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Purpose To evaluate the mononuclear cells in the subretinal exudate in Coats' disease. Design Retrospective case series. Methods Five enucleated globes and 1 cytology sample from a patient with Coats' disease and 1 case of chronic retinal detachment following repair of an open globe injury were examined immunohistochemically to identify intraretinal and subretinal exudative cells. The 2 biomarkers were RPE65 for retinal pigment epithelium and CD163 for histiocytes, each tagged with different chromogens, yellow for pigment epithelium and purple for CD163-positive (CD163+) monocytes/histiocytes. Expression levels were sought from both biomarkers together and singly. A color shift to red in the cells' chromogenic reaction indicated the simultaneous presence of the 2 biomarkers. Results Most of the mononuclear cells in Coats' disease samples were CD163+ (purple), and a minority were RPE65+ (yellow). An intermediate number of cells were RPE65+/CD163+ (orange-red). The eye with a chronic retinal detachment had an equal distribution of CD163+ and RPE65+/CD163+ cells. Conclusions RPE has several well-delineated phenotypes and functions. In normal visual physiology, the pigment epithelium supports photoreceptors and participates in their renewal by phagocytosis of the tips of the photoreceptors. The expression of CD163, a feature of hematopoietically derived monocytes, together with RPE65 in the retinal pigment epithelium, supports differentiation toward histiocytes. Yellow staining of detached pigment epithelial cells were rare. The presence of histiocytoid pigment epithelium at the Bruch membrane probably also has implications for macular degeneration.

Purpose To describe the clinical and pathologic features of a case of epibulbar proliferative fasciitis and to compare it with other focal or diffuse myxoid lesions. Methods A clinical, histopathologic, and immunohistochemical analysis was performed. The clinical history, photographic documentation, history, and referred slides were reanalyzed. Additional immunohistochemical stains were performed at our institution. Results A 68-year-old woman developed over a week a brightly vascularized and focally hemorrhagic placoid lesion on the temporal side of the OS. She had had earlier augmentation breast surgery that had been mistakenly initially reported to us to be for breast carcinoma. Hematoxylin- and eosin-stained reactions revealed microscopically a spindle cell lesion with an intact nonkeratinizing epithelium and a background myxoid stroma with prominent capillaries and a light dispersion of small T-cell lymphocytes. Most striking among the spindle cells were some widely separated large atypical cells. The atypical cells were cytokeratin positive, but an expansive panel of immunohistochemical stains for breast carcinoma was negative. The lesion was diagnosed as proliferative fasciitis and has not recurred after 1-year follow up. Conclusion A rapidly evolving conjunctival lesion is unlikely to be a primary or metastatic carcinoma. In the current case, the large ganglioform or rhabdomyoblast-like cells displayed diffuse cytokeratin positivity, still consistent with a mesenchymal or connective tissue cell lineage. Cytokeratin expression has been a finding previously reported in connective tissue tumors and in lymphoma cells. While the current lesion clinically resembles a conventional nodular fasciitis, the presence of the large atypical cells can lead to the misdiagnosis of a sarcoma, which typically displays a much higher Ki-67 proliferation index in comparison with nodular/proliferative fasciitis.

Introduction: The goal of this study was to histopathologically evaluate the appearance of degrading MIRAgel scleral buckles so that they can be reliably distinguished by ophthalmic pathologists from other foreign materials. Methods: Retrospective chart review and histopathologic study with special stains, including Alcian blue, periodic acid-Schiff, Masson’s trichrome, and Perls’ Prussian blue for iron, of 4 cases between 2017 and 2019. Results: Hydrolyzed MIRAgel scleral buckles from 4 patients had a consistent histopathologic appearance. They had a honeycomb structure with the walls of the lattice ranging from distinct to poorly defined. The walls of the lattice were positive for Alcian blue, while the contents of each cell contained periodic acid-Schiff-positive material. Other special stains were not as valuable in highlighting the material. Discussion: Although the capsules of MIRAgel scleral buckles have been well studied, the material itself has not been. While clinical history and radiographic appearance are often diagnostic of a hydrolyzed MIRAgel scleral buckle, there are instances of preoperative ambiguity where histopathologic confirmation can be useful. Conclusions: MIRAgel scleral buckles have a distinct histopathologic appearance that can be readily distinguished from that of other foreign materials.

Purpose To document a unique case of anorectal squamous cell carcinoma that was metastatic to the microvasculature of the lacrimal gland in a patient with human immunodeficiency virus and to review previously reported cases of metastases to the lacrimal gland. Methods Both a retrospective chart review and comprehensive literature review were performed. The unusual histopathologic pattern of the current case was illustrated with immunohistochemical studies (CD31, D2-40, pancytokeratin, p16, and p63) and in situ hybridization studies for high-risk human papillomavirus types 16 and 18. Results The authors describe the first case of metastatic anorectal squamous cell carcinoma to the lacrimal gland. Only 24 cases of metastatic disease to the lacrimal gland have been reported, the majority from breast carcinomas. The metastasis did not form a macroscopic lesions, instead was composed of microscopic intravascular and intraparenchymal tumor deposits, a subtle phenomena. Immunohistochemistry confirmed the presence of the intravascular neoplastic cells. p16 served as a surrogate marker for human papillomavirus-associated squamous cell carcinoma and was confirmed with in situ hybridization for human papillomavirus 16 and 18. This testing, combined with the clinical history, defined the diagnosis and confirmed human papillomavirus as the tumor driver. Conclusions Metastases to the lacrimal gland remain rare, but clinicians and pathologists alike must be attuned to the possibility of subtle microscopic foci of tumor as a pattern of metastasis in scenarios without a discrete mass-forming lesion, as this may portend a poor prognosis.

Purpose Since the original description of “dacryadenoma” by Jakobiec and associates, the data on this unusual epibulbar lacrimal gland lesion remain sparse. The aim of this study was to characterize clinically, morphologically, and immunohistochemically this isolated epibulbar lacrimal gland lesion. Design Retrospective observational case series. Methods Institutional pathology records between 2000 and 2019 were searched for all cases of isolated epibulbar lacrimal gland lesions. Tissue from 3 normal lacrimal glands and 1 complex choristoma were included for comparative analysis. Clinical, histopathologic, and immunohistochemical findings were recorded. Results Four patients with isolated epibulbar lacrimal gland lesions, 2 male and 2 female, with a median age of 18 years (range, 12-57) were identified. All patients presented with recent onset of unilateral pink-to-orange, well-circumscribed subepithelial juxtaforniceal (3/4, 75%), or nasal (1/4, 25%) bulbar conjunctival nodules, which were asymptomatic (3/4, 75%) or associated with foreign body sensation (1/4, 25%). When compared with the normal lacrimal gland and complex choristoma, all isolated epibulbar lacrimal gland lesions were composed predominantly of variably dilated, branching tubular structures with pseudo-apocrine snouts, and either totally absent (2/2, 50%) or rare (2/2, 50%) ducts and rare acinar zymogen granules (3/4, 75%). Conclusion Our study confirms that a subset of isolated epibulbar lacrimal gland lesions differs morphologically and immunohistochemically from normal lacrimal gland tissue and the lacrimal gland in a complex choristoma. These differences range from subtle to overt, suggesting that isolated epibulbar lacrimal gland lesions may have originated from precursor cellular elements indigenous to the conjunctiva (hamartia) and grew into disorganized lacrimal gland tissue.

