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Year : 2019  |  Volume : 15  |  Issue : 4  |  Page : 947-952

Undifferentiated sarcoma of the soft tissues with cystic degeneration: Case report and review of literature

1 Department of Intervention and Hemangioma, Qilu Children's Hospital of Shandong University, Jinan City, Shandong Province, China
2 Department of Pathology, Qilu Children's Hospital of Shandong University, Jinan City, Shandong Province, China

Date of Web Publication14-Aug-2019

Correspondence Address:
Lei Guo
Department of Intervention and Hemangioma, Qilu Children's Hospital of Shandong University, Room 23976, Jingshi Road, Jinan City, Shandong Province 250022
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_818_18

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 > Abstract 

Undifferentiated sarcoma (UNDS) of the soft tissue is an exceedingly rare disease. Its diagnosis depends mainly on molecular and immunohistochemical analyses to exclude other soft-tissue sarcomas. It is difficult to confirm a positive diagnosis by imaging pathological features because of their rarity and similarity with other conditions. Since 2013, only 13 cases of undifferentiated soft-tissue sarcoma, mostly diagnosed through imaging of solid tumors in infant and children, have been reported. The authors present a rare case of a 3-month-old Chinese boy with UNDS primarily in the left lower extremity and characterized by a cystic and solid growth pattern.

Keywords: Soft tissue sarcoma, undifferentiated sarcoma, UNDS

How to cite this article:
Wu C, Wang L, Guo L, Zhang L, Li J. Undifferentiated sarcoma of the soft tissues with cystic degeneration: Case report and review of literature. J Can Res Ther 2019;15:947-52

How to cite this URL:
Wu C, Wang L, Guo L, Zhang L, Li J. Undifferentiated sarcoma of the soft tissues with cystic degeneration: Case report and review of literature. J Can Res Ther [serial online] 2019 [cited 2020 Dec 4];15:947-52. Available from: https://www.cancerjournal.net/text.asp?2019/15/4/947/264306

 > Introduction Top

Undifferentiated sarcoma (UNDS) is a rare malignant soft-tissue tumor. UNDS is common among infants and children aged between 0 and 20 years.[1],[2] The typical clinical manifestations of this disease are painless masses on the extremities, back, flank, abdominal wall, or on the head and neck.[1],[3] However, confirming a positive diagnosis by imaging is difficult despite the analysis of pathological features because of the rarity of the disease and morphologic similarities with other conditions. Furthermore, it is difficult to distinguish UNDS from other tumors with similar clinicopathological characteristics using limited technology; this may lead to a relatively large number of UNDS cases being reported. The application of new technologies for molecular and immunohistochemical analyses have enabled the exclusion of rhabdomyosarcoma, Ewing sarcoma (ES), synovial sarcoma, and high-grade pleomorphic UNDS while diagnosing UNDS.[4] Thus, the current number of actual UNDS patients is obviously lesser than that in the past,[1],[5],[6] according to a new definition in 2013. Only 13 cases of undifferentiated soft-tissue sarcoma (USTS), mostly including imaging manifestations of solid tumors in infant and children groups, have been reported. The authors present a rare case of a 3-month-old Chinese boy with UNDS primarily within the lower left extremity and characterized by a cystic and solid growth pattern.

 > Case Report Top

A 3-month-old boy was brought to our outpatient department by his father with a complaint of progressive swelling in the left lower extremity [Figure 1]a, which was discovered at birth. Prenatal screening and family histories were unremarkable. Physical examination revealed a vague margin and soft and nontender swelling in the left thigh. Skin of the tumor surface was light purple with nonulceration. Blood tests, including tumor marker examination, showed normal results.
Figure 1: (a) Mass located in the left lower extremity; (b and c) ultrasound images showing a dark, opaque, reticulate area containing fluid (b) measuring 8.1 cm × 6.0 cm × 4.8 cm with a few blood vessels (c) passing through, surrounded by the thickened, density-reinforced soft tissue. (d-f) The MRI revealed a massive tumor, with long T1 and short T2 signal intensities, and multiple cystic lesions separated by fats. Postcontrast inhomogeneous enhancement was seen within the mass, while no enhancement was seen within the cystic lesions. (g) Surgical resection of the tumor

