Pituicytoma: characterization of a unique neoplasm by histology, immunohistochemistry, ultrastructure, and array-based comparative genomic hybridization.
The clinicopathologic features of this interesting neoplasm have recently been reviewed, but subsequent reports have invigorated the debate regarding the tumor's histogenesis. (3-5) In this study, we present the histologic, immunohistologic, and ultrastructural features of 2 cases of pituicytoma and demonstrate genomic copy number imbalances associated with this unique neoplasm by using array-based comparative genomic hybridization (array CGH). These findings clearly illustrate the unique histogenetic features of these neoplasms.
REPORT OF CASES
During a 6-year period between the years 2000 and 2006, 2 patients underwent resection of a sellar mass with a pathologic diagnosis of pituicytoma at the University of California, San Francisco.
A 48-year-old woman presented with a 9-kg weight loss during several months and increased fatigue. Brain magnetic resonance imaging (MRI) revealed a contrast-enhancing 0.2-cm mass with sellar expansion. A subtotal resection was performed via a transsphenoidal approach. The tumor was noted to be extremely vascular, adherent to surrounding tissue at surgery, and involved both cavernous sinuses. Brain MRI demonstrated no evidence of tumor recurrence at 4 months.
A 54-year-old man presented with a 10-year history of diabetes insipidus and panhypopituitarism. Brain MRI demonstrated a contrast-enhancing sellar and suprasellar mass, and the patient underwent a subtotal resection. One year after the initial resection, a second resection was performed for residual/recurrent tumor adjacent to the optic nerve. There was no tumor recurrence noted at 4 months.
The histopathologic features of the tumors were similar for both patients and are illustrated in Figure 1, A through D. The tumors were composed of bipolar spindle cells with round to elongate nuclei arranged in intersecting fascicles. No cytoplasmic granularity or vacuolization was present, and only rare mitotic figures were identified. In one sample, adjacent normal tissue was present and there was no evidence of tumor infiltration. The tumors contained numerous thin-walled blood vessels. No eosinophilic granular bodies, Rosenthal fibers, or Herring bodies were identified within the tumors.
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Immunohistochemical staining of the tumors demonstrated diffuse, strong positive staining for S100 and vimentin (Figure 1, E and F). Tumor cells from both patients exhibited diffuse, strong cytoplasmic Bcl-2 immunostaining (Figure 2, A and B). In the normal adenohypophysis, Bcl-2 immunostains only scattered spindled cells (Figure 2, C). The tumor cells were immunonegative for synaptophysin, glial fibrillary acidic protein, and chromogranin A and B (Figure 2, D through F). There was no immunostaining of tumor cells by neurofilament (data not shown).
The ultrastructural features of the 2 neoplasms and a characteristic pituitary adenoma are demonstrated in Figure 3. The tumors from patient 1 (Figure 3, A and B) and patient 2 (Figure 3, C and D) were composed of bipolar spindle cells with occasional intermediate filaments, no definitive secretory granules, and no significant accumulation of mitochondria. Note the variation in the density of mitochondria between the tumors of patient 1 and patient 2. Scattered intercellular junctions were present with minimal interdigitation of cell membranes. Focal basal lamina production was present in the tumor from patient 2. Figure 3, E and F, illustrates the characteristic features of a prolactin-secreting pituitary adenoma with prominent secretory granules and absence of basal lamina.
To determine if there were genetic alterations associated with this neoplasm, array CGH was performed on tumor DNA isolated from patient 1 (Figure 4, A through E). Multiple chromosomal imbalances were detected, including losses for chromosome arms 1p, 14q, and 22q and overrepresentation on chromosome arm 5p. Array CGH was performed in parallel on 5 pituitary adenomas. The pituitary adenomas also contained various chromosomal imbalances; however, these were distinct from those identified in the pituicytoma (data not shown).
The pituicytoma is a rare neoplasm of the sellar region. As illustrated in our 2 cases, a number of features common to the pituicytoma help to distinguish it from other, more common, lesions of the sellar and suprasellar region, including pituitary adenoma, meningioma, and schwannoma (summarized in the Table). Patients present with a discrete, solid sellar mass that is isointense to surrounding brain by T1-weighted MRI and homogeneously contrast enhancing after administration of gadolinium. Surgical resection is the primary treatment, and the tumors are often noted to be highly vascular and sometimes difficult to excise. On pathologic examination, the tumors are composed of bipolar spindle cells with round to elongate nuclei, in a fascicular arrangement, with rare mitotic activity. Immunohistochemistry demonstrates strong, diffuse S100 and vimentin staining; variable Bcl-2 and glial fibrillary acidic protein immunopositivity; and no immunostaining for synaptophysin, chromogranin A and B, and neurofilament. Ultrastructural analysis can assist in the diagnosis of these neoplasms. (7,8) Unlike pituitary adenomas, there is an absence of definitive secretory granules. There is no significant accumulation of mitochondria, interdigitation of cell membranes, or accumulation of pericellular basal lamina. Occasional intermediate filaments can be identified.