Purpose The purpose of this study was to investigate an enlarged dacryoadenotic lacrimal gland and normal lacrimal glands for the presence of goblet cells (mucocytes). Design Retrospective clinicopathologic series. Methods An enlarged lacrimal gland (dacryoadenosis) without obvious histopathologic alterations was extensively evaluated histochemically, immunohistochemically, and ultrastructurally to detect the presence of goblet cells and to compare the findings with those in five normal lacrimal glands. Results Granular, zymogen-rich pyramidal acinar cells in normal glands predominated over a previously not reported subpopulation of nongranular, pale-staining cells in both dacryoadenotic and normal lacrimal glands. These cells histochemically stained positively with mucicarmine and Alcian blue. Immunohistochemical and electron microscopic evaluations established that there was a displacement or replacement of cytoplasmic gross cystic disease fluid protein-15 and CK 7-positive tonofilaments in the pale acinar cells by myriad mucus granules. The goblet cells constituted approximately 2% of the normal acinar cells and 5% of dacryoadenotic acinar cells. A depletion of myoepithelial cells and ectopic intra-acinar ductular cells were also observed in dacryoadenosis. Conclusion Dacryoadenosis is caused by an increase in the number of acini without individual acinar cell hyperplasia. A normal cytologic feature of the lacrimal gland is the presence of acinar goblet cells that had been long overlooked; they are increased in number in dacryoadenosis. Intra-acinar ductular cells and the scattered loss of myoepithelial cells are other abnormalities in dacryoadenosis. The presence of lacrimal gland goblet cells may have physiologic implications for the precorneal tear film and its derangements as well as for the histogenesis of mucus-producing carcinomas.

Purpose To document a unique case of a corneal/conjunctival epithelial inclusion cyst located in the orbicularis oculi muscle with a comprehensive review of variant conjunctival cysts and simulating conditions. Methods Clinicopathologic case report with detailed histopathologic and immunohistochemical evaluation for cytokeratins combined with a tabulation of mimicking lesions and relevant literature citations. Results A 59-year-old man experienced severe blunt left periorbital trauma that resulted in a limbal partial-thickness corneal wound with an associated epithelial abrasion and a full-thickness eyelid laceration extending from the superior fornix to the margin. Several months after surgical repair of the eyelid a cyst appeared in the superior pretarsal skin. Histopathologic and immunohistochemical investigations supplied data suggesting that the cyst had a high probability of a corneoscleral limbal stem cell origin. Distinctive features of the lesion are contrasted with those of allied or simulating cysts. Conclusions Stem cells are now believed to be located at the corneoscleral limbus, in the inferior fornix, in the medial canthal region, and at the eyelid margin where transitions from conjunctival epithelium to epidermal epithelium occur. Due to their replicative, hardy and robust nature, stem cells displaced to alien environments are most likely to survive and produce cysts. The cyst's corneal-type cytologic characteristics, the absence of goblet cells, and the expression of a broad spectrum of cytokeratin biomarkers in the current case give support to the proposal that limbal stem cells in the region of the corneal laceration were displaced to the eyelid orbicularis muscle and were responsible for this most extraordinary cyst. Comparison with other epithelial cystic linings lends further evidence for this conclusion.

Over several months, a painless, multinodular, non-erythematous swelling of the deep tissues of his left upper eyelid developed in a 63-year-old man. An excisional biopsy with histopathologic evaluation disclosed a unique sebaceous papilloma within a cyst lined by non-keratinizing squamous epithelium that focally displayed a variably thick, superficial, eosinophilic cuticular layer. Immunohistochemical staining demonstrated that the tumor and its epithelial cystic lining had a profile consistent with Meibomian gland duct epithelium. Adipophilin highlighted cytoplasmic vacuolar lipid positivity. The encapsulation of the lesion, absence of nuclear atypia, and Ki-67 nuclear positivity restricted to the basilar cells established its intrinsically benign nature. The patient's clinical history was remarkable for pulmonary and colonic carcinomas resected, respectively, 20 years and 8 years earlier. DNA mismatch repair protein expression studies disclosed loss of nuclear immunostaining of MSH6 protein, pointing to the possibility of an underlying rare MSH6 variant of the Muir-Torre syndrome, not yet described in the ophthalmic literature. p16 nuclear positivity was also found in the tumor cells, indicating the possible role of high-risk human papillomavirus as an additional factor in the genesis of the tumor. Genetic evaluation of normal and tumoral tissues in future similar cases will detect if there is an underlying germline mutation versus a somatic mutation limited to the tumor. This will be required to fully establish a predictable linkage with this new subtype of the Muir-Torre syndrome.

A yellow cyst of the caruncle in a 68-year-old man displayed the characteristic sebaceous glands and sebocytes of steatocystoma within the cyst wall, with a unique configuration of multiple branching compartments. The cyst lining was of trichilemmal character, lacking a keratohyalin granular layer, and replicated the immunohistochemical characteristics of a previously reported caruncular steatocystoma with the exception of a positive trichilemmal marker, calretinin, in the present case. Four previous cases of caruncular steatocystoma have been described, only one of which incorporated immunohistochemical analysis. Steatocystoma develops from a sebaceous gland duct, which displayed in this case multiple chambers subdividing what is usually a single round lumen.

Purpose To determine if there is a biologic rationale for using checkpoint inhibitor drugs targeting programmed cell death ligand 1 (PD-L1) and PD-L2 in the treatment of adenoid cystic carcinoma of the orbit. Methods Twenty-three cases of adenoid cystic carcinoma involving the orbit (13 primary lacrimal gland, 5 secondarily extending into the orbit, and 5 unspecified) were examined histopathologically. Immunohistochemistry for PD-L1, PD-L2, and CD8 was performed. Charts were reviewed for clinical correlations. Results Expression of PD-L1 and of PD-L2 was overall low in adenoid cystic carcinoma (mean expression 1.4 ± 0.9 of 5 for PD-L1, mean 0.83 ± 1.1 of 5 for PD-L2), and tumor-infiltrating CD8-positive T-lymphocytes were sparse (mean 1.1 ± 0.51 of 3). Only 13 of the 23 (57%) cases expressed PD-L1 as a combined positive score ≥1 of cells. No associations were found between expression levels of these markers and patient sex, tumor site of origin, Tumor, Node, Metastasis stage, or patient outcome. A significant association was observed between stromal PD-L1 expression and tumor histopathologic subtype (p = 0.05), and between tumor PD-L1 expression and prior exposure to radiation (p = 0.03). Conclusions Checkpoint inhibitor drugs may have limited impact in the treatment and clinical course of orbital adenoid cystic carcinoma based on the low frequency of CD8 infiltrate and low expression of PD-L1 and PD-L2. Pretreatment with radiation, however, may improve tumor response to checkpoint inhibitor drugs.

