Which conditions are included in the differential diagnoses of primitive neuroectodermal tumor of the thoracopulmonary region (PNET)?

Updated: Dec 25, 2019
  • Author: Joseph F Tomashefski, Jr, MD; more...
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The histological distinction between PNET and extraskeletal EWS is not well defined. Previous studies have emphasized the presence of Homer-Wright rosettes and immunohistochemical neural markers as evidence of PNET. [96] Recent studies, however, have failed to reveal significant clinical differences between these two entities. A current recommendation is to classify these tumors as members of the EWS/PNET family, with a comment regarding the presence or absence of neural differentiation. [96]

Other entities in the differential diagnoses of Askin tumor include small cell carcinoma, neuroblastoma, alveolar rhabdomyosarcoma, poorly differentiated synovial sarcoma, and DSRCT. Metastatic pulmonary small cell carcinoma usually affects older adult smokers and presents as a primary lung mass. Histologically, the neoplastic cells of small cell carcinoma are more pleomorphic than those of PNET, and immunohistochemical markers show typically staining for cytokeratin and neuroendocrine markers such as synaptophysin and CD56.

Alveolar rhabdomyosarcoma may have a focally diffuse histological pattern that resembles PNET; however, an alveolar pattern is usually seen. Although rhabdomyosarcoma may sometimes stain for CD99, myogenic markers such as desmin, myogenin, or MyoD will be positive. [96] Alveolar rhabdosarcoma also exhibits a characteristic cytogenetic marker t(2;13)(q35;q14).

In young patients, neuroblastoma enters the differential diagnoses of PNET. However, compared to PNET, neuroblastoma includes the histological features of neuropil and ganglionic differentiation. Neuroblastoma rarely expresses the immunomarker CD99. Patients with neuroblastoma also have elevated levels of urinary catecholamine metabolites. Finally, neuroblastoma lacks the t(11;22) translocation found in the EWS/PNET family of tumors. [96]

Poorly differentiated synovial sarcoma may be difficult to distinguish from PNET owing to the presence of small round cells in poorly differentiated synovial sarcoma, lack of cytokeratin expression, and presence of membranous CD99 staining on immunohistochemistry. [96] In difficult cases, detection of the signature t(X;18) translocation or the SSX1/SYT or SSX2/SYT fusion products is diagnostic of synovial sarcoma.

Pleural DSRCT differs histologically from PNET by the presence of islands of small round tumor cells separated by fibrous bands. Immunohistochemically, DSRCT expresses the polyphenotypic expression of cytokeratin, vimentin, desmin, and neural markers. Staining for desmin is present as a perinuclear dot configuration. Up to 20% of DSRCTs may express CD99. DSRCT also usually shows nuclear expression of WT1, unlike PNET. In difficult cases, detection of the unique cytogenetic abnormality t(11;22)(p13;q12) with the detection of the EWS/WT1 fusion product supports the diagnosis of DSRCT. [96]

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