Dilip Kumar Mishra

Punctal stenosis: histopathology, immunology, and electron microscopic features-a step toward unraveling the mysterious etiopathogenesis.

Purpose: To study the histologic, immunohistochemical, and electron microscopic features of puncta and proximal vertical canaliculi to understand the etiopathogenesis of punctal stenosis. Methods: Prospective study of 26 stenosed punctae that were collected following a punctoplasty. Sixteen were from lower eyelid and 10 from upper eyelid. Histopathological examination was performed on 20 punctae using hematoxylin-eosin, periodic acid-Schiff, and Masson trichrome staining. Immunohistochemical patterns were analyzed after staining with leukocyte common antigen or CD45, CD3, CD5, CD10, CD20, CD138, and smooth muscle actin. Six punctae (3 upper, 3 lower) were separately processed for electron microscopic studies as per standard protocols. Results: All punctae showed evidence of subepithelial and subconjunctival fibrosis. Thirty percent (6/20) showed extensive fibrosis. Inflammation was noted in 80% (16/20) of the samples; however, 20% (4/20) showed severe inflammation. Strong immunoreactivity was noted, with CD45 and CD3 in 80% (16/20) with predominance in the subepithelial areas. Focal immunoreactivity was noted for CD10, CD20, and CD138. Immunoreactivity was negative for CD5. Electron microscopic features include blunted epithelial microvilli, numerous fibroblasts, extensive and irregularly arranged collagen bundles, mononuclear infiltration in the vicinity of fibroblasts or in between collagen bundles, and inter- and intracellular edema in areas of inflammation. Conclusions: Chronic inflammation and subsequent fibrosis appear to be the basic ultrastructural response to various noxious stimuli. Mononuclear inflammatory infiltration in the vicinity of fibroblasts could possibly reflect a close cellular interaction between these 2 cells.

Ocular Surface Squamous Neoplasia in 200 Patients: A Case-Control Study of Immunosuppression Resulting from Human Immunodeficiency Virus versus Immunocompetency

PURPOSE To describe and compare the clinical presentation, treatment outcomes, and histopathologic features of ocular surface squamous neoplasia (OSSN) based on human immunodeficiency virus (HIV) status. DESIGN Case-control study. PARTICIPANTS A total of 200 patients with OSSN, of whom 83 (41%) had positive results for HIV and were classified as cases and 117 (59%) had negative results for HIV and were classified as controls. METHODS Enzyme-linked immunosorbent assay for HIV, conjuntival excision biopsy, extended enucleation, orbital exenteration. MAIN OUTCOME MEASURES Clinical features, treatment outcomes, and histopathologic characteristics. RESULTS The mean age at presentation of OSSN in both cases and controls was 40 years (median, 40 years; range, 13-65 years) and in controls was 40 years (median, 38 years; range, 15-80 years). On comparison of cases versus controls with OSSN, HIV-positive individuals had larger (12 vs. 8 mm; P < 0.001) and thicker (3.2 vs. 2.3 mm; P = 0.041) tumors, with a higher incidence of corneal (60% vs. 40%; P = 0.007), scleral (19% vs. 9%; P = 0.044), and orbital (13% vs. 3%; P = 0.019) invasion and a higher need for extended enucleation or exenteration (27% vs. 11%; P < 0.001). The bilateral presentation (11% vs. 4%; P = 0.13), need for lamellar sclerectomy (13% vs. 8%; P = 0.29), and tumor recurrence after primary treatment (30% vs. 20%; P = 0.12) was higher in HIV-positive cases compared with HIV-negative controls. However, these features were not statistically significant. Based on American Joint Committee on Cancer classification, T1 tumor was more common in controls (13% in cases vs. 35% in controls; P = 0.0009), and T4 tumor was more common in cases (13% in cases vs. 4% in controls; P = 0.019). None of the patients demonstrated systemic metastases or died of disease during a mean follow-up period of 10 months (median, 4 months; range, <1-75 months) in cases and 9 months (median, 4 months; range, <1-99 months) in controls. CONCLUSIONS Ocular surface squamous neoplasia in HIV-positive individuals is aggressive with larger and thicker tumors and with higher incidence of corneal, scleral, and orbital invasion. These patients are associated with poor ocular prognosis with higher need for extended enucleation, exenteration, or both.