A 55-year-old woman developed a painless, non-ulcerated left upper eyelid swelling over 6 months. Examination disclosed a fluctuant mass that permitted movement of the eyelid skin over the lesion. A full-thickness eyelid resection contained a well-encapsulated cyst with milky contents that was predominantly located in the tarsus. The cyst’s lining was partially composed of segments of ciliated respiratory-type and non-keratinizing squamous epithelia. Immunohistochemical evaluation with cytokeratins 17, 18, and 19 confirmed the staining pattern of a respiratory-type epithelial cell (whether or not cilia were present in the non-squamous epithelial zones). In the squamous region, entirely different cytokeratin results were obtained vis-a-vis the non-squamous regions of the lining. The current lesion is interpreted as congenital and representing an in situ persistence of embryonic ciliated glandular epithelium that normally exists only transitorily. A more remote possibility is that the lesion was the result of ectopic epithelial cells displaced from an adjacent sinus. A recurrence has not developed during 6 months of follow-up.

Purpose To highlight the histopathologic diagnostic challenges of small-cell predominant extranodal nasal-type natural killer/T-cell lymphoma (ENTNKT) of the orbit. Methods Retrospective chart review and histopathologic study with immunohistochemistry and in situ hybridization of 3 cases. Results Three cases of ENTNKT presented to the Mass Eye and Ear emergency room as orbital cellulitis over 1 year. The first case was unusual in that there was a predominance of small cells, giving the ENTNKT the histopathologic appearance of a nonmalignant inflammatory process. This challenging case is juxtaposed alongside 2 other cases, which exhibited the more typical lymphomatous microscopic appearance. Discussion ENTNKT can extend into the orbit from the adjacent sinuses or rarely arise primarily in the orbit. A diagnosis is typically made with a biopsy. Occasionally, however, the histopathologic diagnosis can be elusive when a predominance of small lymphomatous cells that are virtually indistinguishable from non-neoplastic inflammatory cells is present. Demonstration of CD56 positivity by immunostaining and in situ hybridization for Epstein-Barr virus are essential in confirming the diagnosis. Conclusions ENTNKT should be considered both in the clinical and histopathologic differential diagnoses of orbital infections and idiopathic inflammations (pseudotumor).

Rhabdomyosarcoma (RMS) is the most common sarcoma of childhood and adolescence. Approximately 10% arise in the orbit, where the embryonal type is most common variant. The alveolar variant is less frequent and has a worse prognosis. Cytogenetic studies have revealed that most alveolar rhabdomyosarcomas have translocations involving the PAX and the FOX01 genes, giving rise to fusion genes that contribute to lack of differentiation and proliferation of the tumor cells. However, approximately 20% of alveolar rhabdomyosarcomas lack translocations and have been found to behave more similarly to embryonal cases. Histopathology remains the basis of diagnosis, but cytogenetic features and molecular signatures are becoming part of the routine analysis of RMS, since they determine not only prognosis, but also management and treatment regimens. A comprehensive review of the recent published literature in relation to orbital rhabdomyosarcomas and their cytogenetic features as well as clinical and therapeutic implications will be discussed.

PURPOSE: Novel cancer immunotherapies, called immune checkpoint inhibitors, have demonstrated clinical efficacy in the treatment of squamous cell carcinomas of the head and neck. Tissue expression of programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2) has been shown to predict tumor response to these drugs. We examine the expression of prognostic immune biomarkers, PD-L1 and PD-L2, in invasive ocular surface squamous neoplasia. DESIGN: Retrospective case series. METHODS: Eighteen cases of ocular surface or ocular adnexal invasive squamous cell carcinomas were identified in pathology case files of the Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary and at the Wills Eye Hospital accessioned between January 1, 2014 and January 1, 2017. Immunohistochemical staining for PD-L1, PD-L2, CD8, and p16 was performed and graded in a standardized fashion. RESULTS: PD-L1 and PD-L2 were expressed on tumor cells to varying degrees, and also on some stromal cells and endothelial cells. Stromal and endothelial cell expression was also seen in control conjunctival specimens. Tumor expression of PD-L1 and PD-L2 was present on the cell membranes. All 18 (100%) of the tumors expressed PD-L1: 7 (39%) expressed a high level, 3 (17%) expressed a medium level, and 8 (44%) expressed a low level. Only 9 (50%) tumors expressed PD-L2 and it was at a low level. The expression of PD-L1 in tumor cells correlated with the presence of CD8-positive cytotoxic T lymphocytes among tumor cells (P < .01) and with the presence of CD8-positive cells in the surrounding stroma (P = .04). CONCLUSIONS: A subset of ocular invasive conjunctival squamous carcinomas express high levels of PD-L1 and CD8 and therefore may respond therapeutically to immune checkpoint inhibition.

Purpose To document a case of actinic granuloma (AG) of the conjunctiva, provide an extensive histopathologic and immunohistochemical description, review previously reported cases, and supply a differential diagnosis. Methods Both a retrospective chart review and comprehensive literature review were performed. The distinctive histopathologic pattern of the current case was defined with histochemical and immunohistochemical stains (CD163, p63, and a Verhoeff-Van Gieson elastic stain). Clinical follow up was obtained. Results A granulomatous process composed of CD163-positive mononuclear epithelioid cells and multinucleated giant cells was characterized by displaced extracellular actinic-related elastic fibers to the base of the lesion. Small elastic fibers were phagocytosed in epithelioid cells. Pseudoepitheliomatous hyperplasia of the overlying squamous epithelium was present; p63 assisted in defining the squamous proliferation and highlighted its noninvasive nature. Conjunctival AGs, according to the literature review, occur almost exclusively in young females, clinically manifest as nodular foci with painless injection over the course of weeks, and histologically featured granulomatous inflammation and elastophagocytosis. The etiology of this entity is likely multifactorial, but its genesis revolves around actinic injury. Conclusion AGs of the conjunctiva have likely been an underreported entity in the past. The authors' review underscores the importance of including conjunctival AGs in the differential diagnosis of painless, subacute injected masses of the perilimbal conjunctiva. While it is benign, histopathologically separating AGs from neoplasia and other mimickers such pinguecula, foreign body granulomas, allergic, or rheumatoid nodules is essential for optimal management.

A yellow cyst of the caruncle in a 68-year-old man displayed the characteristic sebaceous glands and sebocytes of steatocystoma within the cyst wall, with a unique configuration of multiple branching compartments. The cyst lining was of trichilemmal character, lacking a keratohyalin granular layer, and replicated the immunohistochemical characteristics of a previously reported caruncular steatocystoma with the exception of a positive trichilemmal marker, calretinin, in the present case. Four previous cases of caruncular steatocystoma have been described, only one of which incorporated immunohistochemical analysis. Steatocystoma develops from a sebaceous gland duct, which displayed in this case multiple chambers subdividing what is usually a single round lumen.

