Merkel Cell Carcinoma Metastases to Caruncle With Orbital Extension: Report and Literature Review.

Merkel cell carcinoma (MCC) is an uncommon and aggressive skin cancer of neuroendocrine origin. The tumor usually presents with a locoregional spread and most frequently metastasizes to the skin, liver, bone, lung, and brain. Despite the orbit being a relatively common site of metastases, it has rarely been reported in patients with MCC. The authors present a case of biopsy-proven orbital metastatic MCC in an 86-year-old male who presented with a rapidly enlarging right caruncle/subconjunctival mass with orbital extension and a history of forearm MCC excision 3 years prior. There are only 3 reported cases of distant metastatic MCC to the orbit, all presenting as a mass originating from extraocular muscles; and no cases of caruncle involvement.

Bulbar conjunctival metastasis from mucoepidermoid carcinoma of parotid-a case report and review of literature.

BACKGROUND: Mucoepidermoid carcinoma of salivary glands usually metastasizes to the lungs, liver, bone, brain, and skin. We report a rare case of distant metastasis of high-grade mucoepidermoid carcinoma of the parotid to the ipsilateral bulbar conjunctiva of the eye. CASE PRESENTATION: Sixty-year-old male of Kashmiri origin presented to our tertiary care referral cancer institute with exophytic lesion of the left bulbar conjunctiva following his treatment for mucoepidermoid cancer of ipsilateral parotid gland, 9 months back. The lesion was biopsied and reported as high-grade mucoepidermoid carcinoma. Radiological imaging showed no other site of recurrence. The patient underwent orbital exenteration and final histopathological evaluation reported the lesion as mucoepidermoid carcinoma. CONCLUSIONS: Distal metastasis from mucoepidermoid carcinoma to bulbar conjunctiva is very rare and to the best of our knowledge has not been previously reported.

Immune Checkpoint Inhibitors for Treatment of Metastatic Melanoma of the Orbit and Ocular Adnexa.

Programmed cell death 1 (PD-1) inhibitors are members of a new class of drugs known as immune checkpoint inhibitors and have proven efficacy in the treatment of metastatic melanoma. Herein, the authors report the use of nivolumab and pembrolizumab, 2 recently Food and Drug Administration-approved PD-1 inhibitors, in 3 patients: 1 with metastatic conjunctival melanoma and 2 with metastatic cutaneous melanoma and orbital involvement. The patients' metastatic disease responded well to drug treatment. As of this writing, 2 patients have completed therapy and remain disease free at least 1 year after treatment completion; the other patient is still receiving treatment, and his orbital disease is responding. The authors herein describe the use of PD-1 inhibitors as a new alternative in the treatment of metastatic melanoma to the orbit or metastatic ocular adnexal melanomas in these clinical settings.

Orbital and conjunctival metastasis from lobular breast carcinoma.

This article examines the clinical presentation of ocular metastasis from an infiltrating lobular breast carcinoma. We examined a conjunctival biopsy from a 69-year-old woman who developed unilateral conjunctival inflammation together with a neurotrophic corneal ulcer and proptosis. Infiltrating lobular breast carcinoma (ILBC) was diagnosed using routine histology and immunohistochemistry. She had a past history of a hormone receptor-positive infiltrating ILBC 11 years ago with cutaneous and diffuse osteoblastic metastases, and she was kept under treatment with lezotrol. Treatment was initiated with systemic corticosteroids but an annular conjunctival perilimbal infiltration was found to have spread, which did not respond either to local radiotherapy (total dose 60 Gy, 2 Gy per day). A new extensive corneal epithelial defect recurred, and because it had not responded to matrix therapy agent (RGTA, Cacicol®) eye drops, autologous serum eye drops and a therapeutic contact lens, a permanent total tarsorrhaphy was performed. Progression of the diffuse bone metastases was detected and the treatment with lezotrol was replaced by fulvestrant.Infiltrating lobular breast carcinoma is a rare cause of conjunctival metastasis. This aggressive malignancy did not respond to external beam radiotherapy.

Squamous Cell Carcinoma of the Caruncle.

