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Pathology International 2014; 64: 346–351
doi:10.1111/pin.12176
Case Report
Dendritic fibromyxolipoma: A variant of spindle cell lipoma with extensive myxoid change, with cytogenetic evidence
Yin-Ping Wong,1 Wai Kit Chia,2 Soo Fin Low,3 Nor Hazla Mohamed-Haflah4 and Noor Akmal Sharifah1 Departments of 1Pathology, 2Diagnostic Laborator Services, 3Radiology, 4Orthopaedic and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia
Dendritic fibromyxolipoma (DFML), a rare, recently described distinct benign soft tissue tumor, has many clinicopathological features reminiscent of spindle cell lipoma and solitary fibrous tumor with myxoid change. It is distinguished histologically from both entities by the presence of spindle and stellate cells with dendritic cytoplasmic prolongations, prominent myxoid stroma with abundant keloidal collagen and occasional small plexiform vascular proliferation. We describe a case of histologically confirmed DFML of the left shoulder in a 67-year-old male, in which subsequent cytogenetic analysis revealed deletion involving 13q14.3 region in all the tumor cells, typically detected in spindle cell lipoma. In the presence of many clinicopathological similarities between DFML and spindle cell lipoma including chromosomal abnormalities, we postulate that DFML is merely a rare variant of spindle cell lipoma with extensive myxoid degeneration, and may not be considered as a separate entity. The possible differential diagnosis and their distinguishing features are briefly discussed. Key words: dendritic, fibromyxolipoma, myxoid liposarcoma, spindle cell lipoma
Dendritic fibromyxolipoma (DFML) is a rare, recently described distinct benign, superficial soft tissue tumor. It shares many clinicopathological features with the rare myxoid variant of spindle cell lipoma and the unusual form of solitary fibrous tumor with myxoid stroma.1 It has distinctive histological features which distinguish it from both entities
Correspondence: Noor Akmal Sharifah, M.B.Ch.B, D.C.P, M.D, F.I.A.C, Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Jalan Yaacob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. Email: [email protected] Disclosure: All authors declare that there is no conflict of interest. Received 20 February 2014. Accepted for publication 28 May 2014. © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
(spindle cell lipoma and solitary fibrous tumor). It is characterized histologically by the presence of spindle and stellate cells with dendritic cytoplasmic processes, prominent myxoid stroma with abundant keloidal collagen and occasional small plexiform vascular proliferation.1 A review of literature showed only seventeen cases of DFML described to date, and this is the first case which has cytogenetic analysis performed to further characterize the tumor.
CLINICAL SUMMARY A 67-year-old Chinese male presented with a one-year history of a gradually enlarging, painless left shoulder swelling. There were no associated constitutional symptoms. No family history of significance. Physical examination revealed a 7-cm subcutaneous, soft, non-tender mass over the left shoulder region. It was mobile and not adherent to the overlying skin or underlying muscle. The features were that of a benign lesion and a diagnosis of lipoma was made at this stage. Sonography revealed a well encapsulated mass situated between the subcutaneous fat and the muscle. The mass was echogenic in nature with irregular hypoechoic areas within (Fig. 1a). No calcification or cystic component was detected within the mass. Color Doppler interrogation demonstrated vascularity within the mass (Fig. 1b). The sonographic findings were suggestive of a soft tissue tumor, liposarcoma was the possible diagnosis. In the light of this finding, a tru-cut biopsy was performed which confirmed our initial diagnosis of a lipoma. Thus, an excision of the left shoulder mass under local anesthesia was performed. No local recurrence was reported during his follow up postoperatively.
PATHOLOGICAL FINDINGS Macroscopically, the mass was well circumscribed, soft with grayish gelatinous, mucoid cut surface (Fig. 2a). No areas of
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BCL2 (clone BCL2/124, Dako) (Fig. 3b). The dendritic nature of the spindle to stellate cells was accentuated by CD34 immunostain, by demonstrating their thin, complex cytoplasmic dendritic meshwork. Staining for S100 (Dako) was negative, with intervening mature adipocytes as positive internal control. STAT6 (Dako), a recently discovered diagnostic marker for solitary fibrous tumor, was also negative (Fig. 3c). Based on the histomorphological and immunohistochemical findings, a diagnosis of DFML was rendered. However, the possibility of a myxoid variant of spindle cell lipoma cannot be entirely excluded due to the overlapping clinical features, topographic distribution as well as histological features of both lesions.
Cytogenetic analysis
Figure 1 Sonographic findings of the lesion. (a) There is a well encapsulated solid mass situated between the subcutaneous fat (white asterisk) and muscle layer (black asterisk). The mass is echogenic in nature with irregular hypoechoic areas within. (b) Color , Dist Doppler interrogation exhibits intralesional vascularity. 3.71 cm; , Dist 1.67 cm.
necrosis or hemorrhage were present. Histologically, the tumor mass was sparsely cellular, comprised predominantly of spindle to stellate shaped cells embedded within abundant myxoid stroma with strands of ropey collagen bundles (Fig. 2b). The spindle to stellate cells were small, bland looking, exhibiting hyperchromatic nuclei with inconspicuous nucleoli and relatively scanty cytoplasm. Thin, complex cytoplasmic dendritic processes extending from the spindle to stellate cells were observed at higher magnification (Fig. 2c). Neither cellular atypia nor mitosis was present. Focal areas exhibiting plexiform, myxoid liposarcoma-like vascular pattern were also observed (Fig. 2d). In areas, mature adipocytes were seen intermingled among the spindle to stellate cells within the myxoid background. Scattered lymphocytes and mast cells were noted throughout. No lipoblasts or primitive non-lipogenic mesenchymal cells were identified to suggest a myxoid liposarcoma.