Purpose To document a case of a biphenotypic sinonasal sarcoma that impinged on the orbit via a tumor-induced mucocele and review the previous literature devoted to this condition. Methods A clinicopathologic case report with detailed histopathologic, immunohistochemical, and radiological studies with tabulations of previously reported cases and immunohistochemical stains for ruling out mimicking lesions. Results A biphenotypic sinonasal sarcoma arose from the ethmoid sinus in a middle-aged man. The tumor induced a mucocele that bowed the medial orbital lamina papyracea into the orbit and caused diplopia and mild proptosis. The biopsy's dual positivity for S100 and smooth muscle actin together with positive paired box 3 immunohistochemical staining established the diagnosis of biphenotypic sinonasal sarcoma. Conclusion Biphenotypic sinonasal sarcoma, which can involve the orbit in 25% of cases, is a rare head and neck malignancy that has only recently been described. Biphenotypic sinonasal sarcoma is a low-grade, locally aggressive, nonmetastasizing sarcoma displaying both neural and muscle differentiation. It is further characterized by rearrangements of the PAX3 gene with multiple fusion partners, most commonly MAML3 (Mastermind like transcriptional coactivator 3). It occurs predominantly in middle-aged women and exclusively in the sinonasal tract. However, it can spread throughout the central facial structures to invade the brain if not detected early. Ophthalmologists should be aware of this new entity to avoid delays in diagnosis and treatment. The previous literature devoted to this condition was reviewed and analyzed for clinical, radiological, histopathological, and immunohistochemical features. In circumstances where molecular testing is not available, paired box 3 immunohistochemical staining can be used as an alternative diagnostic marker. The current case is most unusual because the orbital findings were induced by a mucocele caused by the tumor that obstructed the sinus ostium. This produced diplopia without direct tumor invasion into the orbital fat.

This is a case report involving 3 siblings, ages 22, 21, and 3 years old, of consanguineous parents and Syrian descent with a particularly unique clinical phenotype and eyelid/gingival findings that have not been previously characterized. Full-thickness eyelid biopsies for 2 of the siblings were evaluated by ophthalmic pathology showed generalized fibrosis without any active destructive process or amyloid. Three of the 9 siblings were affected by this order with no familial history. Ophthalmic plastic surgeons should be aware of this new entity as genetic localization and further identification may help families affected by this disorder.

Purpose To evaluate the expression of programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) in ocular adnexal sebaceous carcinoma (OASC), and to appraise these findings within the context of recent comparable studies. Designs Retrospective case series. Methods Twenty cases of primary OASC were immunostained for PD-L1, PD-L2 and CD8. PD-L1 and PD-L2 expression were graded with both the combined positive score (CPS) and the tumor proportion score (TPS). Both raw CPS and TPS were reported, as well as positivity with TPS and CPS ≥1. CD8 expression was graded on a 0-3 scale. Charts were reviewed for clinical correlations. The results of the current study were compared with results of similar recent investigations. Results For the 20 cases, mean expression of PD-L1 with CPS was 29.7 (range 0-101.5) and with TPS was 12.2 (range 0-95.8); mean expression of PD-L2 with CPS was 7.9 (range 0-37.3) and with TPS was 1.9 (range 0-12.9). PD-L1 CPS ≥1 was detected in 95% of OASC, while PD-L1 TPS ≥1 was found in 75%. PD-L2 CPS ≥1 was present in 60%, while only 20% had PD-L2 TPS ≥1. Immune cells appeared to contribute to a substantial proportion of PD-L1 and PD-L2 positivity, and a conspicuous CD8-positive T-lymphocytic infiltrate was present in most tumors. Significant correlations were identified between tissue expression of PD-L1, PD-L2, and CD8. Tissues with greater levels of PD-L1 tended to express higher levels of PD-L2 and CD8. The degree of PD-L1 and PD-L2 expression was also associated with the area in millimeters squared of the immunostained tumor, suggesting that tumor sampling may influence interpretation of PD-L1 and PD-L2 expression in ocular adnexal tumors. Conclusions The current and preceding studies confirm that PD-L1 and PD-L2 are expressed in a high percentage of OASCs. These results support the premise that checkpoint inhibitor drugs hold considerable therapeutic promise for patients with OASC and stimulate the institution of clinical trials.

A 68-year-old woman developed an asymptomatic left caruncular multilobular lesion over one year. Excision of the lesion displayed a benign sebaceous neoplasm taking origin from the surface squamous epithelium which invaginated into the stroma to create crypts resembling the conjunctival pseudoglands of Henle or the glands of Lieberkuhn of the small intestine. Scattered sebaceous cells were also discovered in the surface squamous epithelium. The cryptal walls spawned lateral sebaceous gland lobules that were adipophilin positive. p16 was positive in the surface epithelium, the cryptal walls, and in the basal cells of the sebaceous lobules. No defects in nuclear mismatch repair protein expression were identified, which together with the absence of a familial cancer history, rendered unlikely an association with the Muir-Torre syndrome.

Purpose To describe outcomes of globe-preserving surgery combined with high-dose proton beam radiation (PBR) in treating primary adenoid cystic carcinoma (ACC) of the lacrimal gland. Design Retrospective case series. Methods Twenty-nine patients with primary ACC of the lacrimal gland were identified in the records of a single institution between 1990 and 2017. Patients with nonorbital primary tumor origins or with inadequate follow-ups were excluded. Eighteen patients met inclusion criteria. Clinical data, imaging studies, histopathology, treatment modality, local recurrences, visual outcomes, metastases, and survivals were assessed. Disease-free survivals for the current patients were measured and compared to those of other studies. Results The eighteen patients (14 female, 4 male) were followed for a median of 12.9 years (range 0.6–22.3 years) after treatment completion. Their median age was 40 years. Four were children (median age 12 years). All were treated with globe-preserving tumor resection and radiation (median dose of 72 cobalt gray equivalents). Three adult patients died of metastatic disease (median of 4.2 years after treatment). Four had local recurrences. Useful vision (20/40 or better) was retained for a median 3 years (range 1–12.9 years). Radiation morbidity included brain injury, retinopathy, optic neuropathy, keratopathy, and cataract. Overall and disease-free survivals were significantly better compared to historical treatments, but did not differ statistically from other modern approaches. Conclusions Globe-preserving surgery with PBR, although imperfect, has a favorable long-term survival compared to other modern modalities, and offers a variable period of useful vision.