Clinical Features Predictive of High-Risk Retinoblastoma in 403 Asian Indian Patients: A Case-Control Study

PURPOSE To identify the clinical features predictive of high-risk retinoblastoma on histopathology. DESIGN Case-control study. PARTICIPANTS A total of 145 cases with histopathologic high-risk features of retinoblastoma and 258 controls without high-risk features. METHODS Enucleation and adjuvant chemotherapy. MAIN OUTCOME MEASURES High-risk features on histopathology were defined as the presence of anterior chamber seeds, iris infiltration, ciliary body infiltration, massive (≥ 3 mm) choroidal invasion, postlaminar optic nerve invasion, invasion of optic nerve transection, combined nonmassive choroidal and prelaminar/laminar optic nerve invasion, or scleral/extrascleral infiltration. RESULTS Of 403 patients who underwent primary enucleation for the treatment of retinoblastoma, 145 (36%) had high-risk features on histopathology (cases) and 258 (64%) had no high-risk features (controls). High-risk retinoblastoma occurred in 16% of (8/50) group D eyes and 39% of (137/353) group E eyes. The histopathologic high-risk features in these 145 patients included anterior chamber seeds (n = 25, 17%), iris infiltration (n = 12, 8%), ciliary body infiltration (n = 17, 12%), massive (≥3 mm) choroidal invasion (n = 69, 48%), postlaminar optic nerve invasion (n = 71, 49%), invasion of optic nerve transection (n = 3, 2%), combined choroidal and optic nerve invasion (n = 17, 12%), scleral infiltration (n = 20, 14%), and extrascleral involvement (n = 8, 6%). The mean number of high-risk features was 2 (median, 2; range, 1-7). The significant clinical features in cases versus controls included prolonged duration of symptoms of >6 months (21% vs. 7%; P < 0.001), poor visual acuity at presentation (74% vs. 64%; P = 0.05), buphthalmos (16% vs. 7%; P = 0.005), secondary glaucoma (47% vs. 15%; P < 0.001), iris neovascularization (46% vs. 22%; P < 0.001), ectropion uveae (39% vs. 14%; P < 0.001), and orbital cellulitis (3% vs. <1%; P = 0.05). On the basis of International Classification of Intraocular Retinoblastoma, group E tumor had a statistically significant higher incidence of high-risk retinoblastoma compared with controls (39% vs. 16%; P = 0.01). Multivariate analysis of clinical features at presentation that predicted high-risk features on histopathology included prolonged duration of symptoms of >6 months (P = 0.008) and secondary glaucoma (P = 0.021). CONCLUSIONS In this study, the clinical features at presentation predictive of high-risk features on histopathology included prolonged duration of symptoms of >6 months and secondary glaucoma. Globe-preserving methods of treatment should be used with caution in patients with these features.

Sebaceous gland carcinoma of the eyelid: clinicopathological features and outcome in Asian Indians

PurposeTo study the clinical and histopathological features of eyelid sebaceous gland carcinoma (SGC) and to evaluate the prognosis in the Asian-Indian population.MethodsThis is a retrospective study of 191 patients with SGC.ResultsThe mean age at presentation of eyelid SGC was 57 years (median, 56 years). The tumor epicenter was most commonly located in the upper eyelid (n=125, 65%). The mean tumor basal diameter was 15 mm (median, 10 mm). There was evidence of tumor extension into the orbit (n=30, 16%), paranasal sinuses (n=3, 2%), and brain (n=1, 1%). Wide excision biopsy (n=146, 78%) was the most common treatment modality. Tumor recurrence was noted in 42 (24%) patients over a mean follow-up period of 29 months (median, 20 months). On the basis of the Kaplan–Meier estimate, lymph node metastasis occurred in 18%, systemic metastasis was detected in 10%, and death occurred in 2% of patients at 10 years. On multivariate analysis, the factors predicting locoregional lymph node and systemic metastasis were medial canthal involvement (P=0.004; P=0.013), lateral canthal involvement (P=0.013; P=0.025), tumor basal diameter >10 mm (P=0.002; P=0.002), and perivascular invasion (P=0.043; P<0.001), respectively. The factors predicting death due to metastasis on multivariate analysis were medial canthal involvement (P=0.012) and tumor basal diameter >10 mm (P=0.001).ConclusionAdvanced eyelid SGC is a tumor associated with poor prognosis. In this study, canthal involvement, larger tumor diameter, and perivascular invasion were poor prognostic factors.

