Prognostic value of chromosomal imbalances, gene mutations, and BAP1 expression in uveal melanoma.

Uveal melanoma (UM) exhibits recurring chromosomal abnormalities and gene driver mutations, which are related to tumor evolution/progression. Almost half of the patients with UM develop distant metastases, predominantly to the liver, and so far there are no effective adjuvant therapies. An accurate UM genetic profile could assess the individual patient's metastatic risk, and provide the basis to determine an individualized targeted therapeutic strategy for each UM patient. To investigate the presence of specific chromosomal and gene alterations, BAP1 protein expression, and their relationship with distant progression free survival (DPFS), we analyzed tumor samples from 63 UM patients (40 men and 23 women, with a median age of 64 years), who underwent eye enucleation by a single cancer ophthalmologist from December 2005 to June 2016. UM samples were screened for the presence of losses/gains in chromosomes 1p, 3, 6p, and 8q, and for mutations in GNAQ, GNA11, BAP1, SF3B1, and EIF1AX. BAP1 protein expression was detected by immunohistochemistry (IHC). Multivariate analysis showed that the presence of monosomy 3, 8q gain, and loss of BAP1 protein were significantly associated to DPFS, while BAP1 gene mutation was not, mainly due to the presence of metastatic UM cases with negative BAP1 IHC and no BAP1 mutation detected by Sanger sequencing. Loss of BAP1 protein expression and monosomy 3 represent the strongest predictors of metastases, and may have important implications for implementation of patient surveillance, properly designed clinical trials enrollment, and adjuvant therapy.

Prevalence of oral human papillomavirus in men attending an Italian sexual health clinic.

A high-risk population, formed by 79 consecutive male attendees of our sexually transmissible infections clinic, and who did not have any overt signs of human papillomavirus (HPV) infection, were examined. Oral HPV prevalence (37%) was much higher than previously reported. Periurethral HPV-DNA was found in 49% of the patients and anal HPV-DNA was found in 43% of the patients. Considering the high prevalence of oral HPV obtained in the current study, it is important to further investigate the burden of oral HPV, not only in men who have sex with men, but also in heterosexual men and in women.

Myenteric plexitis: A frequent feature in patients undergoing surgery for colonic diverticular disease.

BACKGROUND: Diverticular disease of the colon is frequent in clinical practice, and a large number of patients each year undergo surgical procedures worldwide for their symptoms. Thus, there is a need for better knowledge of the basic pathophysiologic mechanisms of this disease entity. OBJECTIVES: Because patients with colonic diverticular disease have been shown to display abnormalities of the enteric nervous system, we assessed the frequency of myenteric plexitis (i.e. the infiltration of myenteric ganglions by inflammatory cells) in patients undergoing surgery for this condition. METHODS: We analyzed archival resection samples from the proximal resection margins of 165 patients undergoing left hemicolectomy (60 emergency and 105 elective surgeries) for colonic diverticulitis, by histology and immunochemistry. RESULTS: Overall, plexitis was present in almost 40% of patients. It was subdivided into an eosinophilic (48%) and a lymphocytic (52%) subtype. Plexitis was more frequent in younger patients; and it was more frequent in those undergoing emergency surgery (50%), compared to elective (28%) surgery (p = 0.007). All the severe cases of plexitis displayed the lymphocytic subtype. CONCLUSIONS: In conclusion, myenteric plexitis is frequent in patients with colonic diverticular disease needing surgery, and it might be implicated in the pathogenesis of the disease.

Lymph Node Metastasis from Tall-Cell Thyroid Cancer Negative on 18F-FDG PET/CT and Detected by 18F-Choline PET/CT.

A 77-year-old woman underwent thyroidectomy and (131)I remnant ablation for tall-cell differentiated cancer (DTC) of the left lobe. Detectable Tg levels (4.1 µg/L) under TSH suppression, with undetectable serum Tg-antibody levels, prompted neck ultrasonography, which revealed a lymph node in the left laterocervical region and in the right retroclavicular region. (18)F-FDG PET/CT showed uptake by the left lymph node. (18)F-choline PET/CT showed increased uptake by both lymph nodes. Histopathology revealed DTC solid metastasis in the left lymph node and solid and cystic metastasis in the right one. (18)F-choline PET/CT can locate virulent DTC recurrence, thereby increasing (18)F-FDG PET/CT information.

