A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors.

Metastatic tumors with an uncertain primary site can be a difficult clinical problem. In tens of thousands of patients every year, no confident diagnosis is ever issued, making standard-of-care treatment impossible. Gene expression profiling (GEP) tests currently available to analyze these difficult-to-diagnose tumors have never been directly compared with the diagnostic standard of care, immunochemistry (IHC). This prospectively conducted, blinded, multicenter study compares the diagnostic accuracy of GEP with IHC in identifying the primary site of 157 formalin-fixed paraffin-embedded specimens from metastatic tumors with known primaries, representing the 15 tissues on the GEP test panel. Four pathologists rendered diagnoses by selecting from 84 stains in 2 rounds. GEP was performed using the Pathwork Tissue of Origin Test. Overall, GEP accurately identified 89% of specimens, compared with 83% accuracy using IHC (P=0.013). In the subset of 33 poorly differentiated and undifferentiated carcinomas, GEP accuracy exceeded that of IHC (91% to 71%, P=0.023). In specimens for which pathologists rendered their final diagnosis with a single round of stains, both IHC and GEP exceeded 90% accuracy. However, when the diagnosis required a second round, IHC significantly underperformed GEP (67% to 83%, P<0.001). GEP has been validated as accurate in diagnosing the primary site in metastatic tumors. The Pathwork Tissue of Origin Test used in this study was significantly more accurate than IHC when used to identify the primary site, with the most pronounced superiority observed in specimens that required a second round of stains and in poorly differentiated and undifferentiated metastatic carcinomas.

Lobular capillary hemangioma of the neonatal larynx.

OBJECTIVE: To describe a previously unreported condition of the neonatal larynx. DESIGN: Case series of 4 neonates with an uncommon laryngeal lesion. SETTING: Tertiary care children's hospital. PATIENTS: Four neonates in the first 10 days of life with stridor, hoarseness, and respiratory distress. INTERVENTION: The patients were examined using flexible fiberoptic laryngoscopy, and laryngeal lesions were identified and subsequently removed using microlaryngoscopy. Photodocumentation of the lesions was performed. Microscopic evaluation of biopsy specimens by a pathologist followed. MAIN OUTCOME MEASURES: Each patient's medical record was carefully reviewed for prenatal history, birth history, neonatal history, pathologic findings, and office follow-up. RESULTS: All 4 neonates were delivered atraumatically and developed symptoms of upper airway obstruction within the first few minutes to days of life. Each neonate was found to have an obstructive laryngeal lesion requiring surgical intervention. No child had other congenital abnormalities or a history of obvious laryngeal trauma. Pathologic review of each laryngeal specimen revealed inflammatory lesions with characteristic features of a lobular capillary hemangioma (or a pyogenic granuloma). CONCLUSIONS: The diagnosis of a lobular capillary hemangioma of the larynx should be considered in the differential diagnosis of a newborn with stridor, hoarseness, or respiratory distress. The cases seem to be of congenital origin, although acquired pathogenesis cannot be ruled out. Treatment of these lesions includes microscopic surgical excision.