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Year : 2010  |  Volume : 58  |  Issue : 5  |  Page : 778-780

Malignant prolactinoma: A rare case report

1 Department of Pathology, Gujarat Cancer and Research Institute (M. P. Shah Cancer Hospital), Ahmedabad, Gujarat, India
2 Department of Neurosurgery, Gujarat Cancer and Research Institute (M. P. Shah Cancer Hospital), Ahmedabad, Gujarat, India

Date of Acceptance22-Jul-2010
Date of Web Publication28-Oct-2010

Correspondence Address:
Priti Trivedi
Room #412, Department of Pathology, The Gujarat Cancer and Research Institute, NCH Campus, Asarwa, Ahmedabad - 380 016, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.72205

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 » Abstract 

Pituitary carcinomas are rare adenohypophyseal tumors with cerebrospinal or extracranial metastasis. None of the histologic findings distinguish pituitary adenoma from carcinoma. We describe clinico-pathological and immunohistological features of malignant prolactinoma. The patient initially presented with a prolactin-secreting pituitary adenoma. The tumor showed aggressive clinical course presenting with repeated recurrences and eventually metastasized to multiple bones. MIB-1 and p53 labeling indices were also compared in primary adenoma, recurrent invasive adenoma and metastatic tumor.

Keywords: MIB-1, pituitary carcinoma, p53

How to cite this article:
Trivedi P, Gupta A, Pasricha S, Patel D. Malignant prolactinoma: A rare case report. Neurol India 2010;58:778-80

How to cite this URL:
Trivedi P, Gupta A, Pasricha S, Patel D. Malignant prolactinoma: A rare case report. Neurol India [serial online] 2010 [cited 2022 Aug 15];58:778-80. Available from: https://www.neurologyindia.com/text.asp?2010/58/5/778/72205

 » Introduction Top

Pituitary carcinomas are extremely rare tumors with cerebrospinal or extracranial metastasis, representing only 0.1% to 0.2% of all pituitary neoplasms. [1] The vast majority of pituitary carcinomas are as endocrinologically active as their benign counterparts, with most secreting adrenocorticotrophic hormone (ACTH) or prolactin (PRL). [2] None of the histologic findings distinguish pituitary adenoma from carcinoma. Demonstration of metastatic spread to remote areas of central nervous system (CNS) or outside the CNS is mandatory for diagnosis of pituitary carcinoma. Till now, 49 cases of malignant prolactinoma have been documented in literature, [3],[4],[5] but none in the Indian literature. Here, we present a case of PRL-secreting pituitary carcinoma with multiple skeletal metastases.

