[1904] Correlation of Cytomorphology and Molecular Findings in EGFR, KRAS, and ALK-Positive Lung Carcinomas

Zaibo Li, Sanja Dacic, Liron Pantanowitz, Walid Khalbuss, Marina Nikiforova, Sara E Monaco. University of Pittsburgh Medical Center, Pittsburgh, PA

Background: There is increasing emphasis on the subclassification of non-small cell lung carcinomas (NSCLC) and the molecular features in order to guide treatment. Histological studies have suggested some morphological features that predominate in mutation positive tumors. Our aim was to look at cytology cases that were positive for EGFR, KRAS, or ALK and to determine if these positive cases had distinct cytomorphology.
Design: FNA cases of NSCLC that had mutation studies for EGFR or KRAS or FISH studies for ALK were identified from our archives between 2007-2012. The slides were evaluated for cytological features, and correlated with histological follow-up and molecular data.
Results: 62 (39%) out of 160 cases were positive for mutation, including 39 (31%) positive for KRAS and 20 (14%) for EGFR (12 EGFR 19, 7 EGFR 21, 1 EGFR 20), and 4 (3%) for ALK. One case (0.6%) was positive for EGFR 19 and ALK. The majority of the cases were primary lung FNAs (60%), and 50 (79%) were available for review. Table 1 summarizes the findings. More of the ALK and KRAS cases had a diagnosis of NSCLC, favor adenocarcinoma (ADC) or NSCLC NOS than EGFR cases (25% and 51%, vs. 5%). Eosinophilic granular cytoplasm was seen in more ALK and KRAS cases than EGFR cases (100% and 32% vs. 6%). The mean nuclear grade was higher in KRAS and ALK cases than in EGFR cases (2.2 and 2.3 vs. 1.9). Necrosis was also more common in ALK and KRAS cases (67% and 65% vs. 13%). Sixteen cases with histological follow-up showed ADC in 14 cases (88%) and NSCLC NOS in 2 cases (12%).

Table 1. Summary of mutation-positive cases.
Type of CaseALK1+KRAS+EGFR+Total
Cytology DiagnosisAdeno # (%)3 (75)19 (49)19 (95)41 (65)
 NSCLC, favor Adeno # (%)1 (25)11 (28)1 (5)13 (21)
 NSCLC, NOS # (%)0 (0)9 (23)0 (0)9 (14)
Cytology findingsNuclear grade10/33/315/168/50
 CytoplasmEosinophilic, granular3/310/311/1614/50
  vacuolated, glassy0/321/3115/1636/50
*Note: 1 case was positive for both EGFR exon 19 mutation and ALK rearrangement. Legend: ADC, adenocarcinoma; NSCLC, non-small cell lung carcinoma NOS

Conclusions: These data show a similar proportion of cytology cases positive for EGFR, KRAS, or ALK as reported in the literature. The cytological features of ALK and KRAS-positive tumors in our series included more nuclear pleomorphism, necrosis and less vacuolated cytoplasm, than in EGFR-positive tumors, which may explain the less definitive subclassification in the ALK and KRAS-positive tumors.
Category: Pulmonary

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 291, Monday Morning


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