Keywords
ganglion cell - pituitary adenoma - unusual demographic and radiologic features
Introduction
A preoperative diagnosis of a ganglion cell component in a pituitary adenoma is very
difficult, because most of these cases present clinically and radiologically as pituitary
adenomas. The definitive diagnosis is determined by histopathologic study.
The aim of the article is to report a ganglion cell component in a pituitary adenoma
seen as single-scattered cells amidst the larger component of pituitary adenoma. The
awareness of this entity prompts a pathologist to proceed with immunohistochemical
(IHC) marker studies and confirm the presence of ganglion cells in a pituitary adenoma.
Case Report
A 25-year-old man was admitted to our hospital with a 2-year history of headache and
6-month history of memory disturbances and behavioral changes. Physical examination,
hematologic, and biochemical parameters were within normal limits.
Magnetic resonance imaging (MRI) revealed a sellar lesion eroding the right sphenoidal
sinus and extending up to the medial temporal gyrus and pons ([Fig. 1]) with engulfment of internal carotid, basilar, middle, and anterior carotid artery.
Fig. 1 Sellar lesion eroding the left sphenoidal sinus and extending up to the medial temporal
gyrus and pons.
The patient underwent partial excision of the pituitary tumor by transsphenoidal endoscopic
endonasal approach. The postoperative period was uneventful.
Histologically, the tumor was composed of sheets and nodules of medium to large polygonal
cells with pleomorphic round to oval vesicular nuclei, one or more prominent nucleoli,
and moderate to abundant acidophilic granular cytoplasm. Few cells showed bizarre
nuclei (pituitary adenoma component) intermingled with the few scattered multinucleated
cells having dark staining nuclei and dense cytoplasm (ganglion cell component) ([Fig. 2]). Mitosis was rare, and no necrosis or endovascular proliferation was noted. On
IHC, synaptophysin was positive in both components ([Fig. 3]) and neurofilament protein (NFP) was positive in cytoplasm of larger multinucleated
ganglion cells ([Fig. 4]). Glial fibrillary acidic protein (GFAP) () was negative in both types of tumor
cells. Ki 67 index was 2%. IHC for pituitary hormones including growth hormone (GH), adrenocorticotropic
hormone (ACTH), prolactin, and follicle-stimulating hormone (FSH) showed positivity
for prolactin ([Fig. 5]) in the adenoma component.
Fig. 2 High-power view (40x) showing medium to large polygonal cells (adenoma component)
admixed with multinucleated cells (ganglion cell component).
Fig. 3 Immunohistochemical markers for synaptophysin was positive in both components (10x).
Fig. 4 Neurofilament protein was positive in cytoplasm of large ganglion cell (40x).
Fig. 5 Immunohistochemical markers for prolactin was positive in the adenoma component (10x).
Discussion
Ganglion cell containing pituitary adenomas are rare entities. They represent tumors
originating in the sella turcica, which are composed of adenomatous and ganglion cell
components. Different terminologies have been used to describe pituitary ganglion
cell lesions, including pituitary adenoma with neuronal choristoma (PANCH), hypothalamic
hamartomas, and hamartomatous gangliocytomas, which have led to nosologic confusion.[1]
A review of previous studies reveals that most of the cases of these tumors have been
reported in women.[2] This patient was an adult male. Most cases were macroadenomas (> 1 cm). However,
to the best of our knowledge, this is the first case of a ganglion cell containing
pituitary adenoma with neuronal differentiation presenting as a giant adenoma (> 4
cm).[3] The anterior growth was also unusual for an adenoma that usually grows superiorly,
inferiorly, or posteriorly. The cases reported in literature were diagnosed as GH
secreting, while in a few cases, the tumor presented with symptoms of Cushing's disease
and hyperprolactinemia. Although this patient's endocrinologic status was unavailable,
the lack of clinical symptoms and negativity for hormones on IHC (except prolactin)
favor a nonfunctioning pituitary adenoma which is exceptional.[1] These tumors have demonstrated a benign clinical course.
Histopathologic study and IHC markers are essential to the diagnosis of this entity.
The infrequent recognition of ganglion cells may, in part, be due to (1) infrequent
IHC evaluation for its presence; (2) prominent nucleoli, particularly GH-secreting
adenomas, obscuring its presence; (3) widespread synaptophysin immunoreactivity that
may obscure the presence of coexisting small neurons; and (4) the presence of intermediately
differentiated neuronal forms (as seen in ganglion cell tumors) that are difficult
to recognize. Hence, pathologists need to be aware of this entity to arrive at the
correct diagnosis.
The origin of these tumors is controversial, and the three main hypotheses have been
proposed. The first hypothesis states that such tumors arise from the adenohypophyseal
parenchyma into which hypothalamic neurons have abnormally migrated during the early
phase of embryogenesis. The second hypothesis states that the pituitary adenoma is
caused by excessive stimulation of the hypothalamic hormones by the heterotopic intrasellar
ganglion cells. The third and presently accepted hypothesis suggests that the neuronal
and adenomatous components originated from the transitional cells between neurons
and adenohypophyseal cells of the embryonic rests (uncommitted stem/progenitor cells.[1] Based on the findings of this case and review of literature, we partly agree with
the first and third hypotheses, that this type of tumor may relate to embryonic cells.
This lesion may develop from the abnormal migration of gangliocytic cells in the embryonic
brain due to internal or external disturbance. Then, the ectopic ganglion cells keep
the immature features in the abnormal location and lead to the tumorigenesis of the
pituitary adenoma. If cells can be isolated and cultured from the specimen of this
type of tumor, it would endow us with the ability to understand this entity better.[4]
