Management of the skull base invasion in spheno-orbital meningiomas.

BACKGROUND: The tumor invasion of the skull base structures is very frequent in spheno-orbital meningiomas. The aim of the present study is to evaluate the invasion rate of skull base structures and the best surgical approach and management. METHODS: The surgical series of 80 spheno-orbital meningiomas was reviewed. The tumors were classified according to the intraorbital location with respect to the optic nerve axes into three types: I-lateral: II-medial; III-diffuse. The invasion of the orbital apex, optic canal, superior orbital fissure, anterior clinoid, ethmoid-sphenoid sinuses, and infratemporal fossa was evaluated. The rate and extension of involvement of these structures was correlated with the intraorbital location and the surgical approach. The preoperative ophtalmological symptoms and signs and their outcome were also evaluated. RESULTS: Proptosis was found in 79 patients (97%), variable decrease of the visual function in 47 patients (59%), and deficits of the eye movements in 28(35%). The invasion of the optic canal (74%), superior orbital fissure (65%), anterior clinoid (60%), and orbital apex (59%) was more frequently found, whereas the tumor extension into the ethmoid-sphenoid sinuses (4%) and infratemporal fossa (4%) was rare. Types II and III meningiomas showed significantly higher involvement of the skull base structures than type I ones, which only had 15% invasion of the optic canal. Remission or significant improvement of the visual function occurred postoperatively in 24 among 47 cases (51%), with a higher rate for type I meningiomas vs. other types (p = 0.021, p = 0.019) and worsening in 7 (15%). CONCLUSIONS: Spheno-orbital meningiomas growing in the lateral orbital compartment show no involvement of the skull base structures excepting the optic canal as compared to those growing medially or diffusely. The surgical resection of tumor invading the skull base structures should be more extensive as possible, but the risk of optic and oculomotor deficits must be avoided.

Risks and Benefits of Surgical Excision of Orbital Cavernous Venous Malformations (So-Called Cavernous Hemangioma): Factors Influencing the Outcome.

PURPOSE: To assess risks and benefits associated with surgical excision of orbital cavernous venous malformation and analyze factors influencing the outcome. METHODS: Design: cohort study. Participants: 164 consecutive patients undergoing surgical removal of orbital cavernous venous malformation. Intervention: lateral or anterior orbitotomy. Outcome measures: visual acuity, visual field, pupillary function, ocular motility, and fundus examination. Influence of the mass volume and tumor location on the outcome was evaluated. The threshold value and risk group for the volume were evaluated using the receiver operating characteristic analysis; 8 orbital different quadrants, extraconal/intraconal position, and orbital apex extension were considered as variables to evaluate the location. RESULTS: Postoperatively overall visual acuity (p = 0.0084), visual field (p < 0.0001), diplopia (p < 0.0001), proptosis (p < 0.0001), ocular motility (p = 0.02), ptosis (p = 0.033), choroidal fold (p < 0.0001), disk edema (p = 0.0004) were significantly improved. The commonest location was the lateral quadrant (28%). Choroidal folds were associated with tumor greater than 1100 mm3 (p = 0.001). Visual loss occurred in 2 patients (1.2%) and tonic pupil in 5 (3%,) Visual deterioration was associated with the apical extension (p = 0.001). Pupil efferent defect was associated with lateral quadrant location (p = 0.011) and apical extension (p = 0.05). CONCLUSIONS: Surgical removal of orbital cavernous venous malformation is a useful treatment modality, particularly for large size tumors. Removal of cavernous venous malformations located at the lateral aspect of the orbit carries an increased risk of permanent tonic pupil. Postoperative blindness is rarely seen and is often associated with the apical extension. Tailoring the surgical approach, depending on the relative position to the optic nerve, may have an important bearing on outcome.

Conjunctival Carcinomas Arising in the Anophthalmic Socket.

