Muir-Torre Syndrome Associated Periocular Sebaceous Neoplasms: Screening Patterns in the Literature and in Clinical Practice

26 Aug 2020

Eiger-Moscovich M. · Eagle Jr. R.C. · Shields C.L. · Racher H. · Lally S.E. · Silkiss R.Z. · Shields J.A. · Milman T.

Background: Muir-Torre syndrome (MTS) is defined clinically as the association of cutaneous sebaceous neoplasm and visceral malignancy. Ancillary tests are considered crucial for diagnosis. Although screening guidelines for MTS, including the Mayo MTS scoring system, have been proposed, there are no ophthalmic site-specific guidelines. Summary: A literature review conducted by PubMed search for articles describing patients with periocular sebaceous neoplasm and MTS disclosed 31 publications describing 60 patients, 36 (60%) of whom fulfilled clinical criteria for MTS, 6 (10%) whose diagnosis was based on screening ancillary studies, 14 (23%) who fulfilled clinical criteria and had supporting screening ancillary studies, and 4 (7%) who fulfilled clinical criteria and had supporting diagnostic genetic testing. Most patients were male (34 vs. 15 females), with a median age of 59 years (range 37–79 years). The most common diagnosis was sebaceous carcinoma (40/60, 67%), followed by sebaceous adenoma (16/60, 27%), followed by other tumors with sebaceous differentiation (4/60, 6%). The periocular lesions were identified prior to visceral malignancy in 10 out of 45 (22%) cases, after visceral malignancy in 34 out of 45 (76%) cases, and concurrently with visceral malignancy in 1 out of 45 (2%) cases. Immunohistochemistry for mismatch repair proteins was performed in 41 out of 60 (68%) and 14 out of 38 (37%) of the tumors had lost MSH2. Based on Mayo-MTS scores of 2 or greater, and after removing visceral malignancies not included in their scoring algorithm, 26 out of 30 of patients (87%) with complete data were considered to be appropriate candidates for further work-up. A survey of current practice was conducted by questionnaires, distributed to ophthalmic pathologists, ocular oncologists, and oculoplastic surgeons from national and international professional societies. Of the 103 physicians who participated in the survey, 91 (88%) felt that MTS evaluation guidelines were not sufficiently clear. Key Messages: Our findings suggest that Mayo MTS screening guidelines may be applicable to periocular sebaceous neoplasms. The uncertainty of ophthalmic specialists about optimal screening guidelines for MTS reflects the heterogeneity of defining criteria for MTS and limited molecular genetic data. Larger studies with detailed clinical, histopathologic, and molecular genetic data are required to formally assess screening guidelines for MTS in patients with periocular sebaceous neoplasms.

https://www.karger.com/Article/FullText/504984

Journal : Ocular Oncology & Pathology

Ref : Muir–Torre syndrome Ocular Oncolgy Sebaceous adenomas

Long-Term Clinical Results and Management following Vitrectomy in Undetected Retinoblastoma Eyes

26 Aug 2020

Biewald E. · Schlüter S. · Bechrakis N.E. · Kiefer T. · Rating P. · Geismar D. · Metz K.A. · Göricke S. · Ketteler P. · Bornfeld N.

Introduction: Given the rarity of retinoblastoma and the consequences of accidental vitrectomy in the event of misdiagnosis, reporting on clinical experience in this area is important. Objective: The aim of this study was to analyse the management and complications with a focus on local orbital recurrence and metastatic disease in 10 children vitrectomized in an undetected retinoblastoma eye. Methods: This is a retrospective descriptive case series conducted in a single-centre referral university hospital. Results: From October 1991 to June 2019, 10 patients with a vitrectomy in an unsuspected retinoblastoma eye were included in this study. The main preoperative diagnoses were unilateral inflammation with a suspected lymphoma, uveitis or toxocariasis in 5 cases, vitreous haemorrhage after trauma in 2 cases, and the last 3 were misdiagnosed with Coats disease, rhegmatogenous retinal detachment and congenital cataract. Mean age at surgery was 3 years, ranging from 14 months to 6 and a half years. Nine patients were suffering from unilateral retinoblastoma; these were enucleated and treated with 4–6 cycles of chemotherapy and/or radiation therapy. The sclerotomy sites were infiltrated with tumour cells in 3 cases. In 1 patient, the differential diagnosis of a malignant medulloepithelioma could not be excluded. One patient had bone marrow infiltration on initial presentation; all other patients are healthy without any signs of orbital recurrence or metastatic disease with a mean follow-up of 5.4 years. Conclusion: In children, intraocular tumours, including retinoblastoma and medulloepithelioma, should be ruled out before pars plana vitrectomy is performed. If no doubtless preoperative diagnosis can be established, preoperative magnetic resonance imaging is mandatory. If a vitrectomy in a retinoblastoma eye has been performed, immediate enucleation of the eye with subsequent chemotherapy and orbital radiation is effective to avoid local recurrence and systemic metastases.

https://www.karger.com/Article/Abstract/505732

Journal : Ocular Oncology & Pathology

Ref : Ocular Oncolgy RB Retinoblastoma Vitrectomy

Intra-Scleral Blue Nevus Arising within Oculodermal Melanocytosis: Melanoma or Not?

