|Year : 2020 | Volume
| Issue : 4 | Page : 630-633
|Dedifferentiated liposarcoma with heterologous spindle cell rhabdomyoblastic de-differentiation: An unusual pattern expanding the morphological spectrum
Bharat Rekhi1, Akshay D Baheti2, Shraddha Patkar3
1 Department of Surgical Pathology, HBNI University, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
2 Department of Radiodiagnosis, HBNI University, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
3 Department of Surgical Oncology (Gastrointestinal Surgery), HBNI University, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
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|Date of Submission||27-Nov-2019|
|Date of Decision||06-Jan-2020|
|Date of Acceptance||07-Jan-2020|
|Date of Web Publication||28-Oct-2020|
| Abstract|| |
Dedifferentiated liposarcoma (DDLS) is characterized by a wide histopathological spectrum. Spindle cell type of rhabdomyoblastic dedifferentiation has been rarely described in case of DDLS. A 39-year-old male presented with a recurrent retroperitoneal tumor mass, diagnosed as well-differentiated liposarcoma, for which he underwent surgical excisions on two occasions, followed by adjuvant radiation therapy previously. Computed tomogram scan his of abdomen revealed a large-sized, fat-containing recurrent, retroperitoneal mass, measuring 18.1 cm in the largest dimension. Histopathologic examination of the resected tumor revealed distinct areas of well- and dedifferentiated liposarcoma, including areas reminiscent of a myxofibrosarcoma, further progressing into a high-grade spindle cell sarcoma with fascicular and “Herringbone-like” growth patterns (fibrosarcoma-like). Immunohistochemically, high-grade spindle cell sarcomatous (dedifferentiated) component displayed distinct positivity for desmin and MyoD1, along with focal tumor nuclei, showing nuclear positivity for myogenin. Both well-differentiated liposarcomatous and dedifferentiated components displayed diffuse, intense nuclear positivity for MDM2 (overexpression) and p16INK4A. Furthermore, upon testing tumor sections displaying spindly sarcomatous areas for MDM2 amplification, by FISH technique, nearly all tumor cells displayed MDM2 gene amplification. This case constitutes one of the rare cases of DDLS displaying spindle cell rhabdomyoblastic dedifferentiation. Its diagnostic and treatment implications are discussed herewith.
Keywords: Dedifferentiated liposarcoma, MDM2, MDM2, MYOD1, retroperitoneal tumors, spindle cell rhabdomyosarcoma
|How to cite this article:|
Rekhi B, Baheti AD, Patkar S. Dedifferentiated liposarcoma with heterologous spindle cell rhabdomyoblastic de-differentiation: An unusual pattern expanding the morphological spectrum. Indian J Pathol Microbiol 2020;63:630-3
|How to cite this URL:|
Rekhi B, Baheti AD, Patkar S. Dedifferentiated liposarcoma with heterologous spindle cell rhabdomyoblastic de-differentiation: An unusual pattern expanding the morphological spectrum. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 Nov 25];63:630-3. Available from: https://www.ijpmonline.org/text.asp?2020/63/4/630/299337
| Introduction|| |
A dedifferentiated liposarcoma (DDLS) is a soft tissue tumor of adipocytic differentiation, displaying an atypical lipomatous tumor/well-differentiated liposarcoma (WDLS), either as a primary or as a recurrent lesion, progressing into a sarcoma, mostly nonadipocytic. Most cases of WDLS and DDLS are characterized by MDM2 gene amplification.
A spectrum of histopathological features has been described in a DDLS, especially in the dediffentiated component, including areas resembling an undifferentiated pleomorphic liposarcoma, myxofibrosarcoma, fibrosarcoma, inflammatory myofibroblastic tumor, fibromatosis, solitary fibrous tumor, gastrointestinal stromal tumor, myofibrosarcoma and rarely, a pleomorphic liposarcoma (homologous differentiation).,,,,
Nearly 5–10% DDLSs exhibit heterologous differentiation in the form of myogenic (smooth muscle or rhabdomyoblastic), osteocartilagenous, angiosarcomatous, and “meningothelial-like” whorling pattern, often associated with bone formation.,,,, Rarely, leiomyosarcomatous and small round cell component, reminiscent of Ewing sarcoma have been described within a DDLS.
