This case was originally published in 2018. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.
A 51-year-old woman presented with acute onset left facial weakness and was found on brain MRI to have a cerebral infarct and a skull base tumor. For the following six years she experienced chronic headaches but declined surgical treatment. The tumor was followed with imaging studies that showed slow and progressive enlargement. Most recently, brain MRI demonstrated the tumor to be a contrast-enhancing, 3 cm mass in the infundibulum (Image A). She underwent tumor resection.
Whole Slide Image
The whole slide image provided is an H&E stained slide of infundibular mass from a tumor resection.
Which of the following is the CORRECT diagnosis?
Hemangiopericytoma/solitary fibrous tumor
This tumor has a positive immunoprofile for which of the following sets of stains?
Bcl-2, CD34, CD99
Bcl-2, S100, TTF-1
CD34, EMA, PR
EMA, GFAP, S100
GFAP, MIB-1, Synaptophysin
What is the MOST appropriate treatment for this condition?
Complete surgical resection
Laser interstitial thermal therapy
Radiation of the entire neuraxis
Discussion and Diagnosis
The diagnosis is WHO grade I pituicytoma. On MRI, the lesion is circumscribed, T1-isointense and T2-hyperintense with homogeneous contrast enhancement and no surrounding edema (Image A). Intraoperatively, the tumor is hypervascular and appears tan-red and soft. An intraoperative frozen section shows a spindle cell neoplasm consisting of elongated cells in a vaguely fascicular arrangement (Image B). Paraffin-embedded sections show a moderately cellular neoplasm of elongated cells between capillaries with fascicular, storiform, or haphazard arrangements (Image C and Image D). Occasional sinusoidal spaces lined by epithelioid tumor cells in a pseudoalveolar fashion can be found (Image E). Tumor cells have oval nuclei, varying amounts of eosinophilic cytoplasm, and relatively indistinct cellular borders (Image F). No nuclear anaplasia, mitotic figures, apoptotic bodies, tumor necrosis, microvascular proliferation, oncocytic or granular cytoplasm, Herring bodies (pale eosinophilic dilated axons), Rosenthal fibers, or eosinophilic granular bodies are recognized. On IHC studies, most tumor cells stain positive for S100 (Image G), TTF-1 (Image H), and Bcl-2 (Image I). Some tumor cells are EMA-positive, while rare scattered tumor cells are GFAP-positive (Image J). Tumor cells are negative for CD34, progesterone receptor (PR), synaptophysin, and chromogranin-A. MIB-1 labeling among tumor cells is low, and the estimated maximal labeling index is 2% (Image K).
Pituicytoma (also known as infundibuloma and posterior pituitary astrocytoma) is a rare, circumscribed, low-grade glial neoplasm of uncertain histogenesis in the sellar/suprasellar region. Rare cases may have a cystic component. It has been postulated that pituicytoma arises from pituicytes (specialized spindled or stellate glia) in neurohypophysis and infundibulum, but an alternative origin from the folliculostellate cells (S100- and Bcl-2-positive) in the adenohypophysis has been proposed. It has been reported in patients aged seven through 83 years with a mean age of diagnosis in the fifth decade and a slight male predominance. Clinical presentations vary and depend on mass effect on surrounding structures, such as visual disturbance, hyperprolactinemia, hypopituitarism, and headache. The majority of reported cases are slow growing, and some cases are asymptomatic. Surgical resection is the treatment of choice, and incompletely resected cases may recur. CSF spread has not been reported. Some believe in the benefit of radiation to residual tumor, but its efficacy remains unclear.
