Desmoplastic small round cell tumor of the kidney with bone metastasis: A case report

Abstract

Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive sarcoma that predominantly affects adolescent and young adult males. DSRCT typically arises from the serosal surface of the abdominal cavity with a high propensity for metastatic disease and, subsequently, poor prognosis. The diagnosis is often challenging due to its nonspecific clinical presentation and overlapping imaging features with other abdominopelvic entities. Consequently, imaging, particularly computed tomography (CT) and positron emission tomography-computed tomography (PET–CT), plays a central role in the initial evaluation. Ultimately, a definitive diagnosis requires histopathologic confirmation, given that DSRCT shares imaging and histologic characteristics with other round cell neoplasms. In this article, we report a case of a primary DSRCT of the kidney in a 23-year-old male, highlighting the clinical presentation, imaging features, and aggressive course of this tumor.

Introduction

Desmoplastic small round cell tumor (DSRCT) is an exceedingly rare sarcoma with aggressive behavior originally described in 1989 by Gerald and Rosai [1]. DSRCT most frequently affects adolescents and young adults, with a male predominance (80%) [2]. The mass typically originates from the serosal surface of the abdominal cavity and has a high propensity for metastasis. Despite existing and improving management strategies, the prognosis for DSRCT remains poor, and many patients experience recurrence or have extensive metastasis at the time of diagnosis [2,3].

DSRCT typically presents with abdominal pain and distension, weight loss, constipation, and ascites [4]. Computed tomography (CT) is the first-line modality for imaging, but other imaging modalities may also be used [5]. However, a definitive diagnosis is achieved by histological analysis of a biopsy. DSRCT is known to be associated with a distinct chromosome translocation t(11;22) resulting in the EWSR1::WT1 fusion which is a different t (11;22) than the EWSR1::FLI1 fusion of Ewing sarcoma. Here, we report the case of a 23-year-old male who presented with severe, intermittent back and hip pain secondary to a primary renal desmoplastic small round cell tumor. We discuss and correlate the imaging findings with clinical and histological evaluation in the management of this rare entity.

Case report

A 23-year-old male presenting with lower back and bilateral hip pain was referred to our institution for management after recent biopsy of a primary renal mass was confirmed to be DSRCT. A review of the external CT imaging demonstrated an oblong, hypodense mass in the mid- to upper pole of the right kidney (Fig. 1). The mass demonstrated complete encasement of the right renal artery. Bulky aortocaval lymphadenopathy measuring 11.7 × 10.1 × 5.0 cm was identified with associated mass effect on the adjacent inferior vena cava and abdominal aorta. Trace pelvis ascites was noted. PET-CT was performed at our institution and demonstrated avid fluorodeoxyglucose (FDG) uptake in the right renal mass (Fig. 1). Extensive lymphadenopathy was observed in the pericaval, para-aortic, left supraclavicular, and paraesophageal areas, consistent with metastasis. Innumerable sclerotic lesions of varying sizes involving the spine, pelvis, and bilateral femoral heads were also appreciated. The patient was treated with multiple cycles of neoadjuvant and adjuvant chemotherapy, radiation therapy, and radical right nephrectomy, which were overall unsuccessful. Histologic examination of the surgical specimen demonstrated a dominant 7.5 cm renal mass (Fig. 2) composed of sheets of primitive round cells with fine chromatin and somewhat clear cytoplasm within an extensive desmoplastic stroma. While the tumor lacked significant necrosis from the neoadjuvant therapy, scattered bizarre pleomorphic cells were seen suggesting mild treatment-related cytomorphologic changes from the neoadjuvant chemotherapy (Fig. 2). Immunohistochemistry demonstrated dot-like expression of desmin (not shown) but cytokeratin AE1/AE3 was negative. Molecular analysis demonstrated a t(11;22) translocation leading to the EWSR1::WT1 fusion. Additional sites of metastatic disease were identified within the peri-renal soft tissue as well as the pericaval, retrocaval, and aortocaval soft tissues. Treatments were complicated by the progression of metastasis (including liver, lung, and diffuse osseous metastases) with poor chemotherapeutic tolerance, and the patient died of disease 2 years later.

Fig. 1.

A 23-year-old male presenting for evaluation of a known DSRCT in the right kidney. Contrast-enhanced CT in the axial (A-B) and coronal (C-E) views demonstrates a hypodense mass in the mid- to upper pole of the right kidney, consistent with the known DSRCT (Arrow—C). Bulky aortocaval lymphadenopathy was also noted with mass effect on the inferior vena cava and abdominal aorta (Arrows—B, D, E). Complete encasement of the right renal artery was observed (Arrows—A, D). PET-CT performed at our institution (F-H) revealed FDG avidity in the right renal mass extending into the aortocaval lymphadenopathy (Arrows—G, H). Numerous sclerotic lesions were appreciated in the spine, pelvis, and bilaterally in the femoral heads (Arrows—F).

Fig. 2.

DSRCT of the kidney after neoadjuvant chemotherapy and radical nephrectomy. (A) Gross photograph of the radical nephrectomy specimen showing a solid, tan-yellow, intrarenal mass with extrarenal extension (ruler shows cm). (B-D) Low-power hematoxylin and eosin (H&E) views demonstrating a sheet of primitive cells infiltrating native renal parenchyma within a septae of desmoplastic stroma without evidence of necrosis (B-D). E-F: Higher-power H&E views showing nests of small round to oval tumor cells with clear cytoplasm and scattered nuclear anaplasia as seen on the right side of panel F (E, 10x; F, original magnification 20x).

