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Ossified somatotropinoma
Surg Neurol 1994;41:143-46
143
Ossified Somatotropinoma Selguk Palaoglu, M.D., Murad Bavbek, M.D., Selguk Peker, M.D., Behsan Onol, M.D., Arzu Sungur, M.D., and Aykut Erbengi, M.D. Departments of Neurosurgery and Pathology, Hacettepe University, School of Medicine, Sihhiye, Ankara, Turkey
Palao~lu S, Bavbek M, Peker S, Onol B, Sungur A, Erbengi A. Ossified somatotropinoma. Surg Neurol 1993;41:143-46. Calcification of p i t u i t a r y adenomas as a histopathologic f i n d i n g is r e p o r t e d in u p to 25% of all d e g e n e r a t e d adenomas. O n the other hand, ossification of these adenomas is an extremely rare finding, w i t h only one reported case, a p r o l a c t i n o m a . Here, we report a case of s o m a t o t r o p i n o m a in a 42-year-old acromegalic female. T h e adenoma, a b o u t 2 cm in diameter, was removed by the transsphenoidal route. Pathologic e x a m i n a t i o n revealed ossification areas in the a d e n o m a and the p a t i e n t showed dramatic progress w i t h relief of acromegaly signs and n o r m a l i z a t i o n of serum g r o w t h h o r m o n e levels. This case seems to be a u n i q u e report of osteoid metaplasia of a somatotropinoma. KEY WORDS: Ossification; Pituitary adenoma; Somatotropinoma
sphenoid sinus (Figure 1). The patient's preoperative serum growth hormone level was high (18.3 ng/mL) (Table 1). Intravenous digital subtraction angiography displayed no abnormality.
Surgery Transnasal transsphenoidal surgery was performed. A hard, solid tumoral mass about 2 x 1.5 cm in diameter was seen in the sella turcica that had eroded the sellar floor and, after dissection from the surrounding tissues, was removed.
Pathologic Findings Hematoxylin and eosin staining revealed that tumor cells were generally chromophobic with small round nuclei T a b l e 1. Hormone Levels
Bone formation with osteoid metaplasia in pituitary adenomas has rarely been demonstrated. Mukada et al [4] in 1987 reported a case of ossified prolactinoma. Here, we report a case of somatotropinoma showing osteoid metaplasia.
Case R e p o r t A 42-year-old female patient complained of headache and enlargement of her hands and feet during the last 4 years. For 6 years she had hypertension that was controlled by medication. Physical examination revealed acromegaly with a large bulbous nose, prominent supraorbital ridges, protruding mandibula, enlarged hands and feet, and harsh voice. Neuroophthalmologic examination was normal. Sella spot graphy showed calcification in the sella turcica and computed tomography (CT) revealed a calcified intrasellar mass extending into the
Address reprint requests to: Selguk Palaoglu, M.D., Department of
Neurosurgery, Hacettepe University, School of Medicine, Sihhiye, 06100, Ankara, Turkey. Received January 8, 1993; accepted May 25, 1993. © 1994 by ElsevierScienceInc.
Preoperative Hormone Levels Thyroid stimulating hormone (N < 5 v.U/mL) Follicle stimulating hormone (N 15-90 mIU/mL) Luteinizing hormone (N 20-80 mIU/mL) Prolactin (N 13-20.8 ng/mL) Growth hormone (N < 5 ng/mL) Adeno cortico tropin hormone (N 10-100 pg/mL)
0.35 ~zU/mL 4.85 mIU/mL 5.27 mIU/mL 20.95 ng/mL 18.26 ng/mL 47.1 pg/mL
Postoperative Hormone Levels Thyroid stimulating hormone (N < 5 tzU/mL) Follicle stimulating hormone (N 15-90 mlU/mL) Luteinizing hormone (N 20-80 mIU/mL) Prolactin (N 13-20.8 ng/mL) Growth hormone (N < 5 ng/mL) Adeno cortico tropin hormone (N 10-100 pg/mL)
0.53/zU/mL 51.16 mIU/mL 38.81 mIU/mL 16.06 ng/mL 1.6 ng/mL 62.3 pg/mL
0090-3019/94/$7.00
144
Surg Neurol 1994;41:143-46
Palaoglu et al
A
Figure 1. Preoperative computerized tomography; (A) axial," (B and C) coronal sections demonstrating intrasellar ossified mass extending into the sphenoid sinus.
