Unique case of a GLI1 amplified biphasic mesenchymal tumor of the orbit.

GLI1-altered mesenchymal tumors are an emerging entity in soft tissue pathology. In the head and neck region, they are most commonly in the tongue. Limited published data indicate a propensity for local recurrence, regional spread, and distant metastasis in both GLI1-rearranged and GLI1-amplified tumors. The purpose of this report is to present the rare case of a GLI1-amplified spindle cell tumor of the orbit and a focused review of the literature. A 54-year-old woman presented with proptosis, eye pain, and ocular motility restriction in the left eye. Imaging demonstrated a tumor occupying the superomedial intraconal orbit that was distinct from the extraocular muscles, optic nerve, and globe. The tumor was totally resected with a combined open transorbital and endoscopic, endonasal approach. Pathological analysis demonstrated a spindled and epithelioid mesenchymal tumor with diffuse nuclear GLI1 expression. PCR-based, next*-generation sarcoma fusion panel was negative for GLI1 fusions, including GLI1::ACTB fusions; however, DDIT3 breaks apart fluorescence in situ hybridization (FISH), which can be used as a surrogate for GLI1 alterations due to proximity to 12q13.3, showing amplification. Post-operatively, the patient had recovered visual acuity. She received adjuvant radiation therapy (60 Gy in 30 fractions). Surveillance for recurrence, regional spread, and distant metastasis has been negative at a 6-month follow-up. Ultimately, we report the first case of a GLI1-amplified mesenchymal neoplasm of the intraconal orbit managed with gross total resection via a combined approach followed by adjuvant radiation therapy.

Multi-drug resistant, biofilm-producing high-risk clonal lineage of Klebsiella in companion and household animals.

Antimicrobial resistance is a global emergency which needs one health approach to address. The present study was conducted to detect the prevalence of beta-lactamase and biofilm-producing Klebsiella strains in rectal swabs (n = 624) collected from healthy dogs, cats, sheep and goats reared as companion or household animals in India. The dogs and cats were frequently exposed to third- or fourth-generation cephalosporins for therapy. The sheep and goats were occasionally exposed to antibiotics and had environmental exposure. Phenotypical ESBL (n = 93) and ACBL (n = 88)-producing Klebsiella were isolated significantly more (P < 0·05) from companion animals than household animals. Majority of the Klebsiella possessed blaCTX-M-15 . The sequences blaCTX-M-15.2 , blaCTX-M-197 and blaCTX-M-225 are reported first time from the companion animals. All ACBL-producing isolates possessed blaAmpC . The present study detected 65·8% of Klebsiella strains as biofilm producers possessing the studied biofilm associated genes. The isolates showed phenotypical resistance against chloramphenicol, tetracycline, doxycycline, co-trimoxazole, ampicillin, cefotaxime/clavulanic acid. The present study showed that companion and household animals (dogs, cats, sheep, goats) may act as a carrier of ESBL/biofilm-producing, multi-drug resistant, high-risk clonal lineage of Klebsiella.

Ecology of bats and their role in emerging zoonotic diseases: a review.

The order Chiroptera is the second largest order of mammals and shows great physiological and ecological diversity. These animals play significant ecological roles as prey and predator as well as facilitating pollination, seed dispersal, arthropod reduction and nutrient distribution and reutilisation in nature. Bats act as hosts to a range of viral, bacterial, fungal and parasitic zoonoses. Human activities increase the likelihood of exposure to bats, thereby increasing the opportunity for infections to spill over. Continuing ecological processes, emergence and spillover of novel pathogens in naïve hosts, including humans, along with other complex natural phenomena require proper understanding that may help in predicting the next spillover. This review will discuss the ecology of bats and their role in the emergence of different zoonoses, particularly those of viral origin, in an organised manner to increase understanding of the factors that may play significant roles in spillover of these pathogens from bats to other animals, including humans.

