Leukemias Clinical Presentation

  • Author: Lihteh Wu, MD; Chief Editor: Hampton Roy Sr, MD   more...
 
Updated: Jan 17, 2012
 

History

  • In most patients, a diagnosis of leukemia has been made before presenting to an ophthalmologist. However, in some patients, ocular symptoms and examination lead to a diagnosis of leukemia.
  • Most patients do not develop symptoms as a result of intraocular involvement.
Next

Physical

  • Posterior segment manifestations
    • The posterior segment manifestations are protean in nature and may be secondary to direct invasion of the leukemic cells.
    • They result from systemic hematological abnormalities, such as anemia, thrombocytopenia, and hyperviscosity or opportunistic infections secondary to the immune dysfunction.
    • Direct infiltration
      • Retinal grayish white nodules that may be surrounded by hemorrhage manifest direct infiltration.
      • Perivascular sheathing may be another manifestation of a leukemic infiltrate.
      • Roth spots, white-centered retinal hemorrhages, may represent a cluster of leukemic cells. On the other hand, septic emboli or platelet-fibrin material gives a similar funduscopic finding.
      • Rarely, pale gray swelling of the optic nerve head may indicate optic nerve infiltration.
    • Leukemic retinopathy
      • Retinal lesions are the most common ocular manifestation of leukemia. They are found most often in adults and in patients with myeloid leukemia.
      • Retinal hemorrhages are the most common finding in most series and are thought to be secondary to anemia and thrombocytopenia. These hemorrhages may be dot-shaped, flame-shaped, intraretinal, subretinal, or subhyaloid.
      • An impending retinal vein obstruction and intraretinal hemorrhage are shown in the images below.An impending bilateral central retinal vein obstruAn impending bilateral central retinal vein obstruction was discovered during a routine examination of a 76-year-old man. Further workup revealed a WBC count of 709,000, a hemoglobin count of 12 mg/dL, and a platelet count of 104,000. The man was eventually diagnosed with CML. This image is a red-free photograph of the right fundus. Notice the intraretinal hemorrhages. Same patient as in the image above. This image is Same patient as in the image above. This image is a red-free photograph of the left eye showing intraretinal hemorrhages.
      • Cotton-wool spots are known to represent nerve fiber layer infarcts. However, they are not correlated with hematological parameters of anemia or blood viscosity.
      • Retinal vein tortuosity and dilation are thought to be secondary to hyperviscosity.
      • Peripheral retinal microaneurysms and retinal neovascularization may be seen, particularly in patients with CML. They are thought to occur as a result of peripheral nonperfusion and ischemia from hyperviscosity.
      • Sea fans reminiscent of sickle cell retinopathy may be seen.
      • Neovascularization of the disc has been reported in a case where no apparent ischemia was present. It was recognized that angiogenic factors secreted from the tumor may play a role in the pathogenesis of retinal and optic nerve head neovascularization.
      • The vitreous seldom is involved.
      • The choroid is the most commonly affected ocular structure in pathological studies. Clinically, it often is difficult to detect the subtle choroidal changes.
      • Occasionally, serous retinal detachments and retinal pigment epithelium (RPE) changes have been reported. In rare cases, they can be the first sign of relapsing leukemia.[11]
    • Opportunistic infections include cytomegalovirus retinitis, toxoplasma chorioretinitis, endogenous fungal endophthalmitis, and herpetic retinitis.
  • Anterior segment manifestations
    • Anterior segment involvement in leukemia is rare but significant because it often is an extramedullary site of relapse. Anterior segment manifestations occur more commonly in ALL than in all the other types of leukemia.
    • A change in iris color, iris nodules, hyphema, hypopyon, glaucoma, a sterile corneal ring ulcer, and a pannus all have been described in patients with leukemia.
    • Corneal involvement is rare. Scleral, episcleral, and conjunctival involvement usually is silent and is limited to perivascular infiltration that can be demonstrated on pathological sections.
  • Orbital manifestations
    • Leukemic cells may infiltrate the orbit during the course of acute or chronic leukemia. Unusual orbital involvement with leukemia has been reported to include infiltration of the lacrimal gland and drainage system, rectus muscles, and dermis.
    • Orbital involvement in children is more common in acute leukemias, whereas orbital involvement in adults is more common in chronic leukemias.
    • The leukemic infiltrate may range from insignificant, where it is virtually asymptomatic, to a space-occupying lesion with its concomitant symptoms.
    • The patient may have proptosis, ecchymosis, chemosis, diplopia, visual disturbance, or motility disturbances.
    • In children, the orbital involvement is characterized by an acute and rapid process that may be confused with orbital cellulitis. In general, these infiltrates are bilateral and do not destroy bone.
    • Granulocytic sarcoma of the orbit, also known as chloroma, is an extramedullary form of myelogenous leukemia.
    • Unilateral, painless proptosis develops over weeks to months prior to a diagnosis of leukemia. Eyelid redness or violaceous discoloration may be present, which turns into ecchymosis that may be confused with rhabdomyosarcoma or metastatic neuroblastoma. If AML or CML is already present, then a rapid and fulminant bilateral proptosis is characteristic.
    • An example of orbital presentation and outcome of leukemia are shown in the images below. A 4-year-old boy presented with sudden proptosis oA 4-year-old boy presented with sudden proptosis of his left eye. Same patient as in the image above. A CBC revealedSame patient as in the image above. A CBC revealed anemia (Hb 8.6 mg/dL), thrombocytopenia (64,000), and leukocytosis (12,900). The peripheral smear revealed the presence of blasts 28%, lymphocytes 44%, segmented 14%, monocytes 6%, bands 2%, metamyelocytes 1%, and myelocytes 1%. The boy was diagnosed with AML type M4-M5 chloroma of the left orbit. Systemic chemotherapy was instituted, and the propSystemic chemotherapy was instituted, and the proptosis resolved. Unfortunately, 4.5 months later, the boy passed away secondary to multiorgan failure.
Previous
Next

