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[Successful treatment of a periocular lymphoma with radiotherapy].

BACKGROUND: MALT (mucosa associated lymphoma tissues) reveal specific histological specifications, such as cells like B-lymphocytes with circular structure, B-lymphocytes in the epithelium and a region of larger B-lymphocytes, from the centre to the epithelium. The difference between local and systemic infiltration of tissue is important, and hence MALT must be diagnosed via an interdisciplinary approach. PATIENT: A 45-year old female patient presented initially to our institution in December 1997. She complained of swelling and redness of her upper eyelid which had developed during the last 9 months. Additionally, her visual acuity in the involved eye had decreased steadily over the last 6 months. Ophthalmological examination revealed a swollen right upper eyelid associated with bilateral salmon-coloured conjunctival lesions of the inferior fornices. Additionally, there was a serous detachment of the neurosensory retina in the peripapillary area of the right eye. Systemic work-up including biopsy of the ocular lesions revealed the presence of a localised B-cell lymphoma of the MALT type. Initial treatment with topical and systemic steroids resulted only in a temporary improvement of signs and symptoms. Another treatment trial with steroids was unsuccessful and radiotherapy was therefore performed. Radiotherapy resulted in a complete remission and no signs of recurrent disease during a follow-up period of 4 years. CONCLUSIONS: In patients with isolated MALT lymphomas of the periocular regions radiation may be a successful treatment modality. Side effects as observed in former radiation procedures can be avoided by state-of-the-art treatment modalities. Treatment with steroids may be associated with merely temporary improvement of signs and symptoms. In these patients an interdisciplinary approach utilizing ophthalmology, internal medicine, pathology and radiology is imperative.

Biopsy↗

[Optical coherence tomography versus ultrasound biomicroscopy of conjunctival and eyelid lesions].

BACKGROUND: The value of ultrasound biomicroscopy in the diagnosis of conjunctival and eyelid lesions is still unknown. METHOD: For the examination of conjunctival and eyelid lesions, we used an anterior segment OCT (4optics, Lübeck) and an ultrasound biomicroscope (Humphrey, Zeiss, Oberkochen) with high frequency transducer (30 MHz). Included in this study were all patients with conjunctival and eyelid lesions, which were consecutively operated on between December 2002 and January 2003. Histological examination of the excised tissue was performed. RESULTS: 38 tumours of 35 patients, aged 8 - 93 years, were examined. 13 tumours were conjunctival lesions and 25 tumours were eyelid lesions. Histological examination displayed the presence of a pterygium (8/38), a seborrhoic keratosis (7/38), a cyst of the eyelid (5/38), a basal cell carcinoma of the eyelid (4/38), a compound naevus of the conjunctiva (4/38), a chalazion (3/38), a primary acquired melanosis (1/38), an actinic keratosis (1/38), a naevus (1/38), a cavernous haemangioma (1/38), a melanoma in situ (1/38), a foreign body (1/38), and an epidermoid cyst (1/38). Using both ultrasound biomicroscopy and optical coherence tomography (OCT) we were able to demonstrate a cystic tumour in the five patients (13 %) with a cyst of the eyelid. With OCT and with ultrasoundbiomicroscopy in all patients with pterygium a slit was found and in patients with compound naevus very small cystic structures were seen, but with OCT the imaging was more reliable. In patients with solid tumours the definite diagnosis could not be differentiated by ultrasound biomicroscopy or OCT alone. Using OCT, assessment of the margins of the tumours (particularly in depth) was impossible or uncertain. CONCLUSION: Compared to ultrasound biomicroscopy OCT is able to show very small cystic structures more distinctly. For assessing the margins of the tumour ultrasound biomicroscopy is the better tool.

Adolescent↗

Follicular conjunctivitis caused by a mantle cell lymphoma.

BACKGROUND: Lymphoma of the conjunctiva as part of a systemic disease is rare. The follicular appearance of the lymphocyte hyperplasia may mimic the clinical picture of infectious or allergic conjunctivitis. We report on a case of marked chronic follicular conjunctivitis, finally diagnosed as mantle cell lymphoma. HISTORY AND SIGNS: A 52-year old male with a history of epiphora for one year, presented with follicular conjunctivitis in both eyes, a nodal mass in the upper right eyelid and nuchal lymphadenopathy. No infectious or allergic aetiology could be found. Conjunctival biopsy revealed a mantle cell lymphoma. Magnetic resonance tomography showed a bilateral spread into the orbital cavity. Other sites of involvement were the epipharynx and the cervical, axillary and paratracheal lymph nodes. THERAPY AND OUTCOME: Chemotherapy with hyper-CVAD (cyclophosphamide, vincristine, doxorubicine, dexamethasone) was initiated. After 4 of 6 cycles, all clinical tumour manifestations had disappeared completely. CONCLUSIONS: Conjunctival lymphoma may clinically resemble follicular conjunctivitis. Conjunctival biopsy may lead to early diagnosis and initiation of therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Lethal Epstein-Barr virus associated NK/T-cell lymphoma with primary manifestation in the conjunctiva.

