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Squamous Cell Carcinoma of the Lung With Micropapillary Pattern

Open AccessPublished:June 12, 2020DOI:https://doi.org/10.1016/j.jtho.2020.05.023
      A 78-year-old male current smoker underwent right upper lobectomy for lung cancer at our hospital (Fig. 1). The postoperative pathologic examination revealed that the longest diameter of the tumor, identified as moderately differentiated squamous cell carcinoma (SCC), was 27 mm (Fig. 2). Scant keratinization was evident, but tubular or papillary structures were absent. Interestingly, the transition of the micropapillary (MP) pattern from SCC was diffuse (Fig. 2). The regional lymph nodes were found to be positive for metastasis and comprised both squamous and MP histologic patterns (Fig. 2). Immunohistochemical analysis revealed that the periphery of the small MP clusters stained positive for MUC1, which was cell surface associated (Fig. 2) whereas the cytoplasm had a positive diffuse staining for epithelial membrane antigen. Tumor cells in the area, where the SCC and the transition to the MP pattern were located, stained positive for p40 (Fig. 3), although no tumor cells in the area with the pure MP pattern stained positive for p40. Both the SCC and MP components also had a positive diffuse staining for CK5 and 6, a marker of squamous differentiation (Fig. 3).
      • Kriegsmann K.
      • Cremer M.
      • Zgorzelski C.
      • et al.
      Agreement of CK5/6, p40, and p63 immunoreactivity in non-small cell lung cancer.
      However, the tumor cells were not found to have a positive staining for either TTF-1 or napsin A. Periodic acid–Schiff–Alcian blue staining revealed the absence of mucin production. Therefore, there was no evidence supporting the presence of an adenocarcinoma component in the tumor.
      Figure thumbnail gr1
      Figure 1Computed tomography. A tumor with high FDG uptake was located in the right upper lobe of the lung. FDG, fluorodeoxyglucose.
      Figure thumbnail gr2
      Figure 2Histologic findings. The tumor comprised squamous and MP carcinoma components. Transition areas were observed between the two components, where they intermingled. A MP pattern was observed also in the metastatic lymph nodes. The region around the MP portion stained positive for MUC1. MP, micropapillary.
      Figure thumbnail gr3
      Figure 3Immunohistologic findings. Immunohistochemical analysis revealed that both the SCC and MP components stained positive for the following markers of SCC: p40 (upper column) and CK5 and 6 (lower column). MP, micropapillary; SCC, squamous cell carcinoma.
      To determine the tumor phylogeny, we collected tumor cells from different sites in the primary lesion and from the metastasized lymph nodes using laser capture microdissection and performed targeted deep sequencing as previously reported.
      • Higuchi R.
      • Nakagomi T.
      • Goto T.
      • et al.
      Identification of clonality through genomic profile analysis in multiple lung cancers.
      ,
      • Goto T.
      • Hirotsu Y.
      • Mochizuki H.
      • et al.
      Stepwise addition of genetic changes correlated with histological change from “well-differentiated” to “sarcomatoid” phenotypes: a case report.
      The mutation profiles were consistent across the different tumor regions, and their common clonalities were confirmed (Fig. 4).
      • Nakagomi T.
      • Goto T.
      • Hirotsu Y.
      • et al.
      New therapeutic targets for pulmonary sarcomatoid carcinomas based on their genomic and phylogenetic profiles.
      ,
      • Goto T.
      • Hirotsu Y.
      • Mochizuki H.
      • et al.
      Mutational analysis of multiple lung cancers: discrimination between primary and metastatic lung cancers by genomic profile.
      Figure thumbnail gr4
      Figure 4Heatmap of the mutations detected in five different tumor regions. The map depicts the gene mutations in the different tumor regions. A denser color indicates a higher allele fraction. The driver mutations with high allele fractions were consistent among the five samples, suggesting they originated from the same ancestral clone. LN, lymph node; MP, micropapillary; SCC, squamous cell carcinoma.
      MP adenocarcinoma is considered a variant of lung adenocarcinoma; however, there was no evidence of an adenocarcinoma component in our case, as revealed by morphologic and immunohistochemical analyses. Clonal evolution from SCC to an MP component was indicated by genomic analysis. This is the first report, to our knowledge, to describe a case of SCC with a coexistent and derived MP pattern.

      Acknowledgments

      This study was approved by the Institutional Research Ethics Board, and written informed consent was obtained from the patients for the research and publication of the results. Drs. Oyama and Goto have contributed to the conceptualization and methodology of the study. Dr. Oyama has contributed to the investigations carried out in the study. Dr. Oyama, Dr. Goto, Mr. Amemiya, Dr. Hirotsu, and Dr. Omata have contributed to the resources of the article. Drs. Hirotsu and Omata have contributed toward writing—the original draft of the article. Drs. Oyama and Goto have contributed to the writing, review, and editing of the article.

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