Genetic Alterations in Differentiated Thyroid Cancer Patients with Acromegaly.

AIM: Acromegaly is associated with increased thyroid cancer risk. We aimed to analyze the frequency of point mutations of BRAF and RAS genes, and RET/PTC, PAX8/PPARγ gene rearrangements in patients with acromegaly having differentiated thyroid cancers (DTC) and their relation with clinical and histological features. MATERIALS AND METHODS: 14 acromegalic patients (8 male, 6 female) with DTC were included. BRAF V600E and NRAS codon 61 point mutations, RET/PTC1, RET/PTC3, and PAX8/PPARγ gene rearrangements were analyzed in thyroidectomy specimens. We selected 14 non-acromegalic patients with DTC as a control group. RESULTS: 2 patients (14.3%) were detected to have positive BRAF V600E and 3 patients (21.4%) were detected to have NRAS codon 61 mutation. NRAS codon 61 was the most frequent genetic alteration. Patients with positive mutation had aggressive histologic features more frequently than patients without mutations. Comparison of the acromegalic and non-acromegalic patients with DTC revealed that BRAF V600E mutation was more frequent in non-acromegalic patients with DTC (14.2% vs. 64.3%, p=0.02). RET/PTC 1/ 3, PAX8/PPARγ gene rearrangements were not detected in any patient. None of the patients including the patients with positive point mutations had recurrence, and local and/or distant metastasis. CONCLUSION: NRAS codon 61 is the most frequent genetic alteration in this acromegaly series with DTC. Since acromegalic patients have lower prevalance of BRAF V600E mutation, BRAF V600E mutation may not be a causative factor in development of DTC in acromegaly. Despite the relation of BRAF V600E and NRAS codon 61 mutations with aggresive histopathologic features, their impact on tumor prognosis remains to be defined in acromegaly in further studies.

The role of apoptosis in blepharoptosis.

PURPOSE: The purpose of this study is to evaluate the role of apoptosis in the pathogenesis of blepharoptosis. PATIENTS AND METHODS: Forty-five eyelids of 43 consecutive patients (16 female, 27 males) that underwent levator resection surgery for ptosis correction were included in the study. Twenty-six of the eyelids had congenital myogenic ptosis and 19 had aponeurotic ptosis. Levator palpebrae superioris function and height of the vertical palpebral fissure were measured in all patients. After levator resection surgery, the distal part of the levator aponeurosis was fixed and sent for evaluation. Apoptotic cells were detected using Apop Tag Plus Peroxidase In Situ Apoptosis Detection Kit. RESULTS: The mean levator palpebrae superioris function was 8.4 mm (range 5-10 mm) in congenital ptosis group and 12.1 mm (range 10-17 mm) in the aponeurotic ptosis group. The mean height of the vertical palpebral fissure in patients with congenital ptosis and aponeurotic ptosis were 6.5 mm (range 5-9 mm) and 6.1 mm (3-9 mm), respectively. The mean apoptotic index of congenital ptosis and aponeurotic ptosis were 27.3 (16-39) and 29.8 (18-41), respectively. There was no statistically significant difference between congenital and aponeurotic ptosis groups in a mean apoptotic index (P<0.05). Apoptotic index was not correlated with age, levator palpebrae superioris function, palpebral fissure height, and lid crease height in two groups. CONCLUSION: We found no statistically significant difference between two subtypes of blepharoptosis regarding apoptosis. According to this study, apoptosis seems to have no significant role in the development of aponeurotic blepharoptosis.

Chemotherapy for transient myeloproliferative disorder in a premature infant with Down syndrome.

WHAT IS KNOWN AND OBJECTIVE: Congenital leukaemia is the most common leukaemia in newborns with Down syndrome, but it must be differentiated from transient myeloproliferative disorder. The majority of transient myeloproliferative disorders regresses spontaneously during the first few months of life. Data on the treatment outcomes of transient myeloproliferative disorder in premature infants are very rare. We present a case of a very-low-birthweight (1350 g) premature newborn with Down syndrome, diagnosed as having transient myeloproliferative disorder and treated with chemotherapy due to recurrent hyperleucocytosis (WBC: 148 000/mm³) after repeated exchange transfusions. CASE SUMMARY: The patient's WBC count regressed to 24 000/mm(3) without treatment. During the follow-up period, the WBC increased on consecutive days and reached 95 000/mm(3) on the 16th day of the hospitalization. Therefore, chemotherapy was started. Single-agent cytarabine infusion was administered over five days. After the therapy, the WBC count stayed stable and remained steady in the range 4600-13600/mm(3) in the second month. WHAT IS NEW AND CONCLUSION: A very-low-birthweight infant with Down syndrome and recurrent transient myeloproliferative disorder was successfully treated with cytarabine.