PURPOSE: The aim of this study was to report management and outcomes of patients in which conjunctival carcinomas arose in the anophthalmic socket. METHODS: The authors retrospectively analyzed the data of patients which presented the anophthalmic socket after surgery. The clinical records of 4 patients with histological diagnosis of conjunctival carcinoma in the anophthalmic socket, referred to our Department, between January 2014 and December 2019 was collected. RESULTS: The study included 4 men (median age 58 years). A previous enucleation surgery had been performed in all patients due to previous ocular trauma for three patients (Case 1, 3, and 4) and due to a retinoblastoma for 1 patient (Case 2). All patients underwent surgical excision of the lesion and only 1 patient (case 3) underwent orbital exenteration due to the high-grade of the cancer. The most common tumor was the squamous cell carcinoma (2 cases) followed by 1 case of high-grade mucoepidermoid carcinoma and 1 case of carcinoma in situ. Systemic work-up was performed for all the patients. Conjunctival TNM, according to the American Joint Committee on Cancer TNM staging system was used to stage the lesions. The median follow-up time was 15 months. CONCLUSION: Considering the severity and rarity of these tumors, a careful ophthalmological examination of the cavity and a correct revision of the prosthesis should be mandatory in order to ensure the elimination of any macro and microscopic irregularities that can then in the long-term cause chronic inflammation of the tissues and consequently promote the growth of carcinomas.

Epidemiological Analysis of Venous Malformation of the Orbit.

Orbital venous malformation (OVM) is one of the most common orbital mass of adults, accounting for approximately 5% to 15% of all vascular abnormalities in the central nervous system and representing 9% of orbital lesions. Clinical presentation is variable from asymptomatic cases to symptomatic ones. The purpose of the authors' work is to analyze OVM incidence and prevalence in a cohort of patients referred over the last 40 years to the Orbital Unit, tertiary center for orbital diseases.Records of 224 patients diagnosed with CVM in a 40-year period were retrospectively reviewed extracting prevalence/year and incidence/year based on data obtained from Eurostat population statistics. Data were aggregate and analyzed with a Microsoft Excel (Microsoft Corporation, Redmond, WA) spread sheet.The incidence rate was measured as the number of new cases of OVM observed in Orbital Unit, a tertiary center. Incidence was about 1 case out (0.94) every 10 million people. The incidence rate was measured also as the number of new cases of OVM observed in Campania, considering in the latter case patients residents in this region (112 patients). Incidence was less than 1 case out (0.58) every 10 million people.The prevalence rate was measured as the proportion of individuals with OVM observed in our Orbital Unit and is equal to 5%. This indicator resulted to increase from 1977 to 2017.The management of OVM is still under discussion, but in agreement with data present in the literature the authors still believe that the surgical indication is only for symptomatic lesions.

Treatment of Metastatic Eyelid Carcinoma.

PURPOSE: The aim of this study was to report management and outcomes in patients affected by eyelids carcinomas involving regional lymph nodes. METHODS: We have retrospectively analyzed the data of patients affected by eyelids carcinoma with nodal involvement. The clinical records of 10 patients with malignant eyelid carcinoma and regional nodal metastasis treated between September 2011 and March 2015 have been analyzed. RESULTS: The study included 5 women and 5 men (median age 54,5 years; range 37-80 years). The most common tumor was the squamous cell carcinoma (4 cases) followed by sebaceous carcinoma (2 cases): 1 case of epidermoid carcinoma, 1 case of malignant melanoma, 1 case of Merkel carcinoma, and 1 case of basal cell carcinoma. All patients were treated by surgical resection; in 2 cases, orbital exenteration was required. The treatment of regional nodal metastasis consisted of parotidectomy and radical neck dissection followed by radiation therapy. None of the patients developed local recurrence. Three patients died: one, affected by Merkel cell carcinoma, died after 2 months because of metastatic dissemination to the lung; another one, affected by epidermoid carcinoma involving the orbit, died because of liver metastasis; the third one, affected by malignant melanoma, died because of other causes. The follow-up time ranged from 9 to 36 months (median 19.3 months). CONCLUSIONS: Patients affected by advanced malignant eyelid carcinoma need to be strictly controlled because metastasis can develop at least 5 years after surgical treatment. Therapy may include a combination of local surgery, neck dissection, and radiation.

