Skip to main content

Advertisement

SpringerLink
Log in

Invasive adenoma and pituitary carcinoma: a SEER database analysis

  • Original Article
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

Invasive pituitary adenomas and pituitary carcinomas are clinically indistinguishable until identification of metastases. Optimal management and survival outcomes for both are not clearly defined. The purpose of this study is to use the Surveillance, Epidemiology, and End Results (SEER) database to report patterns of care and compare survival outcomes in a large series of patients with invasive adenomas or pituitary carcinomas. One hundred seventeen patients diagnosed between 1973 and 2008 with pituitary adenomas/adenocarcinomas were included. Eighty-three invasive adenomas and seven pituitary carcinomas were analyzed for survival outcomes. Analyzed prognostic factors included age, sex, race, histology, tumor extent, and treatment. A significant decrease in survival was observed among carcinomas compared to invasive adenomas at 1, 2, and 5 years (p = 0.047, 0.001, and 0.009). Only non-white race, male gender, and age ≥65 were significant negative prognostic factors for invasive adenomas (p = 0.013, 0.033, and <0.001, respectively). There was no survival advantage to radiation therapy in treating adenomas at 5, 10, 20, or 30 years (p = 0.778, 0.960, 0.236, and 0.971). In conclusion, pituitary carcinoma patients exhibit worse overall survival than invasive adenoma patients. This highlights the need for improved diagnostic methods for the sellar phase to allow for potentially more aggressive treatment approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Oruçkaptan HH, Senmevsim O, Ozcan OE, Ozgen T (2000) Pituitary adenomas: results of 684 surgically treated patients and review of the literature. Surg Neurol 53:211–219

    Article  PubMed  Google Scholar 

  2. Scheithauer BW, Kovacs KT, Laws ER Jr, Randall RV (1986) Pathology of invasive pituitary tumors with special reference to functional classification. J Neurosurg 65:733–744

    Article  CAS  PubMed  Google Scholar 

  3. Selman WR, Laws ER, Scheithauer BW et al (1986) The occurrence of dural invasion in pituitary adenomas. J Neurosurg 64:402–407

    Article  CAS  PubMed  Google Scholar 

  4. Scheithauer BW, Kurtkaya-Yapicier O, Kovacs KT et al (2005) Pituitary carcinoma: a clinicopathologic review. Neurosurgery 56:1066–1074

    PubMed  Google Scholar 

  5. Beatriz M, Lopes S, Scheithauer BW et al (2005) Pituitary carcinoma. Endocrine 28:115–121

    Article  Google Scholar 

  6. Chacko G, Chacko AG, Kovacs K et al (2010) The clinical significance of MIB-1 labeling index in pituitary adenomas. Pituitary 13:337–344

    Article  PubMed  Google Scholar 

  7. Hussaini IM, Trotter C, Zhao Y et al (2007) Matrix metalloproteinase-9 is differentially expressed in nonfunctioning invasive and noninvasive pituitary adenomas and increases invasion in human pituitary adenoma cell line. Am J Pathol 170:356–365

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Lau Q, Scheithauer B, Kovacs K et al (2010) MGMT immunoexpression in aggressive pituitary adenoma and carcinoma. Pituitary 13:367–379

    Article  PubMed  Google Scholar 

  9. Pernicone PJ, Scheithauer BW, Sebo TJ et al (1997) Pituitary carcinoma: a clinicopathologic study of 15 cases. Cancer 79:804–812

    Article  CAS  PubMed  Google Scholar 

  10. Thapar K, Kovacs K, Scheithauer BW et al (1996) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38:99–107

    Article  CAS  PubMed  Google Scholar 

  11. Thapar K, Scheithauer BW, Kovacs K et al (1996) p53 expression in pituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions. Neurosurgery 38:765–771

    Article  CAS  PubMed  Google Scholar 

  12. Kaltsas GA, Grossman AB (1998) Malignant pituitary tumours. Pituitary 1:69–81

    Article  CAS  PubMed  Google Scholar 

  13. Zada G, Woodmansee WW, Ramkissoon S et al (2011) Atypical pituitary adenomas: incidence, clinical characteristics, and implications. J Neurosurg 114:336–344

    Article  PubMed  Google Scholar 

  14. Kaltsas GA, Nomikos P, Kontogeorgos G et al (2005) Clinical review: diagnosis and management of pituitary carcinomas. J Clin Endocrinol Metab 90:3089–3099

    Article  CAS  PubMed  Google Scholar 

  15. Clarke SD, Woo SY, Butler EB et al (1993) Treatment of secretory pituitary adenoma with radiation therapy. Radiology 188:759–763

    CAS  PubMed  Google Scholar 

  16. Grigsby PW, Simpson JR, Emami BN et al (1988) Prognostic factors and results of surgery and postoperative irradiation in the management of pituitary adenomas. Int J Radiat Oncol Biol Phys 16:1411–1417

