53 F Retroperitoneum 30 R0 Positive Positive NA 29 55 F Retroperitoneum 14 R1 Positive Positive NA 30 38 F Buttock 25 R0 Positive Positive NA 31 50 F Intra-abdominal 60 R0 Positive Positive NA 32 60 F Pelvic cavity NA NA Positive Positive NA 33 36 M Calf NA NA NA NA NA 34 55 F Groin 5 NA NA NA NA ANED indicates alive with no evidence of disease; DOC, died of other causes; NA, not available.
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