Impression cytology using celiulose acetate paper has been used in various ocular surface disorde... more Impression cytology using celiulose acetate paper has been used in various ocular surface disorders as a simple non-invasive diagnostic test. To assess its value in differentiating melanocytic tumours, 24 patients with a range of pigmented lesions of the conjunctiva were examined using this technique. Cytological and histological diagnoses were compared in 23 cases. In 73% of cases impression cytology predicted the histological diagnosis by detec- tion of superficial atypical melanocytes and Institute of their proportion relative to benign epithelial Ophthalmology, cells. This pilot study shows impression Department of Pathology cytology to be a useful diagnostic aid in the A D A Paridaens differentiation of pigmented tumours of the A C E McCartney bulbar conjunctiva. St Bartholomew's Hospital, Department of Cytology o M Curling The management of pigmented lesions of the conjunctiva depends on the ability to distinguish Ophthalmology between benign, premalignant, and frankly J L Hungerford malignant conditions. Conjunctival malignant melanoma is uncommon but potentially lethal. Moorfields Eye Hospital, Most conjunctival melanomas arise in associa-
Uveal Melanoma (UM) micro-metastases can be present prior to diagnosis and relapse after treatmen... more Uveal Melanoma (UM) micro-metastases can be present prior to diagnosis and relapse after treatment. Earlier detection resulted in an increased incidence of small (T1 and T2) tumors allowing for novel eyepreserving treatment strategies, but reducing available tumor tissue needed for prognostic genomic pro ling. Thus, creating the need for minimal-invasive detection and novel prognostication methods. We determined whether tumor presence can be con rmed using metabolite patterns in blood plasma and evaluated if these patterns differ between high risk (BRCA1-associated protein-1, BAP1), intermediate risk (Splicing Factor 3b Subunit 1, SF3B1) and low risk (Eukaryotic Translation Initiation Factor 1A X-Linked, EIF1AX) mutated tumors. In this retrospective observational study, samples of UM-patients in a discovery (n = 53) and replication (n = 42) set were compared to unaffected control-participants (n = 46) as well as across mutation-based subgroups. Peripheral blood plasma was collected prior to treatment. Metabolite pro les of patients and control-participants were generated as mass/charge (m/z) features using ultra-high performance liquid chromatography mass-spectrometry. After normalization, discriminatory feature patterns were determined using a random forest classi er and a leave-one-out cross-validation procedure. We detected differential metabolic patterns between UM-patients and control-participants with a sensitivity of 0.95 and 0.90 and a speci city of 0.98 and 0.98 in the positive and negative ion modes, respectively. Overall, the performance of the model for classifying the subgroups was insu cient in both the positive (merged dataset F1 scores: BAP1: 0.64, SF3B1: 0.37, and EIF1AX: 0.35) and negative (merged dataset F1 scores: BAP1: 0.60, SF3B1: 0.32, and EIF1AX: 0.36) ion modes, respectively. Pathway analysis using annotated metabolites indicated upregulation of tRNA charging, and glycine usage for the creatine biosynthesis. Purine ribonucleosides degradation and the super pathway of citrulline metabolism were downregulated in UM-patients. An increased salvage of bases or decreased purine degradation could indicate a higher energy consumption. Minimally-invasive metabolomics has the potential to allow for minimally invasive screening as it distinguishes metabolite patterns, that are putatively associated with oncogenic processes, in peripheral blood derived plasma of UM-patients from control-participants at the time of diagnosis.
A 39-year-old Caucasian woman with a history of recurrent conjunctival melanoma of her right eye ... more A 39-year-old Caucasian woman with a history of recurrent conjunctival melanoma of her right eye developed an intrastromal heavily pigmented malignant melanoma, which involved the whole corneal diameter. The patient was treated by corneoscleral lamellar keratoplasty and there has been no evidence of recurrent neoplasm during 4 years of foliow- up. This apparently unique presentation of malignant melanoma ofthe cornea is illustrated and the differential diagnosis of corneal pigmentation is discussed. Malignant melanoma of the cornea is very uncommon. Though primary corneal melanoma has been reported'"5 this neoplasm is usually seen in association with an adjacent limbal or con- junctival melanocytic lesion. We describe a patient with a history of recurrent conjunctival melanoma who presented with a black cornea due to extensive malignant melanocytic invasion into corneal stroma.
