Clinical and imaging characteristics of orbital leukemic tumors

PURPOSE: To characterize the clinical and imaging features of orbital leukemic tumors in 27 patients seen and treated at St. Jude Children's Research Hospital. METHODS: A retrospective review was performed on the clinical and imaging records of 27 consecutive patients with a diagnosis of orbital leukemic tumors. The following data were extracted from the patients' records: age at diagnosis of orbital leukemic tumors, sex, race, national origin, type of leukemia, temporal relationship of orbital disease to diagnosis of leukemia, survival from diagnosis of orbital leukemic tumor, laterality of the orbital disease, location of the mass within the orbit, imaging features of the mass, chemotherapeutic protocol, treatment with bone marrow transplant, and orbital radiation. RESULTS: The median age at diagnosis of orbital leukemic tumor was 8 years (range, 1-18 years). Nineteen of the 27 patients were male, and 21 patients were born and lived in the United States. Twenty-one patients had acute myeloid leukemia, five had acute lymphoblastic leukemia, and one had chronic myelogenous leukemia. In 85% of patients (n = 23), the diagnosis of leukemia was based on the bone marrow examination findings. Orbital imaging revealed homogenous masses that molded to one or more orbital walls without bony destruction. Nine patients had bilateral orbital involvement. All patients received multiagent systemic chemotherapy, and 14 underwent bone marrow transplantation. Five patients received external beam radiation for the treatment of orbital disease. Fifteen (55.6%) of the 27 patients were alive at the time of the study. The median survival for all patients was 4.75 years (range, 0.1-24 years) after the diagnosis of orbital disease. CONCLUSIONS: Orbital leukemic tumors occur most commonly in the first decade of life, in association with acute myeloid leukemia. They appear as homogenous masses along the orbital walls. Although the overall survival rate for patients with leukemia has improved over the past 3 decades, the mortality of patients who develop orbital leukemic tumors remains high.     

Anterior segment infiltration of acute lymphoblastic leukemia: case report and systematic review

Acute lymphoblastic leukemia (ALL) relapse implies a poor prognosis and demands emergency treatment. Leukemic infiltration of the anterior segment can masquerade as intraocular inflammation; a high index of suspicion for this complication is essential. We describe a case of ocular relapse in a 2-year-old male on maintenance therapy for ALL. A systematic review of all known cases of similar leukemic infiltration of the anterior segment of the eye in ALL was performed. A total of 106 patients in 43 reports described leukemic infiltration of the eye as an initial presentation of ALL or relapse. Ocular relapse may be the first visible manifestation of systemic disease, with concurrent disease in the CNS, bone marrow, or testes. Prognosis for ALL patients with ocular relapse is poor, with death after initial presentation reported as early as 16 days. Patients with a history of ALL presenting with any sign of ocular inflammation should be assessed for relapse and leukemic infiltration. As soon as a diagnosis of relapse has been confirmed, appropriate leukemia therapy should be initiated.     

Anterior chamber infiltration in a patient with Ph+ acute lymphoblastic leukemia in remission with imatinib

PURPOSE: Anterior chamber involvement is unusual in patients with acute lymphoblastic leukemia (ALL) and has never been described in the setting of Ph+ (Philadelphia chromosome-positive) ALL. Moreover, there have been no reports of this complication as a primary relapse in a patient treated with imatinib. DESIGN: Interventional case report. METHODS: A 55-year-old woman with Ph+ ALL in complete remission with imatinib and presenting unilateral anterior uveitis at initial examination was clinically evaluated. Hematologic and ocular studies were performed: blood films, bone marrow smears, and anterior chamber paracentesis with aqueous fluid cytology. RESULTS: Although there was no evidence of leukemia in the blood or bone marrow samples, aqueous fluid cytology identified Ph+ positive lymphoblastic leukemic cells. CONCLUSIONS: The patient had developed anterior chamber infiltration without hematological relapse while treated with imatinib. In our opinion, paracentesis should be performed without delay when uveitis develops in ALL, regardless of systemic relapse.     