Discussion

Desmoplastic small round cell tumor (DSRCT) is a rare but aggressive sarcoma that predominantly affects adolescent and young adult males with an age-adjusted incidence between 0.2 and 0.5 cases/million [6]. DSRCT typically arises from the peritoneum, often invading the omentum, retroperitoneum, and various other abdominal structures [7]. About 50% of patients present with metastatic disease at the time of diagnosis, most commonly to the liver and lung [6,8,9]. Symptoms are often related to tumor burden and the location thereof, but abdominal pain is commonly observed. The prognosis of DSRCT is poor, with 5-year overall survival between 12% and 33% [6,10,11].

Nearly all examples of DSRCT harbor an oncogenic chromosomal translocation t(11;22) which was first characterized by Gerald and Rosai in 1989 [1]. This translocation results in an oncogenic fusion between the EWSR1 and WT1 genes [12,13]. For many years, the t(11;22) EWSR1::FLI1 fusion was considered to be pathognomonic for DSRCT; however, there have been recent reports of neoplasms other than DSRCT containing this characteristic gene fusion that lack the clinical and pathologic features of DSRCT. For example, Schoolmeester et al. [14] described 3 instances of non-DSRCT neoplasms with the EWSR1::WT1 fusion in the female genital tract, and Warmke et al. [15] recently reported 3 additional cases occurring in the abdominopelvic cavity (n = 2) and 1 in the axillary soft tissue. Ultimately, it is now clear that the diagnosis of DSCRT requires an integration of clinical, radiologic, and pathologic data for which not 1 standalone test (a molecular fusion assay, for example) is diagnostic in isolation.

As DSRCT often presents with nonspecific symptoms, cross-sectional imaging remains a crucial step in its workup and diagnosis. CT is the most frequently employed imaging modality, but cases have been documented in which ultrasound, PET/CT, or magnetic resonance imaging were used [5,16]. DSRCT typically presents on CT imaging with multiple lobulated, peritoneal, soft-tissue masses, often without a clear organ of origin [5,7]. Ascites is also commonly observed. However, the case which we report exhibited a dominant mass in the upper pole of the right kidney, unlike many instances of DSRCT. Regions of heterogeneity on CT are proposed to correspond to focal hemorrhage or necrosis within the tumor [5]. Extensive diffuse nodularity is often observed on cross-sectional imaging within the peritoneal cavity, omentum, mesentery, and even the chest [4,5,17]. Although DSRCT is well known to metastasize to the liver and lungs, it rarely exhibits osseous involvement, as in the case reported above [17].

The radiologic differential for DSRCT is broad and includes multiple solid peritoneal masses. Infiltrative masses of the peritoneal cavity may occur secondary to various abdominopelvic etiologies, including inflammatory processes and urogenital or gastrointestinal malignancies [18,19]. The marked nodularity often observed in DSRCT may be mimicked by malignant lymphoma, Castleman disease, mycobacteriosis, and other conditions with a propensity for lymphadenopathy [[20], [21], [22]]. The presence of an organ-based primary mass typically favors carcinomatosis over DSRCT. However, the dominant mass centered in this patient’s right kidney rendered this case unique, as DSRCT typically presents without a clear organ of origin. Furthermore, radiologic evidence of bone metastases complicated this patient’s presentation, as this finding is also characteristic of Ewing sarcoma, another tumor defined by a translocation between chromosomes 11 and 22. In any event, the often-overlapping radiological features of DSRCT and other entities render pathological analysis necessary for definitive diagnosis.

Histologically, DSRCT manifests as a high-grade sarcoma composed of sharply demarcated hypercellular islands, nests, and cords of monotonous small round primitive nuclei [23]. However, DSRCT may mimic a number of other round cell tumors including Ewing sarcoma (ES), alveolar rhabdomyosarcoma (ARMS), neuroblastoma, and lymphoma [24]. The diagnosis of DSRCT requires a constellation of data points, including immunohistochemistry in which most DSRCTs will harbor the characteristic dot-like pattern of desmin as well as cytokeratin positivity. Co-expression of keratin and desmin is an unusual immunophenotype which, in concert with a primitive round cell sarcoma growing within desmoplastic stroma, and the typical clinical and radiologic pattern of DSRCT, the presence of the EWSR1::WT1 fusion is a helpful diagnostic adjunct which distinguishes DSRCT from other round cell malignancies [7].

The current standard of treatment for DSRCT includes chemotherapy and aggressive surgery. However, surgical intervention is only employed after the response to neoadjuvant chemotherapy reaches a plateau, typically after 4-6 months of treatment [4]. Even after chemotherapy and gross surgical resection, microscopic residual disease is common. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an emerging treatment option performed immediately after gross surgical resection, but its efficacy in reducing micrometastases remains uncertain [25]. Whole-abdomen radiotherapy has also been used postoperatively, but there is a high risk of severe hematological and gastrointestinal toxicities [4,26]. Ultimately, the nonspecific symptomatology and propensity for metastasis of DSRCT render cross-sectional imaging, such as CT, crucial for diagnosis. Given the high incidence of metastasis at the time of diagnosis, the prognosis of DSRCT remains poor, with a 5-year overall survival estimated between 15% and 30%. There remains a need for improved diagnostic and therapeutic modalities given the aggressive nature of this disease.

Data availability

Data sharing is not applicable to this article as no new data was created or analyzed in this study.

Patient consent

Written informed consent was obtained from the patient’s legal guardian for publication of this case report and accompanying images.