Background/aims: Adult xanthogranulomatous disease involving the ocular tissues is rare and poorl... more Background/aims: Adult xanthogranulomatous disease involving the ocular tissues is rare and poorly understood. Adult onset xanthogranuloma (AOX), adult onset asthma and periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX), and Erdheim-Chester disease (ECD) are the four syndromes within this disorder, which is diagnosed by characteristic histopathology. Experience with eight cases prompted a multi-institutional effort to study the histopathology, immunohistochemistry, clinical findings, and systemic associations in this disorder. Methods: 22 cases, including histopathological slides, were compiled. Published reports were identified by an English language Medline search (1966-2005) and review of reference citations. Each case in this series and the literature was classified as one of four syndromes and then analysed for age onset, sex, skin xanthoma, orbital location, immune dysfunction, internal organ and bone lesions, treatment, and outcome. The histopathology in each of these cases was reviewed by two pathologists. Immunhistochemical stains (CD3, CD4, CD8, L26) were performed in 14 cases where unstained slides were available. Results: 137 cases were compiled. There was no sex or age difference between syndromes. AOX, AAPOX, NBX affect the anterior orbit, ECD tends to be diffuse and intraconal. Skin lesions are found in all the syndromes. Immune dysfunction was noted in all cases of AAPOX and NBX; 11% of NBX and all ECD patients had internal organ disease. Treatment included surgery, corticosteroids, other chemotherapeutic agents, radiotherapy, and combinations of these. No AOX or AAPOX deaths occurred; 66% of ECD patients died. All 22 cases had xanthoma cells; most had Touton giant cells. Lymphocytes were present in all cases and occurred as aggregates (mostly in AAPOX) or diffuse populations mixed with fibroblasts (mostly in ECD). Immunohistochemistry revealed the majority of these to be CD8+. Necrosis was most marked in NBX. Conclusion: Adult xanthogranuloma of the orbit is rare, making prospective evaluation or meta-analysis impossible. The best treatment is unknown but seems to be with multiagent chemotherapy guided by histopathological, immunohistochemical, and systemic findings.
Using a silver staining technique, argyrophilic nucleolar organiser region-associated proteins (A... more Using a silver staining technique, argyrophilic nucleolar organiser region-associated proteins (AgNORs) have been studied in routinely processed paraffin sections of 46 invasive malignant melanomas (MM) of the conjunctiva. The aim of this retrospective study was to assess the value of the AgNOR method as a prognostic indicator for this neoplasm. The 46 cases were divided into two groups: (A) 14 cases of MM that metastasised and caused death of the patient within 5 years of (histological) diagnosis, and (B) 32 cases of MM that did not metastasise and in which patients survived beyond 5 years. The mean of the AgNOR counts per nucleus was 7 03 (95% CI: 5.81-8.24) in group A, and 7*15 (95% CI: 6-53- 7.77) in group B. A comparison using a multi- factor analysis of variance (ANOVA) model, which corrected for possible confounding effect of tumour thickness, site, and cell type showed no significant difference in AgNOR counts between groups A and B (p=0.8). Analysis by the Cox proportional hazards regression model showed that survival was not influenced significantly by the mean AgNOR number (hazard ratio: 0.92). Whereas the AgNOR technique may be used to distinguish benign from malignant melanocytic lesions of the conjunctiva, we conclude it has no value in predicting the outcome for patients with conjunctival MM.
In a group of 15 women with conjunctival malignant melanoma six cases (40%) were shown to have oe... more In a group of 15 women with conjunctival malignant melanoma six cases (40%) were shown to have oestrogen receptor positivity using a monoclonal antibody to oestrogen receptor related antigen (ER-D5, Amersham RPN.710) on formalin fixed, paraffin wax sections. Receptors were also present in the epithelium of these six cases but not in controls and cases without ER-D5 positivity in their tumours. A subset of these aggressive, intractable unilateral tumours may therefore be amenable to hormone treat- ment.
In our experience 5% of invasive malignant melanomas of the conjunctiva arising from areas ofprim... more In our experience 5% of invasive malignant melanomas of the conjunctiva arising from areas ofprimary acquired melanosis with atypia spread to the ipsilateral nasal cavity and paranasal sinuses. Twenty one years after orbital exenteration for multicentric conjunctival melanoma an 82-year-old man was seen with an orbital recurrence, which had extended to the nasal cavity and paranasal sinuses through the nasolacrimal duct without invading the mucosa. This previously undescribed way of spread after the longest symptom-free interval following exenteration ever reported is illus- trated.
Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma... more Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma of the conjunctiva in association with 'acquired melanosis sine pigmento' are reported. The absence ofconjunctival pigmentation in this extremely rare combination of lesions prevented early diagnosis and clinical monitoring. As a result orbital exenteration was required in three cases. This multicentric non-pigmented variety of conjunctival malig- nant melanoma tends to present later than pigmented forms and may require exenteration of the orbit as a primary procedure. ing in amelanotic acquired melanosis of the conjunctiva.' Griffith et all referred to the amelanotic precursor as 'acquired melanosis sine pigmento'. Jackobiec et all encountered a further four cases of multifocal conjunctival melanoma in association with amelanotic PAM, but did not mention the degree ofpigmentation of the malignant melanomas. We studied the clinical and histopathological features of four cases of multifocal amelanotic conjunctival melanoma arising in association with acquired melanosis sine pigmento.
The role of orbital exenteration in the manage- ment of malignant melanoma of the conjunctiva has... more The role of orbital exenteration in the manage- ment of malignant melanoma of the conjunctiva has been underexplored. The outcome in 95 patients with this condition, who underwent exenteration as a primary treatment (n=36) or after failure of other treatment (n=59) for early to advanced stages of the disease, was evalu- ated. The majority of treated cases had multi- centric melanomas sited at prognosticaily unfavourable locations. In the group of tumours with a maximum thickness of 10 mm no melanoma related mortality was noted. Melanomas thicker than 1-0 mm were associated with a mortality varying between 33% and 50%, independent of whether exenteration was performed as primary or secondary treatment. An especially poor outcome was noted for the group of caruncular melanomas despite exenteration. These findings indicate that total eradication of tumour should be performed at an early stage. For this purpose, a combination of debulking surgery and adjunctive cryo- therapy or ,3 radiotherapy is more appropriate than orbital exenteration which causes dis- figurement and blindness. Exenteration of the orbit should be reserved as a palliative pro- cedure for advanced stages of neoplastic disease.
medRxiv (Cold Spring Harbor Laboratory), Sep 23, 2022
Chromosome 8q gain is associated with poor prognosis. Here, we show that the predictive value of ... more Chromosome 8q gain is associated with poor prognosis. Here, we show that the predictive value of chromosome 8q gain depends on the mutation status and is true for BAP1 but not for SF3B1-mutated tumors.
Purpose Retrospective analysis of the effect of retrobulbar irradiation on exophthalmos, ductions... more Purpose Retrospective analysis of the effect of retrobulbar irradiation on exophthalmos, ductions and soft tissue signs in patients with Graves' ophthalmopathy. Methods We analysed the charts of 111 consecutive patients who were treated with retrobulbar irradiation according to standardised intake criteria between 1992 and 1997. After exclusion of patients who underwent other treatment (with steroids or orbital decompression) shortly before or within 6 months after irradiation, and on whom insufficient data were available, 90 patients were included. For these 90 patients, we analysed the exophthalmometry, ductions, soft tissue signs and visual acuity shortly before irradiation and after 3 and 6 months, respectively. In the whole group, the Hertel value was on average 22 mm (SO 2.9) both before irradiation and after 3 and 6 months of follow up. Separate analysis of data on 25 patients with bilateral exophthalmos of more than 24 mm also revealed no change in exophthalmos at follow up. In the whole group, both abduction and elevation had improved by about 1° (SO 6.6°; P = 0.05) after 3 months. This improvement has little clinical significance. In a subgroup of 14 patients who showed more than 10° of restricted eye motility in one or more directions, both abduction and elevation had increased by about 4° (SO 10°; P = 0.02) at 3 and 6 months follow-up. Soft tissue signs had improved at 6 months after irradiation. We found no change in visual acuity after irradiation. ophthalmopathy does not seem to reduce exophthalmos. It probably improves eye motility in patients with severe restrictions. The late improvement in soft tissue signs may either be a late effect of irradiation or be related to the natural history of the disease.