Simultaneous diagnosis of ipsilateral adenoid cystic carcinoma of the lacrimal gland and orbital cavernous hemangioma: case report.

To describe a patient with coexistence of ipsilateral adenoid cystic carcinoma of the lacrimal gland and orbital cavernous hemangioma. The patient presented a 2-month history of painful swelling of left upper eyelid, which did not resolve on a course of oral steroid. On clinical examination, she had moderate medial and inferior dislocation of the eye globe, edema of the temporal superior eyelid and moderate restriction upgaze. Magnetic resonance imaging identified two left orbital tumors: one was a lesion that arose from the lacrimal gland, and the second was a well-defined, ovoid, intraconal mass. The patient underwent lateral orbitotomy and excision of both lesions. Postoperative histological features demonstrated two different lesions: an adenoid cystic carcinoma of the lacrimal gland and a cavernous hemangioma. The clinical presentation of the present case was strongly suggestive of a lacrimal gland malignancy, although the imaging features did not show typical invasive aspects. This is the first report of coexistence of lacrimal gland adenoid cystic carcinoma and cavernous hemangioma in the ipsilateral orbit.

Unilateral proptosis in thyroid eye disease with subsequent contralateral involvement: retrospective follow-up study.

BACKGROUND: The purpose of this retrospective follow-up study is to evaluate the prevalence of patients with thyroid eye disease presenting with apparent unilateral proptosis and determine the occurrence of exophthalmos in contralateral non-proptotic eye over the time. Associated features with this event were evaluated. METHODS: A cohort of 655 consecutive patients affected by thyroid eye disease with a minimum follow-up of 10 years was reviewed. Exophthalmos was assessed by using both Hertel exophthalmometer and computed tomography (CT). The influence of age, gender, hormonal status and of different therapies such as corticosteroids, radiotherapy and surgical decompression on this disease progression was evaluated. RESULTS: A total of 89 patients (13.5%) (95% confidence interval [CI] 15%-10%) had clinical evidence of unilateral exophthalmos at the first visit. Among these, 13 patients (14%) (95% CI 22%-7%) developed subsequent contralateral exophthalmos. The increase of protrusion ranged from 2 to 7 mm (mean of 4.2). The time of onset varied from 6 months to 7 years (mean time: 29 months). Smoking status, young age and surgical decompression are significantly associated with development of contralateral proptosis (p< .05). CONCLUSIONS: Asymmetric thyroid eye disease with the appearance of unilateral exophthalmos at the initial examination is a fairly frequent event, while subsequent contralateral proptosis occurs less commonly. However, physicians should be aware that young patients, particularly if smokers, undergoing orbital decompression in one eye may need further surgery on contralateral side over time.

Surgical unroofing of the optic canal and visual outcome in basal meningiomas.