A 38-year-old woman presented with multiple bilateral recurrent eyelid cysts. Her medical history was notable for Gorlin (nevoid basal cell carcinoma) syndrome. Histopathologic and immunohistochemical examinations revealed that the lesions were intratarsal keratinous cysts. They were similar in appearance to sporadic intratarsal keratinous cysts and closely resembled odontogenic keratocysts of the jaw. Eyelid cysts occur in up to 40% of patients with Gorlin syndrome; however, their description has been cursory and, for the most part, outside of the ophthalmic literature. Although ophthalmologists are familiar with the periocular basal cell carcinomas that occur in patients with Gorlin syndrome, up to 10% of patients never develop a basal cell carcinoma, but they may manifest other ophthalmic findings. Awareness of these other features may contribute to the earlier diagnosis of the syndrome. We discuss the clinical and histopathologic features of intratarsal keratinous cysts in Gorlin syndrome, comparing them to sporadic intratarsal keratinous cysts, other eyelid cysts, and jaw cysts that also characterize this syndrome. We briefly review the ocular and systemic manifestations of Gorlin syndrome and recent genetic and therapeutic developments so that the eyelid cysts may be appreciated within the appropriate context of Gorlin syndrome as a whole.

The purpose of this study was to describe the histopathologic appearance of dermal eyelid fillers that were unexpectedly encountered in ophthalmic plastic surgery samples from patients with mild eyelid disfigurements, and to review eyelid cases with complications that had previously been described in the literature. A retrospective histopathologic study with Alcian blue, elastic, and Masson trichrome stains of 2 cases that were submitted to the Ocular Pathology Department was conducted, and a critical review of previously published cases of the histopathologic characteristics of dermal filler material in the periocular region was also conducted. Two periocular tissue samples were found to contain dermal filler material. In one case, porcine collagen appeared as amorphous or indistinctly microfibrillar aggregates that stained light blue with the Masson trichrome method. In the other case, hyaluronic acid gel appeared as vivid blue amorphous pools of material in extracellular locules after staining with the Alcian blue method. An inflammatory response was not observed in either case. Patients who undergo facial filler procedures may, at a later time, require a surgical excisional procedure from which a specimen is generated. Previously injected dermal filler that the patient neglected to mention may be present in the pathologic sample, potentially perplexing the unsuspecting pathologist. Both ophthalmic plastic surgeons and ocular pathologists should be aware of the histopathologic features of dermal fillers. It is helpful if a surgeon who submits a specimen to the pathology service makes note of any known prior use of facial filler material or is alert to its possible presence when unfamiliar foreign material is discovered in the dermis of the eyelids.

Over a 2-year period, swellings of all 4 eyelid margins developed in a 32-year-old woman and was accompanied by complete loss of eyelashes. An inflammatory dermatologic condition was considered the most likely cause. A full-thickness right lower eyelid biopsy revealed a multinodular lymphoid tumor at the eyelid margin which immunophenotypically and genetically was diagnosed as an extranodal marginal zone lymphoma. The mode of presentation of the disease was considered to be most unusual, as was its B cell lineage, since the majority of primary cutaneous lymphomas are of T-cell origin. Systemic workup demonstrated bilateral involvement of the external auditory canals.

Linear scleroderma en coup de sabre with ophthalmic findings has been previously described in the literature on numerous occasions. A 57-year-old woman presented with focal trichiasis secondary to tarsal thinning, adjacent to a linear brow and forehead deformity consistent with linear scleroderma en coup de sabre. Cases of linear scleroderma en coup de sabre involving the eyelids have been reported, most often with madarosis, ptosis, or skin atrophy; however, to the authors' knowledge, this is the first reported case of linear scleroderma associated with trichiasis and involvement of the deeper eyelid tissues, particularly the tarsus.

An 87-year-old woman not known to have either a lymphoma or leukemia developed a left multinodular, fish-flesh superior epibulbar and forniceal mass. A biopsy disclosed a blastic tumor with scattered multinucleated immature megakaryoblasts. Immunophenotyping of bone marrow cells revealed strong positivity for CD7, CD31, CD43, CD45, CD61, and CD117; CD71, myeloperoxidase, and lysozyme were also positive in scattered cells. Forty percent of the neoplastic cells were Ki-67 positive. Cytogenetic studies indicated a trisomy 8 (associated with worse prognosis) and a t(12; 17) translocation. Desmin, smooth muscle actin, pancytokeratin, CAM 5.2, adipophilin, tryptase, S100, SOX10, MART1, and E-cadherin were negative, ruling out a nonhematopoietic tumor. The conjunctival lesion was diagnosed as a myeloid sarcoma with megakaryoblastic differentiation, a rare variant. It probably arose from a myelodysplastic syndrome. This is the first case of its type to develop in the conjunctiva.

Purpose To analyze 3 unusual mesenchymal transformations within the eye: adipose or osseous metaplasia of the lens and adipose tissue in the vitreous cavity. Design Observational case series. Methods Reevaluation of clinicopathologic diagnoses and histopathologic findings in sections stained with hematoxylin-eosin, periodic acid–Schiff (PAS) reaction, and Masson trichrome method. Results The 3 cases of mesenchymal transformation occurred in microphthalmic eyes with persistent hyperplastic primary vitreous (more recently termed persistent fetal vasculature). In 1 case there was total lens replacement with lamellar bone; in another, total replacement of the crystalline lens by adipose tissue; and in a third, an anomalous pocket of adipose tissue in the central vitreous. Multifocal remnants of the lens capsule were seen in the osseous case but were absent from the adipocytic cases. The vitreous adipose tissue was surrounded by an elaborate capillary plexus with an empty, collapsed PAS-positive lens capsule in the pupillary region. Anterior pigmented neuroectodermal disorganization, dysgenesis of angle structures, and a hypoplastic or disorganized iris were also observed in the 3 cases. Conclusions After review of the literature, it appears that lenticular osseous replacement occurs more often than adipocytic. In addition to vascularization of the lens through a capsular dehiscence, other causes are explored, including direct epithelial-mesenchymal transformations of the lens epithelium or, less likely, of the disorganized adjacent neuroectoderm. The focus of vitreous adipose tissue may represent a transformed luxated lens extruded from its capsule, which was left behind in the pupillary zone.

Choristomatous lacrimal gland tissue has been detected in many different sites of the ocular adnexa, but has never before been convincingly described in the submucosa of the lacrimal sac. A 77-year-old woman with epiphora had a biopsy of the sac wall preformed during a dacryocystorhinostomy that contained such a lacrimal choristoma. Zymogen granules were found in the cytoplasm of the secretory cells with the periodic acid-Schiff reaction. No mucus-producing cells, as found in normal sac submucosal glands, were detected using the Alcian blue, mucicarmine, and Gomori methenamine silver histochemical stains. Gross cystic fluid protein-15 positivity was demonstrated immunohistochemically. The clinical implications of this choristoma are explored.