BACKGROUND: Lethal midline granulomas (LMG) are very rare angiocentric NK/T-cell lymphomas in association with Epstein-Barr virus. LMG are reported mainly in East Asia occurring in immune compromised patients. HISTORY AND SIGNS: A 41-year old male patient presented with a conjunctival swelling of his upper left eyelid. The lesion had increased over a period of 2 months despite topical corticosteroid treatment. Conjunctival biopsy revealed a highly malignant, CD3 + and BCL2 + extranodal T-cell lymphoma with features of an NK/T-cell origin (CD56 +, TIA + TCR-rearrangement: germline). All lymphoma cells were positive for Epstein-Barr virus RNA. The proliferation rate was highly elevated at 100 %. THERAPY AND OUTCOME: Systemic 1 (st) cycle chemotherapy with cyclophosphamide, doxorubicin, vincristin and prednisone resulted in a complete remission of the swelling within 4 days. However, one week later a massive conjunctival tumour reappeared with only partial regression after combined chemo- and radiotherapy. The patient died within a month because of untreatable pancytopenia due to malignant bone marrow infiltration. CONCLUSIONS: LMG is a rare but highly malignant Epstein-Barr virus associated NK/T-cell lymphoma that can occur in healthy, immune competent Caucasians. This is the first reported case of an LMG in an immune-competent Caucasian patient with primary ocular manifestation. The LMG has a high mortality rate despite systemic treatment and can be lethal within a few months or even weeks.

Antineoplastic Combined Chemotherapy Protocols↗

[Bilateral large conjunctival tumours as primary manifestation of sarcoidosis--successful treatment with steroid-depot-injections].

INTRODUCTION: Ocular manifestations of sarcoidosis vary enormously. They include the conjunctiva, lacrimal gland, orbita, intraocular structures and eye-lid, either isolated or combined. We describe a female patient who presented with unusually large, bilateral conjunctival tumours as a primary manifestation of sarcoidosis. PATIENT: A 79-year-old white woman was referred to us for further management of a persisting "conjunctivitis", which had been refractory to treatment with multiple medications. Initial examination disclosed swollen eye-lids and bilateral large hard tumours of the inferior fornix. The obtained brush smear, which was cytopathologically evaluated, revealed epitheloid cells and multinucleate giant cells. After 4 weeks she developed three reddish-brown maculopapular lesions on her face. The subsequent biopsy from the left inferior fornix and the skin showed histopathologically a granulomatous epitheloid cell inflammation without central necrosis and without acid-proof bacilli. Therefore a sarcoidosis was included into the differential diagnosis. The systemic evaluation revealed no other manifestation. At first we tried to reduce the chronically inflammatory tumours with different immunomodulating local treatment forms. Only the repeated intralesional injection of a steroid depot showed a complete disappearance of all conjunctival and skin tumours. CONCLUSION: An isolated bilateral primary manifestation of sarcoidosis with large massive conjunctival tumours is very rare and clinically not typical. The non-invasive, cytopathological examination by means of brush smears offers a new perspective in the fast diagnosis of conjunctival manifestation of sarcoidosis. The tumours respond excellently to the intralesional injection of steroid depots.

Aged↗

[Conjunctival chemosis resistant to therapy].

We saw a 62-year-old male with a conjunctival chemosis, which was resistant to local therapy. Excisional biopsy and histological work-up of the tissue were performed. Additional immunohistochemical staining using the Lyve-1 antibody (specific for lymphatic vascular endothelium) allowed the diagnosis of a lymphangioma of the conjunctiva to be made.

Aged↗

Reconstruction of large orbital exenteration defects after resection of periorbital tumors of advanced stage.