Our findings are consistent with those of other investigators and confirm the unique nature of this rare sellar neoplasm. (1,3-5) Interestingly, we observed strong, diffuse immunopositivity for Bcl-2, an important regulator of apoptosis, in both tumor specimens. As shown in Figure 2, C, Bcl-2 immunostaining of the normal pituitary gland is focal, and some authors (4) have suggested that it is primarily restricted to folliculostellate cells of the adenohypophysis. Our findings, consistent with those of Ulm et al, (4) raise the intriguing possibility that the pituicytoma may arise from folliculostellate cells. Alternatively, Bcl-2 expression in pituicytomas may represent an important factor in tumorigenesis, as has been found in other sellar neoplasms. (9)
To determine if pituicytomas are characterized by unique genetic alterations, we performed array CGH on tumor DNA isolated from patient 1. We identified multiple chromosomal imbalances including losses for chromosome arms 1p, 14q, and 22q and overrepresentation on chromosome arm 5p. Consistent with the notion that pituicytomas are a unique subset of tumors of the sellar region, the overall pattern of genetic alterations was unique when compared to 5 representative pituitary adenomas (data not shown) and previous reports (10-12) of chromosomal imbalances in pituitary adenomas. Although the pattern of genetic changes was unique, it is interesting to note that some of the individual genetic changes in pituicytoma, including chromosomal imbalances on 1p, 5p, 14q, and less frequently 22q, have been reported in individual pituitary adenomas. This suggests that there may be some similarities in the mechanisms of tumorigenesis in sellar region neoplasms.
The histologic, ultrastructural, and genetic findings in this study support the unique identity of the pituicytoma. As this is the first report on genetic alterations in pituicytoma, we hope to both contribute to the knowledge of this neoplasm and stimulate future research on its tumorigenesis. Future studies are needed to (1) identify how common these chromosomal imbalances are in pituicytomas and to (2) elucidate critical genes in pathogenesis that may reside in these regions of copy number aberration.
This study was supported by grants NS42927 (Dr Tihan), NS063456 (Dr Phillips), and CA85799 (Dr Tihan) from the National Institutes of Health, Bethesda, Maryland; and the National Brain Tumor Foundation (Dr Tihan), San Francisco, California.
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Joanna J. Phillips, MD, PhD; Anjan Misra, PhD; Burt G. Feuerstein, MD, PhD; Sandeep Kunwar, MD; Tarik Tihan, MD, PhD
Accepted for publication July 1, 2009.
From the Division of Neuropathology, Department of Pathology (Drs Phillips and Tihan); Brain Tumor Research Center, Department of Neurosurgery (Drs Phillips, Misra, and Feuerstein); Comprehensive Cancer Center (Drs Misra and Feuerstein); the Department of Laboratory Medicine (Dr Feuerstein); and the Department of Neurosurgery (Dr Kunwar), University of California San Francisco, San Francisco. Drs Misra and Feuerstein are now with the Department of Neurology, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, Arizona.
The authors have no relevant financial interest in the products or companies described in this article.
Presented in part at the XVI International Congress of Neuropathology, San Francisco, California, September 10-15, 2006.
Reprints: Joanna J. Phillips, MD, PhD, Neuropathology Unit, University of California San Francisco, 505 Parnassus Ave, Room M551, San Francisco, CA 94143-0102 (e-mail: joanna.phillips@ucsf. edu).
Characteristic Features of Select Tumors in the Sellar/Parasellar Region Histology Immunohistochemistry Pituicytoma Bipolar spindle cells S100 (+) arranged in Variable GFAP intersecting fascicles Schwannoma Spindle cells in an S100 (+) Antoni A or B pattern, Variable GFAP (+) Verocay bodies Blood vessel Pericellular hyalinization collagen IV (+) Meningioma Heterogeneous, Membranous EMA (+) including Variable S100 (+) meningoepithelial and more spindled cells, whorls, psammoma bodies, and nuclear pseudoinclusions Spindle cell Spindled to epitheliod S100 (+) oncocytoma cells; eosinophilic, EMA (+) finely granular cytoplasm Granular cell tumor Polygonal to fascicular S100 (+) cells, prominent PAS (+), granular cytoplasm diastase-resistant cytoplasm Pituitary adenoma Neuroendocrine tumor Synaptophysin (+) Salt and pepper Chromagranin (+) chromatin Pilocytic astrocytoma Biphasic arrangement of GFAP (+) elongate spindled cells Eosinophilic granular bodies Rosenthal fibers Ultrastructure Pituicytoma Bipolar spindle cells with occasional intermediate filaments Schwannoma Accumulation of pericellular basal lamina Meningioma Intermediate filaments, well- defined desmosomes, interdigitation of membranes (less prominent in fibrous variant) (13) Spindle cell Abundant abnormal oncocytoma mitochondria Granular cell tumor Abundant heterolysosomes Pituitary adenoma Neurosecretory granules Pilocytic astrocytoma Amorphous, electron-dense material and intermediate filaments; membrane-bound dense bodies Abbreviations: EMA, epithelial membrane antigen; GFAP, glial fibrillary acidic protein; PAS, periodic acid-Schiff.
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|Author:||Phillips, Joanna J.; Misra, Anjan; Feuerstein, Burt G.; Kunwar, Sandeep; Tihan, Tarik|
|Publication:||Archives of Pathology & Laboratory Medicine|
|Date:||Jul 1, 2010|
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