C and small cytoplasm and in some parts eosinophilic cells with large cytoplasm were identified (Figure 2A). Sections of the specimen nearest the neurohypophysis revealed invasion of the neurohypophysis by the tumor cells. In addition osteoid tissue with osteoblasts and osteocytes with calcium deposits were identified indicating different stages of bone formation (Figure 2B). Immunocytochemistry staining by the peroxidase-antiperoxidase method demonstrated growth hormone positive cells.
(Figure 3). Because the adenoma was accepted as invasive, radiotherapy was administered. The growth hormone serum level decreased to 4.8 ng/mL 6 months later. Fourteen months after surgery the growth hormone level was 1.6 ng/mL and after an oral glucose tolerance test it was 0.07 ng/mL (Figure 4). The anterior lobe hormone levels were normal (Table 1). Magnetic resonance imaging (GE MR Max Plus 0.5 T, USA) SE sagittal and coronal sections with contrast (Gd-DTPA, Schering, Germany) and noncontrast revealed normal pituitary gland without tumor recurrence.
Postoperative Course
The postoperative course was normal and the early serum growth hormone level was 8.1 ng/mL. Postoperative CT revealed total removal of the intrasellar mass
Discussion Metaplasia denotes the change of one type of adult cell or tissue to another. Fibroblasts may become trans-
Ossified Somatotropinoma
Surg Neurol 1994;41:143-46
145
Figure 2. Photomicrographofthetumorandosteoid tissue with calcification (Hematoxylin and eosin × I 15); (B) Photomicrograph of the somatotropin positive cellswith immune peroxidase stain (arrows) (immuneperoxidase × 460).
formed to osteoblasts or chondroblasts to produce bone or cartilage in tissues where it is normally not encountered [3]. For example bone is occasionally formed in soft tissues, particularly in foci of injury. On the other hand osteoid metaplasia in tumor ussues has been reported several times [7,9]. Although bone formation in the human pituitary gland as a result of connective tissue proliferation in advanced fibrosis has been known since Shanklin, osteoid metaplasia in pituitary adenomas has rarely been reported [8]. Thus it was Mukada et al [4] who reported an ossified pituitary adenoma, diagnosed as a prolactinoma in 1987. To our knowledge the present
case report is the first about somatotropinoma showing osteoid metaplasia. Osteoid metaplasia in mesenchymal cells may be caused by inflammatory, chemical, or mechanical stimulation. Although the pathogenesis of such a metaplasia needs to be fully elucidated, chronic stimulation induced by the mass compression of the tumor itself and increased intrasellar pressure seem to be a possible cause in the present case. Mukada et al [4] suggested that in their patient long-term human chorionic gonadotropin-human menopausal gonadotropin treatment might have caused intraadenomatous bleeding and degeneration that provoked ossification. Our case
146
Palaoglu et al
Surg Neurol 1994;41:143-46
and also M u k a d a ' s was identified as calcified intrasellar mass. B u t pathologic examination o f both cases revealed ossification with all stages o f b o n e formation. Thus, the m o r p h o l o g i c findings o f o u r case were different f r o m calcified pituitary adenomas. Radiologic studies have revealed 0 . 3 % to 14% [1] and histologic studies 5 . 4 % to 2 5 % [2] p r e s e n c e o f calcification in pituitary a d e n o m a s that suggests slow g r o w t h o f the neoplasm [2,4]. H o w e v e r , calcifications have also b e e n f o u n d in t u m o r s that were radiologically invasive, obviously having a m o r e aggressive g r o w t h pattern [6]. In the present case the t u m o r was invasive in nature and the patient received radiotherapy. C o n s e q u e n t l y , a s o m a t o t r o p i n o m a showing osteoid metaplasia is pre+ sented and discussed.