Serous retinal detachment as a sign of leukemic choroidopathy: A systematic review

Leukemia is a rare disease associated with a high mortality rate. The presence of unilateral or bilateral serous retinal detachment (SRD) as a sign of choroidal infiltration can be one of the manifestations of acute leukemia, both as a primary sign or in a relapse. We consolidated the literature on SRD as a sign of leukemic choroidopathy regarding its epidemiology, clinical manifestations, and main imaging diagnostic tools. Well-documented cases regarding acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), relapsed ALL and relapsed AML published until September, 2020, in peer reviewed journals were included. The literature shows an interesting range of choroidal infiltration cases assessed by modern imaging techniques, such as optical coherence tomography (OCT) with and without enhanced depth imaging (EDI) and fluorescein angiography (FA). These tools allow choroidal assessment and better understanding and characterization of this rare condition. Complete ophthalmological workup should be performed in these patients using both FA and EDI-OCT to assess the choroidal anatomy and integrity. An increase in choroidal thickness measured with EDI-OCT can reveal active disease and potentially diagnose a leukemic relapse promptly.     

Bilateral Acute Proptosis as Initial Manifestation of Acute Myeloid Leukemia

The myeloid sarcoma is an extramedullary finding of acute myeloid leukemia (AML), and orbital leukemic tumors occur most commonly during the first decade of life. To our knowledge, we report the youngest patient with bilateral proptosis of both eyes as an initial manifestation of AML. This case highlights the need for peripheral blood smear and neuro-image work-up for acute proptosis in infancy. AML should be considered in the differential diagnosis of an orbital mass, even in the absence of typical leukemic symptoms.     

Corneal pseudomembrane from acute inflammatory response and fibrin formation to acute myeloid leukemic infiltrate

PURPOSE: To describe an unusual ocular manifestation of a patient with acute myeloid leukemia (AML). DESIGN: Observational case report. METHODS: A 59-year-old woman with a history of preleukemic myelodysplastic syndrome (MDS) and status post bone marrow transplant (BMT) complained of a sudden onset of poor vision associated with a corneal pseudomembrane. Ocular graft vs host disease was suspected, and the pseudomembrane was excised for histopathologic examination. RESULTS: The pseudomembrane showed myeloblasts admixed with an acute inflammatory response suggestive of the development of AML, a complication of MDS. Bone marrow examination confirmed the diagnosis of relapsing AML. CONCLUSIONS: Acute myeloid leukemia could present as a pseudomembrane; thus, examination of relevant ocular tissue is recommended.     

Ocular findings in leukemia in childhood

Primary and therapy-induced ocular manifestations of leukemia in 25 of 103 children suffering from the disease (60 patients with ALL, eight with AML, two with CML, 33 with NHL) were kept under observation for an average period of five years. The lens was involved in 10%, the retina in 9%, the optic nerve in 7%, and the orbit in 4% of these cases. The present authors' findings concurred with those published in the literature to date, in that they could not find a pathognomonic combination or a specific frequency of ocular symptoms related to one of the four types of leukemia.     

Ophthalmic evaluation of survivors of acute lymphoblastic leukemia

Eighty-two survivors of acute lymphoblastic leukemia (ALL) had prospective eye evaluations to determine the ocular sequelae of the disease and its treatment. All patients had completed or nearly completed a 25- to 31-month protocol which included either 3.4 or 10.2 g of systemic prednisone/m2 per year and cranial irradiation (total 1800-2800 rad). The mean interval from the end of treatment to the eye examination was 32 months. Only one patient had reduced vision attributable to the ALL. Ocular morbidity attributed to the treatment only included posterior subcapsular cataracts (PSCs) which occurred in 52% of patients. Posterior subcapsular cataracts (PSCs) developed in none of the 15 survivors of acute myelogenous leukemia (AML) examined who had received neither long-term systemic prednisone nor irradiation (P = 0.0006). Eyes with PSC had a median visual acuity of 20/20 (range, 20/15-20/50). The authors conclude that the ocular morbidity from antileukemia treatment programs at our institutions is minimal.     

