0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letters |

Conjunctival Squamous Cell Carcinoma Harboring Leishmania Amastigotes in a Human Immunodeficiency Virus–Positive Patient FREE

Brett P. Bielory, MD; Hamed B. Lari, MD; Neena Mirani, MD; Rajendra Kapila, MD; Valerie A. Fitzhugh, MD; Roger E. Turbin, MD
[+] Author Affiliations

Author Affiliations: Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida (Dr Bielory); and Departments of Ophthalmology (Drs Lari and Turbin), Pathology and Laboratory Medicine (Drs Mirani and Fitzhugh), and Medicine (Dr Kapila), New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark.


Arch Ophthalmol. 2011;129(9):1230-1231. doi:10.1001/archophthalmol.2011.252.
Text Size: A A A
Published online

Leishmaniasis, a protozoal infection transmitted via the sand fly bite, is endemic to India, the Middle East, and Africa and is periodically found in Central and South America. Visceral leishmaniasis, also known as kala-azar, black fever, or Dumdum fever, is the most severe form. Ocular involvement occurs more frequently in cutaneous than in mucocutaneous and visceral manifestations. We report a unique case of Leishmania donovani chagasi identified by biopsy of squamous cell carcinoma (SCC) of the bulbar conjunctiva in a human immunodeficiency virus (HIV)–positive Hispanic man. Subsequent evaluation revealed kala-azar with histopathological confirmation of the organism in conjunctiva, lacrimal gland, and liver specimens.

A 39-year-old HIV-positive Guatemalan man had decreased vision, epiphora, and pain in the right eye for 18 months. He had been continuously maintained on highly active antiretroviral therapy, azithromycin, and sulfamethoxazole/trimethoprim for 2 years. He denied fever, sweating, or flulike symptoms.

Best-corrected visual acuity was 20/25 OD and 20/20 OS. The pupils were 5 mm on the right and 7 mm on the left, briskly reactive to light, and without relative afferent pupil defect. Extraocular movements were full without restriction. Intraocular pressures were 17 mm Hg in both eyes. The right upper eyelid was mildly ptotic and swollen. The slitlamp biomicroscopic appearance is shown in Figure 1A. Funduscopic examination results were unremarkable. Ultrasound biomicroscopy and B-mode ultrasonography of the globe did not suggest extension into deeper structures or transscleral invasion.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Clinical photograph and photomicrographs. A, Right conjunctival mass, with a yellow gelatinous temporal lesion extending from the 9-o’clock position to the 12-o’clock position with associated symblepharon and feeder vessels. B, Invasive squamous cell carcinoma, moderately differentiated (hematoxylin-eosin, original magnification ×400). C, Conjunctival squamous cell carcinoma and Leishmania amastigotes in histiocytes (hematoxylin-eosin, original magnification ×1000). D, CD68-positive histiocytes containing organisms (immunoperoxidase reaction, original magnification ×1000).

Computed tomography of the orbit revealed disease limited to preseptal soft tissue. Laboratory evaluation demonstrated a viral load of less than 48 copies/mL and a CD4 lymphocyte count of 79 cells/μL. Excisional biopsy of the mass showed moderately differentiated invasive SCC as well as intracellular microorganisms in histiocytes (Figure 1B). Special stains for Histoplasma and Toxoplasma were negative. High-power oil immersion highlighted the Leishmania amastigotes (Figure 1C), and CD68 staining confirmed their presence in macrophages (Figure 1D). The Centers for Disease Control and Prevention confirmed the microorganisms as L donovani chagasi.

Postoperative positron emission tomography showed increased uptake within the right lateral conjunctiva, liver, spleen, and axillary, mediastinal, mesenteric, pelvic, and cervical lymph nodes. Abdominal computed tomography revealed hepatosplenomegaly (Figure 2). A subsequent liver biopsy confirmed the diagnosis of visceral leishmaniasis. The patient was treated with intravenous liposomal amphotericin B (190 mg/d for 14 days and triweekly thereafter).

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Axial abdominal computed tomography scan exhibiting hepatosplenomegaly, with the liver and spleen measuring 26.5 cm and 17 cm, respectively (largest axial dimension).

