ASPS is a rare malignant mesenchymal tumor accounting for less than 1 % of all soft tissue tumors . Clinically, it typically presents as a soft, painless, slow-growing mass and most classically occurs in the deep soft tissue of the extremities in adolescents and young adults (15–35 y of age), with a female predominance [1, 2]. The most common locations include buttocks/thighs, legs/popliteal fossa, chest wall/trunk, and the upper extremities. In children and infants, the head and neck region including the tongue and orbit, is a common location. Unusual primary soft tissue locations include the retroperitoneum, mediastinum, and bone [4, 5]. Visceral organ, such as lung, liver and brain, involving by ASPS mostly represents a metastasis from a primary soft tissue tumor elsewhere. Hovever, sporadic reports have certainly documented primary ASPS of visceral organs including the lung, stomach, liver, breast, larynx, heart, urinary bladder, and female gential tract [8, 7, 6, 10, 9, 13]. Primary ASPS of lung is extraordinarily rare, to the best knowledge of us, our case represents only the third one of such cases that have been reported in the English language literature since the mid 1960’s [14, 8]. The two previously reported cases were from Japan, and Korea, respectively. However, the Japanese case , which was initially described as a tumor arising from the pulmonary vein at the lung hilus, had been questioned by other authors as a tumor origining in the mediastinum rather than in the lung . In contrast to metastatic ASPS of the lung that often radiologically appeared as mutiple and bilateral nodules, both our and the Corean case  presented as a solitary, asymptomatic mass in the lung, similar to primary ASPS that had been reported in other visceral organs.
Histologically, ASPS mostly presents stereotypical morphologic features with round nests and alveoli composed of dyscohesive uniform polygonal neoplastic cells having round nuclei with vesicular chromatin, a prominent nucleolus, and abundant cytoplasm containing PAS positive, distase resistant crystals [2, 1]. However, the organoid appearance may be lacking and the tumor may be composed of sheets of neoplastic cells. Rarely, ASPS may shows light microscopic features that depart from the conventional morphology and cause differential diagnostic confusions. Our case showed several unusual morphologic features of ASPS that have only been occasionally mentioned in the literature, including heavy lymphocytic infiltrate, anaplasia, clear cells, rhabdoid-like cells, and multinucleation [1, 13].
The cell of origin or, better, line of differentiation taken by ASPS is elusive, and attempts to investigate it by ultrastructural and immunohistochemical studies have failed to elucidate the line of differentiation, with controversial results [2, 1]. Recently, the molecular signature of ASPS has been described as a specific unbalanced translocation: der(17)t(X;17)(p11.2;q25) . This translocation results in the fusion of TFE3 transcription factor gene at Xp11.2 with ASPL at 17q25 [3, 12]. Recent studies has shown that the ASPL-TFE3 fusion transcript can be identified by RT-PCR analysis and TFE3 gene rearragement can be detected using a dual-color, break apart FISH assay in paraffin-embedded tissue, both can be uesd as powerful tools for diagnosis of ASPS [12, 16, 17], in addition, the resultant fusion protein can be detected by IHC with an antibody directed to the carboxy terminal portion of TFE3 with high sensitivity and specificity ; all the three tools were used in the current case to confirm the diagnosis of ASPS in the lung. TFE3 gene rearrangment by FISH assay and moderate to strong nuclear TFE3 positivity by IHC are virtually pathognomonic for ASPS, Xp11.2 translocation associated RCC , and a subset of PEComa that harbors TFE3 gene fusion . Xp11.2 translocation associated RCC is a recently described category of renal tumor that is characterized by a papillary architecture composed of cells with voluminous clear or eosinophilic cytoplasm and psammoma bodies. Genetically, Xp11.2 translocation associated RCC harbors a balanced t(X;17)(p11.2;q25) translocation in the majority cases, which is in contrast to that of ASPS [19, 21]. TFE3 gene fusion associated PEComa, a most recently described subtype of PEComa that occurs primarily in young adults of both renal and extrarenal, and features of prominent epithelioid cells with alveolar architecture, as well as an aggressive clinical course . FISH assay and RT-PCR analysis in these tumors have shown TFE3 gene rearrangement and amplification, respectively. However, the partner fusion gene of TFE3 in PEComa is largely unknown nowadays [22, 23]. Distinguishing these tumors may need IHC for additional markers (as discussed below).
Although its high sensitivity and specificity for identification of neoplasms with associated gene fusion, detection of TFE3 reactivity by IHC has been shown to be technically difficult, not inrequently accompanied with strong background stain, or even with false positive and negative results . In addition, significant TFE3 expression can ocassionally be seen in tumors that not harbor an associated gene fusion, such as granular cell tumor , paraganglioma , and adrenocortical carcinoma , these findings are of particular importance since all these tumors may show overlapping morphological features with ASPS.
The differential diagnosis in the current case is relatively broad that includes the rhabdoid or large cell undifferentiated lung carcinoma , paraganglioma , epithelioid PEComa (clear cell sugar tumor) , malignant granular cell tumor , melanoma, and metastatic carcinoma such as RCC, adrenocortical carcinoma, and HCC . Although careful histomorphologic investigation obviously plays a critical role in this differential diagnosis, IHC, and occasionally molecular genetic analysis will prove decisive, as evidenced by the current case. Briefly, carcinomas of pulmonary origin would be expected to show considerable CK expression in most cases, whereas ASPS does not express CK. Metastatic Xp11.2 translocation associated RCC may show only weak CK expression, but generally show strong PAX8 nuclear expression, a finding not seen in ASPS. Metastatic adrenocortical carcinoma and HCC would be expected to show MelanA and HepPar-1 expression in the majority of cases, respectively, whereas ASPS expresses neither of the two markers. Paraganglioma, but not ASPS, expresses neuroendocrine markers, such as chromogranin A and synaptophysin. Granular cell tumor and melanoma typically display strong, uniform S100 protein expression, which is absent in ASPS. Expression of melanocytic markers, such as HMB45 and MelanA, would be seen in melanoma and epithelial PEComa, but not in ASPS.