Uveal melanomas (UM) are detected earlier. Consequently, tumors are smaller, allowing for novel e... more Uveal melanomas (UM) are detected earlier. Consequently, tumors are smaller, allowing for novel eye-preserving treatments. This reduces tumor tissue available for genomic profiling. Additionally, these small tumors can be hard to differentiate from nevi, creating the need for minimally invasive detection and prognostication. Metabolites show promise as minimally invasive detection by resembling the biological phenotype. In this pilot study, we determined metabolite patterns in the peripheral blood of UM patients (n = 113) and controls (n = 46) using untargeted metabolomics. Using a random forest classifier (RFC) and leave-one-out cross-validation, we confirmed discriminatory metabolite patterns in UM patients compared to controls with an area under the curve of the receiver operating characteristic of 0.99 in both positive and negative ion modes. The RFC and leave-one-out cross-validation did not reveal discriminatory metabolite patterns in high-risk versus low-risk of metastasizing...
IntroductionAnterior levator disinsertion/reinsertion and Müllerectomy (ALDM) is generally perfor... more IntroductionAnterior levator disinsertion/reinsertion and Müllerectomy (ALDM) is generally performed to correct upper eyelid retraction in patients with Graves’ orbitopathy (GO). We studied the outcome of this procedure and its correlation with clinical parameters.Patients and MethodsRetrospective analysis of results of ALDM in 305 consecutive euthyroid patients with burnt‐out GO treated in our hospital between 1 January 2000 and 1 January 2016. From the patient files, we recorded data on age, gender, laterality of surgery, smoking history and previous interventions. For outcome analysis, we used a qualitative scoring system with subdivision into three categories (good (MRD‐1 of 4–5 mm, smooth upper eyelid contour and left‐right difference of < 1 mm); acceptable (MRD‐1 of 3–<4 or> 5–6 mm), smooth upper eyelid contour and left‐right difference of < 2 mm; poor: if none of the above criteria was met). We analysed the outcome per eyelid as well as per patient.ResultsOf the 3...
Ophthalmic Plastic and Reconstructive Surgery, 2018
with congenital ptosis and Marcus Gunn jaw-winking synkinesis and cannot draw any conclusions abo... more with congenital ptosis and Marcus Gunn jaw-winking synkinesis and cannot draw any conclusions about this. Our patients come from a variety of sources, but very few come from school screening programs. Most are referred to us by other ophthalmologists or optometrists. The original referral would typically be from a general practitioner or optometrist. For patients with Marcus Gunn jaw-winking synkinesis without ptosis, in our group of 4 patients, 1 was a patient presenting with bilateral involutional changes as an older adult without a history of ptosis, and with a jaw wink on examination. One adolescent had obvious jaw winking and ptosis on the left and a jaw wink in the absence of ptosis on the right. He had attended because of the symptoms on the left side. The final 2 patients were referred for abnormal eyelid movements when feeding and chewing from a general practitioner and pediatric ophthalmologist, respectively. Marcus Gunn jaw-winking synkinesis is often noted very early in life when parents observe the affected eyelid flickering with feeding. Eyelid flickering apparent with eating or jaw movement will usually prompt patients to seek attention, hence few cases of Marcus Gunn jaw-winking synkinesis would be expected to be detected in older patients unaware of the jaw wink. However, with routine testing for aberrant eyelid movements in patients with congenital ptosis, a jaw wink will occasionally be detected in someone who is unaware of it.
Purpose: To describe a posterior lamella-sparing technique to resect nodular basal cell carcinoma... more Purpose: To describe a posterior lamella-sparing technique to resect nodular basal cell carcinoma involving the inferior part of the tarsal skin of the lower eyelid. Surgical Technique: Excision of nodular basal cell carcinoma of the tarsal skin using a grey-linesplitting technique with preservation of the posterior lamella. Specimen was sent for frozen section control. Additional excision was performed in caseof irradicality. The defect was closed with a free skin graft from the ipsi-or contralateral upper eyelid. Results: We show a case series of three patients with lower eyelid basal cell carcinoma and investigated radicality on histology, aesthetic outcome and clinical recurrence during a follow-up of 18 months. Pre, intra, and postoperative photographs were obtained. In all cases radicality was reached. In all patients, the skin graft was viable, with no recurrence after 18 months. Excellent aesthetic results were obtained. Conclusion: Anterior lamellar resection of nodular basal cell carcinomas involving the tarsal lower eyelid skin using a grey line lid-splitting technique is a simple and one-step technique with good clinical outcome. It may avoid the morbidity associated with full thickness eyelid resection and might be useful for other, nonmalignant eyelid lesions.
