An Inflammatory Reaction to Stored Fascia Lata 37 Years Postimplantation.

We report a rare case of a suspected inflammatory reaction to stored fascia lata 37 years post-placement. Clinical, imaging, histopathological, and immunohistochemical findings are presented, with a literature review on reactions to stored fascia lata. A 39-year-old woman had upper eyelid congenital ptosis repaired successfully at 2 years with bilateral frontalis suspension procedures using stored fascia lata. Thirty-seven years later, the patient presented with swelling of her eyelids and forehead, which was tender to the touch, in the same pattern as the fascia lata slings placed earlier. Histopathological examination disclosed a non-necrotizing granulomatous inflammatory infiltrate with numerous asteroid bodies. Initially, it was responsive to oral prednisone, but with recurrent inflammation, long-term methotrexate was required to control the inflammation. To our knowledge, this type of delayed inflammatory reaction has not been previously reported. It raises a concern about the use of allogeneic donor tissue and accepted sterilization techniques that may not be 100% effective in deactivating all components of the donor graft, including potential infectious pathogens, leading to a subsequent latent reaction.

Primary ductal adenocarcinoma of the lacrimal gland: A review and report of five cases.

Primary ductal adenocarcinoma (PDA) is a rare epithelial tumor of the lacrimal gland. Herein we report 5 cases and review 29 published cases of PDA of the lacrimal gland. Among these 5 cases, the most common clinical presentation was painless swelling and/or proptosis of their eye. The size of the lesions ranged from 1.6 to 2.5 cm. Histopathologic examination revealed proliferations of ductal or gland-like cells with vesiculated pleomorphic nuclei and prominent nucleoli. Tumor cells stained positive for epithelial and apocrine differentiation markers. Immunohistochemistry for human epidermal growth factor 2 was positive in 2 of the 4 cases. Four of the five patients were alive at the last follow-up visit. One died with bone metastases, which were diagnosed 25 months after exenteration and then survived an additional 51 months. On reviewing of twenty-nine previously published cases of PDA, the mean age of diagnosis was 58 years, with a male predominance (75%). Fifteen patients (54%) had distant metastases, 1 (4%) had local recurrence, and 10 (37%) suffered from a PDA-related death. PDA is a high-grade aggressive epithelial tumor of the lacrimal gland. Although rare, awareness and recognition of this malignancy are important to help determine prognosis and treatment options.

Immunohistochemical analysis of benign and malignant melanocytic lesions of the conjunctiva using double-staining.

OBJECTIVE: To implement a double-staining technique to identify the most sensitive and specific combinations of melanoma antigen recognized by T cells (Melan-A), microphthalmia-associated transcription factor (MITF), human melanoma black 45 (HMB45), and Ki67 aiming to assist in the diagnosis of atypical melanocytic conjunctival lesions that are more prone to malignant progression. METHODS: Eight specimens of conjunctival melanoma and of primary acquired melanosis with moderate to severe atypia were double-immunostained with a combination of a cytoplasmic marker (anti-Melan-A or anti-HMB45), and a nuclear marker (anti-MITF or anti-Ki67). Eight specimens of normal conjunctiva and of conjunctival nevi served as controls. The specimens were processed using 3,3-diaminobenzidine substrate for nuclear stains and the fast-red substrate for cytoplasmic stains. Each slide was analyzed by light microscopy and provided a percent scale and a 0 to 4+ score for each nuclear and cytoplasmic component. RESULTS: Melan-A and MITF were strongly positive markers for all melanocytic cells, whereas Ki67 and HMB45 provided a variable response for identifying potentially proliferative or aggressive cells. HMB45 and MITF proved to be the best combination for differentiating between atypical and benign lesions on a percent scale and a 0 to 4+ scale (p = 0.0004), with the 3 other combinations providing mainly confirmatory diagnostic information (p < 0.05). CONCLUSIONS: Our study used an immunohistochemical double-staining approach to differentiate between atypical and benign melanocytic lesions of the conjunctiva. Our findings should aid in a more complete immunohistopathological diagnosis of conjunctival melanocytic lesions, particularly in diagnostically difficult cases.

Regression of Sebaceous Carcinoma of the Eyelid after a Small Incisional Biopsy: Report of Two Cases.

