Pulmonary Adenocarcinoma with Signet Ring Features: Detailed Cytomorphologic Analysis Archana George Vallonthaiel, MD, DNB, 1 Deepali Jain, MD, DNB, MIAC, 1 * Karan Madan, MD, DM, 2 and Sudheer Arava, MD 1 Background: Signet ring cell feature in lung adenocarcinoma is no longer considered a distinct subtype, but as a cytologic change that may occur in association with multiple histological patterns. Cases with signet ring cells show a strong association with Anaplastic Lymphoma Kinase (ALK) gene fusions and solid pattern. Methods: The cytomorphological findings of pulmonary adeno- carcinoma with signet ring features (PASRF) was studied. Cases of pulmonary adenocarcinoma which showed presence of signet ring cells either on cytology or histology were included in the study. Results: Out of 218 pulmonary adenocarcinomas diagnosed dur- ing the study period, 11 cases showed presence of signet ring cells (11/218). Out of the 11 cases, 7 had paired histology and cytology available, while the remaining 4 did not have a corre- sponding cytology sample. Majority of the cases (6/11) showed signet ring cells in more than 90% of the tumor area. All cases showed solid growth pattern. TTF-1 was positive in all the cases. Immunopositivity for ALK was seen in seven cases. The cytology smears showed single cells and clusters of signet ring cells, with either intracytoplasmic mucin vacuole and eccentric nucleus or histiocyte-like finely vacuolated cytoplasm with round nucleus and prominent nucleoli, the latter resembling alveolar macrophages. Conclusion: PASRF is commonly associated with a solid histo- logic pattern. Cases with predominant histiocyte-like pattern may be misdiagnosed on cytology; hence a high index of suspi- cion is required for an accurate diagnosis. Diagn. Cytopathol. 2016;44:607–611. VC 2016 Wiley Periodicals, Inc. Key Words: pulmonary adenocarcinoma; signet ring cells; cytology Lung carcinomas are the third most common malignancy in the world and results in significant mortality and mor- bidity. 1 Adenocarcinoma which constitutes a major bulk of lung carcinomas was reclassified in 2011, based on a multidisciplinary approach, with special emphasis on molecular alterations of the tumor. 2 Pulmonary adenocar- cinoma with signet ring features (PASRF) was considered as a distinct subtype of pulmonary adenocarcinoma in 2004 WHO classification of lung tumors, designated as signet ring adenocarcinoma. 3 However, currently in 2015 WHO classification of lung tumors, PASRF is viewed as a cytologic change that may occur in association with various histological patterns rather than as a separate sub- type, as they do not have a prognostic significance. 2,4 The poor prognosis that had been associated with PASRF can be attributed to its strong association with solid sub- type. 5–7 They constitute 1.5% of surgically resected pri- mary pulmonary carcinomas. 5 PASRF are commonly associated with specific molecular alteration involving ALK gene rearrangement with formation of ALK-EML4 fusion gene and they benefit from targeted therapy using Crizotinib. 6 Cytological features of PASRF have been described in the literature, however as single or multiple case reports. We aimed to analyze cytomorphological fea- tures of PASRF in detail, subsequent to a case of PASRF (case 1) misinterpreted as benign due to innocuous histiocyte-like morphology of signet ring cells. Materials and Methods Cases of pulmonary adenocarcinoma diagnosed over a period of 1.5 years (January 2014–June 2015) were 1 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India 2 Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi, India Funding: Nil. None of the authors have any conflicts of interest. *Correspondence to: Dr. Deepali Jain, MD, DNB, MIAC, Assistant Professor; Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. E-mail: deepalijain76@gmail.com Received 28 December 2015; Revised 7 April 2016; Accepted 8 April 2016 DOI: 10.1002/dc.23492 Published online 20 April 2016 in Wiley Online Library (wileyonlinelibrary.com). VC 2016 WILEY PERIODICALS, INC. Diagnostic Cytopathology, Vol. 44, No 7 607