Tetsuhiko Sakoguchi

Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae

OBJECTIVE Somatotropinomae are classified as densely and sparsely granulated adenomae, which typically exhibit a perinuclear pattern (PP) and a dot pattern (DP) in cytokeratin (CK) immunostaining respectively. Some exhibit a mixed pattern (MP). We studied the relationship between these somatotropinoma subtypes and their clinico-pathological features. METHODS The study population consisted of 141 Japanese acromegalic patients. We evaluated their clinical presentation and their response to provocation tests with TRH and LHRH and to suppression (octreotide) test. Tumour tissues were subjected to immunostaining for CAM-5.2, MIB-1, CD34, E-cadherin (CDH1) and p53 (TP53). In 43 cases (30 non-DP and 13 DP), we analysed gsp mutations (constitutively activating mutations of the G(s)α protein that is encoded by GNAS gene). RESULTS The 141 adenomae were categorised into three subtypes based on their CK staining patterns; 30 (21.3%) exhibited DP, 83 (58.9%) exhibited PP, and 28 (19.9%) exhibited MP. Compared with the other subtypes, DP adenomae were significantly larger, and their E-cadherin expression and response to TRH, LHRH and octreotide challenge were lower. The postoperative cure rate tended to be lower in DP adenomae. gsp mutations were detected in 25 of 43 cases examined (58.1%); 20 of the 30 non-DP (66.7%) and 5 of the 13 DP tumours (38.5%) were affected by the mutation. CONCLUSION DP somatotropinomae exhibit characteristic features. Compared with the non-DP subtypes, DP adenomae manifested a larger tumour size, a lower incidence of abnormal responses to TRH and LHRH challenge, a poor response to octreotide test and a lower expression of E-cadherin. gsp mutation was not exclusive for non-DP somatotropinomae.

Role of PROPELLER diffusion-weighted imaging and apparent diffusion coefficient in the evaluation of pituitary adenomas

OBJECTIVE The relationship between tumor consistency and apparent diffusion coefficient (ADC) values is controversial. We evaluated the role of the ADC using an advanced diffusion-weighted imaging (DWI) technique. We employed periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) DWI acquired on a 3-T magnetic resonance imaging (MRI) scanner to assess the consistency of pituitary adenomas and examined the relationship between the ADC and the hormone secretion status of the tumors and their MIB-1 labeling index (MIB-1 LI). MATERIALS AND METHODS The study protocol was approved by our institutional review board. We retrospectively studied 24 operated patients with pituitary adenomas who had undergone PROPELLER DWI on a 3-T MRI scanner. Conventional MRI findings were expressed as the ratio of the signal intensity (SI) in the lesions to the SI of the normal white matter and the degree of contrast enhancement. Minimum-, mean-, and maximum ADC (ADCmin, ADCmean, ADCmax) values were calculated. The consistency of the tumors was determined by neurosurgeons. All surgical specimens were submitted for histological study to calculate the MIB-1 LI and the percent collagen content. Preoperative MRI-, intraoperative-, and histological findings were analyzed by a statistician. RESULTS Our study included 15 soft-, 5 fibrous-, and 4 hard tumors. Tumor consistency was strongly associated with the percent collagen content. However, neither the tumor consistency nor the percent collagen content was correlated with MRI findings or ADC values. The SI of growth hormone-producing adenomas on T2-WI was lower than of the other pituitary adenomas studied (p<0.01); no other significant difference was found in the ADC or on conventional MRI between pituitary adenomas with different secretory functions. The MIB-1 LI of pituitary adenomas was not correlated with their appearance on conventional MRI or their ADC values. CONCLUSION Using the PROPELLER DWI technique we confirmed that the ADC was not correlated with the consistency of pituitary adenomas. We also demonstrate that the ADC was not associated with the hormone-secreting status or the MIB-1 LI of pituitary adenomas.

Role of PROPELLER diffusion weighted imaging and apparent diffusion coefficient in the diagnosis of sellar and parasellar lesions

OBJECTIVE To evaluate the role of the apparent diffusion coefficient (ADC) using periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) diffusion weighted imaging (DWI) in the differentiation between sellar and parasellar mass lesions. MATERIALS AND METHODS The study protocol was approved by our institutional review board. We retrospectively studied 60 patients with sellar and parasellar lesions who had undergone PROPELLER DWI on a 3-T MR imager. Conventional MRI findings were expressed as the ratio of signal intensity (SI) in the lesions to the normal white matter and the degree of contrast enhancement. ADC values were calculated as the minimum (ADC-MIN), mean (ADC-MEAN), and maximum (ADC-MAX). All patients underwent surgery and all specimens were examined histologically. Logistic discriminant analysis was performed by using the SI ratios on T1- and T2-weighted images (T1-WI, T2-WI), the degree of enhancement, and absolute ADC values as independent variables. RESULTS ADC-MIN of hemorrhagic pituitary adenomas was lower than of the other lesions with similar appearance on conventional MRI (non-hemorrhagic pituitary adenomas, craniopharyngiomas, Rathkes cleft cysts; accuracy 100%); the useful cut-off value was 0.700 x 10(-3)mm(2)/s. ADC-MAX of meningiomas was lower than of non-hemorrhagic pituitary adenomas (accuracy 90.3%; p<0.01). ADC-MIN of craniopharyngiomas was lower than of Rathkes cleft cysts (accuracy 100%; p<0.05). CONCLUSION As PROPELLER DWI is less sensitive to susceptibility artifacts than single-shot echoplanar DWI, it is more useful in the examination of sellar and parasellar lesions. Calculation of the ADC values helps to differentiate between various sellar and parasellar lesions.

