Craniopharyngiomas

Niki Karavitaki, Simon Cudlip, Christopher B. T. Adams and John A. H. Wass

Department of Endocrinology (N.K., J.A.H.W.), Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford OX3 7LJ, United Kingdom; and Department of Neurosurgery (S.C., C.B.T.A.), Radcliffe Infirmary, Oxford OX2 6HE, United Kingdom

Endocrine Review, June 2006, 27(4): 371-397

Craniopharyngiomas are rare tumors with an overall incidence of 0.13 cases per 100,000 person-years . They account for 2–5% of all the primary intracranial neoplasms and 5.6–15% of the intracranial tumors in children . Although they are the commonest lesions to involve the hypothalamopituitary region in childhood populations, almost half of the total cases are diagnosed in adults . They may be detected at any age, even in the prenatal and neonatal periods , and a bimodal age distribution has been shown, with peak incidence rates in children of ages 5–14 yr and adults of ages 50–74 yr . In population-based studies from the United States and Finland, no gender differences have been found . Craniopharyngioma cases have been

reported within two families , but it is not as yet clear whether there is any underlying

genetic susceptibility. This seems unlikely with the numbers involved.

Epidemiology

FIG. 1. Adamantinomatous craniopharyngioma. A, The epithelium consists of palisaded basal layer of cells (arrowhead), the intermediate stellate reticulum, and a layer of flattened, keratinized squamous cells. Nodules of "wet" keratin (arrow) are a distinctive feature (HE. x 10). B, Gliotic reaction rich in Rosenthal fibers (arrow) in the surrounding parenchyma (HE. x 40). [Courtesy of Dr O. Ansorge, Neuropathology Department, Radcliffe Infirmary, Oxford, UK.].

FIG. 2. Papillary craniopharyngioma. The characteristic epithelium in this histological type consists of mature squamous epithelium forming pseudopapillae downward into the underlying tissues. The absence of adamantinomatous epithelium and keratinizing nodules is characteristic (A, HE. x 5; B, HE. x 20). [Courtesy of Dr. O. Ansorge, Neuropathology Department, Radcliffe Infirmary, Oxford, UK.].

Feature

Gross pattern of epithelium

Keratin

Keratohyaline granules

Mucinous cells

Ciliated cells

Hyalinized stroma

Calcification

Necrosis

Cholesterol

Adamantinomatous craniopharyngioma

Complex adamantinomatous

Billowy 'wet' keratin forming discrete nodules

Absent

Rare

Absent

Absent

Frequent

Frequent

Frequent

Papillary craniopharyngioma

Papillary squamous

Individual cells, nodules of keratinized cells

Absent

Frequent

Rare

Frequent

Rare

Absent

Rare

Rathke’s cleft cyst

Simple columnar or cuboidal; focally squamous1

Absent

Absent

Frequent

Frequent

Absent

Absent

Absent

Absent

Epidermoid cyst

Stratified squamous

Flaky, laminated

Frequent

Absent

Absent

Absent

Absent

Absent

Absent

TABLE 1. Comparative pathological features of craniopharyngiomas and related lesions

No. of patients

57

67

241

74

61

56

121

122

75

119

Age (yr)

All < 16

All < 16

38 < 18

All < 21

26 < 19

32 16≦

29 < 16

All <16.4

41 < 16

Ref.

12

96

40

86

145

44

89

90

15

74

Range

Headache (%)

81

66

78

50

77

7 adults, 15 children

74

53

65

56 adults, 78 children

7–81

Nausea/vomiting (%)

68

37

34

43

21

49

26 adults, 54 children

21–68

Papillo-edema (%)

53

31

25

29

10

16

32

6 adults, 29 children

6–53

Cranial nerves palsy

(%)

6

20

8 children

2

3

15

9 adults, 27 children

2–27

Ataxia/unsteadine

ss (%)

18

17

3 adults, 7 children

3–18

Cognitive dysfunction

(%)1

32

36

20 adults, 8 children

10

13

17 adults, 10 children

3–36

Decreased consciousness/co

ma (%)

7

3

29

8

16

4 adults, 10 children

3–29

Optic atrophy

(%)

20

15

40

40

14 adults, 5 children

5–40

Visual field defects (%)

58

35

713

72

594

60 adults, 54 children

62

79

44

60 adults, 46 children

35–79

TABLE 2A. Most common presenting clinical manifestations of craniopharyngiomas in children and adults

No. of patients

57

67

241

74

61

56

121

122

75

119

Age (yr)

All < 16

All < 16

38 < 18

All < 21

26 < 19

32   16

29 < 16

All < 16.4

41 < 16

Ref.