L'ordre des Chiroptères, le deuxième des mammifères en nombre d'espèces, présente des caractéristiques physiologiques et écologiques très diverses. Ces animaux jouent un rôle écologique majeur à divers titres, en tant que proies et prédateurs, mais aussi parce qu'ils interviennent dans la pollinisation, la dispersion des semences, la réduction des populations d'arthropodes et la répartition et réutilisation des nutriments dans la nature. Les chauves-souris sont les hôtes d'un large éventail de virus, bactéries, champignons et parasites zoonotiques. Les activités humaines entraînent une probabilité accrue d'exposition aux chauves-souris, ce qui à son tour multiplie les situations à la faveur desquelles les maladies infectieuses peuvent se transmettre d'une espèce réservoir à des hôtes accidentels. Les processus écologiques continus, l'émergence d'agents pathogènes nouveaux et l'atteinte accidentelle d'une espèce réceptive mais habituellement non touchée, y compris l'homme, ainsi que d'autres phénomènes naturels complexes, doivent être correctement appréhendés afin de pouvoir prédire la prochaine occurrence de ce type de transmission inter-espèces. Les auteurs examinent l'écologie des chauves-souris et leur rôle dans l'émergence de plusieurs zoonoses, notamment d'origine virale, en les présentant sous forme raisonnée afin de mieux faire comprendre les facteurs susceptibles de jouer un rôle significatif dans la transmission de ces agents pathogènes des chauves-souris à d'autres espèces, y compris l'homme.

El orden de los quirópteros, que es el segundo más grande de los órdenes de mamíferos, presenta una gran diversidad fisiológica y ecológica. Estos animales cumplen importantes funciones ecológicas como presas y predadores, además de facilitar la polinización, la dispersión de semillas, la reducción de las poblaciones de artrópodos y la distribución y reutilización de nutrientes en el medio natural. Los murciélagos son hospedadores de una serie de zoonosis víricas, bacterianas, fúngicas y parasitarias. Las actividades humanas aumentan la probabilidad de exposición a murciélagos, acrecentando con ello las posibilidades de extensión secundaria de una infección. Los continuos procesos ecológicos, la aparición de nuevos patógenos y su extensión a hospedadores no expuestos previamente, incluidas las personas, junto con otros fenómenos naturales complejos, obligan a conocer cabalmente estos procesos para ayudar a predecir dónde puede darse la siguiente extensión secundaria. Los autores examinan la ecología de los murciélagos y la función que estos cumplen en el surgimiento de diferentes zoonosis, en especial las de origen vírico, de manera organizada para conocer mejor los factores que pueden influir sustancialmente en el paso de esos patógenos del murciélago a otros animales, en particular el ser humano.

Diagnostic accuracy of FNAC and cyto-histopathological correlation in testicular and paratesticular mass lesions.

OBJECTIVE: FNAC has a definitive role and has proved extremely useful in diagnosis of testicular and paratesticular mass lesions. In view of the dearth of literature of studies involving large cohorts of patients, the present study describes at length the detailed cytological evaluation of testicular and paratesticular mass lesions. METHODS: Our study consisted of 85 cases in 5-year retrospective and 1-year prospective analyses carried out in the Department of Pathology, Government Medical College, Jammu. The study depicts cytomorphological findings of testicular and paratesticular mass lesions. We evaluate the concordance rate of cytological diagnosis with the histological diagnosis as a percentage and assess the diagnostic accuracy of FNAC by calculating sensitivity and specificity. RESULTS: Out of 85 cases, inflammatory lesions comprised the largest group comprising 47 cases (55.29%) followed by 20 cases (23.5%) of cystic lesions. In addition, there were 10 cases (11.76%) of malignant tumours and three cases (3.5%) of benign tumours. Overall, acute orchitis was the most common inflammatory lesions (12.94%) followed by tubercular epididymitis (9.4%). The most common cystic lesion was benign epididymal cyst (10.5%) and the most common malignant tumours were seminoma and embryonal carcinoma. Cytohistological correlation was available for 16 (18.82%) cases only and cytological diagnosis was concordant with the histological diagnosis in all these cases. Sensitivity and specificity of FNAC was 100% in our study. CONCLUSION: FNAC is a useful diagnostic modality for testicular and paratesticular mass lesions due to its high sensitivity and specificity in discriminating between different types of lesions and high concordance rates with histopathological diagnosis.

