Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) of the gallbladder is a rare tumor that is defined in the World Health Organization (WHO) 2019 digestive system tumor classification as the presence of a neuroendocrine neoplasm admixed with a non-neuroendocrine carcinoma, each component constituting at least 30% of the neoplasm. The exact pathogenesis of MiNENs remains unclear. We present a case of a 74-year-old Filipino woman who presented with nonspecific clinical and radiologic findings and subsequently underwent cholecystectomy. Histopathologic and immunohistochemical evaluation of the gallbladder confirmed the diagnosis of a mixed well-differentiated adenocarcinoma (30%) and large cell neuroendocrine carcinoma (70%). The adenocarcinoma and neuroendocrine carcinoma components were separately microdissected and submitted for targeted 15-gene sequencing using the Illumina Trusight Tumor 15 (TST15) panel. NGS identified a TP53 missense mutation leading to a stop codon in both components. The finding of similar molecular signatures in the two morphologically distinct components supports the hypothesis that MiNEN arises from a common precursor stem cell capable of divergent phenotypic differentiation.
Background. Epidermal Growth Factor Receptor (EGFR) mutation status has been shown to have a significant prognostic and predictive role in the management of Non-small Cell Lung Carcinoma (NSCLC), significantly prolonging patients' survival. Thus, EGFR mutational analysis before initiation of treatment is now recommended in several clinical practice guidelines. Although EGFR mutation testing in NSCLC has been a part of clinical care in the Philippines, there is little data on the EGFR mutation spectrum among Filipinos.
Introduction. The current management of advanced non-small cell lung cancer (NSCLC) includes the characterization of Programmed Death Ligand-1 (PD-L1) expression for potential immune checkpoint inhibitor treatment. There is currently no available data regarding the patterns of PD-L1 expression in NSCLC, as well as their association with clinicopathologic profile in Filipino patients.Methodology. Clinicopathologic characteristics of 187 consecutive NSCLC clinical samples with PD-L1 testing using the clone 22C3 pharmaDx kit were collected. The presence of stromal tumor-infiltrating lymphocytes (TILs) were assessed in hematoxylin and eosin-stained slides. PD-L1 expression on tumor cells (TC) and stromal TILs were evaluated.Results. Of the 187 cases, there were 112 males and 75 females. The mean age at diagnosis was 66.4 years old (32-92 years old). It is composed of 131 cases of adenocarcinoma, 15 squamous cell carcinoma, 4 adenosquamous carcinoma, 32 non-small cell carcinoma, not otherwise specified, 3 poorly differentiated malignancy, 1 large cell carcinoma, and 1 mucinous carcinoma. Specimen types included 17 pleural fluid cell blocks, 60 tumor cell block samples, and 110 tissue biopsies. Tumor cell PD-L1 expression was identified in 59.1% of the 110 tissue biopsies. PD-L1 TPS for histologic specimens are as follows: TPS ≥50%, TPS 1-49%, and TPS <1% were observed in 23.6%, 35.5%, and 40.9% in our lung cancer cohort, respectively. Of the 77 cytology specimens, 50.6% presented with TC PD-L1 expression. TPS for this subgroup include: 49.4% with no PD-L1 expression, 35.1% with low PD-L1 expression, and 15.6% showing high PD-L1 expression. PD-L1 expression on TC did not correlate with age, sex, or histology for both specimen type subgroups. Stromal tumor-infiltrating lymphocytes were noted in 74.5% of tissue biopsies. Tumor cell block samples did not demonstrate stromal TILs. For tissue biopsies, female gender and TPS 1-49% were more likely to have <50% PD-L1 expression on TILs.
Conclusion.Overall TC PD-L1 expression was observed in more than half (55.6%) of NSCLC patients in our cohort. The prognostic value of PD-L1 and clinical response to immune checkpoint inhibitors in the Filipino population needs to be further investigated.
Molecular genotyping of gastrointestinal stromal tumors is not yet available in the Philippines. We report a case of a 75-year old male with a gastric submucosal mass, who underwent gastroscopic/laparoscopic wedge resection. Histopathology and subsequent immunohistochemical staining with CD117 (CKIT) and DOG1 revealed diagnosis of gastrointestinal stromal tumor, spindle cell variant. On genotyping, the tumor harbored PDGFRA D842V mutation, a subtype resistant to Imatinib treatment.
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