The association of molybdenum cofactor deficiency and pyloric stenosis.

Molybdenum cofactor deficiency (MoCD) is a rare autosomal recessive disorder that may present during the neonatal period with intractable seizures. Co-existence of MoCD and pyloric stenosis is previously reported as a coincidence or common etiology. The etiology of the two conditions is unclear; however, reports demonstrate neuronal deficiency in both. We report a neonate who was diagnosed with MoCD and hypertrophic pyloric stenosis.

Challenging diagnosis: oligodendroglioma versus extraventricular neurocytoma.

Diagnosis of oligodendroglioma from other clear cell neoplasms of central nervous system (CNS) is still challenging despite advances in neuroradiology and molecular diagnostic tools. Herein, we present a 44-year-old male patient who had a diagnosis of right parietal oligodendroglioma grade II in 1994 which recurred in 2002. He presented with intratumoral hemorrhage and he underwent radical resection of tumor in 2003. Histopathological examination of the recurrent tumor showed anaplastic progression with confusing immunohistochemical (IHC) results; the tumor was positive for NeuN and synaptophysin staining. The question arisen was whether the recurrent tumor was an oligodendroglioma with neuronal differentiation or an extraventricular neurocytoma initially misdiagnosed as oligodendroglioma. Repeated IHC staining showed negative results for NeuN and synaptophysin. Chromosomal analysis revealed 1p/19q deletion, which led to the diagnosis ofanaplastic oligodendroglioma grade III. Accurate diagnosis of oligodendroglioma is crucial due to recent advances and promises in its treatment. Current diagnostic methods of oligodendroglial tumors are discussed in context of differentiating oligodendrogliomas from other clear cell neoplasms of CNS, especially from extraventricular neurocytomas.

A glioma with an arteriovenous malformation: an association or a different entity?

A 58-year-old male was admitted with headache to our neurosurgery clinic. His neurological examination revealed slight left hemiparesis. The radiological evaluation with contrast administred magnetic resonance imaging (MRI) scan demonstrated a right temporo-parietal ring enhancing mass lesion surrounded by edema which was resembling a typical glioma (Fig. 1). The patient was operated on via a temporo-parietal craniotomy and an arteriovenous malformation surrounded by abnormal glial tissue was observed during the exposure. A nidus supplied by several branches arising from the middle cerebral artery (MCA) was obvious. The venous drainage of the malformation was to the superficial venous system. The observed arterial feeders and the draining vein were coagulated and the nidus was macroscopically totally excised. The frozen examination from surrounding glial tissue revealed a high grade glioma. The tumor was also macroscopically totally excised. Postoperatively, the cerebral angiogram demonstrated a right temporal arteriovenous malformation with a centrally excised nidus. The remaining major feeders involved the angular gyrus and the posterior temporal arteries. The venous drainage was to the straight and sigmoid sinuses (Fig. 2). The final histopathological examination of the specimen revealed an arteriovenous malformation surrounded by a high grade glioma (Fig. 3). The patient refused a second operation for total removal of the AVM. Postoperatively, he is doing well with improvement of his left hemiparesis.

Alterations in the morphology of lamina cribrosa pores in glaucomatous eyes.

AIMS: To determine alterations which occur in the size and shape of lamina cribrosa (LC) pores in glaucomatous eyes over a period of time. METHODS: Baseline and follow up optic disc photographs were retrospectively studied in 39 eyes of 39 patients with glaucoma. Only eyes with a vertical cup to disc ratio equal to or greater than 0.6 were included in the study. In addition, all selected eyes had to have serial optic disc photographs obtained at least 3 years apart allowing clear visualisation of LC surface. The association of the alterations in LC surface morphology with patient specific and eye specific characteristics was statistically analysed. RESULTS: During a mean study period of 3.90 (SD 0.7) years, individual pore size (mean pore area to disc area ratio) exhibited a significant decrease between baseline and follow up measurements of each eye (p<0.0001). However, during the study period, total pore area to disc area ratio did not change (p>0.05), and the change in pore shape in some eyes (from circular to more oval and elongated) was statistically insignificant (p = 0.12). Although a relation was detectable between the optic disc and lamina cribrosa parameters at a given time, which reflects cumulative effects, during the study period, there was no significant association between the changes of the LC parameters and neural tissue damage. The rate and the magnitude of the changes in individual pore size during the study period were not significantly different among the eyes exhibiting progressive neural rim damage and those staying stable (p>0.05). CONCLUSION: These findings demonstrate that the LC surface morphology exhibits changes along with the glaucomatous optic disc damage. However, the clinical appearance of LC surface in glaucomatous eyes may continue to change, even when the neural rim damage is clinically stable. These findings are probably associated with the chronic cellular events of tissue remodelling that occur in the glaucomatous optic nerve head.

