Auris Nasus Larynx 41 (2014) 586–588
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Thyroid-stimulating hormone-secreting ectopic pituitary adenoma of the nasopharynx Suetaka Nishiike a,b,*, Ke-ita Tatsumi c, Takashi Shikina a, Chisako Masumura a, Hidenori Inohara a a b c
Department of Otorhinolaryngology – Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Japan Department of Otorhinolaryngology – Head and Neck Surgery, Osaka Rosai Hospital, Sakai, Japan Department of Laboratory Medicine, Osaka University Graduate School of Medicine, Suita, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 25 March 2014 Accepted 29 July 2014 Available online 5 September 2014
Thyroid-stimulating hormone-secreting ectopic pituitary adenoma of the nasopharynx is highly unusual, with only three reported cases in the world literature. We describe the clinical presentation and radiologic findings in one patient with such rare lesions. A 46-year-old male with typical symptoms of Grave’s disease was found to have a mass on magnetic resonance imaging. An otolaryngologic examination revealed a nasopharyngeal mass lesion, which was endoscopically resected. The results of immunohistochemical staining for thyroid-stimulating hormone were positive. After the resection, the patient’s TSH was within normal limits. The clinical significance of the case and a brief literature review are presented. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Hyperthyroidism TSH Ectopic pituitary adenoma Rathke’s pouch Extracranial
1. Introduction Ectopic pituitary adenomas are rare. Because it has been reported that they are mostly found in the sphenoid sinus or bone [1], an ectopic pituitary adenoma in the nasopharynx is more unique. Moreover, ectopic pituitary adenoma that secretes thyroid-stimulating hormone (TSH) is exceedingly rare [2–4]. Herein, we report an ectopic TSH-secreting extracranial pituitary adenoma in the nasopharynx. To our knowledge, this is the fourth such reported case in the literature.
2. Case report A 46-year-old male was referred for evaluation of a nasopharyngeal mass found on magnetic resonance imaging (MRI), which was suspected of ectopic TSH-secreting pituitary adenoma. In 2000, he began to complain of sweating and palpitations. In 2007, he visited the hospital for the first time with a complaint of
* Corresponding author at: Department of Otorhinolaryngology – Head and Neck Surgery, Osaka Rosai Hospital, 1179-3 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan. Tel.: +81 72 252 3561; fax: +81 72 255 3349. E-mail addresses: [email protected], [email protected] (S. Nishiike). http://dx.doi.org/10.1016/j.anl.2014.07.004 0385-8146/ß 2014 Elsevier Ireland Ltd. All rights reserved.
migraine, and in 2009, thyroid goiter was found. Thyroid function tests showed high basal levels of free thyroxine and free triiodothyronine, while the serum TSH levels were normal. A thyroid scintigraphy showed an increased uptake of radionuclide (123-I) in the area of the thyroid gland. Thyrotropin-releasing hormone test showed poor stimulation of TSH. Inappropriate secretion of TSH due to a TSH-secreting pituitary adenoma or the syndrome of resistance to thyroid hormone was suspected. Cerebral MRI with gadolinium contrast showed normal pituitary gland, but a mass in the nasopharynx (Fig. 1). To examine whether the mass is a neoplastic disease, the positron emission tomography imaging was performed, and it detected high accumulation in the mass. Ectopic TSHsecreting pituitary adenoma of the nasopharynx was suspected. He was referred to our department in 2010. A posterior nasopharyngeal midline septal mass was seen with the nasal endoscope (Fig. 2A). The mass appeared cystic, round, and smooth. Computer tomography scan indicated an approximate 14 mm mass protruding inferiorly from the roof of the nasopharynx (Fig. 2B and C). Under general anesthesia, the mass was removed en block using an endoscopic endonasal approach. The resection also encompassed the bony septum. The postoperative course was uneventful and the patient was discharged on the 8th postoperative day. Histologically, the tumor consisted of nests of monomorphic polygonal epithelial cells with round to ovoid nucleus with dispersed chromatin and granular eosinophilic cytoplasm
S. Nishiike et al. / Auris Nasus Larynx 41 (2014) 586–588
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At 3 years’ follow-up, the patient’s TSH was within normal limits and there was no recurrence. 3. Discussion
Fig. 1. MRI with gadolinium contrast showed normal pituitary gland, but a mass (white arrow) in the nasopharynx. The mass was slightly enhanced.
