Glioblastoma Multiforme With Epithelial Differentiation: A Potential Diagnostic Pitfall in Cerebrospinal Fluid Cytology Simpal K. Gill, M.D.,1,2 Vijayalakshmi Padmanabhan, M.D.,1,2 William F. Hickey, M.D.,1,2 and Jonathan D. Marotti, M.D.1,2*
Cerebrospinal fluid (CSF) cytology provides valuable diagnostic and prognostic information for diseases of the central nervous system (CNS) and remains the gold standard for the detection of neoplastic meningitis. Metastatic involvement of the CSF by non-CNS neoplasms far surpasses that of primary brain tumors, although conventional glioblastoma multiforme (GBM) can occasionally be identified in the CSF. GBM with epithelial differentiation is an uncommon variant that may contain features such as adenoid structures, signet ring cells, or squamous metaplasia. Herein, we present a case of GBM with epithelial differentiation to highlight a potential diagnostic pitfall in CSF cytology. A 55-year-old man presented with neurological symptoms and a 6.4 cm left temporal lobe cystic mass. Primary resection revealed GBM with focal epithelial differentiation confirmed by cytokeratin, epithelial membrane antigen, and glial fibrillary acidic protein immunohistochemical studies. Four months following primary resection, the patient developed severe headache for which a lumbar puncture with CSF cytologic evaluation was performed. The cytospin preparation showed numerous malignant epithelioid cells with high nuclear–cytoplasmic ratio and prominent cytoplasmic vacuoles resembling metastatic carcinoma. However, the lesional cells were cytomorphologically identical to the epithelial component present in the patient’s recently diagnosed GBM. This case illustrates the potential for GBM with epithelial differentiation to closely mimic metastatic carcinoma from a non-CNS site in CSF cytology, which expands the differential diagnosis and emphasizes the necessity of clinical correlation. Diagn. Cytopathol. 2015;43:638–641. VC 2015 Wiley Periodicals, Inc.
1 Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 2 Geisel School of Medicine at Dartmouth, Hanover, New Hampshire *Correspondence to: Jonathan D. Marotti, MD, Department of Pathology, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA. E-mail: [email protected] Received 9 November 2014; Revised 16 February 2015; Accepted 30 March 2015 DOI: 10.1002/dc.23274 Published online 23 April 2015 in Wiley Online Library (wileyonlinelibrary.com).
638
Diagnostic Cytopathology, Vol. 43, No 8
Key Words: cytology
cerebrospinal fluid; glioblastoma multiforme;
Cytologic examination of cerebrospinal fluid (CSF) assists in diagnosing neurological conditions and identifying the origin of neoplastic cells.1 Non-central nervous system (CNS) neoplasms are the most commonly identified metastatic malignancy in CSF; however, primary CNS tumors such as medulloblastoma, ependymoma, anaplastic astrocytoma, and glioblastoma multiforme (GBM) can also cause leptomeningeal metastases.2–4 CSF cytology has been shown to be highly specific (>95%) for the detection of leptomeningeal involvement by neoplasms but lacks sensitivity (
Cerebrospinal fluid (CSF) cytology provides valuable diagnostic and prognostic information for diseases of the central nervous system (CNS) and remains the gold standard for the detection of neoplastic meningitis. Metastatic involvement of the CSF by non-CNS neoplasms far surpasses that of primary brain tumors, although conventional glioblastoma multiforme (GBM) can occasionally be identified in the CSF. GBM with epithelial differentiation is an uncommon variant that may contain features such as adenoid structures, signet ring cells, or squamous metaplasia. Herein, we present a case of GBM with epithelial differentiation to highlight a potential diagnostic pitfall in CSF cytology. A 55-year-old man presented with neurological symptoms and a 6.4 cm left temporal lobe cystic mass. Primary resection revealed GBM with focal epithelial differentiation confirmed by cytokeratin, epithelial membrane antigen, and glial fibrillary acidic protein immunohistochemical studies. Four months following primary resection, the patient developed severe headache for which a lumbar puncture with CSF cytologic evaluation was performed. The cytospin preparation showed numerous malignant epithelioid cells with high nuclear–cytoplasmic ratio and prominent cytoplasmic vacuoles resembling metastatic carcinoma. However, the lesional cells were cytomorphologically identical to the epithelial component present in the patient’s recently diagnosed GBM. This case illustrates the potential for GBM with epithelial differentiation to closely mimic metastatic carcinoma from a non-CNS site in CSF cytology, which expands the differential diagnosis and emphasizes the necessity of clinical correlation. Diagn. Cytopathol. 2015;43:638–641. VC 2015 Wiley Periodicals, Inc.
1 Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 2 Geisel School of Medicine at Dartmouth, Hanover, New Hampshire *Correspondence to: Jonathan D. Marotti, MD, Department of Pathology, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA. E-mail: [email protected] Received 9 November 2014; Revised 16 February 2015; Accepted 30 March 2015 DOI: 10.1002/dc.23274 Published online 23 April 2015 in Wiley Online Library (wileyonlinelibrary.com).
638
Diagnostic Cytopathology, Vol. 43, No 8
Key Words: cytology
cerebrospinal fluid; glioblastoma multiforme;
Cytologic examination of cerebrospinal fluid (CSF) assists in diagnosing neurological conditions and identifying the origin of neoplastic cells.1 Non-central nervous system (CNS) neoplasms are the most commonly identified metastatic malignancy in CSF; however, primary CNS tumors such as medulloblastoma, ependymoma, anaplastic astrocytoma, and glioblastoma multiforme (GBM) can also cause leptomeningeal metastases.2–4 CSF cytology has been shown to be highly specific (>95%) for the detection of leptomeningeal involvement by neoplasms but lacks sensitivity (