Cranial infantile myofibromatosis: report of three cases.

BACKGROUND: Infantile myofibromatosis is a proliferative disorder of infancy and early childhood characterized by the development of single or multiple nodular lesions arising from cutaneous or subcutaneous tissue, muscle, bone or visceral organs. In approximately one-third of cases, this myofibroblastic proliferation involves the head and neck region. CASE REPORT: In this paper we report on three cases of cranial infantile myofibromatosis in infants. The clinical presentation and the deceptive histopathological features can make diagnosis difficult. CONCLUSION: The significance of recognizing this entity is stressed, since its indolent clinical behavior might prevent diagnosis.

Clinical factors associated with progression of glaucomatous optic disc damage in treated patients.

BACKGROUND: Reducing intraocular pressure (IOP) in glaucomatous eyes does not always prevent disease progression. OBJECTIVE: To determine the clinical factors associated with progressive optic disc damage in glaucomatous eyes receiving treatment to reduce IOP. METHODS: Baseline and follow-up optic disc photographs as well as demographic and clinical data were retrospectively studied in 186 eyes of 93 patients with primary open-angle glaucoma, and in 138 eyes of 69 patients with normal-pressure glaucoma. The patients with primary open-angle glaucoma were included in the study only if their treated IOPs during a follow-up period of 5 years were less than 21 mm Hg. The patients with normal-pressure glaucoma were included only if their IOPs were reduced by at least 20% during the follow-up period. The association of progressive optic disc damage with patient- and eye-specific characteristics was examined using multivariate analysis. RESULTS: During the 5-year study period, 141 (43.5%) of the 324 eyes exhibited progressive optic disc damage defined by at least a 5% decrease in the neural rim area-to-disc area ratio. Using multivariate analysis, the following were found to be strongly associated with progressive neural rim damage: a baseline smaller neural rim area-disc area ratio (P<.001); a baseline larger zone beta area-disc area ratio (P =.04); a baseline larger parapapillary atrophy length-disc circumference ratio (P =.05); a diagnosis of normal-pressure glaucoma (P =.01); and combined medical and surgical treatment prior to the study period (P =.01). CONCLUSIONS: Clinical factors other than IOP may be important indicators of subsequent progression of glaucomatous optic disc damage. Our findings suggest that eyes with advanced glaucomatous optic disc damage and normal-pressure glaucoma are more likely to progress despite receiving treatment to reduce IOP.

TNF-alpha and TNF-alpha receptor-1 in the retina of normal and glaucomatous eyes.

PURPOSE: To determine the expression and localization of tumor necrosis factor (TNF)-alpha and TNF-alpha receptor-1 in the retina of normal and glaucomatous eyes. METHODS: Using immunohistochemistry and in situ hybridization, retinal expression and localization of TNF-alpha and TNF-alpha receptor-1 were studied in retina sections from 20 eyes of donors with glaucoma, and 20 eyes of age-matched normal donors. RESULTS: According to immunohistochemistry, the intensity of the immunostaining and the number of labeled cells for TNF-alpha or its receptor were greater in retina sections of glaucomatous eyes than in control eyes of age-matched normal donors. In situ hybridization showed that mRNA signals for TNF-alpha or TNF-alpha receptor-1 were similarly more intense in glaucomatous eyes than in age-matched control eyes. Both protein and mRNA of TNF-alpha or TNF-alpha receptor-1 were predominantly localized to the inner retinal layers. Double-immunofluorescence labeling demonstrated that retinal immunostaining for TNF-alpha was predominantly positive in the glial cells, whereas immunostaining for TNF-alpha receptor-1 was mainly positive in the retinal ganglion cells. CONCLUSIONS: Upregulation of TNF-alpha and its receptor-1 in glaucomatous retina suggest that TNF-alpha-mediated cell death is involved in the neurodegeneration process of glaucoma.