Is tobacco smoking protective for sarcoidosis? A case-control study from North India.

BACKGROUND: While tobacco smoking is commonly believed to be negatively associated with the occurrence of sarcoidosis, the relationship of environmental tobacco smoke (ETS) exposure with sarcoidosis is largely un-explored. We studied the impact of active smoking and ETS exposure on disease severity in newly diagnosed cases of sarcoidosis from India. METHODS: Data on demographic variables, smoking habits and exposure to environmental tobacco smoke (ETS) among non-smoker sarcoidosis patients was collected prospectively. Presence of smoking and ETS exposure were compared among cases and controls. Among the sarcoidosis patients, clinical manifestations, radiology, spirometry and histopathological grading of lung biopsy were compared between the smokers vs. non-smokers and ETS exposed vs. not-exposed. RESULTS: We studied 98 newly diagnosed cases of sarcoidosis and 196 age, sex and religion- matched healthy volunteers. The study group comprised of 62 (63%) men and 36 (37%) women. The prevalence of smoking was similar in cases and controls (12.2% vs. 15.3%, p = 0.48). Among the never smoker patients with sarcoidosis, 20 (23%) reported ETS exposure vis-a-vis 57 (34%) in the matched controls. A conditional logistic regression analyses showed insignificant negative association with active smoking (OR 0.75; 95% CI, 0.35-1.56) or ETS exposure (OR 0.58; 95% CI, 0.32-1.06) after adjusting for age, gender, religion, and education. There were no differences in the clinical manifestations, radiological staging, spirometry and histopathological grading of lung biopsy in any of the group comparisons studied. CONCLUSION: Smoking or ETS exposure may not have significant negative association with sarcoidosis. Also, tobacco smoke might not have any effect on the clinical behavior or disease severity in sarcoidosis. The belief that smoking is protective for sarcoidosis is not substantiated in this study and appears to be misfounded.

Rarity of somatic and germline mutations of the cyclin-dependent kinase 4 inhibitor gene, CDK4I, in melanoma.

Evidence from cytogenetics, multipoint linkage analyses of familial melanoma, and loss of heterozygosity studies of familial and sporadic melanomas support localization of a melanoma susceptibility or tumor suppressor gene at chromosomal region 9p21-23. Recently, the inhibitor of cyclin-dependent kinase 4 (CDK4I; also known as p16INK4, multiple tumor suppressor 1, or CDKN2 gene) has been mapped to 9p21 and shown to be mutated or deleted in a large fraction of cell lines derived from many tumor types, including melanoma, suggesting that this gene could be a melanoma suppressor gene. In order to test for somatic mutations in the CDK4I gene in tumors, DNAs from 30 surgically resected melanomas of both cutaneous and uveal origins were sequenced. No mutations were detected in the coding region of the CDK4I gene, while mutations or deletions were detected in 60% (9 of 15) of the cultured melanoma cell line DNAs. Among presumptive familial cases, nine of which were members of families with one or two other documented melanoma cases, no germline mutations were detected by sequence analysis. A deletion in the second exon of the CDK4I gene was found in one germline allele of a familial melanoma patient from a family with eight affected first degree relatives. These results not only support the suggestion that the CDK4I gene is a familial malignant melanoma gene, they also suggest the presence of another suppressor gene locus within 9p21 which is the target of loss of heterozygosity in sporadic melanomas.

Ultrastructural changes in the sublingual salivary gland of prenatal buffalo (Bubalus bubalis).