BACKGROUND: To define from a series of surgically treated suprasellar, anterior clinoid, and sphenoid wing meningiomas, an unequivocal criterion for performing optic canal deroofing in patients with basal meningiomas with deteriorated vision. METHODS: One hundred-fifty consecutive patients with suprasellar and parasellar meningiomas (44 tuberculum sellae, 46 clinoidal, and 60 spheno-orbital) who underwent surgery between 1988 and 2008 are retrospectively analyzed. The rate of preoperative visual deficit, the incidence of optic canal involvement, the related surgical management, and its influence on visual outcome are reviewed in all tumor localizations. RESULTS: All 44 patients with tuberculum sellae meningiomas had variable preoperative visual impairment. All were operated on by transcranial approach. Unroofing of the optic canal was performed in the two cases with intracanalar tumor extension. Postoperatively, the visual function improved in 27 patients (61.4 %) and was unchanged in 17 (25 %). Among 46 patients with clinoidal meningiomas, visual dysfunction was found in 30 (65.2 %). The first 32 patients were operated on by classical pterional approach, with selective opening of the optic canal in six cases (group A), whereas all the last 14 underwent routine anterior clinoidectomy and opening of the optic canal (group B). The visual function improved postoperatively in 17 among 30 patients (56.7 %), with a significantly higher rate in group B cases (80 % versus 45 %). Among 60 patients with spheno-orbital meningiomas, 36 (60 %) had visual dysfunction and 43 (71.6 %) involvement of the optic canal. The visual function improved in 18 cases (50 %), was unchanged in 13 (36 %), and worsened in 5 (14 %). Lateral tumors had the lowest rate of optic canal involvement and a 100 % rate of visual improvement; on the other hand, all orbital apex and diffuse tumors had concentric invasion of the optic canal with a 18.6 % rate of visual worsening. CONCLUSIONS: UOC seems to be a safe procedure not associated with immediate postoperative impairment of the vision. We recommend routine deroofing of the optic canal coupled with extradural anterior clinoidectomy in all clinoidal meningiomas in order to obtain early and complete exposure of both intradural and extradural segments of the optic nerve. For tuberculum sellae meningiomas, we advise to open the optic canal only in cases with intracanalar tumor extension. Finally, for spheno-orbital meningiomas, we recommend UOC through a cranio-orbital approach in almost all cases, except for lateral meningiomas, where the involvement of the lateral wall of the optic canal is rare and may be successfully managed through a lateral orbitotomy without craniotomy.

An analysis of 2,480 space-occupying lesions of the orbit from 1976 to 2011.

PURPOSE: To evaluate the frequencies of orbital space-occupying lesions seen at single orbital unit in a period of 35 years. METHODS: In this retrospective case series, the authors reviewed the medical records of 2,480 consecutive patients referred to the authors' Orbital Unit for evaluation of an orbital mass between 1976 and 2011. The final diagnosis in each case was established by a combination of history, ocular findings, diagnostic imaging, and histopathologic analysis, when available. The number and percentage of benign and malignant tumors were determinated, also according to the age of the patients and the tumor location within the orbit. This study adhered to the principles of the Declaration of Helsinki. RESULTS: Of the 2,480 lesions, 1,697 (68%) were benign and 783 (32%) were malignant. The most frequent benign tumors were dermoid cyst (14%) and cavernous hemangioma (9%). The most common malignant tumors were non-Hodgkin lymphoma (12%), basal cell carcinoma (3%), and orbital metastases (3%). In patients younger than 60 years, benign tumors are more frequent, whereas in patients older than 60 years, the frequency of malignant tumors increased. Regarding the distribution in the orbit, the most common tumors were dermoid cyst (206 cases) in the upper-outer quadrant, mucocele (155 cases) in the upper-inner quadrant, basal cell epithelioma (35 cases) in the lower-inner quadrant, cavernous hemangioma (68 cases) in the lower-outer quadrant, and meningioma (90 cases) in central space. Most of the tumors were located in the upper-outer quadrant. In the lower-inner quadrant, malignant tumors were more frequent than benign tumors. CONCLUSIONS: The authors' findings highlight the distinctive nature of the orbital oncology experience at an ocular oncology department.

Recurrences of Spheno-Orbital Meningiomas: Risk Factors and Management.