12

96

40

86

145

44

89

90

15

74

Range

Decreased visual acuity or visual

deterioration (%)

58

47 adults,50 children

62

80

47

40 adults, 39 children

39–80

Growth failure1 (%)

39

7 (42% with retarded bone

age)

93

25

8

17

45

33

32

7–93

Failure of sexual

development1 (%)

20 (of pubertal children)

4

14

5

24

4–24

Hypo-gonadism (adults)

(%)

85

10

40

28

10–85

Poor energy (%)

23

32 adults, 22 children

22–32

Somnolence (%)

9

20

20

10 adults, 5 children

5–20

Anorexia/poor weight gain or

weight loss (%)

31

8 adults, 20 children

8–31

Obesity or weight

gain (%)

4 children

8

15

13 adults, 5 children

4–15

Polyuria/polydipsia

(%)

9

12

6

23

13

3 adults

12

18

28

15 adults, 15 children

3–28

TABLE 2B.

No. of patients

42

74

61

35

75

143

18

121

Age (yr)

All   17.2≦

38 < 18

All < 21

13 < 19

All < 16.3

30 < 16

No age range reported

42 < 16

Ref.

205

86

145

87

204

88

190

74

Range

GH deficiency

13/18 (72)

12/34 (35)

27/35 (77)

13/15 (87)

59/82 (72), 17/23 in children (74)

7/18 (39)

21/22 (95), 15/15 in children (100)

35–100

FSH/LH deficiency1

3/8 (38)

27/33 (82)

3/6 (50)

96/143 (77), 10/11 in children (91)

10/18 (56)

40/54 (74)2

38–91

ACTH deficiency

4/17 (24)

18/74 (24)

7/34 (21)

12/35 (34)

16/50 (32)

45/143 (32), 8/30 in children (27)

9/18 (50)

40/65 (62), 15/22 in children (68)

21–68

TSH deficiency

7/29 (24)

31/74 (42)

7/34 (21)

13/35 (37)

20/62 (32)

35/143 (25), 6/30 in children (20)

7/18 (39)

29/81 (36), 7/28 in children (25)

20–42

Hyper-prolactinemia

7/29 (24)

12/37 (32)

59/143 (41), 5/30 in children (17)

6/18 (33)

24/44 (55)2

17–55

DI

4/24 (17)

8/74 (12)

8/34 (23)

13/35 (38)

22/75 (29)

23/143 (16), 3/30 in children (10)

1/18 (6)

19/104 (18), 7/32 in children (22)

6–38

TABLE 3. Pituitary hormone deficits and hyperprolactinemia at presentation in children and adults with craniopharyngioma

FIG. 3. Skull x-ray film: craniopharyngioma causing enlarged sella with sellar destruction and suprasellar flocculonodular calcification. [Reprinted from A. S. Kashyap: Postgrad Med J 76:513–514, 2000 with permission from the BMJ Publishing Group.].

FIG. 4. Axial unenhanced (A) and contrast-enhanced (B) CT demonstrating an inhomogeneously enhancing soft-tissue mass (straight arrows) in the suprasellar cistern extending into the third ventricle. Specks of calcium (curved arrows) and small cysts are also shown. [Reprinted with permission from O. P. Eldevik et al.: Am J Neuroradiol 17:1427–1439, 1996 . © American Society of Neuroradiology.]

FIG. 5. Axial CT brain demonstrating a suprasellar lesion with coarse calcification and dilatation of the temporal horns of the lateral ventricles. [Reprinted from D. R. Warakaulle and P. Anslow: Clin Radiol 58:922–933, 2003, with permission from the Royal College of Radiologists.]

FIG. 6. Sagittal T1-weighted MRI noncontrast (A) and contrast-enhanced (B)

showing an intra-/suprasellar craniopharyngioma with a hyperintense cystic peripherally enhancing mass and a small solid inhomogeneously enhancing portion. [Reprinted with permission from S. Sartoretti-Schefer et al.: Am J Neuroradiol 18:77–87, 1997 . © American Society of Neuroradiology.]

FIG. 7. Sagittal noncontrast (A) and contrast-enhanced (B) T1-weighted MRIs

demonstrating a hypointense suprasellar tumor with peripherally enhancing cystic areas and an inhomogeneously enhancing solid tumor part. [Reprinted with permission from S. Sartoretti-Schefer et al.: Am J Neuroradiol 18:77–87, 1997 . © American Society of Neuroradiology.]