Causes

  • The etiology of the leukemias appears to be multifactorial. Genetic, viral, and environmental factors, such as ionizing radiation, drugs, and chemicals, have been implicated in the pathogenesis of leukemia.
  • It is believed that the final common pathway is damage to the DNA. This damage may rearrange the genetic material, thereby allowing previously silent oncogenes to be expressed.
  • Patients with an abnormal number of chromosomes (eg, trisomy 21) and chromosomal translocations are at an increased risk of developing ALL.
  • Risk factors implicated in the development of AML include the following:
    • Myelotoxic agents (eg, ionizing radiation, benzene, alkylating agents)
    • Chromosomal abnormalities (eg, Down syndrome, chromosomal instability syndromes)
    • Predisposing hematological disorders (eg, aplastic anemia, chronic myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria)
  • Chromosomal abnormalities, especially trisomy 12, are common in patients with CLL. Familial case clusters have been reported in CLL. HTLV-1 infection has also been implicated in CLL.
  • Damage to the bone marrow by agents, such as benzene and ionizing radiation, may cause CML.
  • Of patients with CML, 90% have an acquired chromosomal abnormality, the Philadelphia chromosome, which is a translocation of half of the long arm of chromosome 22 to another chromosome, usually chromosome 9.
Previous
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

Lihteh Wu, MD  Consulting Surgeon, Department of Ophthalmology, Vitreo-Retinal Section, Instituto De Cirugia Ocular, Costa Rica

Lihteh Wu, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Association for Research in Vision and Ophthalmology, Pan-American Association of Ophthalmology, and Retina Society

Disclosure: Nothing to disclose.

Coauthor(s)

Teodoro Evans, MD  Retina Fellow, St Michael's Hospital, University of Toronto, Canada

Disclosure: Nothing to disclose.

Joaquin Martinez, MD  Consulting Staff, Department of Ophthalmology, Hospital Nacional de Ninos and Clinica Dr. Clorito Picado; Director of Retinal and Vitreous Clinic at Hospital Nacional de Ninos; Consulting Staff in Ultrosonography and Angiography, Clinica Oftalmologica Costarricense; Private Practice, San Rafael de Escazu, San Jose, Costa Rica

Joaquin Martinez, MD is a member of the following medical societies: Costa Rican Ophthalmology Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Andrew W Lawton, MD  Medical Director of Neuro-Ophthalmology Service, Section of Ophthalmology, Baptist Eye Center, Baptist Health Medical Center

Andrew W Lawton, MD is a member of the following medical societies: American Academy of Ophthalmology, Arkansas Medical Society, and Southern Medical Association

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD  Associate Professor of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Brian R Younge, MD  Professor of Ophthalmology, Mayo Clinic School of Medicine

Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society

Disclosure: Nothing to disclose.