 » Case Report Top

In August 2004, a 28-year-old woman presented with a 4-month history of amenorrhea and blurring of vision. Neurological examination revealed right ptosis and right sixth cranial nerve palsy. Preoperative magnetic resonance imaging (MRI) revealed pituitary macroadenoma. Serum PRL levels were 122 ng/mL (normal range, 3.5-16.3 ng/mL). Serum cortisol, growth hormone, thyroid function tests were within normal range. The patient was initially treated with bromocriptine (1.25 mg, t.i.d.). Initially, she had improvement in vision and fall in PRL levels, but later she had deterioration in vision with a rise in PRL levels. Subtotal excision of the tumor was done. Histopathological examination of the tumor revealed monomorphic population of round-to-spindly cells with bland chromatin, inconspicuous nucleoli and moderate amount of eosinophilic-to-clear cytoplasm [Figure 1]a. Immmunohistochemically, the tumor cells were positive for synaptophysin and PRL. Thus a diagnosis of pituitary adenoma (prolactinoma) was made. Postoperative MRI scan (September 2004) revealed residual lesion in the sellar, parasellar, suprasellar regions. The patient was given radiotherapy (60 Gy over a period of 2 months). Marked improvement in vision was noted. Serum PRL levels dropped to 59 ng/mL. The patient remained asymptomatic for the next three years, except for panhypopituitarism. PRL levels stayed within the normal range while the patient received a 15-mg per day dose of bromocriptine. In September 2007, she again developed blurring of vision and diplopia. Serum PRL level was elevated (306 ng/mL). MRI scan showed a well-defined lobulated intensely enhancing sellar and suprasellar mass measuring 35×40×38 mm extending to right parasellar region. The mass invaded right cavernous sinus, engulfing cavernous segment of right internal carotid artery (ICA), partially encasing cavernous segment of left ICA, elevating and compressing optic chiasma, suggesting recurrent invasive pituitary adenoma [Figure 2]a. The patient was operated upon for the same. Histopathology confirmed the diagnosis of recurrent pituitary adenoma. In the next 2 years, the tumor recurred twice and was operated upon twice. In September 2009, the patient was given radiotherapy (total dose of 5,560 cGy over a period of 2 months). Post radiotherapy, there was little reduction in tumor volume. Few weeks later, the patient developed backache. MRI revealed altered-intensity lesions involving multiple dorsolumbar vertebral bodies and their posterior elements with epidural soft tissue component, suggesting a possibility of metastases [Figure 2]b. Laminectomy was performed to relieve the cord compression. On Hematoxylin and eosin-stained sections, the tumor was disposed in nests. Individual cells were monomorphic and round to polygonal in shape with abundant eosinophilic cytoplasm, vesicular nucleus and distinct nucleoli. Occasional mitosis was present [Figure 1]b. Tumor cells were positive for PRL and synaptophysin. Thus a diagnosis of pituitary carcinoma was established. MIB-1 and p53 expressions were compared in the primary, recurrent and metastatic tumors [Figure 3] and [Figure 4]. The Ki-67 labeling index (LI) in the primary, recurrent invasive, and metastatic tumors was 1.6%, 4.2%, and 8.7%, respectively. Similarly the p53 LI in the primary, recurrent invasive, and metastatic tumors was <1%, 2.3%, and 6.5%, respectively. Bone scan was performed, which suggested multiple bone metastases. Serum PRL levels continued to rise. She died in February 2010, 6 years after the initial presentation with pituitary macroadenoma.
Figure 1: Comparison of histological features of pituitary adenoma, recurrent invasive adenoma and pituitary carcinoma.(a) Tumor revealing monomorphic population of round-to-spindly cells. (b) Invasive adenoma showing monomorphic tumor withan entrapped bony trabecula. (c) Pituitary carcinoma showing compact tumor cells.

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Figure 2: (a) Post-contrast T1-weighted coronal image showing invasive pituitary adenoma. (b) Post-contrast T1-weighted MRI image of lumbar spine revealing metastasis in vertebrae

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Figure 3: Comparison of expression of MIB-1 in (a) pituitary adenoma, (b) recurrent invasive adenoma and (c) pituitary carcinoma

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Figure 4: Comparison of expression of p53 in (a) pituitary adenoma, (b) recurrent invasive adenoma and (c) pituitary carcinoma

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 » Discussion Top

Pituitary neoplasms are classified into three groups according to their biologic behavior: benign, invasive adenoma and carcinoma. The diagnosis of pituitary carcinomas is reserved for pituitary neoplasms showing evidence of craniospinal or systemic metastases. Craniospinal metastases may arise via invasion into the subarachnoid space with subsequent tumor seeding along brain and spinal cord surfaces. [6],[7] Dissemination outside the cerebrospinal axis may occur via hematogenous or lymphatic spread. Vast majority of reported pituitary carcinomas are endocrinologically active, with 42% secreting ACTH and 33% secreting PRL. [2] Kars et al. reviewed 47 cases of malignant prolactinomas and found that 65% of the patients were male and the mean age of presentation was 44 years. [3] The presenting symptoms were related to hyperprolactinemia in 35% of reported cases, including amenorrhea, galactorrhea, impotency and decreased libido. At presentation, 75% had symptoms related to local compression, such as headache and bitemporal hemianopsia. The time interval between the onset of symptoms at presentation and subsequent metastases in the published cases was highly variable, with a median duration of 7 years (ranging from 1 month to 20 years). Local recurrence followed by repeated surgical interventions for local regrowth and extension of the pituitary tumor is frequently observed. Our patient was a 28-year-old woman who presented with reduced vision and amenorrhea. The patient was operated upon four times for repeated recurrence but eventually 6 years later developed multiple bone metastases and died within 2 months.

