Growth pattern and rate in residual nonfunctioning pituitary adenomas: correlations among tumor volume doubling time, patient age, and MIB-1 index.

OBJECT Surgical cure can be achieved in pituitary adenomas when they are completely removed. It is controversial whether postoperative radiation therapy should be given to prevent recurrence, and whether an early reoperation should be performed for residual adenomas, because we have little information about the natural history of postoperative residual adenomas. METHODS The residual tumor volume was serially measured in 40 nonfunctioning pituitary adenomas (NFPAs) and the tumor volume doubling time (TVDT) was calculated. Correlations between the patients' age, tumor volume, log TVDT, and MIB-1 index were examined. Other factors including the patient's sex, cavernous sinus (CS) invasion by the tumor, or presence of an intratumoral cyst were analyzed to assess their influence on the TVDT. Values are expressed as the means +/- standard deviations. Thirty-eight adenomas increased in volume and two decreased during a follow-up period ranging from 4 to 141 months (mean 52.5 months). Exponentially linear tumor growth was observed in the 38 growing adenomas regardless of the residual tumor volume, with the TVDT ranging from 506 to 5378 days (mean 1836 days). The patients' age was 57.1 +/- 15.7 years (range 15-79 years), the tumor volume at the beginning of the magnetic resonance imaging observation period was 2.5 +/- 2.2 cm3 (range 0.07-14.5 cm3), and the MIB-1 index was 0.73 +/- 0.68% (range 0.1-2.9%). There was a correlation between the log TVDT and patient age (R = 0.73), an inverse correlation between the log TVDT and MIB-1 index (r = -0.49), and an inverse correlation between the MIB-1 index and patient age (r = -0.61). A significant difference (p = 0.0001) was noted between the TVDT (1,106 days) in the 19 patients younger than 61 years of age and the TVDT (2566 days) in the 19 patients who were 61 years of age or older. There was also a significant difference (p = 0.0002) between the age (50.8 +/- 15.3 years) of the patients with rapidly growing tumors (TVDT < 1,836 days, 24 patients) and the age (69.1 +/- 7.6 years) of the patients with slowly growing tumors (TVDT> 1836 days, 14 patients). Other factors including the patients' sex, CS invasion, and intratumoral cyst formation did not affect the TVDT of residual NFPAs. CONCLUSIONS The tumor growth rate of residual NFPAs is strongly influenced by the patient's age. The TVDT in elderly patients is much longer than that previously reported. Treatment strategies that take into consideration the natural history of residual adenomas should be established especially in the elderly population.

[1]  T. Kokunai,et al.  Clinical features and growth fractions of pituitary adenomas. , 1997, Surgical neurology.

[2]  P. Kleihues,et al.  Growth rate of human pituitary adenomas. , 1987, Journal of neurosurgery.

[3]  J. Hardy,et al.  The clinical and endocrine outcome to trans‐sphenoidal microsurgery of nonsecreting pituitary adenomas , 1991, Cancer.

[4]  Radiotherapy for nonfunctional pituitary adenoma: analysis of long-term tumor control. , 1998 .

[5]  B. Scheithauer,et al.  Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas. , 1986, Journal of neurosurgery.

[6]  Charles B. Wilson,et al.  The Case for Initial Surgical Removal of Certain Prolactinomas , 1997 .

[7]  M. Molitch,et al.  Therapeutic controversy : Management of prolactinomas , 1997 .

[8]  T. Erbas,et al.  Radiotherapy in the management of giant pituitary adenomas. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[9]  R. Tsang,et al.  Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors. , 1994, International journal of radiation oncology, biology, physics.

[10]  C. Wilson A decade of pituitary microsurgery. The Herbert Olivecrona lecture. , 1984, Journal of neurosurgery.

[11]  M. Key,et al.  Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. , 1991, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[12]  C. Burke,et al.  An audit of selected patients with non‐functioning pituitary adenoma treated by transsphenoidal surgery without irradiation , 1994, Clinical endocrinology.

[13]  J. Gerdes,et al.  Immunohistological detection of tumour growth fraction (Ki-67 antigen) in formalin-fixed and routinely processed tissues. , 1992, The Journal of pathology.

[14]  M. Mikhael,et al.  Transsphenoidal microsurgery of pituitary macroadenomas with long-term follow-up results. , 1983, Journal of neurosurgery.

[15]  E. Hedley‐Whyte,et al.  Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence. , 1993, Journal of neurosurgery.

[16]  K. Lillehei,et al.  Reassessment of the role of radiation therapy in the treatment of endocrine-inactive pituitary macroadenomas. , 1998, Neurosurgery.

[17]  K. Kurisu,et al.  MIB1 immunopositivity is associated with rapid regrowth of pituitary adenomas , 2005, Acta Neurochirurgica.

[18]  J. Flickinger,et al.  Radiotherapy of nonfunctional adenomas of the pituitary gland. Results with long‐term follow‐up , 1989, Cancer.

[19]  A. Detta,et al.  Pituitary adenoma proliferative indices and risk of recurrence. , 1992, British journal of neurosurgery.

[20]  T. Ohnishi,et al.  The correlation of Ki-67 staining indices with tumour doubling times in regrowing non-functioning pituitary adenomas , 2005, Acta Neurochirurgica.

[21]  E. Knosp,et al.  Proliferation activity in pituitary adenomas: measurement by monoclonal antibody Ki-67. , 1989, Neurosurgery.

[22]  A. Karameris,et al.  Apoptosis in human pituitary adenomas: a morphologic and in situ end-labeling study. , 1997, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[23]  B. Scheithauer,et al.  Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. , 1996, Neurosurgery.

[24]  F. Mangili,et al.  Proliferation Index of Nonfunctioning Pituitary Adenomas: Correlations with Clinical Characteristics and Long-term Follow-up Results , 2000, Neurosurgery.

[25]  E. Laws,et al.  Neurosurgical management of acromegaly. Results in 82 patients treated between 1972 and 1977. , 1979, Journal of neurosurgery.

[26]  N. Watts,et al.  Transsphenoidal adenomectomy for growth hormone-secreting pituitary adenomas in acromegaly: outcome analysis and determinants of failure. , 1993, Journal of neurosurgery.

[27]  B. Scheithauer,et al.  Pituitary adenomas associated with hyperprolactinemia: a clinical and immunohistochemical study of 97 patients operated on transsphenoidally. , 1985, Mayo Clinic proceedings.

[28]  S. DeArmond,et al.  The proliferative potential of human pituitary tumors in situ. , 1986, Journal of neurosurgery.