Radiographically, pituicytoma needs to be differentiated from other mass lesions found in this region, such as pituitary adenoma, craniopharyngioma, hypothalamic hamartoma, chordoid glioma, pilocytic astrocytoma, optic glioma, germ cell tumors, hypophysitis, and neurosarcoidosis. The list of histopathologic differential diagnoses is shorter and includes normal neurohypophysis, astrocytoma (pilocytic or infiltrating), schwannoma, meningioma, ependymoma, and hemangiopericytoma/solitary fibrous tumor. Normal neurohypophysis is less cellular than pituicytoma and consists of slender, elongated and bipolar pituicytes arranged loosely and haphazardly between cellular processes, capillaries, axons, and occasional Herring bodies (both demonstrated by neurofilament IHC). The IHC phenotype of pituicytoma is relatively unique and helps in its definitive diagnosis: diffusely positive for TTF-1, S100, vimentin, galectin-3, and Bcl-2; focally positive for EMA and GFAP; and negative for cytokeratins, CD34, PR, synaptophysin, and chromogranin-A. High mitotic counts and MIB-1 labeling index do not appear to portend a more aggressive behavior.
Spindle cell oncocytoma and granular cell tumor are two other rare TTF-1-positive low-grade tumors occurring in the sellar/suprasellar region. Cells of spindle cell oncocytoma are elongated or epithelioid with plump, mitochondria-rich oncocytic cytoplasm focally or extensively. Large pleomorphic atypical nuclei and infiltrating lymphocytes may be seen, but mitoses or anaplastic features are absent. The recurrence rate after incomplete resection is higher than that of pituicytoma with no known histologic predictors or metastatic potential, but the number of reported cases is low. There is increasing evidence to suggest that pituicytomas, spindle cell oncocytomas, and granular cell tumors are related based on a similar immunoprofile. Histologically distinct, the rare chordoid glioma of third ventricle also expresses TTF-1 and adds to the variety of TTF-1-positive midline skull base tumors with a possible common histogenesis.
Take Home Points
- Pituicytomas are rare and indolent tumors in the sellar/suprasellar region presenting clinically with varying symptoms of local mass effects.
- Histologically, pituicytoma differs from normal neurohypophysis in showing a higher cellularity, a more compact architecture, and no Herring bodies or admixed axons.
- In a spindle cell neoplasm in the sellar/suprasellar region, the immunoprofile of S100(+), TTF-1(+), and Bcl-2(+) supports a diagnosis of pituicytoma.
- Spindle cell oncocytoma and granular cell tumor in the sellar/suprasellar region share a similar IHC phenotype with pituicytoma.
- Brat DJ, Scheithauer BW, Staugaitis SM, et al. Pituicytoma: a distinctive low-grade glioma of the neurohypophysis. Am J Surg Pathol. 2000;24:362-8.
- Hagel C, Buslei R, Buchfelder M, et al. Immunoprofiling of glial tumors of the neurohypophysis suggests a common pituicytic origin of neoplastic cells. Pituitary. 2017;20:211-7.
- Kleinschmidt-DeMasters BK, Lopes MB. Update on hypophysitis and TTF-1 expressing sellar region masses. Brain Pathol. 2013;23:495-514.
- Mete O, Lopes MB, Asa SL. Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. Am J Surg Pathol. 2013;37:1694-9.
- Phillips JJ, Misra A, Feuerstein BG, et al. Pituicytoma: characterization of a unique neoplasm by histology, immunohistochemistry, ultrastructure and array-based comparative genomic hybridization. Arch Pathol Lab Med. 2010;134:1063-9.
- Wang J, Liu Z, Du J, et al. The clinicopathological features of pituicytoma and the differential diagnosis of sellar glioma. Neuropathol. 2016;36:432-40.
- Which of the following is the CORRECT
- A. Hemangiopericytoma/solitary fibrous tumor
- B. Meningioma
- C. Pilocytic astrocytoma
- D. Pituicytoma
- E. Schwannoma
- This tumor has a positive immunoprofile for which of the following sets of stains?
- A. Bcl-2, CD34, CD99
- B. Bcl-2, S100, TTF-1
- C. CD34, EMA, PR
- D. EMA, GFAP, S100
- E. GFAP, MIB-1, Synaptophysin
- What is the MOST appropriate treatment for this condition?
- A. Complete surgical resection
- B. Immunosuppressive therapy
- C. Laser interstitial thermal therapy
- D. Radiation of the entire neuraxis
- E. Temozolomide chemotherapy