(Fig. 3A). The cell nests were separated by a delicate fibrovascular stroma. Cellular pleomorphism was minimal, and necrosis or mitotic activity was not seen. The neoplastic cells were immunoreactive for TSH (Fig. 3B).
Ectopic pituitary adenomas are accessory masses of anterior pituitary tissue that have no connection to the intrasellar pituitary gland. Up to date, dozens of such cases [5,6] were reported. Women are affected twice as often as men. The mean age at diagnosis is 49 years [1]. The majority involved the sphenoid sinus and cavernous sinus [6], and those involving the nasopharynx exclusively were rare. It has been reported that most functioning pituitary adenomas are intrasellar lesions without signs of mass effect, and TSH-secreting pituitary adenomas are uncommon accounting for about 1–2% of all pituitary adenomas [7]. An extracranial ectopic functioning pituitary tumor that secretes TSH is exceedingly rare. The majority of adenomas arising from ectopic hypophysial tissue are adenocorticotropin-secreting adenomas [8]. Three cases of TSH-secreting ectopic pituitary adenoma of the nasopharynx have been reported in the literature [2–4], and our case is believed to be the fourth. It is generally considered that ectopic pituitary tumors arise from embryologic remnants of pituitary tissue in the pharyngeal region and in other regions in the migration path of Rathke’s pouch [8]. Ingrowth of Rathke’s pouch extends towards the third ventricle region of the diencephalon, and remnants can be retained in the sphenoid bone, sphenoid sinus, or possibly within the sella turcica and separate from the normal pituitary gland. Another subtype of pituitary adenoma, the suprasellar or subdiaphragmatic tumor may arise from anterior lobe cells attached to the supradiaphragmatic portion of the pituitary stalk [1].
Fig. 2. Left posterior nasal cavity (A) and CT findings (B and C). (A) The endoscopic finding indicated a midline septal mass (white arrow). (B and C) The mass (white arrows) protruding from the roof of the nasopharynx was shown on the axial (B) and coronal (C) images. NS: nasal septum.
Fig. 3. (A) Large, ovoid cells with eosinophilic granular cytoplasm and round to ovoid nuclei (hematoxylin and eosin staining, 150). (B) The neoplastic cells were immunoreactive for TSH (avidin-biotin complex peroxidase staining, 150).
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S. Nishiike et al. / Auris Nasus Larynx 41 (2014) 586–588
In the syndrome of the inappropriate secretion of TSH due to a TSH-secreting pituitary adenoma or the syndrome of resistance to thyroid hormone, generally patients present with high peripheral thyroid hormone levels, inappropriately normal or elevated levels of TSH and symptoms of thyrotoxicosis [9]. Not all patients show high level of TSH. In the previous three cases of TSH-secreting ectopic pituitary adenoma [2–4], one case showed normal level of TSH at his first examination [4]. In our case, preoperatively we supposed the mass to be a neoplastic disease as the positron emission tomography imaging detected high accumulation, but did not have evidence whether it is functioning benign tumor or malignant disease. Inappropriate secretion of TSH was identified, and cerebral MRI showed normal pituitary gland, but a mass in the nasopharynx. Although ectopic TSH-secreting pituitary adenoma of the nasopharynx is very rare [2–4], it was preoperatively suspected based on the abovementioned findings. The patient underwent surgery for the purpose of both diagnosis and treatment. Ectopic pituitary adenomas must be differentiated from other neuroendocrine tumors, such as an atypical carcinoid or neuroendocrine carcinoma, a site-specific malignant epithelial neoplasm (e.g., adenocarcinoma), or a metastatic neoplasm [3]. Intrasellar pituitary adenomas with sphenoid sinus invasion must also be considered. Radiographic images that demonstrate a normal intrasellar pituitary gland rule out the latter. The presence of immunoreactivity with cytokeratin, synaptophysin, and various neuroendocrine markers and neuron-specific enolase does not differentiate a pituitary neoplasm from other neuroendocrine tumors [3]. The presence of immunoreactivity with pituitary hormones would be diagnostic of a pituitary-derived neoplasm differentiating it from other neuroendocrine tumors. In our case definite diagnosis was made with no delay, but the majority of cases with TSH-secreting ectopic pituitary adenoma needed long time for diagnosis. The patients were mistakenly treated for 9 years in Cooper et al.’s report [3] and 18 years in Pasquini et al’s report [4]. In the latter case, the patient still