Immunohistochemical stains Immunophenotypically, the spindle to stellate cells stained positively for CD34 (Dako, Glostrup, Denmark) (Fig. 3a) and
To further characterize the tumor, cytogenetic analysis was carried out. To the best of our knowledge, no cytogenetic analysis was performed on the seventeen cases reported in the literature to date. Deletion of the long arm of chromosome 13 (del(13q)), a chromosomal aberration which is commonly observed in spindle cell lipoma, was analyzed by fluorescence in situ hybridization (FISH) using Vysis D13S319/ 13q34 FISH probe kit (Abbott Molecular, Des Plaines, IL, USA). The kit is intended to detect the copy number of the LSI D13S319 (labeled with Spectrum Orange) targeting the 13q14.3 locus and the copy number of the LSI13q34 (labeled with Spectrum Green) targeting the 13q34 locus. A total of 100 non-overlapping spindle shaped nuclei of the neoplastic cells were scored. All (100%) of them showed abnormal cell hybridization signals (two green and one orange signal pattern), indicating deletion involving the 13q14.3 region (Fig. 3d), characteristic of spindle cell lipoma.
DISCUSSION Dendritic fibromyxolipoma (DFML) is an extremely rare, recently described unique benign soft tissue tumor. It was first proposed by Suster et al. describing twelve cases, based strictly on the dendritic nature of the tumor cells with fibromyxoid and adipocytic differentiation.1 Since then, only six cases, including the present case, have been reported (Table 1).2–6 Dendritic fibromyxolipoma has many similarities with spindle cell lipoma (SCL), including clinical and topographic distribution.1 Both are typically present in the older age population (median age, 64 years), and with a male preponderance. Sites of predilection are the head and neck and shoulder regions.1 Generally, most cases of DFML and SCL occur in the dermis or subcutaneously, although rare occurrence in the intramuscular region has been described.3 Both
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
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Figure 2 Gross and histological features. (a) Macroscopically, there is a well circumscribed mass with gelatinous yellow-gray cut surface. (b) Sparsely cellular mass composed of bland spindle to stellate cells in abundant myxoid stroma. Occasional keloidal collagen fibers are seen. (c) Bland mitotically inactive spindle to stellate tumor cells with complex cytoplasmic processes. Inset shows stellate shaped tumor cells at higher magnification. (d) Focal areas showing plexiform vascular proliferation pattern, resemblance that of myxoid liposarcoma.
are essentially benign lesions and local recurrence is exceptionally rare even with incomplete surgical excision.7 Macroscopically, DFML is usually well circumscribed, thinly encapsulated, displaying yellowish to grayish, mucoid or gelatinous cut surface, resembling that of myxoid variant of SCL.1,7 Histologically, DFML closely resemble myxoid variant of SCL, which suggests a close relationship between the two entities.1,7 Both tumors are composed of a proliferation of uniform, bland-looking spindle cells admixed with mature adipose tissue in the background of abundant myxoid stroma. Both also demonstrate strong immunoreactivity for CD34 and BCL2. The presence of mast cells is also a common feature.1,7 However, Suster et al. highlighted that DFML can be readily distinguished from SCL by three distinctive histological features, namely: (i) dendritic nature of
the spindle cells; (ii) abundance of keloidal-type collagen; and (iii) occasional plexiform proliferation of capillary-sized vessels.1 The molecular characteristic of DFML has never been investigated, and this is the first case to have cytogenetic analysis performed. Interestingly, deletion of 13q14.3 region that is also present in SCL,8 was detected in the present case, suggesting a histogenetic link between these tumors. Other cytogenetic aberrations that are frequently detected in SCL are monosomy for chromosome 16, deletion of 16q, monosomy for chromosome 13 and partial loss of 13q material.7,8 Differential diagnosis of DFML is broad, ranging from benign to malignant myxoid spindle cell neoplasms (Table 2). Solitary fibrous tumors (SFT) are classically composed of bland spindle cells that are singly separated by rope-like
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
A rare case of dendritic fibromyxolipoma
349
Figure 3 Immunohistochemistry studies and FISH analysis. (a) Spindle to stellate tumor cells are diffusely positive for CD34, accentuating their complex cytoplasmic processes network. (b) Labelling for BCL2 shows strong expression in the neoplastic spindle cells. (c) The neoplastic spindle cells display STAT6 immunonegativity. (d) Fluorescence in situ hybridization (FISH) analysis using Vysis D13S319/13q34 FISH probe kit shows abnormal cell hybridization signals (two green and one orange signal pattern) in the nuclei of neoplastic spindle cells, indicating deletion involving 13q14.3 region.
