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. 2024 Sep 12:11:1453211.
doi: 10.3389/fmed.2024.1453211. eCollection 2024.

Diagnostic challenges in cutaneous leishmaniasis due to atypical Leishmania infantum: pathologists' insights from re-emergence zones

Affiliations

Diagnostic challenges in cutaneous leishmaniasis due to atypical Leishmania infantum: pathologists' insights from re-emergence zones

Suheyla Ekemen et al. Front Med (Lausanne). .

Abstract

Background: Leishmaniasis, a parasitic infection affecting both humans and animals, is increasingly spreading across Mediterranean and European regions, largely driven by human migration and environmental changes. In countries like Türkiye and across Europe, which have seen large influxes of migrants, the incidence of cutaneous leishmaniasis (CL) is rising, with cases now appearing in cities where the disease was previously undocumented. In these previously non-endemic areas, physicians unfamiliar with the characteristic lesions may misdiagnose CL, particularly in cases with only cutaneous manifestations. This study aims to evaluate the impact of re-emerging CL on the routine diagnostic practices of pathologists in Türkiye, by retrospectively reviewing cases.

Methods: We conducted a retrospective analysis of CL cases diagnosed between 2013 and 2022 at a single pathology center in Türkiye, covering multiple provinces. Twelve cases of CL were identified and analyzed based on clinical presentation, pre-diagnosis, histopathological findings, and molecular diagnostics. DNA extraction and PCR were performed on paraffin-embedded tissue samples to identify the Leishmania species involved.

Results: Out of the twelve CL cases reviewed, seven exhibited morphological findings strongly suggestive of CL (MFSS of CL), warranting further microbiological evaluation. All patients presented with non-healing skin lesions characterized by central ulceration, crater-like formations, or papulonodular lesions. Notably, CL was included in the clinical pre-diagnosis in only 58.3% of cases, while it was not considered in the remaining 41.7% of cases. Clinicians initially pre-diagnosed skin tumors in six cases (50%), four of which led to wide surgical excision. Histopathological examination in all cases revealed chronic or mixed (acute/chronic) inflammation, predominantly rich in histiocytes. To further investigate the role of Leishmania species in the pre-diagnosis, DNA extraction and PCR were performed on paraffin-embedded tissue samples, identifying L. infantum as the causative agent in 10 cases and L. major in two cases. Notably, L. infantum was the causative agent in all five cases initially misdiagnosed as skin tumors, which were also associated with a granulomatous type of chronic inflammation.

Keywords: Leishmania infantum; PCR; cutanaous leishmaniasis; dermatopathology; misdiagnosis; reemergence; skin tumors; surgery.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Case #2, a case with necrotizing granulomatous dermatitis (NGD) initially clinically misdiagnosed as keratoacanthoma. (A,B) Orthokeratosis and focal parakeratosis (white arrow) in the epidermis, and necrotizing granuloma formations (white arrows), and granuloma structures and intense chronic inflammation (grey arrow) in the dermis [H&E staining, Scale bars 5 mm (A) and 1 mm (B)]. (C) Granuloma structure with dotted-square in B, and histiocytic infiltration around grey arrow necrotizing area (H&E, Scale bar 200 μm). (D) Leishmania amastigotes (example small yellow arrows among many) within histiocytes (example black dotted circles with their nuclei) (Giemsa stain, 100 x magnification with oil). L. infantum detected by PCR.
Figure 2
Figure 2
Case #8, a typical case with chronic inflammation, initially clinically pre-diagnosed as leishmaniasis. (A) An irregular proliferation in the epidermis, and diffuse infiltration in the dermis rich in histiocytes, including lymphocytes and plasma cells (H&E stain, Scale bar 1 mm). (B) Magnified area from the dotted-square in A (H&E stain, Scale bar 500 μm). (C) Area shown around white arrow in B. Leishmania amastigotes (example small yellow arrows among many) within large histiocytes (example black dotted circles with their nuclei) (Giemsa stain, 100 x magnification with oil). L. infantum detected by PCR.
Figure 3
Figure 3
Case #12, a case with mixed (acute and chronic) type inflammation, initially clinically pre-diagnosed with leishmaniasis and other diseases such as Tbc, sarcoidosis and DLE. (A) Granulomatous inflammation with necrosis in the dermis (white arrow shows granuloma structure) (H&E stain, Scale bar 5 mm). (B) Magnified area in A showing intense inflammation in the dermis and granuloma structure marked with white arrow (H&E stain, Scale bar 1 mm). (C) Closer look at the granuloma structure in B. A few thick yellow arrows showing Leishmania amastigotes in necrotic areas (H&E stain, Scale bar 25 μm). (D) Giemsa staining of the area in C showing clusters of Leishmania amastigotes (example thin yellow arrows among many, residing in clusters shown as small yellow-dotted circles) within histiocytes (Giemsa stain, magnified with oil). L. infantum detected by PCR.
Figure 4
Figure 4
Case #10, a case with NGD initially clinically pre-diagnosed as skin adnexal tumor (SAT), and the lesion was completely excised. (A) Irregular acanthosis, spongiotic changes in the epidermis, and edema in the dermis with chronic inflammation rich with diffuse histiocytes (H&E stain, Scale bar 500 μm). (B) White arrow area in A. Yellow arrows show amastigotes (H&E stain, Scale bar 50 μm). (C) Oil magnified Giemsa stained sections. Thin yellow arrows show Leishmania amastigotes within giant histiocytes (example black dotted circle) (Giemsa stain, magnified with oil). L. infantum detected by PCR.
Figure 5
Figure 5
Quantitative real time PCR (RT-PCR) analysis using primers and probes specific for the ITS-1 region of Leishmania. The graph shows melting curve analyses of L. major, L. tropica and L. infantum reference strains and 12 patient isolates.

References

    1. WHO . Weekly Epidemiological Record. Geneva: WHO; (2023).
    1. Elmahallawy EK, Sampedro Martínez A, Rodriguez-Granger J, Hoyos-Mallecot Y, Agil A, Navarro Mari JM, et al. . Diagnosis of leishmaniasis. J Infect Dev Ctries. (2014) 8:961–72. doi: 10.3855/jidc.4310 - DOI - PubMed
    1. Schwing A, Pomares C, Majoor A, Boyer L, Marty P, Michel G. Leishmania infection: misdiagnosis as cancer and tumor-promoting potential. Acta Trop. (2019) 197:104855. doi: 10.1016/j.actatropica.2018年12月01日0, PMID: - DOI - PubMed
    1. Gurel MS, Tekin B, Uzun S. Cutaneous leishmaniasis: a great imitator. Clin Dermatol. (2020) 38:140–51. doi: 10.1016/j.clindermatol.201910008 - DOI - PubMed
    1. de Vries HJC, Schallig HD. Cutaneous Leishmaniasis: a 2022 updated narrative review into diagnosis and management developments. Am J Clin Dermatol. (2022) 23:823–40. doi: 10.1007/s40257-022-00726-8, PMID: - DOI - PMC - PubMed

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