Association of Human Herpesvirus Type 8 (HHV-8) expression in patients with Kaposi’s sarcoma: A clinico-immunohistochemical study
Keywords:Kaposi’s Sarcoma, Immunohistochemistry, Human Herpesvirus type 8
AbstractAbstract Background: Kaposi’s sarcoma (KS) is an angioproliferative neoplastic disorder that occurs in different epidemiological forms. Human Herpesvirus type 8 (HHV-8) is established as a causative agent of KS that has been mentioned in textbooks and literature. In the last two decades, KS cases were up searched through many Iraqi medical researches which have been published, but unfortunately, none of which had confirmed this association. Objectives: To assess the association of latent nuclear antigen-1(LANA-1) of HHV-8 among KS patients with clinicopathological parameters and to evaluate if this procedure is valuable for diagnosing this disease through the first immunohistochemical study in Iraq. Methods: This is a clinico-immunohistochemical descriptive study conducted at the Dermatology Center/Medical City, Baghdad, Iraq. Thirty-two KS cases diagnosed by clinical and histopathological means in the Dermatology/Pathology Departments /Medical City and three Private Medical Laboratories were studied from the first of January 2016 to the first of October 2022. Retrospectively, 20 KS cases with clinical and histopathological data were extracted from a patient’s registry while the remaining 12 cases were collected prospectively. All clinical and sociodemographic data were recorded then immuno-histopathological evaluations were done for them. Results: The most common type of KS was classical 27(84%) of cases followed by iatrogenic 4(13%) and HIV-associated 1(3%) case. Histomorphologically, 15(46.9%) of the cases were in the plaque stage, 11(34.3%) nodular stage and 6(18.8%) patch stage. The overall HHV-8 expression was detected in 27(84.4%) of the cases. The total histoscore was calculated by combining the staining intensity score and positive cell percentage score and shows a significant correlation with the stage of progression (P=0.02). No significant associations between HHV-8 expression and age, sex, disease recurrence, site of biopsy, and clinical types while the association with the disease duration was significant (P=0.032). Conclusions: Immunohistochemistry for HHV-8 is a sensitive and specific diagnostic method for KS. The majority of cases that did not express HHV-8 staining were in the early patch stages, with a relatively lower median duration than that of HHV-8 positive cases. Negative immunostaining for HHV-8 does not necessarily exclude KS in an appropriate clinicopathological setting.
Lebbe C, Garbe C, Stratigos AJ, et al. Diagnosis and treatment of Kaposi’s sarcoma: European consensus-based interdisciplinary guideline (EDF/EADO/EORTC). European Journal of Cancer. 2019;114:117-127.
Kenneth Y. Tasi. Kaposi’s Sarcoma. In: Christophoer. Griffiths, Jonathan Barker, Bleiker, Chalmers, Creamer. Rook’s Textbook of Dermatology 9th ed. John Wiley & Sons; 2016;(139):1-6.
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians. 2021;71(3):209–49.
Dow DE, Cunningham CK, Buchanan AM. A review of human herpesvirus 8, the Kaposi’s sarcoma-associated herpesvirus, in the pediatric population. Journal of the Pediatric Infectious Diseases Society. 2014;3(1):66–76.
Safaei NZ, Saberi S, Gransar A et al. Immunohistochemical Detection of the Human Herpes Virus 8 (HHV8) Latent Nuclear Antigen-1 in Kapasi Sarcoma Cases. Iranian Journal of Pathology. 2011;6(2):73-8.
Hong A, Davies S, Lee CS. Immunohistochemical detection of the human herpes virus 8 (HHV8) latent nuclear antigen-1 in Kaposi’s sarcoma. Pathology. 2003;35(5):448-450.
Cheuk W, Wong KO, Wong CS, et al. Immunostaining for human herpesvirus 8 latent nuclear antigen-1 helps distinguish Kaposi sarcoma from its mimickers. American Journal of Clinical Pathology. 2004;121(3):335-342.
Pereira PF, Cuzzi T, Galhardo MCG. Immunohistochemical detection of the latent nuclear antigen-1 of the human herpesvirus type 8 to differentiate cutaneous epidemic Kaposi’s Sarcoma and its histological simulators. Anais Brasileiros de Dermatologia. 2013;88:243–6.
Sharquie KE, Noaimi AA, Taha SF. Kaposi’s Sarcoma is Increasing over Years. American Journal of Dermatology and Venereology. 2019;8(5):84–7.
Al-Waiz M, Sharquie KE, Al-Hamdani GA. An upsurge of new cases of Kaposi’s sarcoma in Iraqi patients. Saudi Medical Journal. 2003;24(2):224–5.
Bhutani M, Polizzotto MN, Uldrick TS, et al. Kaposi’s Sarcoma –associated herpesvirus-associated malignancies: epidemiology, pathogenesis, and advances in treatment. In: Seminars in oncology. WB Saunders, 2015; 223-246.
Radu O, Pantanowitz L. Kaposi’s Sarcoma. Archives of Pathology & Laboratory Medicine. 2013;137(2):289–94.
Pantanowitz L, Caponetti G, Dezube BJ. The immunohistochemistry of Kaposi’s sarcoma. Methods of Cancer Diagnosis, Therapy and Prognosis. 2010;405–31.
Van Bogaert L. Immunostaining by Human Herpes Virus 8 Latent Nuclear Antigen-1 of Kaposi’s sarcoma: A Potential Biomarker of Severity of Disease. J Mol Biomark Diagn. 2013;5:002.
Manuraj S, Steve M, Heinz K, et al. Negative HHV-8 immunoreactivity in HIV associated Kaposi’s sarcoma. Journal of Cutaneous Pathology. 2016;43(7):626-628.
Kumar P. Human herpes virus-8-negative kaposiform sarcoma in a HIV-positive male: Novel variant. Journal of Cancer Research and Therapeutics. 2020;16(1):177.
Martí N, Monteagudo C, Pinazo I, et al. Negative herpesvirus‐8 immunoreactivity does not exclude a diagnosis of Kaposi sarcoma. British Journal of Dermatology. 2011;164(1):209-211.