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Int J Clin Exp Pathol 2012;5(9):972-976

Case Report
Leptomeningeal carcinomatosis as initial presentation in adenocarcinoma of lung with
signet ring cell features: an autopsy case report

Eunice Choi, Annisa L Lewis, Hidehiro Takei, Jae Y Ro

Department of Pathology and Genomic Medicine, The Methodist Hospital, Houston, TX, USA; Department of Pathology and Laboratory
Medicine, Weill Cornell Medical College of Cornell University, New York, NY, USA.

Received August 29, 2012; Accepted September 23, 2012; Epub October 20, 2012; Published October 30, 2012

Abstract: Signet ring cell (SRC) features are rare but well-recognized cytological changes of pulmonary adenocarcinoma (PA). PA with SRC
features (PA-SRC) is frequently associated with anaplastic lymphoma kinase (ALK) gene rearrangement, and recognition of PA-SRC may be
important for the administration of targeted treatment. To the authors’ knowledge, leptomeningeal carcinomatosis (LMC) as an initial
presentation of PA-SRC has not yet been reported. We report an autopsy case from a 59-year-old female who presented with intractable
headache for 6 weeks and died of LMC as a result of metastatic PA-SRC. Premortem brain MRI showed nonspecific leptomeningeal
enhancement. At autopsy, a tan rubbery mass was found in the hilar area of the right lung, which also surrounded the lower trachea and carotid
arteries. A right posteromedial middle lobe mass was also found. Leptomeninges were slightly thickened, without discrete masses.
Microscopic examination of the lung mass and leptomeninges showed solid sheets and nests of malignant cells with pleomorphic nuclei and
frequent SRC features which comprised 50% of the mass. Immunohistochemically, the tumor cells demonstrated strong diffuse expression of
cytokeratin (CK)-7, TTF-1, and napsin-A. Immunostains for CK-20 and ALK were negative. These features were consistent with PA-SRC. It has
been reported that approximately 70% of PAs demonstrate ALK gene rearrangement when SRCs comprised >10% of the tumor cells. The
presence of SRCs can be indicative of a lung primary and, because of frequent ALK gene rearrangement in PA-SRC, proper recognition of PA-
SRC may be important in determining whether further testing is advisable (e.g., ALK immunostaining and/or ALK gene rearrangement).
(IJCEP1208026).

Keywords: Anaplastic lymphoma kinase, leptomeningeal carcinomatosis, pulmonary adenocarcinoma, signet ring cell

Address all correspondence to:
Dr. Jae Y Ro
Department of Pathology and Genomic Medicine
The Methodist Hospital, 6565 Fannin Street
Suite M227, Houston, TX 77030, USA.
Tel: 713-441-2263; Fax: 713-793-1603.
E-mail: jaero@tmhs.org