Ophthalmic manifestations of acute leukemia

Orbital and ocular lesions are the third most frequent extramedullar locations of acute leukemia after the meninges and testicles. These lesions are treated as a central nervous system lesion; therefore diagnosis is essential to therapeutic adjustment. We present a retrospective study on charts of children treated for acute leukemia between 1996 and 1998. Ophthalmic examination was carried out when there were ocular symptoms. One hundred ninety-six children were treated for acute leukemia. Twelve children (6.1%) had an ocular and orbital lesion: 7 boys and 5 girls, with an average age of 6 years. Six had acute lymphoblastic leukemia, 6 had acute myeloid leukemia. Visual acuity was 1/10 in 9 children. Four children had an initial orbital lesion with a rapidly progressing exophthalmos. The hemogram and myelogram showed a granulocytic sarcoma. Two children who had been previously treated for acute leukemia presented a bilateral anterior uveitis with hypopyon; anterior chamber paracentesis showed blast cells and confirmed the ocular relapse. A corneal lesion was found in 2 children and in 2 cases, the optic nerve had edema; a decrease in visual acuity was the sign of the optic nerve lesion. Two patients had retinal infiltration with hemorrhages in the posterior pole. Prophylaxis consists of intrathecal injection of methotrexate and reinforcement of chemotherapy. Central nervous system irradiation is seldom used in children. Orbital and ocular lesions carry a poor prognosis according to the majority of authors. Two years after diagnosis of the ocular lesions, only 1 of the children studied remains alive.     

Ophthalmic manifestations of acute and chronic leukemias presenting to a tertiary care center in India

Context:Screening for ocular manifestations of leukemia, although not a routine practice, is important as they may antedate systemic disease or form an isolated focus of its relapse.Aims:This study evaluates the spectrum of ocular manifestations in acute and chronic leukemias presenting to a tertiary care center in India.Results:The study subjects (n = 96) comprised 61 males and 35 females whose age ranged from 18 months to 91 years (mean = 39.73, ±22.1). There were 79 adults and 17 children, 53 new and 43 existing patients, 68 acute and 28 chronic, 61 myeloid and 35 lymphoid patients. Ocular lesions were found in 42 patients (43.8%). The ocular manifestations of leukemia were significantly (P = 0.01467) more frequent in acute 35/68 (51.9%) than chronic 7/28 (25%) leukemias. Primary or direct leukemic infiltration was seen in 8 (8.3%) subjects while secondary or indirect involvement due to anemia, thrombocytopenia, hyperviscosity, total body irradiation, and immunosuppression were seen in 42 (43.8%) subjects. Ocular changes were present in 37/79 (46.8%) adults and 5/17 (29.4%) children (P = 0.09460). Twenty-eight males (28/61) 45.9% and 14/35 (40%) females had ocular manifestations (P = 0.2874). The ocular manifestations were significantly (P = 0.01158) more frequent in myeloid leukemias 32/61 (52.9%) than lymphoid leukemias 10/35 (28.6%).Conclusions:Leukemic ophthalmic lesions were found in 42/96 (43.8%) patients. Ocular involvement is more often seen in adults, acute and myeloid leukemias. All the primary leukemic manifestations were seen in males. A periodic ophthalmic examination should be mandatory for all leukemic patients, as ocular changes are often picked up in asymptomatic patients.AimTo study the spectrum of ocular manifestations in acute and chronic leukemias presenting to a tertiary center in India.     

Leopard spot chorioretinopathy. Initial manifestation of recurrent acute lymphocytic leukemia]

An 11-year-old girl with a history of acute lymphocytic leukemia of the central nervous system had attained complete remission for almost 3 1/2 years after combination chemotherapy and radiotherapy when she developed iritis and chorioretinopathy of the right eye. Neither an anterior chamber tap nor a diagnostic vitrectomy revealed leukemic cells. Both nonspecific anti-inflammatory therapy and antiviral treatment were unsuccessful. Finally, lymphoblasts were detected in the cerebrospinal fluid and in the bone marrow after repeated lumbar puncture and bone marrow aspiration. Combination chemotherapy alone was resumed, resulting in the resolution of all acute ocular symptoms and bone marrow involvement. Only the leopard-spot-like pigmentary fundus changes persisted. The child has now remained in continuous complete remission for 1 1/2 years.     

Ocular manifestations of leukemia. A review

Ophthalmologists are familiar with the commonly observed leukemic retinopathy and orbital infiltration in patients with both acute and chronic leukemia. With the advent of more successful and aggressive chemotherapeutic regimens and more sophisticated radiation therapy, the eye is not uncommonly involved in patients who are in either meningeal or hematological relapse. In rare instances, ophthalmologic involvement may be the only manifestation of recurrence of the leukemic process. In addition, retinal microaneurysms, capillary closure, and neovascularization have been documented in individuals with chronic leukemia. This paper will review leukemic retinopathy and leukemic infiltration of the orbit. In addition, a discussion of the frequency and pathogenesis of the retinal vascular abnormalities will be presented. The clinical picture and treatment of optic nerve, choroid and iris infiltration will be discussed. Unusual ocular manifestations as the presenting sign of leukemia will also be detailed.     