Squamous cell carcinoma (SCC) of the lacrimal caruncle is a rare entity. The authors report the management and outcomes of 3 cases of caruncle SCC. Case 1 underwent wide margin surgical excision with adjuvant topical chemotherapy for a poorly differentiated SCC. He later developed regional lymph node metastasis and required modified radical neck dissection. Case 2 underwent wide margin surgical excision with cryotherapy and adjuvant topical chemotherapy for an invasive moderately differentiated SCC. She later developed a recurrence and underwent orbital exenteration. Case 3 was a moderately differentiated SCC treated with wide margin excision alone and had no recurrence during 5-year follow up. Careful surveillance of caruncle SCC is required, given the observed propensity for local recurrence and/or regional metastasis.

Conjunctival metastasis as the presenting sign for stage IV lung cancer.

PURPOSE: Lung cancer is the leading cause of cancer-related death in North America. It is often diagnosed at an advanced stage, lending to a poor prognosis. Symptoms of lung cancer often do not present until more advanced stages. Common sites of lung cancer metastasis are the bones, liver, and brain. The etiology of eye masses ranges from the relatively benign to those with tremendous risk of morbidity, and the differentiation is often difficult clinically. This case highlights the importance of more detailed workup, including biopsy, to determine the exact nature of the lesion. CASE REPORT: A 50-year-old white man was referred for evaluation of a "bump" on his right upper eyelid. He had noticed it for 1 month and noted enlargement during the past 2 weeks. He also reported that he had been smoking about one pack per day since 1969. External examination was remarkable for a 1.5-cm nodule pushing up from under the right upper lid. When the lid was everted, there was a 0.9-cm red and black vascularized sessile lesion on the palpebral conjunctiva. The patient was referred to an oculoplastics specialist to rule out a malignant or metastatic conjunctival neoplasm. The oculoplastics service performed an excisional biopsy, and the pathologic examination showed a poorly differentiated and highly aggressive non-small-cell lung cancer (NSCLC). After systemic evaluation, he was diagnosed as having stage IV NSCLC, with metastases to the right eyelid, brain, liver, and right lung. He underwent multiple radiotherapy sessions. He died 5 months after our initial examination. CONCLUSIONS: Stage IV NSCLC is incurable, and its treatment is often palliative. Conjunctival metastasis of stage IV NSCLC is rare, and it is clinically difficult to differentiate eyelid tumors as benign or concerning by examination alone. This case highlights the importance of a thorough history, referral, proper imaging, and biopsy to diagnose a metastatic neoplasm in a patient at high risk for cancer.

Carcinoid tumor metastatic to the tarsal conjunctivae.

A 64-year-old woman who had been diagnosed with carcinoid tumor of the large intestine over a decade earlier presented with an acute right periorbital inflammatory reaction. On examination, 2 disc-shaped, gelatinous masses were noted on the right upper and lower tarsal conjunctivae. Excisional biopsies of these masses revealed metastatic carcinoid tumor. Her total burden of metastatic carcinoid tumor continued to increase during 2 years of follow-up, with new metastatic foci in the right choroid, in the left upper and lower eyelids, and subcutaneously in the neck and chest. Despite a comprehensive treatment approach including radionuclide therapy with the somatostatin peptide analog, Y-DOTATOC, the patient succumbed to the disease and died. The authors report an unusual case of a gastrointestinal carcinoid tumor metastatic to the tarsal conjunctivae, eyelids, choroid, and orbit.

Vitreoretinal lymphoma occurring after systemic chemotherapy for primary conjunctival diffuse large B cell lymphoma: A case report.

INTRODUCTION: Ocular adnexal lymphoma and vitreoretinal lymphoma are rare forms of non-Hodgkin lymphoma. They are regarded as distinct disease entities due to the differences in molecular mechanism, management, and outcome. We present a rare case of conjunctival diffuse large B cell lymphoma (DLBCL) that developed to vitreoretinal lymphoma after systemic chemotherapy. PATIENT CONCERNS: A 60-year-old man presented with a left salmon-colored conjunctival mass. DIAGNOSIS: A biopsy was performed, and histopathologic examination showed DLBCL. Immunohistochemical staining was positive for CD20 with increased κ to λ light chain ratio. INTERVENTIONS: Bone marrow biopsy also revealed DLBCL. Gallium-67 scintigraphy showed abnormal uptake only in the left orbital lesion. Ann Arbor stage was estimated as IV. The patient underwent systemic combination chemotherapy and immunotherapy. OUTCOMES: Four months after the last course of chemotherapy, primary conjunctival DLBCL relapsed, manifesting vitreous opacity. Diagnostic vitrectomy confirmed a diagnosis of vitreoretinal lymphoma. LESSONS: Conjunctival DLBCL and vitreoretinal lymphoma are both DLBCL. After systemic chemotherapy for conjunctival DLBCL, the lymphoma may relapse in intraocular sites as secondary vitreoretinal lymphoma.