collagen fibers. Solitary fibrous tumors with prominent myxoid change (myxoid SFT) has been previously reported.9 Myxoid SFT has significant histological overlap with DFML, which include cytologically bland spindle cells with strong immunoreactivity for CD34 and BCL2, and abundant pale myxoid stroma. Major differentiating features are the haphazard ‘patternless’ arrangement of the spindle cells, that are singly separated by small bands of collagen fibers and the staghorn haemangiopericytomatous vascular pattern, which are more characteristic of myxoid SFT.9 In addition, lack of adipose tissue component and inconspicuous mast cells in myxoid SFT are helpful distinguishing features.1 Several studies have recently discovered a recurrent intrachromosomal fusion between the NAB2 and STAT6
genes on chromosome 12 in 50–100% of SFT.10,11 The resultant NAB2-STAT6 fusion gene has not been found in other soft tissue neoplasms.10,11 Following the molecular breakthrough, nuclear expression of STAT6 by immunohistochemical analysis was detected in almost 100% of SFT, being currently the most specific immunomarker for these tumors.12 Due to their relatively large size, DFML can mimic myxoid liposarcoma to perfection, especially if the former specimen is focally sampled, which are composed predominantly of bland mitotically inactive spindle cells, delicate plexiform vascular network and abundant myxoid matrix. Macroscopically, myxoid liposarcoma are usually well circumscribed, showing tan, gelatinous cut surface, indiscernible from DFML.13 Careful observation for the absence of signet-ring lipoblasts
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
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Table 1
Y.-P. Wong et al.
Summary of reported cases of dendritic fibromyxolipoma
References
Case
Age /sex
Suster et al. (1998)1
1
33/M
NA
2 3 4 5
54/M 58/M 63/M 66/M
6
Kim et al. (2001)2 Karim et al. (2003)3 Al-Maskery et al. (2011)4 Dahlin et al. (2012)5 Zhang et al. (2013)6 Present case
Interval
Initial interpretation at biopsy/resection
Tumor descriptions
IHC CD34+, BCL2+
Solitary fibrous tumor
NA
NA NA NA 4 years
11-cm mass in left posterior shoulder, acromium region 5 × 5 × 4 cm, right posterior neck 7.5 × 5.5 × 3 cm, right shoulder 6 × 5.5 × 2 cm, upper back 8 × 3.5 × 2.5 cm, back of the neck
CD34+, CD34+, CD34+, CD34+,
NA A&W, 7 years NA NA
66/M
NA
9 × 7 × 6.5 cm, back, posterior axilla
CD34+, BCL2+
7 8
70/M 73/M
NA NA
2 × 2 × 2 cm, face, right nasal area 7 × 5.5 × 2.5 cm, right posterior neck
CD34+, BCL2+ CD34+, BCL2+
9 10
77/M 79/M
NA NA
3 × 2 × 1.5 cm, back of neck 3.5 × 3 × 2.5 cm, right chest wall
CD34+, BCL2+ CD34+, BCL2+
11 12 13 14
81/M 50/F 28/M 73/M
NA NA 4 months NA
CD34+, CD34+, CD34+, CD34+,
15
36/F
? years
3.5 × 3 × 3 cm, left chest wall 6 × 5.5 × 5 cm, right upper back 11 × 7 × 5 cm, right shoulder 13.0 × 8.0 × 5.5 cm, between infraspinatus and deltoid muscles 2.0 × 2.0 × 2.0 cm, lower lip
Myxoid liposarcoma Myxoid liposarcoma Solitary fibrous tumor Spindle cell lipoma with prominent myxoid changes Spindle cell lipoma with prominent myxoid changes Schwannoma Atypical lipoma with myxoid features Spindle cell lipoma Myxoid malignant fibrous histiocytoma Fibromyxolipoma Myxoid liposarcoma Dendritic myxofibrolipoma Low grade liposarcoma
CD34+, BCL2+
Dendritic myxofibrolipoma
A&W, 2 years
16
65/F
NA
CD34+, BCL2+
Dendritic fibromyxolipoma
NA
17
32/F
3 years
CD34+, BCL2+
Dendritic fibromyxolipoma
A&W, 9 months
18
67/M
1 year
2.0 × 3.2 × 1.0 cm, adherent to median nerve of left forearm 24.0 × 10.5 × 5.0 cm, right inguinal & perineum 7 cm, left shoulder region
CD34+, BCL2+
Dendritic fibromyxolipoma
A&W, 4 months
BCL2+ BCL2+ BCL2+ BCL2+
BCL2+ BCL2+ BCL2+ BCL2+
Follow up
NA A&W, 11 years A&W, 13 years A&W, 5 years Died of unrelated disease A&W, 5 years NA A&W, 8 months
+, positive; −, negative; A&W, alive and well; F, female; M, male; NA, not available.