PURPOSE: To report 2 cases of regression of sebaceous carcinoma of the eyelid after a small incisional biopsy. METHODS: Clinical, imaging, and histopathological findings are presented, with a literature review on regressing ocular tumors. RESULTS: Our first patient was a 79-year-old man who presented with a 10-month history of progressive left upper eyelid ptosis caused by an eyelid tumor with orbital involvement and confirmed on magnetic resonance imaging. Our second patient was a 70-year-old woman who presented with ptosis with a left upper eyelid mass. Both patients underwent a small incisional biopsy of their lesion. The histopathological diagnoses in both cases were consistent with sebaceous carcinoma. Both patients refused exenteration. Follow-up clinical examination and imaging disclosed total regression of the ptosis and of the neoplasm with no sign of recurrence in both patients over a 4-year period for Case 1 and a 7-year period for Case 2. CONCLUSION: Regression following incisional biopsy of basal cell, squamous cell, and Merkel cell carcinoma, including of the eyelid, is well documented. To the best of our knowledge, our 2 cases of sebaceous carcinoma are the first to be reported with total involution clinically and on imaging of the tumor following partial incisional biopsy.

Pilomatrixoma of the ocular adnexa: report of 3 cases with variations in the histopathological findings.

OBJECTIVE: To report the clinical and variations in the histopathological features of pilomatrixoma of the ocular adnexa in 3 young individuals. DESIGN: A retrospective case series was performed with clinical, histological, and immunohistochemical analysis. PARTICIPANTS: Case 1 is an 18-year-old male who presented with a reddish-blue swelling under the left eyebrow. The lesion measured 2 × 1 cm. Case 2 is a 2-year-old female who presented with a reddish-blue nodule inferior to the right eyebrow with telangiectatic vessels. The lesion measured 6 × 4 × 4 mm. Case 3 is a 14-year-old female who presented with a subcutaneous lesion under the right upper eyebrow with fluctuating inflammation. The lesion measured 12 × 3 × 2 mm. Histopathological examination of case 1 disclosed peripheral basaloid cells and central shadow cells containing calcific foci, separated by a transition zone. In case 2, histopathological analysis revealed central calcific foci in islands of shadow cells with more peripheral basaloid cells. In case 3, we observed numerous clusters of shadow cells with focal calcifications, as well as basaloid cells in a disorganized configuration. CONCLUSION: Pilomatrixoma is an uncommon benign skin neoplasm originating from the matrix of the hair root. We describe a spectrum of histopathological findings in pilomatrixoma of the ocular adnexal in 3 young individuals.

Histopathological Study on the Proposed Pathogenesis of Intratarsal Keratinous Cysts.

PURPOSE: Intratarsal keratinous cysts (IKCs) are a recently described entity that is frequently misdiagnosed clinically as chalazia and mislabeled in the literature as "intratarsal epidermal inclusion cysts" or "epidermoid cysts." It is important to accurately diagnose IKCs and distinguish them from chalazia because IKCs require a complete surgical excision and can exhibit multiple recurrences following curettage. The authors performed a retrospective case series to further elucidate the pathogenesis of IKCs and to determine the diagnostically optimal panel of stains for diagnosis. METHODS: A study group of 8 specimens of IKCs and control specimens of epidermal inclusion cysts were obtained from their pathology laboratories. The authors compared the histological and immunohistochemical profile of IKCs and epidermal inclusion cysts by staining sections from each specimen with hematoxylin and eosin, periodic acid-Schiff, Masson trichrome, cytokeratin 5, cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen. The immunoreactivity data were then analyzed using a 2-tailed Mann-Whitney test, assuming a nonparametric population (p < 0.05 is significant). RESULTS: Histopathologically, IKCs are embedded in the tarsus lined by stratified squamous epithelium with an inner undulating cuticle filled with a compact keratinous-appearing material. The authors demonstrate that IKCs develop progressively from dilated meibomian ducts to the formation of complete cysts with their markers. The most valuable immunochemical stains to diagnose IKC were cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen (p < 0.05 with each). CONCLUSIONS: These findings provide a better understanding of the pathogenesis and the immunohistochemical findings of this relatively new entity allowing for more appropriate diagnosis of IKCs aiming to reduce future complications from their management.

Benign Solitary Fibrous Histiocytoma of Xanthomatous Subtype of the Perilimbal Conjunctiva and Adjacent Sclera in a Youth.

AIMS: To report the clinical and pathological features of a benign fibrous histiocytoma of the xanthomatous subtype in the perilimbal conjunctiva and adjacent sclera in a youth. METHODS: An 11-year-old Caucasian boy presented with a yellowish dome-shaped conjunctival mass abutting the inferotemporal limbus of the left eye. The tumor measured 4 mm in its maximum diameter. The lesion was excised and was noted to extend into the sclera. Three years postoperatively, there was no evidence of recurrence. RESULTS: Histopathological examination disclosed a highly cellular lesion composed predominantly of benign-appearing foamy histiocytes without multinucleated giant cells. The tumor contained sparse fibrous septa without a storiform configuration. Immunohistochemical analysis showed diffuse cytoplasmic positive staining with adipophilin, CD34, and CD163. CONCLUSION: A lesion comprised of numerous homogeneous foamy histiocytes without multinucleated giant cells in the perilimbal conjunctiva and adjacent sclera of a youth is presented as a unique case of a rare variant of fibrous histiocytoma of the xanthomatous subtype.