Primary pituitary carcinomas have varied histologic features, from monotonous proliferation of cells to cellular pleomorphism and prominent nucleoli. The cytologic atypia does not predict the tumor behavior. Majority of the metastases display nuclear pleomorphism or hyperchromasia. [8] In our patient, morphology at the metastatic site was benign-looking, but there was significant difference in the MIB-1 LI and p53 LI in the primary and metastatic tumors. In two studies done by Thapar et al., the Ki-67 LI and p53 LI of noninvasive adenoma, invasive adenoma, and primary pituitary carcinomas were 1.37%±0.15%, 4.66%±0.47%, and 11.91%±3.41%; and 0%, 15.2%, and 100%, respectively. [9],[10] In a similar study by Gaffe et al., the MIB-1 LI and p53 LI in invasive adenoma and carcinoma were 1.7%, 8%; and 37.3%, 49.9%, respectively. [11] Similarly our case showed progressive increase in MIB-1 LI and p53 LI in primary noninvasive adenoma, recurrent invasive adenoma and metastatic carcinoma.

To conclude, pituitary carcinoma is a rare tumor. Irrespective of the morphology, the behavior of pituitary neoplasms cannot be predicted. Pituitary adenomas with a benign morphology may recur and eventually metastasize after several years. Increased MIB-1 LI and p53 LI in recurrent adenomas should alert the doctors, and a close follow-up should be done.

 » Acknowledgments Top

The authors wish to express their thanks to Dr. P. M. Shah, Honorary Director; Dr. K. M. Patel, Dr. S. N. Shukla, Deputy Directors, Dr. M. J. Shah, Head of the department of pathology, of The Gujarat Cancer & Research institute

to allow us to publish this original article.

 » References Top

1.Pernicone PJ, Scheithauer BW, Sebo TJ, Kovacs KT, Horvath E, Young WF Jr, et al. Pituitary carcinoma: A clinicopathologic study of 15 cases. Cancer 1997;79:804-12.  Back to cited text no. 1
2.Ragel BT, Couldwell WT. Pituitary carcinoma: A review of the literature. Neurosurgical Focus 2004;16:e7.  Back to cited text no. 2
3.Kars M, Roelfsema F, Romijn A, Pereira AM. Malignant prolactinoma: Case report and review of the literature. Eur J Endocrinol 2006;155:523-34.   Back to cited text no. 3
4.Guastamacchia E, Triggiani V, Tafaro E, De Tommasi A, De Tommasi C, Luzzi S, et al. Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: A case report. 2007;32:231-6.  Back to cited text no. 4
5.Choi G, Choi HJ, Kim YM, Choi SH, Cho YC, Kim Y, et al. Pituitary carcinoma with mandibular metastasis: A case report. J Korean Med Sci 2007;22:S145-8.  Back to cited text no. 5
6.Landman RE, Horwith M, Peterson RE, Khandji AG, Wardlaw SL. Long term survival with ACTH-secreting carcinoma of the pituitary: A case report and review of literature. J Clin Endocrinol Metab 2002;87:3084-9.  Back to cited text no. 6
7.Frost AR, Tenner ST, Tenner M, Rollhauser C, Tabbara SO. ACTH-producing pituitary carcinoma presenting as cauda equine syndrome. Arch Pathol Lab Med 1995;119:93-6.  Back to cited text no. 7
8.Pernicone PJ, Scheithauer BW. Invasive pituitary adenoma and pituitary carcinoma. In: Thapar K, Kovacs K, Scheithauer BW, et al. editors. Diagnosis and Management of Pituitary Tumors. Totowa, NJ: Humana Press; 2001. p. 369-86.  Back to cited text no. 8
9.Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horvath E, Pernicone PJ, et al Proliferative activity and invasiveness among pituitary adenomas and carcinomas: An analysis using the MIB-1 antibody. Neurosurgery 1996;38:99-107.   Back to cited text no. 9
10.Thapar K, Scheithauer BW, Kovacs K, Pernicone PJ, Laws ER Jr p53 expression in pituitary adenomas and carcinomas: Correlation with invasiveness and tumor growth fractions. Neurosurgery 1996;38:763-71.  Back to cited text no. 10
11.Gaffey TA, Scheithauer BW, Lloyd RV, Burger PC, Robbins P, Fereidooni F, et al. Corticotroph carcinoma of pituitary: A clinicopathological study. Report of four cases. J Neurosurg 2002;96:352-60.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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