BACKGROUND: The extent of resection constitutes one of the most important predictive risk factors of recurrence for spheno-orbital meningiomas; although gross total resection represents the gold standard, it is not always achievable, with a consequent high rate of recurrence. Management of these tumors is a surgical challenge and is represented by maximal safe resection with preservation of function. The aim of the present study is to discuss the risk factors for recurrence and the best management of the recurrent tumors. METHODS: Eighty patients operated on for spheno-orbital meningiomas were retrospectively reviewed. Two groups were identified: group 1 comprised 30 patients (37.5%) who experienced recurrence and group 2 comprised 50 patients with no recurrence from 5 to 28 years after the initial surgery. The analyzed factors in both groups include the involvement of the skull base structures, the extent of resection, and World Health Organization grade. In the recurrence group, the pattern of tumor regrowth, the entity of resection, and the management were also analyzed. RESULTS: The invasion of the whole orbit, the involvement of the orbital apex, superior orbital fissure, infratemporal fossa, and sphenoidal-ethmoidal sinuses, and World Health Organization grade II are risk factors of recurrence. All 30 patients with recurrence underwent reoperation, 9 of whom had 2 or 3 reoperations. Overall, 70 of the 80 patients (88%) had tumor control and no progression after one or more reoperations. CONCLUSIONS: We suggest re-surgery for spheno-orbital meningioma recurrences to prevent worsening of visual function and proptosis. Because of their slow natural course, even multiple reoperations may be performed, resulting in long overall survival with stable symptoms and good quality of life.

Outcomes after eye-sparing surgery vs orbital exenteration in patients with lacrimal gland carcinoma.

BACKGROUND: This study examined whether eye-sparing surgery is associated with better or worse outcomes than exenteration for the treatment of lacrimal gland carcinomas. METHODS: Forty-six patients treated for lacrimal gland carcinoma were retrospectively reviewed and compared. A statistical analysis was performed using Kaplan-Meier plots. RESULTS: The overall survival rates for eye-sparing surgery were 52% and 37% at 5 and 10 years, and those for exenteration were 37% and 25% at 5 and 10 years, respectively (P = .73). The proportion of patients with local regional control at both 5 and 10 years after eye-sparing surgery was 0.75, and that for exenteration was 0.47 (P = .30). For eye-sparing surgery, the proportions of distant metastasis-free survival at 5 and 10 years were 0.51 and 0.39 for eye-sparing surgery and 0.29 and 0.14 for exenteration (P = .50). CONCLUSION: Because the outcomes were not significantly different, the authors suggest that eye-sparing surgery can be proposed as a reasonable approach for lacrimal gland carcinomas in appropriately selected patients.

Primary optic nerve sheath meningioma in children.

Primary optic nerve sheath meningioma represents a proliferation of meningothelial cap cells of the arachnoid villi within the optic nerve sheath. Patients younger than 20 years of age make up less than 5% of all cases of pediatric primary optic nerve meningiomas. Histopathologically, the most common subtypes in children are transitional (54%) and meningotheliomatous (38%). This tumor has been called aggressive in the pediatric population, with surgical excision recommended. However, the tumor may spread intraorbitally, intracranially, or intraocularly after subtotal surgical resection. Recent studies examined the use of fractionated, stereotactic radiation in children with this tumor; however, follow-up is limited. Neurofibromatosis type 2 is concomitantly diagnosed in 28% of patients with pediatric primary optic nerve sheath meningioma. There have been no known deaths attributed primarily to this tumor.

Expression of apoptosis-related markers in malignant epithelial tumours of the lacrimal gland and their relation to clinical outcome.

