An invasive nasopharyngeal carcinoma with extension to the pituitary gland mimicking an invasive pituitary macroadenoma: A case report

Abstract

Herein, we report a rare case of invasive nasopharyngeal carcinoma with extension to the pituitary gland misdiagnosed as a pituitary macroadenoma. A 50-year-old woman was referred to our department with a diagnosis of pituitary macroadenoma. She presented with headache, visual disturbances, weakness, nausea, vomiting, and hypoglycemia. Polyuria was not reported. On pituitary magnetic resonance imaging, a large mass was observed to extend from the sella turcica to the sphenoid sinus, optic chiasm, and nasopharynx, leading to the initial diagnosis of an invasive pituitary macroadenoma. Biochemical investigations revealed corticotropin deficiency, secondary hypothyroidism, hypogonadotropic hypogonadism, and moderate hyperprolactinemia. Hormone replacement therapy was initiated. After hydrocortisone initiation, diabetes insipidus was revealed. Subsequent magnetic resonance imaging showed an infiltration of the nasopharynx with an extension to the pituitary gland. An endoscopic biopsy confirmed the diagnosis of undifferentiated nasopharyngeal carcinoma. The patient was referred to the oncology department for chemo and radiotherapy. Invasive nasopharyngeal carcinoma presenting with pituitary extension is very rare. It should be considered in the differential diagnosis of pituitary macroadenoma with hypopituitarism. Proper management of such cases requires a multidisciplinary approach.

Introduction

Nasopharyngeal cancer (NPC) stands apart from other upper aerodigestive tract cancers because of its particular anatomic situation as well as its specific distribution and frequency among young people.^1,2 The most frequent histological type is undifferentiated carcinoma, which is closely associated with Epstein-Barr virus infection. ¹

NPC is difficult to diagnose because of the deep location of the nasopharynx, its difficult access for physical examination, and the often misleading symptoms caused by the invasion of surrounding structures. Its most common symptoms are nasal and ear-related signs (80%). However, in one-third of cases, it may have a skull base invasion and very rarely it affects the pituitary gland. ³

Herein, we report a case of an invasive NPC with extension to the pituitary gland misdiagnosed as a pituitary macroadenoma.

Case presentation

A 50-year-old woman was referred to the Department of Endocrinology for suspicion of pituitary apoplexy. Her past medical history was unremarkable. She had secondary amenorrhea since the age of 40 years. Data concerning the etiology of amenorrhea were missing.

The patient presented with headache, visual disorders, weakness, nausea, vomiting, and hypoglycemia. No polyuria was reported. Biochemical exploration performed 4 months before her admission to the Department of Endocrinology revealed an 8-h cortisol level of 502 nmol/L, FT4 level of 10.6 pmol/L, thyroid stimulating hormone (TSH) level of 0.66 mIU/L, follicle-stimulating hormone level of 25 IU/L, luteinizing hormone level of 2.5 IU/L, and prolactin level of 71 μg/L. Pituitary magnetic resonance imaging (MRI) showed a large mass in the sella turcica involving the sphenoid sinus and the nasopharynx, suggesting an invasive pituitary macroadenoma.

On physical examination upon admission to our Department, she had a body weight of 51 kg, a height of 153 cm, a body mass index of 21.7 kg/m², a blood pressure of 100/60 mmHg, and a regular pulse of 80 beats/min. Thyroid, abdominal, and neurological examinations were normal.

Biochemical parameters showed corticotropin, thyrotropin, and gonadotropin deficiencies with disconnection hyperprolactinemia (Table 1). The diagnosis of thyrotropin deficiency was made based on a low thyroid stimulating hormone index (TSHI) of 0.71.^4,5 TSHI was calculated using the following formula: TSHI = log TSH (mIU/L) + 0.1345 × FT4 (pmol/L).^4,5 The growth hormone axis was not explored.

Table 1.

Laboratory blood investigations before and after chemo-radiotherapy.

