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• W3136144992 abstract "Invasive mucinous adenocarcinoma (IMA) is an uncommon adenocarcinoma variant defined by goblet or columnar cells containing intracytoplasmic mucin and extensive extracellular mucin. Historically, IMAs have been associated with a poorer prognosis. However emerging evidence indicates a majority harbour potentially actionable driver oncogenes and IMA may be associated with downregulation of lung lineage-specifying transcription factor NKX2-1/TTF-1 resulting in a mid/hindgut phenotype. Morphologic features of IMA have also not been well characterised. Patients (pts) with early stage resected pulmonary IMA (n=38) at our institution between 2009-19 were included. Morphologic features, including cell and stroma type, cytologic atypia, mitotic rate and spread through air spaces (STAS) were described. Immunohistochemistry for CDX2, CK7, CK20, Napsin-A and TTF-1 was conducted. Whole genome sequencing (WGS) was performed in a subset of pts. Histologic and genomic profiles were correlated. Median age was 66 years (range 42-82), 59% were male, 89% were of Chinese ethnicity and 55% were current/ex-smokers. Stage distribution after resection (AJCC 8th edition) was IA (50%), IB (16%), IIA (3%), IIB (18%), IIIA (8%), IIIB (3%) and IV (3%). Adjuvant therapy was given in 5 (13%) pts. Driver oncogenes were detected with mutations in EGFR (5%), and fusions in ALK (11%) and RET (3%). Histologically, most (61%) showed typical histomorphology, consisting of columnar tumour cells with basally located nuclei and apical mucin vacuole with mild degree of stratification/complexity, while the remainder (39%) showed a combination of typical mucinous subtype with other more cuboidal or polygonal cells and densely eosinophilic cytoplasm. The stroma was markedly fibrotic and desmoplastic in 68%, with a focal small fibrotic scar in 32%. The mitotic rate was low at 0-5 mitoses/10HPFs (92%), with rarely a higher mitotic rate corresponding to focal areas or more cytologic atypia (8%). Similarly, the cytologic atypia tended to be mild to moderate in 90%. Lymphovascular invasion (LVI) was rarely present (13%), and involvement of the pleura (26%) and parenchymal resection margin (5%) was uncommon. STAS was present in 68%. Pure mucinous tumours were associated with mainly columnar type tumour cells (r2=0.83, p<0.001), only mild-moderate cytologic atypia (r2=0.42, p=0.008) and absence of LVI (r2=0.48, p=0.002). Immunohistochemistry showed tumours positive for CK7 (100%), CK20 (84%), TTF-1 (71%), Napsin-A (63%) and CDX2 (45%). CDX2 positivity was associated with the presence of extensive fibrotic stroma (r2=0.38, p=0.02). After median 2.9 yrs follow-up, 6 (16%) pts had recurred – all stage II/III at baseline – with 2-year DFS of 84% and 5-year DFS of 76%. WGS in 9 (24%) pts revealed lung cancer oncogenic drivers in KRAS (33%), EGFR (11%), ERBB2 (11%), ERBB3 (11%) or no driver mutation/fusion detected (33%). Median TMB was 1.3 mutations/Mbp (range 0.03-2.1). Overall, the presence of known oncogenic drivers was associated with negative staining for CK20 (r2=0.45, p=0.005) and CDX2 (r2=0.31, p=0.06). IMA is characterised by circumscribed nodules with extensive fibrotic stroma, mild to moderate cytological atypia and low mitotic rate, with good survival outcomes. CDX2 positivity is associated with fibrotic and desmoplastic stroma and absence of an oncogenic driver." @default.
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• W3136144992 date "2021-03-01" @default.
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• W3136144992 title "P38.03 Immunohistochemical, Histologic and Genomic Characterisation of Early Stage Pulmonary Invasive Mucinous Adenocarcinoma" @default.
• W3136144992 doi "https://doi.org/10.1016/j.jtho.2021.01.784" @default.
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