Diagnosis by molecular pathology of an early and atypical histoplasmosis lesion in the duodenum of an immunocompromised patient: A case report

Abstract

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum (HC), which can occasionally be aggressive resulting in the formation of granulomatous lesions. These are usually located in the lungs; however, immunocompromised patients may occasionally develop disseminated lesions in other organs as well. Human immunodeficiency virus (HIV) primarily infects cells of the immune system expressing CD4 molecules. Not only does HIV multiply within these cells, but it can also kill them or otherwise cause loss of cellular function, leading to an immunocompromised state. As a result, in an immunocompromised patient, infection with HC can have serious implications, often the development of visceral histoplasmosis in different organs. Although several types of lesions are formed in HC-infected organs, it may be difficult to distinguish the causative organism from other pathogens based on morphology alone. The present case report describes the case of a 57-year-old woman, from South America, who may have been infected with HC >20 years previously, remaining asymptomatic over the years. She later developed a lesion in the duodenum associated with immunodeficiency caused by HIV infection. The differential diagnosis of this case was made on the basis of several specific morphological findings using histopathological analysis and molecular pathological techniques. The pathogenesis of characteristic lesions caused by HC in the presence of HIV infection was also reviewed.

Keywords: HIV; duodenum; histopathology; histoplasmosis; pathogenesis.

Figure 1

Endoscopic findings in the duodenum. The image shows a yellowish fine granular punctate and patchy lesions in the mucosa of the descending portion of the duodenum (arrow heads).

Figure 2

Histopathological findings in the duodenal mucosa based on hematoxylin and eosin staining. (A) Numerous foamy cells infiltrated the expanded lamina propria. Magnification, x10. (B) Several granular bodies with clear halos were present in the cytoplasm of the foamy cells. Magnification, x20. Based on histopathological analysis, the cytoplasmic granular bodies showed (C) a positive periodic acid-Schiff reaction (magnification, x20) and (D) Grocott staining (magnification, x40) as shown by the arrow heads.

Figure 3

Histochemical findings. (A) Foamy cells were CD68⁺. (B) CD8⁺ lymphocytes had mostly infiltrated into the lamina propria of the duodenal mucosa and only a few (C) CD4⁺ and (D) CD20⁺ lymphocytes were present. Magnification, x10.

Figure 4

Results of PCR and direct sequencing. (A) Agarose gel electrophoresis: Lane 1, molecular size markers; Lane 2, the first PCR product from the ITS primers (ITS1 and ITS4); Lane 3, the product from the histoplasma first round (Hcl and HcII primers); and Lane 4, the product from the histoplasma second round (HcIII and HcIV primers). (B) Additional PCR product from the ITS region. (C) Analysis of the amplicon reveals sequences specific for HC (GenBank accession nos. LC523625 and LC517841). ITS, internal transcribed subunit; HC, Histoplasma capsulatum.