Silicone Granulomas of the Eyelids-A Case Series Illustrating a Distant Migratory Phenomenon.

PURPOSE: Exogenous silicone has been reported to migrate to anatomic sights far from an initial injection or implantation site; this phenomenon has been rarely described in the ocular adnexa, especially in the eyelids. We document 3 additional cases of distant migration of silicone implanted elsewhere in the body to the eyelids and review the prior literature on this uncommon event. METHODS: A retrospective chart review of 3 patients was conducted along with analysis of diagnostic histopathology. A comprehensive review of the literature regarding dissemination or migration of silicone to the eyelids in patients with either silicone breast implants or silicone facial filler use was performed. RESULTS: Cases of silicone migrating to the eyelids from silicone breast implants and silicone-based facial filler are outlined in Tables 1 and 2, respectively. There are 4 total reports of women with silicone breast implants, including the 2 described here, with evidence of migration of silicone to the eyelid. Similarly, 5 cases of silicone-based facial filler with resultant migration of filler to the eyelids were identified, including 2 of the cases presented in this report (1 patient had both silicone breast implants and silicone facial filler). CONCLUSION: Silicone is chemically inert, but is known to travel throughout the body, causing a resultant foreign body response in tissue that can adversely affect even the eyelids. Silicone has a relatively characteristic histologic appearance and diagnosis of silicone granuloma highlights the importance of obtaining a thorough clinical history, particularly regarding prior cosmetic injections or breast enhancement surgery. Foreign material/foreign body granuloma is important to consider in patients with deep eyelid nodules of unclear etiology.

Primary vitreoretinal involvement and immunopositivity for BRAFV600E help distinguish metastatic from primary intraocular melanoma: a detailed histopathologic study of metastatic cutaneous melanoma to the eye.

OBJECTIVE: To evaluate the clinicopathologic characteristics of metastatic cutaneous melanoma to the eye and identify potential distinguishing characteristics from the more common primary uveal melanoma; particularly, tumour location within the eye, cytomorphology and immunohistochemical/specific molecular genetic features. METHODS: A retrospective observational case series using surgical enucleation and diagnostic vitrectomy cytologic specimens from seven patients with suspected intraocular melanoma, eventually diagnosed as metastatic melanoma, was conducted. Haematoxylin and eosin-stained sections of tumour and immunohistochemical (IHC) stains for BRAFV600E and Ki-67 were critically reviewed; BAP1 IHC was also evaluated in cases where additional tissue was available. Clinical imaging studies and medical records were reviewed. RESULTS: The majority of patients (86%) with metastatic melanoma have primary vitreoretinal (not uveal) involvement and epithelioid, highly malignant cytomorphology (100%); many (50%) harbour BRAFV600E mutations, a finding not seen in large cohorts of primary uveal melanoma. CONCLUSIONS: Characteristics favouring or defining metastatic intraocular melanoma over primary uveal melanoma include high-grade epithelioid cytology, predominant involvement of the vitreous cavity and/or retina, and presence of positive immunostaining for BRAFV600E.

Lymphoma of the Lacrimal Sac: The Massachusetts Eye and Ear Experience With a Comparison to the Previously Reported Literature.

PURPOSE: To describe the frequency, clinical features, and histologic subtypes of biopsy proven lacrimal sac lymphomas, and to compare these results to the previously published literature. METHODS: A retrospective chart review was performed at a single institution from 2004 to 2017. Pathology reports, operative notes, and patients' medical charts were reviewed. RESULTS: Of 566 lacrimal sacs submitted for routine histopathologic evaluation, 16 cases of lymphoma were identified. All were low-grade, non-Hodgkin B-cell lymphomas, biopsied at an average age of 71 years. Thirteen patients (81.25%) had a pre-existing lymphoma diagnosis; the average interval between the diagnosis of systemic or nonocular adnexal lymphoma and lacrimal sac lymphoma was 7.9 years (range 2-26 years; median 5.5 years). Three cases of primary lacrimal sac lymphoma were identified. Histopathology showed 3 cases (18.75%) of follicular lymphoma, 3 (18.75%) of extranodal marginal zone lymphoma, and 10 (62.5%) of chronic lymphocytic leukemia/small lymphocytic lymphoma. Primary cases presented with epiphora and nasolacrimal duct obstruction, while secondary cases predominantly manifested as dacryocystitis. All lacrimal sac neoplasms were locally responsive (without local recurrence) to chemotherapy, radiation, or both. CONCLUSIONS: Lacrimal sac lymphoma is uncommon but should be suspected among patients with known lymphoma who develop dacryocystitis. In this series, primary lacrimal sac lymphoma most often presented as a mass or nasolacrimal duct obstruction. Chronic lymphocytic leukemia/small lymphocytic lymphoma was the most commonly identified cause of secondary lacrimal sac lymphoma. Distinguishing primary from secondary lacrimal sac lymphomas is important, as the extent of disease and histopathologic subtypes differ, which may affect patient management.

