Acta Neurochirurgica

, Volume 159, Issue 11, pp 2187–2192 | Cite as

Clinical characteristics of pituitary adenomas with radiological calcification

  • Toshihiro Ogiwara
  • Alhusain Nagm
  • Yasunaga Yamamoto
  • Takatoshi Hasegawa
  • Akihiro Nishikawa
  • Kazuhiro Hongo
Original Article - Brain Tumors

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Pituitary adenoma Calcification Transsphenoidal surgery Surgical strategy 

Introduction

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.

Results

Our patients ranged in age from 16 to 79 (mean, 49.5) years, and 91 of them were female (56.9%). Eighty-one patients had hormone-secreting pituitary adenomas (growth hormone-secreting pituitary adenoma, n = 39; Cushing’s disease, n = 8; prolactinoma, n = 30; thyroid-stimulating hormone-secreting pituitary adenoma, n = 1; mixed growth hormone and prolactin-secreting pituitary adenoma, n = 3), and 79 patients had nonfunctioning pituitary adenoma. The 160 cases included 9 consecutive patients (5.6%) with calcified pituitary adenoma on preoperative neuroimaging studies (Table 1). The mean age of these nine patients was 40.4 (20–75) years. Among the participants (five males and four females), four patients had hormone-secreting pituitary adenomas [1 of the 30 cases (3.3%) with prolactinoma and all 3 cases (100%) with both growth hormone- and prolactin-secreting pituitary adenoma] and five [of 79 patients (6.3%)] had nonfunctioning pituitary adenomas. There were no cases with pure growth hormone-secreting pituitary adenoma, thyroid-stimulating hormone-secreting pituitary adenoma or Cushing’s disease. The mean tumor diameter was 30.4 mm (range 7–44 mm). Three of five cases of nonfunctioning pituitary adenoma were confirmed to have hyperprolactinemia due to the stalk effect. Two cases of calcified pituitary adenomas (cases 1 and 9) had soft granular intratumoral calcifications, pituitary stones (Fig. 1) [12]. Regarding the texture of calcification, in a single patient (11%) (case 6), evidence of thick hard capsular calcification was seen surrounding the soft tumor component (Fig. 2: a,b). The other eight cases (89%) had soft calcifications, including two cases with pituitary stones and six with small eggshell-like calcified structures surrounding the tumor. Among patients with soft calcifications, in three cases (cases 3, 4 and 9, pituitary stones), the intraoperative findings revealed that pituitary adenomas with calcification were soft with granular texture interspersed with soft tumor components. In all patients (100%) successful tumor resection was achieved in the usual manner via the transsphenoidal or transcranial approach without any complications (Fig. 3). Total tumor resection was accomplished in cases with soft calcified pituitary adenomas (89%). On the other hand, subtotal removal of the adherent calcified component (to avoid subsequent potential complications) was selected in the patient with hard thick capsular calcification (11%) (Fig. 2: c,d). There were no cases in which special intraoperative techniques were needed because of calcification of the pituitary adenoma (Table 1).
Table 1

Summary of clinical data in nine patients with surgical resection of calcified pituitary adenoma

Case

Age (years)

Sex

Diagnosis

Tumor size (mm)

Calcification type

PRL (ng/ml)

Approach

Hardness of tumor

1

33

M

NFPA

35

Stone

22.3

TCS

Soft

2

47

F

NFPA

30

Capsular

99.8

TSS

Soft

3

22

M

PRL

40

Capsular

357.4

TSS

Soft (granular)

4

55

M

NFPA

33

Capsular

17.6

TSS

Soft

5

20

F

GH-PRL

19

Capsular

N.A.

TSS

Soft (granular)

6

48

M

NFPA

33

Capsular

6.1

TSS

Hard

7

75

F

NFPA

33

Capsular

5.3

TSS

Soft

8

35

M

GH-PRL

44

Capsular

143.0

TSS

Soft

9

29

F

GH-PRL

7

Stone

32.8

TSS

Soft (granular)

NFPA, nonfunctioning pituitary adenoma; PRL, prolactinoma; GH-PRL, both growth hormone and prolactin-secreting adenoma; TCS, transcranial surgery; TSS, transsphenoidal surgery; granular, granular gritty texture; soft, easily suckable; N.A., not available

Fig. 1

Preoperative neuroimaging (case 9) showing the pituitary stone in the right side of sellar turcica (red arrows). There is no enlargement of the sellar turcica (CT: a, b; MRI: c, d)

Fig. 2

Preoperative CT scan (case 6) revealed an unusual eggshell cap-like calcified structure surrounding the lower part of the sellar tumor with evidence of thick capsular calcification surrounding the top of the tumor (a, b). Postoperative CT confirmed subtotal removal of the tumor with significant downward shifting of the upper hard calcified component following sufficient decompression (c, d)

Fig. 3

Postoperative CT (a) and MRI (b) (case 9) showing total resection of the pituitary stone

Discussion

Radiographically proven calcifications in pituitary adenomas were reported with prevalence rates of 0.2% to 14% [5.6% based on our data (Fig. 4)] [3, 4, 5, 7, 11, 12]. Pituitary calcifications are radiologically classified into two types: dense or granular calcification within the tumor called a pituitary stone (Fig. 1) and capsular or linear calcification surrounding the tumor (Fig. 2) (Table 1) [4, 5, 12, 13]. These calcification patterns can be helpful for distinguishing between various calcified pituitary tumors [6]. In this study, we investigated the pituitary calcification based on our sensitive CT protocol (Figs. 1, 2 and 3) in correlation with the intraoperative findings (Fig. 5).
Fig. 4

Inclusion and exclusion criteria are shown. Among these 160 patients, 9 cases (5.6%) with proven radiological calcification on preoperative neuroimaging examinations were included in this study

Fig. 5

Calcifications were interpreted according to two major items. The first was according to the pattern (blue boxes) based on the neuroimaging characteristics and including two major categories: (1) pituitary stone and (2) capsular (eggshell-like or thick) calcification surrounding the tumor. The second was according to the texture (red boxes): (1) soft or (2) hard calcifications were identified based on the intraoperative findings

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 [5]. Nonsecreting and gonadotroph adenomas are considered to be seldom calcified [2]. 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 [12]. 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.

Conclusions

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.

Notes

Compliance with ethical standards

Disclosures

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.

Patient consent

The patient/next of kin/guardian has consented to the submission of this Original Article for submission to the journal.

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Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  • Toshihiro Ogiwara
    • 1
  • Alhusain Nagm
    • 1
    • 2
  • Yasunaga Yamamoto
    • 1
  • Takatoshi Hasegawa
    • 1
  • Akihiro Nishikawa
    • 1
  • Kazuhiro Hongo
    • 1
  1. 1.Department of NeurosurgeryShinshu University School of MedicineMatsumotoJapan
  2. 2.Department of NeurosurgeryAl-Azhar University Faculty of Medicine-Nasr cityCairoEgypt

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