received antithyroid drugs when the inappropriate secretion of TSH was suspected and neuroradiological examination of the sella turcica showed no lesion there. From their experience, Cooper et al. [3] suggested that an extrasellar site should be sought in patients who appear to have a pituitary-related endocrine syndrome whose radiography is normal. In conclusion, although TSH-secreting extracranial ectopic pituitary adenomas are quite unusual, they could be added to the list of the possible causes of inappropriate secretion of TSH. The question has been raised whether cases reported in the literature with non-neoplastic inappropriate TSH secretion could also have harbored an occult ectopic pituitary neoplasm [3]. Conflict of interest None. References [1] Langford L, Baksakis J. Pathology consultation pituitary gland involvement of the sinonasal tract. Ann Otol Rhinol Laryngol 1995;104:167–9. [2] Collie RB, Collie MJ. Extracranial thyroid-stimulating hormone-secreting ectopic pituitary adenoma of the nasopharynx. Otolaryngol Head Neck Surg 2005;133:453–4. [3] Cooper DS, Wenig BM. Hyperthyroidism caused by an ectopic TSH-secreting pituitary tumor. Thyroid 1996;6:337–43. [4] Pasquini E, Faustini-Fustini M, Sciarretta V, Saggese D, Roncaroli F, Serra D, et al. Ectopic TSH-secreting pituitary adenoma of the vomerosphenoidal junction. Eur J Endocrinol 2003;148:253–7. [5] Luk IS, Chan JK, Chow SM, Leung S. Pituitary adenoma presenting as sinonasal tumor: pitfalls in diagnosis. Hum Pathol 1996;27:605–9. [6] Hori A, Schmidt D, Rickels E. Pharyngeal pituitary: development, malformation, and tumorigenesis. Acta Neuropathol 1999;98:262–72. [7] Beck-Peccoz P, Brucker-Davis F, Persani L, Smallridge RC, Weintraub BD. Thyrotropin-secreting pituitary tumors. Endocr Rev 1996;17:610–38. [8] Lloyd RV, Chandler WF, Kovacs K, Ryan N. Ectopic pituitary adenomas with normal anterior pituitary glands. Am J Surg Pathol 1986;10:546–52. [9] Kienitz T, Quinkler M, Strasburger CJ, Ventz M. Long-term management in five cases of TSH-secreting pituitary adenomas: a single center study and review of the literature. Eur J Endocrinol 2007;157:39–46.
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Thyroid-stimulating hormone-secreting ectopic pituitary adenoma of the nasopharynx Suetaka Nishiike a,b,*, Ke-ita Tatsumi c, Takashi Shikina a, Chisako Masumura a, Hidenori Inohara a a b c
Department of Otorhinolaryngology – Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Japan Department of Otorhinolaryngology – Head and Neck Surgery, Osaka Rosai Hospital, Sakai, Japan Department of Laboratory Medicine, Osaka University Graduate School of Medicine, Suita, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 25 March 2014 Accepted 29 July 2014 Available online 5 September 2014
Thyroid-stimulating hormone-secreting ectopic pituitary adenoma of the nasopharynx is highly unusual, with only three reported cases in the world literature. We describe the clinical presentation and radiologic findings in one patient with such rare lesions. A 46-year-old male with typical symptoms of Grave’s disease was found to have a mass on magnetic resonance imaging. An otolaryngologic examination revealed a nasopharyngeal mass lesion, which was endoscopically resected. The results of immunohistochemical staining for thyroid-stimulating hormone were positive. After the resection, the patient’s TSH was within normal limits. The clinical significance of the case and a brief literature review are presented. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Hyperthyroidism TSH Ectopic pituitary adenoma Rathke’s pouch Extracranial
1. Introduction Ectopic pituitary adenomas are rare. Because it has been reported that they are mostly found in the sphenoid sinus or bone [1], an ectopic pituitary adenoma in the nasopharynx is more unique. Moreover, ectopic pituitary adenoma that secretes thyroid-stimulating hormone (TSH) is exceedingly rare [2–4]. Herein, we report an ectopic TSH-secreting extracranial pituitary adenoma in the nasopharynx. To our knowledge, this is the fourth such reported case in the literature.