Histopathologic alterations in the eyelid after Hughes tarsoconjunctival flap: loss of Meibomian glands with preservation of accessory lacrimal glands.

A 71-year-old female with invasive squamous cell carcinoma of the lower eyelid involving the ocular surface underwent surgical excision with negative margins and a subsequent reconstruction. The posterior lamellar defect was reconstructed with a Hughes tarsoconjunctival flap, and the anterior lamellar defect was reconstructed by advancing the lower eyelid skin. Three years later, the patient presented with signs suspicious for recurrence involving the tarsoconjunctival graft: a nodule along the mucocutaneus junction, symblepharon, and forniceal shortening. Repeat scouting biopsies showed variable degrees of moderate to severe squamous dysplasia so the patient underwent a staged full thickness excision of the lower eyelid and involved conjunctiva followed by reconstruction. Direct immunofluorescence was not diagnostic for ocular cicatrcial pemphigoid. Permanent histopathologic sections did not show any carcinoma, but the full thickness excisions involving the prior Hughes tarsoconjunctival flap highlighted two notable alterations: the Meibomian glands were absent and the accessory lacrimal glands of Wolfring were transposed to the mucocutaneous junction of the reconstructed lower eyelid.

Conjunctival Actinic Granuloma: A Clinicopathological and Immunohistochemical Study With a Review of the Literature and a Differential Diagnosis.

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.

Lacrimal Gland Intravascular Micrometastasis From a Human Papillomavirus-Driven Anorectal Squamous Cell Carcinoma With a Review of Metastatic Disease to the Lacrimal Gland.

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.

Eccrine poroma of the eyelid.

Clinical and histopathologic case of an eyelid eccrine poroma, a benign adnexal neoplasm rarely found on the periorbital skin.

MAGEL2-related disorders: A study and case series.

Pathogenic MAGEL2 variants result in the phenotypes of Chitayat-Hall syndrome (CHS), Schaaf-Yang syndrome (SYS) and Prader-Willi syndrome (PWS). We present five patients with mutations in MAGEL2, including the first patient reported with a missense variant, adding to the limited literature. Further, we performed a systematic review of the CHS and SYS literature, assess the overlap between CHS, SYS and PWS, and analyze genotype-phenotype correlations among them. We conclude that there is neither a clinical nor etiological difference between CHS and SYS, and propose that the two syndromes simply be referred to as MAGEL2-related disorders.

Sympathetic Ophthalmia in Patients with Enucleation or Evisceration: Pathology Laboratory and IRIS® Registry Experience.

