|Year : 2022 | Volume
| Issue : 2 | Page : 67-70
Pituitary adenoma with gangliocytoma: A rare mixed tumor in the sellar region
Archana Buch, Neha Agarwal, Tushar Kambale, Charusheela Gore
Department of Pathology Dr. D.Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, India
|Date of Submission||08-Mar-2022|
|Date of Acceptance||17-May-2022|
|Date of Web Publication||13-Jun-2022|
Dr. Tushar Kambale
Department of Pathology, Dr. D.Y. Patil Medical College, Hospital and Research Center, Dr. D.Y. Patil Vidyapeeth, Pimpri, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
Sellar gangliocytomas are exceedingly rare, well-differentiated, low-grade neoplasms that frequently occur in the presence of a pituitary adenoma (PA). We report a case of a sellar gangliocytoma coexisting with growth hormone (GH) secreting PA. A 43-year-old man was brought to our hospital with right-eye visual disturbances for 2 months, along with headaches, acromegaly, temporal hemianopia in the right eye, and recent onset of Type 2 diabetes mellitus. Endocrinological studies found elevated serum level of GH. A computed tomographic scan showed a mass in the sellar region with suprasellar extension and thus a diagnosis of an expanding pituitary macroadenoma was established. It was removed by transnasal transsphenoidal surgery. On histopathological examination of the resected specimen, diagnosis of mixed gangliocytoma-PA was confirmed as it showed two distinct morphological components of the tumor comprising neoplastic ganglionic cells and adenomatous cells.
Keywords: Gangliocytoma, pituitary adenoma, sellar region
|How to cite this article:|
Buch A, Agarwal N, Kambale T, Gore C. Pituitary adenoma with gangliocytoma: A rare mixed tumor in the sellar region. J Clin Sci 2022;19:67-70
| Introduction|| |
Pituitary adenoma (PA) is the most prevalent tumor encountered in the sellar region. It is responsible for 10%–15% of all the intracranial neoplasms. Gangliocytomas (WHO Grade I) are extremely rare benign neoplasms of the sympathetic nerve fibers that arise from neural crest cells. They are well differentiated and consist of randomly oriented bizarre neoplastic ganglion cells. Gangliocytoma is most frequent in children and young adults (40%–60%), but it can afflict people of any age. This tumor can develop both extracranially and intracranially, with a 0.5% incidence rate at the intracranial site. An unusual occurrence of PA with gangliocytoma in the sellar region is presented in the current study.
| Case Report|| |
A 43-year-old male presented with chief complaints of blurring of vision in the right eye for 2 months with occasional frontal headache. The patient was a newly diagnosed case of Type 2 diabetes mellitus. There were no episodes of limb weakness, slurring of speech, hearing disturbances, tingling or numbness, vomiting, loss of consciousness, seizures, vertigo, or trauma. There was no history of hypertension, asthma, allergy, chest pain, and relevant previous surgeries.
On examination, the patient's vitals were normal. Features of acromegaly such as enlarged hands and temporal hemianopia in the right eye were present. On fundoscopy, fundus was unremarkable and the pupils were reactive and regular. Extraocular movements were full, free, and painless in all direction of gazes. The patient was well conscious and oriented to time, place, and person, and no other abnormalities were detected in systemic examination.
Diagnostic nasal endoscopy revealed hypertrophied mucosa with bilateral middle and inferior turbinate hypertrophy. Sphenoid sinus could not be visualized.
A contrast-enhanced computed tomography (CECT) scan of the brain and PNS (Para-Nasal Sinus) [Figure 1] revealed a well-defined mildly hyperdense heterogeneously enhancing lesion with few calcifications measuring 3.9 cm × 3.4 cm × 2.5 cm in the sellar and suprasellar region causing widening of the sella with thinning and bulging of the floor of the sella into the sphenoid sinus. There is extension into cavernous sinus. These findings were suggestive of pituitary macroadenoma.
|Figure 1: CECT scan showing hyperdense heterogeneously enhancing lesion with few calcifications in the sellar region extending into the suprasellar region and cavernous sinus. CECT = Contrast-enhanced computed tomography|
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Magnetic resonance imaging (MRI) was also done, and it showed sellar mass measuring 3.2 cm × 2 cm × 1 cm causing compression of the optic chiasma and optic nerve, thus explaining visual disturbances in the patient and confirming the CECT diagnosis.