Uveal Melanoma Metastasis to the Contralateral Eye Structures: A Retrospective Comparative Analysis of 13 Consecutive Patients.

PURPOSE: To report uveal melanoma (UM) metastasis to the contralateral ocular and periocular structures. DESIGN: Retrospective study. PARTICIPANTS: Thirteen patients with UM metastasis to the contralateral ocular and periocular structures were included. METHODS: Clinical records were reviewed retrospectively. MAIN OUTCOME MEASURES: The development and time to onset of contralateral ocular and periocular metastasis, systemic metastasis, and death. RESULTS: Of the 13 000 treated UM patients, 13 patients were diagnosed with UM metastasis to the contralateral ocular and periocular structures. Mean patient age at primary UM diagnosis was 60 years (median, 60 years; range, 37-87 years). The primary uveal melanoma was in the choroid (n = 11) or ciliary body (n = 2) and was treated with brachytherapy (n = 11), proton beam radiotherapy (n = 1), or enucleation (n = 1). Systemic metastasis developed in 11 patients (85%) at a mean of 66 months (median, 34 months; range, 12-216 months) after diagnosis of the primary UM. All 11 patients (100%) showed liver metastasis and 8 patients (62%) also showed extrahepatic metastasis. The sites of metastasis to the contralateral ocular or periocular structures included the choroid in 4 patients (31%), the orbit in 7 patients (54%), and the eyelid in 2 patients (15%). One patient with eyelid metastasis demonstrated concurrent conjunctival nodule. Mean time to diagnosis of contralateral ocular or periocular metastasis was 94 months (median, 48 months; range, 9-375 months). Contralateral choroidal metastasis was multifocal in 3 of 4 patients (75%). Of 7 patients with orbital metastasis, 5 showed extraocular muscle involvement with restricted ocular motility. Treatment for contralateral choroidal metastasis included brachytherapy (n = 2), transpupillary thermotherapy (n = 1), and observation (n = 1). Treatment for contralateral periocular (orbit or eyelid) metastasis was excision (n = 5), external beam radiotherapy (n = 2), and observation (n = 2). Of 13 patients, death was documented in 11 patients at a mean of 17 months (median, 9 months; range, 3-54 months) as a result of systemic UM metastasis (n = 10) or unrelated cause (n = 1). CONCLUSIONS: Metastasis resulting from UM to the contralateral ocular and periocular structures is rare and generally occurs in patients with disseminated metastasis. Orbital tissue is the most common site of involvement, and these patients have short life expectancy.

Immunotherapy With Programmed Cell Death 1 Inhibitors for 5 Patients With Conjunctival Melanoma.

Importance: Conjunctival melanoma has the potential for regional lymphatic and distant metastasis. There is an urgent need for effective treatment for patients with metastatic or locally advanced conjunctival melanoma. Objective: To describe the use of immune checkpoint inhibitors for the treatment of conjunctival melanoma in 5 adult patients. Design, Setting, and Participants: A retrospective review was conducted of the medical records of 5 patients with conjunctival melanoma who were treated with immune checkpoint inhibitors from March 6, 2013, to July 7, 2017. Main Outcomes and Measures: Response to treatment and disease-free survival. Results: Of the 5 patients (4 women and 1 man) with metastatic conjunctival melanoma, 4 were treated with a programmed cell death 1 (PD-1) inhibitor, nivolumab, and had a complete response to treatment with no evidence of disease at 1, 7, 9, and 36 months after completing treatment. One patient with metastatic conjunctival melanoma was treated with another PD-1 inhibitor, pembrolizumab, and had stable metastases during the first 6 months of treatment. Later disease progression resulted in treatment cessation after 11 months and switching to another therapy. Two patients treated with nivolumab developed autoimmune colitis that necessitated stopping the immunotherapy; these patients subsequently were managed with systemic corticosteroids or infliximab. Conclusions and Relevance: This case series report suggests that anti-PD-1 therapy can be used to treat metastatic conjunctival melanoma. Longer follow-up is needed to determine the long-term disease-free survival. Future studies might assess the potential for immune checkpoint inhibitors to obviate the need for orbital exenteration in selected patients with locally advanced disease.

