Another Nasty Lung Fungus

[Tom Jones]

Here's another image from the clinical laboratory.

This is a photo of the dimorphic fungus Histoplasma capsulatum, the causative agent of Histoplasmosis, inside neutrophils in a peripheral blood smear.

In the wild, H. capsulatum grows as a mycelial fungus, producing microconidia that can be inhaled. It is the inhalation of the microconidia spores that results in pulmonary infection. Once inside the lungs the warmer temperature causes the microconidia to morph into budding yeast cells.

This image is a composite of three taken of adjacent fields. Two of the neutrophils from the adjacent images have been moved into this frame to provide a more pleasing image. The neutrophils were only moved, no other manipulations were done save for normal color balance, contrast enhancement and sharpening. You can also see a nucleated red blood cell just to the right of the central neutrophil.

Olympus BX-40, UPlanFl 100x oil, Canon 10D, PE 2.5x. Photoshop CS3 and Camera Raw. The stain used is a modified Wright-Giemsa.


Most infections are subclinical with no apparent symptoms. Those that do show symptoms will generally have a cold or flu-like, non-specific respiratory disease. In a small number of cases the organism disseminates to other organs and is often fatal if left untreated. One reference estimated around 90% of those living in areas where the fungus is endemic will be skin test positive, indicating prior infection. It is endemic in areas along the Ohio and lower Mississippi Rivers. As with many fungal infections, those with compromised immune systems, such as HIV patients, are at a higher risk of disseminated disease.

In this particular case the disease had disseminated, and the yeast cells were being phagocytized in huge numbers in the peripheral circulation. Most of the neutrophils had taken up several yeast cells. The organisms were found during a routine CBC when the patient was admitted to the hospital.

This is pretty rare here in Southern California, and this is only the second case I've seen where the yeast cells are visible in the circulating blood. Unfortunately, an infection of this magnitude is very, very difficult to treat. This patient succumbed to his disease the next morning.

Tom

[Pau]

Very impressive!

The stained oval particle outside neutrophils, is a fungal cell?

[Tom Jones]

Hi Pau,

Good catch! Yes. There is one extracellular yeast cell just below the upper left neutrophil. All of the rest are intracellular, having been phagocytized. The other stained, more diffuse looking objects are platelets.

Tom

[ChrisLilley]

Does the presence of reticulocytes indicate raised red blood cell production due to haemorrhage? (Not that once could estimate this from a single example of course).

[Tom Jones]

Chris,

The presence of reticulocytes does provide an imprecise indicator of red cell production. It can't distinguish between reasons for blood loss, only the response. It's used more to determine whether you are responding, and whether the reduced red cell mass is due to lack of production or blood loss such as an undectected gastrointestinal bleed.

It can also be used to determine the need for transfusion in non-acute cases. If you are anemic from lack of iron, and we give you iron, your retic count will increase dramatically. Since you are producing a lot of new red cells, transfusion may not be necessary. If you're anemic due to bone marrow supression for some reason, your retic count will be low indicating the need to transfuse.

There aren't any reticulocytes visible in this photo. They would show as bluer red cells (polychromasia), possibly with small dark blue granules (called basophilic stippling or pappenheimer bodies depending on their size). The numbers are generally estimated (few, moderate, many) and are not really countable using a Wright/Giemsa stain. Counting requires a special stain such as new methylene blue to adequately demonstrate the remaining ribosomal RNA. Some of the newer hematology analyzers count them using flow cytometry methods.

The presence of the nucleated red cell is most likely due to its being pushed out of the bone marrow early as a result of increased neutrophil production and expulsion from the marrow. Kind of collateral damage if you will, where the rbc is pushed out of the nest before its time and in such a manner as the nucleus isn't expelled in the processes.

Tom