Lance L Brown, OD, MD  Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD  Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

References

  1. Wang L, Lawrence MS, Wan Y, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med. Dec 29 2011;365(26):2497-506. [Medline].

  2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. Jul-Aug 2009;59(4):225-49. [Medline]. [Full Text].

  3. Karesh JW, Goldman EJ, Reck K, Kelman SE, Lee EJ, Schiffer CA. A prospective ophthalmic evaluation of patients with acute myeloid leukemia: correlation of ocular and hematologic findings. J Clin Oncol. Oct 1989;7(10):1528-32. [Medline].

  4. Schachat AP, Markowitz JA, Guyer DR, Burke PJ, Karp JE, Graham ML. Ophthalmic manifestations of leukemia. Arch Ophthalmol. May 1989;107(5):697-700. [Medline].

  5. Kincaid MC, Green WR. Ocular and orbital involvement in leukemia. Surv Ophthalmol. Jan-Feb 1983;27(4):211-32. [Medline].

  6. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. Mar-Apr 2005;55(2):74-108. [Medline]. [Full Text].

  7. Zimmerman LE, Font RL. Ophthalmologic manifestations of granulocytic sarcoma (myeloid sarcoma or chloroma). The third Pan American Association of Ophthalmology and American Journal of Ophthalmology Lecture. Am J Ophthalmol. Dec 1975;80(6):975-90. [Medline].

  8. Radich JP. How I monitor residual disease in chronic myeloid leukemia. Blood. Oct 15 2009;114(16):3376-81. [Medline].

  9. Kaufman M, Rubin J, Rai K. Diagnosing and treating chronic lymphocytic leukemia in 2009. Oncology (Williston Park). Nov 15 2009;23(12):1030-7. [Medline].

  10. Russo V, Scott IU, Querques G, Stella A, Barone A, Delle Noci N. Orbital and ocular manifestations of acute childhood leukemia: clinical and statistical analysis of 180 patients. Eur J Ophthalmol. Jul-Aug 2008;18(4):619-23. [Medline].

  11. Wu L, Calderon M, Hernandez G, Marbis J, Ramirez V. Bilateral exudative retinal detachment as the first sign of relapsing acute myelogenous leukaemia. Clin Experiment Ophthalmol. Aug 2006;34(6):623-5. [Medline].

  12. Hoover DL, Smith LE, Turner SJ, Gelber RD, Sallan SE. Ophthalmic evaluation of survivors of acute lymphoblastic leukemia. Ophthalmology. Feb 1988;95(2):151-5. [Medline].

  13. Abramson DH, Wachtel A, Watson CW, Jereb B, Wollner N. Leukemic hypopyon. J Pediatr Ophthalmol Strabismus. May-Jun 1981;18(3):42-4. [Medline].

  14. Ayliffe W, Foster CS, Marcoux P, Upton M, Finkelstein M, Kuperwaser M, et al. Relapsing acute myeloid leukemia manifesting as hypopyon uveitis. Am J Ophthalmol. Mar 1995;119(3):361-4. [Medline].

  15. Baumal CR, Levin AV, Read SE. Cytomegalovirus retinitis in immunosuppressed children. Am J Ophthalmol. May 1999;127(5):550-8. [Medline].

  16. Brooks HW, Evans AE, Glass RM, Pang EM. Chloromas of the head and neck in childhood. The initial manifestation of myeloid leukemia in three patients. Arch Otolaryngol. Oct 1974;100(4):306-8. [Medline].

  17. Camera A, Piccirillo G, Cennamo G, Tranfa F, Rosa N, Frigeri F, et al. Optic nerve involvement in acute lymphoblastic leukemia. Leuk Lymphoma. Sep 1993;11(1-2):153-5. [Medline].