OBJECTIVE: To investigate the correlation between the expression of apoptosis-related markers and prognosis in malignant epithelial tumours of the lacrimal gland. MATERIALS AND METHODS: Series of cases. PARTICIPANTS: Twenty one cases with malignant epithelial tumours of the lacrimal gland. Histological diagnosis was re-examined and blocks selected were evaluated for the following parameters: incidence of apoptosis with TUNEL assay, expression of p53 and Bcl-2 using monoclonal antibody. Predictors factors for survival, local recurrence and cumulative probability of death were statistically evaluated. RESULTS: Re-eximination of the 21 specimens was as follow: 11 adenoid cystic carcinomas, 4 mucoepidermoid carcinomas, 3 squamous cell carcinomas and 3 adenocarcinomas. Eleven of the 21 patients (53%) died during the follow-up period (4-192 months; mean 71). Bcl-2 staining >6% was significantly correlated with the death of patients. A statistically significant positive relationship for TUNEL and p53, and an inverse correlation for Bcl-2 staining, was demonstrated with overall survival. CONCLUSION: The correlation with survival of apoptotic index, p53 and Bcl-2 expression suggest the more tumour cells go in apoptosis, upregulating p53 and down-regulating Bcl-2, the better the survival of patients. This study establishes a role of apoptosis-regulatory proteins in the pathogenesis of malignant epithelial lacrimal gland tumours, and supports the hypothesis that evaluation of the expression of apoptosis-related markers in these tumours may provide a prognostic tool.

Delayed Recovery of Visual Acuity after Sphenoorbital Meningioma Surgical Removal: Case Report and Review of the Literature. Is Visual Acuity Recovery Possible after an Initial Decline?

BACKGROUND AND STUDY AIMS: To report a case of late recovery of visual acuity after surgical removal of a sphenoorbital meningioma (SOM). MATERIALS AND METHODS: A 42-year-old woman was referred for progressive proptosis of the right eye for 5 years. Her best-corrected visual acuity (BCVA) was 10/10 in her right eye and 10/10 in her left eye, and thyroid function tests were negative. Ophthalmic examination showed slight exophthalmos of her right eye, but eye movements and pupillary light reflexes were normal. Intraocular pressure and fundus examination (FE) in both eyes were normal. Computed tomography scan of the orbits showed hyperostosis and an increase in the thickness of the lateral wall of the orbit, volume reduction of the right orbit, the optic canal, and the sphenoidal fissure, edema, and medial displacement of the lateral rectus muscle. We performed coronal orbitotomy and removed the tumor via a frontotemporal-orbitozygomatic approach and lateral orbitotomy. RESULTS: Three hours postoperatively, her right eye was blind with signs of orbital apex syndrome. A high dose of intravenous corticosteroid was then administered. Twenty-four hours postoperatively, BCVA of right eye was motu manu (hand motion), and pupillary light reflexes in the right eye were absent. Five days postoperatively, BCVA allowed counting fingers at 5 m, and ocular motility was partially recovered. Fifteen days postoperatively, BCVA was 1/15, and eye movements were totally recovered. Eight months postoperatively, BCVA was 3/10, pupillary light reflexes were still absent, and FE in the right eye showed a slightly pale temporal half of the optic disc. Twenty months postoperatively, BCVA in the right eye was 7/10. CONCLUSIONS: Late recovery of visual acuity after sphenoorbital meningioma removal may be possible despite an initial decline.

Orbital metastases in Italy.

AIM: To describe a series of Italian patients with orbital metastasis focusing on the outcomes in relation to the different primary site of malignancy. METHODS: Retrospective chart review of 93 patients with orbital metastasis collected in a tertiary referral centre in a period of 38y and review of literature. RESULTS: Out of 93 patients, 52 were females and 41 were males. Median age at diagnosis was 51y (range 1 to 88y). The patients have been divided into four groups on the basis of the year of diagnosis. The frequency of recorded cases had decreased significantly (P<0.05) during the last 9.5y. Primary tumor site was breast in 36 cases (39%), kidney in 10 (11%), lung in 8 (9%), skin in 6 (6%); other sites were less frequent. In 16 case (17%) the primary tumor remained unknown. The most frequent clinical findings were proptosis (73%), limited ocular motility (55%), blepharoptosis (46%) and blurred vision (43%). The diagnosis were established by history, ocular and systemic evaluation, orbital imaging studies and open biopsy or fine needle aspiration biopsy (FNAB). Treatment included surgical excision, irradiation, chemotherapy, hormone therapy, or observation. Ninety-one percent of patients died of metastasis with an overall mean survival time (OMST) after the orbital diagnosis of 13.5mo. CONCLUSION: Breast, kidney and lung are the most frequent primary sites of cancer leading to an orbital metastasis. When the primary site is unknown, gastrointestinal tract should be carefully investigated. In the last decade a decrease in the frequency of orbital metastasis has been observed. Surgery provides a local palliation. Prognosis remains poor with a OMST of 13.5mo ranging from the 3mo in the lung cancer to 24mo in the kidney tumor.