Neoadjuvant Systemic Chemotherapy in the Management of Extensive Eyelid Sebaceous Gland Carcinoma: A study of 10 Cases.

Purpose: To report the efficacy of neoadjuvant systemic chemotherapy in the management of eyelid sebaceous gland carcinoma (SGC). Methods: Retrospective study of 10 patients that received neoadjuvant systemic chemotherapy (Cisplatin/Carboplatin and 5-Fluorouracil) for eyelid SGC. Results: The mean age at presentation of eyelid SGC was 58 years (median, 55 years; range, 45 to 72 years). There were 6 females and 4 males. The mean tumor basal diameter was 36 mm (median, 31 mm, range, 20 to 65 mm), with orbital tumor extension in 9 cases. On the basis of TNM Classification, the tumors were classified as T3 (n = 10), N1 (n = 6), and M1 (n = 2). The mean number of cycles of neoadjuvant systemic chemotherapy per patient was 3 (median, 3; range, 3 to 4). The mean percentage reduction of tumor basal diameter after neoadjuvant chemotherapy was 74% (median, 80%; range, 30% to 100%). None of them had any major systemic side-effects of neoadjuvant chemotherapy. Postchemotherapy, surgical treatment for residual tumor was performed in 7 cases. Five cases underwent excision biopsy and 2 cases with residual orbital component underwent eyelid-sparing orbital exenteration. No tumor recurrence was noted in any of the 7 cases at a mean follow-up period of 18 months (median, 14 months; range, 3 to 63 months). One patient died due to systemic metastasis. Conclusion: Neoadjuvant systemic chemotherapy is effective and safe in the management of eyelid sebaceous gland carcinoma.

Histopathology and Immunophenotyping of Congenital Lacrimal (Anlage) Fistulae.

Purpose: To report the histopathological and immuno histochemical features of congenital lacrimal fistulae. Methods: Retrospective chart review of all patients who underwent a fistulectomy for congenital lacrimal fistulae, over a 3-year period from a single surgeon’s (M.J.A.) database, were included in the study. A detailed lacrimal system evaluation was performed, and intraoperative findings were documented. The excised fistulae were studied using hematoxylin and eosin and periodic acid-Schiff staining. Immunophenotyping was performed using CD3, CD5, CD10, and CD20. Results: Twelve excised fistulae of 12 patients were studied. The mean age at presentations was 5.3 years (range, 3–11 years). The deeper parts of the fistulae were lined with hypertrophied stratified squamous epithelium similar to canalicular tissue in 83.3% (10/12), reflecting its origin from the canalicular tissue, and 16.7% (2/12) originated from the lacrimal sac and were lined with columnar epithelium with areas of squamous metaplasia. The subepithelial areas showed presence of fibrosis and chronic inflammatory infiltrate. The infiltrates were lymphoplasmacytic and were positive for CD3, CD5, and CD20 and negative for CD10 immunostaining. Conclusion: Hypertrophied stratified squamous lining was the commonest finding. Immunophenotyping revealed features of chronic inflammatory infiltrate composed of a mixture of both T and B lymphocytes. Histopathological analysis of fistulae may be of adjunctive value in determining the origin of the anlage.