Orbital exenteration is a devastating procedure because of the social impact and psychological stress put upon the patient. Besides cancer ablative surgery, reconstruction after removal of the tumor constitutes a major problem and the final aesthetic result is quite important. Both obliteration of the orbital cavity and continuation of the epithelial lining are required. Free rectus abdominis muscle and musculocutaneous flaps are versatile flaps which both enable filling the cavity and reconstituting the skin defect with a cutaneous portion or with a skin graft. Both free rectus abdominis muscle and musculocutaneous flaps were used for reconstruction of orbital exenteration defects in 19 patients. All suffered partial maxillectomy as well. The flaps provided satisfactory aesthetic results in all patients.

Adult↗

[Detection of human papillomavirus types in tumors and inflammations of the eye].

BACKGROUND: Infections by the human papillomavirus occur in the skin and in the mucosa. They may play a significant role in the neoplastic transformation of cells. At least half of all the epithelial tumours of the ocular surface and the lacrimal drainage system have been shown to be HPV associated. However, in ca. 50% of these tumors only a limited number of mucosal HPV types could be detected by commercially available test systems. This study reports of HPV specific sequences in putatively HPV associated tumorous and inflamed tissues of the eye. MATERIALS AND METHODS: 32 biopsies of 26 patients suffering from chronic hyperplastic lesions of the lid, conjunctiva and lacrimal drainage system were examined using DNA extraction, amplification of HPV specific sequences by nested polymerase chain reaction (PCR), cloning and sequencing of the PCR products. RESULTS: Ten HPV types could be detected in 11 biopsies of 8 patients with papillo-mas, seborrheic and actinic keratosis, dacryocystitis and syringoma. In 5 of 9 histologically verified papillomas HPV 6, 20, 23, DL 332 (HPV 5b-related), DL 284 (HPV 20-related) and NN-AA44 were detected, HPV 5b, 38 and DL 284 in seborrheic keratoses, HPV 36 in actinic keratosis, NN-AA44 und NN-AA45 in dacryocystitis and HPV 20, 23 and DL 332 in syringoma. CONCLUSIONS: The DNA techniques used in this study represent important methods for the detection of HPV types and allow an association of HPV types with defined tumours and inflammations of the eye. In two of the biopsies putatively new HPV types could be identified.

Adolescent↗

[Intraocular invasion of melanoma of the conjunctiva].

BACKGROUND: The treatment of a localised conjunctival melanoma usually requires local excision combined with cryotherapy, brachytherapy and/or local chemotherapy. CASE REPORT: A 71 year old woman suffering from a conjunctival melanoma located at the limbus of her left eye was treated by local excision and cryotherapy. After this therapeutic procedure two recurrences occurred which had been again treated by excision and cryotherapy and finally brachytherapy. Nevertheless, a third recurrent tumor developed and was treated again with deep lamellar sclerectomy and keratectomy. During this procedure the anterior chamber was opened inadvertently in a tiny spot. Some months later an intraocular invasion of the melanoma was diagnosed clinically and the eye had to be enucleated 5 years after the first treatment. Histological examination revealed extended melanoma growth into iris, ciliary body, anterior choroid, and tumor cell seedings in the antertior chamber. CONCLUSIONS: Removing a conjunctival melanoma especially such a tumor growing at the limbus, the surgeon has to pay attention not to open the anterior chamber during sclerectomy and keratectomy. The possibility that prior local surgical excision aided the intraocular extension is discussed.

Aged↗

[Atypical non-Hodgkin's lymphoma of the conjunctiva as an incidental finding in lower lid entropion].

PURPOSE: We want to demonstrate an unusual conjunctival Non-Hodgkin-Lymphoma with bleedings. PATIENT: A 77-year-old female patient presented with an entropion of the left lower eye-lid. Bilaterally reddish, soft tumors showed in the lower fornices with circumscript bleedings. On account of an absolute arrhythmia of the heart the patient has been on a medication of cumarine-derivates since 9 years. Histologically we found underneath the epithelium densely packed lymphocytic cells with small uniform nuclei intermingled with many erythrocytes. The immunohistological investigations revealed a Non-Hodgkin-Lymphoma of B-cell origin. CONCLUSIONS: Bleedings in a conjunctival Non-Hodgkin-Lymphoma can alter the clinical aspect of the tumor. It is necessary to inspect each entropion thoroughly in order to rule out any other pathological lesions.

Aged↗

[Mitomycin C in treatment of conjunctival melanoma and primary acquired melanosis].