  18. Candoni A, Simeone E, Bandello F, Fanin R. Leukaemic infiltration of the retina at onset of Philadelphia-positive acute lymphoblastic leukaemia revealed by stratus optical coherence tomography. Br J Haematol. Jun 2006;133(5):455. [Medline].

  19. Consul BN, Kulshrestha OP, Mehrotra AS. Bilateral proptosis in acute myeloid leukaemia. Br J Ophthalmol. Jan 1967;51 (1):65-7.

  20. Cook BE Jr, Bartley GB. Acute lymphoblastic leukemia manifesting in an adult as a conjunctival mass. Am J Ophthalmol. Jul 1997;124(1):104-5. [Medline].

  21. Davis JL, Parke DW 2nd, Font RL. Granulocytic sarcoma of the orbit. A clinicopathologic study. Ophthalmology. Dec 1985;92(12):1758-62. [Medline].

  22. De Juan E, Green WR, Rice TA, Erozan YS. Optic disc neovascularization associated with ocular involvement in acute lymphocytic leukemia. Retina. 1982;2(2):61-4. [Medline].

  23. Ells A, Clarke WN, Noel LP. Pseudohypopyon in acute myelogeneous leukemia. J Pediatr Ophthalmol Strabismus. Mar-Apr 1995;32(2):123-4. [Medline].

  24. Guyer DR, Schachat AP, Vitale S, Markowitz JA, Braine H, Burke PJ, et al. Leukemic retinopathy. Relationship between fundus lesions and hematologic parameters at diagnosis. Ophthalmology. Jun 1989;96(6):860-4. [Medline].

  25. Harnett AN, Plowman PN. The eye in acute leukaemia. 2. The management of solitary anterior chamber relapse. Radiother Oncol. Nov 1987;10(3):203-7. [Medline].

  26. Jordan DR, Noel LP, Carpenter BF. Chloroma. Arch Ophthalmol. May 1991;109(5):734-5. [Medline].

  27. Kaikov Y. Optic nerve head infiltration in acute leukemia in children: an indication for emergency optic nerve radiation therapy. Med Pediatr Oncol. Feb 1996;26(2):101-4. [Medline].

  28. Kerty E, Vigander K, Flage T, Brinch L. Ocular findings in allogeneic stem cell transplantation without total body irradiation. Ophthalmology. Jul 1999;106(7):1334-8. [Medline].

  29. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1999. CA Cancer J Clin. Jan-Feb 1999;49(1):8-31, 1. [Medline].

  30. Leonardy NJ, Rupani M, Dent G, Klintworth GK. Analysis of 135 autopsy eyes for ocular involvement in leukemia. Am J Ophthalmol. Apr 15 1990;109(4):436-44. [Medline].

  31. Lopez-Jimenez J, Sanchez A, Fernandez CS, Gutierrez C, Herrera P, Odriozola J. Cyclosporine-induced retinal toxic blindness. Bone Marrow Transplant. Aug 1997;20(3):243-5. [Medline].

  32. MacLean H, Clarke MP, Strong NP, et al. Primary ocular relapse in acute lymphoblastic leukemia [see comments]. Eye. 1996;10 (Pt 6):719-22. [Medline].

  33. Mehta AB, Goldman JM, Kohner E. Hyperleucocytic retinopathy in chronic granulocytic leukaemia: the role of intensive leucapheresis. Br J Haematol. Apr 1984;56(4):661-7. [Medline].

  34. Ng JS, Lam DS, Li CK, Chik KW, Cheng GP, Yuen PM, et al. Ocular complications of pediatric bone marrow transplantation. Ophthalmology. Jan 1999;106(1):160-4. [Medline].

  35. Ohkoshi K, Tsiaras WG. Prognostic importance of ophthalmic manifestations in childhood leukemia. Br J Ophthalmol. Nov 1992;76(11):651-5. [Medline].

  36. Pakisch B, Langmann G, Langmann A, Slavc I, Poier E, Urban C, et al. Ocular sequelae of multimodal therapy of hematologic malignancies in children. Med Pediatr Oncol. 1994;23(4):344-9. [Medline].