Somatostatin receptor genes are expressed in lymphocytes from retroorbital tissues in Graves' disease.

The radiolabeled somatostatin (SST) analog octreotide accumulates within the orbits of active Graves' ophthalmopathy (GO), and octreotide and lanreotide have been proposed to treat this disorder. It is still unclear which retroorbital cells the SST analogs target. Lymphocytic infiltration of retroorbital tissues is a peculiarity of GO, and labeled octreotide could accumulate at specific sites on retroorbital-activated lymphocytes. The accumulation of radiolabeled analogs is due to the interaction with specific cell surface SST receptors. Five subtypes of somatostatin receptors (SST1-5), member of the G protein-coupled, seven-transmembrane superfamily, are described. It still unknown which SST subtype is expressed in retroorbital activated lymphocytes. The aim of this study was to evaluate the expression of SST1-5 genes in lymphocytes recovered from retroorbital tissues obtained from patients with GO undergoing orbital decompression. Cultured phytohemagglutinin-stimulated lymphocytes from retroorbital blood samples, drawn during orbital surgery in five patients with GO and in two control patients without autoimmune or thyroid diseases and without orbital inflammatory conditions, were also studied. RT-PCR of total RNA extracted from lymphocytes was performed using primers for SST1-5 and, as internal control, for glyceraldehyde-3-phosphate dehydrogenase. All SSTs transcripts were found in lymphocytes both from GO retroorbital tissues and blood samples. The levels of expression of SST1, -2, and -4 mRNA were higher than those of the SST3 and -5 transcripts. In the lymphocytes from control subjects, the SST subtypes with high affinity for octreotide were barely found. The presence, even if at different concentrations, of all SST1-5 receptors in retroorbital lymphocytes from GO shows that they are targeted by SST analogs and could explain the effects described in GO patients treated with SST analogs.

All-trans retinoic acid- and N-(4-hydroxyphenil)-retinamide-induced growth arrest and apoptosis in orbital fibroblasts in Graves' disease.

In this study, we evaluated by reverse transcription-polymerase chain reaction (RT-PCR) the expression pattern of retinoic acid receptors (RAR) alpha, beta, and gamma and cellular retinoic acid binding protein-I (CRBP-I) genes in 12 primary cultures of fibroblasts (F) from orbital tissue of Graves' ophthalmopathy (GO) patients. We also studied the in vitro effects of all-trans retinoic acid (RA) and N-(4-hydroxyphenil)-retinamide (4HPR), a less toxic and better tolerated synthetic derivative of RA, on cell morphology, growth, apoptosis, and cyclic adenosine monophosphate (cAMP) accumulation. All primary cultures expressed RAR alpha, beta, gamma, and CRBP-I. FGO treated with RA and 4HPR (10(-7) mol/L) presented morphologic changes and significantly inhibited cell growth after 72 hours. At 96 hours of drug exposure, apoptosis was detected in 15% and 50% of RA- and 4HPR (10(-7) mol/L)-treated cells, and p53 protein increased in cell lysates. 4HPR induced a 70% decrease of Bcl-2 protein. After 30 minutes of RA and 4HPR (10(-7) mol/L) exposure, a 20% decrease of basal cAMP accumulation was seen, and forskolin cAMP-induced increase was abolished. The expression of RAR alpha, beta, gamma, and CRBP-I in primary cultures of FGO indicates that they are targets for retinoids. Moreover, we show that RA and 4HPR are able to induce morphologic changes, inhibition of cell growth, and apoptosis in FGO exerting their effects through RAR-modulated pathways. The rapid inhibition of cAMP accumulation indicates that a novel nonclassic retinoid pathway may also be involved. Finally, the potent in vitro effects of 4HPR, a retinoid derivative with fewer adverse reactions in vivo, could justify further investigations on a clinical application of retinoids in GO.