Diagnostic value of MRI proton density fat fraction for assessing liver steatosis in chronic viral C hepatitis.

OBJECTIVE: To assess the diagnostic performance of a T1-independent, T2*-corrected multiecho magnetic resonance imaging (MRI) technique for the quantification of hepatic steatosis in a cohort of patients affected by chronic viral C hepatitis, using liver biopsy as gold standard. METHODS: Eighty-one untreated patients with chronic viral C hepatitis were prospectively enrolled. All included patients underwent MRI, transient elastography, and liver biopsy within a time interval <10 days. RESULTS: Our cohort of 77 patients included 43/77 (55.8%) males and 34/77 (44.2%) females with a mean age of 51.31 ± 11.27 (18-81) years. The median MRI PDFF showed a strong correlation with the histological fat fraction (FF) (r = 0.754, 95% CI 0.637 to 0.836, P < 0.0001), and the correlation was influenced by neither the liver stiffness nor the T2* decay. The median MRI PDFF result was significantly lower in the F4 subgroup (P < 0.05). The diagnostic accuracy of MRI PDFF evaluated by AUC-ROC analysis was 0.926 (95% CI 0.843 to 0.973) for S ≥ 1 and 0.929 (95% CI 0.847 to 0.975) for S = 2. CONCLUSIONS: Our MRI technique of PDFF estimation allowed discriminating with a good diagnostic accuracy between different grades of hepatic steatosis.

Late-onset metastasis of renal cell carcinoma into a hot thyroid nodule: an uncommon finding not to be overlooked.

We report the case of a 74-year-old man with a four-year history of right nephrectomy for clear cell renal carcinoma (CCRC) who was diagnosed with hyperthyroidism. On ultrasound (US), a 5 cm solid isohypoechoic nodule with intranodular vascularization was found in the left thyroid lobe. The nodule was deemed autonomous on (99m)Tc thyroid scan. Methimazole was started and serum thyroid hormone levels quickly normalized; euthyroidism was maintained with a very low dosage of antithyroid drug. Over time, compressive symptoms and local pain occurred and US revealed growth of the nodule. Total thyroidectomy was performed and the combined histological and immunohistochemical evaluation deemed the nodule compatible with metastasis of CCRC; on 2-year follow-up, no tumor relapse was ascertained. In patients with a history of cancer, a thyroid nodule, even if hyperfunctioning, must be suspected of being a metastasis and investigated. Hot nodules, which are largely benign, may be vulnerable to metastatic colonization owing to their rich vascularization. In these cases, surgery may be curative.

Focus on high-risk DTC patients: high postoperative serum thyroglobulin level is a strong predictor of disease persistence and is associated to progression-free survival and overall survival.

INTRODUCTION: No parameters predicting recurrence are available for high-risk differentiated thyroid cancer (DTC) patients, and 2-year-follow-up is required to modify the initial prognostic classification. High thyroglobulin (Tg) levels before ¹³¹I-remnant-ablation, during L-thyroxine-withdrawal (ablation-Tg) have undetermined predictive/prognostic significance in low-risk DTC patients. Our study aimed to assess the positive predictive value (PPV) of ablation-Tg in high-risk DTC patients and to evaluate whether high ablation-Tg levels were associated with progression-free-survival (PFS) and overall survival (OS). PATIENTS AND METHODS: We selected 243 high-risk DTC patients. All patients underwent total thyroidectomy and ¹³¹I-remnant-ablation (initial therapy). Clinical data obtained during a median 5-year follow-up were used to assess the response and outcome. The association between disease persistence/recurrence after initial therapy, ablation-Tg, and other risk-factors (T, N, G, histology, and MACIS score) was evaluated through univariate and multivariate analyses, as was the association between PFS, OS ablation-Tg, and other risk factors. RESULTS: Ablation-Tg of 50 µg/L or greater displayed the highest PPV(97%) for disease persistence. In the univariate analysis, high levels of ablation-Tg were confirmed in patients with persistent disease after initial therapy: the higher the odds ratios, the higher the ablation-Tg levels. On multivariate analysis, ablation-Tg was the best predictive factor, especially on comparing patients with ablation-Tg levels of 50 µg/L or greater and those with ablation-Tg less than 2 µg/L (adjusted OR, 818). In a multivariate Cox model, ablation-Tg was the factor most closely associated with PFS (HR, 65.9). The prognostic value of ablation-Tg was confirmed by the overall-survival curves and adjusted risk estimates (adjusted HR=26.7). CONCLUSIONS: Ablation-Tg levels of 50 µg/L or greater are a valuable initial predictor of disease persistence/recurrence in high-risk DTC patients. A significant association emerged between high ablation-Tg levels of 50 µg/L or greater and both progression-free survival (PFS) and overall survival (OS).