This can create a diagnostic challenge, especially in limited biopsies, wherein the WDLS component might not be sampled, leading to a misdiagnosis, based on the dedifferentiated component; for example, a DDLS with rhabdomyosarcomatous differentiation, misdiagnosed as a rhabdomyosarcoma. Awareness of the wide morphological spectrum of a DDLS is crucial. An index of suspicion, coupled with MDM2, CDK4, and p16 immunostaining, along with MDM2 (12q15) gene amplification constitutes the diagnostic gold standard, especially in such cases., Within the histopathological spectrum of DDLS, spindle cell rhabdomyoblastic differentiation has been rarely described.
| Case Report|| |
A 39-year-old male presented with a recurrent retroperitoneal tumor mass for which he underwent prior surgical excisions on two occasions, three and four years back, respectively, followed by adjuvant radiation therapy, two years back.
Computed tomogram scan of his abdomen revealed a large-sized, fat-containing retroperitoneal mass, measuring 16.8 cm × 14.9 cm × 18.1 cm, along with a soft tissue nodule, measuring 5.7 cm × 6 cm, abutting the right kidney anteriomedially and inferiorly, extending beyond the midline to the left posterior side of superior mesenteric vessels [Figure 1]a.
|Figure 1: (a) Computed tomogram scan of abdomen showing a large-sized, fat-containing retroperitoneal mass, including a soft tissue nodule, with focal fat stranding, abutting the right kidney, anteromedially and crossing the midline.(b) Gross examination of resected specimen displaying a large soft tissue tumor mass with adjacent segments of ileum measuring and colon. Cut surface showing a lobulated yellowish white tumor with a fleshy, brownish nodule|
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He underwent tumor excision with right-sided nephrectomy and hemicolectomy.
Gross examination revealed a soft tissue tumor mass measuring 25 cm × 13 cm × 10 cm, with adjacent segments of ileum and colon, the latter surrounded by the tumor. On serial sectioning, the tumor appeared yellowish, with a fleshy brownish nodule [Figure 1]b. Microscopic features:
Multiple sections (n = 21) studied revealed distinct areas of WDLS and DDLS, including areas reminiscent of a myxofibrosarcoma, further progressing into a high-grade spindle cell sarcoma with fascicular and “Herringbone-like” growth patterns (fibrosarcoma-like) (two sections) [Figure 2]. Mitotic figures were noticed, exceeding 3/10 high power fields, in the spindly sarcomatous areas. There were no “strap-shaped” rhabdomyoblastic cells.
|Figure 2: Microscopic features. (a) Variable-sized adipocytes exhibiting nuclear atypia, including lipoblasts. Hematoxylin and Eosin (H and E) ×400. (b) Tumor areas with myxoid stroma and interspersed thin-walled blood vessels, reminiscent of myxofibrosarcomatous appearance. H and E, ×200. (c) Dedifferentiated tumor areas in the form of cellular spindly sarcomatous cells in the form of fascicles, reminiscent of “fibrosarcomatous” appearance. H and E, ×200. (d) “Herringbone” like arrangement of tumor cells with intervening mitotic figures. H and E, ×400|
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By immunohistochemistry, distinct tumor areas, especially DDLS component, displayed positivity for desmin and MyoD1, along with focal tumor nuclei, showing nuclear positivity for myogenin [Figure 3]. In addition, the well-differentiated liposarcomatous and dedifferentiated components displayed diffuse, intense nuclear positivity for MDM2 (overexpression) and p16INK4A [Figure 4]a.
|Figure 3: Immunohistochemical results. (a) Distinct spindly sarcomatous areas revealing desmin immunoreactivity. Diaminobenzidine (DAB), ×200. (b) MyoD1 positivity reinforcing rhabdomyosarcomatous dedifferentiation in the spindly sarcomatous cells. DAB, ×400. (c) Focal myogenin positivity. DAB, ×400. (d) Diffuse p16INK4 positivity within the areas of dedifferentiation|
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|Figure 4: (a) Diffuse MDM2 positivity in the spindly sarcomatous areas. DAB × 200. (b) MDM2 gene amplification in almost all cells of the spindly sarcomatous area, in the form of several green and few red signals, seen more clearly in the inset. DAPI, ×1000|
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Subsequently, the tumor section showing dedifferentiated spindly sarcomatous pattern was tested for MDM2 gene amplification by fluorescence in situ hybridization (FISH), using with ZytoLight® SPEC MDM2(green)/CEN12 (red) dual color fusion probes (ZytoVision GmbH, Bremerhaven, Germany), on 4-μm-thick paraffin sections. The sections were counterstained with 4'-6-diamidino-2-phenylindole (DAPI) and examined with a fluorescent microscope (Axio Imager Z1, Carl Zeiss, Germany) using Axio Cam MRc 5 camera and AxioVision Rel 4.5 software, Germany.
