Clinical characteristics of pituitary adenomas with radiological calcification
Radiographic detection of calcification in pituitary adenoma is relatively rare, and the clinical characteristics of pituitary adenoma with calcification remain unclear. Herein, the clinical characteristics of pituitary adenoma with radiological calcification were investigated.
A total of 160 patients who underwent surgical resection of pituitary adenomas between February 2004 and December 2016 were reviewed. Eighty-one patients had hormone-secreting pituitary adenomas, and 79 patients had nonfunctioning pituitary adenoma. Among these 160 patients, cases with radiological calcifications on preoperative neuroimaging were included in this study, and clinical characteristics with intraoperative findings were analyzed, retrospectively.
Pituitary adenoma with calcification on preoperative neuroimaging was observed in only nine cases (5.6%). The study population consisted of these nine patients with nonfunctioning pituitary adenoma (n = 5), mixed growth hormone and prolactin-secreting pituitary adenomas (n = 3), and a prolactinoma (n = 1). In 89% of cases (n = 8), calcified pituitary adenoma was soft enough for suction despite the presence of a granular gritty texture intraoperatively. Besides, in a single patient (11%), evidence of hard thick capsular calcification was seen surrounding a soft tumor component; however, it did not interfere with adequate removal of the soft part, and tumor resection was possible in all cases without any complications.
Pituitary adenoma presenting with calcification is relatively rare, but should be kept in mind to avoid making a wrong preoperative diagnosis. As not all pituitary adenomas with calcification are hard tumors, preoperative radiological calcification should not affect decision-making regarding surgical indications.
KeywordsPituitary adenoma Calcification Transsphenoidal surgery Surgical strategy
The most common sellar-region lesion with calcification is craniopharyngioma, while radiographic detection of calcification in pituitary adenoma is relatively rare. This distinguishing finding is useful for differentiation from pituitary adenoma and other parasellar lesions. The incidence of calcification in pituitary adenoma on imaging findings varies from only 0.2% to 14.0% [3, 4, 5, 7, 11, 12]. As the published literature lacks large series with calcified pituitary adenoma treated by surgery, the clinical aspects of this pathology remain to be elucidated [1, 2, 5, 6, 7, 11, 12, 13, 14]. It is important to clarify whether the presence or absence of calcification is associated with surgical difficulty or not. This study was performed to clear up the clinical characteristics of pituitary adenoma with radiological calcification.
Materials and methods
We retrospectively analyzed our series of 160 consecutive patients who underwent surgery for pituitary adenomas between February 2004 and December 2016 at Shinshu University Hospital. All surgeries were performed via the transsphenoidal or transcranial approach. Post-radiotherapy cases and scans with artifacts or other non-calcified hyperdense materials were excluded from the study. The definitive diagnosis was based on histopathological evaluation. Among these 160 patients, 9 cases (5.6%) with proven radiological calcification on preoperative neuroimaging examinations were included in this study, and their clinical characteristics with intraoperative findings were analyzed retrospectively (Fig. 4).
Computed tomography (CT) protocol and criteria for determining pituitary calcification
In all included patients, from 2004 to 2016, the criteria for determining pituitary calcification were evaluated based on a well-designed CT protocol as follows: In the period between 2004 to 2008, with a LightSpeed Ultra 16-column CT scanner, thin-cut sellar imaging (0.625 mm) was obtained with a provided matrix 512 × 512. From 2009 to 2016, the LightSpeed VCT Vision 64-column CT scanner was used to provide the same thin-cut sellar imaging with the same parameters.
Based on CT with the DICOM viewer format, calcifications were meticulously assessed by an experienced evaluating investigator (second author: AN) who was blinded to the patients’ clinical data [8, 9]. To avoid subjective errors, scans with artifacts (such as motion or metal artifacts), blood, amyloid or other hyperdense materials were excluded. A scaling evaluation table was designed based on the DICOM pixel map to be completed by the rater. Regions of interest (ROIs) were selected and defined on a slice-by-slice basis. The calcification volumes were calculated by multiplying the (slice thickness + gap) term by the total lesion area. Calcifications were interpreted according to two major items (Fig. 5). The first was according to the pattern, which was based on the neuroimaging characteristics and included two major categories: (1) pituitary stone and (2) capsular (eggshell-like or thick) calcification surrounding the tumor [4, 5, 12, 13]. The considerable differences in the calcification volumes were compared based on the pre- and postoperative CT scans. The second was according to the texture: (1) soft or (2) hard calcifications were identified based on the intraoperative findings.
Diagnostic protocol of the included pituitary adenomas
The final diagnoses of various pituitary adenomas were made based on histopathological and immunohistochemical studies.
Summary of clinical data in nine patients with surgical resection of calcified pituitary adenoma
Tumor size (mm)
Hardness of tumor
The actual pathogenesis of osteoid metaplasia in pituitary adenomas has yet to be elucidated. Many authors have reported calcifications in prolactinomas and explained hyperprolactinemia by persistence of prolactin granules in the calcified adenomatous tissue [2, 4, 12]. It also appears that calcification can occur in any type of not only prolactinoma but also other pituitary hormone-producing adenomas . Nonsecreting and gonadotroph adenomas are considered to be seldom calcified . Totally or partially calcified lesions could be nonsecreting adenoma with moderate hyperprolactinemia due to pituitary stalk compression [2, 3]. However, there were three cases of calcified pituitary adenoma without hyperprolactinemia in our series. This result suggested that there are other causes of pituitary calcification (inflammatory, apoplexy or insufficient tumor blood supply, which may trigger proliferation of connective tissue that subsequently undergoes osteoid metaplasia) besides hormonal factors [2, 13].
Gross total resection is generally considered difficult to accomplish in cases with extensive pituitary calcification, which dictates further management and follow-up to achieve disease control. Previous reports presented details of cases with calcified pituitary adenoma in which only partial removal was possible because of the hardness of the tumor [1, 14]. In our case 6, despite hard thick capsular calcification, adequate removal of the soft component while intentionally leaving the adherent calcification to avoid subsequent potential complications was possible (Figs. 1, 2). On the other hand, some previous reports presented calcified pituitary adenomas that could be resected completely via the transsphenoidal or transcranial approach [4, 12]. In particular, ossified pituitary stones that were small and located within the sella turcica on the floor could be easily removed by transsphenoidal surgery, as in our case 9 . Furthermore, neuroendoscopy provides an excellent intraoperative view and improves the removal rate of these tumors [10, 13].
Based on our unique analysis of pituitary calcification (Fig. 5), the present study confirmed the possible occurrence of pituitary adenomas with radiological calcification and highlighted the importance of preoperative imaging in evaluating such lesions before surgical resection. Although gross total resection is considered to be technically challenging in heavily calcified adenomas, our results indicated that this is not necessarily the case. Hence, neurosurgeons should not hesitate to perform surgery in patients with calcification in pituitary adenoma.
Pituitary adenoma presenting with calcification is relatively rare, and making the correct preoperative diagnosis for proper management should be kept in mind. Although calcification may be caused by increased serum levels of prolactin, other pathologies, including nonfunctioning pituitary adenoma, can be calcified. As not all pituitary adenomas with calcification are hard tumors, preoperative radiological calcification should not affect decision-making regarding surgical indications.
Compliance with ethical standards
The authors have no personal financial or institutional interests in any of the drugs, materials or devices discussed in the article. All authors, who are members of The Japan Neurosurgical Society (JNS), have registered online Self-reported COI Disclosure Statement Forms through the website for JNS members.
The patient/next of kin/guardian has consented to the submission of this Original Article for submission to the journal.
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