Parameters	Before	After	Normal ranges
Fasting blood glucose (mmol/L)	6.38	4.97	3.88–5.83
Sodium (mmol/L)	134	141	136–145
Potassium (mmol/L)	4	4.5	3.5–5.1
Calcium (mmol/L)	2.35	2.38	85–105
Phosphorus (mmol/L)	1.2	–	0.8–1.4
Urea (mmol/L)	2.83	3.59	2.5–7.6
Creatinine (μmol/L)	53.0	75.38	53–97
8h-Cortisol (nmol/L)	60.70	137.20	110.36-551.80
ACTH (pmol/L)	7.48	–	1.54–13.87
TSH (mIU/L)	0.284	0.01	0.35–4.95
FT4 (pmol/L)	9.39	14.15*	9.01–19.30
FSH (IU/L)	7.9	–	3–8
TSHI	0.71	–	2.70 ± 0.676
LH (IU/L)	0.95	–	0.6–12
Prolactin (ug/L)	31	15.12	<25

ACTH: adrenocorticotropic hormone; FSH: follicle-stimulating hormone; FT4: free thyroxine; LH: luteinizing hormone; TSH: thyroid-stimulating hormone; TSHI: thyroid-stimulating hormone index.

*

The patient was treated with levothyroxine.

The ophthalmologic examination showed decreased visual acuity on the left eye at 5/10, normal fundus, and visual field loss with upper temporal left quadrantanopia.

A second pituitary MRI was performed and showed a nodular nasopharyngeal thickening that continues into the sella turcica, which was enlarged, forming a heterogeneous intra- and suprasellar mass with a fluid-filled area inseparable from the pituitary gland, measuring 20 × 17 mm. This mass compressed the optic chiasm, which appeared swollen with T2 hyperintensity extending to both optic tracts. There was also an enhanced nodular thickening of the pituitary stalk (Figure 1). The diagnosis of an invasive nasopharyngeal mass with diffuse perineural, endocranial, and meningeal infiltration, and extension to the sella turcica was suspected. An endoscopic biopsy was performed. Histopathological examination confirmed the diagnosis of undifferentiated NPC (Figure 2).

Figure 1.

Pituitary magnetic resonance images of the patient before (a) and (b) and after chemo-radiotherapy (c) and (d). (a) and (b) These show enlarged sella turcica forming a heterogeneous intra- and suprasellar mass measuring 20 × 17 mm with a nodular thickening of the pituitary stalk. This mass compressed the optic chiasm. (c) and (d) Magnetic resonance imaging 6 months after the end of oncologic treatment shows the disappearance of pituitary infiltration.

Figure 2.

(a) Hematoxylin and eosin × 40: Undifferentiated carcinomatous proliferation organized in clusters within a lymphoid stroma. (b) Immunohistochemistry × 40: The tumor cells express cytokeratin.

The patient was treated with hydrocortisone (Cortef®) and levothyroxine (Levothyrox®). After hydrocortisone treatment initiation, she developed diabetes insipidus. She was treated with desmopressin (Minirinmelt®).

The patient was referred to the oncology department. She underwent an induction chemotherapy regimen with TPF: cisplatin 60 mg/m², 5-fluorouracil 600 mg/m², and docetaxel 60 mg/m² for two cycles, followed by radiotherapy with a total delivered dose of 70 Gy in 35 fractions. The outcome was marked by the disappearance of pituitary infiltration and the absence of nasopharyngeal tumor recurrence on the MRI performed 6 months after the end of the oncologic treatment (Figure 1). Ophthalmologic examination showed a visual acuity of 10/10 on both eyes and the visual field was normal. However, hypopituitarism persisted warranting a lifelong replacement therapy with hydrocortisone, levothyroxine, and desmopressin.