    Article  Google Scholar 

  17. Kovalic JJ, Mazoujian G, McKeel DW et al (1993) Immunohistochemistry as a predictor of clinical outcome in patients given postoperative radiation for subtotally resected pituitary adenomas. J Neurooncol 16:227–232

    Article  CAS  PubMed  Google Scholar 

  18. Pinchot SN, Sippel R, Chen H (2009) ACTH-producing carcinoma of the pituitary with refractory Cushing's disease and hepatic metastases: a case report and review of the literature. World J Surg Oncol 7:39

    Article  PubMed Central  PubMed  Google Scholar 

  19. van der Klaauw AA, Kienitz T, Strasburger CJ et al (2009) Malignant pituitary corticotroph adenomas: report of two cases and a comprehensive review of the literature. Pituitary 12:57–69

    Article  PubMed  Google Scholar 

  20. Surveillance Epidemiology and End Results Program (2010) SEER*Stat database: incidence - SEER 17 regs research data + Hurricane Katrina impacted Louisiana cases, Nov 2010 sub (1973–2008 varying)-linked to county attributes–total U.S., 1969–2009 counties. Nov edn. National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch

  21. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) version 7.0.4

  22. StataCorp. 2005. Stata Statistical Software: Release 9. College Station, TX: StataCorp LP 9

  23. Raverot G, Wierinckx A, Dantony E et al (2010) Prognostic factors in prolactin pituitary tumors: clinical, histological, and molecular data from a series of 94 patients with a long postoperative follow-up. J Clin Endocrinol Metab 95:1708–1716

    Article  CAS  PubMed  Google Scholar 

  24. Grossman R, Mukherjee D, Chaichana K et al (2010) Complications and death among elderly patients undergoing pituitary tumour surgery. Clin Endocrinol 73:361–368

    Article  Google Scholar 

  25. Benbow SJ, Foy P, Jones B et al (1997) Pituitary tumours presenting in the elderly: management and outcome. Clin Endocrinol 46:657–660

    Article  CAS  Google Scholar 

  26. Cohen DL, Bevan JS, Adams CB (1989) The presentation and management of pituitary tumours in the elderly. Age Ageing 18:247–252

    Article  CAS  PubMed  Google Scholar 

  27. Rogne SG, Konglund A, Meling TR et al (2009) Intracranial tumor surgery in patients >70 years of age: is clinical practice worthwhile or futile? Acta Neurol Scand 120:288–294

    Article  CAS  PubMed  Google Scholar 

  28. Hong J, Ding X, Lu Y (2010) Clinical analysis of 103 elderly patients with pituitary adenomas: transsphenoidal surgery and follow-up. J Clin Neurosci 15:1091–1095

    Article  Google Scholar 

  29. Sheehan JM, Douds GL, Hill K, Farace E (2008) Transsphenoidal surgery for pituitary adenoma in elderly patients. Acta Neurochir (Wien) 150:571–574

    Article  CAS  Google Scholar 

  30. Delgrange E, Trouillas J, Maiter D et al (1997) Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study. J Clin Endocrinol Metab 82:2102–2107

    CAS  PubMed  Google Scholar 

  31. Schaller B (2005) Gender-related differences in prolactinomas. A clinicopathological study. Neuro Endocrinol Lett 26:152–159

    PubMed  Google Scholar 

  32. Schaller B (2003) Gender-related differences in non-functioning pituitary adenomas. Neuro Endocrinol Lett 24:425–430

    PubMed  Google Scholar 

  33. Dudziak K, Honegger J, Bornemann A et al (2011) Pituitary carcinoma with malignant growth from first presentation and fulminant clinical course—case report and review of the literature. J Clin Endocrinol Metab 96:2665–2669

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Tara M. Hansen

  2. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Sachin Batra, Michael Lim, Gary L. Gallia & Alfredo Quinones-Hinojosa

  3. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Michael Lim & Gary L. Gallia

  4. Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Michael Lim

  5. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Peter C. Burger

  6. Division of Endocrinology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Roberto Salvatori & Gary Wand

  7. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, 401 North Broadway, Suite 1440, Baltimore, MD, 21231, USA

    Lawrence Kleinberg & Kristin J. Redmond

Authors
  1. Tara M. Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sachin Batra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gary L. Gallia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter C. Burger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Roberto Salvatori
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gary Wand
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alfredo Quinones-Hinojosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lawrence Kleinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kristin J. Redmond
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kristin J. Redmond.

Additional information

Comments

Ludwig Benes, Arnsberg Germany

This well-written and interesting article deals with the rare pathologies of invasive pituitary adenomas and carcinomas collected over a 35-year time period. The data from a large series of 117 individuals suffering from these pathologies is illustrated comprehensively. Information is given regarding the role of genetic studies on this topic and also the prognostic significance of molecular markers. The authors nicely point out the differences in survival outcomes in these patients during a long follow-up period of 10 years underlining what most of the readers may have thought but could not really prove on the basis of a robust data analysis.