Systemic metastasis following hyphema drainage in an unsuspected retinoblastoma.

A 6-year-old girl had total hyphema and elevated left intraocular pressure following trivial trauma. B-scan with vector A-scan revealed vitreous opacities consistent with hemorrhage. The drained hyphema did not recur. A left vascular conjunctival mass and massive cervical lymphadenopathy occurred 7 months later. Biopsy revealed extraocular retinoblastoma and lymph node metastasis. Computed tomography showed an intraocular mass with intracranial extension. She died of metastatic disease despite intensive chemotherapy. Retinoblastoma should be suspected in a child with hyphema following trivial trauma.

Screening for conjunctival melanoma metastasis: literature review.

Local tumour control in conjunctival melanoma has improved in recent years. However the tumour-related death rate of these patients is still 14% at 5 years up to 33% at 15 years. With the introduction of sentinel node biopsies for conjunctival melanomas with a poor prognosis and screening for locoregional and distant metasases prognosis might be improved.

Unilateral conjunctival infiltration of Adult T-cell leukemia/lymphoma. Case report and literature review.

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by human T-cell leukemia virus type 1 infection. Although conjunctival lymphoma is commonly reported with B-cell lymphoma, it rarely occurs in cases of ATLL. A 73-year-old Japanese female patient was admitted to our institution with evidence of abnormal lymphocytes, lymphadenopathy, and lung nodular lesions. Acute type ATLL was diagnosed, and therapy following the mLSG15 protocol was initiated. At the end of the second course, new bone lesions were detected. A modified treatment regimen was scheduled, but was postponed due to the appearance of gastrointestinal symptoms. Close observation resulted in a diagnosis of cytomegalovirus enteritis. One month after the diagnosis, the patient developed pain and discomfort in her left eye, which was determined to be due to a bulbar conjunctival tumor. Pathological findings revealed conjunctival infiltration of ATLL. Mogamulizumab treatment was initiated and was successful in eradicating the conjunctival lesions after the first course. However, at the end of the third course of therapy, pancytopenia was noted. Therefore, mogamulizumab therapy was discontinued, and the patient was on follow-up observation. Although there was no relapse of the conjunctival lesions, the patient died 1 year after the initial diagnosis, following therapy resistance.

Transmission of Donor-Derived Breast Carcinoma as a Recurrent Mass in a Keratolimbal Allograft.

PURPOSE: To report a case of local transmission of invasive lobular carcinoma from a donor to a recipient in a keratolimbal allograft after cessation of systemic immunosuppressive therapy. METHODS: This is a case report including the clinicopathologic findings. Sections of the donor breast tumor and recipient conjunctival lesions were stained with hematoxylin and eosin. Immunohistochemical studies were performed using pancytokeratin, CK7, CK20, CAM 5.2, CD138, TTF1, estrogen receptor, progesterone receptor, GATA-3, GCDFP-15, and mammaglobin. Polymerase chain reaction-based DNA profiling of tumor cells was performed. RESULTS: Histopathologic examination revealed an infiltrate of atypical cells with large hyperchromatic nuclei consistent with carcinoma. Immunohistochemical analysis showed pancytokeratin, CK7, CAM 5.2, GATA-3, and estrogen receptor positivity and progesterone receptor absence, consistent with the previously determined phenotype of the donor's breast carcinoma. Results of polymerase chain reaction analysis were also consistent with the donor's tumor. After reduced dosing of tacrolimus and mycophenolate mofetil, 2 limbal tumors occurred in the recipient. The immunosuppressive treatment had been stopped completely before the appearance of the third lesion. The recipient had no history of malignancy, and she had routine screenings for breast cancer. CONCLUSIONS: We report a case of donor-derived breast carcinoma in a keratolimbal allograft recipient. The grafted tissue harbored donor-derived tumor cells for more than 4 years after surgery even after systemic immunosuppression was discontinued. Although no similar reports of tumor transfer could be found in the literature, this case suggests the need for increased stringency in donor selection and heightened surveillance for such tumor transmission.

