Abstract:Thyroid transcription factor-1 (TTF-1) is traditionally used to identify tumors of lung and thyroid primary. However, the specificity of this marker has recently come under increasing scrutiny as tumors from other organ systems are shown to also stain positively for TTF-1. On the basis of an index case of TTF-1-positive gastric adenocarcinomas, we evaluated a retrospective cohort (n=91) of these tumors for TTF-1 staining. Archived paraffin-embedded blocks of gastric adenocarcinoma cases from 2008 to 2013 were … Show more
“…6 Also, the results for the TTF-1 clone SPT24 have been reported to be more frequently positive than those for the clone 8G7G3/1 and napsin A in various nonpulmonary carcinomas. [21][22][23][24] On the other hand, the TTF-1 clone SPT24 was the most sensitive marker for AC. There was limited gain from mucin staining in our material in addition to the using IHC markers for AC differentiation (although the use of mucin staining may be of greater value in small specimens).…”
The fourth edition of the WHO Classification of Lung Tumours leads to changes in histological type in 5% of resected NSCCs. The incorporation of IHC staining into NSCC diagnostics demands awareness that the choice of ancillary stains has an effect on diagnosis.
“…6 Also, the results for the TTF-1 clone SPT24 have been reported to be more frequently positive than those for the clone 8G7G3/1 and napsin A in various nonpulmonary carcinomas. [21][22][23][24] On the other hand, the TTF-1 clone SPT24 was the most sensitive marker for AC. There was limited gain from mucin staining in our material in addition to the using IHC markers for AC differentiation (although the use of mucin staining may be of greater value in small specimens).…”
The fourth edition of the WHO Classification of Lung Tumours leads to changes in histological type in 5% of resected NSCCs. The incorporation of IHC staining into NSCC diagnostics demands awareness that the choice of ancillary stains has an effect on diagnosis.
“…TTF-1 reacts with cells differentiating towards follicular thyroid epithelium, 25 some gastric adenocarcinomas, 26 and some pulmonary adenocarcinomas and small cell carcinomas. 27,28 The sensitivity and specificity of TTF-1 for the separation of pulmonary adenocarcinoma from squamous cell carcinomas are ~85% 17,29 and 97%, 29 respectively.…”
The Papanicolaou Society of Cytopathology has developed a set of guidelines for respiratory cytology including indications for sputum examination, bronchial washings and brushings, CT-guided FNA and endobronchial ultrasound guided fine needle aspiration (EBUS-FNA), as well as recommendations for classification and criteria, ancillary testing and post-cytologic diagnosis management and follow-up. All recommendation documents are based on the expertise of committee members, an extensive literature review, and feedback from presentations at national and international conferences. The guideline documents selectively present the results of these discussions. The present document summarizes recommendations for ancillary testing of cytologic samples. Ancillary testing including microbiologic, immunocytochemical, flow cytometric, and molecular testing, including next-generation sequencing are discussed.
“…In a differential diagnosis using immunohistochemical staining, TTF-1 is a specific marker of the lung and thyroid gland and is also used to identify the primary lesion of adenocarcinoma of unknown primary. Although a metastatic gastric tumor could have been highly suspected if TTF-1 had been evaluated at the time of biopsy, there are reports describing TTF-1-positive gastric cancer, colorectal cancer, or schwannoma [ 15 , 16 , 23 , 24 ]. Thus, TTF-1-positive primary gastric cancer could not be completely ruled out.…”
Section: Discussionmentioning
confidence: 99%
“…S1a, b). However, TTF-1-positive primary gastric cancer could not be completely ruled out because there are reports describing TTF-1-positive gastric adenocarcinoma [ 15 , 16 ]. Fig.…”
Background
When a patient has multiple tumors in different organs, it is very important to identify whether the tumors are multiple cancers or metastasis from one tumor in order to establish an optimal treatment strategy. However, it is difficult to obtain an accurate diagnosis from conventional diagnostic strategies, including immunohistochemistry. We report two patients with multiple tumors in which a somatic mutation comparison using next-generation sequencing (NGS) was useful for the diagnosis of a metastatic tumor.
Case presentations
Patient 1: A 64-year-old man was diagnosed with gastric and lung cancer. After radical chemoradiotherapy for lung cancer, gastrectomy was planned for gastric cancer. At gastrectomy, the patient underwent a multiple omics analysis for “Project HOPE”. The gene mutational signature of the gastric tumor showed signature 4 of COSMIC mutational signature version 2, which was associated with smoking and has not been found in gastric cancer. To confirm that the gastric tumor was metastasis from lung cancer, we conducted a somatic mutation comparison of the two tumors with 409-gene panel sequencing, which revealed that 28 of 97 mutations in the lung tumor completely matched those of the gastric tumor. Based on these findings, the gastric tumor was diagnosed as metastasis from lung cancer. Patient 2: A 47-year-old woman underwent distal gastrectomy for gastric cancer. A colon tumor was detected 6 years after gastrectomy. The colon lesion was a submucosal tumor-like elevated tumor, and was suspected to be metastasis from gastric cancer. The patient underwent sigmoidectomy, and participated in “Project HOPE”. The possibility of primary colon cancer could not be ruled out, and we conducted a somatic mutation comparison of the two tumors as we did with Patient 1. Panel sequencing revealed 11 mutations in the gastric tumors, 4 of which completely matched those of the colon tumor. The colon tumor was diagnosed as metastasis from gastric cancer.
Conclusion
We reported two patients with multiple tumors in which a somatic mutation comparison using NGS was useful for the diagnosis of a metastatic tumor.
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