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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Arch Pathol Lab Med. Author manuscript; available in PMC 2011 August 24.
Published in final edited form as:
PMCID: PMC3161118

Pituicytoma Characterization of a Unique Neoplasm by Histology, Immunohistochemistry, Ultrastucture, and Array-Based Comparative Genomic Hybridization

Joanna J. Phillips, MD, PhD, Anjan Misra, PhD, Burt G. Feuerstein, MD, PhD, Sandeep Kunwar, MD, and Tarik Tihan, MD, PhD


The pituicytoma is a rare neoplasm whose histogenesis is debated partly because of the diversity of tissue types present in the sellar region. In this article we illustrate the characteristic histologic, immunohistologic, and ultrastructural features of this unique neoplasm. Furthermore, we use array-based comparative genomic hybridization to demonstrate a unique pattern of genomic copy number aberrations in pituicytomas. Tumors were composed of bipolar, spindle cells that were immunopositive for S100, vimentin, and Bcl-2 and immunonegative for synaptophysin, chromogranin, and glial fibrillary acidic protein. Ultrastructural analysis was remarkable for absence of secretory granules. Array comparative genomic hybridization demonstrated genomic copy number imbalances, including losses on chromosome arms 1p, 14q, and 22q and gains on 5p. This pattern of genetic changes only partially overlaps with the genomic alterations reported in pituitary adenomas. In summary, our data suggest that pituicytomas are a unique subset of tumors of the sellar region.

The pituicytoma, or infundibuloma, is a rare tumor of the sellar region that displays a spindle cell morphology, fascicular arrangement of tumor cells, and variable glial fibrillary acidic protein (GFAP) immunoreactivity.1-5 Despite the characteristic histologic features of pituicytomas, they can be confused with other more common sellar or suprasellar neoplasms on the basis of their location and their solid, uniformly contrast-enhancing appearance on neuroimaging. By their morphology and immunostaining pattern, pituicytomas are thought to arise from pituicytes, specialized glial cells of the neurohypophysis. Recent data, however, suggest that pituicytomas may also share some features with the folliculostellate cell.3,4 Folliculostellate cells are nonendocrine, spindle-shaped cells of the adenohypophysis that express S100 and Bcl-2.4,6 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.


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.

Patient 1

A 48-year-old woman presented with a 9-kg weight loss over 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.

Patient 2

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.

Figure 1
Histopathologic and immunohistochemical features of the 2 tumors. A through D, Tumors composed of bipolar spindle cells with elongate or oval nuclei arranged in intersecting fascicles. Tumors exhibit diffuse, strong positive staining for S100 (E) and ...

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).

Figure 2
Immunohistochemical features of the 2 pituicytomas. A and B, Bcl-2 exhibits diffuse, strong cytoplasmic staining of tumor cells for both patients. C, Within the normal adenohypophysis, Bcl-2 immunostained only scattered spindled cells. The tumor cells ...

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.

Figure 3
Ultrastructural features of the pituicytomas and a representative prolactin-secreting pituitary adenoma. The tumors from patient 1 (A and B) and patient 2 (C and D) were composed of bipolar spindle cells with occasional intermediate filaments, with no ...

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).

Figure 4
A through E, Array comparative genomic hybridization (CGH) of the tumor from patient 1. Chromosomes such as chromosome 3 (shown) did not demonstrate any genomic copy number imbalances by array CGH. In contrast, the following genomic copy number imbalances ...


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.

Characteristic Features of Select Tumors in the Sellar/Parasellar Region

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, Bcl-2 immunostaining of the normal pituitary gland is focal, and some authors4 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 reports10-12 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) and NS063456 (Dr Phillips) from the National Institutes of Health, Bethesda, Maryland; grant CA85799 (Dr Tihan); and the National Brain Tumor Foundation (Dr Tihan).


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.


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