In HIV-infected individuals, SCC occurs at an earlier age and may be more aggressive than in immunocompetent individuals. The oropharynx, cervix, and anorectum are most frequently involved, but the disease can manifest in the eyelids,1 conjunctiva,2 and iris.3 Rare cases of Leishmania infection within basal cell carcinoma4 and SCC5 have been reported, including a single Brazilian case of mucocutaneous leishmaniasis of the conjunctiva with an ensuing epidermoid carcinoma in the orbit.5 To our knowledge, we report the first case of visceral leishmaniasis within conjunctival SCC.

Visceral leishmaniasis commonly affects the liver and spleen. There is a strong association between HIV and visceral leishmaniasis, with an increasing incidence in nonendemic regions.6 Exploiting the host immune system, Leishmania upregulates HIV via nuclear factor κ B, interferon γ,7 interleukin 12, and/or interleukin 18.8 There are reports of the ocular manifestations of Leishmania including blepharoconjunctivitis,9,10 anterior uveitis,9,10 thrombocytopenic intraretinal hemorrhages,11 and optic neuropathy12 from an orbital apex lesion. Pentavalent antimonial compounds such as sodium stibogluconate and meglumine antimoniate have been the traditional pharmacologic intervention. However, polyene antifungals such as amphotericin B or the antiprotozoal medication miltefosine are the current standards of care. Plans for additional treatment of the SCC will be directed by the patient's response to antimicrobial therapy.

Correspondence: Dr Turbin, Institute of Ophthalmology and Visual Science, 90 Bergen St, DOC Bldg, Ste 6177, Newark, NJ 07103 (turbinre@umdnj.edu).

Financial Disclosure: None reported.

Funding/Support: This work was supported in part by an unrestricted grant from Research to Prevent Blindness, New York, New York, The Eye Institute of New Jersey, Newark, and the Gene C. Coppa Memorial Fund, Newark.

Role of the Sponsors: The sponsors have provided general academic support for Dr Turbin's academic work but have had no role in collection, analysis, interpretation, preparation, or review.

Maclean H, Dhillon B, Ironside J. Squamous cell carcinoma of the eyelid and the acquired immunodeficiency syndrome.  Am J Ophthalmol. 1996;121(2):219-221
PubMed
Lewallen S, Shroyer KR, Keyser RB, Liomba G. Aggressive conjunctival squamous cell carcinoma in three young Africans.  Arch Ophthalmol. 1996;114(2):215-218
PubMed   |  Link to Article
Tulvatana W, Tirakunwichcha S. Multifocal squamous cell carcinoma of the conjunctiva with intraocular penetration in a patient with AIDS.  Cornea. 2006;25(6):745-747
PubMed   |  Link to Article
Suster S, Ronnen M. Basal cell carcinoma arising in a Leishmania scar.  Int J Dermatol. 1988;27(3):175-176
PubMed   |  Link to Article
Matayoshi S, Baddina-Caramelli C, Goldbaum M, Takei LM, Honda M, Kara-José N. Epidermoid carcinoma arising in an ocular Leishmania lesion.  Br J Ophthalmol. 2000;84(11):1331-1332
PubMed   |  Link to Article
Auyeung P, French MA, Hollingsworth PN. Immune restoration disease associated with Leishmania donovani infection following antiretroviral therapy for HIV infection.  J Microbiol Immunol Infect. 2010;43(1):74-76
PubMed   |  Link to Article
Bernier R, Barbeau B, Tremblay MJ, Olivier M. The lipophosphoglycan of Leishmania donovani up-regulates HIV-1 transcription in T cells through the nuclear factor-kappaB elements.  J Immunol. 1998;160(6):2881-2888
PubMed
Wolday D, Berhe N, Britton S, Akuffo H. HIV-1 alters T helper cytokines, interleukin-12 and interleukin-18 responses to the protozoan parasite Leishmania donovani AIDS. 2000;14(8):921-929
PubMed   |  Link to Article
el Hassan AM, Khalil EA, el Sheikh EA, Zijlstra EE, Osman A, Ibrahim ME. Post kala-azar ocular leishmaniasis.  Trans R Soc Trop Med Hyg. 1998;92(2):177-179
PubMed   |  Link to Article
el-Hassan AM, el-Sheikh EA, Eltoum IA,  et al.  Post-kala-azar anterior uveitis: demonstration of Leishmania parasites in the lesion.  Trans R Soc Trop Med Hyg. 1991;85(4):471-473
PubMed   |  Link to Article
Montero JA, Ruiz-Moreno JM, Sanchis E. Intraretinal hemorrhage associated with leishmaniasis.  Ophthalmic Surg Lasers Imaging. 2003;34(3):212-214
PubMed
Huna-Baron R, Warren FA, Miller W, Jacobs J, Green J, Kupersmith MJ. Mucosal leishmaniasis presenting as sinusitis and optic neuropathy.  Arch Ophthalmol. 2000;118(6):852-854
PubMed