Introduction: Sympathetic ophthalmia (SO) is a rare bilateral granulomatous panuveitis that can follow surgical or nonsurgical ocular trauma in one eye. Because its diagnosis requires clinical-pathologic correlation, the true incidence of SO is unknown, and there is a need to understand the recent trends in risk factors and frequency of this condition. Methods: Pathology records of all enucleated or eviscerated (ENEV) eyes at three pathology laboratories were reviewed. Data collected included patient demographics, procedure indication, pathology diagnosis, and clinical history of trauma and uveitis. IRIS® Registry (Intelligent Research in Sight) was searched for all patients with SO, acquired absence of eye (AAE), and/or ENEV. Data obtained included patient demographics, ocular procedures, and preoperative diagnoses within 30 days of AAE/ENEV. Results: In the pathology laboratory setting, the incidence of SO over a 36-year period in patients who underwent ENEV was 0.2% (20/9,092); the 5-year incidence ranged from 0.0 to 0.3%. Among the 20 eyes with SO, the inciting event was surgical trauma in 50% (10/20), nonsurgical trauma in 45% (9/20), and missing/undetermined in 5% (1/20). SO was suspected preoperatively in 7/20 (35%) patients. Clinical concern for SO and ruptured globe were indications for ENEV in 50/9,092 (0.5%) and 872/9,092 (10%) patients, respectively. In the IRIS Registry, 0.7% (199/27,830) of patients with AAE/ENEV had diagnosis of SO. The frequency of SO between 2015 and 2020 was 0.01% (7,371/62,318,249); of these 7,371 cases, 199 (3%) had AAE/ENEV. In 25,975 patients with available data, injury and SO were listed as diagnoses less than 30 days prior to AAE/ENEV in 909 (4%) and 63 (0.2%) cases, respectively. Conclusion: The frequency of SO in recent decades has been low. Most cases of SO are not managed with eye removal. In histopathology-confirmed SO, surgical trauma is as frequent as nonsurgical trauma as an inciting etiology of disease.

The Histopathology of Two Eyes Enucleated after Continuous Transscleral and Micropulse Transscleral Cyclophotocoagulation for Refractory Secondary Glaucoma.

Introduction: Cyclodestructive procedures, which target the nonpigmented epithelium of the ciliary body, have been utilized to treat recalcitrant glaucoma since the early 1930s. There are now various types of cyclophotocoagulation (CPC) available. The authors provide a retrospective description that details the histopathologic findings in 2 patients who underwent CPC for uncontrolled uveitic and neovascular glaucoma (NVG) with subsequent enucleation. Case Presentations: Two enucleated globes from 2 patients with secondary refractory glaucoma underwent cilioablative therapy: one with uveitic glaucoma and a remote history of micropulse transscleral CPC (MP-TSCPC) and the other with NVG and a recent history of traditional continuous transscleral CPC (CW-TSCPC). The clinical histories are summarized, and light microscopy reviewed for degree of coagulative necrosis and inflammation of the ciliary body and surrounding structures, as well as the underlying pathology of the glaucoma. Conclusion: Both patients ultimately experienced pain and vision loss with either a recrudescence of elevated intraocular pressure or inflammatory hypotony and subsequently underwent enucleation of the affected eye. One globe was enucleated shortly after CW-TSCPC and found to have near full-thickness coagulative necrosis of the pigmented and nonpigmented ciliary epithelium and ciliary muscle as well as necrosis of adjacent nontarget tissues with fibrin in the anterior chamber. The second patient underwent enucleation many months after MP-TSCPC with partial healing fibrosis of the ciliary body and some remaining viable ciliary processes. The histopathologic findings post-CPC may vary based on the method used and evolve over time; additional study is needed.

Stevens Johnson syndrome: A review of a vision and life-threatening mucocutaneous disease including histopathology with updates on pathogenesis and genetic risk factors.

BACKGROUND: The Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) spectrum of diseases are devastating blistering disorders involving mucosal surfaces with ocular sequelae that manifest particularly profound long-term morbidity. Advances in deoxyribonucleic acid (DNA) sequencing, genome-wide association studies, and both molecular and pharmacogenetics have helped clarify genetic susceptibility and characterize the iatrogenic risk of SJS for a given patient. METHODS: A review of peer reviewed publications featured on PubMed pertaining to the clinical, pathologic, pharmacogenetic and molecular genetic features of SJS/TEN was conducted. Propose: To provide an in-depth clinicopathologic description of the ocular, ocular adnexal, and cutaneous findings in SJS/TEN, summarize pathogenesis and related conditions, and provide an update on the molecular genetic modifications that contribute to the phenotypic variations and genetic susceptibilities of SJS. CONCLUSIONS: HLA subtyping and other genetic testing may eventually be valuable in the appropriate context to prevent the debilitating ocular sequelae of SJS, particularly as it relates to medication use.

Mucopolysaccharidosis Type I-Associated Corneal Disease: A Clinicopathologic Study.