Impression cytology using celiulose acetate paper has been used in various ocular surface disorde... more Impression cytology using celiulose acetate paper has been used in various ocular surface disorders as a simple non-invasive diagnostic test. To assess its value in differentiating melanocytic tumours, 24 patients with a range of pigmented lesions of the conjunctiva were examined using this technique. Cytological and histological diagnoses were compared in 23 cases. In 73% of cases impression cytology predicted the histological diagnosis by detec- tion of superficial atypical melanocytes and Institute of their proportion relative to benign epithelial Ophthalmology, cells. This pilot study shows impression Department of Pathology cytology to be a useful diagnostic aid in the A D A Paridaens differentiation of pigmented tumours of the A C E McCartney bulbar conjunctiva. St Bartholomew's Hospital, Department of Cytology o M Curling The management of pigmented lesions of the conjunctiva depends on the ability to distinguish Ophthalmology between benign, premalignant, and frankly J L Hungerford malignant conditions. Conjunctival malignant melanoma is uncommon but potentially lethal. Moorfields Eye Hospital, Most conjunctival melanomas arise in associa-
Uveal Melanoma (UM) micro-metastases can be present prior to diagnosis and relapse after treatmen... more Uveal Melanoma (UM) micro-metastases can be present prior to diagnosis and relapse after treatment. Earlier detection resulted in an increased incidence of small (T1 and T2) tumors allowing for novel eyepreserving treatment strategies, but reducing available tumor tissue needed for prognostic genomic pro ling. Thus, creating the need for minimal-invasive detection and novel prognostication methods. We determined whether tumor presence can be con rmed using metabolite patterns in blood plasma and evaluated if these patterns differ between high risk (BRCA1-associated protein-1, BAP1), intermediate risk (Splicing Factor 3b Subunit 1, SF3B1) and low risk (Eukaryotic Translation Initiation Factor 1A X-Linked, EIF1AX) mutated tumors. In this retrospective observational study, samples of UM-patients in a discovery (n = 53) and replication (n = 42) set were compared to unaffected control-participants (n = 46) as well as across mutation-based subgroups. Peripheral blood plasma was collected prior to treatment. Metabolite pro les of patients and control-participants were generated as mass/charge (m/z) features using ultra-high performance liquid chromatography mass-spectrometry. After normalization, discriminatory feature patterns were determined using a random forest classi er and a leave-one-out cross-validation procedure. We detected differential metabolic patterns between UM-patients and control-participants with a sensitivity of 0.95 and 0.90 and a speci city of 0.98 and 0.98 in the positive and negative ion modes, respectively. Overall, the performance of the model for classifying the subgroups was insu cient in both the positive (merged dataset F1 scores: BAP1: 0.64, SF3B1: 0.37, and EIF1AX: 0.35) and negative (merged dataset F1 scores: BAP1: 0.60, SF3B1: 0.32, and EIF1AX: 0.36) ion modes, respectively. Pathway analysis using annotated metabolites indicated upregulation of tRNA charging, and glycine usage for the creatine biosynthesis. Purine ribonucleosides degradation and the super pathway of citrulline metabolism were downregulated in UM-patients. An increased salvage of bases or decreased purine degradation could indicate a higher energy consumption. Minimally-invasive metabolomics has the potential to allow for minimally invasive screening as it distinguishes metabolite patterns, that are putatively associated with oncogenic processes, in peripheral blood derived plasma of UM-patients from control-participants at the time of diagnosis.
A 39-year-old Caucasian woman with a history of recurrent conjunctival melanoma of her right eye ... more A 39-year-old Caucasian woman with a history of recurrent conjunctival melanoma of her right eye developed an intrastromal heavily pigmented malignant melanoma, which involved the whole corneal diameter. The patient was treated by corneoscleral lamellar keratoplasty and there has been no evidence of recurrent neoplasm during 4 years of foliow- up. This apparently unique presentation of malignant melanoma ofthe cornea is illustrated and the differential diagnosis of corneal pigmentation is discussed. Malignant melanoma of the cornea is very uncommon. Though primary corneal melanoma has been reported'"5 this neoplasm is usually seen in association with an adjacent limbal or con- junctival melanocytic lesion. We describe a patient with a history of recurrent conjunctival melanoma who presented with a black cornea due to extensive malignant melanocytic invasion into corneal stroma.
