The Investigation of the Association of Cutaneous Leishmaniasis in Biopsy Specimens of the Patients with Granulomatous Disease and Skin Cancer Using the Molecular Method
Background: Clinically, cutaneous leishmaniasis (CL) can be confused with granulomatous diseases and skin cancers, and it may lead to erroneous diagnosis and treatment. Diagnosis based and histopathology can have some difficulties due to low number of parasites, especially in chronic CL cases. We aimed to emphasize the necessity of considering CL in the differential diagnosis for cases of granulomatous diseases and basal cell carcinoma, particularly in areas where CL is endemic.
Methods: One hundred and seven paraffin-embedded tissue biopsy specimens were selected from the archive, as of 2002, of Pathology Department, School of Medicine, University of Hatay Mustafa Kemal in Hatay, Turkey. After DNA isolation, performed with the samples were used for PCR analysis with specific 13A, 13B primers targeting kinetoplastid DNA (kDNA) found in all Leishmania species. Another PCR was performed with LITSR and L5.8S primers targeting ITS-1 internal-transcribed-spacer-1 (ITS-1) region to subtype positive samples. Then these samples were further analyzed for subtyping with PCR-RFLP using HaeIII enzyme (BsuRI).
Results: Ten out of 107 tissue specimens were positive via kDNA-PCR. Lupus vulgaris, sarcoidosis, skin lymphoma and Leishmania cutis appeared in 9 out of 10 positive specimens. One of the cases presented with a mass on the cheek and was pre-diagnosed with hemangioma, but leishmaniasis did not appear. All of 10 specimens were diagnosed as granulomatous dermatitis. Two out of 10 samples, found positive with kDNA-PCR, were analyzed with ITS-1-PCR and identified as L. infantum/donovani after RFLP.
Conclusion: Molecular methods should be utilized in the differential diagnosis of CL to eliminate false diagnoses of granulomatous diseases and skin cancers.
2. WHO Technical Report Series-949. Report of a meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22–26 March 2010.
3. Çavuş İ, Ocak F, Kaya T, et al. Cryopreservation of Leishmania Species in Manisa Province. Turkiye Parazitol Derg. 2007;41(3):152-5.
4. Culha G, Akyar I, Zeyrek FY, et al. Leishmaniasis in Turkey: determination of Leishmania species by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Iran J Parasitol. 2014; 9(2): 239-48.
5. Özbilgin A, Töz S, Harman M, et al. The current clinical and geographical situation of cutaneous leishmaniasis based on species identification in Tur-key. Acta Trop. 2019; 190: 59-67.
6. Aksoy M, Doni N, Yeşilova Y, et al. Bazal Hücreli Karsinomu Taklit Eden Kutanöz Layşmanyazis. Dermatoz. 2017.
7. Uzun S, Gürel MS, Durdu M, et al. Clinical practice guidelines for the diagnosis and treatment of cuta-neous leishmaniasis in Turkey. Int J Dermatol. 2018; 57(8): 973-982.
8. Kurban AK, Malak JA, Farah FS. Histological spec-trum of cutaneous leishmaniasis. Arch Dermatol. 1966; 93:396-401.
9. Culha G, Uzun S, Ozcan K, et al. Comparison of conventional and polymerase chain reaction diag-nostic techniques for leishmaniasis in the endemic region of Adana, Turkey. Int J Dermatol. 2006; 45(5): 569-72.
10. Schönian G, Schnur L, El Fari M, et al. Genetic heterogeneity in the species Leishmania tropica re-vealed by different PCR-based methods. Trans R Soc Trop Med Hyg. 2001; 95(2): 217-24.
11. Toz SO, Culha G, Zeyrek FY, et al. A real-time ITS1-PCR based method in the diagnosis and spe-cies identification of Leishmania parasite from hu-man and dog clinical samples in Turkey. PLoS Negl Trop Dis. 2013; 7(5): e2205.