Survey of 1264 patients with orbital tumors and simulating lesions: The 2002 Montgomery Lecture, part 1

OBJECTIVE: To determine the incidence of specific orbital tumors based on patients referred to an ocular oncology center. DESIGN: Retrospective, observational case series. PARTICIPANTS: A total of 1264 consecutive patients referred to an ocular oncology service because of space-occupying orbital lesions. METHODS: A retrospective chart review was carried out for 1264 consecutive patients referred for a suspected orbital mass over a 30-year period. The lesions were grouped into general categories, as shown in "Results." The specific diagnosis in each case was based on clinical findings, computed tomography scan results, magnetic resonance imaging results, and histopathologic analysis results, when available. The number and percentage of benign and malignant tumors per age group also was determined. MAIN OUTCOME MEASURES: The incidence of orbital tumors and pseudotumors. RESULTS: Among 1264 consecutive patients, the number and percentage of lesions in each general category were as follows: cystic, 70 cases (6%); vasculogenic, 213 cases (17%); peripheral nerve lesions, 23 (2%); optic nerve and meningeal tumors, 105 (8%); fibrocytic lesions, 13 (1%); osseous and fibro-osseous tumors, 21 (2%); cartilaginous lesions, 1 (<1%); lipocytic and myxoid lesions, 64 (5%); myogenic tumors, 36 (3%); lacrimal gland lesions, 114 (9%); primary melanocytic lesions, 11 (<1%); metastatic tumors, 91 (7%); lymphoma and leukemia lesions, 130 (10%); secondary orbital tumors, 142 (11%); histiocytic lesions, 17 (1%); thyroid-related orbitopathy, 67 cases (5%); other inflammatory lesions, 133 cases (11%); and miscellaneous other lesions, 13 (1%). The most common diagnoses were: lymphoid tumor (139 cases;11%), idiopathic orbital inflammation (135 cases; 11%), cavernous hemangioma (77 cases; 6%), lymphangioma (54 cases; 4%), meningioma (53 cases; 4%), optic nerve glioma (48 cases; 4%), metastatic breast cancer (44 cases;4%), orbital extension of uveal melanoma (41 cases; 3%), capillary hemangioma (36 cases;3%), rhabdomyosarcoma (35 cases; 3%), dermolipoma (31 cases; 3%), herniated orbital fat (30 cases; 2%), dermoid cyst (26 cases; 2%), varix (26 cases; 2%), dacryops (19 cases; 2%), and other less common lesions. Of the 1264 lesions, 810 (64%) were benign and 454 (36%) were malignant. The percentage of malignant lesions was 20% in children (age range, 0-18 years), 27% in young adults and middle-aged patients (age range, 19-59 years), and 58% in older patents (age range, 60-92 years). Rhabdomyosarcoma was the most common malignancy in children, representing 3% of all orbital masses, and lymphoma was the most common malignancy in older patients, representing 10% of cases. CONCLUSIONS: A variety of tumors and pseudotumors can involve the orbit. In this series of 1264 lesions, 64% were benign and 36% were malignant. The percentage of malignant tumors increased with age, with malignancies being common in older patients because of the higher incidence of lymphoma and metastasis in the elderly.     

Acute megakaryoblastic leukemia in Down syndrome: orbital infiltration

PURPOSE: To describe an uncommon ocular presentation of acute megakaryoblastic leukemia in a child with Down syndrome. METHOD: Case report. Initial manifestation of disease was bilateral proptosis with secondary exposure keratitis caused by leukemic infiltration of the orbits. RESULTS: Bone marrow biopsy and immunophenotyping established the diagnosis of acute megakaryoblastic leukemia (FAB-M7). The leukemia was treated successfully with chemotherapy, with resolution of proptosis. The patient remained in remission more than 1 year after cessation of treatment. CONCLUSIONS: Bilateral proptosis can be a presenting sign of acute megakaryoblastic leukemia, a malignancy associated with Down syndrome.     