Table 2
Differential diagnosis of dendritic fibromyxolipoma and their distinguishing features
Differential diagnosis
Macroscopic features
Dendritic fibromyxolipoma1,7
Well circumscribed, encapsulated with yellow-gray, mucoid or gelatinous cut surface
Myxoid spindle cell lipoma7,8
Well circumscribed, encapsulated with yellow-gray, mucoid or gelatinous cut surface
Myxoid solitary fibrous tumor9–12
Well circumscribed, partially encapsulated, multinodular with myxoid appearance
Myxoid liposarcoma13,14
Well circumscribed, multinodular intramuscular mass with tan, gelatinous cut surface Multiple, variably gelatinous or firm nodules
Low grade myxofibrosarcoma15
Microscopic features
IHC
Cytogenetic aberrations
Bland mitotically inactive spindle to stellate (dendritic) tumor cells with complex cytoplasmic processes. Abundant myxoid stroma with keloidal collagen fibers and adipose tissue. Occasional plexiform vascular pattern. Bland mitotically inactive spindle shaped tumor cells. Abundant myxoid stroma with ropey collagen fibers and adipose tissue. Blood vessels generally inconspicuous, rarely, plexiform, haemangiopericytomatous, pseudoangiomatous vascular pattern. Patternless haphazard arrangements of spindle cells. Intervening small bands of collagen fibers separate single cells. Staghorn haemangiopericytomatous vascular pattern. Primitive non lipogenic mesenchymal cells and variable lipoblasts. Delicate, arborizing, chicken-wire capillary vascular pattern.
CD34+ BCL2+ S100−
No information as never been closely studied
CD34+ BCL2+ S100−
Monosomy or partial loss of chromosome 13 and/or 16
STAT6+ CD34+ BCL2+ CD99+ S100−
NAB2-STAT6 fusion gene
CD34− S100+
t(12; 16)(q13; p11), rarely t(12; 22) (q13; q12)
Non cohesive, plump, atypical spindled to stellate tumor cells with enlarged hyperchromatic nuclei. Prominent elongated, curvilinear, thin walled blood vessels.
SMA+ DesminCD68−
Highly complex, non specific
+, positive; −, negative.
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
A rare case of dendritic fibromyxolipoma
and primitive non-lipogenetic mesenchymal cells, which are classically present in myxoid liposarcoma, is helpful to differentiate DFML from myxoid liposarcoma.13 In addition, clinical and radiological information of a deep-seated soft tissue mass with infiltrative borders, although not always the case, is a feature of malignancy. While routine immunohistochemical study is not required in classical cases of myxoid liposarcoma, unlike DFML, all the neoplastic cells are diffusely positive for S100 protein and are CD34 negative.13 Recurrent translocation t(12;16)(q13;p11), and rarely, t (12;22)(q13;q12), with resultant generation of FUS/DDIT3 and EWS/DDIT3 hybrid protein respectively, are cytogenetic hallmarks of myxoid liposarcoma.14 Hence, demonstration of DDIT3 genomic rearrangement is a valuable adjunct to exclude other morphologic mimics in difficult cases.14 The other superficial myxoid soft tissue tumor that is included in the differential diagnosis is low grade myxofibrosarcoma. Low grade myxofibrosarcoma is characteristically sparsely cellular and displays abundant myxoid stroma mimicking DFML. However, it can be easily distinguished from DFML by the presence of atypical, enlarged spindle cells with classically curvilinear blood vessels in the former.15 We highlighted an exceedingly rare case of DFML of the left shoulder in a 67-year-old male, which we propose to be the first reported case with cytogenetic analysis performed. Although the deletion of the 13q14.3 region detected in the present case is not unique to SCL and warrants a larger scale study to prove its validity, we postulate that DFML is merely an unusual myxoid variant of SCL on the basis of the striking overlapping clinical, histomorphological and immunohistochemical features. A similar speculation has been previously expressed.3,16 Although rare, DFML is an important entity to recognize as it can be potentially confused with malignant myxoid spindle cell neoplasm. Careful observation for distinctive histological cues in the right clinical context as well as valuable cytogenetic input will help reach to an accurate diagnosis.
ACKNOWLEDGMENT We would like to thank all the laboratory staffs of Universiti Kebangsaan Malaysia Medical Center for their excellent technical support.
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REFERENCES 1 Suster S, Fisher C, Moran CA. Dendritic fibromyxolipoma: Clinicopathologic study of a distinctive benign soft tissue lesion that may be mistaken for a sarcoma. Ann Diagn Pathol 1998; 2: 111–20. 2 Kim SN, Kwon KH, Suh YL. Dendritic myxofibrolipoma. A case report. Korean J Pathol 2001; 35: 447–50. 3 Karim RZ, McCarthy SW, Palmer AA, Bonar SF, Scolyer RA. Intramuscular dendritic fibromyxolipoma: Myxoid variant of spindle cell lipoma? Pathol Int 2003; 53: 252–8. 4 Al-Maskery AY, Al-Sidairy SM, Al-Hamadani AS. Dendritic myxofibrolipoma: Often misdiagnosed as sarcoma. Craniomaxillofac Trauma Reconstr 2011; 4: 171–4. 5 Dahlin LB, Ljungberg O. Dendritic fibromyxolipoma adherent to the median nerve in the forearm. J Plast Surg Hand Surg 2012; 46: 120–3. 6 Zhang XJ, Zhou S, Nie K, Chen DF, Kui GJ, Zhang XH. Dendritic fibromyxolipoma in the right inguinal and perineum regions: A case report and review of the literature. Diagn Pathol 2013; 8: 157 (7 pages) doi:10.1186/1746-1596-8-157. 7 Goldblum JR, Folpe AL, Weiss SW. Benign lipomatous tumors. In: Goldblum JR, Folpe AL, Weiss SW, eds. Enzinger and Weiss’s Soft Tissue Tumors. Philadelphia: Elsevier Saunders, 2014; 456–63. 