Background/Aims: Xanthelasma is an unreliable indicator of systemic hyperlipidemia. A review in search of unusual histopathologic features of cellular composition that might correlate with systemic hyperlipidemia was conducted. Methods: An observational case series of 3 cases was performed. Slides were stained and analyzed with hematoxylin and eosin, Masson trichrome, and periodic acid-Schiff as well as for iron. Three lesions displayed an atypical morphologic finding and were subjected to immunohistochemical analysis for CD3, CD20, CD68, CD163, S100, and adipophilin. Results: The three lesions comprised in this study had classical xanthoma cells with densely packed fine vacuoles. The xanthoma cells were CD68, CD163, and adipophilin positive and S100 negative. In case 1, extracellular, nonpolarizing cholesterol crystalloids displayed totally negative staining for all biomarkers. In cases 2 and 3, the cholesterol granulomas were surrounded and permeated by CD68- or CD163-positive epithelioid and giant cells and by CD3-positive T lymphocytes. The 3 cases each harbored squamous cysts. Conclusion: In case 1, the uninflamed extracellular cholesterol crystalloids were associated with severely dysregulated systemic hyperlipidemia. In cases 2 and 3, the cholesterol granulomas were interpreted as a local manifestation of a cyst that might have partially ruptured and did not portend serious hyperlipidemia.

Purpose: To investigate the source of fibrous astrocytes and neuroblasts in a small ciliary body medulloepithelioma appearing as a leukocoria in a 3-week-old baby girl. Methods: Histopathologic and immunohistochemical studies included Alcian blue, periodic acid-Schiff, and antisera for the detection of S100 protein, CD99, glial fibrillary acidic protein (GFAP), CRX, NeuN, neurofilaments, synaptophysin, desmin, and myogenin. Results: A small, nonteratoid ciliary body medulloepithelioma with collections of Alcian blue+ mucoplysaccharides was present in the enucleated globe. The retinal mass displayed multilaminar dysplastic rosettes that were CRX+, NeuN-, and synaptophysin-. Intraretinal neurofilaments and scattered NeuN+ neurocytes were also identified. At the base of the retinal mass ribbons and pseudopapillae of CRX+, NeuN- medullary epithelium were found. The latter developed from an S100+ and weakly CD99+ monolayer of premedullary epithelium. GFAP+ fibrous astrocytes and NeuN- neuroblasts streamed from the medullary epithelium. Conclusions: A multilaminar medullary epithelium and a precursor monolayer of premedullary epithelium were both identified. Neuroblasts and fibrous astrocytes were determined to arise separately from the medullary epithelium. The early stage of tumorigenesis afforded by a small tumor provided the opportunity to discover morphologic and immunohistochemical evidence for these differentiations.

Primary orbital natural killer T-cell lymphoma (NKTCL) is a rare condition with only a few published cases in the literature. Over 1 month, an 81-year-old man developed progressive left periocular inflammation unresponsive to treatment. Clinical examination and imaging studies demonstrated a left lacrimal gland enlargement. Bilateral anterior uveitis and erythematous nontender cutaneous lesions were also found. Biopsies of the skin and lacrimal gland on the back revealed histopathologic and immunohistochemical findings confirming Epstein-Barr virus-positive NKTCL. Metastatic work up disclosed multifocal involvement in the pancreas, stomach, and chest wall. Palliative treatment consisting of nonanthracycline-based chemotherapy and radiation was instituted, but the patient died 5 months after the onset of symptoms. This is the first example of acute dacryoadenitis, and the second of bilateral anterior uveitis, in the setting of NKTCL. Absence of naso-sinus involvement in the current case is rare in NKTCL. Despite treatment, the prognosis remains dismal. Orbital specialists should include NKTCL in the differential diagnosis of lacrimal gland/orbital masses and perform an incisional biopsy if the clinical scenario so dictates.

The purpose of this study was to describe a possible causal relationship between ocular cicatricial pemphigoid (OCP) and ocular surface squamous neoplasia. Two middle-aged female patients with already diagnosed OCP were studied in regard to the subsequent onset of conjunctival squamous neoplasia. Their clinical histories, ocular examinations, clinical photographs, and results of biopsies and any ancillary immunofluorescent laboratory evaluation studies were carefully reviewed. One patient had a preinvasive squamous dysplasia and the other an invasive squamous cell carcinoma, both in the unequivocal setting of OCP with bilateral conjunctivitis, symblephara, and forniceal foreshortening. The patients had been receiving intensive immunotherapy consisting of some combination of corticosteroids, rituximab, and interferon alpha. Both patients had a positive immunofluorescent study demonstrating immunoreactants at the level of the epithelial basement membrane. Each patient had 2 earlier negative immunofluorescent studies before a third was positive. While rare, there is 1 previous report of an association between OCP and conjunctival squamous neoplasia. The current report provides more data supporting the proposal that this conjunction is more than a random event. Repeat immunofluorescent studies after an initial negative result in a patient with strong clinical signs of OCP are imperative due to the frequency of false negative studies in the context of clinically persuasive disease.

To further define the histopathologic features of breast carcinoma conducive to orbital metastasis. Ten new female patients with orbital or eyelid breast cancer metastases encountered between 2011 and 2016 had their medical records reviewed for determining their clinical characteristics. Microscopic glass slides from biopsies and immunohistochemical test results were also analyzed. Biomarkers studied included cytokeratin 7, nuclear estrogen and progesterone receptors, HER2, and E-cadherin. All orbital metastatic lesions were lobular (nonductal) carcinomas that could arise as late as 24 years after the diagnosis of the primary breast tumors. The average age of patients at the time or orbital presentation was 64 years. Metastases were composed of small tumor cells with round, orthochromatic nuclei, and a small amount of cytoplasm. The cells were disposed in a variably fibrotic tumor-associated stroma. Two lesions were variants of lobular carcinoma—namely, alveolar and pleomorphic (the latter displaying cellular crowding, with some degree of nuclear atypia and less stroma). Three of the 9 orbital metastases presented with enophthalmos and 2 displayed euphthalmos despite variably sized orbital masses. In 2 cases, synchronous bilateral orbital metastases prevented any relative difference in globe position. Estrogen and progesterone receptors were usually detectable whereas E-cadherin could not be demonstrated. Breast pathologists no longer refer to primary breast carcinomas and their orbital metastases as “scirrhous.” It has been determined that the majority of orbital breast metastases are lobular carcinomas. This may be due to their lack of intercellular cohesiveness and the absence of E-cadherin which normally is expressed in many neoplastic cell types including ductal breast carcinomas, limiting their dispersion. In contrast, the majority of primary breast carcinomas are ductal. The ubiquitous collagenous matrix in breast metastases retracts, partially accounting for enophthalmos. The presence of euphthalmos despite an orbital mass additionally suggests some retraction of fibrous tissue (with or without fat atrophy) that suppresses relative proptosis. Metastatic lobular breast carcinoma is further implicated if there is a concomitant limitation in extraocular motility or vision decline.

