Abstract We report a case of Endemic African Cutaneous Kaposi Sarcoma (EACKS) on the lower extremity of an immunocompetent 31-yr-old male service member from Cameroon. Diagnosis was made using clinical and histologic findings. The service member was treated with local radiation therapy with resolution of his tumor. The goal of this article is to educate practitioners to counsel susceptible service members and leadership on the risk of developing EACKS when traveling to Sub-Saharan Africa, monitor for disease development, and guide in the diagnosis and treatment of patients with this rare disease. Introduction Kaposi Sarcoma (KS) was first described in 1872 by Moritz Kaposi as “idiopathic multiple pigmented sarcomas of the skin.”1 It is known to be endemic to Italian, South American Amerindian, and Sub-Saharan Africa populations.2 According to a recent article by the New York Times, the United States Armed Forces continue to undertake 96 missions in 21 African countries.3 Soldiers, like our patient, also regularly travel to these areas for personal reasons. Consequently, it is important to be familiar with the presentation and pathogenesis of KS. We present a case of Endemic African Cutaneous Kaposi Sarcoma (EACKS) on the lower extremity of an immunocompetent 31-yr-old male service member from Cameroon. This case is being presented to emphasize and educate practitioners on this rare clinical entity and the need to counsel service members who are traveling to endemic countries. Case Presentation We report a case of a 31-yr-old male from Cameroon who presented to Dermatology at Walter Reed National Military Medical Center for evaluation of asymptomatic persistent hyperpigmented patches on his left inner leg, ankle, and foot that appeared 6 mo before initial presentation (Figs 1 and 2). The patient stated he previously lived in Cameroon until he was a teenager and then moved to the United States and joined the U.S. Army. Since that time, the soldier has made annual trips to Cameroon to visit his family. He denied any symptoms of pruritus or pain associated with the patches. The patient’s HIV test performed via fourth generation Ab/Ag assay 4 wk before evaluation was negative. A chart review revealed the patient had no history of immunosuppressive therapy. Figure 1. View largeDownload slide Clinical photo at the time of initial presentation, before biopsy, displaying hyperpigmented patches localized to medial ankle characteristic of Kaposi Sarcoma. Figure 1. View largeDownload slide Clinical photo at the time of initial presentation, before biopsy, displaying hyperpigmented patches localized to medial ankle characteristic of Kaposi Sarcoma. Figure 2. View largeDownload slide Clinical photos at the time of follow-up showing persistent hyperpigmented patches with extension up the patient’s calf. Figure 2. View largeDownload slide Clinical photos at the time of follow-up showing persistent hyperpigmented patches with extension up the patient’s calf. A biopsy was taken from his left leg and stained with hematoxylin and eosin. The stain displayed significant bland slit-like vascular proliferations in the superficial and deep dermis along with perivascular lymphocytes consistent with a vascular proliferative disorder (Figs 3–5). Immunohistochemical staining of the biopsy-highlighted vessels with CD31 confirmed that they were indeed vascular endothelial cells (Fig. 6). Slides stained for HHV-8 displayed weakly positive cells in clusters (Fig. 7). The biopsies taken in corroboration were consistent with KS. To rule out a more aggressive variant, computed tomography of the chest, abdomen, and pelvis was obtained, which did not show any evidence of systemic infiltration. The patient was then diagnosed with EACKS from his history of extensive time in Cameroon, negative HIV antibodies, and normal T + B cell subsets. Figure 3. View largeDownload slide Hematoxylin and eosin stain at 20× magnification shows an unremarkable epidermis. There is a proliferation of bland appearing slit-like cells that infiltrate the superficial and deep aspects of the dermis. Figure 3. View largeDownload slide Hematoxylin and eosin stain at 20× magnification shows an unremarkable epidermis. There is a proliferation of bland appearing slit-like cells that infiltrate the superficial and deep aspects of the dermis. Figure 4. View largeDownload slide Hematoxylin and eosin staining of sections at 40× magnification further define the proliferation of bland appearing slit-like cells that infiltrate into the deep dermis labeled with the black arrow. Extravasation of erythrocytes and focal hemosiderin deposition is associated with these slit-like cells. Focal lumen are labeled with the yellow arrow. Figure 4. View largeDownload slide Hematoxylin and eosin staining of sections at 40× magnification further define the proliferation of bland appearing slit-like cells that infiltrate into the deep dermis labeled with the black arrow. Extravasation of erythrocytes and focal hemosiderin deposition is associated with these slit-like cells. Focal lumen are labeled with the yellow arrow. Figure 5. View largeDownload slide Hematoxylin and eosin stain at 100× magnification display perivascular lymphocytes and plasma cells associated with the vascular proliferation. These findings are consistent with a vascular proliferation. Figure 5. View largeDownload