8 Nishio J. Contributions of cytogenetics and molecular cytogenetics to the diagnosis of adipocytic tumors. J Biomed Biotechnol 2011; 2011: 1–9 doi:10.1155/2011/524067. 9 de Saint Aubain Somerhausen N, Rubin BP, Fletcher CDM. Myxoid solitary fibrous tumor: A study of seven cases with emphasis on differential diagnosis. Mod Pathol 1999; 12: 463– 71. 10 Robinson DR, Wu YM, Kalyana-Sundaram S et al. Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nat Genet 2013; 45: 180–5. 11 Chmielecki J, Crago AM, Rosenberg M et al. Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors. Nat Genet 2013; 45: 131–2. 12 Doyle LA, Vivero M, Fletcher CD, Mertens F, Hornick JL. Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol 2014; 27: 390–5. 13 Antonescu CR, Ladanyi M. Myxoid liposarcoma. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, eds. WHO Classification of Tumours of Soft Tissue and Bone. Lyon: IARC, 2013; 39–41. 14 Powers MP, Wang WL, Hernandez VS et al. Detection of myxoid liposarcoma-associated FUS-DDIT3 rearrangement variants including a newly identified breakpoint using an optimized RT-PCR assay. Mod Pathol 2010; 23: 1307–15. 15 Mentzel T, Hogendoorn PCW, Huang HY. Myxofibrosarcoma. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, eds. WHO Classification of Tumours of Soft Tissue and Bone. Lyon: IARC, 2013; 93–4. 16 Guillou L, Coindre JM. Newly described adipocytic lesions. Semin Diagn Pathol 2001; 18: 238–49.
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Pathology International 2014; 64: 346–351
doi:10.1111/pin.12176
Case Report
Dendritic fibromyxolipoma: A variant of spindle cell lipoma with extensive myxoid change, with cytogenetic evidence
Yin-Ping Wong,1 Wai Kit Chia,2 Soo Fin Low,3 Nor Hazla Mohamed-Haflah4 and Noor Akmal Sharifah1 Departments of 1Pathology, 2Diagnostic Laborator Services, 3Radiology, 4Orthopaedic and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia
Dendritic fibromyxolipoma (DFML), a rare, recently described distinct benign soft tissue tumor, has many clinicopathological features reminiscent of spindle cell lipoma and solitary fibrous tumor with myxoid change. It is distinguished histologically from both entities by the presence of spindle and stellate cells with dendritic cytoplasmic prolongations, prominent myxoid stroma with abundant keloidal collagen and occasional small plexiform vascular proliferation. We describe a case of histologically confirmed DFML of the left shoulder in a 67-year-old male, in which subsequent cytogenetic analysis revealed deletion involving 13q14.3 region in all the tumor cells, typically detected in spindle cell lipoma. In the presence of many clinicopathological similarities between DFML and spindle cell lipoma including chromosomal abnormalities, we postulate that DFML is merely a rare variant of spindle cell lipoma with extensive myxoid degeneration, and may not be considered as a separate entity. The possible differential diagnosis and their distinguishing features are briefly discussed. Key words: dendritic, fibromyxolipoma, myxoid liposarcoma, spindle cell lipoma
Dendritic fibromyxolipoma (DFML) is a rare, recently described distinct benign, superficial soft tissue tumor. It shares many clinicopathological features with the rare myxoid variant of spindle cell lipoma and the unusual form of solitary fibrous tumor with myxoid stroma.1 It has distinctive histological features which distinguish it from both entities
Correspondence: Noor Akmal Sharifah, M.B.Ch.B, D.C.P, M.D, F.I.A.C, Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Jalan Yaacob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. Email: [email protected] Disclosure: All authors declare that there is no conflict of interest. Received 20 February 2014. Accepted for publication 28 May 2014. © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
(spindle cell lipoma and solitary fibrous tumor). It is characterized histologically by the presence of spindle and stellate cells with dendritic cytoplasmic processes, prominent myxoid stroma with abundant keloidal collagen and occasional small plexiform vascular proliferation.1 A review of literature showed only seventeen cases of DFML described to date, and this is the first case which has cytogenetic analysis performed to further characterize the tumor.
CLINICAL SUMMARY A 67-year-old Chinese male presented with a one-year history of a gradually enlarging, painless left shoulder swelling. There were no associated constitutional symptoms. No family history of significance. Physical examination revealed a 7-cm subcutaneous, soft, non-tender mass over the left shoulder region. It was mobile and not adherent to the overlying skin or underlying muscle. The features were that of a benign lesion and a diagnosis of lipoma was made at this stage. Sonography revealed a well encapsulated mass situated between the subcutaneous fat and the muscle. The mass was echogenic in nature with irregular hypoechoic areas within (Fig. 1a). No calcification or cystic component was detected within the mass. Color Doppler interrogation demonstrated vascularity within the mass (Fig. 1b). The sonographic findings were suggestive of a soft tissue tumor, liposarcoma was the possible diagnosis. In the light of this finding, a tru-cut biopsy was performed which confirmed our initial diagnosis of a lipoma. Thus, an excision of the left shoulder mass under local anesthesia was performed. No local recurrence was reported during his follow up postoperatively.
