Desmoplastic small round cell tumor of the lung: case report

Desmoplastic small round cell tumor (DSRCT) is a clinically and morphologically well-defined neoplasm.1 This highly aggressive malignant small cell neoplasm tends to affect adolescents and young adults and occurs predominantly in the abdomen, pelvis, and omentum.1,2 DSRCT in the lung is extremely rare. Here we present a case of pulmonary DSRCT with description of its histopathological characteristics and discuss its differential diagnosis. CASE REPORT A 19-year-old man presented with 20-day history of low fever, cough, and right chest pain. He was a nonsmoker and had no prior history of tuberculosis. He had been treated for presumed pneumonia with antibiotics, and his symptoms were temporarily improved after treatment. However, 5 days prior to presentation, he had progressive shortness of breath and cough. Chest computed tomography (CT) scans revealed a 12 cm × 10 cm high signal intensity mass located in the right low lung with moderate pleural effusion (Fig. 1). There was no abdominal involvement. Clinical diagnosis was malignant tumor of right lung. At surgery, it was found that the tumor occupied the whole right low lung and extended into chest wall and mediastinum. The tumor could not be excised completely because of the extensive invasion into mediastinum and surrounding thoracic aorta. The patient died 9 months after the initial presentation.Fig. 1.: A 12 cm×10 cm high signal intensity mass located in the right low lung with moderate pleural effusion was revealed on chest computed tomography scan.Pathological findings: Grossly, the tumor measured 10 cm × 6 cm × 3.5 cm and was gray-white on cross-section. Foci of hemorrhage and necrosis were noted. Microscopically, the tumor was composed of sharply demarcated nests of small rounded or oval cells. The cellular aggregates were surrounded and separated by abundant fibrous connective tissue. The tumor cells were uniform in size and shape, and showed small to moderate amounts of pale cytoplasm with indistinct cell borders. The nuclei were round to oval, with clumped chromatin and marked hyperchromasia. Some cells had one or two indistinct nucleoli (Fig. 2). Numerous mitotic figures and areas of necrosis were identified. The tumor displayed features that have been described as being characteristic of intra-abdominal DRSCT. Immunohistochemically, the tumor cells showed diffuse and strong positive for cytokeratin (CK), epithelial membrane antigen (EMA), and Vimentin. There was focal positive staining for desmin with a perinuclear dot-like pattern (Fig. 3). Wilms' tumor protein (WT1) showed focal strong nuclear positivity (Fig. 4). Chromogranin, S-100, and CD99 were also noted focal positive. However, the tumor cells were negative for CK5/6, leucocyte common antigen (LCA), calretinin, HMB45, and MyoD1. Pathological diagnosis was made as desmoplastic small round cell tumor of right low lung.Fig. 2.: Angulated nests of small round cells embedded in a cellular fibroblastic stroma (HE, original magnification ×150).Fig. 3.: Immunostaining for desmin was noted with a perinuclear dot-like pattern (ABC, original magnification ×200).Fig. 4.: The tumor cells showed focal nuclear staining for WT1 (ABC, original magnification ×250).DISCUSSION DSRCT is a primitive polyphenotypic sarcoma with distinct clinical and histopathological features that suggest divergent differentiation and is a highly aggressive neoplasm with a poor prognosis.1 The tumor mainly affects adolescents and young males between 15 and 35 years of age and predominantly involves in the abdomen. Only one case of pulmonary DSRCT and six cases of pleura were reported in English literature.3-6 The patients with pleural and pulmonary DSRCT usually presented with chest pain and pleural effusion. The tumor shows the same characteristic features as intra-abdominal DRSCT. The diagnosis of pulmonary DSRCT can be established with correlation of clinical, histological and immunohistochemical features. Histologically, angulated nests of small round cells embedded in a cellular fibroblastic stroma are the typical feature of DSRCT. Immunohistochemically, perinuclear dot-like staining for desmin is unique. The histological and immunohistochemical features in this case are similar to those described in the literature.3-6 Demonstration of a divergent phenotype and the reciprocal translocation characteristic of DSRCT are critical to the diagnosis. Cytogenetically, the tumor cells also have a unique cytogenetic abnormality: t(11; 22)(p13; q12). The breakpoints involve the EWS gene on 22q12 and Wilms gene (WT1) on 11q13. The EWS/WT1 fusion transcript has been found only in DSRCT.7 Recently, Werner et al8 reported a novel EWS/WT1 gene fusion product, EWS-WT1 5/10, in a 6-year-old boy diagnosed with DSRCT. The novel EWS/WT1 gene fusion product was able to stimulate expression of the insulin-like growth factor-I receptor, a potent antiapoptotic receptor tyrosine kinase that may play an important role in DSRCT etiology.8 The recently developed polyclonal anti-WT1 antibody has been used to detect the WT1 protein in DSRCT. Lae et al9 detected positive staining to WT1 antibody in 29 out of 32 cases of DSRCT. Our case was also positive for WT1 protein. The differential diagnosis of pulmonary DSRCT includes following small round cell tumors of this region. (1) Small cell mesothelioma: Our case was initially considered as malignant mesothelioma based on clinical and radiological findings. However, primary mesothelioma is extremely rare in children and young adults. Histologically, angulated nests of small round cells embedded in a cellular fibroblastic stroma is typical feature of DSRCT. The dot-like immunostaining for desmin and negative for CK5/6 and calretinin can distinguish DSRCT from small cell mesothelioma.4 (2) primitive neuroectodermal tumor (PNET)/Ewing's sarcoma family of tumors. The age of presentation is similar. Histologically, they are composed of small round, undifferentiated blue cells with scant cytoplasm. Immunohistologically, PNET/ Ewing's sarcomas usually show a unidirectional differentiation toward neural elements. DSRCT appears to show multidirectional differentiation toward muscle, neural, and epithelial elements. At cytogenetic level, the abnormal translocation in PNET/Ewing's sarcoma is t(11;22)(q24;q12).7 (3) Malignant non-Hodgkins lymphoma: It is excluded by the negative immunostaining for LCA of the tumor cells. (4) Small cell carcinoma: It lacks a desmoplastic stroma and the tumor cells are negative immunostaining for desmin and S100. In summary, DSRCT should be considered in the differential diagnosis of small round cell tumors of the lung. Immunostaining profiling is helpful for the diagnosis of this tumor.