A randomized, placebo-controlled, preoperative trial of allopurinol in subjects with colorectal adenoma.

Inflammation and oxidative stress play a crucial role in the development of colorectal cancer (CRC) and interference with these mechanisms represents a strategy in CRC chemoprevention. Allopurinol, a safe molecular scavenger largely used as antigout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies. We conducted a randomized, double-blind, placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis. After complete colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol (100 mg or 300 mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the immunohistochemical (IHC) expression of NF-κB, ß-catenin, topoisomerase-II-α, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in adenomatous polyps and normal adjacent colonic tissue. Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas ß-catenin and NF-κB expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of -10.6%, 95% confidence interval (CI), -20.5 to -0.7, and -8.1%, 95% CI, -22.7 to 6.5, respectively. NF-κB also decreased significantly in normal adjacent tissue (-16.4%; 95% CI, -29.0 to -3.8). No dose-response relationship was noted, except for NF-κB expression in normal tissue. Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity.

Fast growing penis ulcer: an unusual coincidence.

A 57-year-old man was seen with a 2-week history of progressive enlargement of an asymptomatic genital ulcer associated with bilateral inguinal lymphadenomegaly. Multiple unprotected heterosexual contacts were reported. The family doctor misdiagnosed primary syphilis with the following laboratory results: negative findings on the Venereal Disease Research Laboratory test, positive findings on the Treponema pallidum particle agglutination assay (titer 1:1280), and IgM negative on the Treponema pallidum particle agglutination assay. The patient was treated with penicillin G for the diagnosis of indeterminate latent syphilis and initially denied authorization for a skin biopsy. After 2 weeks, fast enlargement of the lesion was documented. He underwent skin biopsy, and the histopathologic examination revealed squamous cell carcinoma, and polymerase chain reaction for human papillomavirus 16 was positive.

Accuracy in melanoma detection: a 10-year multicenter survey.

BACKGROUND: Early excision is the only strategy to reduce melanoma mortality, but unnecessary excision of benign lesions increases morbidity and healthcare costs. OBJECTIVE: To assess accuracy in melanoma detection based on number-needed-to-excise (NNE) values over a 10-year period. METHODS: Information was retrieved on all histopathologically confirmed cutaneous melanomas or melanocytic nevi that were excised between 1998 and 2007 at participating clinics. NNE values were calculated by dividing the total number of excised lesions by the number of melanomas. Analyses included changes in NNE over time, differences in NNE between specialized clinical settings (SCS) versus non-specialized clinical settings (NSCS), and patient factors influencing NNE. RESULTS: The participating clinics contributed a total of 300,215 cases, including 17,172 melanomas and 283,043 melanocytic nevi. The overall NNE values achieved in SCS and NSCS in the 10-year period were 8.7 and 29.4, respectively. The NNE improved over time in SCS (from 12.8 to 6.8), but appeared unchanged in NSCS. Most of the effect on NNE in SCS was due to a greater number of excised melanomas. Higher NNE values were observed in patients younger than 40 years and for lesions located on the trunk. LIMITATIONS: No data concerning the use of dermatoscopy and digital monitoring procedures were collected from the participating centers. CONCLUSION: Over the 10-year study period, accuracy in melanoma detection improved only in specialized clinics maybe because of a larger use of new diagnostic techniques such as dermatoscopy.

Primary undifferentiated large cell carcinoma of the lacrimal gland.