Almost all tumor cells, including from the spindly sarcomatous areas, displayed MDM2 over amplification, in the form of numerous green signals, with an isolate or at the most two red signals in tumor nuclei [Figure 4]b.
Earlier excised tumors revealed features of WDLSs.
| Discussion|| |
Rhabdomyoblastic differentiation in a DDLS is rarely reported. In an earlier published series of 25 DDLSs, over a period of eight years, focal rhabdomyoblastic differentiation in the form of “strap” or “tadpole-shaped” cells was reported in two cases. None of the cases, showing fibrosarcomatous dedifferentiation in that study, revealed rhabdomyoblastic differentiation. In another study, Binh et al., observed rhabdomyosarcomatous component in 20 cases, including spindle cell type in eight cases. Among those eight cases, only four cases revealed pure spindle cell rhabdomyosarcomatous component (without “tadpole” or “strap shaped” rhabdomyoblastic cells), similar to the present case. Shimada et al. reported three cases of DDLS, exhibiting rhabdomyosarcomatous differentiation in form of rhabdomyoblastic cells. While desmin and myogenin were positively expressed in the rhabdomyoblastic cells in all their three cases, only desmin was positively expressed in the spindle cells in their two cases, while myogenin was not expressed in spindle cells in any of their cases. Recently, a case of a DDLS producing human chorionic gonadotropin has been reported. While only four such cases were confirmed with MDM2 gene amplification, none of those cases displayed spindle cell rhabdomyosarcomatous components.
While distinct areas of WDLS and myxofibrosarcomatous component were helpful in confirming a DDLS in the present case, spindly sarcomatous component was initially considered as a fibrosarcomatous component., Immunohistochemical results, including significant desmin and MyoD1, along with focal myogenin immunoexpression, led to a spindle cell rhabdomyosarcomatous dedifferentiation. It is debatable whether adjuvant radiation therapy offered two years back led to the development of the spindle cell rhabdomyosarcomatous differentiation in our case, which on prior excisions harbored WDLSs. There are few reports on postradiation spindle cell rhabdomyosarcoma in sites, such as mandible. Furthermore, diffuse MDM2 immunostaining and MDM2 gene amplification confirmed a diagnosis of a DDLS in the present case.
Lately, awareness of a spindle cell rhabdomyosarcoma has led to the identification of this component/growth pattern in other tumors exhibiting dedifferentiation; for example, a recent report of a malignant peripheral nerve sheath tumor (MPNST) with spindle cell type of rhabdomyosarcomatous differentiation. In view of MDM2 gene amplification in the present case, we did not test this tumor for MyoD1(L122R) mutation, considering DDLSs and spindle cell/sclerosing rhabdomyosarcomas harbor mutually exclusive genetic signatures.
The importance of differentiating a spindle cell rhabdomyosarcoma from a spindle cell rhabdomyoblastic differentiation in tumors, such as DDLSs or MPNSTs has prognostic and treatment implications. A DDLS with myogenic, including rhabdomyoblastic dedifferentiation has been found to be associated with lower metastatic potential than a leiomyosarcoma. A spindle cell RMS is treated similarly as a RMS, with a specific chemotherapy regimen, unlike the other tumors which are relatively chemoresistant. There is growing evidence toward targeting MDM2 and CDK4 in dedifferentiated liposarcomas, especially large-sized, recurrent tumors, which cannot be completely resected and lack specific tailored chemotherapy.
To conclude, the present case constitutes a rare case of spindle cell rhabdomyosarcomatous differentiation in a DDLS, further expanding its morphological spectrum. Awareness of this growth pattern would be helpful in avoiding a misdiagnosis of a spindle cell rhabdomyosarcoma, especially on limited biopsy samples. An exact diagnosis has significant treatment implications.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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Department of Surgical Pathology, Room Number 818, 8th Floor, Annex Building, Tata Memorial Hospital, Dr E.B. Road, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
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