Giant Hemorrhagic Prolactinoma with Sparse Prolactin Expression Presenting with Thalamic Infarction—A Case Report

US Endocrinology, 2014;10(2):124–8 DOI: http://doi.org/10.17925/USE.2014.10.02.124

Abstract:

Pituitary tumors are the most common form of intracranial neoplasms. However, clinically relevant pituitary tumors presenting with disturbances of hormonal secretion or mass effect are rare and they only represent about 10 % of all surgically resected intracranial neoplasms. Prolactinomas are the most common types of pituitary adenomas. Generally, hormonal expression patterns provided by immunohistochemistry (IHC) studies are correlated with the clinical features and endocrine activity of the patients. Nonetheless, exceptions occur where the immunocytochemical staining is not concordant with the clinical picture. Pituitary adenomas presenting with apoplexy are well known. However, pituitary adenomas causing cerebral stroke and resulting in hemiplegia are unusual. Here, we report an unusual case of prolactinoma with cerebral stroke and sparse prolactin (PRL) expression. A 25-year-old woman complaining of amenorrhea, dysphasia, and left hemiplegia presented with serum PRL level in excess of 4,700 ng/ml. Pre-operational radiology images revealed a giant macroadenoma and a thalamic infarct due to carotid compression. Transcranial surgery was performed. IHC study of the adenoma revealed no hormonal expression other than sparse PRL immunoreactivity. Therefore, a sparsely granulated PRL cell adenoma was diagnosed. The patient is still under follow-up with continuing cabergoline treatment.
Keywords: Adenoma, prolactinoma, apoplexy, stroke, craniotomy
Disclosure: Ali Genc, MD, MSc, Halil Ibrahim Sun, MD, Burcu Kasapoglu, PhD, Pinar Oz, PhD, Murat Aydın Sav, MD, and Mustafa Necmettin Pamir, MD, have no disclosures to declare. No funding was received for the publication of this article.
Received: September 23, 2014 Accepted November 17, 2014
Correspondence: Ali Genc, MD, MSc, Acıbadem Bodrum Hospital, Department of Neurosurgery, Mugla, Turkey. E: draligenc@gmail.com

Compliance with Ethics: Where applicable, all procedures were followed in accordance with the responsible committee on human experimentation and with the Helsinki Declaration of 1975 and subsequent revisions. Informed consent was received from the patient involved in this case study.

Pituitary tumors are the most common form of intracranial neoplasms. Their prevalence in autopsy series was reported as 5–20  %.1 However, clinically relevant pituitary tumors presenting with disturbances of hormonal secretion or mass effect are rare, with an estimated prevalence of 200/1,000,000 and an incidence of 2/100,000 per year.2 Therefore, they only represent about 10 % of all surgically resected intracranial neoplasms.3,4

Their prevalence increases with advancing age: both sexes are affected equally. They can cause a variety of endocrine syndromes and disorders1 including panhypopituitarism, acromegaly, Cushing’s disease, infertility, and visual disturbances. Recently, the diagnosis of pituitary adenomas has increased as a result of the advances in neuroimaging technologies. Due to endocrine hyperfunction, hormonally active adenomas are usually diagnosed at an earlier stage than hormonally inactive ones, which are mostly diagnosed due to the effect of local pressure exerted by the growing tumor.5

Based on their size, pituitary adenomas can be divided into microadenomas and macroadenomas, the latter being reserved for adenomas larger than 10 mm in diameter. On the other hand, the first histologic classification of pituitary tumors was based on tinctorial characteristics using hematoxylineosin stains on resected tissue. Tumors were accordingly classified as eosinophilic, basophilic, or chromophobic adenomas4 and were suggested to be associated with acromegaly, Cushing’s syndrome and nonfunctioning adenomas, respectively. Later studies made such a classification irrelevant by showing that some acidophilic tumors do not produce growth hormone (GH) and some GH-producing tumors are not acidophilic. Similarly, some basophilic tumors do not cause Cushing’s syndrome and more than half of the chromophobic tumors are endocrinologically active, secreting various hormones.4

Fortunately, with the development of immunohistochemistry (IHC), correlation of clinical features and endocrine activity became possible. IHC studies permit a conclusive identification of the various cell types in the pituitary adenomas. Currently, the standard immunohistochemical battery includes the use of antibodies to GH, prolactin (PRL), adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and the a-subunit of the glycoprotein hormones.4 Generally these hormones are expressed either singly or in various combinations. Although cellular hormonal immunoreactivity is common in pituitary tumors, there are many exceptions where the immunocytochemical staining is not concordant with the clinical or biochemical features. Classic examples are the silent corticotroph and somatotroph adenomas, in which tumor cells stain positively for ACTH and GH, respectively, and yet patients have no clinical or biochemical features of excessive hormone secretion.1,6–9 Silent or nonfunctioning adenomas have no clinical expression of produced hormones, either because they produce inactive molecules or do not release sufficient amount of hormones from cells to create a detectable blood level.4