AIM: The present study was aimed to elucidate ultrastructural changes in the development of sublingual salivary gland of buffalo during prenatal life. MATERIALS AND METHODS: The study was carried out on sublingual salivary gland of 36 buffalo fetuses ranging from 13.2 cm curved crown-rump length (CVRL) (88(th) day) to full term. The fetuses were categorized into three groups based on their CVRL. RESULTS: The cells lining the terminal tubules were undifferentiated with poorly developed cytoplasmic organelles but lacked secretory granules (SGs) at 13.2 cm CVRL (88(th) day). The SGs appeared first in the form of membrane-bound secretory vesicles with homogeneous electron-dense as well as electron-lucent contents at 21.2 cm CVRL (122(nd) day); however, mucous acinar cells contained electron-lucent granules, while serous secretory cells as well as serous demilunes showed electron-dense granules at 34 cm CVRL (150(th) day) of prenatal life. At 53.5 cm CVRL (194(th) day), both mucous and serous acini were differentiated by the density of SGs. CONCLUSION: The cytoplasm of acinar cells was filled with mitochondria, rough endoplasmic reticulum, and Golgi profiles in mid and late fetal age groups. The SGs were increased in number during the late fetal age group. The myoepithelial cells (MECs) were located at the base of the acinar cells as well as intercalated and striated ducts and were stellate in shape. The ultrastructure of MEC revealed a parallel stream of myofilaments in the cytoplasm and its processes. The mucous cells were predominantly present in the sublingual salivary gland and were pyramidal in shape.

Regression of invasive conjunctival squamous carcinoma in an HIV-positive patient on antiretroviral therapy.

Case history of an African woman presenting with advanced HIV and a painful conjunctival lesion is presented. A conjunctival biopsy revealed invasive squamous cell carcinoma, with orbital invasion on computed tomography scan. She was commenced on antiretroviral therapy. She refused surgery to remove the eye and orbital contents (exenteration), and was referred to palliative care. Gradually, her immune status and ocular symptoms improved. At ophthalmic review, the tumour had apparently completely regressed. This unprecedented phenomenon may be due to antiretroviral therapy. Discussion covers conjunctival carcinoma and behaviour of HIV-related tumours with antiretroviral therapy. Antiretroviral drugs may offer a better alternative to disfiguring surgery in the future.

Basal cell adenoma-clinicopathological, immunohistochemical analysis and surgical considerations of a rare salivary gland tumor with review of literature.

INTRODUCTION: Basal cell adenoma (BCA) of the salivary glands is a rare benign salivary gland tumour. Differentiation of BCA from varied entities involving maxillofacial area is mandatory. AIM: To analyze the clinicopathological, histopathologic features, immunohistochemcal analysis and surgical considerations of this rare entity. MATERIALS AND METHODS: This study included 12 cases of BCA from archives of department reported over the period of 13 years. All the pertaining clinicopathologic features such as incidence, age, sex and site of lesions were assessed. Tissue sections were stained by using panel of immunohistochemical markers, i.e. Pan CK, CK 5/6 and S100, Calponin, p63, CD 117 and smooth muscle actin. RESULTS: BCA was observed in 26-52 years age group (mean age, 38.75 years) with female propensity of 7:5 male to female ratio. It is seen more commonly in parotid gland, followed by upper lip, buccal mucosa and palate. Solid type is the most common histopathologic type followed by tubular, membranous and trabecular. Only one case of membranous type of BCA showed recurrence. Pan CK, CK 5/6 showed strong immunoreactivity, calponin showed moderate staining, p63 and Ki-67 mild staining, whereas CD 117 and SMA showed negative immunostaining. CONCLUSION: Vigilant comprehensive analysis of all the pertaining clinicopathologic and histopathologic features and immunohistochemical analysis are required for differentiating from other lesions with basaloid differentiation having varying prognosis.

Diagnosis and treatment of uveal melanoma.