Langerhans cell histiocytosis in an 18-month-old child presenting as periorbital cellulitis.

Langerhans cell histiocytosis (LCH) is a rare multi-system disease. It presents infrequently as a childhood orbital tumor, and can mimic more common inflammatory orbital disease processes. We report the clinical, histopathological, and electron microscopic findings of orbital LCH in an 18-month-old child, along with a review of the recent literature regarding molecular pathogenetic analysis of LCH. The child presented with a two-week history of progressive left periorbital edema and redness. He was initially diagnosed and treated empirically for bacterial periorbital cellulitis, but subsequently underwent ophthalmological consultation after he failed to improve. Histopathological examination of an orbital biopsy specimen revealed numerous Langerhans-type cells, which stain positive for CD1A and CD207 (langerin). Electron microscopic examination demonstrated characteristic Birbeck granules within the Langerhans-type cells. Three year follow-up did not demonstrate recurrence or disease progression.

Unsuspected and misdiagnosed posterior uveal melanoma following enucleation and evisceration in Ottawa-Gatineau.

OBJECTIVE: There is a gap in the recent literature on the topic of clinically misdiagnosed and unsuspected posterior uveal melanomas (PUM) with a calculation of the frequency of these events for a specific geographical area. As the only ophthalmic pathology laboratory in our region, we determined the rate of these outcomes over a 16-year period. METHODS: We retrospectively reviewed 2558 consecutive ophthalmic pathologic specimens in the Ottawa-Gatineau region, of which 334 were eviscerations and 227 were enucleations. We calculated the frequency of clinically misdiagnosed PUM and of clinically unsuspected PUM. We also determined the rate of uveal melanoma undergoing enucleation. RESULTS: From 100 diagnoses of PUM, 2 (2.0%) cases were clinically unsuspected and 2 (2.0%) cases were clinically misdiagnosed. The rate of uveal melanoma undergoing enucleation was 5.6 cases per 1 000 000 of population per annum. From 2009 to 2012, the incidence of this event was 3.8 cases per 1 000 000 per annum, which was lower than the previous three 4-year increments. CONCLUSIONS: We present the first and only single-centred, population-based data on the rates of unsuspected PUM and of clinical misdiagnosis of PUM in the era of modern diagnostic imaging. Our rate of clinical misdiagnosis is within the range of recent reports of this event. Unsuspected PUM occurred at a rate substantially lower than previously published. The incidence of uveal melanoma undergoing enucleation has decreased despite an increase in population, which reflects a shift in management from enucleation to radiation therapy.

Secondary corneal amyloidosis after perforating corneal trauma: A series of 5 cases and review of the literature.

We retrospectively reviewed the clinical and surgical histories of 5 patients with traumatic secondary corneal amyloidosis, a relatively rare sequela of nonsurgical and surgical perforating corneal trauma. Four had history of nonsurgical trauma, and 1 had surgical trauma to the cornea. Three specimens were obtained by penetrating keratoplasties and 2 by excision of the cornea during evisceration of the ocular contents. All the corneal specimens showed full-thickness scars of a prior perforating wound with congophilic amyloid deposits that exhibited apple-green birefringence under polarized light and dichroism. All cases had variable degrees of predominantly chronic nongranulomatous inflammation. Ultrastructural examination in 1 patient disclosed 8-nm diameter fibrils in disarray, consistent with amyloid. Amyloid P immunostaining was positive in all 3 patients tested for this protein.

Usefulness of a red chromagen in the diagnosis of melanocytic lesions of the conjunctiva.