Preoperative laboratory investigations such as complete blood count, liver and renal function tests, and electrolytes were within normal limits. Glycated hemoglobin (HbA1C) was 8.6%. Hormonal assay (HGH – 17 ng/ml, luteinizing hormone – 5.4 IU/L, cortisol – 7.20 ug/dl, Follicle stimulating hormone – 10.6 IU/L, ACTH – 44.6 pg/ml, prolactin – 15.61 ng/ml, T3 – 110.54 ng/dl, T4 – 7.6 ug/dl, and thyroid stimulating hormone – 2.69 uIU/ml) was done to assess pituitary gland. All the hormones were within the normal biological reference range except elevated levels of human growth hormone (GH).
The patient was brought to the hospital in view of a space-occupying lesion located in the sellar area. Endoscopic transnasal transsphenoidal pituitary tumor excision was done. Intraoperative findings showed that the tumor was grayish red in appearance and had a variable consistency. Both soft and firm tumor sections were removed and studied under microscope. Grossly, the specimen was received as multiple tissue bits ranging from 0.3 cm to 1.2 cm, grayish white in color.
Microscopy revealed two distinct morphologies of the tumor [Figure 2]. One component of the tumor was comprised of sheets and nests of round-to-oval cells with scant-to-moderate amount of cytoplasm and monomorphic nuclei with stippled chromatin. The second component showed ganglionic element which consists of randomly oriented multipolar neuronal ganglion cells in a dense fibrillary background. There was no evidence of necrosis. Therefore, histopathological examination established the diagnosis of intrasellar mixed gangliocytoma-PA. Reticulin stain was done, and it showed that the reticulin architecture and acinar pattern of the pituitary gland were largely effaced as seen in PA. On immunohistochemistry, tumors are positive for synaptophysin and negative for glial fibrillary acidic protein (GFAP) [Figure 3].
|Figure 2: (a) Photomicrograph showing two components of tumor. On the left side, tumor cells are arranged in nests having uniform round nuclei, and on the right side, randomly oriented large neoplastic ganglion cells are seen (H and E stain, ×20). (b) Pituitary adenoma showing round cells with monomorphic nuclei with stippled chromatin, and moderate-to-scanty eosinophilic cytoplasm (H and E stain, ×40). (c) Gangliocytoma showing haphazardly arranged neoplastic ganglion cells in a dense fibrillary background (H and E stain, ×20). (d) Reticulin stain showing effacement of the reticulin architecture suggesting pituitary adenoma (×40)|
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|Figure 3: Photomicrograph showing two components of tumor which are positive for the synaptophysin. (b) Photomicrograph showing two components of tumor which are negative for GFAP. GFAP = Glial fibrillary acidic protein|
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The patient's vision was returned to its previous state as preoperatively during a 1-month follow-up period, with no notable modifications. The patient appeared to be in good health and was not in any pain. Informed consent of the patient is taken for the publication and research purpose.
| Discussion|| |
PAs are common benign neoplasms and comprise 10%–15% of all intracranial neoplasms. They arise in the anterior hypophysis and are initially intrasellar, but these tumors have a strong tendency to spread outside the pituitary fossa, occupying suprasellar or parasellar areas. Gangliocytomas are rare well-differentiated neuroepithelial tumors which originate from the posterior hypophysis. However, cases of PA with gangliocytoma in the sellar region are infrequently reported globally.
