This 70-year-old male patient was found to have a single 3.5 cm ring-enhancing left frontal lobe lesion with surrounding edema and mass effect on neuroimaging (brain MRI). CT of the chest demonstrated a 15.0 cm lung mass with associated enlarged hilar lymph nodes. CT of the abdomen and pelvis were unremarkable.
What is your diagnosis?
A. Glioblastoma
B. Meningioma
C. Metastatic melanoma
D. Metastatic carcinoma
Low magnification view shows a cellular neoplasm arranged in nests, acini, and somewhat papillary-type structures. Note the areas of necrosis (N)
Higher magnification shows that the neoplastic cells in this area have cuboidal to columnar shape, hyperchromic, relatively monotonous appearing, oval to round nuclei, or areas of cytoplasmic clearing Note that the cytoplasmic clearing is below (subnuclear) and above (supranuclear) the tumor cell nuclei. This appearance has been likened to “piano keys.”
Higher magnification shows that the neoplastic cells in this area are: -arranged in a somewhat more crowded and disorganized fashion -more mitotically active (arrows)
The neoplastic cells show strong positive cytoplasmic staining for cytokeratin (AE1/3). Cytokeratin is an intermediate filament commonly seen within the cytoplasm of neoplastic cells which show epithelial differentiation (i.e. carcinoma or adenocarcinoma).
Answer: Metastatic carcinoma
The best answer to the question is “metastatic carcinoma”. However, this neoplasm has distinctly unusual histologic features; i.e. “piano key-like” appearance that resembles fetal lung. This morphologic appearance is a characteristic feature of fetal adenocarcinoma of lung and the epithelial component of pulmonary blastoma (pleuropulmonary blastoma). Both of these are relatively rare lung neoplasms. Please see references below.
This particular neoplasm showed diffuse membranous immunohistochemical staining for beta-catenin, diffuse nuclear staining for CDX2, patchy cytoplasmic positive staining for synaptophysin, and weak patchy nuclear staining for TTF1. Given the presence of necrosis and brisk mitotic activity this was felt to represent a high grade lesion.
Reference(s) / additional reading:
Ricaurte LM, et al. Comprehensive review of fetal adenocarcinoma of the lung. Lung Cancer (Auckl). 2018 Aug 23;9:57-63. doi: 10.2147/LCTT.S137410. PMID: 30197546; PMCID: PMC6112786.
Suzuki M, et al. Comprehensive molecular analysis of genomic profiles and PD-L1 expression in lung adenocarcinoma with a high-grade fetal adenocarcinoma component. Transl Lung Cancer Res. 2021 Mar;10(3):1292-1304. doi: 10.21037/tlcr-20-1158. PMID: 33889510; PMCID: PMC8044470.
Morita S, et al. High-grade lung adenocarcinoma with fetal lung-like morphology: clinicopathologic, immunohistochemical, and molecular analyses of 17 cases. Am J Surg Pathol. 2013 Jun;37(6):924-32. doi: 10.1097/PAS.0b013e31827e1e83. PMID: 23629442.
Messinger YH, Stewart DR, Priest JR, Williams GM, Harris AK, Schultz KA, Yang J, Doros L, Rosenberg PS, Hill DA, Dehner LP. Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer. 2015 Jan 15;121(2):276-85. doi: 10.1002/cncr.29032. Epub 2014 Sep 10. PMID: 25209242; PMCID: PMC4293209.
Fetal lung in first part of second trimester: https://webpath.med.utah.edu/HISTHTML/NORMAL/NORM161.html
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