ECP 2023 Abstracts

S340 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 for gene fusions can be useful in confirming the diagnosis but given the similarity to their counterparts in the salivary glands, exclusion of secondary involvement by clinical and radiology findings is mandatory. Although our results are limited by the small number of cases included, they are similar to those described in the literature. E-PS-21-009 Distinct RET rearrangements in an unusual case of intratumoral metastases of a papillary thyroid carcinoma in a primary lung adenocarcinoma A. Coutada*, J. Azevedo, A. Lapa, C. Escudeiro, N. Coimbra *Department of Pathology, Portuguese Oncology Institute of Porto / Porto Comprehensive Cancer Center Raquel Seruca, Portugal Background & objectives: Uncommon phenomenon known as tumour-to-tumour-metastasis (TTM) occurs when a metastasis from one primary-tumour deposits within another primary-tumour. Lung is a typical site for TTM. Herein, we describe a case of lung adenocarci- noma with metastases of papillary thyroid carcinoma. Methods: A 61-year-old woman was diagnosed with a classic papillary carcinoma of the thyroid in 1999. Almost 20 years later, during the fol- low-up presented multiple lung nodules detected by thoracic computed tomography. Lung biopsy was performed on the largest nodule with 19mm. The patient later underwent a left lobectomy. Both biopsy and surgical specimen underwent histopathological examination, immuno- histochemistry and molecular tests. Results: Histological examination of the biopsy showed an adenocar- cinoma with acinar, papillary and lepidic pattern, that stained for CK7 and TTF-1. Additionally, there were areas of papillary architecture with nuclear features such as pseudoinclusions and grooves, that stained for CK7 and TTF-1, but also for PAX-8 and thyroglobulin. Histologi- cal examination of the surgical specimen confirmed the presence of a primary lung adenocarcinoma with multiple intratumoral metastases of papillary thyroid carcinoma and also involvement of the adjacent parenchyma. Molecular analysis revealed RET rearrangements in both neoplasms: lung adenocarcinoma presented a KIF5B-RET fusion gene, while metastases of the papillary thyroid carcinoma showed a CCDC6- RET fusion gene. Conclusion: TTM diagnosis can be challenging since it requires a high level of suspicion/clinical correlation and careful examination of the tumours’ histological features. There is no evidence that the occurrence of RET fusion genes in both tumours results from genetic susceptibility in this patient. Although the partners are different, the presence of these RET fusion genes might be considered a thera- peutic target for both lung adenocarcinoma and papillary thyroid carcinoma. E-PS-21-010 Pulmonary silico-tuberculosis mimicking metastatic carcinoma – a case report L. D’Sa*, F. Pezzuto, F. Lunardi, F. Scalvenzi, M. Tinè, G. Comacchio, C. Giraudo, F. Calabrese *Addenbrooke’s Hosital, Cambridge, United Kingdom Background & objectives: Silicosis caused by inhalation/deposition of free silica particles is characterized by pulmonary inflammation/ fibrosis. Among the clinical disorders associated with silicosis, tuber- culosis is by far the most prominent. The diagnosis is challenging espe- cially in patients with a previous neoplasia. Methods: A 66-year-old male non-smoker, originally from North Africa, reported a dry cough and significant weight loss. He was a foundry worker. He had a medical history of bladder carcinoma asso- ciated with schistosomiasis. CT and PET/CT showed bilateral multi- ple hypermetabolic lung nodules, some with cavitation. The patient underwent surgical resection of the largest nodule, highly suspicious of lung metastasis. Results: Surgical resection showed well-circumscribed small nodules. The histological examination revealed multiple nodular formations mainly localized in subpleural and peribronchial sites. Several lesions showed characteristic features of silicotic nodules with a central zone of cellular hyalinized collagen with a whorled appearance and a peripheral zone of dust-laden macrophages. Polarized light microscopy showed bright white crystals of varying sizes. There were adjacent well-formed granulomas some with central caseous necrosis. Microdissection of the largest necrotising granuloma was performed for molecular investiga- tion of mycobacteria. Real time polymerase chain reaction, performed for the identification and quantification of the DNA of Mycobacterium tuberculosis complex, was positive. The final diagnosis was pulmonary silico-tuberculosis. Conclusion: Silico-tuberculosis is often encountered in patients with a history of silica exposure in tuberculosis endemic areas. This case serves as a reminder to never underestimate patient occupational exposure and geographic origin. A careful histological diagnosis and molecular investigation are mandatory to approach difficult cases espe- cially for patients with a prior cancer history and clinical/ radiological features suggestive of tumour recurrence/metastasis. E-PS-21-011 Immunohistochemistry as an adjunct to molecular testing in dif- ficult cases: using phenotype to ascertain the relevance of genotypic variants U. Oedema*, K. Krishnamurthy, D. Goldstein *Montefiore Medical Center, USA Background & objectives: Novel variants are being identified in lung adenocarcinomas by next generation sequencing (NGS) with increasing frequency. Predictive analysis and literature are often limited, complicating interpretation. Herein, we investigate whether immunohistochemistry (IHC) can clarify the nature of some of these variants. Methods: Primary lung adenocarcinoma cases with ambiguous vari- ants were identified. Formalin-fixed, paraffin-embedded tissue sections marked by a pathologist, were manually micro-dissected for tumour DNA, which was amplified using Ion AmpliSeqTM Cancer Hotspot Panel v2 multiplex PCR primer set. Sequencing was performed on an Ion Torrent PGM™ NGS. β-catenin and p53 immunohistochemical staining was performed using the Dako Autostainer systems (Agilent Technologies). Results: Three lung adenocarcinoma cases, two resections and one cytology, were selected. APC c.3949G>C, p.E1317Q vari- ant was identified in two cases while a TP53 splice donor variant c.559+1G>A was identified in the third case, at variant allele frac- tions (VAFs) congruent with the estimated tumour content. Two of the cases had concomitant driver mutations in KRAS at similar VAFs. The NGS run met all quality control criteria. Corresponding immunostains for β-catenin showed cytoplasmic staining (wild-type) in both cases with APC variants, while P53 showed heterogenous (wild-type) staining pattern in the isolated case with TP53 variant. In the light of the above findings, these variants were interpreted to be likely benign. Conclusion: APC p.E1317Q has been reported a possible pathogenic driver in a subset of lung adenocarcinomas. TP53 splice donor variant is well-described in adenocarcinomas. Wild-type β-catenin and P53 IHC staining provides some evidence of maintained WNT and p53 pathway homeostasis and may help identify these as incidental variants resulting from genomic instability in tumour cells. This case series exemplifies the role of IHC as an adjunct to NGS by ascertaining the phenotype in tumour cells, aiding variant classification in difficult cases.