Figure 3. Postoperativecomputerized tomography revealing total removal
PREOP 18.3ng/ml
/ I G R O W T H H O R M O N E LEVELS I POSTOP 1 st WEEK 8. lng/ml
~
POSTOP 8 th MONTH
POSTOP 14th MONTH 1.6ng/rnl ~,
4.8njg/ml
AFTER OGTT
Figure 4. Preoperativeand postoperative growth hormone serum levels.
of the mass.
References 1. Cecchini A. Le calcificazioni negli adenomi ipofisari. Minerva Radiol 1968;13:490-5. 2. Cotran SR, Kumar V, Robbins SL. Robbins Pathologic Basis of Disease. 4th ed. Philadelphia: W.B. Saunders Company, 1989:34. 3. Guay AT, Freeman R, Rish BL, Sperber E, Woolf PD. Calcified pituitary tumor with hyperprolactinemia: selective removal by transsphenoidal adenectomy. Fertil Steril 1978;29:585-8. 4. Mukada K, Ohta M, Uozumi T, Arita K, Kurisu K, Inai K. Ossified prolactinoma: case report. Neurosurgery 1987;20:473-5. 5. Rasmussen C, Larsson SG, Bergh T. The occurrence ofmacroscopical pituitary calcifications in prolactinomas. Neuroradiology 1990;31:507-11. 6. Reynier Y, HassounJ, Vittini F, Gambarelli-Dubois D, Vigouroux RP. Fibrosarcomes meninges. Neurochirurgie 1984;30:1-10. 7. Rilliet B, Mohr G, Robert F. Hardy J. Calcifications in pituitary adenomas. Surg Neurol 1981;15:249-55. 8. Shanklin WM. On the presence of calcific bodies, cartilage, bone, follicular concretions and the so-called hyaline bodies in the human pituitary. Anat Rec 1948;102:469-91. 9. Yoneda F, Kagawa S, Kurokawa K: Dystrophic calcifying nodule with osteoid metaplasia of the testis. BrJ Urol 1979;51:413.
143
Ossified Somatotropinoma Selguk Palaoglu, M.D., Murad Bavbek, M.D., Selguk Peker, M.D., Behsan Onol, M.D., Arzu Sungur, M.D., and Aykut Erbengi, M.D. Departments of Neurosurgery and Pathology, Hacettepe University, School of Medicine, Sihhiye, Ankara, Turkey
Palao~lu S, Bavbek M, Peker S, Onol B, Sungur A, Erbengi A. Ossified somatotropinoma. Surg Neurol 1993;41:143-46. Calcification of p i t u i t a r y adenomas as a histopathologic f i n d i n g is r e p o r t e d in u p to 25% of all d e g e n e r a t e d adenomas. O n the other hand, ossification of these adenomas is an extremely rare finding, w i t h only one reported case, a p r o l a c t i n o m a . Here, we report a case of s o m a t o t r o p i n o m a in a 42-year-old acromegalic female. T h e adenoma, a b o u t 2 cm in diameter, was removed by the transsphenoidal route. Pathologic e x a m i n a t i o n revealed ossification areas in the a d e n o m a and the p a t i e n t showed dramatic progress w i t h relief of acromegaly signs and n o r m a l i z a t i o n of serum g r o w t h h o r m o n e levels. This case seems to be a u n i q u e report of osteoid metaplasia of a somatotropinoma. KEY WORDS: Ossification; Pituitary adenoma; Somatotropinoma
sphenoid sinus (Figure 1). The patient's preoperative serum growth hormone level was high (18.3 ng/mL) (Table 1). Intravenous digital subtraction angiography displayed no abnormality.
Surgery Transnasal transsphenoidal surgery was performed. A hard, solid tumoral mass about 2 x 1.5 cm in diameter was seen in the sella turcica that had eroded the sellar floor and, after dissection from the surrounding tissues, was removed.
