Frederick A. Jakobiec

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.

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: 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.

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.

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.

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.