Discussion

NPC presents frequently with erosion of the skull base and involvement of cranial nerves. This can be explained by its proximity to the skull base as well as its locally infiltrative potential. ³ The involvement of the skull base in locally advanced tumors causes difficulties in discerning direct invasion from intracranial metastasis. Nasopharyngeal tumors can spread into the cranial cavity through various pathways such as foramen lacerum and foramen ovale, or by eroding the skull base. ⁶ Different routes of metastasis have been suggested, with hematogenous spread being the most common. ⁷

Nasopharyngeal tumors with intracranial extension are classified as T4 tumors according to the tumor-node-metastasis (TNM) staging system.^1,3 Invasion of the skull base is considered a prognostic factor indicating a high risk of local recurrence and poor survival. ³

Pituitary extension of NPC is very rare, leading to diagnostic difficulties by mimicking a pituitary adenoma as in the present case.^8,9 Pituitary metastasis is considered as an important differential diagnosis of other pituitary lesions, especially because of the absence of clinical and radiographic characteristic features of metastasis.^8,10 Cases of pituitary metastasis mimicking pituitary adenoma were reported in the literature.^8,11–14 In only three cases, NPC was the underlying cancer.^7,15,16 Gunn et al. ⁷ reported a case of pituitary metastasis from NPC in a 49-year-old man who presented with symptoms of optic chiasm compression and panhypopituitarism 8 months after definitive radiation therapy for invasive undifferentiated NPC. The two other cases of NPC metastasis to the pituitary gland were described by Kovacs ¹⁵ and Morita et al. ¹⁶ among a series of pituitary metastasis from various primary cancer sites. However, no detailed data were provided to differentiate between true metastasis and direct invasion. To the best of our knowledge, the direct involvement of the pituitary gland was reported in only one case. ¹⁷

The initial and only presentation of the primary cancer might occur through metastasis or local infiltration of the sella turcica.^8,13

Patients may present with symptoms of gonadotropin, thyrotropin, somatotropin, and corticotropin deficiencies, resulting from the compression or destruction of the pituitary gland. Antidiuretic hormone deficiency may be masked in case of coexisting corticotropin deficiency until corticosteroid treatment is initiated. ¹¹ Diabetes insipidus was found in 28%–70% of patients with pituitary metastases, whereas it is very rare in cases of pituitary adenomas. ¹⁰ A modest hyperprolactinemia may be observed as in the present case. It is caused by the compression or infiltration of the pituitary stalk, which disrupts the release of dopamine. Central nerve palsies were reported in approximately 10% of patients with NPC. ¹⁸ Headache and visual disturbances were also reported. The coexistence of ophthalmoplegia, diabetes insipidus, and/or pituitary dysfunction, the rapid onset of these symptoms, and the presence of lateral extension and infundibulum thickening on neuroimaging should lead clinicians to suspect pituitary metastases or direct invasion by an NPC.^10–12

The diagnosis of NPC is made by biopsy via nasal endoscopy.

Concomitant radio-chemotherapy in the management of undifferentiated NPC is the gold standard for locally advanced stages.^19,20 It has been proved that it increased survival rates without recurrence of disease. ²¹ Induction chemotherapy is indicated in locally advanced disease followed by concurrent radio-chemotherapy. For radiotherapy, the prescribed dose of 70 Gy in 33–35 fractions (2.0–2.12 Gy per fraction) delivered over 7 weeks (once daily, five fractions per week) is recommended. ¹⁹

Hypopituitarism may persist after the NPC recovery as in the present case. This can be explained by the chronic destruction of the pituitary gland or appear as a complication of radiotherapy. ²² In the case reported by Kokatsu et al., ¹⁷ pituitary hormones had recovered to normal levels after chemo-radiotherapy.

Conclusion

In the present report, we described a rare case of an invasive NPC with extension to the pituitary gland, misdiagnosed as a pituitary macroadenoma. Clinical symptoms such as ophthalmoplegia, visual field defects, visual acuity disorders, and diabetes insipidus can help clinicians in making the correct diagnosis. The definitive diagnosis of NPC is made through histopathological examination. Hormone replacement therapy and chemo-radiotherapy are necessary to improve the patient’s outcome.