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All imaging examinations suggesting vascular anomalies included color Doppler ultrasound and magnetic resonance imaging (MRI). The color Doppler images showed a reticulate opaque dark area of fluid [Figure 1]b measuring 8.1 cm × 6.0 cm × 4.8 cm with a few blood vessels [Figure 1]c passing through, surrounded by thickened, density-reinforced soft tissue. The size of tumor was 11.6 cm × 6.1 cm × 3.7 cm, as measured by the color Doppler ultrasound. The contrast-enhanced MRI also revealed a massive tumor, with long T1 and short T2 signal intensities, and multiple cystic lesions separated by fats [Figure 1]d and [Figure 1]e. Postcontrast inhomogeneous enhancement was seen within the mass, while no enhancement was seen within the cystic lesions [Figure 1]f; the biopsy revealed undifferentiated carcinoma. The child underwent surgical treatment after the contraindications of surgery were eliminated; a cystic and solid aggressive lesion 18 cm × 13 cm × 10 cm in size, grossly adhering to the subcutaneous tissue and muscle, was seen [Figure 1]g. Histopathological examination revealed malignant nuclear features with cellular polymorphism [Figure 2]a and [Figure 2]b. In addition, Vimentin positivity and weak Ki-67 positivity were seen, consistent with the diagnosis of high-grade, undifferentiated (embryonal) sarcoma [Figure 2]c, [Figure 2]d, [Figure 2]e. Immunohistochemistry (IHC) did not show Myogenin and MyoD1 positivity, making rhabdomyosarcoma unlikely. In addition, the tumor cells were negative for CD33, SMA, Desmin, S-100, CD34, CD99, and CK. He was administered VAC chemotherapy with vincristine (0.05 mg/kg for day 1), actinomycin D (0.045 mg/kg for day 1), and cyclophosphamide (40 mg/kg for day 1) after surgical treatment. Repeated systemic imaging revealed no evidence of local tumor recurrence or distant metastasis during multicycle chemotherapy.
Figure 2: Pathology of UNDS: (a and b) Hematoxylin and eosin-stained sections an intermediate (×400). (c-e) Representative high-magnification images (×400) of immunohistochemical staining for Vimentin+ (c), CD99− (d), and Ki67+/− (e)

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 > Discussion Top

UNDS is defined as a highly malignant mesenchymal neoplasm evolved from malignant fibrous histiocytoma; it lacks specific diagnostic morphological features. These tumors were originally designated as “small round-cell sarcoma, type indeterminate,” incorporating all sarcomas without identifying a specific lineage. In 2013, the World Health Organization reviewed the classification of soft-tissue tumors and established the classification and nomenclature of UNDS, further subclassifying them into the spindle-cell, round-cell, epithelioid, and pleomorphic subsets; however, individual morphologic patterns often coexist.[7],[8] Previous literatures have reported 13 cases of USTS in infant and children groups after 2013, with a relatively complete description of clinicopathologic features [Table 1].[9],[10],[11],[12],[13],[14],[15],[16] In these 13 cases, the mean age at the time of diagnosis was 8.68 years (range: 8 days–18 years).
Table 1: Clinicopathologic features of 1 tumor in this current series and 12 previously reported tumors

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The major complaint in newly diagnosed patients is a rapidly growing lesion on the body surface. The group of UNDS emphasized their primitive mesenchymal nature became smaller and more refined profited from the new diagnostic adjuncts such as IHC, cytogenetics, and molecular genetics. Fortunately, the presence of certain morphological and immunohistochemical features raised the possibility of a specific sarcoma subtype in individual cases, for example, S100 positivity occurs with malignant peripheral nerve sheath tumor (MPNST) and PEComa, and CD99 positivity occurs with Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET); however, these are not perfectly equivalent. In a recent study of infantile UNDS, IHC showed Vimentin (92%) CD117 (92%) and vascular endothelial growth factor (69%) positivity; 8%–23% of the cells showed focal positivity for epithelial, neural, or myogenic markers.[4] However, research has shown that virtually all the neoplastic cells were Vimentin positive and showed positive nuclear staining with INI-1 antibodies; approximately 5% of the cells showed membranous CD99 immunoreactivity.[13] In our case, Vimentin positivity was also shown, but with poor specificity. In addition, the immunohistochemical characteristics of UNDS s associated with CIC-DUX4 and BCOR-CCNB3 fusion genes, showing not only a small round-cell component but also a myxoid/epithelioid component with low mitotic activity, were reported by Yamada et al.[17]

A thorough morphological and molecular genetic analysis of pediatric soft-tissue sarcoma is necessary to reveal features such as a sheet-like proliferation of densely packed, round-, or spindled-shaped tumor cells. In children, UNDS is mostly characterized by round- or spindle-shaped cells and shows a morphologic overlap with a variant of ES, once called atypical ES.[18]