Most malignant melanomas in the ocular region arise in the uveal tract (iris, ciliary body, and choroid). Uveal melanoma generally has characteristic clinical features and the diagnosis can usually be made by an experienced ophthalmologist using slit lamp biomicroscopy or indirect ophthalmoscopy. Ancillary studies such as fluorescein angiography, ultrasonography, magnetic resonance imaging, and fine needle biopsy can occasionally be used to establish the diagnosis in atypical cases. Today, most affected patients are managed by specialists in ocular oncology. The management of uveal melanoma has been the subject of considerable controversy. Iris melanoma can usually be excised without enucleation of the affected eye. With regard to posterior uveal melanoma (ciliary body and choroid), enucleation of the affected eye was once the undisputed method of treatment. More recently, however, removal of the eye is performed less often and alternatives to enucleation have gained popularity. Several years ago, laser photocoagulation and plaque brachytherapy were the most popular alternatives to enucleation. Now, techniques of local tumor excision and transpupillary thermotherapy are gaining popularity in selected cases. Even more recently, various combinations of these methods have been judiciously used in many instances. The selected method of treatment in a given case depends on a number of complex clinical factors. Philosophies regarding the management of these lesions continue to change. This review covers the current diagnosis and management of uveal melanoma with emphasis on methods of management.

Genetic aspects of uveal melanoma: a brief review.

Uveal melanoma usually occurs sporadically in the absence of obvious genetic predisposing factors. However, in rare patients, there is a suggestion that there may be genetic predisposition. Rare occurrences of familial uveal melanoma are believed to be inherited in an autosomal dominant mode. There are a few clinical conditions that can predispose to or be associated with uveal melanoma, including ocular melanocytosis, neurofibromatosis type I, and familial atypical mole and melanoma syndrome. Nonrandom cytogenetic changes in uveal melanoma are characterized by monosomy 3, trisomy 8, and structural or numerical abnormalities of chromosome 6. Alterations of chromosome 9p are less frequently observed. CDKN2 gene, a cutaneous melanoma predisposition gene, is probably not a uveal melanoma predisposition gene as evidenced by the lack of somatic mutations involving this gene in uveal melanoma samples and the absence of germline mutations in familial uveal melanoma patients. Transgenic mouse models developed using a tyrosinase promoter tagged with a mutated ras gene or SV40-Tag oncoprotein develop retinal pigment epithelium tumors that resemble uveal melanoma. We propose that uveal melanoma cases be categorized on genetic basis according to a new classification system. This classification scheme will help to identify and uniformly categorize uveal melanoma patients with genetic predisposition. Such patients offer unique opportunities for studying the genetic aspects of uveal melanoma and, therefore, appropriate tissue samples should be obtained from them for molecular genetic studies. Further studies are needed to fully understand the genetic aspects of uveal melanoma.

Uveal melanoma in young patients.

OBJECTIVE: To study the clinical profile of young patients with uveal melanoma. DESIGN: Retrospective case-control series. SETTING: Tertiary referral center. PATIENTS: Data on 63 patients aged 20 years or younger with uveal melanoma were reviewed for clinical profile and association with oculo(dermal) melanocytosis, familial uveal melanoma, dysplastic nevus syndrome, cutaneous melanoma, and other second malignant neoplasms. RESULTS: Of 8000 patients with uveal melanoma, 63 (0.8%) were found in patients who were 20 years of age or younger. The median age at diagnosis was 16 years, and the youngest patient was 3 years old. Sixty-two patients (98%) were white, and uveal melanoma was unilateral in all cases. Seven patients (11%) had oculo(dermal) melanocytosis. Two patients (3%) had dysplastic nevi syndrome, and personal history of cutaneous melanoma was observed in 1 patient (2%). No other second cancers were present in any patient. The 5- and 15-year posttreatment survival estimates were 0.95 (95% confidence interval, 0.87-1.00) and 0.77 (95% confidence interval, 0.52-1.00), respectively. CONCLUSIONS: Uveal melanoma is rare in children or teenagers. It occurs in a heterogeneous group displaying various associations, especially with oculo(dermal) melanocytosis. Oculo(dermal) melanocytosis is 9 times (95% confidence interval, 3.6-22.8) more common in young patients with uveal melanoma than in the general population with uveal melanoma. Young patients with uveal melanoma have short-term (5-year) survival better than that of adults, but the long-term (15-year) survival is similar to that of adults. Arch Ophthalmol. 2000;118:918-923

Acquired tumors arising from congenital hypertrophy of the retinal pigment epithelium.