Histopathology, Immunohistochemistry, and Electron Microscopic features of a Dacryocystorhinostomy Ostium Cicatrix

Purpose: The aim of this study is to report the histopathological, Immunohistochemical, and ultrastructural features of a dacryocystorhinostomy ostium cicatrix. Methods: A prospective histopathological study was performed in a tertiary eye care setting. Scarred nasal mucosal tissues obtained during endoscopic revisions of 10 previously failed dacryocystorhinostomies secondary to complete cicatricial closure of the ostia were studied. The tissue specimens were analyzed using hematoxylin and eosin, periodic acid-Schiff staining. Special stains used include Masson’s trichrome and Alizarin red. Immunohistochemistry was performed using vimentin, smooth muscle actin, CD3, CD5, and CD20. Specimens were processed for ultrastructural analysis as per standard protocols for transmission electron microscopy. Results: The respiratory epithelial regeneration was noted to be complete. Irregular laying of deeply eosinophilic and hyalinized collagen with intervening fibroblasts was noted. Focal areas of new bone formation were seen within the cicatricial tissue with osteocytes and ongoing osteoblastic rimming. The infiltrates were mixture of both T and B lymphocytes and were positive for CD3, CD5, and CD20 immunostaining. Electron microscopy showed disorganized collagen fibrils with numerous fibroblasts and mononuclear inflammatory infiltrate. Amorphous bony osteoid within a fibrillar background with metabolically active osteoblasts showed a vesicular cytoplasm, hyperplastic proliferating mitochondria, large Golgi apparatus, and dense endoplasmic reticulum. Conclusion: There is new bone formation within the dense connective tissues of a dacryocystorhinostomy cicatrix. This study may provide useful inputs for further basic science studies aimed at better understanding of wound healing in failed dacryocystorhinostomy.

Acute dacryocystitis as a presenting sign of chronic lymphocytic leukaemia.

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Conjunctival Leiomyosarcoma: A Report of Two Cases.

ABSTRACT Purpose: Leiomyosarcoma is a common soft tissue tumor in the body. However, ocular leiomyosarcoma is rather uncommon. Herein, we describe the clinical and histopathological features of two cases of conjunctival leiomyosarcoma. There have only been three previously documented cases of conjunctival leiomyosarcoma. Results: A 34-year-old male presented with a 2-year history of a whitish mass in the right eye. He underwent an incisional biopsy of the mass, which supported the diagnosis of leiomyosarcoma on histopathological examination. Computed tomography showed orbital extension of the mass, following which he underwent an eyelid sparing orbital exenteration of the right side. The second case was that of a 39-year-old male, who had a history of a whitish limbal mass, which had been previously excised elsewhere. The pre-operative clinical photographs and histopathology slides of the excised mass were reviewed. A histopathological diagnosis of conjunctival leiomyosarcoma was established and due to base positivity, he was treated with plaque radiotherapy. Both the cases showed no tumor recurrence or systemic metastasis at one-year follow-up. Conclusion: Primary conjunctival leiomyosarcoma is uncommon. Appropriate treatment of the tumor is associated with good prognosis.

Foam sclerotherapy for periorbital dermoid cysts.

Purpose: To report nonsurgical treatment of periorbital dermoid cysts with foam sclerotherapy using sodium tetradecyl sulfate (STS). Methods: Single-center, retrospective, interventional case series. Clinical records of all patients diagnosed to have congenital orbital dermoid cyst and treated with STS foam sclerotherapy between 2012 and 2013 were reviewed. The ectodermal contents of the dermoid cyst were aspirated through a stab incision with 18G needle, followed by saline lavage. Intraluminal foam sclerotherapy was then performed using STS (30 mg/ml) in a proportion of 10% of the total aspirate volume. Retrospective data analysis included demographic profile, clinicoradiologic findings, and treatment outcomes of foam sclerotherapy. Results: Four patients were treated in the given period. Average age at presentation was 20.2 years. All cysts were reported to be congenital in nature, and the location was medial angular in 2 cases, lateral angular in 1 case, and lateral orbitotemporal in 1 case. The average aspirate of the pultaceous cyst content was 3.75 ml (range, 2–5 ml). Of the 4 patients, 2 dermoid cysts resolved completely within 8 weeks. Two cysts showed partial response and required a second foam sclerotherapy to achieve complete resolution. At an average follow up of 13.25 months (range, 11–16 months), complete cyst resolution was noted. No sclerotherapy-related complications were observed. Conclusions: Foam sclerotherapy is successful in obliterating periorbital dermoid cysts and provides a minimally invasive nonsurgical approach to achieve an aesthetic result.