PATHOLOGICAL FINDINGS Macroscopically, the mass was well circumscribed, soft with grayish gelatinous, mucoid cut surface (Fig. 2a). No areas of
A rare case of dendritic fibromyxolipoma
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BCL2 (clone BCL2/124, Dako) (Fig. 3b). The dendritic nature of the spindle to stellate cells was accentuated by CD34 immunostain, by demonstrating their thin, complex cytoplasmic dendritic meshwork. Staining for S100 (Dako) was negative, with intervening mature adipocytes as positive internal control. STAT6 (Dako), a recently discovered diagnostic marker for solitary fibrous tumor, was also negative (Fig. 3c). Based on the histomorphological and immunohistochemical findings, a diagnosis of DFML was rendered. However, the possibility of a myxoid variant of spindle cell lipoma cannot be entirely excluded due to the overlapping clinical features, topographic distribution as well as histological features of both lesions.
Cytogenetic analysis
Figure 1 Sonographic findings of the lesion. (a) There is a well encapsulated solid mass situated between the subcutaneous fat (white asterisk) and muscle layer (black asterisk). The mass is echogenic in nature with irregular hypoechoic areas within. (b) Color , Dist Doppler interrogation exhibits intralesional vascularity. 3.71 cm; , Dist 1.67 cm.
necrosis or hemorrhage were present. Histologically, the tumor mass was sparsely cellular, comprised predominantly of spindle to stellate shaped cells embedded within abundant myxoid stroma with strands of ropey collagen bundles (Fig. 2b). The spindle to stellate cells were small, bland looking, exhibiting hyperchromatic nuclei with inconspicuous nucleoli and relatively scanty cytoplasm. Thin, complex cytoplasmic dendritic processes extending from the spindle to stellate cells were observed at higher magnification (Fig. 2c). Neither cellular atypia nor mitosis was present. Focal areas exhibiting plexiform, myxoid liposarcoma-like vascular pattern were also observed (Fig. 2d). In areas, mature adipocytes were seen intermingled among the spindle to stellate cells within the myxoid background. Scattered lymphocytes and mast cells were noted throughout. No lipoblasts or primitive non-lipogenic mesenchymal cells were identified to suggest a myxoid liposarcoma.
Immunohistochemical stains Immunophenotypically, the spindle to stellate cells stained positively for CD34 (Dako, Glostrup, Denmark) (Fig. 3a) and
To further characterize the tumor, cytogenetic analysis was carried out. To the best of our knowledge, no cytogenetic analysis was performed on the seventeen cases reported in the literature to date. Deletion of the long arm of chromosome 13 (del(13q)), a chromosomal aberration which is commonly observed in spindle cell lipoma, was analyzed by fluorescence in situ hybridization (FISH) using Vysis D13S319/ 13q34 FISH probe kit (Abbott Molecular, Des Plaines, IL, USA). The kit is intended to detect the copy number of the LSI D13S319 (labeled with Spectrum Orange) targeting the 13q14.3 locus and the copy number of the LSI13q34 (labeled with Spectrum Green) targeting the 13q34 locus. A total of 100 non-overlapping spindle shaped nuclei of the neoplastic cells were scored. All (100%) of them showed abnormal cell hybridization signals (two green and one orange signal pattern), indicating deletion involving the 13q14.3 region (Fig. 3d), characteristic of spindle cell lipoma.
DISCUSSION Dendritic fibromyxolipoma (DFML) is an extremely rare, recently described unique benign soft tissue tumor. It was first proposed by Suster et al. describing twelve cases, based strictly on the dendritic nature of the tumor cells with fibromyxoid and adipocytic differentiation.1 Since then, only six cases, including the present case, have been reported (Table 1).2–6 Dendritic fibromyxolipoma has many similarities with spindle cell lipoma (SCL), including clinical and topographic distribution.1 Both are typically present in the older age population (median age, 64 years), and with a male preponderance. Sites of predilection are the head and neck and shoulder regions.1 Generally, most cases of DFML and SCL occur in the dermis or subcutaneously, although rare occurrence in the intramuscular region has been described.3 Both
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
348
Y.-P. Wong et al.
Figure 2 Gross and histological features. (a) Macroscopically, there is a well circumscribed mass with gelatinous yellow-gray cut surface. (b) Sparsely cellular mass composed of bland spindle to stellate cells in abundant myxoid stroma. Occasional keloidal collagen fibers are seen. (c) Bland mitotically inactive spindle to stellate tumor cells with complex cytoplasmic processes. Inset shows stellate shaped tumor cells at higher magnification. (d) Focal areas showing plexiform vascular proliferation pattern, resemblance that of myxoid liposarcoma.