FIG. 8. Unenhanced (A) and contrast-enhanced (B) sagittal T1-weighted MRIs

showing an intra-/suprasellar multilobular cystic craniopharyngioma (straight arrows) with areas of calcification (curved arrows). [Reprinted with permission from O. P. Eldevik et al.: Am J Neuroradiol 17:1427–1439, 1996. © American Society of Neuroradiology.]

FIG. 9. Nonenhanced (A) and contrast-enhanced (B) coronal T1-weighted MRIs

demonstrating an intra-/suprasellar craniopharyngioma extending into the third ventricle (two-toned arrows) with multiple calcifications (curved arrows) and small cysts (white arrows). [Reprinted with permission from O. P. Eldevik et al.: Am J Neuroradiol 17:1427–1439, 1996 . © American Society of Neuroradiology.]

Diagnosis Characteristics on CT and/or MRI

Rathke’s cleft cyst Small, round, purely cystic lesion lacking calcification (58 ). On CT, typically a homogeneous, hypodense mass, which usually does not enhance. The MRI signal returned by the cyst is variable depending on its content [that of CSF or of a protein-rich fluid or of altered hemorrhage (113 115 )]. Some contain a nonenhancing intracystic proteinaceous nodule thought to be indicative of the diagnosis (249 ).

Dermoid cyst On CT, round or lobulated, often with negative density values and foci of calcification; no contrast enhancement or surrounding edema. On T1-weighted MRI,

high signal, due to the lipid content (250 ).Epidermoid cyst On CT, a lobulated mass with attenuation values similar to CSF. Calcification may be

present. The MRI signal characteristics are usually similar to CSF. It does not enhance (250 ).

Pituitary adenoma On CT, macroadenomas are isodense or hypodense relative to brain tissue with variable patterns of enhancement after contrast administration. Calcification may be seen occasionally. On MRI, they have homogeneous low intensity on T1-weighted

images and homogeneous enhancement after contrast administration that is less intense than the enhancement in the adjacent pituitary. Cysts or areas of necrosis cause foci of moderate hypointensity on T1- and hyperintensity on T2-weighted

sequences, and heterogeneous enhancement with gadolinium. Hemorrhage in the subacute or chronic phase shows high signal on T1-weighted images. On CT,

microadenomas show little inherent contrast to the normal pituitary tissue, and iv contrast demonstrates nonenhancement against a background of normal gland enhancement. On MRI, they are hypointense on T1-weighted sequences, and this

contrast may or may not be amplified after gadolinium (113 249 ).

TABLE 4. Differential diagnosis of craniopharyngioma in CT or MRI

Germinoma On CT, well-delineated masses, usually hyperdense on noncontrast scans. Calcification is common. Most cases show strong homogeneous enhancement. On MRI, isointense on T1-weighted images and iso-to-hyperintense on T2-weighted

images. Enhancement is intense and often heterogeneous (251 ).

Hamartoma Typically, a pedunculated mass, isodense on CT and isointense on MRI, relative to gray matter. It does not calcify or enhance after administration of contrast media (113 ).

Suprasellar aneurysm On unenhanced CT, slightly denser than the cerebral tissue, or if a large clot is present, substantially denser; it shows enhancement after contrast administration. On MRI, flowing blood within the aneurysm usually has a characteristic 'signal void,' often associated with regions of high signal intensity on T1-weighted images,

suggesting blood. The presence of a clot or turbulent flow within the aneurysm may create a variety of different patterns. Angiography will confirm the diagnosis (249 252 ).

Arachnoid cyst Cystic lesion with a clearly defined border. The density on CT and the signal intensity on MRI are similar to that of the CSF. It does not show calcification and does not enhance after contrast administration (113 ).

Suprasellar abscess On CT, a central area of hypodensity surrounded by a ring of increased density, which shows marked enhancement after iv contrast material. On MRI, the T1-

weighted images show a marked hyperintense lesion with significant enhancement of the abscess wall after contrast administration. The T2-weighted scans show

hyperintensity of the abscess contents surrounded by an area of increased signal intensity indicating edema (253 ).

Langerhans cell histocytosis Hypothalamus and pituitary are frequent sites of involvement, showing enhancing mass lesions on CT or bright, gadolinium-enhancing areas on MRI. An enhancing, thickened infundibulum may also be seen (252 254 ).