Background/aims: Adult xanthogranulomatous disease involving the ocular tissues is rare and poorl... more Background/aims: Adult xanthogranulomatous disease involving the ocular tissues is rare and poorly understood. Adult onset xanthogranuloma (AOX), adult onset asthma and periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX), and Erdheim-Chester disease (ECD) are the four syndromes within this disorder, which is diagnosed by characteristic histopathology. Experience with eight cases prompted a multi-institutional effort to study the histopathology, immunohistochemistry, clinical findings, and systemic associations in this disorder. Methods: 22 cases, including histopathological slides, were compiled. Published reports were identified by an English language Medline search (1966-2005) and review of reference citations. Each case in this series and the literature was classified as one of four syndromes and then analysed for age onset, sex, skin xanthoma, orbital location, immune dysfunction, internal organ and bone lesions, treatment, and outcome. The histopathology in each of these cases was reviewed by two pathologists. Immunhistochemical stains (CD3, CD4, CD8, L26) were performed in 14 cases where unstained slides were available. Results: 137 cases were compiled. There was no sex or age difference between syndromes. AOX, AAPOX, NBX affect the anterior orbit, ECD tends to be diffuse and intraconal. Skin lesions are found in all the syndromes. Immune dysfunction was noted in all cases of AAPOX and NBX; 11% of NBX and all ECD patients had internal organ disease. Treatment included surgery, corticosteroids, other chemotherapeutic agents, radiotherapy, and combinations of these. No AOX or AAPOX deaths occurred; 66% of ECD patients died. All 22 cases had xanthoma cells; most had Touton giant cells. Lymphocytes were present in all cases and occurred as aggregates (mostly in AAPOX) or diffuse populations mixed with fibroblasts (mostly in ECD). Immunohistochemistry revealed the majority of these to be CD8+. Necrosis was most marked in NBX. Conclusion: Adult xanthogranuloma of the orbit is rare, making prospective evaluation or meta-analysis impossible. The best treatment is unknown but seems to be with multiagent chemotherapy guided by histopathological, immunohistochemical, and systemic findings.
Using a silver staining technique, argyrophilic nucleolar organiser region-associated proteins (A... more Using a silver staining technique, argyrophilic nucleolar organiser region-associated proteins (AgNORs) have been studied in routinely processed paraffin sections of 46 invasive malignant melanomas (MM) of the conjunctiva. The aim of this retrospective study was to assess the value of the AgNOR method as a prognostic indicator for this neoplasm. The 46 cases were divided into two groups: (A) 14 cases of MM that metastasised and caused death of the patient within 5 years of (histological) diagnosis, and (B) 32 cases of MM that did not metastasise and in which patients survived beyond 5 years. The mean of the AgNOR counts per nucleus was 7 03 (95% CI: 5.81-8.24) in group A, and 7*15 (95% CI: 6-53- 7.77) in group B. A comparison using a multi- factor analysis of variance (ANOVA) model, which corrected for possible confounding effect of tumour thickness, site, and cell type showed no significant difference in AgNOR counts between groups A and B (p=0.8). Analysis by the Cox proportional hazards regression model showed that survival was not influenced significantly by the mean AgNOR number (hazard ratio: 0.92). Whereas the AgNOR technique may be used to distinguish benign from malignant melanocytic lesions of the conjunctiva, we conclude it has no value in predicting the outcome for patients with conjunctival MM.
In a group of 15 women with conjunctival malignant melanoma six cases (40%) were shown to have oe... more In a group of 15 women with conjunctival malignant melanoma six cases (40%) were shown to have oestrogen receptor positivity using a monoclonal antibody to oestrogen receptor related antigen (ER-D5, Amersham RPN.710) on formalin fixed, paraffin wax sections. Receptors were also present in the epithelium of these six cases but not in controls and cases without ER-D5 positivity in their tumours. A subset of these aggressive, intractable unilateral tumours may therefore be amenable to hormone treat- ment.
In our experience 5% of invasive malignant melanomas of the conjunctiva arising from areas ofprim... more In our experience 5% of invasive malignant melanomas of the conjunctiva arising from areas ofprimary acquired melanosis with atypia spread to the ipsilateral nasal cavity and paranasal sinuses. Twenty one years after orbital exenteration for multicentric conjunctival melanoma an 82-year-old man was seen with an orbital recurrence, which had extended to the nasal cavity and paranasal sinuses through the nasolacrimal duct without invading the mucosa. This previously undescribed way of spread after the longest symptom-free interval following exenteration ever reported is illus- trated.
Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma... more Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma of the conjunctiva in association with 'acquired melanosis sine pigmento' are reported. The absence ofconjunctival pigmentation in this extremely rare combination of lesions prevented early diagnosis and clinical monitoring. As a result orbital exenteration was required in three cases. This multicentric non-pigmented variety of conjunctival malig- nant melanoma tends to present later than pigmented forms and may require exenteration of the orbit as a primary procedure. ing in amelanotic acquired melanosis of the conjunctiva.' Griffith et all referred to the amelanotic precursor as 'acquired melanosis sine pigmento'. Jackobiec et all encountered a further four cases of multifocal conjunctival melanoma in association with amelanotic PAM, but did not mention the degree ofpigmentation of the malignant melanomas. We studied the clinical and histopathological features of four cases of multifocal amelanotic conjunctival melanoma arising in association with acquired melanosis sine pigmento.
The role of orbital exenteration in the manage- ment of malignant melanoma of the conjunctiva has... more The role of orbital exenteration in the manage- ment of malignant melanoma of the conjunctiva has been underexplored. The outcome in 95 patients with this condition, who underwent exenteration as a primary treatment (n=36) or after failure of other treatment (n=59) for early to advanced stages of the disease, was evalu- ated. The majority of treated cases had multi- centric melanomas sited at prognosticaily unfavourable locations. In the group of tumours with a maximum thickness of 10 mm no melanoma related mortality was noted. Melanomas thicker than 1-0 mm were associated with a mortality varying between 33% and 50%, independent of whether exenteration was performed as primary or secondary treatment. An especially poor outcome was noted for the group of caruncular melanomas despite exenteration. These findings indicate that total eradication of tumour should be performed at an early stage. For this purpose, a combination of debulking surgery and adjunctive cryo- therapy or ,3 radiotherapy is more appropriate than orbital exenteration which causes dis- figurement and blindness. Exenteration of the orbit should be reserved as a palliative pro- cedure for advanced stages of neoplastic disease.
medRxiv (Cold Spring Harbor Laboratory), Sep 23, 2022
Chromosome 8q gain is associated with poor prognosis. Here, we show that the predictive value of ... more Chromosome 8q gain is associated with poor prognosis. Here, we show that the predictive value of chromosome 8q gain depends on the mutation status and is true for BAP1 but not for SF3B1-mutated tumors.
Purpose Retrospective analysis of the effect of retrobulbar irradiation on exophthalmos, ductions... more Purpose Retrospective analysis of the effect of retrobulbar irradiation on exophthalmos, ductions and soft tissue signs in patients with Graves' ophthalmopathy. Methods We analysed the charts of 111 consecutive patients who were treated with retrobulbar irradiation according to standardised intake criteria between 1992 and 1997. After exclusion of patients who underwent other treatment (with steroids or orbital decompression) shortly before or within 6 months after irradiation, and on whom insufficient data were available, 90 patients were included. For these 90 patients, we analysed the exophthalmometry, ductions, soft tissue signs and visual acuity shortly before irradiation and after 3 and 6 months, respectively. In the whole group, the Hertel value was on average 22 mm (SO 2.9) both before irradiation and after 3 and 6 months of follow up. Separate analysis of data on 25 patients with bilateral exophthalmos of more than 24 mm also revealed no change in exophthalmos at follow up. In the whole group, both abduction and elevation had improved by about 1° (SO 6.6°; P = 0.05) after 3 months. This improvement has little clinical significance. In a subgroup of 14 patients who showed more than 10° of restricted eye motility in one or more directions, both abduction and elevation had increased by about 4° (SO 10°; P = 0.02) at 3 and 6 months follow-up. Soft tissue signs had improved at 6 months after irradiation. We found no change in visual acuity after irradiation. ophthalmopathy does not seem to reduce exophthalmos. It probably improves eye motility in patients with severe restrictions. The late improvement in soft tissue signs may either be a late effect of irradiation or be related to the natural history of the disease.