PURPOSE: To report a unique case of primary undifferentiated large cell carcinoma (LCCA) of the lacrimal gland, a tumor not previously described in the ophthalmic literature. DESIGN: Single interventional case report. PARTICIPANTS: A patient affected by undifferentiated LCCA of the lacrimal gland. METHODS: A 65-year-old white man with a 3-month history of a painful mass in the left lacrimal gland fossa underwent an incisional biopsy that revealed a "high-grade" epithelial malignancy. Systemic workup revealed enlargement of the regional lymph nodes, and subsequently the patient underwent extended exenteration with clear histologic margins and radical neck lymphadenectomy followed by adjunctive radiotherapy. Fifteen months postoperatively, the patient is alive and well without evidence of local recurrence or metastatic disease. MAIN OUTCOME MEASURES: Treatment result, evidence of local recurrences or distant metastasis, and follow-up. RESULTS: Histologic examination revealed a poorly circumscribed tumor composed of large cells invading orbital fat, lateral rectus muscle, and peripheral nerves. The surrounding orbital bone was infiltrated, but the surgical margins were clear. The cell population was composed of large cells (>30 µm) with eosinophilic cytoplasm and ovoid and irregular nuclei containing a prominent nucleoli and coarse chromatin. The cell borders were well defined. Mitosis figures were abundant, and Ki-67 was positive in more than 60% of the cells. The cells were arranged in cords and trabeculae or irregular sheets of discohesive cells. The immunophenotype analysis showed positivity for cytokeratin but negative cytokeratin 20 stains, which is considered a distinctive feature of LCCA. CONCLUSIONS: Undifferentiated LCCAs are rare tumors of the major salivary glands, especially the parotid gland. Primary undifferentiated LCCA of the lacrimal gland has never been reported in the literature. Differential diagnosis must include a primary source in another organ. Given the aggressive nature of the tumor, radical surgery followed by radiotherapy is recommended, but evidence-based indications regarding the preferred line of treatment are lacking and the prognosis remains guarded. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prognostic significance of fluorescent in situ hybridisation in the follow-up of non-muscle-invasive bladder cancer.

AIM: To evaluate the potential contribution of a fluorescent in situ hybridization (FISH) as prognostic indicator of the risk of recurrence or progression in patients undergoing follow-up for non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: A total of 126 consecutive patients with a history of NMIBC being followed-up with urinary cytology and cystoscopy at a referral centre were studied. Patients with carcinoma in situ, or tumour stage higher than pT1 were excluded. A UroVysion FISH kit was used to detect four chromosomal abnormalities, specifically, locus 9p21, Ch 3, 7, and 17. Three FISH patterns were defined: negative; low-risk positive, i.e. positive staining for 9p21 and/or Ch3 abnormalities; and high-risk positive, i.e. positive staining for Ch7 and/or 17. RESULTS: Overall 73 out of 126 patients (57.9%) had a positive urinary FISH test. After a median time of 14 months, 46 FISH-positive patients underwent recurrence (36.5%) and in 15 patients there was progression of disease (11.9%). Among positive patients, the low-risk category was found in 34, and the high-risk in 39. Low-risk FISH-positive patients had a higher rate of recurrence as compared to FISH-negative patients, with a hazard ratio (HR) of 1.6. The recurrence rate was even greater in patients with a high-risk positive test, with an HR of 1.9. The limitation of the study was that the impact of intravesical treatment was not assessed. CONCLUSION: The urinary FISH test can be used as an aid in predicting the risk of recurrence during follow-up of patients with history of NMIBC.

Overexpression and functional relevance of somatostatin receptor-1, -2, and -5 in endometrium and endometriotic lesions.

CONTEXT: Somatostatin plays a role in physiological and pathological cell proliferation and angiogenesis. Five subtypes of somatostatin receptors have been identified, and the therapeutic use of somatostatin receptor-selective agonists has been reported in several diseases. OBJECTIVES: The aim was to describe the expression and the functional relevance of three human somatostatin receptors (sst1, sst2, and sst5) in tissues of women with and without endometriosis. PATIENTS AND METHODS: This pilot study analyzed endometrium, ovarian endometriomata, and peritoneal lesions in 15 patients affected by endometriosis and the endometrium of five women without endometriosis. 111In-pentetreotide scintigraphy was used to detect endometriotic lesions; real-time RT-PCR and immunohistochemistry for sst1, sst2, and sst5 were performed. Migration and proliferation assays were performed on human endometrial stromal cells (ESC) treated with somatostatin and octreotide for 48 h. RESULTS: 111In-pentetreotide scintigraphy was able to correctly identify and locate pelvic endometriotic lesions as confirmed by computed tomography scans. The endometrium of women with endometriosis expressed significantly more sst1, sst2, and sst5 in comparison to that of control women. Moreover, sst1, sst2, and sst5 were highly expressed in ovarian endometriomata and peritoneal lesions. The sst receptor ligand octreotide significantly inhibited ESC migration and proliferation with a maximum effect at 10(-6) m, whereas somatostatin was effective only on ESC growth. CONCLUSIONS: This is the first report characterizing the overexpression and functional relevance of somatostatin receptors in eutopic endometrium and lesions of patients affected by endometriosis. Thus, the use of these receptors may provide new strategies for the diagnosis and treatment of endometriosis.