BACKGROUND: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is widely recognized to be a flat, stationary condition. Although it can show minimal increase in diameter, it has not been known to spawn nodular tumor that is evident ophthalmoscopically. OBJECTIVES: To report 5 cases of CHRPE that gave rise to an elevated lesion and to describe the clinical features of these unusual nodules. METHODS: Retrospective medical record review. RESULTS: Of 5 patients with a nodular lesion arising from CHRPE, there were 4 women and 1 man, 4 whites and 1 black. Three patients were followed up for typical CHRPE for longer than 10 years before the tumor developed; 2 patients were recognized to have CHRPE and the elevated tumor concurrently. Visual acuity was decreased in 3 patients, mainly due to cystoid macular edema. The tumor was located between the equator and ora serrata in all 5 patients. There was no predilection for quadrant of the fundus. The flat part of the lesion was black and had visible lacunae in all 5 patients. The CHRPE ranged in basal diameter from 3 x 3 mm to 13 x 11 mm. The size of the elevated lesion ranged from 2 x 2 x 2 mm to 8 x 8 x 4 mm. The nodular component in all cases was supplied and drained by slightly prominent, nontortuous retinal blood vessels. Yellow retinal exudation occurred adjacent to the nodule in all 5 patients and 1 patient developed a secondary retinal detachment. Two tumors that showed progressive enlargement, increasing exudation, and progressive visual loss were treated with iodine 125-labeled plaque brachytherapy, resulting in deceased tumor size but no improvement in the visual acuity. CONCLUSIONS: Congenital hypertrophy of the retinal pigment epithelium can spawn a nodular growth that slowly enlarges, attains a retinal blood supply, and causes exudative retinopathy and chronic cystoid macular edema. Although no histopathologic evidence is yet available, we believe that the tumor probably represents either an acquired adenoma or a reactive proliferation of the retinal pigment epithelium. The best treatment of these lesions is not yet established.

Metastatic neoplasms in the optic disc: the 1999 Bjerrum Lecture: part 2.

BACKGROUND: Little information is available on metastatic tumors to the optic disc. OBJECTIVE: To determine the clinical features and prognosis of patients with optic disc metastasis. DESIGN: Retrospective chart review. RESULTS: Of 660 consecutively evaluated patients with intraocular metastasis, 30 (4.5%) (31 eyes) had metastatic cancer to the optic disc; 24 (80%) were women and 6 (20%) were men. Mean age at the time of ocular diagnosis was 55 years. The primary neoplasm was in the breast in 13 patients (43%), in the lung in 8 (27%), in the intestine in 1 (3%), in the kidney in 1 (3%), and in the prostate in 1 (3%); the primary neoplasm was never determined in 6 patients (20%). The optic disc metastasis was unilateral in 29 patients (97%) and bilateral in 1 (3%). Ophthalmoscopically, the disc metastasis appeared as a diffuse enlargement of the optic disc in 26 eyes (84%) and as a distinct nodule in 5 (16%). There was an adjacent juxtapapillary choroidal component to the metastatic disc lesion in 23 eyes (74%), and the optic disc was involved without a retinal or choroidal component in 8 (26%). Other associated findings included some degree of secondary disc edema in all eyes, buried disc blood vessels in 23 (74%), and splinter hemorrhages in 13 (42%). Fine needle aspiration biopsy was useful in establishing the diagnosis in all 5 eyes in which it was performed. Mean survival was 13 months after diagnosis of the disc metastasis. CONCLUSIONS: Metastasis to the optic disc accounts for 5% of all intraocular metastases. It can occur as invasion from a juxtapapillary choroidal metastasis or as isolated optic disc metastasis. Breast and lung cancers are the most common primary neoplasms that account for metastasis to the optic disc. The primary site is never determined in 20% of patients. The characteristic clinical features of optic disc metastasis should help differentiate it from other causes of swollen optic disc. Patient prognosis is poor.