Eyelid Myeloid Sarcoma: Ominous Presentation of Acute Myelogenous Leukemia

A 19 year-old African American man presented to our clinic for a second opinion about a right upper eyelid mass which had been recalcitrant to treatment for nonspecific orbital inflammation by an outside facility. Examination for systemic causes of the patients eyelid lesion led to a diagnosis of acute myelogenous leukemia (AML) FAB subtype M1. A subsequent biopsy of the eyelid tumor confirmed the diagnosis of a myeloid sarcoma. The patient succumbed to complications from his leukemia within 13 months of presentation. This case report is the first, to our knowledge, of an eyelid myeloid sarcoma as the presenting sign of AML and demonstrates the poor prognosis of this lesion.     

Changes in the organ of vision in pathological tortuosity and atherosclerotic stenosis of the carotid arteries

Pathological tortuosity of the carotid arteries is a cause of not only cerebral circulatory disorders, but also visual impairments. There are nonspecific and specific signs of circulatory disorders in the anterior ocular segment - bulbar conjunctiva. In pathological tortuosity of the carotid arteries visual impairments are divided into transient, acute, and chronic. Transient impairments include amaurosis fugax, ocular and orbital pains; acute impairments involve ischemic uveitis, acute retinal ischemia, acute ischemic oculopathy, anterior and posterior ischemic optic neuropathy; chronic visual impairments comprise ischemic uveal, chorioidal, retinal, and ocular neuropathy. Noninvasive ultrasound techniques involving carotid duplex scanning and color Doppler mapping of ocular and orbital vessels are the most objective studies of patients with visual impairments in pathological tortuosity of the carotid arteries.     

Ocular involvement in leukemia--a study of 288 cases

Two hundred and eighty-eight newly diagnosed cases of leukemia (164 males and 124 females, 167 adults and 121 children, 245 acute and 43 chronic, 151 myeloid and 137 lymphoid), aged between 6 weeks and 78 years, were examined for eye changes in the oncology wards within 2 days of diagnosis before starting chemotherapy. Ocular lesions were present in 102 patients (35.4%)--retinal vascular changes in 91 (31.6%); infiltration of ocular tissues in 5 (1.7%), and neuro-ophthalmic signs in 6 (2.1%) cases. Some of the patients had more than one ocular lesion in one or both eyes. The eye changes were seen more often in adults (49.1%) than in children (16.5%), and in myeloid leukemia (41.0%) than in lymphoid leukemia (29.2%). Eye symptoms were present in 29 patients (10%) at initial diagnosis. Since ocular lesions were detected in many asymptomatic leukemia patients, eye examination should be included as a part of routine evaluation at initial diagnosis in these patients.     

Cytomegalovirus retinitis in children following bone marrow transplantation

The authors describe three children, aged one, 13 and 24 months, who developed cytomegalovirus (CMV) retinitis seven to 18 months following allogeneic BMT. The underlying disease in two patients was severe combined immunodeficiency disease (SCID) and acute myeloid leukemia (AML) M5 in the third. All three patients developed chronic graft-versus-host-disease (GVHD) and received massive immunosuppressive therapy. The CMV retinitis was treated with ganciclovir. Clinical improvement was observed in the two SCID patients. The AML patient whose acute inflammatory retinitis was controlled, nevertheless developed optic atrophy in both eyes and VEP and ERG responses disappeared. The incidence of cytomegalovirus retinitis in our pediatric population of bone marrow transplant (BMT) recipients in the last three years was higher than expected: 3/85 (3.5%). Alertness to the possibility of intraocular complications is advocated. Early detection of CMV retinitis and intensive treatment with ganciclovir can save vision. It is therefore suggested to perform ocular examinations as part of the routine follow-up of BMT patients, especially in children with profound immune deficiency.     

Ocular relapse in acute myeloid leukemia (M4) with normal bone marrow

A patient with the rare occurrence of ocular relapse of acute myeloid leukemia (AML) M4 while the bone marrow was normal is reported in this paper. A 47-year-old woman with AML was treated with chemotherapy and went successfully into remission. Four months later, she presented with pain, redness, and a mass over the left eye. The ocular relapse involved the subconjunctival space and anterior chamber of the left eye and, presumably, the left lacrimal gland. There were also multiple subcutaneous nodules on both of her forearms. Incisional biopsy from the subconjunctival lesion was performed. Histopathological examination of the specimen showed diffuse blast cell infiltration. Her bone marrow was still in remission. Although exceedingly rare, ocular extramedullary relapse in AML M4 heralds bone marrow recurrence and, despite intensive chemotherapy, the prognosis is dismal. The authors have no financial interests in any of the drugs used in the management of the patient subject in this report.