2. Case report A 46-year-old male was referred for evaluation of a nasopharyngeal mass found on magnetic resonance imaging (MRI), which was suspected of ectopic TSH-secreting pituitary adenoma. In 2000, he began to complain of sweating and palpitations. In 2007, he visited the hospital for the first time with a complaint of
* Corresponding author at: Department of Otorhinolaryngology – Head and Neck Surgery, Osaka Rosai Hospital, 1179-3 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan. Tel.: +81 72 252 3561; fax: +81 72 255 3349. E-mail addresses: [email protected], [email protected] (S. Nishiike). http://dx.doi.org/10.1016/j.anl.2014.07.004 0385-8146/ß 2014 Elsevier Ireland Ltd. All rights reserved.
migraine, and in 2009, thyroid goiter was found. Thyroid function tests showed high basal levels of free thyroxine and free triiodothyronine, while the serum TSH levels were normal. A thyroid scintigraphy showed an increased uptake of radionuclide (123-I) in the area of the thyroid gland. Thyrotropin-releasing hormone test showed poor stimulation of TSH. Inappropriate secretion of TSH due to a TSH-secreting pituitary adenoma or the syndrome of resistance to thyroid hormone was suspected. Cerebral MRI with gadolinium contrast showed normal pituitary gland, but a mass in the nasopharynx (Fig. 1). To examine whether the mass is a neoplastic disease, the positron emission tomography imaging was performed, and it detected high accumulation in the mass. Ectopic TSHsecreting pituitary adenoma of the nasopharynx was suspected. He was referred to our department in 2010. A posterior nasopharyngeal midline septal mass was seen with the nasal endoscope (Fig. 2A). The mass appeared cystic, round, and smooth. Computer tomography scan indicated an approximate 14 mm mass protruding inferiorly from the roof of the nasopharynx (Fig. 2B and C). Under general anesthesia, the mass was removed en block using an endoscopic endonasal approach. The resection also encompassed the bony septum. The postoperative course was uneventful and the patient was discharged on the 8th postoperative day. Histologically, the tumor consisted of nests of monomorphic polygonal epithelial cells with round to ovoid nucleus with dispersed chromatin and granular eosinophilic cytoplasm
S. Nishiike et al. / Auris Nasus Larynx 41 (2014) 586–588
587
At 3 years’ follow-up, the patient’s TSH was within normal limits and there was no recurrence. 3. Discussion
Fig. 1. MRI with gadolinium contrast showed normal pituitary gland, but a mass (white arrow) in the nasopharynx. The mass was slightly enhanced.
(Fig. 3A). The cell nests were separated by a delicate fibrovascular stroma. Cellular pleomorphism was minimal, and necrosis or mitotic activity was not seen. The neoplastic cells were immunoreactive for TSH (Fig. 3B).
Ectopic pituitary adenomas are accessory masses of anterior pituitary tissue that have no connection to the intrasellar pituitary gland. Up to date, dozens of such cases [5,6] were reported. Women are affected twice as often as men. The mean age at diagnosis is 49 years [1]. The majority involved the sphenoid sinus and cavernous sinus [6], and those involving the nasopharynx exclusively were rare. It has been reported that most functioning pituitary adenomas are intrasellar lesions without signs of mass effect, and TSH-secreting pituitary adenomas are uncommon accounting for about 1–2% of all pituitary adenomas [7]. An extracranial ectopic functioning pituitary tumor that secretes TSH is exceedingly rare. The majority of adenomas arising from ectopic hypophysial tissue are adenocorticotropin-secreting adenomas [8]. Three cases of TSH-secreting ectopic pituitary adenoma of the nasopharynx have been reported in the literature [2–4], and our case is believed to be the fourth. It is generally considered that ectopic pituitary tumors arise from embryologic remnants of pituitary tissue in the pharyngeal region and in other regions in the migration path of Rathke’s pouch [8]. Ingrowth of Rathke’s pouch extends towards the third ventricle region of the diencephalon, and remnants can be retained in the sphenoid bone, sphenoid sinus, or possibly within the sella turcica and separate from the normal pituitary gland. Another subtype of pituitary adenoma, the suprasellar or subdiaphragmatic tumor may arise from anterior lobe cells attached to the supradiaphragmatic portion of the pituitary stalk [1].
Fig. 2. Left posterior nasal cavity (A) and CT findings (B and C). (A) The endoscopic finding indicated a midline septal mass (white arrow). (B and C) The mass (white arrows) protruding from the roof of the nasopharynx was shown on the axial (B) and coronal (C) images. NS: nasal septum.
Fig. 3. (A) Large, ovoid cells with eosinophilic granular cytoplasm and round to ovoid nuclei (hematoxylin and eosin staining, 150). (B) The neoplastic cells were immunoreactive for TSH (avidin-biotin complex peroxidase staining, 150).