Uveal melanomas (UM) are detected earlier. Consequently, tumors are smaller, allowing for novel e... more Uveal melanomas (UM) are detected earlier. Consequently, tumors are smaller, allowing for novel eye-preserving treatments. This reduces tumor tissue available for genomic profiling. Additionally, these small tumors can be hard to differentiate from nevi, creating the need for minimally invasive detection and prognostication. Metabolites show promise as minimally invasive detection by resembling the biological phenotype. In this pilot study, we determined metabolite patterns in the peripheral blood of UM patients (n = 113) and controls (n = 46) using untargeted metabolomics. Using a random forest classifier (RFC) and leave-one-out cross-validation, we confirmed discriminatory metabolite patterns in UM patients compared to controls with an area under the curve of the receiver operating characteristic of 0.99 in both positive and negative ion modes. The RFC and leave-one-out cross-validation did not reveal discriminatory metabolite patterns in high-risk versus low-risk of metastasizing...
IntroductionAnterior levator disinsertion/reinsertion and Müllerectomy (ALDM) is generally perfor... more IntroductionAnterior levator disinsertion/reinsertion and Müllerectomy (ALDM) is generally performed to correct upper eyelid retraction in patients with Graves’ orbitopathy (GO). We studied the outcome of this procedure and its correlation with clinical parameters.Patients and MethodsRetrospective analysis of results of ALDM in 305 consecutive euthyroid patients with burnt‐out GO treated in our hospital between 1 January 2000 and 1 January 2016. From the patient files, we recorded data on age, gender, laterality of surgery, smoking history and previous interventions. For outcome analysis, we used a qualitative scoring system with subdivision into three categories (good (MRD‐1 of 4–5 mm, smooth upper eyelid contour and left‐right difference of < 1 mm); acceptable (MRD‐1 of 3–<4 or> 5–6 mm), smooth upper eyelid contour and left‐right difference of < 2 mm; poor: if none of the above criteria was met). We analysed the outcome per eyelid as well as per patient.ResultsOf the 3...
Ophthalmic Plastic and Reconstructive Surgery, 2018
with congenital ptosis and Marcus Gunn jaw-winking synkinesis and cannot draw any conclusions abo... more with congenital ptosis and Marcus Gunn jaw-winking synkinesis and cannot draw any conclusions about this. Our patients come from a variety of sources, but very few come from school screening programs. Most are referred to us by other ophthalmologists or optometrists. The original referral would typically be from a general practitioner or optometrist. For patients with Marcus Gunn jaw-winking synkinesis without ptosis, in our group of 4 patients, 1 was a patient presenting with bilateral involutional changes as an older adult without a history of ptosis, and with a jaw wink on examination. One adolescent had obvious jaw winking and ptosis on the left and a jaw wink in the absence of ptosis on the right. He had attended because of the symptoms on the left side. The final 2 patients were referred for abnormal eyelid movements when feeding and chewing from a general practitioner and pediatric ophthalmologist, respectively. Marcus Gunn jaw-winking synkinesis is often noted very early in life when parents observe the affected eyelid flickering with feeding. Eyelid flickering apparent with eating or jaw movement will usually prompt patients to seek attention, hence few cases of Marcus Gunn jaw-winking synkinesis would be expected to be detected in older patients unaware of the jaw wink. However, with routine testing for aberrant eyelid movements in patients with congenital ptosis, a jaw wink will occasionally be detected in someone who is unaware of it.
Purpose: To describe a posterior lamella-sparing technique to resect nodular basal cell carcinoma... more Purpose: To describe a posterior lamella-sparing technique to resect nodular basal cell carcinoma involving the inferior part of the tarsal skin of the lower eyelid. Surgical Technique: Excision of nodular basal cell carcinoma of the tarsal skin using a grey-linesplitting technique with preservation of the posterior lamella. Specimen was sent for frozen section control. Additional excision was performed in caseof irradicality. The defect was closed with a free skin graft from the ipsi-or contralateral upper eyelid. Results: We show a case series of three patients with lower eyelid basal cell carcinoma and investigated radicality on histology, aesthetic outcome and clinical recurrence during a follow-up of 18 months. Pre, intra, and postoperative photographs were obtained. In all cases radicality was reached. In all patients, the skin graft was viable, with no recurrence after 18 months. Excellent aesthetic results were obtained. Conclusion: Anterior lamellar resection of nodular basal cell carcinomas involving the tarsal lower eyelid skin using a grey line lid-splitting technique is a simple and one-step technique with good clinical outcome. It may avoid the morbidity associated with full thickness eyelid resection and might be useful for other, nonmalignant eyelid lesions.
Uploads
Papers by Dion Paridaens