Objective: To distinguish between a multifocal orbital lymphoid tumor and a major simulator represented by a diffuse lymphaticovenous malformation. Methods: We performed a comparison of clinical and radiographic (magnetic resonance imaging [MRI]) findings of these two disparate entities and demonstrated how a misdiagnosis can be prevented. Results: Orbital lymphoid tumors develop in adults at around 60 years of age, whereas extensive lymphaticovenous malformations are generally detected in the first decade. Despite these differences, this is the first description of clinical confusion between them. MRI with gadolinium injection in the current lymphoid tumor displayed a low signal on T2-weighted images, rapid and uniform enhancement, and reduced diffusion. Lymphaticovenous malformations are heterogeneous, display poor or only focal perfusion, and fail to exhibit diminished diffusion. Newer techniques such as diffusion-weighted imaging and dynamic contrast-enhanced imaging may be able to provide additional differential diagnostic information. The final pathologic diagnosis was an extranodal marginal zone lymphoma. Conclusions: Despite the obvious distinctions between orbital lymphoid tumors and lymphaticovenous malformations, several clinical radiologic specialists misdiagnosed the present orbital lesion as a vascular lesion. A combined clinicoradiographic analysis should obviate such errors and facilitate the correct diagnosis in the future.

An unprecedented pigmented caruncular apocrine hidrocystoma with the additional feature of an oncocytic transformation of the cyst's lining cells is reported. Over a year, a 79-year-old woman developed a centrally pigmented lesion of her right caruncle with translucent borders. Because of concern about a melanoma, a carunculectomy with adjunctive cryotherapy and placement of an amniotic membrane graft were performed, and the excised specimen was evaluated microscopically. A large cyst dominated the caruncle and was lined by an inner layer of columnar eosinophilic and granular cells with an outer, interrupted layer of flattened myoepithelial cells. Phosphotungstic acid hematoxylin staining disclosed myriad cytoplasmic, dot-like mitochondria signifying an oncocytic change. Immunohistochemistry revealed gross cystic fluid disease protein-15 and cytokeratin 7-positivity indicative of apocrine differentiation. Oncocytic change is characteristically encountered in lacrimal ductal cysts and tumors.

Excised redundant, forniceal "conjunctival" tissue from a 67-year-old man who experienced a chemical injury to his OS 25 years earlier was evaluated histopathologically with the hematoxylin-eosin, periodic acid Schiff (PAS) with and without diastase, mucicarmine, and Alcian blue methods. Additional immunoperoxidase testing for gross cystic disease fluid protein-15 (GCDFP-15) was undertaken. Non-keratinizing squamous epithelium composed of 8 to 10 layers of swollen keratinocytes without goblet cells surmounted a variably dense and well-vascularized collagenized lamina propria deep to which, in submucosal fibroadipose tissue, was embedded an accessory gland. The acini of the gland were composed of both GCDFP-15-positive serous cells and mucicarmine-positive goblet cells, indicating they were seromucinous rather than entirely serous, as is characteristic of normal lacrimal glandular tissue. Different features of the surface epithelium, the lamina propria, and the submucosa can separate the conjunctival and oral mucous membranes. A close analysis of the cytologic composition of associated accessory glands can reinforce the correct diagnosis of an oral mucous membrane graft when the past surgical history is unclear, because only serous cells but not mucocytes comprise the lacrimal glandular units.

Undifferentiated lymphoepithelial carcinoma (exhibiting both begin lymphoid and malignant epithelial components) most commonly arises in the head and neck, especially in the nasopharynx. It may also be encountered in various ocular adnexal sites, including the nasolacrimal duct. A 63-year-old woman developed a swelling in the region of the right lacrimal sac accompanied by epiphora. CT scanning revealed an enlargement of the nasolacrimal duct from the lacrimal sac to the inferior nasal meatus. A biopsy during dacryocystorhinostomy for symptomatic epiphora revealed hypercellular sheets of small lymphocytes which were interpreted as evidence for a chronic dacryocystitis. Two years later the subtotally excised lesion had substantially grown in size. Repeat CT scans demonstrated an inferonasal anterior orbital mass with further enlargement of the nasolacrimal duct with a solid mass in its lumen, and bone erosion. The biopsy combined a rich background of lymphocytes within which were clusters of undifferentiated carcinoma cells that were cytokeratin and p63 positive. Critical review of the earlier biopsy led to the detection of the same cells, but in smaller numbers, that had been overlooked. An awareness of the possibility of lymphoepithelial carcinoma of the lacrimal sac/duct should improve diagnostic accuracy with the aid of immunohistochemistry. Radiation therapy is often successful in managing this highly sensitive malignant tumor.

Importance To describe presenting patterns of breast cancer metastases to the orbit and eyelids. Background To provide clinical, radiographic and pathologic correlations of breast metastases to the orbit or eyelids and evaluate radiographic volumetric orbital changes. Design Retrospective review in an academic centre. Participants Ten female patients with periocular metastatic breast carcinoma who were seen at the Massachusetts Eye and Ear Infirmary Oculoplastics Clinic. Methods Retrospective review of patient records, imaging and pathology findings. Main Outcome Measures Presenting clinical characteristics, radiographic findings and histopathological features were assessed and correlated to discover distinctive presenting patterns. Volumetric measurements of the tumours and orbital soft tissue structures were made on magnetic resonance imaging studies. Results The breast cancer metastases included eleven orbital lesions and one eyelid lesion. Two distinct clinical presentations were observed. The first consisted of seven patients who had either enophthalmos or euphthalmos, a radiographically indistinct intraconal lesion and a histologically classic invasive lobular breast carcinoma with a prominent fibrotic stroma. The second group consisted of two proptotic patients with discrete mass lesions on imaging and an atypical invasive lobular breast carcinoma pathological subtype (pleomorphic or alveolar). One patient had diffusely indurated eyelid fullness. Volumetric analyses demonstrated variable tumour sizes with an inconsistent impact on the orbital volume and fat. Conclusions and Relevance This correlative study provides the clinical-radiographic-histopathologic basis for separating two overarching phenotypic presentations of metastatic breast carcinoma to the orbit. Previously postulated mechanisms for the distinctive finding of tumour-induced enophthalmos are re-examined in the light of the foregoing conclusions.

Synovial sarcoma is a soft-tissue sarcoma of the extremities developing in young adults that has rarely been reported in the orbit. Synovial sarcoma is associated with a unique translocation, resulting in an SYT-SSX fusion gene. We analyze 7 published periocular cases, together with the current one, to gain a better appreciation of the features of the tumor in this location and to compare the findings with those derived from nonophthalmic studies. An inferior orbital mass developed in a 31-year-old woman after experiencing periorbital and hemifacial pain for more than a decade. Radiographically, the mass was circumscribed and displayed coarse internal calcifications. A large but subtotal excision with histopathologic examination disclosed a primitive tumor composed of spindled and ovoid cells. Immunohistochemistry demonstrated positivity for nuclear transducin-like enhancer of split 1 and membranous CD99, typical for synovial sarcoma. Fluorescence in situ hybridization identified a (X,18) translocation in the tumor cells. The patient underwent postoperative adjuvant proton beam radiotherapy with a good response that has been maintained during 1 year of follow-up. Orbital soft-tissue tumors of all types are increasingly identified by their distinctive genetic signatures that offer more specificity than standard immunohistochemical tests.

