The role of next-generation sequencing in the differential diagnosis of composite neoplasms.

Composite neoplasms (CNs) are rare and diagnostically challenging lesions that require differentiating between mixed clonal tumors with divergent phenotypes (MT), collision of 2 independent tumors adjacent to each other (CT), and tumor-to-tumor metastasis (TTM). To that end, pathologists have traditionally used immunohistochemistry and limited molecular studies, such as Sanger sequencing. Herein we evaluate the potential application of NGS in the differential diagnosis of these rare neoplasms. Four CNs were included in the study. Two were diagnosed as MT (mixed adenoneuroendocrine carcinoma of the gallbladder and metastatic papillary thyroid carcinoma with squamous dedifferentiation) and 2 were interpreted as TTM (esophageal adenocarcinoma to lung adenocarcinoma and small cell carcinoma of the lung to meningeal melanoma). Diagnoses were made using clinical, histologic, and immunophenotypic information, with the aid of limited molecular studies in 2 cases. Formalin-fixed, paraffin-embedded tissue was dissected for DNA and RNA extraction, and NGS was performed using the Oncomine Comprehensive Panel. The 2 tumors initially interpreted as MT showed shared genetic aberrations in the different neoplastic components, supporting the pathologic diagnosis. NGS results for the lesion diagnosed as esophageal adenocarcinoma metastatic to lung adenocarcinoma did not support the histopathologic interpretation and were deemed inconclusive. However, the identification of an identical CDKN2A mutation in all components and in the adjacent benign lung parenchyma suggests a possible germline aberration. Sequencing results in the last case were clearly supportive of TTM. This study illustrates the role of NGS in the diagnostic workup of CNs, as an adjunct to light microscopy and immunohistochemistry.

Tumor necrosis in radical prostatectomies with high-grade prostate cancer is associated with multiple poor prognostic features and a high prevalence of residual disease.

The Gleason grading system and the recently defined Grade Groups are strong, well-established predictors of outcome in prostate cancer. Each Gleason score, however, is the result of a sum of categories (Gleason patterns or GPs) that are intrinsically heterogeneous, as each individual pattern encompasses several tumor morphologies. Although the prognostic value of specific morphologic components of GP4 has recently been demonstrated, the significance of the different patterns of GP5 is largely unknown. We reviewed 344 consecutive prostatectomies performed at the Hospital of the University of Illinois at Chicago between 2011 and 2016 and selected 56 cases with primary or secondary GP5 with archival material available for review. Subsequently, we sorted the cases according to the presence or absence of tumor necrosis in invasive adenocarcinoma GP5-designated G5 (+N) and G5 (-N), respectively-for comparison of histopathologic and clinical characteristics. The GP5 (+N) group demonstrated higher prevalence of biochemical recurrence (P=.0006) and seminal vesicle invasion (P=.02), with a trend toward a higher frequency of lymph node metastases (P=.07) and multifocal surgical margin involvement (P=.09). Also, G5 (+N) patients showed higher preoperative prostate-specific antigen values (P=.005) and a larger percentage of submitted tissue involved by tumor (P<.0001). Our results show that GP5 with tumor necrosis is associated with poor prognostic histopathologic features and high rates of residual disease after prostatectomy.