26 Aug 2020

Roelofs K.A. · O’Day R. · Thaung C. · Damato B.

Journal : Ocular Oncology & Pathology

Ref : Blue nevus Ocular Oncolgy Oculodermal Melanocytosis

Conjunctival squamous cell carcinoma: prognostic factors for the recurrence and metastasis and clinicopathological characteristics at an oncological hospital in Peru

7 Jul 2020

Deivy Cruzado-Sanchez, Walter Andree Tellez, Beltran Villarreal-Aguilar, Monica Melendez, Anibal Olivera, Fiorella Moran, Solon Serpas-Frias, Raul Cordero-Garcia

Journal : BJO

Ref : Conjunctival Squamous cell carcinoma Exenteration Ocular Oncolgy OSSN

Controlling Conjunctival Melanoma—To Infinity and Beyond

8 Jun 2020

Carol L. Shields, MD; Sara E. Lally, MD; Marlana Orloff, MD

Journal : JAMA Ophthal

Ref : Conjunctival Melanoma Ocular Oncolgy

Primary intraocular mesenchymal chondrosarcoma: a histopathological surprise in an enucleated eye

7 Jun 2020

Ratnesh Ranjan, Parag K. Shah, Sarang Giratkar, Santhi Ramachandran, Narendran Venkatapathy

The incidence of clinical and histopathological discordance in eyes enucleated for retinoblastoma, though not rare, has reduced significantly over a period of years.

Benign ocular lesions such as coats’ disease and persistent hyperplastic primary vitreous in end-stage conditions simulate retinoblastoma.

Nonmalignant ocular tumours such as ocular teratoma, astrocytic hamartoma, and retinal astrocytoma can also mimic retinoblastoma, clinically as well as on imaging, resulting in potentially avoidable enucleation.

Mesenchymal chondrosarcoma (MCS), a rare cartilage-forming tumour with potential aggressive course, is usually found in the skeleton. However, about one-third of the cases are also found in extra-skeletal sites, including orbit.

Although primary intraocular chondrosarcomas have been reported in fish and other mammals such as cats and dogs, there is no report of intraocular MCS in human eye. We are reporting the first case of presumed primary intraocular MCS confirmed on histopathological examination in an eye enucleated for retinoblastoma.

A 9-year-old girl was brought to our outpatient department with complaints of redness and pain in the right eye (RE) of 3 days’ duration. There was history of squinting and white reflex in the same eye for the past 3 years, but no prior ophthalmic consultation was taken. On examination, there was no perception of light in RE, and the best-corrected visual acuity in the left eye (LE) was 6/6. Anterior segment examination of RE revealed circumcorneal congestion, microcystic corneal oedema, shallow anterior chamber depth with 3+ cells, mid-dilated pupil, neovascularisation iris, and clear lens with retrolental white reflex (Fig. 1A). Findings of anterior segment and fundus examinations of LE were within normal limits. During examination under anaesthesia, same findings were noted in anterior segment of RE. Fundus examination showed exudative retinal detachment with white intraocular mass lesion. Intraocular pressure measured was 50 mm Hg in RE and 15 mm Hg in LE. Ultrasound B-scan showed well-defined mass lesion with intralesional calcification in the vitreous cavity with exudative retinal detachment suggestive of endophytic retinoblastoma (Fig. 1B). Magnetic resonance imaging (MRI) showed well-defined endophytic lesion in the temporal half of the right globe having features suggestive of retinoblastoma with scleral involvement in RE as detailed in Figure 2.

A diagnosis of stage 0 group E retinoblastoma was made, and the patient underwent enucleation with implant in RE. Enucleated globe was sent for histopathological analysis. Gross appearance of the cut open eye globe showed an intraocular multilobular greyish white well-defined tumour, measuring 1.2 cm × 1.4 cm, with interspersed tiny hemorrhagic foci arising from the posterior pole and extending anteriorly. The tumour appeared to be originating from choroid pushing retinal pigment epithelium, and causing retinal detachment (Fig. 3). Anterior chamber, sclera, and optic nerve were found uninvolved. Microscopic analysis of hematoxylin and eosin–stained sections from the eye ball showed intraocular tumour tissue involving choroid and vitreous, and closely intricated with retina. Tumour tissue showed sheets of undifferentiated round, oval, and spindle cells with abrupt transition. Small well-defined nodules of well-differentiated hyaline cartilage with central calcification and ossification were also seen. Areas of cartilaginous foci blending in hemangiopericytomatous pattern with undifferentiated cell tumour, haemorrhage, and necrosis were present. Immunohistochemical analysis confirmed the presence of cartilage by positive staining for S100 (Fig. 4). The histopathological features were suggestive of intraocular MCS.

