Primary cerebrospinal fluid diagnosis of pineal germinoma

Extragonadal germ cell tumors are rare and predominantly develop in midline structures of adolescents, with the pineal gland being the most common site. Herein, we present a case of pineal germinoma diagnosed by cytological examination of cerebrospinal fluid (CSF). A 29-year-old man was admitted with a 6 week history of left-sided facial numbness, facial droop, and clinical symptoms of diabetes insipidus. Imaging studies of the brain revealed a 2.5 cm hyperdense pineal region mass with eccentric calcifications and diffuse intraventricular, subependymal, and subarachnoid metastatic disease (Figs. 1 and 2). Biopsy was avoided due to potential adverse effects associated with this highrisk procedure. Instead, a lumbar puncture was performed for cytologic assessment of the CSF. Cytospin smears were either air-dried or alcohol-fixed and stained with Romanowsky and Papanicolaou stains, respectively. Cytomorphology was characterized by hypercellular smears composed of a discohesive population of large atypical cells with a scant to moderate amount of clear cytoplasm, vesicular chromatin pattern, and prominent nucleoli in a background of mature and activated lymphocytes (Figs. 3 and 4). Immunohistochemical stains performed on the cell block material revealed reactivity with placental alkaline phosphatase (PLAP) in the large atypical cells (Fig. 5) and positive staining with leukocyte common antigen in small lymphocytes. The microscopic appearance and immunohistochemical staining were consistent with the diagnosis of germinoma. Based on the cytologic diagnosis of germinoma, targeted chemotherapy followed by cerebrospinal irradiation was implemented. Follow-up imaging studies revealed marked interval decrease in size of the primary tumor and associated metastatic lesions which were no longer clearly discernible. Subsequent CSF cytology analysis failed to display abnormal cells. In general, only 10% of positive CSF cytology specimens are from primary CNS tumors. Detection of malignant cells in CSF indicates involvement of leptomeninges. Patients with leptomeningeal metastases (LM) may present with variable clinical symptoms including headache and mental changes. Among primary brain tumors, <1% are located in the pineal region. Germinomas, or dysgerminomas, account for about 60% of pineal tumors and are the most common intracranial germ cell neoplasm. They commonly occur in children and young adults, present with hypothalamic-pituitary axis malfunction and are more common in males than females. High levels of alpha-feto-protein (AFP), beta-HCG (human chorionic gonadotropin), and PLAP in serum or CSF are strongly suggestive of the presence of a CNS germinoma in dubious cases. Histologically and cytologically, germinomas are indistinguishable from their gonadal counterparts. Cytomorphologically, germinomas typically present as discohesive, cellular populations characterized by large, atypical cells with scant to moderate clear cytoplasm, pleomorphic nuclei with irregular nuclear contours and vesicular chromatin with prominent nucleoli, in a background of small, mature appearing lymphocytes. Intracranial germinomas, however, may show a variety of divergent morphology, such as pseudopapillary or papillary pattern, granulomatous pattern, epithelioid clusters, gliosis, and crush artifact. This wide variety of architectural patterns that may be seen in intracranial germinomas broadens the differential diagnosis to Department of Pathology and Laboratory Medicine, University of Florida College of Medicine, Jacksonville, Florida *Correspondence to: Melanie J. Kubik, MD, University of Florida College of Medicine, Jacksonville, 655 w 8th St Box C-504, Jacksonville, FL 32209, USA. E-mail: melanie.kubik@gmx.net Received 16 June 2014; Revised 13 November 2014; Accepted 17 December 2014 DOI: 10.1002/dc.23252 Published online 22 January 2015 in Wiley Online Library (wileyonlinelibrary.com).