Prolactinomas represent the majority of clinically recognized pituitary adenomas, accounting for approximately 40–45  % of all.3 However, their incidence among reported surgical series is lower because of the medical therapeutic option of these tumors.3 They are reported to occur more frequently in women than in men, particularly between the second and third decades of life, when the ratio is estimated to be 10:1. Prolactinomas vary in size at presentation with most women presenting with microadenomas, whereas men tend to have macroadenomas at diagnosis. In women, hyperprolactinemia causes oligomenorrhea or amenorrhea as well as galactorrhea. In men, however, the main presenting symptom is impotence and diminished libido, which can often be overlooked and attributed to other causes.1

Generally, Immunohistochemical study of prolactinomas, show a high rate of PRL expression in concordance with serum PRL levels. They grow slowly with Ki-67 staining of less than 2 %.8 Here, we report an interesting case of pituitary adenoma with high serum levels of PRL and histologically confounding sparse PRL expression. The patient manifested a longstanding history of amenorrhea and presented with abrupt apoplectic hemiplegia due to a thalamic infarction resulting from carotid compression by the tumor.

References:
1. Arafah BM, Nasrallah MP, Pituitary tumors: pathophysiology, clinical manifestations and management, Endocr Relat Cancer, 2001;8:287–305.
2. Yamaguchi-Okada M, Inoshita N, Nishioka H, et al., Clinicopathological analysis of nonfunctioning pituitary adenomas in patients younger than 25 years of age, J Neurosurg Pediatrics, 2012;9:511–6.
3. Buurman H, Saeger W, Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data, Eur J Endocrinol, 2006;154:753–8.
4. Balinisteanu B, Ceausu RA, Cimpean AM, et al., Conventional examination versus immunohistochemistry in the prediction of hormone profile of pituitary adenomas, An analysis on 142 cases, Rom J Morphol Embryol, 2011;2(Suppl. 3):1041–5.
5. Saeger W, Ludecke DK, Buchfelder M, et al., Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry, Eur J Endocrinol, 2007;156:203–16.
6. Sav A, Syro LV, Scheithauer BW, et al., Silent Somatotroph Adenoma: A Morphologic, Immunohistochemical and Electron Microscopic Study: A Case Report, J Med Cases, 2012;3(1):43–8.
7. Wade AN, Baccon J, Grady JKD, et al., Clinically silent somatotroph adenomas are common, Eur J Endocrinol, 2011;165:39–44.
8. Sav A, Rotondo F, Syro LV, et al., Biomarkers of pituitary neoplasms, Anticancer Res, 2012;32:4639–54.
9. Ogawa Y, Watanabe M, Tominaga T, Somaostatin-producing atypical null cell adenoma manifesting as svere hypopituiarism and rapid deterioration – case report, Endocr Pathol, 2010;21:130–4.
10. Kovacs K, Horvath E, Corenblum B, et al., Pituitary chromophobe adenomas consisting of prolactin cells: a histologic, immunocytological and electron microscopic study, Virchows Arch A Pathol Anat Histol, 1975; 366:113–23.
11. Maiter D, Delgrange E, Therapy of endocrine disease: the challenges in managing giant prolactinomas, Eur J Endocrinol, 2014;170:213–27.
12. Delgrange E, Raverot G, Bex M, et al., Giant prolactinomas in women, Eur J Endocrinol, 2014;170:31–8.
13. Vilar L, Fleseriu M, Bronstein MD, Challenges and pitfalls in the diagnosis of hyperprolactinemia, Arq Bras Endocrinol Metabol, 2014;58:9–22.
14. Feigenbaum SL, Downey DE, Wilson CB, Jaffe RB, Transsphenoidal pituitary resection for preoperative diagnosis of prolactin-secreting pituitary adenoma in women: long term follow-up, J Clin Endocrinol Metab, 1996;81:1711–9.
15. Kim W, Clelland C, Yang I, Pouratian N, Comprehensive review of stereotactic radiosurgery for medically and surgically refractory pituitary adenomas, Surg Neurol Int, 2012;3 (Suppl. 2):S79–89.
16. Möller-Goede DL, Brändle M, Landau K, et al., Pituitary apoplexy: re-evaluaion of risk factors for bleeding into pituitary adenomas and impact on outcome, Eur J Endocrinol, 2011;164:37–43.
17. Navarro-Bonnet J, Martinez-Anda JJ, Balderrama-Soto A, et al., Stroke associated with pituitary apoplexy in a giant prolactinoma: A case report, Clin Neurol Neurosurg, 2014;116:101–3.
18. Rey Dios R, Payner TD, Cohen-Gadol AA, Pituitary macroadenoma causing symptomatic internal carotid artery compression: Surgical reatment through transsphenoidal tumor resection, J Clin Neurosci, 2014;21:541–6.
19. Zayour DH, Selman WR, Arafah BM, Extreme elevation of intrasellar pressure in patients with pituitary tumor apoplexy: relation to pituitary function, J Clin Endocrinol Metab, 2004;89:5649–54.
Keywords: Adenoma, prolactinoma, apoplexy, stroke, craniotomy