Use of the hydroxyapatite ocular implant in the pediatric population.

OBJECTIVES: There is always a hesitancy to use an ocular implant after enucleation in children, especially in cases of eyes enucleated for retinoblastoma. DESIGN AND SETTING: In this prospective study, we report our experience of 60 consecutive cases in which we used the hydroxyapatite ocular implant after enucleation in children younger than age 10 years. RESULTS: The mean age at the time of enucleation and hydroxyapatite placement was 27 months (range, 1 to 108 months). The histopathologic diagnoses after enucleation included retinoblastoma in 51 patients, endophthalmitis in two patients, persistent hyperplastic primary vitreous in two patients, neovascular glaucoma resulting from Coats' disease in one patient, uveal melanoma in two patients, undifferentiated intraocular neoplasm in one patient, and blind painful traumatized eye in one patient. After a mean follow-up of 19 months (range, 6 to 36 months), two cases of conjunctival erosion and five cases of conjunctival thinning were recorded. These problems were associated with a flat posterior prosthesis vault in all seven cases. There were no cases of orbital cellulitis, implant extrusion, or implant migration. All children showed good small-degree prosthesis motility despite the lack of peg placement. Only one older child underwent drilling and peg placement and she had excellent small- and large-degree prosthesis motility. We generally postpone the drilling and peg placement stage and tedious prosthesis revision in children until they are able to fully cooperate with the ocularist. CONCLUSIONS: The hydroxyapatite ocular implant is well tolerated and provides good prosthesis motility in children with few complications. It is critical for the ocularist to fit the prosthesis comfortably with a high posterior vault.

Primitive neuroectodermal tumor of the orbit.

A 10-year-old girl developed a lump in the lateral aspect of the right eyebrow over a 3-week period. Computed tomography and magnetic resonance imaging revealed a soft-tissue mass in the superolateral aspect of the right orbit associated with zygo-maticofrontal bone erosion and hyperostosis. An incisional biopsy specimen was studied using light microscopy, immunohistochemical staining, and electron microscopy, resulting in a diagnosis of peripheral primitive neuroectodermal tumor. The results of an extensive evaluation for systemic involvement were negative. The patient was subsequently treated with chemotherapy and radiation therapy. Primary primitive neuroectodermal tumor of the orbit is rare. The differential diagnosis and the diagnostic features of this entity are discussed herein.

Iris mammillations as the only sign of ocular melanocytosis in a child with choroidal melanoma.

An 8-year-old girl had visual loss in her left eye over 2 months. Ocular examination showed that visual acuity was counting fingers in the left eye. The left iris was moderately pigmented and thickened with numerous confluent, dome-shaped elevations on its surface, consistent with iris mammillations arising from ocular melanocytosis. There was total retinal detachment and an inferiorly located large amelanotic choroidal mass compressing the optic nerve. A specimen from a fine-needle aspiration biopsy showed spindle and epithelioid melanoma cells. The eye was enucleated. Pathologic examination showed that the bland melanocytes comprising the anterior border layer of iris formed focal aggregates, corresponding to the iris mammillations observed clinically. The uvea was diffusely thickened. Arising from the posterior choroid and obscuring the optic nerve head was a moderately pigmented spindle and epithelioid cell choroidal melanoma with diffuse lymphocytic infiltration and high mitotic activity. This case demonstrates that iris mammillations can be the initial manifestation of ocular melanocytosis in the absence of scleral pigmentation.

Observations on 17 patients with retinocytoma.