12. Suster S, Ronnen M. Basal cell carcinoma arising in a Leishmania scar. Int J Dermatol. 1988;27(3):175-6.
13. Friedman R, Hanson S, Goldberg LH. Squamous cell carcinoma arising in a Leishmania scar. Dermatol Surg. 2003; 29(11): 1148-9.
14. Ünlü RE, Altun S, SSensöz Ö. Leishmania scar: a risk factor for the development of basal cell carci-nomas. J Craniofac Surg. 2007;18(3):708-10.
15. Tomasini C, Moneghini L, Barbui AM. Chronic amastigote-negative cutaneous leishmaniasis: A clin-ical, histopathologic and molecular study of 27 cases with emphasis on atypical and pseudolymphomat-ous presentations. J Cutan Pathol. 2017;44(6):530-37.
16. Akkafa F, Dilmec F, Alpua Z. Identification of Leishmania parasites in clinical samples obtained from cutaneous leishmaniasis patients using PCR-RFLP technique in endemic region, Sanliurfa prov-ince, in Turkey. Parasitol Res. 2008;103(3):583-6.
17. Ertabaklar H, Özlem SÇ, Boduç E, et al. Compari-son of direct microscopy, culture and polymerase chain reaction methods for the diagnosis of cutane-ous leishmaniasis. Mikrobiyol Bul. 2015;49(1):77-84.
18. Mohaghegh MA, Fata A, Salehi GH, et al. Molecu-lar identification of Leishmania species using samples obtained from negative stained smears. Iran J Para-sitol. 2013;8(2): 337-41.
19. Akcali C, Baba M, Inaloz S, et al. Cutaneous leish-maniasis mimicking squamous cell carcinoma. Ann Acad Med Singap. 2008;37(5):435-6.
20. Çulha G, Doğramacı AÇ, Savaş N, et al. Kutanöz leishmaniasis ve Hatay İlindeki durumu. Türk Hi-jyen ve Deneysel Biyoloji Dergisi. 2014;71(4);171-8.
21. Laskay T, Mikó TL, Negesse Y, et al. Detection of cutaneous Leishmania infection in paraffin-embedded skin biopsies using the polymerase chain reaction. Trans R Soc Trop Med Hyg. 1995;89(3):273-5.
22. Safaei A, Motazedian MH, Vasei, M. Polymerase chain reaction for diagnosis of cutaneous leishmani-asis in histologically positive, suspicious and negative skin biopsies. Dermatology. 2002;205(1):18-24.
23. Shirian S, Oryan A, Hatam GR, et al. Comparison of conventional, molecular, and immunohisto-chemical methods in diagnosis of typical and atypi-cal cutaneous leishmaniasis. Arch Pathol Lab Med. 2014;138(2):235-40
24. Prieto MD, Uribe-Restrepo AF, Arcos D, et al. Case Report: Squamous Cell Carcinoma Referred for Mohs Surgery Found to be Cutaneous Leish-maniasis. Am J Trop Med Hyg. 2018;99(6):1537-40.
25. Hashemi SA, Badirzadeh A, Sabzevari S, et al. First case report of atypical disseminated cutaneous leishmaniasis in an opium abuser in Iran. Rev Inst Med Trop São Paulo. 2018;60:e5.
26. Keleş E, Şengül S, Harman M, et al. Aurikuler Kutanöz Leişmanyazis: Olgu Sunumu. KBB Ve BCC Dergisi. 2015; 23(2):66-9.
27. Erdem H, Topal İO, Yıldırım Ü. Alısılmamıs görünümde kutanöz Leishmaniasis: Olgu sunumu. Dicle Tıp Derg/Dicle Med J. 2009;36(3); 216-218.
28. Youssef A, Yaseer S, Harfouch R, et al. Chiclero's ulcer: An unusual presentation of Leishmania tropica in Syria. Avicenna J Med. 2018;8(3):117-9.
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