Phase I-II trial of weekly bicalutamide in men with elevated prostate-specific antigen and negative prostate biopsies.

BACKGROUND: Men with elevated prostate-specific antigen (PSA) and negative prostate biopsies are at risk for prostate cancer. The antiandrogen bicalutamide has a prolonged half-life, thus potentially allowing an intermittent administration to retain activity while reducing toxicity. We conducted a phase I-II trial of weekly bicalutamide in men with PSA >4 ng/mL and negative biopsies. METHODS: Eighty subjects were nonrandomly assigned to a three-arm trial to either bicalutamide 50 mg/wk (n = 26) or 100 mg/wk (n = 28) or no treatment (n = 26) for 6 months. Blood samples were obtained at 0, 3, and 6 months, and prostate biopsies were repeated after 6 months. The outcome measures were 6-month changes of tissue Ki-67 (primary end point), high-grade prostatic intraepithelial neoplasia (HG-PIN), proliferative inflammatory atrophy, circulating PSA, and sex hormones. RESULTS: Ki-67 expression was higher in HG-PIN than in normal tissue (10% versus 3%; P < 0.01) but was not modulated by bicalutamide in normal luminal cells. A trend toward an improvement of HG-PIN status was found in treated subjects (26% improved, 60% had no change, 15% worsened) as compared with the no-treatment arm (4% improved, 83% had no change, 13% worsened; P = 0.07). Proliferative inflammatory atrophy prevalence was not reduced by bicalutamide. Bicalutamide reduced PSA by 50% in both arms and raised testosterone and estradiol levels. Asymptomatic breast swelling was noted in 40% of the treated cases. CONCLUSIONS: A weekly administration of bicalutamide seems to be reasonably safe and shows an encouraging signal of activity on HG-PIN prevalence, supporting further studies of this schedule in men at high risk despite the negative primary end-point findings on Ki-67.

Fluorescent in situ hybridization as a screening test for HER2 amplification in G2 and G3 breast cancers of lobular and ductal histotype and metastases.

The aim of the present study was to evaluate the effectiveness of fluorescence in situ hybridisation (FISH), as a screening test, in moderately- (G2) or poorly- (G3) differentiated breast cancers of the ductal (IDC) and lobular (ILC) histotypes and distant metastases. HER2 FISH was performed on 486 G2 and 477 G3 both of IDC and ILC histotypes and in 241 metastases. A significant difference in the HER2 amplification was observed between G2 (14.8%) and G3 (31.9%), with no difference according to the histotype. However, the rate of amplification increased to 36% in the G2/hormone receptor-negative cases as compared to 10.6% in the G2/receptor-positive cases (p<0.0001). HER2 was amplified in 17% of metastases with some differences depending on the location. These data suggest that the HER2 FISH analysis may be an effective screening test in breast cancer metastases and G3 tumors, irrespective of the hormone receptor status or presence of lymphovascular invasion.

The UroVysion F.I.S.H. test compared to standard cytology for surveillance of non-muscle invasive bladder cancer.

OBJECTIVE: To evaluate the potential contribution of urinary fluorescent in situ hybridization in the prediction of the risk of recurrence and progression of men undergoing followup for NMIBC. MATERIALS AND METHODS: Patients with a history of NMIBC being followed with urinary cytology and cystoscopy were included in the study. Patients with Carcinoma in situ or tumour stage higher than pT1 were excluded from this analysis. F.I.S.H. Test consisted in the UroVysion kit, able to detect four chromosomal abnormalities, specifically, 9p21, Ch 3, 7 and 17. RESULTS: Of a total of 133 evaluable patients that constitute the subject of the present report 87 patients had a positive urinary F.I.S.H. At a median follow up time of 36 mos 58 patients underwent recurrence (43.6%). In this group 42 (72.6%) and 27 (46.6%) patients had a positive F.I.S.H. and UC, respectively (p = 0.005). A total of 17 patients (12.8%) underwent progression of stage or grade; of those with a positive F.I.S.H. Test and positive UC were 14 (82.4%) and 8 (47.1%), respectively (p = 0.049). CONCLUSION: In patients with history of NMIBC, F.I.S.H. showed a statistically significantly greater capability that UC in identifying patients with recurrence and progression of disease.