OBJECTIVE: To study the clinical features and natural history of 17 patients with retinocytoma. DESIGN: A retrospective case series. SETTING: Tertiary referral center. PATIENTS: Data on 17 patients with retinocytoma were reviewed for clinical features. The natural history of retinocytoma and its risk for malignant transformation were also evaluated. RESULTS: Among 920 consecutive patients who had retinoblastoma, retinocytoma, or both, we identified 24 tumors in 17 patients (1.8%) with clinical features compatible with retinocytoma. The median age at diagnosis was 15 years (range, 4-45 years). Of the 24 tumors, the retinocytoma was bilateral in 3 cases (13%) and the family history of retinoblastoma was positive in 3 cases (13%). Seventeen (71%) of the tumors were extramacular in location, and 7 (29%) were located in the macular area. Ophthalmoscopic features characteristic of retinocytoma included the presence of a translucent retinal mass in 21 (88%), calcification in 15 (63%), and retinal pigment epithelial alteration in 13 (54%) of the 24 tumors. A combination of all 3 features was observed in 8 (33%) of the 24 tumors. In 13 (54%) of the tumors, a zone of chorioretinal atrophy could be observed. In 1 patient, subtle tumor regression was documented photographically. Only 1 retinocytoma (4%) underwent malignant transformation into retinoblastoma. At the last follow-up visit, none of the patients had developed a pineoblastoma or another second malignant neoplasm. CONCLUSIONS: Retinocytoma is a rare benign retinal tumor that has characteristic clinical features. The areas of chorioretinal atrophy were suggestive of tumor regression. In our series, the risk for malignant transformation of retinocytoma into retinoblastoma was 4%; therefore, patients with a presumed diagnosis of retinocytoma should be closely observed.

Combination of clinical factors predictive of growth of small choroidal melanocytic tumors.

OBJECTIVE: To better define the effect of individual risk factors and combinations thereof on the growth of small choroidal melanocytic tumors. DESIGN: Retrospective analysis. SETTING: Clinical practice of ocular oncology. PATIENTS: The study included 1287 patients with small suspicious choroidal melanocytic tumors, measuring 3 mm or less in thickness, managed with observation. RESULTS: On multivariate analysis, the clinical risk factors predictive of growth of small choroidal melanocytic tumors include tumor thickness greater than 2.0 mm, posterior tumor margin touching the disc, visual symptoms, orange pigment, and subretinal fluid. Tumor growth was detected in 4% of those patients with no risk factors. Growth was detected in approximately 36% of patients with 1 risk factor, 45% of patients with 2 risk factors, 50% of patients with 3 risk factors, 51% of patients with 4 risk factors, and 56% of patients with all 5 risk factors. The combination of risk factors offering the greatest risk for growth was tumor thickness greater than 2.0 mm, tumor margin touching disc, and subretinal fluid that was associated with tumor growth in 63% of the affected patients. The relative risk for growth was 1.9 for 1 factor, 3.8 for 2 factors, 7.4 for 3 factors, 14.1 for 4 factors, and 27.1 for all 5 risk factors combined. CONCLUSIONS: Five risk factors for growth of small choroidal melanocytic tumors have been identified. The combinations of various factors increase the risk for tumor growth from 4% if no factors are present to more than 50% if 3 or more risk factors are present. These factors may be important when counseling patients with small suspicious choroidal melanocytic tumors.

Adenocarcinoma arising from congenital hypertrophy of retinal pigment epithelium.

Congenital hypertrophy of the retinal pigment epithelium (CHRPE), traditionally regarded as a benign stationary condition, has recently been shown in 5 cases to give rise to an elevated, solid tumor. However, the histopathologic nature of the tumor that arises from CHRPE has not been previously determined. A 65-year-old woman developed a progressively enlarging peripheral fundus tumor that arose from a focus of classic CHRPE. The tumor produced a localized exudative retinal detachment, cystoid macular edema, and surface-wrinkling retinopathy. The mass was removed by local resection, and histopathologic examination revealed a low-grade adenocarcinoma of the retinal pigment epithelium, apparently arising from CHRPE. Although CHRPE is usually a benign nonprogressive lesion, it can give rise to a malignant tumor. Congenital hypertrophy of the retinal pigment epithelium should be observed periodically for development of a neoplasm.