This case was originally published in 2018. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.
A 53-year-old man presents with a one-year history of progressive vision loss which has recently worsened significantly. MRI reveals a pituitary mass measuring 5.4 cm in greatest dimension (Image A). A transsphenoidal hypophysectomy is performed.
Whole Slide Image
The whole slide image provided is an H&E stained slide of pituitary from a resection.
What is the MOST likely diagnosis?
Which is the MOST common of the clinically active pituitary adenomas?
The histochemical stain BEST suited to highlight the loss of normal pituitary acinar architecture in a pituitary adenoma is which of the following?
Discussion and Diagnosis
The diagnosis is pituitary gonadotroph macroadenoma (with “macro-“ defined as measuring at least 1 cm in greatest dimension). MRI in this case demonstrates a sellar mass measuring approximately 5 x 5 x 4 cm which extends into the suprasellar cisterns and cavernous sinuses (Image A). The mass appears to have a central cyst compatible with hemorrhage and possible necrosis (consistent with apoplexy). This central acute hemorrhagic process likely accounts for the patient's recent worsening visual symptoms. The specimen obtained from transsphenoidal hypophysectomy shows a relatively monomorphic population of anterior pituitary cells arranged in sheets, trabeculae, and gland-like structures (Image B). Acute hemorrhage was present, but frank necrosis was not seen on the submitted tissue. A higher-power view shows benign-appearing cells with a fine nuclear chromatin pattern (Image C). Adenoma cells, like normal adenohypophyseal cells, are reliably positive for chromogranin (Image D). The adenoma fails to demonstrate the acinar architecture typical of normal pituitary gland, as highlighted by loss of reticulin staining which normally surround acini (Image E). All hormonal IHC stains (prolactin, ACTH, GH, LH, FSH, TSH, α-subunit [α-SU]) are negative, but nuclear staining for SF1 is positive (Image F). The MIB1 proliferative index is less than 3% (Image G), which is within the range typical for a pituitary adenoma.
The patient's adenoma was “clinically silent” with regard to hormonal activity and remained undetected until it grew large enough to compress adjacent structures. In this case, the macroadenoma compressed the optic chiasm and caused visual dysfunction. Hormonally nonfunctioning adenomas account for about one-third of all adenomas that come to medical attention. Many clinically silent adenomas stain immunohistochemically for one or more gonadotropin hormones (luteinizing hormone [LH] and follicle stimulating hormone [FSH]). Occasionally, hormonally nonfunctioning adenomas stain positively for adrenocorticotropic hormone (ACTH), growth hormone (GH), or prolactin. Presumably these clinically silent corticotroph, somatotroph, and lactotroph adenomas produce insufficient or aberrant hormones that are not detected by the clinical laboratory. In the past, most adenomas that stained negatively for all hormonal markers were designated as “null cell” adenomas. It is now recognized that a significant proportion of these hormone-negative tumors in fact stain positively for steroidogenic factor-1 (SF1), which is a transcription factor that drives gonadotroph adenomas. The current case would likely have been characterized as a “null cell” adenoma in the past, but is now recognized as a gonadotroph adenoma by virtue of positive staining for SF1. A null cell adenoma is now defined as an adenoma that is immunohistochemically negative for all pituitary hormones as well as all driving transcription factors (SF1, Tpit, and Pit-1). The use of SF1 IHC can potentially alleviate the need for FSH/LH IHC.
Pituitary microadenomas may be incidentally found at autopsy or on MRI neuroimaging. About two-thirds of adenomas produce excess hormones. The more common hormonally-active pituitary adenomas secrete prolactin, GH, or ACTH. Nearly one-half of hormonally-active adenomas are prolactinomas. Patients with prolactin-secreting adenomas have serum prolactin levels well above what would be detected from pressure on the pituitary stalk from any growing mass. This so-called “stalk effect” results when a mass compresses the pituitary stalk and thereby inhibits the delivery of prolactin-suppressing dopamine from the hypothalamus to the adenohypophysis. Stalk effect tends not to raise serum prolactin levels above 200 mg/L. Levels higher than that almost always originate from a prolactinoma. About 10% of hormone-producing adenomas secrete GH, while about 5% secrete ACTH. Only 1% secrete TSH.
Take Home Points
- Most hormonally nonfunctioning adenomas exhibit at least focal IHC staining for one of the gonadotropin hormones.
- A significant proportion of hormone-negative tumors stain positively for steroidogenic factor-1 (SF1), which is a transcription factor that drives gonadotroph adenomas.
- The “stalk effect” can raise serum prolactin levels moderately by suppressing the prolactin-inhibiting effect of hypothalamic dopamine.
- Kleinschmidt-DeMasters BK, Lopes MB, Prayson RA. An algorithmic approach to sellar region masses. Arch Pathol Lab Med. 2015 Mar;139:356-72.
- McDonald WC, Banerji N, McDonald KN, et al. Steroidogenic factor 1, Pit-1, and adrenocorticotropic hormone: a rational starting place for the immunohistochemical characterization of pituitary adenoma. Arch Pathol Lab Med. 2017;141:104-12.
- Molitch ME. Diagnosis and treatment of pituitary adenomas: a review. JAMA. 2017 Feb;317:516-624.
- What is the MOST likely diagnosis?
- A. Corticotroph adenoma
- B. Gonadotroph adenoma
- C. Lactotroph adenoma
- D. Somatotroph adenoma
- E. Thyrotroph adenoma
- Which is the MOST common of the clinically active pituitary adenomas?
- A. Corticotroph
- B. Gonadotroph
- C. Lactotroph
- D. Somatotroph
- E. Thyrotroph
- The histochemical stain BEST suited to highlight the loss of normal pituitary acinar architecture in a pituitary adenoma is which of the following?
- A. Alcian blue
- B. Gomori trichrome
- C. Mucicarmine
- D. Periodic acid-Schiff
- E. Reticulin