To document a unique case of granular cell tumor of the orbit, located lateral to and abutting the optic nerve, that benefited from treatment with proton beam irradiation, with a comprehensive review of the literature on granular cell tumor of the orbit.Methods: Clinicopathologic case report with detailed imaging features and histopathologic and immunohistochemical evaluation for cytoplasmic tumor biomarkers differentiating granular cell tumor (GCT) from it mimicking lesions with relevant literature citations. The authors reviewed 20 cases of orbital GCT from 2011 to 2020 in addition to 40 cases from 1948 to 2011 and included a summary of imaging and clinical features, outcomes, and recommended treatment modalities.Results: A 32-year-old man with 1-year history of left retrobulbar pain and diplopia on lateral gaze, intermittent left eyelid swelling, and a tonic left pupil was found to have a fusiform intraconal mass extending toward the orbital apex and abutting the optic nerve. Histopathologic and immunohistochemical investigations collectively supplied data diagnostic of a GCT with an initial low proliferation rate. GCT is a soft tissue neoplasm that originates in the nervous system and can occur anywhere in the body. This enhancing tumor is isointense to gray matter on T1-weighted MRI, hypointense on T2. After an incisional biopsy, the patient's symptoms persisted, and follow-up imaging several months later revealed further growth of the mass. The impossibility of complete surgical removal prompted the decision to treat with proton beam radiation therapy, which resulted in substantial regression in the size of the residual tumor. Most frequently involving the inferior rectus muscle (42%), orbital GCT is usually benign with only 4 reported cases of malignant orbital GCT (7%). Wide surgical resection with complete removal is usually curative for benign orbital GCT, and proton beam radiation therapy can aid in tumor shrinkage.Conclusions: GCT should be considered in the differential diagnosis when encountering patients with mass lesions RESULTSClinical History. A 32-year-old male was initially seen at another institution with a history of left retrobulbar pain. He also complained that his left pupil was larger than the right. CT at the time demonstrated a fusiform intraconal mass located lateral to and abutting the optic nerve. It

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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.

Intratarsal cysts are either congenital, acquired, or develop after trauma or prior surgery. • A cyst's lining governs its diagnosis, and together with its location, helps to determine its origin. • An intratarsal cyst with a partially ciliated respiratory and coexistent squamous epithelial lining has never been reported before. Novel Insights• The ciliated respiratory epithelium of an intratarsal cyst may represent the persistence of a ciliated stage of epithelium during the embryonic development of adnexal structures. • The current lesion displayed the histopathologic and immunohistochemical features of ciliated respiratory epithelium that was probably aberrantly thwarted from complete normal squamous differentiation, rather than the consequence of a displacement of a sinus stem cell. AbstractA 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 con-tained 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 glan-dular 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.

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.

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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.