slide Hematoxylin and eosin stain at 100× magnification display perivascular lymphocytes and plasma cells associated with the vascular proliferation. These findings are consistent with a vascular proliferation. Figure 6. View largeDownload slide Immunohistochemical stains (IHC) for CD31 was performed (all controls valid). At 100× magnification the slit-like cells of interest marked with the black arrows are noted to be positive for CD31 which confirms they are vascular endothelial cells. Figure 6. View largeDownload slide Immunohistochemical stains (IHC) for CD31 was performed (all controls valid). At 100× magnification the slit-like cells of interest marked with the black arrows are noted to be positive for CD31 which confirms they are vascular endothelial cells. Figure 7. View largeDownload slide HHV-8 is positive in clusters of focal cells of interest marked with red arrows. This confirms the diagnosis of Kaposi Sarcoma. Figure 7. View largeDownload slide HHV-8 is positive in clusters of focal cells of interest marked with red arrows. This confirms the diagnosis of Kaposi Sarcoma. The patient was then referred to hematology and oncology where his diagnosis was further defined as stage IA EACKS based on localized involvement with macules and patches without nodularity.4 The patient was referred to radiation oncology for local radiation treatment of his left lower extremity. Although treatment guidelines have not been established for EACKS, treatment for classic KS has been established for typical localized lesions with a 90% success rate.5 Following the guidelines for classic KS, our patient received successful treatment of his disease with localized radiation therapy with 30 Gy in 15 daily 2 Gy fractions.5 The patient’s subsequent radiation-related post-inflammatory hyperpigmentation was treated with topical hydroquinone with improvement. Discussion This case is an example of a susceptible service member diagnosed with EACKS after visiting sub-Saharan Africa. EACKS is an important clinical entity to be cognizant of in service members who are deployed, regularly travel to, or are from endemic areas. The goal of this article is to raise awareness and succinctly educate military practitioners on the history, pathogenesis, transmission, clinical presentation, laboratory and radiologic evaluation, diagnosis, and treatment modalities available for patients. We also urge clinicians to educate their patients on these findings and counsel them on safe practices when traveling to these areas. KS is an angioproliferative tumor resulting from multifactorial pathogenesis to include HHV-8 infection.2,6 HHV-8 was discovered to be a crucial factor in the development of KS in 1994.6 Viral infection appears to be required but is insufficient for the development of KS.2,6 As HHV-8 genes are transduced into cell lines, a “dysregulated autocrine and paracrine angioproliferative signaling” occurs that is inherent in KS tumors.2 Spindle cells biopsied from KS lesions display an increase in vascular endothelial growth factor receptors A, B, C, D, 1, 2, and 3.2 HHV-8 is critical in the development of the tumor by causing cell dysregulation and angioproliferation. In most cases, the virus remains dormant in infected individuals.7 However, populations of sub-Saharan African descent tend to be susceptible to development of KS if infected with HHV-8. Factors involved in progression and subtype development to KS are not fully understood; however, multiple theories of pathogenesis exist.6 Transmission of HHV-8 is thought to occur largely via saliva, but cases have been reported with transmission through blood, body fluids, or by organ transplant.2 There is some evidence that injectable drug use may increase risk as well, but this has not been well defined.2 The morphology of KS is characterized by progressive stages of erythematous to violaceous patches followed by plaques and finally nodules on the skin that are formed by irregular dilated blood vessels and spindle cells.8 The patch stage consists of a diffuse slit-like vasoproliferative process with mild inflammation.8 The plaque stage is characterized by more diffuse dermal vascular infiltrate with greater cellularity.8 Progression continues to the nodular stage with circumscribed dermal expansion and neoplastic spindle cells arranged in fascicles.8 Other variants have been described including hyperkeratotic, keloidal, micronodular, pyogenic granuloma-like, ecchymotic, and intravascular KS that are beyond the scope of this article.8 The cutaneous lesions tend to be asymptomatic but can ulcerate and bleed.8 These lesions may progress rapidly, spontaneously regress,2 or remain stable for years.7 Laboratory and radiologic examination should be performed on any patient with EACKS features to confirm the diagnosis and rule out more aggressive variants. Given the most common cause of KS in the United States is related to HIV, patients should be evaluated for HIV infection. Presence of HHV-8 should also be determined via laboratory analysis. In a study performed by Hammock, HHV-8 was present in 100% of patients with KS by real-time PCR analysis of tumors.7 However, this was present in 30% of non-KS vascular tumor.7 HHV-8 latency-associated nuclear antigen expression in endothelial cells, spindle cells, and serum is another marker that was seen in 92% of KS patients identified