BACKGROUND: Since 1995 we have used Mitomycin C additionally in the treatment of conjunctival melanoma and primary acquired melanosis. METHODS: We report on the therapy results of 14 patients suffering from pigmented conjunctival lesions (malignant melanoma 9 and primary acquired melanosis 5). After local excision, cryotherapy or irradiation all patients received one eye drop Mitomycin C (0.02%) four times daily for four to six weeks. RESULTS: We observed regression of the pigmentations in 11 cases after median follow up of 13.1 months. In one patient there was no change. Two cases showed progression with tumefaction. There were no adverse reactions except conjunctival hyperemia during therapy. CONCLUSIONS: Topical administration of Mitomycin C may be useful in the treatment of pigmented conjunctival lesions. Longer follow-up periods are necessary.

Adolescent↗

[Clinical aspects and histopathology of caruncular tumors].

BACKGROUND: Histologically the lacrimal caruncle represents a transition zone between the conjunctiva and the skin containing cutaneous, conjunctival and lacrimal elements. This accounts for a variety of histopathological changes. METHODS: We conducted a retrospective study on the histopathological findings of 65 caruncular lesions which were referred for excisional biopsy between 1974 and 1995 to the Department of Ophthalmology at the University of Heidelberg. The age of the patients ranged from 10-87 years (mean 42 +/- 18.2). RESULTS: Histopathologic diagnoses included 29 (45%) nevi, 15 (23%) papillomas, 7 (11%) chronic inflammatory lesions and 4 (6%) epidermoid cysts. In addition, 4 (6%) semimalignant and malignant tumours were found including one basalioma, one squamous cell carcinoma and two Kaposi-sarcomas. Among the remaining 8% a dermoid cyst, an accessory lacrimal gland with a retention cyst, an epithelial implantation cyst, a teleangiectatic granuloma and an oncocytoma were diagnosed. CONCLUSION: These findings suggest that malignant caruncular lesions are rare, however excisional biopsy appears prudent in order to establish the histological diagnosis.

Adolescent↗

[Solitary extramedullary plasmacytoma of the conjunctiva].

UNLABELLED: Unpigmented tumorous changes of the conjunctiva can frequently be classified as chalazion, basalioma or carcinoma. PATIENT AND METHODS: In a 70 years old diabetic female a 2.5 x 2.5 cm tumor of the lower conjunctival fornix was observed. After complete excision the tumor was examined by histologic routine procedures and immunohistochemically. The patient was irradiated by 40 Gy with the linear accelerator. RESULTS: The monotypical secretion of the heavy chain gamma and the light chain kappa demonstrated a well differentiated extramedullar plasmocytoma. A MALT lymphoma could be excluded by the absence of centrocytoid cells. The bone cytology and histology did not give any evidence for a medullar plasmocytoma. The patient is free from local or diffuse tumor growth since 2 1/2 years. CONCLUSION: Since the worldwide most important ophthalmopathologic statistics of the AFIP from 1984-1989 describes only 1 plasmocytoma out of 2104 tumors of the lids and conjunctiva, the demonstrated case is an important rarity.

Aged↗

[Lymphangioma of the conjunctiva].

A 23-year-old female presented with a yellow-brownish, asymptomatic tumour of the bulbar conjunctiva in her left eye. The lesion had been detected 5 years previously and had grown since then. Prior to presentation there were 2 episodes of intratumoral hemorrhage. Funduscopy revealed tortuous vessels on the left. Complete tumour excision was performed. Histology showed numerous channels lined by a flat endothelium, and inflammatory cells in the fibrous septae. A diagnosis of a conjunctival lymphangioma was established. The tortuosity of the retinal vessels was probably associated by chance or caused by an undetected orbital lymphangioma.

Adult↗

[Differential diagnosis of rapidly growing tumors--granuloma teleangiectaticum sive pyogenicum].

A clinicopathologic study of a granuloma telangiectaticum is reported in 37 year-old-woman. The tumor has a reddish to white colorit. Its rapid growth, within 2 weeks and appearance as well as clinical examination suggested a neoplastic process (squamous cell carcinoma). The patient had no trauma or surgery. The histopathological examination revealed a granuloma telangiectaticum. Local excision was curative.

Adult↗

[Differential diagnosis and prognosis of 112 excised epibulbar epithelial tumors].