Pathologic Findings Hematoxylin and eosin staining revealed that tumor cells were generally chromophobic with small round nuclei T a b l e 1. Hormone Levels
Bone formation with osteoid metaplasia in pituitary adenomas has rarely been demonstrated. Mukada et al [4] in 1987 reported a case of ossified prolactinoma. Here, we report a case of somatotropinoma showing osteoid metaplasia.
Case R e p o r t A 42-year-old female patient complained of headache and enlargement of her hands and feet during the last 4 years. For 6 years she had hypertension that was controlled by medication. Physical examination revealed acromegaly with a large bulbous nose, prominent supraorbital ridges, protruding mandibula, enlarged hands and feet, and harsh voice. Neuroophthalmologic examination was normal. Sella spot graphy showed calcification in the sella turcica and computed tomography (CT) revealed a calcified intrasellar mass extending into the
Address reprint requests to: Selguk Palaoglu, M.D., Department of
Neurosurgery, Hacettepe University, School of Medicine, Sihhiye, 06100, Ankara, Turkey. Received January 8, 1993; accepted May 25, 1993. © 1994 by ElsevierScienceInc.
Preoperative Hormone Levels Thyroid stimulating hormone (N < 5 v.U/mL) Follicle stimulating hormone (N 15-90 mIU/mL) Luteinizing hormone (N 20-80 mIU/mL) Prolactin (N 13-20.8 ng/mL) Growth hormone (N < 5 ng/mL) Adeno cortico tropin hormone (N 10-100 pg/mL)
0.35 ~zU/mL 4.85 mIU/mL 5.27 mIU/mL 20.95 ng/mL 18.26 ng/mL 47.1 pg/mL
Postoperative Hormone Levels Thyroid stimulating hormone (N < 5 tzU/mL) Follicle stimulating hormone (N 15-90 mlU/mL) Luteinizing hormone (N 20-80 mIU/mL) Prolactin (N 13-20.8 ng/mL) Growth hormone (N < 5 ng/mL) Adeno cortico tropin hormone (N 10-100 pg/mL)
0.53/zU/mL 51.16 mIU/mL 38.81 mIU/mL 16.06 ng/mL 1.6 ng/mL 62.3 pg/mL
0090-3019/94/$7.00
144
Surg Neurol 1994;41:143-46
Palaoglu et al
A
Figure 1. Preoperative computerized tomography; (A) axial," (B and C) coronal sections demonstrating intrasellar ossified mass extending into the sphenoid sinus.
C and small cytoplasm and in some parts eosinophilic cells with large cytoplasm were identified (Figure 2A). Sections of the specimen nearest the neurohypophysis revealed invasion of the neurohypophysis by the tumor cells. In addition osteoid tissue with osteoblasts and osteocytes with calcium deposits were identified indicating different stages of bone formation (Figure 2B). Immunocytochemistry staining by the peroxidase-antiperoxidase method demonstrated growth hormone positive cells.
(Figure 3). Because the adenoma was accepted as invasive, radiotherapy was administered. The growth hormone serum level decreased to 4.8 ng/mL 6 months later. Fourteen months after surgery the growth hormone level was 1.6 ng/mL and after an oral glucose tolerance test it was 0.07 ng/mL (Figure 4). The anterior lobe hormone levels were normal (Table 1). Magnetic resonance imaging (GE MR Max Plus 0.5 T, USA) SE sagittal and coronal sections with contrast (Gd-DTPA, Schering, Germany) and noncontrast revealed normal pituitary gland without tumor recurrence.
Postoperative Course
The postoperative course was normal and the early serum growth hormone level was 8.1 ng/mL. Postoperative CT revealed total removal of the intrasellar mass
Discussion Metaplasia denotes the change of one type of adult cell or tissue to another. Fibroblasts may become trans-
Ossified Somatotropinoma
Surg Neurol 1994;41:143-46
145
Figure 2. Photomicrographofthetumorandosteoid tissue with calcification (Hematoxylin and eosin × I 15); (B) Photomicrograph of the somatotropin positive cellswith immune peroxidase stain (arrows) (immuneperoxidase × 460).