IMPORTANCE: Immunohistochemical analyses may assist in the diagnosis of precancerous and cancerous conjunctival lesions. OBJECTIVE: To use Vector Red (VR) to identify an immunologic marker that is sensitive for all melanocytes and another that is sensitive and specific for activated and/or atypical conjunctival melanocytic lesions (MLs). DESIGN, SETTING, AND PARTICIPANTS: Eight specimens each of control lesions (normal conjunctiva and normal uvea as well as choroidal melanoma) and 8 from the diagnostic categories (conjunctival nevus, primary acquired melanosis with mild or no atypia, primary acquired melanosis with moderate to severe atypia, and conjunctival melanoma) that provided sufficient quantity and quality of tissue were available for processing. The specimens were obtained from the Ophthalmic Pathology Laboratory, The Ottawa Hospital, from 2005 to 2013. The specimens were immunolabeled with human melanoma black 45 (HMB45), melanoma antigen recognized by T cells 1 (Melan-A), S100, and Ki67 using VR and a double panmelanoma cocktail (dPANMEL) using 3,3'-diaminobenzidine (DAB) and VR. The HMB45-immunolabeled specimens were additionally developed with DAB, with and without overnight bleaching with hydrogen peroxide, 4%. Data were collected by 2 pathologists who were masked to sample grouping. MAIN OUTCOMES AND MEASURES: Differentiation between benign and malignant MLs based on immunomarker profile. RESULTS: Immunoreactivity was best visualized in specimens with VR. Melan-A labeled all melanocytes (100% sensitivity; panmelanocyte marker) without discriminating between benign and malignant lesions (0% specificity). Atypical melanocytes were most specifically labeled with HMB45 (96% specificity, 97% sensitivity; atypia marker). In primary acquired melanosis specimens, we found that the percentage of HMB45 (P < .001), S100 (P < .001), and Ki67 (P ≤ .02) positivity increased significantly with worsening atypia. CONCLUSIONS AND RELEVANCE: We recommend VR, which rarely requires specimen bleaching, as the standard substrate for immunohistochemical analysis of conjunctival MLs. We found Melan-A and HMB45 to best characterize MLs. In conjunctival MLs, the use of VR with Melan-A and HMB45 provides substantial sensitivity for all melanocytes and for atypical melanocytes, respectively, and reduces specimen-processing time for laboratories performing immunohistochemistry on MLs.

Ocular metastasis of lung adenocarcinoma with ELM4-ALK translocation: A case report with a review of the literature.

Choroidal metastasis is the most common intraocular neoplasm and is associated with significant morbidity. In a small percentage of patients, ocular manifestation may be the initial presentation of a systemic malignancy and can be diagnostically difficult to distinguish from ocular primary malignancies. Herein, we present a case of a never-smoker whose ocular pathology was integral to the diagnosis and management of a lung adenocarcinoma harboring a rare oncogene. Through this case, we have explored important diagnostic and therapeutic considerations of pulmonary metastases to the choroid.

Dacryops: a series of 5 cases and a proposed pathogenesis.

IMPORTANCE: Lacrimal gland ductal cysts (dacryops) are uncommon, occurring anywhere that lacrimal gland tissue is present. While dacryops has long been recognized, its pathogenesis has not been well established. OBSERVATIONS: Five cases of dacryops were identified at the Ottawa Hospital over a 3-year period (2009-2012). Histopathological examination showed immunoreactivity to IgA on the luminal surface of the epithelial ductal cyst and mild chronic inflammation in the underlying stroma or lacrimal gland. CONCLUSIONS AND RELEVANCE: Our results suggest that a multifactorial mechanism leads to dacryops including chronic inflammation, an immune response, and IgA hypersecretion with an osmotic effect, all contributing to the cyst formation. Further research on the pathogenesis is recommended.

Bilateral necrobiotic xanthogranuloma of the eyelids followed by a diagnosis of multiple myeloma 20 years later.

A uniquely indolent case of necrobiotic xanthogranuloma with bilateral, periorbital involvement was presented. This patient presented with cutaneous eyelid lesions of 20 years' duration. Although symptomless, the patient underwent testing for hematologic malignancy, which led to a diagnosis of multiple myeloma. A review of the literature revealed that this is the longest interval between the onset of the skin manifestations and the diagnosis of the systemic malignancy in this rare disease.

Myxomatous corneal degeneration: a clinicopathological study of six cases and a review of the literature.

Thirteen cases with myxomatous changes of the corneal stroma have been reported to date. We report six additional cases with clinical, histopathological, and immunohistochemical data. The clinical appearance is most often a gelatinous, whitish elevation with insidious onset. Histopathologically, there are inconspicuous spindle- and stellate-shaped cells in a loose, myxoid matrix. The typical location is in the anterior cornea beneath the epithelium, with varying degrees of extension into the stroma. Vimentin and smooth-muscle actin immunohistochemical stains are characteristically positive, and staining occasionally may be seen with muscle-specific actin, whereas CD34 staining usually is negative. In most cases, myxomatous changes are a degenerative process involving transformation of stromal keratocytes into cells with prominent secretory activity and myofibroblastic differentiation. Most occur in corneas with a history of ocular disease or trauma that disrupts Bowman's layer. We suggest labelling lesions with these features as "myxomatous corneal degeneration." So-called "primary corneal myxomas" also exist where there is no significant history. It remains unclear whether the myxomatous changes in such lesions are neoplastic or degenerative. Myxomatous corneal changes are likely under-recognized and under-diagnosed.