BACKGROUND: Epithelial tumors of the epibulbar conjunctiva are rare in northern Europe. There are no reliable clinical criteria to predict the histological nature of the lesion. Even histologically proven malignant tumors typically do not show ocular invasion or metastasis. PATIENTS AND METHODS: From 1980 to 1993, 112 epithelial epibulbar tumors were classified in our ophthalmopathological laboratory. Surgical management of 50 papillomas (mean age 46 +/- 18 years, 58% males), 49 conjunctival/corneal intraepithelial neoplasias (CIN) (28 mild, 21 severe) and 12 squamous cell carcinomas (mean age 63 +/- 13 years, 69% males) included excisional biopsy (61%), with additional lamellar keratectomy (14%), epithelial abrasion (10%), cauterisation (3%), cryotherapy (2%), excimer laser ablation (2%). Other management regimes were lamellar keratoplasty (2%), penetrating keratoplasty (2%), epithelial abrasion (2%). One eye with intraocular invasion of a mucoepidermoid carcinoma was enucleated. RESULTS: Fifty five per cent of the papillomas were located at the caruncle or semilunar fold. Seventy eight percent of the papillomas had a pedunculated appearance. Two lesions involved the epibulbar conjunctiva as well as the opposite tarsal conjunctiva ("kissing papilloma"). Eighty eight percent of CIN/carcinoma were located at the limbus. The clinical differential diagnoses of CIN/carcinoma were squamous cell carcinoma (26%), papilloma (18%), leukoplakia (10%), pinguecula/pterygium (10%), dysplasia (8%), malignant melanoma (5%), trachoma (3%), chronic keratoconjunctivitis with corneal pannus (2%), "granuloma" (2%), non-pigmented naevus (2%). After a mean follow-up of 6.3 +/- 3.5 years, 13% of the papillomas showed a local recurrence. After a mean follow-up of 4.8 +/- 3.7 years, there were 30% local recurrences of CIN/carcinoma (50% each in severe CIN and carcinoma, 9% in mild CIN). But there was no recurrence of CIN/carcinoma in patients who had received a complete tumor resection initially. If the surgical margins were involved, there was a 64% recurrence rate (80% each in severe CIN and carcinoma). Thirteen per cent of the patients with CIN/carcinoma showed an additional malignant tumor elsewhere in the body. CONCLUSIONS: Local recurrences after excision of CIN/carcinoma did occur only if the surgical margins where involved, and most often within the first year following surgery. Dedifferentiation of epithelial tumors in recurrences was not observed. The diagnosis of CIN/carcinoma of the conjunctiva requires the exclusion of an additional extraocular neoplasia. Histopathological classification and assessment of resection margins of epibulbar tumors is indispensable, especially in view of the more aggressive treatment necessary in mucoepidermoid carcinomas.

Adult↗

[Fabry disease, an ophthalmo-neuro-dermato-cardio-nephrologic problem].

We want to present a 47-years-old patient suffering of a histologically and biochemically confirmed M. Fabry. Besides the ocular findings, we list the systemic findings and discuss the diagnostic and therapeutic possibilities. We especially want to point out the interdisciplinary collaboration in dealing with this condition.

Capillaries↗

[Combined surgery, cryocoagulation and radiotherapy for treatment of melanoma of the conjunctiva].

BACKGROUND: Conjunctival melanomas are malignant tumors with a high local recurrence rate after simple surgical excision. The rate of recurrence is particularly high in cases of large size tumor, of widespread tumors and with PAM associated lesions. Tumor recurrences have a bad long-term prognostic significance and often necessitate exenteration. PATIENTS AND METHODS: A method of therapy combining total surgical excision with proton-beam irradiation, cobalt plaque irradiation and cryotherapy is described. This technique is used in particular unfavorable cases with the aim of lowering the rate of recurrences. It was practiced in 19 cases in Lausanne, 10 of which were recurrent tumors. The melanoma invaded 3 quadrants of the bulbar conjunctiva in 8 cases and 4 quadrants in 11 cases. At least one neighbouring tarsal conjunctiva was invaded in 11 cases and both in 7 cases. The skin of the eyelid was infiltrated in 6 cases and the caruncle in 9 cases. Tumor thickness was 1 to 2 mm in 8 cases, 3 to 4 mm in 4 cases and 5 to 10 mm in 7 cases. RESULTS: PAM was present in 16 cases. Follow-up period was less than 1 year in 2 cases, between 1 to 2 years in 5 cases, between 2 to 3 years in 5 cases and more than 3 years in 7 cases. 5 patients had lymph node metastases, 3 died of metastatic disease and 2 had a local recurrence. One of these recurrences was small-sized and was excised, the other was widespread and the patient died soon with metastatic disease. No exenteration was performed. CONCLUSION: The method of therapy that is here described appears to be a valuable alternative to exenteration of the orbit for the treatment of diffuse or large-size conjunctival melanomas which have a high risk of local recurrence.

Adult↗