Immunohistology of malignant rabbit fibroma virus--a comparative study with rabbit myxoma virus.

Malignant rabbit fibroma virus (MV) causes a syndrome that consists of disseminated malignant tumors and immunosuppression complicated by severe Pasteurella multocida infection and death. Tissues from rabbits given MV and rabbit myxoma virus were examined by direct immunofluorescence with the use of antibody against virus antigens. Primary and metastatic tumors caused by MV and rabbit myxoma virus were composed of soft tissue cells containing virus antigens. Skin appendages and epidermis overlying the respective tumors showed scant MV but abundant myxoma virus antigen. Both viruses were present systemically in the reticuloendothelial system. Epithelial cells from the liver, kidney, and lung of myxoma virus-infected rabbits contained virus, whereas in MV tumor-bearing rabbits, these cells were uninvolved. However, nasal mucosal and conjunctival epithelia, the locations of Pasteurella infection, showed squamous metaplasia and contained large amounts of MV and myxoma antigens. By analogy to other respiratory tract pathogens, these epithelial changes were probably etiologically significant for development of pasteurellosis in rabbits bearing virus-induced tumors. Thus by immunopathologic as well as clinical examination, MV produces a syndrome distinct from that seen with rabbit myxoma virus. MV induced severe immunosuppression despite T-lymphocyte hyperplasia in the lymphoid tissues observed. The combination of a systemic virus infection, epithelial alterations that impaired clearance mechanisms, and immunologic dysfunction is likely to contribute to the inability of rabbits given MV to survive their gram-negative infection.

Malignant rabbit fibroma virus: observations on the culture and histopathologic characteristics of a new virus-induced rabbit tumor.

The clinical, histopathologic, and cultural characteristics of a newly isolated poxvirus, malignant rabbit fibroma virus (MV), were investigated. MV was isolated from tumors induced by an uncloned stock of Shope fibroma virus (SFV). MV, SFV, and rabbit myxoma virus were compared. Similarly to myxoma virus, MV grew to higher titer in vitro than did SFV and produced plaques rather than foci on rabbit kidney cell monolayers. Unlike the local, self-limited fibroblastic proliferations observed in SFV recipients, MV and myxoma caused a fulminant clinical syndrome characterized by malignant histology, metastases, and supervening fatal gram-negative infection with Pasteurella multocida. MV induced a large, protuberant local tumor and discrete metastases histologically resembling myxosarcomas. Draining lymph nodes contained metastases and showed diffuse cortical hyperplasia. Kupffer's cells were prominent in the liver, and macrophages were abundant in the splenic sinusoids. The lungs and trachea were spared, but the conjunctiva and nasal mucosa showed squamous metaplasia and atypia, with overlying Pasteurella infection and underlying tumor. Myxoma virus infection produced similar mucosal changes, but both of these as well as the epidermis overlying the myxomas showed cytoplasmic virus inclusions. Neither the skin nor the epithelial surfaces overlying MV-induced tumors nor the tumors themselves contained virus inclusions. Thus the tumor syndrome caused by MV differed from other known rabbit tumors. Endonuclease restriction digests showed that the MV genome resembled, but was distinct from, rabbit myxoma virus. Opportunistic infection associated with MV-induced disseminated tumor may be an experimental model for the infectious complications that often supervene in host-tumor relationships.

Conjunctival metastatic adenocarcinoma of unknown origin.

We describe the case of a presumed metastatic adenocarcinoma discovered in the conjunctival limbus of a 75-year-old male with a history of prostate adenocarcinoma. After an initial clinical diagnosis of pinguecula and unsuccessful topical steroid therapy, the lesion was excised and sent for pathological evaluation and special staining. The histopathological evaluation was consistent with a diagnosis of adenocarcinoma, without evidence of lacrimal tissue. Surprisingly, results from special staining were most consistent with lung adenocarcinoma rather than that from a prostate origin. Systemic radiographic evaluation did not locate the primary tumour, and the patient did not present with any symptoms consistent with malignancy. Watchful waiting was chosen as the therapeutic strategy to manage the patient. This is the first report of an adenocarcinoma, likely metastatic, at the conjunctival limbus.