are essentially benign lesions and local recurrence is exceptionally rare even with incomplete surgical excision.7 Macroscopically, DFML is usually well circumscribed, thinly encapsulated, displaying yellowish to grayish, mucoid or gelatinous cut surface, resembling that of myxoid variant of SCL.1,7 Histologically, DFML closely resemble myxoid variant of SCL, which suggests a close relationship between the two entities.1,7 Both tumors are composed of a proliferation of uniform, bland-looking spindle cells admixed with mature adipose tissue in the background of abundant myxoid stroma. Both also demonstrate strong immunoreactivity for CD34 and BCL2. The presence of mast cells is also a common feature.1,7 However, Suster et al. highlighted that DFML can be readily distinguished from SCL by three distinctive histological features, namely: (i) dendritic nature of
the spindle cells; (ii) abundance of keloidal-type collagen; and (iii) occasional plexiform proliferation of capillary-sized vessels.1 The molecular characteristic of DFML has never been investigated, and this is the first case to have cytogenetic analysis performed. Interestingly, deletion of 13q14.3 region that is also present in SCL,8 was detected in the present case, suggesting a histogenetic link between these tumors. Other cytogenetic aberrations that are frequently detected in SCL are monosomy for chromosome 16, deletion of 16q, monosomy for chromosome 13 and partial loss of 13q material.7,8 Differential diagnosis of DFML is broad, ranging from benign to malignant myxoid spindle cell neoplasms (Table 2). Solitary fibrous tumors (SFT) are classically composed of bland spindle cells that are singly separated by rope-like
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
A rare case of dendritic fibromyxolipoma
349
Figure 3 Immunohistochemistry studies and FISH analysis. (a) Spindle to stellate tumor cells are diffusely positive for CD34, accentuating their complex cytoplasmic processes network. (b) Labelling for BCL2 shows strong expression in the neoplastic spindle cells. (c) The neoplastic spindle cells display STAT6 immunonegativity. (d) Fluorescence in situ hybridization (FISH) analysis using Vysis D13S319/13q34 FISH probe kit shows abnormal cell hybridization signals (two green and one orange signal pattern) in the nuclei of neoplastic spindle cells, indicating deletion involving 13q14.3 region.
collagen fibers. Solitary fibrous tumors with prominent myxoid change (myxoid SFT) has been previously reported.9 Myxoid SFT has significant histological overlap with DFML, which include cytologically bland spindle cells with strong immunoreactivity for CD34 and BCL2, and abundant pale myxoid stroma. Major differentiating features are the haphazard ‘patternless’ arrangement of the spindle cells, that are singly separated by small bands of collagen fibers and the staghorn haemangiopericytomatous vascular pattern, which are more characteristic of myxoid SFT.9 In addition, lack of adipose tissue component and inconspicuous mast cells in myxoid SFT are helpful distinguishing features.1 Several studies have recently discovered a recurrent intrachromosomal fusion between the NAB2 and STAT6
genes on chromosome 12 in 50–100% of SFT.10,11 The resultant NAB2-STAT6 fusion gene has not been found in other soft tissue neoplasms.10,11 Following the molecular breakthrough, nuclear expression of STAT6 by immunohistochemical analysis was detected in almost 100% of SFT, being currently the most specific immunomarker for these tumors.12 Due to their relatively large size, DFML can mimic myxoid liposarcoma to perfection, especially if the former specimen is focally sampled, which are composed predominantly of bland mitotically inactive spindle cells, delicate plexiform vascular network and abundant myxoid matrix. Macroscopically, myxoid liposarcoma are usually well circumscribed, showing tan, gelatinous cut surface, indiscernible from DFML.13 Careful observation for the absence of signet-ring lipoblasts
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
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Table 1
Y.-P. Wong et al.
Summary of reported cases of dendritic fibromyxolipoma
References
Case
Age /sex
Suster et al. (1998)1
1
33/M
NA
2 3 4 5
54/M 58/M 63/M 66/M
6
Kim et al. (2001)2 Karim et al. (2003)3 Al-Maskery et al. (2011)4 Dahlin et al. (2012)5 Zhang et al. (2013)6 Present case
Interval
Initial interpretation at biopsy/resection
Tumor descriptions
IHC CD34+, BCL2+
Solitary fibrous tumor
NA
NA NA NA 4 years
11-cm mass in left posterior shoulder, acromium region 5 × 5 × 4 cm, right posterior neck 7.5 × 5.5 × 3 cm, right shoulder 6 × 5.5 × 2 cm, upper back 8 × 3.5 × 2.5 cm, back of the neck
CD34+, CD34+, CD34+, CD34+,
NA A&W, 7 years NA NA
66/M
NA
9 × 7 × 6.5 cm, back, posterior axilla
CD34+, BCL2+
7 8
70/M 73/M
NA NA
2 × 2 × 2 cm, face, right nasal area 7 × 5.5 × 2.5 cm, right posterior neck
CD34+, BCL2+ CD34+, BCL2+
9 10
77/M 79/M
NA NA
3 × 2 × 1.5 cm, back of neck 3.5 × 3 × 2.5 cm, right chest wall
CD34+, BCL2+ CD34+, BCL2+
11 12 13 14
81/M 50/F 28/M 73/M
NA NA 4 months NA
CD34+, CD34+, CD34+, CD34+,
15
36/F
? years
3.5 × 3 × 3 cm, left chest wall 6 × 5.5 × 5 cm, right upper back 11 × 7 × 5 cm, right shoulder 13.0 × 8.0 × 5.5 cm, between infraspinatus and deltoid muscles 2.0 × 2.0 × 2.0 cm, lower lip
Myxoid liposarcoma Myxoid liposarcoma Solitary fibrous tumor Spindle cell lipoma with prominent myxoid changes Spindle cell lipoma with prominent myxoid changes Schwannoma Atypical lipoma with myxoid features Spindle cell lipoma Myxoid malignant fibrous histiocytoma Fibromyxolipoma Myxoid liposarcoma Dendritic myxofibrolipoma Low grade liposarcoma
CD34+, BCL2+
Dendritic myxofibrolipoma
A&W, 2 years
16
65/F
NA
CD34+, BCL2+
Dendritic fibromyxolipoma
NA
17
32/F
3 years
CD34+, BCL2+
Dendritic fibromyxolipoma
A&W, 9 months
18
67/M
1 year
2.0 × 3.2 × 1.0 cm, adherent to median nerve of left forearm 24.0 × 10.5 × 5.0 cm, right inguinal & perineum 7 cm, left shoulder region
CD34+, BCL2+
Dendritic fibromyxolipoma
A&W, 4 months
BCL2+ BCL2+ BCL2+ BCL2+
BCL2+ BCL2+ BCL2+ BCL2+
Follow up
NA A&W, 11 years A&W, 13 years A&W, 5 years Died of unrelated disease A&W, 5 years NA A&W, 8 months
+, positive; −, negative; A&W, alive and well; F, female; M, male; NA, not available.