Intrathyroidal parathyroid carcinoma as cause of hypercalcemia and pitfall of localization techniques: clinical and biologic features.

OBJECTIVE: To describe an unusual case of intrathyroidal parathyroid carcinoma (PC), which was retrospectively diagnosed in a woman who underwent surgical treatment of a recurrent nodular goiter. METHODS: We report the clinical and biologic features of an intrathyroidal PC, discuss the challenges with distinguishing PC from parathyroid adenoma, and review the related literature. RESULTS: A 67-year-old woman sought medical attention for dysphagia attributable to the recurrence of a normal functioning multinodular goiter. Thyroid ultrasonography disclosed a 3-cm solid inferior nodule. Because she refused surgical treatment and a trial of levothyroxine was unsuccessful, periodic follow-up examinations were scheduled. At 1-year follow-up, hypercalcemia (12.1 to 12.6 mg/dL) and low phosphorus levels (2.0 to 2.3 mg/dL) were found, and parathyroid hormone (PTH) levels were profoundly increased (481 to 721 pg/mL). Neck ultrasonography showed a large hypoechogenic solid nodule, not clearly cleaved from the right thyroid lobe, which was possibly compatible with an enlarged parathyroid gland; however, a sestamibi scan was negative. During total thyroidectomy, intraoperative frozen sections of the intrathyroid nodule were compatible with nodular goiter with cellular pleomorphism. Final histologic examination showed cellular nests with nuclear pleomorphism and invasive behavior into the thyroid tissue and likely into the vessels, in conjunction with immunohistochemical negativity for thyroglobulin and strong positivity for PTH. These findings were highly suggestive of and supported the diagnosis of PC. Postoperatively, calcium levels normalized, and PTH values declined considerably but remained slightly increased. Vitamin D supplementation helped normalize the PTH levels. The patient has undergone follow-up for 5 years and has shown no morphologic or biochemical signs of tumor recurrence. CONCLUSION: PC is a rare entity but should be suspected in patients with hypercalcemia, substantially increased PTH levels, and a neck mass. In such patients, techniques such as sestamibi scanning may fail to localize the neoplasm. Surgical treatment remains the preferred technique for an optimal outcome of the disease. Nevertheless, lifelong follow-up is necessary.

Clinically non-functioning pituitary macroadenomas in the elderly.

BACKGROUND AND AIMS: The aim of the present study was to evaluate the clinical presentation, characteristics and post-surgical outcome of non-functioning pituitary macroadenomas (NFPM) in elderly patients. METHODS: 27 patients (65-81 years; 13 Males, 14 Females) with NFPM (20-45 mm in diameter) were studied. The symptoms prompting neuroradiological studies were vision alterations in 52%, and dizziness, loss of memory, confusion, headache and depression in 29%; in 19% of patients, the disease was incidentally discovered during computed tomography (CT) or magnetic resonance imaging (MRI) for head trauma or cerebral ischemic attacks. RESULTS: Endocrinological evaluation on diagnosis showed global anterior hypopituitarism in 33% and partial hypopituitarism in 37% of patients. Immunohistochemistry showed signs of neurosecretion in most NFPM (chromogranin-A in 55%, gonadotropins in 19%, ACTH in 3.7%). Ki-67 antigen expression was indicative of low proliferative activity. Surgery was highly effective in improving alterations in vision and compressive symptoms, but was unable to restore normal pituitary function in established hypopituitarism in most cases. Eight patients (31%) were free of disease on subsequent MRI (follow-up 1-6 years). In 18 (69%) patients, a post-surgical residue was present. Of these, 6 (33%) underwent radiotherapy in the following years, owing to an increase in the volume of the remnants, and six (33%) underwent additional surgical treatment, followed by radiotherapy for further signs of growth in two. In the remaining patients, a small intrasellar remnant was stable on yearly MRI. CONCLUSIONS: in elderly patients, the development of hypopituitarism is often overlooked and the initial diagnosis of NFPM may be delayed. This can expose patients to the risks of unrecognized hypopituitarism and jeopardize post-surgical outcome.