PURPOSE: To report the anterior segment clinical features and histopathologic and histochemical characteristics of explanted corneas from the largest reported cohort of patients with Hurler syndrome and other variants of mucopolysaccharidosis (MPS) I undergoing corneal transplantation. DESIGN: Retrospective observational case series. METHODS: This institutional study reviewed 15 corneas from 9 patients with MPS I spectrum disease who underwent corneal transplant to treat corneal clouding between May 2011 and October 2020. We reviewed the clinical data, hematoxylin-eosin-stained sections, and histochemical stains, including those for mucopolysaccharides (Alcian blue and/or colloidal iron). The main outcome measures were pathology observed under light microscopy and postsurgical clinical outcomes. RESULTS: Nine patients underwent 15 corneal transplants for corneal clouding (14/15 procedures were deep anterior lamellar keratoplasty). All corneas had mucopolysaccharide deposition visible on hematoxylin-eosin-stained sections, which was highlighted in blue with histochemical stains. All corneas also showed alterations in Bowman's layer and the majority also showed epithelial abnormalities. CONCLUSION: MPS I shows significant corneal clouding that is successfully treated with deep anterior lamellar keratoplasty. The excised corneas show characteristic epithelial changes, disruption or breaks in Bowman's membrane, and amphophilic collections of stromal granular mucopolysaccharides which are visible on hematoxylin-eosin-stained sections and highlighted by special histochemical stains (Alcian blue and collodial iron). These changes, although subtle, should alert the pathologist to the possibility of an underlying lysosomal storage disorder.

Invasive Carcinoma Ex-Pleomorphic Adenoma of the Lacrimal Gland with a Cystadenocarcinoma Component: A Case Report and Review of the Literature.

Lacrimal gland neoplasms comprise up to 18% of all orbital masses clinically and histologically. Much of our current core knowledge regarding lacrimal gland tumors stems from prior study of their more common counterparts, the salivary glands. The prognosis for each lacrimal gland tumor is contingent upon proper clinical evaluation and ultimately the histopathologic diagnosis. We describe a case of an invasive carcinoma ex-pleomorphic adenoma (Ca-ex-PA) with a cystadenocarcinoma component arising from the lacrimal gland in the absence of any previously diagnosed pleomorphic adenoma (benign mixed tumor) or prior incisional surgery. This case illustrates the importance of the histopathologic assessment including immunohistochemistry and genetic testing to narrow a differential diagnosis and potentially aid or guide therapy in the future. Our finding suggests that carcinoma of the lacrimal gland may be derived from previously undiagnosed and perhaps even subclinical pleomorphic adenoma.

Endogenous Clostridium perfringens Panophthalmitis with Potential Entry Port from Diverticulitis Exacerbated by Proliferative Diabetic Retinopathy.

PURPOSE: To report a rapid endogenous fulminating panophthalmitis from Clostridium perfringens in a patient with diverticulitis and proliferative diabetic retinopathy. METHODS: A 61-year-old female with poorly controlled diabetes mellitus, active proliferative diabetic retinopathy, and recent diverticulitis presented with conjunctival injection, ocular discharge, and sudden onset of painful vision loss of the left eye. Patient denied history of ocular trauma, intraocular surgery, or intravenous drug abuse. Examination revealed an erythematous, proptotic eye with restricted extraocular movements, mucopurulent discharge, diffuse corneal edema, and vitreous haze and cell. Orbital computed tomography (CT) confirmed no retained intraocular foreign body. RESULTS: Despite 48 hours of treatment with systemic broad spectrum antimicrobial therapy (vancomycin, meropenem, and amphotericin B), patient underwent enucleation due to declined condition and progressive infection. Patient's culture revealed gram-positive bacillus microbes (Clostridium perfringens). Patient's subsequent CT abdomen showed resolved diverticulitis after antimicrobial therapy. CONCLUSION: Although rare, Clostridium perfringens infection can be a cause of rapid loss of vision from fulminate endogenous panophthalmitis. Urgent extensive systemic work-up to identify potential port of entry from visceral pathology and rapid removal of source of infection are pivotal to avoid high rate of mortality.