The long-term recurrence of Rathke's cleft cysts as predicted by histology but not by surgical procedure

OBJECTIVE Patients with symptomatic Rathkes cleft cysts (RCCs) managed by surgical treatment often experience recurrence. The authors attempted to clarify the outcome of surgically treated RCCs over a long-term follow-up period. METHODS Ninety-one consecutive RCC patients with a follow-up period of more than 12 months (mean 80.2 months, range 12-297 months) were retrospectively studied. The authors examined the clinical features and postoperative course of patients who experienced a reaccumulation of cyst contents visible on MRI after the initial surgery, and they investigated data from the patients who underwent reoperation for symptomatic recurrent RCCs. RESULTS Reaccumulation of cyst contents occurred in 36 patients (39.6%). In 34 of these patients, a reaccumulation occurred in the first 5 years after surgery. The initial cysts in these patients were most often large, with squamous metaplasia in the cyst walls. Thirteen patients (14.3%) with recurrent symptoms underwent a reoperation, and 10 of the 13 patients had a reaccumulation of RCCs within the 1st year after surgery. The reoperations were performed in the 1st year (61.5%) or several years later (23.1%). Patients were likely to initially have had a visual disturbance and the cyst walls likely included squamous metaplasia. However, no association was observed between the incidence of reaccumulation/reoperation of RCCs and the surgical procedure for RCCs. CONCLUSIONS The reaccumulation rate of RCC is high in the long-term period, and it is associated with the histological findings but not with the surgical procedure. Long-term monitoring, for a period of at least 5 years, should therefore be conducted to identify and assess any RCC reaccumulation.

Masked hyperprolactinemia: Tumor-derived factors inhibiting prolactin secretion caused by pituitary-stalk damage

Tumor-induced secondary hyperprolactinemia in patients with non-prolactin (PRL)-secreting pituitary tumors has traditionally been ascribed to pituitary stalk damage. We conducted a retrospective analysis of secondary hyperprolactinemia in 106 patients who underwent surgery for non-PRL-secreting pituitary adenoma. The incidence of hyperprolactinemia was evaluated, and pituitary-stalk damage was assessed radiographically using MRI (size of tumor and extension type) and endocrinologically by monitoring hormonal function using a provocation test. The effect of a tumor-derived intrasellar factor, leukemia inhibitory factor (LIF), on hyperprolactinemia was also investigated. Hyperprolactinemia was observed in 31 of the 106 (29.2%) patients. It was not correlated with either physical stalk compression or endocrinological dysfunction. However, LIF expression was negatively correlated with the incidence of secondary hyperprolactinemia (p<0.01). Although secondary hyperprolactinemia might be caused by pituitary stalk damage, it is possible that LIF masks the effect.

Transsphenoidal Posterior Pituitary Lobe Biopsy in Patients with Neurohypophysial Lesions

OBJECTIVE The differential diagnosis of neurohypophysial lesions is difficult, and surgical biopsies are indispensable in the histologic diagnosis of some patients. Although pituitary stalk biopsies are uniformly performed, there is a considerable risk that they will result in impaired hormonal secretion. We attempt to clarify the usefulness and safety of posterior pituitary lobe biopsy by transsphenoidal surgery (TSS). METHODS The cases of 11 consecutive patients who underwent posterior pituitary lobe biopsies by TSS were retrospectively studied. Patients with cystic sellar lesions were excluded. We examined the clinical findings, endocrinologic data, magnetic resonance imaging findings, and histologic diagnoses of the patients. The locations of neurohypophysial lesions and the histologic diagnoses by posterior pituitary lobe biopsies were examined. RESULTS The major preoperative clinical symptoms were diabetes insipidus (DI) (90.9%), followed by anterior pituitary lobe dysfunction (hypopituitarism) (54.5%). In all the patients, the lesions occupied the pituitary stalk and the posterior pituitary lobe, and the bright spot, which would indicate a normal posterior pituitary gland, disappeared on T1-weighted imaging. The posterior pituitary lobe specimens could be histologically diagnosed in all these cases. DI persisted in 10 patients with preoperative DI after the biopsy, whereas the 1 patient without preoperative DI did not suffer from DI after the biopsy. CONCLUSIONS A posterior pituitary lobe biopsy by TSS may be an alternative to pituitary stalk biopsy in patients with neurohypophysial lesions.