Molecular genetic analysis was useful for the differentiation of UNDS from some other soft-tissue sarcomas, such as synovial sarcoma (SYT/SSX fusion transcript positive), ES/PNET (EWS gene rearrangement, CD99 positive), and infantile fibrosarcoma (ETV6/NTRK3 fusion transcript positive). In fact, up to 60% of tumors expressed some form of so-called lineage-specific antigens.[3] BCOR-CCNB3 fusions have been frequently reported in UNDS;[16],[19] individual cases of undifferentiated small round-cell sarcomas with CIC-DUX4 fusion have also been reported.[13],[20],[21] For the pediatric population, the BCOR-CCNB3 fusion gene mostly resulted from the paracentric inversion of the X chromosome.[22] Using whole transcriptome paired-end RNA sequencing, Peters et al.[19] unexpectedly identified BCOR-CCNB3 fusion transcripts in undifferentiated spindle-cell sarcoma. In particular, gene profiling experiments indicated that BCOR-CCNB3-positive cases are biologically distinct from other sarcomas,[23] particularly ES.[24]

Through a systematic comparison between ES and ES-like cases at the molecular and immunohistochemical levels, individual cases of these UNDS were first recognized to have the characteristic karyotypic translocation.[25] Subsequently, the results of a study on 22 patients suggest the possibility of a newly defined subgroup of primitive round-cell sarcomas characterized by CIC rearrangements.[26] In 2017, a case of pediatric UNDS with a novel variant of t (4;19) CIC-DUX4 fusion transcript was reported.[15] Tsukamoto et al.[27] reported a case of t(10;19) CIC-DUX4 undifferentiated small round-cell sarcoma. As indicated, in addition to CIC-DUX4 fusions, CIC-FOXO4 fusions have also been described in tumors occurring in peripheral soft tissues.[21]

Nevertheless, it is still very difficult to make a definite diagnosis through preoperative imaging without characteristic manifestations. Ultrasonic imaging has been rarely described by UNDS scholars; the ultrasonic parameters in our case are similar to those of undifferentiated embryonal sarcoma of the liver.[28] The color Doppler ultrasound images demonstrate a round hyperechoic lesion within several anechoic spaces, which correspond to fluid-filled spaces. These images represent a diagnostic challenge for sonographers in distinguishing UNDS from lymphatic malformations. In addition, color Doppler flow imaging revealed lots of spots and slices style color blood-flow signals which represent the arteries originating from the superficial femoral artery and supplying blood to the neoplasm. MRI, which is better than computed tomography, has a higher soft-tissue contrast and is the common diagnostic method for soft-tissue sarcoma. Although MRI revealed vascular anomalies, it was responsible for the wrong initial diagnosis in our case. It showed a mass with predominantly inhomogeneous hypointense signals compared to those of the normal surrounding tissue and a lack of marked enhancement of cystic lesions. The tail sign was a common MRI feature of UNDS and was also associated with worse local recurrence-free survival (P = 0.019).[29] According to a study on 35 UNDS patients, the incidence of this feature was nearly 50%. This may contribute to preoperative diagnosis, illness evaluation, and therapeutic effect prediction. Furthermore, the addition of functional MR procedures to a routine MR protocol, Dynamic contrast-enhanced MRI (DCE-MRI) in particular, offers a specificity of >95% for distinguishing recurrent sarcoma from postsurgical scarring.[30]

Clinically, a novel finding of this study was that patients with USTS can achieve long-term survival with multimodal therapy including chemotherapy and surgery. Somers et al.[4] described the cases of 13 children under 16 years of age who were treated for UNDS of the trunk and extremities, of which four received only chemotherapy, one received chemotherapy following radiotherapy, four underwent operation with chemotherapy, and three received a combination of all three; the data for one patient were lost. The 5-year event-free and overall survival rates were 54% and 74%, respectively. The prognosis of UNDS was closely related to tumor invasiveness and size, age at diagnosis, primary tumor site, resection margins, initial resectability, and response to radiotherapy and chemotherapy.[31] Somers et al.[4] have suspected that severe atypia was associated with decreased survival (P = 0.048).

In summary, due to the tremendous development of IHC and molecular biology techniques, the understanding of soft-tissue sarcoma continues to deepen. However, because UNDS is a highly heterogeneous tumor, its diagnosis is based on exclusion. With regard to the diagnosis and treatment of UNDS, we strongly recommend caution, especially during the imaging of cystic solid tumors. Needle biopsy is a wise choice to confirm the initial diagnosis. The presence of certain common morphological and immunohistochemical features in the absence of specific genetic abnormalities allows for the correct diagnosis of pediatric USTS.

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.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

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