Orbital rhabdomyosarcoma: relationship between DNA ploidy, p53, bcl-2, MDR-1 and Ki67 (MIB1) expression and clinical behavior.

BACKGROUND: As for rhabdomyosarcoma (RMS) of other anatomic regions, the evaluation of traditional clinicopathological parameters does not allow the unequivocal outcome prediction of the single cases of orbital RMS. We investigated the role of DNA ploidy and immunohistochemical expression of p53, bcl-2, MDR-1 and Ki67 (MIB1) in the prognostic evaluation of orbital rhabdomyosarcomas. MATERIALS AND METHODS: The study population consisted of 11 selected cases. Serial sections of each tumor, stained with Feulgen's technique, were analyzed for the DNA content, using the QUANTIMET 500c Leica analyzer, QWINVO200A software. The results were compared with the immunohistochemical expression of p53 (wild plus mutated, W&M and mutated), bcl2, MDR-1 and Ki67 (MIB1), and with follow-up data. RESULTS: The statistical analysis of results showed that the cases of tetraploid and/or multiploid RMS, overexpressing p53 (W&M and mutated) and MDR-1, were characterized by an overall worse prognosis. On the contrary, the tumors with a favourable clinical course showed hyperexpression of MIB1 and absence of mutated p53 expression. Significantly higher MIB1 expression was found in the relapse-free group of tumors, with respect to the RMS with relapse (both in primary tumors and relative relapses, p<0.05). This finding could justify the higher sensibility to pharmacological therapy of RMS of the first group. The group of RMS with a worse prognosis (primary tumors and relapses) showed instead p53 overexpression (W&M and mutated), MDR-1 expression and multiploidy, with high 5cEE values and tetraploid peaks. No significant difference was found concerning the expression of bcl-2 among the two groups of RMS (p>0.05). CONCLUSION: The evaluation of DNA ploidy, p53, MIB1 and MDR-1 expression could be used for subtyping of orbital RMS into two prognostically different subcategories, respectively RMS responder to the therapy, with favourable clinical outcome, and RMS with a worse prognosis, requiring more aggressive therapeutic protocols.

Expression of cyclin-D1 in uveal malignant melanoma.

BACKGROUND: Uveal malignant melanoma (MM) is characterized by a marked variability in biological behavior and by an unpredictable clinical course. Therefore the search for reliable prognostic parameters is active. In this study we investigated the immunohistochemical expression of cyclin D1, a cell cycle regulatory molecule, to analyze the possible significance of the protein in the prognostic evaluation of these neoplasms. MATERIALS AND METHODS: Forty-five selected uveal MM were incubated with the anti-cyclin D-1 antibody; the findings were compared with the follow-up data, with the cell type and with the largest tumor dimension. RESULTS: The overexpression of cyclin D1 was found to be inversely related to disease-free interval (p < 0.001) and to the spindle A/B tumors with good prognosis (p = 0.05). On the other hand, a direct correlation was found with epithelioid/spindle B melanomas with poor clinical course (p = 0.05) and with sclera infiltration (p = 0.01). No statistically significant relation emerged between cyclin D1 expression and LTD. CONCLUSION: These data may suggest a possible role of the overexpression of cyclin D1 in the tumorigenesis of uveal MM and in the prognostic evaluation of these tumors, representing a useful tool to subclassify lesions with similar morphological features.