and zero non-KS vascular tumors making this test more specific.7 Therefore, tumors should be evaluated via real-time PCR for the virus as well as HHV-8 latency-associated nuclear antigen expression. Evaluation of systemic KS should include laboratory and radiologic exam of the pulmonary and gastrointestinal tract since KS commonly affects these areas.9 Given that hemorrhagic nodules are common with gastrointestinal involvement,9 an occult blood can be taken to screen for involvement. If pulmonary symptoms are present, chest X-ray should be performed to screen for pulmonary involvement. Diagnosis of KS has traditionally been achieved by biopsy with immunohistochemical analysis. This can be used to detect HHV-8, CD31, and CD34.10 This analysis displays the abundance of HHV-8 within the cells and CD31 and CD34 highlights vascular proliferation characteristic of KS. Many treatment modalities exist for KS, although none have been established specifically for EACKS. Localized treatment typically consists of surgical excision, radiation, cryotherapy, laser therapy, alitretionin, and intralesional injection.11 Systemic therapies include chemotherapy and liposomal doxorubicin or daunorubicin as well as many other experimental therapies.11 Our patient responded well to radiation treatment guidelines established by Hauerstock without sequelae or recurrence. Conclusion/Recommendation In conclusion, susceptible service members have a real risk of developing EACKS when deployed or visiting endemic areas. Practitioners should be aware of sub-Saharan Africa as an endemic area and properly counsel soldiers on use of protection when encountering body fluids, particularly saliva, of people in affected areas. Soldiers should also be counseled on the increased risk of contraction with IV drug use. Patients should be educated on the signs and symptoms of EACKS. When presented with a clinically significant lesion, patients should be sent to dermatology for clinical, laboratory, and if necessary radiologic analysis and biopsy. The pathology may not present immediately, so susceptible populations may need long-term follow-up after travel to endemic areas due to the risk of developing EACKS later in life. Once diagnosed, oncology should be contacted for proper treatment. This article seeks to alert military clinicians to this rare clinical entity, identify susceptible populations, and provide the tools to recognize, diagnose, treat, and counsel soldiers on this disease. Further research is needed to determine the extent that EACKS affects the military population. This case is being reported to highlight that it does occur and in the authors opinion should be monitored so our soldiers may receive the high-quality care they deserve. References 1 Nggada HA, Dogo D, Khalil MI, Harry TO: Disseminated endemic Kaposi’s Sarcoma in a young man without evidence of HIV infection. Afr J Clin Exp Microbiol 2007; 8( 3): 145– 9. Google Scholar CrossRef Search ADS 2 Uldrick TS, Whitby D: Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma. Cancer Lett 2011; 305( 2): 150– 62. Google Scholar CrossRef Search ADS PubMed 3 Okeowo A: The Enduring American Military Mission in Africa, The New Yorker 2017. Available at http://www.newyorker.com/news/daily-comment/the-enduring-american-military-mission-in-africa; accessed June 29, 2017 4 Brambilla L, Boneschi V, Taglioni M, Ferrucci S: Staging of classic Kaposi’s Sarcoma: a useful tool for therapeutic choices. Eur J Dermatol 2003; 13: 83– 6. Google Scholar PubMed 5 Hauerstock D, Gerstein W, Vuong T: Results of radiation therapy for treatment of classic Kaposi Sarcoma. J Cutan Med Surg 2009; 13( 1): 18– 21. Google Scholar CrossRef Search ADS PubMed 6 Ruocco E, Ruocco V, Tornesello ML, Gambardella A, Wolf R, Buonaguro FM: Kaposi’s Sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies. Clin Dermatol 2013; 31( 4): 413– 22. Google Scholar CrossRef Search ADS PubMed 7 Hammock L, Reisenauer A, Wang W, Cohen C, Birdsong G, Folpe AL: Latency-associated nuclear antigen expression and human herpesvirus-8 polymerase chain reaction in the evaluation of Kaposi Sarcoma and other vascular tumors in HIV-positive patients. Mod Pathol 2005; 18( 4): 463– 8. Google Scholar CrossRef Search ADS PubMed 8 Grayson W, Pantanowitz L: Histologic variants of cutaneous Kaposi Sarcoma. Diagn Pathol 2008; 3: 31. Google Scholar CrossRef Search ADS PubMed 9 Bower M, Pria A, Coyle C, et al. : Prospective stage-stratified approach to AIDS-related Kaposi Sarcoma. J Clin Oncol 2014; 32( 6): 409– 14. Google Scholar CrossRef Search ADS PubMed 10 Radu O, Pantanowitz L: Kaposi Sarcoma. Arch Pathol Lab Med 2013; 137( 2): 289– 94. Google Scholar CrossRef Search ADS PubMed 11 Hengge UR, Ruzicka T, Tyring SK, et al. : Update on Kaposi Sarcoma and other HHV8 associated diseases. Part 1: epidemiology, environmental predispositions, clinical manifestations, and therapy. Lancet Infect Dis 2002; 2( 5): 281– 92. Google Scholar CrossRef Search ADS PubMed Author notes The views expressed in this document are those of the author(s) and do not reflect the official policy of William Beaumont Army Medical Center, the Department of the Army, or the United States Government. Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Military Medicine – Oxford University Press
Published: Mar 26, 2018
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