Paolo Cappabianca, Teresa Somma, Naples, Italy

The authors present a retrospective analysis pointing out the differences in terms of survival outcomes in patients with invasive pituitary adenomas and carcinomas over a 10-year follow-up period. Once again, the importance of early differential diagnosis has been emphasized to provide patients with an adequate treatment.

Though, this manuscript offers the possibility to draw many considerations.

The invasive adenoma is identified as a benign pituitary tumor, even if it exhibits an aggressive biological behavior, infiltrating the dura mater, cranial bone, or sphenoid sinus. Our experience constantly teaches us to warn these “false benign” lesions; they, indeed, require difficult management to achieve an adequate disease control. The pituitary carcinoma is defined as a tumor of the pituitary gland exhibiting cerebrospinal and/or systemic metastasis.

In our opinion, clinical evaluation of the patient needs to be completed by head and spinal MR and total body PET/CT to diagnose the presence of eventual metastasis indicative of a neoplastic progression. The metastatic dissemination more commonly involves the CSF axis, including virtually any site within the supratentorial, infratentorial, and spinal compartments. Extradural dissemination occurs less frequently and also exhibits less geographic restraint; bone, liver, lymph nodes, lung, kidney, and heart have all been reported as evidence of malignancy.

Furthermore, we believe that the genetic analysis can be useful not only to evaluate the biological behavior, as affirmed in the article, but also to define the therapeutic efficacy.

In the manuscript, the authors affirm the need of an aggressive treatment for these lesions.

We think that surgery must be completed by medical and radiation therapy.

The drug temozolomide has recently been documented to be effective against these lesions (1, 5, 7) especially if they show low levels of MGMT expression or present the immunopositivity of MSH6 (2, 4, 8), though new targeted therapies have been studied for lesions resistant to temozolomide (3, 6, 9). Finally, the radiotherapy plays an important role in the management of these lesions, especially in those of incomplete surgical resection and low effectiveness of medical treatment.

References

Colao A, Grasso LF, Pivonello R, Lombardi G. Therapy of aggressive pituitary tumors. Expert Opin Pharmacother. 2011 Jul;12(10):1561–70. doi: 10.1517/14656566.2011.568478. Epub 2011 Mar 24.

McCormack AI, Wass JA, Grossman AB. Aggressive pituitary tumours: the role of temozolomide and the assessment of MGMT status. Eur J Clin Invest. 2011 Oct;41(10):1133–48. doi: 10.1111/j.1365-2362.2011.02520.x. Epub 2011 Apr 18.

Jouanneau E, Wierinckx A, Ducray F, Favrel V, Borson-Chazot F, Honnorat J, Trouillas J, Raverot G. New targeted therapies in pituitary carcinoma resistant to temozolomide. Pituitary. 2012 Mar;15(1):37–43. doi: 10.1007/s11102-011-0341-0.

Kovacs K, Scheithauer BW, Lombardero M, McLendon RE, Syro LV, Uribe H, Ortiz LD, Penagos LC. MGMT immunoexpression predicts responsiveness of pituitary tumors to temozolomide therapy. Acta Neuropathol. 2008 Feb;115(2):261–2. Epub 2007 Oct 10.

Losa M, Mazza E, Terreni MR, McCormack A, Gill AJ, Motta M, Cangi MG, Talarico A, Mortini P, Reni M. Salvage therapy with temozolomide in patients with aggressive or metastatic pituitary adenomas: experience in six cases. Eur J Endocrinol. 2010 Dec;163(6):843–51. doi: 10.1530/EJE-10-0629. Epub 2010 Sep 24.

Ortiz LD, Syro LV, Scheithauer BW, Ersen A, Uribe H, Fadul CE, Rotondo F, Horvath E, Kovacs K. Anti-VEGF therapy in pituitary carcinoma. Pituitary. 2012 Sep;15(3):445–9. doi: 10.1007/s11102-011-0346-8.

Ortiz LD, Syro LV, Scheithauer BW, Rotondo F, Uribe H, Fadul CE, Horvath E, Kovacs K. Temozolomide in aggressive pituitary adenomas and carcinomas. Clinics (Sao Paulo). 2012;67 Suppl 1:119–23.

Salehi F, Scheithauer BW, Kros JM, Lau Q, Fealey M, Erickson D, Kovacs K, Horvath E, Lloyd RV. MGMT promoter methylation and immunoexpression in aggressive pituitary adenomas and carcinomas. J Neurooncol. 2011 Sep;104(3):647–57. doi: 10.1007/s11060-011-0532-6. Epub 2011 Feb 11.

Thearle MS, Freda PU, Bruce JN, Isaacson SR, Lee Y, Fine RL. Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor. Pituitary. 2011 Dec;14(4):418–24. doi: 10.1007/s11102-009-0211-1.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hansen, T.M., Batra, S., Lim, M. et al. Invasive adenoma and pituitary carcinoma: a SEER database analysis. Neurosurg Rev 37, 279–286 (2014). https://doi.org/10.1007/s10143-014-0525-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10143-014-0525-y

Keywords

Search

Navigation