  37. Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin. Jan-Feb 1999;49(1):33-64, 2. [Medline].

  38. Pauleikhoff D, Messmer E, Beelen DW, Foerster M, Wessing A. Bone-marrow transplantation and toxoplasmic retinochoroiditis. Graefes Arch Clin Exp Ophthalmol. 1987;225(3):239-43. [Medline].

  39. Phillips WB, Shields CL, Shields JA, Eagle RC, Masciulli L, Yarian DL. Nocardia choroidal abscess. Br J Ophthalmol. Nov 1992;76(11):694-6. [Medline].

  40. Primack JD, Smith ME, Tychsen L. Retinal detachment in a child as the first sign of leukemic relapse: histopathology, MRI findings, treatment, and tumor-free follow up. J Pediatr Ophthalmol Strabismus. Jul-Aug 1995;32(4):253-6. [Medline].

  41. Reddy SC, Jackson N, Menon BS. Ocular involvement in leukemia--a study of 288 cases. Ophthalmologica. Nov-Dec 2003;217(6):441-5. [Medline].

  42. Reddy SC, Menon BS. A prospective study of ocular manifestations in childhood acute leukaemia. Acta Ophthalmol Scand. Dec 1998;76(6):700-3. [Medline].

  43. Rootman J, Gudauskas G. Treatment of ocular leukemia with local chemotherapy. Cancer Treat Rep. Jan 1985;69(1):119-22. [Medline].

  44. Rosenthal AR. Ocular manifestations of leukemia. A review. Ophthalmology. Aug 1983;90(8):899-905. [Medline].

  45. Rubinfeld RS, Gootenberg JE, Chavis RM, Zimmerman LE. Early onset acute orbital involvement in childhood acute lymphoblastic leukemia. Ophthalmology. Jan 1988;95(1):116-20. [Medline].

  46. Shibasaki H, Hayasaka S, Noda S, Masaki Y, Yamamoto D. Radiotherapy resolves leukemic involvement of the optic nerves. Ann Ophthalmol. Oct 1992;24(10):395-7. [Medline].

  47. Suh DW, Ruttum MS, Stuckenschneider BJ, Mieler WF, Kivlin JD. Ocular findings after bone marrow transplantation in a pediatric population. Ophthalmology. Aug 1999;106(8):1564-70. [Medline].

  48. Takahashi T, Oda Y, Isayama Y. Leukemic optic neuropathy. Ophthalmologica. 1982;185(1):37-45. [Medline].

 
Previous
Next
 
A 4-year-old boy presented with sudden proptosis of his left eye.
Same patient as in the image above. A CBC revealed anemia (Hb 8.6 mg/dL), thrombocytopenia (64,000), and leukocytosis (12,900). The peripheral smear revealed the presence of blasts 28%, lymphocytes 44%, segmented 14%, monocytes 6%, bands 2%, metamyelocytes 1%, and myelocytes 1%. The boy was diagnosed with AML type M4-M5 chloroma of the left orbit.
CT scan reveals infiltration in the left orbit. Notice that the bone is uninvolved. A lumbar puncture revealed that the cerebral spinal fluid was clean of leukemic cells.
Systemic chemotherapy was instituted, and the proptosis resolved. Unfortunately, 4.5 months later, the boy passed away secondary to multiorgan failure.
An impending bilateral central retinal vein obstruction was discovered during a routine examination of a 76-year-old man. Further workup revealed a WBC count of 709,000, a hemoglobin count of 12 mg/dL, and a platelet count of 104,000. The man was eventually diagnosed with CML. This image is a red-free photograph of the right fundus. Notice the intraretinal hemorrhages.
Same patient as in the image above. This image is a red-free photograph of the left eye showing intraretinal hemorrhages.
A 14-year-old boy with a past medical history of ALL complained of a sudden loss of vision OD. Visual acuities were counting fingers OD and 20/20 OS. Notice the macular hemorrhage responsible for the loss of vision. Courtesy of Dr Rafael Jiménez.
Same patient as in Media file 7. The hematological workup revealed a hemoglobin count of 5.6, a WBC count of 1800, and a platelet count of 3000. Courtesy of Dr Rafael Jiménez.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.