Gangliocytomas are WHO Grade I tumors that arise from the neuron, and are regarded as being caused by neuronal and mixed neuronal–glial tumors. Neuroblastoma, ganglioneuroblastoma, and gangliocytoma are the common subtypes of neuroblastic tumors. The degree of maturation of these three tumors varies, and the most benign one among these is gangliocytoma.,
Gangliocytoma can develop both extracranially and intracranially, with a 0.5% incidence rate at the intracranial location. The temporal lobe, end of the third ventricle, and any part of neuraxis are all intracranial sites for gangliocytoma, and it is hardly ever present in the sellar area.,
Sellar gangliocytomas are challenging diagnosis and should be distinguished from PAs. Pituitary gangliocytomas coexist with PAs in 65% of cases, and the two are clinically indistinguishable. Larger PAs produce signs and symptoms due to their mass effect. In the present case, suprasellar extension caused visual field disturbances and headaches whereas functional adenomas and gangliocytomas caused endocrine symptoms such as acromegaly and elevated serum GH levels.,
The various genesis theories given for this mixed tumor are: (i) in induced theory, primary tumor occurs first which induces other types of tumor; (ii) the stem cell differentiation theory; (iii) the metaplasia theory, where one tumor is primary and the second one is metaplastic tumor; (iv) in the encounter theory, different origins tumors occur seperately and later mix together; and (v) in the gene theory, tumorigenic factors work on the oncogenes of the anterior and posterior pituitary, and causes activation of cell tumorigenesis either simultaneously or consecutively.
The preferred methods for imaging are MRI and computed tomography (CT). Tumor calcifications are rarely detected. CT results are dependent on tumor size. For determining the extent of the lesion, MRI is the preferred method. On MRI, gangliocytomas appear to be homogeneous and have a signal intensity that is relatively intermediate across all the pulse sequences. Since the signal, density, and contrast manifestations are same as that of a PA, it can be tricky to identify them preoperatively using MRI or any other radiological investigations.
The presence of an associated ganglion cell lesion is not usually suspected until the PA is excised and examined histologically. Furthermore, to distinguish gangliocytomas from malignant neuroblastoma, a biopsy is needed, and excision is usually curative. As gangliocytomas do not have the tendency to metastasize, they do not require significant surgical resections or chemotherapy.,
Microscopy of gangliocytoma shows haphazardly arranged neoplastic ganglion cells in a dense fibrillary background. They may be uni/bi/multipolar and have abundant dense eosinophilic granular cytoplasm. Immunohistochemical studies show positive staining for neurofilament, neuron-specific enolase, synaptophysin, and chromogranin A and negative for GFAP.,
| Conclusion|| |
The mixed gangliocytoma-pituitary tumors although rare and difficult to conclude should be included in the differential diagnosis of all the cases of tumor in the sellar region.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kovacs K, Horvath E, editors. Atlas of tumor pathology fascicle 21. In: Tumors of the Pituitary Gland. 2nd
Ser. Washington, D.C: Armed Forces Institute of Pathology; 1986. p. 1-269.
Chen D, Xu J, Zhong P, Huang X, Xu M. Pituitary adenoma with gangliocytoma: Report of two cases. Oncol Lett 2014;8:781-4.
Puchner MJ, Hecnnann HD. Intrasellar pituitary gangliocyto-adenoma presenting with acromegaly: Case report. Neurosurgery 1998;42:1197-9.
Ulm AJ, Yachnis AT, Brat DJ, Rhoton AL Jr. Pituicytoma: Report of two cases and clues regarding histogenesis. Neurosurgery 2004;54:753-7.
Lonergan GJ, Schwab CM, Suarez ES, Carlson CL. Neuroblastoma, ganglioneuroblastoma and gangliocytoma: Radiologic-pathologic correlation. Radiographics 2002;22:911-34.
Yang B, Yang C, Sun Y, Du J, Liu P, Jia G, et al.
Mixed gangliocytoma-pituitary adenoma in the sellar region: A large-scale single-center experience. Acta Neurochir (Wien) 2018;160:1989-99.
[Figure 1], [Figure 2], [Figure 3]