Table 2
Differential diagnosis of dendritic fibromyxolipoma and their distinguishing features
Differential diagnosis
Macroscopic features
Dendritic fibromyxolipoma1,7
Well circumscribed, encapsulated with yellow-gray, mucoid or gelatinous cut surface
Myxoid spindle cell lipoma7,8
Well circumscribed, encapsulated with yellow-gray, mucoid or gelatinous cut surface
Myxoid solitary fibrous tumor9–12
Well circumscribed, partially encapsulated, multinodular with myxoid appearance
Myxoid liposarcoma13,14
Well circumscribed, multinodular intramuscular mass with tan, gelatinous cut surface Multiple, variably gelatinous or firm nodules
Low grade myxofibrosarcoma15
Microscopic features
IHC
Cytogenetic aberrations
Bland mitotically inactive spindle to stellate (dendritic) tumor cells with complex cytoplasmic processes. Abundant myxoid stroma with keloidal collagen fibers and adipose tissue. Occasional plexiform vascular pattern. Bland mitotically inactive spindle shaped tumor cells. Abundant myxoid stroma with ropey collagen fibers and adipose tissue. Blood vessels generally inconspicuous, rarely, plexiform, haemangiopericytomatous, pseudoangiomatous vascular pattern. Patternless haphazard arrangements of spindle cells. Intervening small bands of collagen fibers separate single cells. Staghorn haemangiopericytomatous vascular pattern. Primitive non lipogenic mesenchymal cells and variable lipoblasts. Delicate, arborizing, chicken-wire capillary vascular pattern.
CD34+ BCL2+ S100−
No information as never been closely studied
CD34+ BCL2+ S100−
Monosomy or partial loss of chromosome 13 and/or 16
STAT6+ CD34+ BCL2+ CD99+ S100−
NAB2-STAT6 fusion gene
CD34− S100+
t(12; 16)(q13; p11), rarely t(12; 22) (q13; q12)
Non cohesive, plump, atypical spindled to stellate tumor cells with enlarged hyperchromatic nuclei. Prominent elongated, curvilinear, thin walled blood vessels.
SMA+ DesminCD68−
Highly complex, non specific
+, positive; −, negative.
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
A rare case of dendritic fibromyxolipoma
and primitive non-lipogenetic mesenchymal cells, which are classically present in myxoid liposarcoma, is helpful to differentiate DFML from myxoid liposarcoma.13 In addition, clinical and radiological information of a deep-seated soft tissue mass with infiltrative borders, although not always the case, is a feature of malignancy. While routine immunohistochemical study is not required in classical cases of myxoid liposarcoma, unlike DFML, all the neoplastic cells are diffusely positive for S100 protein and are CD34 negative.13 Recurrent translocation t(12;16)(q13;p11), and rarely, t (12;22)(q13;q12), with resultant generation of FUS/DDIT3 and EWS/DDIT3 hybrid protein respectively, are cytogenetic hallmarks of myxoid liposarcoma.14 Hence, demonstration of DDIT3 genomic rearrangement is a valuable adjunct to exclude other morphologic mimics in difficult cases.14 The other superficial myxoid soft tissue tumor that is included in the differential diagnosis is low grade myxofibrosarcoma. Low grade myxofibrosarcoma is characteristically sparsely cellular and displays abundant myxoid stroma mimicking DFML. However, it can be easily distinguished from DFML by the presence of atypical, enlarged spindle cells with classically curvilinear blood vessels in the former.15 We highlighted an exceedingly rare case of DFML of the left shoulder in a 67-year-old male, which we propose to be the first reported case with cytogenetic analysis performed. Although the deletion of the 13q14.3 region detected in the present case is not unique to SCL and warrants a larger scale study to prove its validity, we postulate that DFML is merely an unusual myxoid variant of SCL on the basis of the striking overlapping clinical, histomorphological and immunohistochemical features. A similar speculation has been previously expressed.3,16 Although rare, DFML is an important entity to recognize as it can be potentially confused with malignant myxoid spindle cell neoplasm. Careful observation for distinctive histological cues in the right clinical context as well as valuable cytogenetic input will help reach to an accurate diagnosis.
ACKNOWLEDGMENT We would like to thank all the laboratory staffs of Universiti Kebangsaan Malaysia Medical Center for their excellent technical support.
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