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Clinical photograph and photomicrographs. A, Right conjunctival mass, with a yellow gelatinous temporal lesion extending from the 9-o’clock position to the 12-o’clock position with associated symblepharon and feeder vessels. B, Invasive squamous cell carcinoma, moderately differentiated (hematoxylin-eosin, original magnification ×400). C, Conjunctival squamous cell carcinoma and Leishmania amastigotes in histiocytes (hematoxylin-eosin, original magnification ×1000). D, CD68-positive histiocytes containing organisms (immunoperoxidase reaction, original magnification ×1000).

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Axial abdominal computed tomography scan exhibiting hepatosplenomegaly, with the liver and spleen measuring 26.5 cm and 17 cm, respectively (largest axial dimension).

Tables

References

Maclean H, Dhillon B, Ironside J. Squamous cell carcinoma of the eyelid and the acquired immunodeficiency syndrome.  Am J Ophthalmol. 1996;121(2):219-221
PubMed
Lewallen S, Shroyer KR, Keyser RB, Liomba G. Aggressive conjunctival squamous cell carcinoma in three young Africans.  Arch Ophthalmol. 1996;114(2):215-218
PubMed   |  Link to Article
Tulvatana W, Tirakunwichcha S. Multifocal squamous cell carcinoma of the conjunctiva with intraocular penetration in a patient with AIDS.  Cornea. 2006;25(6):745-747
PubMed   |  Link to Article
Suster S, Ronnen M. Basal cell carcinoma arising in a Leishmania scar.  Int J Dermatol. 1988;27(3):175-176
PubMed   |  Link to Article
Matayoshi S, Baddina-Caramelli C, Goldbaum M, Takei LM, Honda M, Kara-José N. Epidermoid carcinoma arising in an ocular Leishmania lesion.  Br J Ophthalmol. 2000;84(11):1331-1332
PubMed   |  Link to Article
Auyeung P, French MA, Hollingsworth PN. Immune restoration disease associated with Leishmania donovani infection following antiretroviral therapy for HIV infection.  J Microbiol Immunol Infect. 2010;43(1):74-76
PubMed   |  Link to Article
Bernier R, Barbeau B, Tremblay MJ, Olivier M. The lipophosphoglycan of Leishmania donovani up-regulates HIV-1 transcription in T cells through the nuclear factor-kappaB elements.  J Immunol. 1998;160(6):2881-2888
PubMed
Wolday D, Berhe N, Britton S, Akuffo H. HIV-1 alters T helper cytokines, interleukin-12 and interleukin-18 responses to the protozoan parasite Leishmania donovani AIDS. 2000;14(8):921-929
PubMed   |  Link to Article
el Hassan AM, Khalil EA, el Sheikh EA, Zijlstra EE, Osman A, Ibrahim ME. Post kala-azar ocular leishmaniasis.  Trans R Soc Trop Med Hyg. 1998;92(2):177-179
PubMed   |  Link to Article
el-Hassan AM, el-Sheikh EA, Eltoum IA,  et al.  Post-kala-azar anterior uveitis: demonstration of Leishmania parasites in the lesion.  Trans R Soc Trop Med Hyg. 1991;85(4):471-473
PubMed   |  Link to Article
Montero JA, Ruiz-Moreno JM, Sanchis E. Intraretinal hemorrhage associated with leishmaniasis.  Ophthalmic Surg Lasers Imaging. 2003;34(3):212-214
PubMed
Huna-Baron R, Warren FA, Miller W, Jacobs J, Green J, Kupersmith MJ. Mucosal leishmaniasis presenting as sinusitis and optic neuropathy.  Arch Ophthalmol. 2000;118(6):852-854
PubMed

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

840 Views
3 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
Jobs
JAMAevidence.com

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed
Clarifying Your Question

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed
Three Examples of Question Clarification