Sarcoidosis On CT, isodense lesion with contrast enhancement and generally without surrounding edema or calcification. On MRI, more variable appearance, but usually hyperintense on T2-weighted images (113 254

).

Tuberculosis On contrast-enhanced CT, an enhancing mass with hypodense central necrosis and hypodense surrounding edema. A T1 gadolinium-

enhanced MRI scan shows a strong rim enhancement, whereas a T2

gadolinium-enhanced scan shows hyperintense vasogenic edema, hypointense granuloma ring, and a hyperintense central necrosis (253 ).

Hypothalamic or optic pathway glioma

On MRI, sharply marginated homogeneous suprasellar mass, clearly separate from the pituitary gland. Usually hypointense or isointense with gray matter and may or may not enhance. It is rarely calcified and usually lacks a cystic component (249 255 ).

Meningioma On CT, isodense to slightly hyperdense dural-based lesion, with homogeneous enhancement after contrast administration. Minimal to extensive peritumoral edema and calcification may be present (256 ). On MRI, usually an isointense with gray matter lesion in both T1- and

T2-weighted images. It shows dense uniform enhancement after

contrast administration. Typical are the presence of a thickened dura in the region of the meningioma ('dural tail sign'), bony hyperostosis adjacent to the lesion, and normal sellar dimensions (249 ).

Recurrence rates at 10-yr follow-up (%)

RT

23

0

Surgery + RT

Adults 51, children 22 (SR, PR, biopsy + aspiration)

23 (biopsy or aspiration), 12 (PR or SR), 0 (GTR)

14 (biopsy-aspiration-VP shunt-combination of the above-SR-GTR)

63 (SR)

Details of RT

Mean dose adults: 5700 rads (4000–6900) in 4–8 wk; children: 5500 rads (5000–6000) in 5–7 wk

Median dose: 56 Gy (6–70) in 24–34 daily fractions (32% of patients) in 5–7 wk; 50 Gy (50–56) in 30–33 daily fractions (68% of patients) in 6–7 wk

Median dose: 5464 cGy (5040–6598) in 180–200 cGy/d fractions over a median of 43 d (31–55)

5000–5500 cGy, no further details reported

Median dose: 50 Gy (40–60)

Ref.

107 1

132 2

145 3

44 4

123 5

118 6

111 7

No. of patients

109

173

61

56

57

73

115

Age (yr)

43 < 16

77 < 16

All   21

26 < 21

7 < 18

All < 16.4

29 Children

GTR

Adults 84, children 53

17

0

22

19

Limited surgery (PR/SR)

Adults 90, children 93 (SR)

69 (SR + GTR)

50 (SR)

33 (SR), 25 (PR)

72

51 (SR), 84 (PR)

Follow-up period, follow-up duration (range)

1950–1977, no data on follow-up duration

1950–1986, median 12 yr (0.08–35)

1970–1990, median 10 yr (2–20.5)

1981–1991, mean 49 months (7–187)

No data on follow-up period, mean 6.5 yr (2.5–15.5)

1973–1994, mean 6.5 yr

1983–1997, median 55.5 months (0.07–175)

TABLE 5. Recurrence rates in patients with craniopharyngioma treated by various modalities

19

62

26

34

53

0

59 (SR)

49 (SR), 77 (PR)

100

78 at 2.5 yr (SR)

62 (PR)

89 8

133

90 9

143

144 10

74 11

Ref.

121

36

122

25

71

103

No. of patients

31   16≦

All < 16

29 < 16

All < 16

All 1.5–24.8

37 < 16

Age (yr)

Recurrence rates at 10-yr follow-up (%)

Mean dose: 5381 rads (4400–6480)

No details of RT reported

Median dose: 54 Gy (44–55.8)

Median dose: 5000 cGy (4000–5400, apart 1 patient with 3500), 25–30 fractions (apart 2 patients with 13 fractions)

Details of RT

1974–1991, no data on follow-up duration

1986–1998, 52 months (1–149)

1975–2000, 7 yr (0.4 month–21 yr)

1983–1996, median 10 yr (3–16)

1974–2001, median 7.6 yr

1964–2003, mean 94 months (0.3–468)

Follow-up period, follow-up duration (range)GTR

10 (SR)

16 (SR)

0 (GTR), 23 (PR)

Limited surgery (PR/SR)

Surgery + RT RT

TABLE 5. Recurrence rates in patients with craniopharyngioma treated by various modalities

FIG. 10. Treatment algorithm for craniopharyngiomas