formed to osteoblasts or chondroblasts to produce bone or cartilage in tissues where it is normally not encountered [3]. For example bone is occasionally formed in soft tissues, particularly in foci of injury. On the other hand osteoid metaplasia in tumor ussues has been reported several times [7,9]. Although bone formation in the human pituitary gland as a result of connective tissue proliferation in advanced fibrosis has been known since Shanklin, osteoid metaplasia in pituitary adenomas has rarely been reported [8]. Thus it was Mukada et al [4] who reported an ossified pituitary adenoma, diagnosed as a prolactinoma in 1987. To our knowledge the present
case report is the first about somatotropinoma showing osteoid metaplasia. Osteoid metaplasia in mesenchymal cells may be caused by inflammatory, chemical, or mechanical stimulation. Although the pathogenesis of such a metaplasia needs to be fully elucidated, chronic stimulation induced by the mass compression of the tumor itself and increased intrasellar pressure seem to be a possible cause in the present case. Mukada et al [4] suggested that in their patient long-term human chorionic gonadotropin-human menopausal gonadotropin treatment might have caused intraadenomatous bleeding and degeneration that provoked ossification. Our case
146
Palaoglu et al
Surg Neurol 1994;41:143-46
and also M u k a d a ' s was identified as calcified intrasellar mass. B u t pathologic examination o f both cases revealed ossification with all stages o f b o n e formation. Thus, the m o r p h o l o g i c findings o f o u r case were different f r o m calcified pituitary adenomas. Radiologic studies have revealed 0 . 3 % to 14% [1] and histologic studies 5 . 4 % to 2 5 % [2] p r e s e n c e o f calcification in pituitary a d e n o m a s that suggests slow g r o w t h o f the neoplasm [2,4]. H o w e v e r , calcifications have also b e e n f o u n d in t u m o r s that were radiologically invasive, obviously having a m o r e aggressive g r o w t h pattern [6]. In the present case the t u m o r was invasive in nature and the patient received radiotherapy. C o n s e q u e n t l y , a s o m a t o t r o p i n o m a showing osteoid metaplasia is pre+ sented and discussed.
Figure 3. Postoperativecomputerized tomography revealing total removal
PREOP 18.3ng/ml
/ I G R O W T H H O R M O N E LEVELS I POSTOP 1 st WEEK 8. lng/ml
~
POSTOP 8 th MONTH
POSTOP 14th MONTH 1.6ng/rnl ~,
4.8njg/ml
AFTER OGTT
Figure 4. Preoperativeand postoperative growth hormone serum levels.
of the mass.
References 1. Cecchini A. Le calcificazioni negli adenomi ipofisari. Minerva Radiol 1968;13:490-5. 2. Cotran SR, Kumar V, Robbins SL. Robbins Pathologic Basis of Disease. 4th ed. Philadelphia: W.B. Saunders Company, 1989:34. 3. Guay AT, Freeman R, Rish BL, Sperber E, Woolf PD. Calcified pituitary tumor with hyperprolactinemia: selective removal by transsphenoidal adenectomy. Fertil Steril 1978;29:585-8. 4. Mukada K, Ohta M, Uozumi T, Arita K, Kurisu K, Inai K. Ossified prolactinoma: case report. Neurosurgery 1987;20:473-5. 5. Rasmussen C, Larsson SG, Bergh T. The occurrence ofmacroscopical pituitary calcifications in prolactinomas. Neuroradiology 1990;31:507-11. 6. Reynier Y, HassounJ, Vittini F, Gambarelli-Dubois D, Vigouroux RP. Fibrosarcomes meninges. Neurochirurgie 1984;30:1-10. 7. Rilliet B, Mohr G, Robert F. Hardy J. Calcifications in pituitary adenomas. Surg Neurol 1981;15:249-55. 8. Shanklin WM. On the presence of calcific bodies, cartilage, bone, follicular concretions and the so-called hyaline bodies in the human pituitary. Anat Rec 1948;102:469-91. 9. Yoneda F, Kagawa S, Kurokawa K: Dystrophic calcifying nodule with osteoid metaplasia of the testis. BrJ Urol 1979;51:413.