Anatomic pathology selected abstracts

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Menz A, Bauer R, Kluth M, et al. Diagnostic and prognostic impact of cytokeratin 19 expression analysis in human tumors: a tissue microarray study of 13,172 tumors. Hum Pathol. 2021;115:19–36.

Correspondence: Dr. Ronald Simon at r.simon@uke.de

An analysis of urinary large-cell neuroendocrine carcinoma

Large-cell neuroendocrine carcinoma of the urinary tract is a rare disease, accounting for less than one percent of all urothelial neoplasms. There is no consensus on standard treatment. The authors described a large cohort of large-cell neuroendocrine carcinoma (LCNEC) and addressed the clinicopathologic and immunohistochemical features of the disease. They searched their institution’s database from 2006 to 2020 and found 22 cases of LCNEC of the urinary tract, including 20 from the urinary bladder and two from the ureter. The patients included 16 men and six women who were a median age of 74.5 years. Most LCNEC presented at an advanced stage, with tumors invading the muscularis propria and beyond (21 of 22). Eight cases were pure LCNEC, while 14 were mixed with other histologic types, including conventional urothelial carcinoma (n = 9), carcinoma in situ (n = 7), small cell carcinoma (n = 6), and urothelial carcinoma with glandular features (n = 3). Most LCNEC expressed the neuroendocrine markers synaptophysin (22 of 22), chromogranin (13 of 16), CD56 (seven of seven), TTF1 (eight of eight), and INSM1 (two of three). They were negative for common urothelial markers, including HMWCK (zero of three), p40/p63 (zero of six), and CK20 (zero of 10), and they had variable GATA3 staining (four of eight). Ki-67 stained 25 percent to nearly 100 percent of the tumor cell nuclei in seven cases examined. Patient survival was associated with cancer stage. Pure LCNEC showed worse survival than mixed LCNEC. Compared with small cell carcinoma at similar stages analyzed in a prior study, LCNEC had a worse prognosis only when patients developed metastatic disease. The authors concluded that neoadjuvant chemotherapy followed by radical resection can lead to long-term survival in patients who have organ-confined LCNEC.

Wang G, Yuan R, Zhou C, et al. Urinary large cell neuroendocrine carcinoma: A clinicopathologic analysis of 22 cases. Am J Surg Pathol. 2021;45:1399–1408.

Correspondence: Dr. Gang Wang at gang.wang1@bccancer.bc.ca

Reappraisal of the relevance of morphologic criteria from the 2019 WHO classification of a CRC cohort

The World Health Organization reclassified colorectal carcinoma subtypes in the 2019 WHO classification of CRC and introduced tumor budding as a second major grading criterion while condensing conventional grading into a two-tiered system. How CRC subtypes, tumor budding, and WHO grade interact with each other and whether they have an independent impact on patient prognosis remains largely unexplored. To address these topics, the authors conducted a retrospective study in which they investigated a large single-center cohort of 1,004 CRC patients. The study reclassified CRCs from two decades based on WHO grade (low versus high), tumor budding (Bd1/Bd2/Bd3), and CRC subtype (adenocarcinoma not otherwise specified, micropapillary, mucinous, serrated, medullary, adenoma like, signet ring cell, mixed adenoneuroendocrine carcinoma/neuroendocrine carcinoma, and undifferentiated) according to the criteria of the 2019 WHO classification. The authors investigated the interaction of these parameters, their connection to stage and microsatellite status, and their significance relative to patient survival for the various subgroups. Specific subtypes, other than adenocarcinoma not otherwise specified, represented one-third of all CRCs and were unevenly distributed throughout stages and microsatellite subgroups. Subtypes, WHO grade, and tumor budding profoundly impacted all survival parameters (P< 0.001 for all analyses), with CRC subtypes and tumor budding—but not WHO grade—being stage-independent prognosticators for all survival comparisons. WHO grade had very limited prognostic value in CRC subtypes, while tumor budding retained its strong prognostic impact in most scenarios. Accurate delineation of CRC subtypes introduced in the 2019 WHO classification provided strong stage-independent prognostic information, supporting the assertion that the subtypes should be considered for inclusion in pathology reports and clinical trials. Within the morphology-based grading schemes included in the 2019 WHO classification, tumor budding outperformed WHO grade.

Jesinghaus M, Schmitt M, Lang C, et al. Morphology matters: a critical reappraisal of the clinical relevance of morphologic criteria from the 2019 WHO classification in a large colorectal cancer cohort comprising 1004 cases. Am J Surg Pathol. 2021;45(7):969–997.

Correspondence: Dr. Wilko Weichert at wilko.weichert@tum.de