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S. Nishiike et al. / Auris Nasus Larynx 41 (2014) 586–588
In the syndrome of the inappropriate secretion of TSH due to a TSH-secreting pituitary adenoma or the syndrome of resistance to thyroid hormone, generally patients present with high peripheral thyroid hormone levels, inappropriately normal or elevated levels of TSH and symptoms of thyrotoxicosis [9]. Not all patients show high level of TSH. In the previous three cases of TSH-secreting ectopic pituitary adenoma [2–4], one case showed normal level of TSH at his first examination [4]. In our case, preoperatively we supposed the mass to be a neoplastic disease as the positron emission tomography imaging detected high accumulation, but did not have evidence whether it is functioning benign tumor or malignant disease. Inappropriate secretion of TSH was identified, and cerebral MRI showed normal pituitary gland, but a mass in the nasopharynx. Although ectopic TSH-secreting pituitary adenoma of the nasopharynx is very rare [2–4], it was preoperatively suspected based on the abovementioned findings. The patient underwent surgery for the purpose of both diagnosis and treatment. Ectopic pituitary adenomas must be differentiated from other neuroendocrine tumors, such as an atypical carcinoid or neuroendocrine carcinoma, a site-specific malignant epithelial neoplasm (e.g., adenocarcinoma), or a metastatic neoplasm [3]. Intrasellar pituitary adenomas with sphenoid sinus invasion must also be considered. Radiographic images that demonstrate a normal intrasellar pituitary gland rule out the latter. The presence of immunoreactivity with cytokeratin, synaptophysin, and various neuroendocrine markers and neuron-specific enolase does not differentiate a pituitary neoplasm from other neuroendocrine tumors [3]. The presence of immunoreactivity with pituitary hormones would be diagnostic of a pituitary-derived neoplasm differentiating it from other neuroendocrine tumors. In our case definite diagnosis was made with no delay, but the majority of cases with TSH-secreting ectopic pituitary adenoma needed long time for diagnosis. The patients were mistakenly treated for 9 years in Cooper et al.’s report [3] and 18 years in Pasquini et al’s report [4]. In the latter case, the patient still
received antithyroid drugs when the inappropriate secretion of TSH was suspected and neuroradiological examination of the sella turcica showed no lesion there. From their experience, Cooper et al. [3] suggested that an extrasellar site should be sought in patients who appear to have a pituitary-related endocrine syndrome whose radiography is normal. In conclusion, although TSH-secreting extracranial ectopic pituitary adenomas are quite unusual, they could be added to the list of the possible causes of inappropriate secretion of TSH. The question has been raised whether cases reported in the literature with non-neoplastic inappropriate TSH secretion could also have harbored an occult ectopic pituitary neoplasm [3]. Conflict of interest None. References [1] Langford L, Baksakis J. Pathology consultation pituitary gland involvement of the sinonasal tract. Ann Otol Rhinol Laryngol 1995;104:167–9. [2] Collie RB, Collie MJ. Extracranial thyroid-stimulating hormone-secreting ectopic pituitary adenoma of the nasopharynx. Otolaryngol Head Neck Surg 2005;133:453–4. [3] Cooper DS, Wenig BM. Hyperthyroidism caused by an ectopic TSH-secreting pituitary tumor. Thyroid 1996;6:337–43. [4] Pasquini E, Faustini-Fustini M, Sciarretta V, Saggese D, Roncaroli F, Serra D, et al. Ectopic TSH-secreting pituitary adenoma of the vomerosphenoidal junction. Eur J Endocrinol 2003;148:253–7. [5] Luk IS, Chan JK, Chow SM, Leung S. Pituitary adenoma presenting as sinonasal tumor: pitfalls in diagnosis. Hum Pathol 1996;27:605–9. [6] Hori A, Schmidt D, Rickels E. Pharyngeal pituitary: development, malformation, and tumorigenesis. Acta Neuropathol 1999;98:262–72. [7] Beck-Peccoz P, Brucker-Davis F, Persani L, Smallridge RC, Weintraub BD. Thyrotropin-secreting pituitary tumors. Endocr Rev 1996;17:610–38. [8] Lloyd RV, Chandler WF, Kovacs K, Ryan N. Ectopic pituitary adenomas with normal anterior pituitary glands. Am J Surg Pathol 1986;10:546–52. [9] Kienitz T, Quinkler M, Strasburger CJ, Ventz M. Long-term management in five cases of TSH-secreting pituitary adenomas: a single center study and review of the literature. Eur J Endocrinol 2007;157:39–46.
