European Journal of Cardiovascular Medicine

A 60-year-old female presented with two years duration history of insidious onset and gradually progressive diminution of vision in both eyes being more severe on the left side. There was no history suggestive of raised intra-cranial pressure like nausea, vomiting, early morning headache, double vision or lethargy. On examination, she had left side relative afferent pupillary defect (RAPD), her visual acuity was 6/9 in nasal field of right side and inaccurate projection of rays with hand movement close to face was present on left side. Bitemporal hemianopia was present (on confrontation test), extra-ocular muscle movements were full and free. On Fundoscopy, she had features of primary optic atrophy on left side; no other neurological deficit was found. Perimetry revealed temporal hemianopia on right side. Left side could not be evaluated due to failure of adequate stimulus perception.

On CT scan (Fig 1a,b & c), there was large solid-cystic lesion occupying the sellar-suprasellar region with extension into the right side sphenoid sinus associated with complete destruction of the sellar anatomy and erosion of the sellar floor. Most remarkably, there was associated curvi-linear peripheral calcification in the postero-superior aspect.

Fig 1A,B & C: Axial, coronal and sagittal CT scan images showing curvilinear/egg shell calcification in a large solid-cystic sellar-suprasellar lesion.

On CEMRI (Fig 2A, B & C), there was a large solid-cystic sellar–suprasellar mass which was hypointense on T1 and enhanced on contrast T1 images with optic chiasm displaced postero-superiorly.

Fig 2a, b & c: Contrast enhanced MRI images showing large solid-cystic enhancing sellar-suprasellar mass lesion with optic chiasm displaced postero-superiorly. Imaging features were those of Craniopharyngioma. 

Accordingly, she was taken up for transcranial surgery via a left pterional craniotomy. Per-op findings revealed a large, yellowish white tumor; fleshy in appearance and consistency; moderately vascular, suckable in nature; extending from the floor of sphenoid sinus and occupying the sellar-parasellar space with suprasellar extension causing posterior and superior displacement of both optic nerves and the chiasm; significant compression of both optic nerves was noted; tumor capsule was encasing both carotid arteries. Satisfactory decompression of the optic apparatus was achieved and gross total excision was done. Intra-op frozen study was suggestive of pituitary macroadenoma. Post-op recovery was uneventful and patient showed significant improvement in her visual status. Final Histopathology was concluded as pituitary adenoma (Fig 3a, b & c) which included Immunohistochemistry evaluation in the form of Synaptophysisn and Chromogranin.

Fig 3A,B & C: (H & E) showing monomorphous tumor cells arranged in nests, gyriform pattern, cords and rosettes like arrangement. Cells show abundant eosinophilic granular cytoplasm, round nuclei, stippled chromatin and inconspicuous nucleoli without evidence of necrosis, nuclear pleomorphism or mitosis. These are features of pituitary adenoma.

 Fig 3b: Synaptophysin IHC staining positivity suggestive of pituitary adenoma

 Fig 3c: Chromogranin IHC staining positivity suggesting pituitary adenoma

Physiological intracranial calcification is most commonly found in basal ganglia, pineal gland, falx and choroid plexus⁵. Physiological calcification are commonly punctate in appearance and seldom measure greater than 10 mm⁵. Pathological states known to induce calcification are trauma, surgery, irradiation, parathyroid disorders and various tumours^5,6. The differential diagnosis of lesions associated with calcification in the sellar/parasellar region includes craniopharyngioma, meningioma, aneurysm, optic pathway glioma, germ cell tumours and rarely Rathke’s cleft cyst⁵. Craniopharyngioma is the most common lesion in this region which shows both cystic changes and calcification ^3,5. Calcification associated with pituitary adenoma is relatively rare, with a reported prevalence in lterature varying between 0.2 and 2%^4,6.There are three types of calcification on the basis of radiological appearance. These are curvilinear/capsular or egg shell type, dense/nodular type and ‘pituitary stone’ type⁵. A curvilinear pattern has been suggested to be a feature associated with pituitary adenomas, in contrast to the nodular/dense pattern which is more commonly observed in craniopharyngiomas^5,6. The pathophysiological mechanism of calcification in pituitary adenomas is because of dystrophic calcification due to progressive tumour growth and associated ischaemic effects. This may also lead to osteoid metaplasia when well-differentiated lamellar bone tissue is identified histologically which are seen as pituitary stones on imaging ^3,5. Small foci of calcification are found in 10–15% of pituitary adenomas which may appear microscopically as psammoma bodies^4,5. The other mechanism proposed is that calcification is induced by secondary degenerative changes as a sequel to silent pituitary apoplexy or intra-tumoral hemorrhage⁵.

Heterotopic calcification secondary to tumour compression and increased intrasellar pressure is also thought as alternate explanation for pituitary calcification⁷. The autocrine and paracrine effects of PRL, GH, VEGF and osteocalcin may also induce calcification⁷. It is important to recognise the presence and also the type of calcification in a sellar-parasellar mass as it may influence the choice of surgical approach^1,2,6. In previously reported cases, surgery was carried out via a transsphenoidal route, but these cases had a lesser extent of calcification, smaller tumour size and limited lateral or suprasellar extension. Calcification can occur in any type of pituitary hormone-producing adenoma⁵. Intense hormonal activity may correlate with the development of intratumoral calcification⁵. Most common are Prolactin-producing adenomas because of their higher incidence⁵.It is of paramount significance to differentiate pre-operatively between Craniopharyngioma and Pituitary macroadenoma, especially with significantsolid component and suprasellar extension, to make decisions regarding surgical approach^1,2. Only 11 cases have been described in literature (which comprised of  five patients with prolactinomas, three patients with growth hormone (GH)-secreting adenomas , two patients with TSH production and one patient with gonadotrophin-secreting tumour) where pituitary adenoma was associated with macroscopic calcification⁵. More than 95% of pituitary adenoma cases can be safely and completely removed via trans-sphenoidal route whereas trans-cranial route is the preferred choice for Craniopharyngiomas⁶. Gross total resection may not always be feasible when there is dense calcification in large pituitary adenomas. In such cases, adjunct treatment in the form of medical therapy and/or radiotherapy are usually required to achieve biochemical remission⁵.

Our case confirms the possible rare occurrence of combined gross calcification in non-functioning pituitary macroadenomas and cystic change in pituitary adenomas. It also highlights the importance of thorough preoperative assessment with imaging in such lesions before deciding the surgical approach. Gross total resection may not be feasible in heavily calcified large pituitary adenomas. In such cases, adjunct treatment with radiation may be required ⁵.

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