A 52-year-old male presented with a perilimbal-epibulbar, flat, pigmented lesion of 7 months’ duration. Microscopic evaluation disclosed a proliferation of intraepithelial dendritic melanocytes without frank atypia, a lesion formerly termed “primary acquired melanosis.” Within the lesion there were also intraepithelial basal junctional nevocytic nests and occasional small subepithelial nevocytic clusters which were positive for MART-1, HMB-45, and SOX-10 and negative for Ki-67. This remarkable lesion was suggestive of dendritic melanocytes transforming into rounded nevocytes lacking dendrites. The embryologic and biologic implications of these findings are explored, notably in regard to the unusual acquisition in mature adults of common nevomelanocytic nevi.

An 88-year-old man presented with diplopia, limitation of extraocular movements, and a firm palpable mass in the superolateral orbit. Biopsy revealed a sclerosing signet ring cell carcinoma with histopathologic features mimicking those of a primary signet ring cell (histiocytoid) carcinoma of the eyelid of eccrine or apocrine gland origin, a metastasis from an invasive lobular breast carcinoma or a metastatic diffuse-type gastric carcinoma. An extensive panel of immunohistochemical stains and molecular genetic analyses unequivocally failed to establish a precise diagnosis. Electron microscopy demonstrated features of a primary lacrimal gland lesion with intracytoplasmic lumens and zymogen granules typical of lacrimal secretory pyramidal cells. A thorough initial systemic work-up failed to reveal a primary visceral malignancy. Fifteen months of follow-up have failed to detect the emergence of another primary malignancy. To the best of our knowledge, a tumor with the morphology of the current lesion has not been previously described in the major or accessory lacrimal glands.

Over a period of 1 year, a 74-year-old man slowly developed a painless left upper eyelid intratarsal mass. The skin was movable over the lesion. At surgery, a well-circumscribed, yellow-white, partially cystic tumor was encountered. Histopathologically it was composed of a random mixture of basaloid and sebaceous cells arranged in interconnecting cords. Immunohistochemical evaluation disclosed epithelial membrane antigen, adipophilin, and cytokeratin 14 positivity. These findings led to the diagnosis of a sebaceoma. The tumor cells abnormally failed to express mismatch repair proteins for MLH1 and PMS2. The patient did not have a personal history of any visceral malignancy, but his father had died at the age of 46 years and a daughter at the age of 33 years from colonic carcinomas. The implications of this periocular sebaceoma for the Muir-Torre syndrome are explored.

Purpose The objective of this article is to document a unique case of a primary hemangioma and review epibulbar vascular tumors of the conjunctiva and episclera. Methods A case report with detailed histopathologic, histochemical, and immunohistochemical studies coupled with a comprehensive review of the relevant literature with a tabulation of previously reported epibulbar vascular lesions was performed. Results A vascular tumor developed in a 46-year-old woman over 2-3 months that histopathologically was located in the superficial third of the normally avascular sclera and was composed of capillary caliber vessels. CD31 and CD34 positivity established the vascular nature of the lesion. Despite its adult onset, the tumor was also glut-1 positive, a vascular characteristic of childhood capillary hemangiomas that will ultimately involute. Smooth muscle actin was positive in the endothelial cells and associated pericytes. An ectatic muscular vessel identified in the midst of the lesion was interpreted as an anomalous intrascleral branch of an epibulbar anterior ciliary artery, where it perforated the sclera in the vicinity of the insertion of an extraocular rectus muscle. It was deduced to be the source of the capillary proliferation. A literature review failed to identify any previously reported epibulbar vascular tumor that originated primarily in the sclera or secondarily infiltrated this ocular tunic. Conclusion An adult primary capillary intrascleral neoplasm is described as the rarest of all epibulbar vascular tumors and in keeping with the exceptional status of the ocular endothelium was glut-1 positive. This lesion must be distinguished from an array of other common and esoteric epibulbar vascular conditions.

A 53-year-old man presented with smooth-domed, variegated cysts (polycystic disease) of all 4 eyelids, worse on the left side. Some of the cysts were clear, while others were creamy-white colored. In addition, multiple, very fine vesicopapules were noted along the eyelid margins. Histopathologic examination revealed a trichilemmal cyst, several pure apocrine hidrocystomas displaying multiple chambers, a hybrid cyst, and many small eccrine cysts of the deep dermis. The apocrine lesions, including the small ones at the eyelid margins, predominated. Smooth muscle actin sometimes positively stained outer myoepithelial cells in some of the apocrine cysts, which helped to distinguish them from eccrine cysts. Most noteworthy was the fact that the patient had been diagnosed with a prolactinoma 20 years earlier. There is only 1 previous report of multiple apocrine cysts and an antecedent prolactinoma in the dermatologic literature. This syndrome should be separated from that of Schöpf-Schulz-Passarge, which manifests multiple small eyelid apocrine cysts and other ectodermal dysplasias without any association with neoplasia, and from that of focal dermal hypoplasia (Goltz-Gorlin) syndrome with apocrine cysts but again without neoplasia.

The purpose of this study is to codify the microscopic diagnostic criteria for ocular adnexal brow and caruncular sebaceous gland hyperplasias (pseudoadenomatoid) that distinguish it from an adenoma. Clinical records and photographs were critically reviewed and microscopic slides were stained with hematoxylin and eosin and immunochemically stained for adipophilin, androgen receptor, p16, p53, a spectrum of cytokeratins, Ki-67 and mismatch repair nuclear protein expression for MLH1, MSH2, PMS2, and MSH6. The patients and their close relatives had no history of cancer. Cytokeratin 7 and especially cytokeratin 17 highlighted the presence of ducts in the hyperplastic lesion, which are not present in adenomas. p16 and p53 were negative and Ki-67 immunostaining demonstrated similar low proliferation indices for normal and hyperplastic glands. The mismatch repair nuclear protein expressions were preserved in both lesions. Histopathologic misdiagnosis of adenomatoid sebaceous gland hyperplasia as an adenoma can lead to the impression of an association with the Muir-Torre syndrome. Cytokeratins 7 and 17 immunostaining can be helpful in highlighting compressed ducts that in exuberant sebaceous gland hyperplasias may lead to a diagnosis of an adenoma (in which ducts are absent). Negative immunostaining for p16 rules out a possible etiologic role of human papillomavirus in hyperplasias and the negative p53 staining indicates the lesions are not truly neoplastic. The preservation of mismatch repair nuclear protein expression rules out the likelihood of the Muir-Torre syndrome. The current cases convincingly establish that sebaceous hyperplasia is not associated with the Muir-Torre syndrome by both clinical findings and immunohistochemical testing.Two yellow lesions, from the brow and caruncle, were examined microscopically and immunohistochemically to establish the diagnosis of sebaceous gland hyperplasia and to rule out the Muir-Torre syndrome.