Postenucleation computed tomography (CT) scan of the right orbit showed no residual lesion, whereas CT scan of the left orbit was normal. The child was referred to paediatric oncologist for systemic evaluation, but no other tumours or skeletal lesions were identified, ruling out the possibility of ocular metastasis.

Extraskeletal MCS is a very rare tumour, with orbit being the third most common site following meninges and lower extremities.

Since the first case reported by Cardenas-Ramirez et al in 1971, approximately 40 cases of primary orbital MCS are reported in literature till now, highlighting the rarity of primary intraocular MCS.

No case of intraocular MCS, primary or metastatic, in human being has been previously reported in literature.

Naturally occurring cartilage in fish eyes could be the source of origin for primary intraocular MCS in fish.

Mammals do not have cartilage or bone within their globes, and hence the source of origin of intraocular MCS is not clear in mammals. In mammals, the multipotent mesenchymal stem cells derived from the trabecular meshwork or from pericytes of bovine retina are found to have potential to differentiate into osteoblasts and chondrocytes, and hence could be the possible origin for the tumour in our case.

Extraskeletal MCS is usually seen in younger age group compared with conventional chondrosarcoma. Although orbital MCS commonly presents in second or third decades of life, paediatric cases, including congenital orbital MCS, are also reported.

Orbital MCS tends to present like benign orbital tumours with globe compression resulting in progressive proptosis, diplopia, reduction in visual acuity, and pain of variable severity.

In our case, due to its highly unusual location and late presentation, tumour mimicked as end-stage retinoblastoma and presented with pain and redness.

Imaging features of orbital MCS on CT and MRI scan are well described. CT scan shows well-defined, heterogeneously enhancing mass with calcification seen as high-intensity signal.

It usually causes widening of bony orbit without bone erosion.

MRI shows hypo- or isointense signal in T₁-weighted scans, isointense signal in T₂-weighted scans, and moderate to marked heterogenous enhancement of the soft-tissue component. Intralesional calcifications are seen as low-signal-intensity spots.

As an orbital tumour, ultrasonographic feature of MCS is very rarely reported in literature appearing as well-demarcated hypoechoic mass lesion with heterogenous echogenicity.

In our case, intraocular MCS appeared as large, well-defined, moderately echoic mass lesion with intralesional calcification causing high echogenicity and back-shadowing.

Macroscopic and microscopic features of tumour in our case were consistent with histological features of orbital MCS. Macroscopically, MCS appears as lobulated, soft-to-firm, grey-white mass with focal calcification or cartilaginous component

Microscopically, bimorphic appearance is the pathognomonic feature of MCS characterized by the presence of undifferentiated, round, or spindle-shaped mesenchymal cells arranged in sheets or small clusters, and islands of mature hyaline cartilaginous tissue. This cartilaginous differentiation is crucial for diagnostic confirmation, which often shows central calcification and even ossification.

Some tumours may show arrangement of mesenchymal cell surrounding vascular space resembling hemangiopericytoma.

Immunohistochemical analysis often reveals strong positivity for the S-100 protein by the cartilaginous component, whereas the cellular component shows positivity for CD99, vimentin, and Leu7. For diagnostic confirmation, however, immunohistostaining is used only in case of doubt when tumours such as malignant lymphoma, hemangiopericytoma, Ewing sarcoma, and soft-tissue chondroma mimic MCS.

Radical surgical excision with negative margins is the most effective treatment modality for MCS. Vision and globe salvaging resection is possible in cases of extraskeletal orbital MCS.

In our case, MCS being intraocular, enucleation was the only option for complete surgical removal, though it was done for a suspected diagnosis of retinoblastoma. Role of radiotherapy or chemotherapy in the management of MCS is limited for cases with incomplete removal or histologically aggressive tumour.

To the best of our knowledge, this is the first case to report intraocular MCS in the human eye. The presentation of intraocular MCS can mimic retinoblastoma. Imaging studies are of little use in differentiating intraocular MCS from retinoblastoma due to common imaging features. Being a malignant tumour with risk of distant metastasis, enucleation is the best treatment modality for intraocular MCS. Diagnostic confirmation is possible only after histopathological study of enucleated specimen.

https://www.canadianjournalofophthalmology.ca/article/S0008-4182(19)30546-0/fulltext

Journal : CJO

Ref : Mesenchymal chondrosarcoma Ocular Oncolgy RB Retinoblastoma