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Diagnostics Histology, Training and education

Case of the Month

A five-year-old girl presented with headache and vomiting for one week. MRI showed a large, round, relatively well-circumscribed tumor measuring 6x5x4.5 cm in the right thalamic region. The lesion displayed heterogeneous signal intensity and showed enhancement of its superomedial aspect, which also contained an irregular area of necrosis. A biopsy was obtained and a diagnosis of diffuse midline glioma, H3K27 mutant, was made.

Which statement about diffuse midline glioma is true?

a. Despite its name, it is typically not found in the midline.
b. It often lacks high-grade histologic features, but is still considered grade IV.
c. The diagnosis includes midline gliomas that are diffusely infiltrating but have not been tested for the H3 K27M mutation.
d. The prognosis varies based on the histologic features.

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The Case of the Month series is curated by Anamarija M. Perry, University of Michigan.

B. Disseminated histoplasmosis

Disseminated histoplasmosis is a systemic infection caused by Histoplasma capsulatum, a dimorphic fungus. Most Histoplasma capsulatum infections are asymptomatic; however, those with impaired cell-mediated immunity are at risk of developing a severe systemic infection. Histoplasma capsulatum is among the most common fungi found in bone marrow specimens and is rarely found in peripheral blood smears. In tissues, Histoplasma capsulatum var. capsulatum consists of 2–4 μm yeasts with narrow-based budding, crescent-shaped eccentric chromatin, and a pseudocapsule caused by cytoplasmic retraction. Yeasts are typically inside phagocytes; however, extracellular forms are also possible. Systemic histoplasmosis can be associated with hemophagocytic lymphohistiocytosis (as in this case). Morphologic differential diagnoses in peripheral blood and bone marrow specimens include Candida spp., Toxoplasma gondii, Talaromyces marneffei, and Leishmania organisms causing visceral leishmaniasis. All of these organisms can be found within leukocytes in varying proportions and have overlapping sizes. Candida (2–4 μm) is the most common cause of fungemia in hospitalized patients and is the most frequently identified fungus in the peripheral blood; as well as budding yeasts, it also demonstrates pseudohyphae. Leishmania (3 μm) is typically present within macrophages in bone marrow specimens and consists of oval organisms with a single nucleus and a paranuclear kinetoplast, which give the organisms a “double dot” appearance. Toxoplasma gondii tachyzoites are rarely found in peripheral blood smears, but can sometimes be identified in bone marrow specimens as either intracellular (within phagocytes) or extracellular organisms; they lack a pseudocapsule. Systemic Talaromyces marneffei infection primarily occurs in immunosuppressed patients that have resided or visited southeast Asia. Talaromyces marneffei consists of small (2–5 μm), sausage-shaped yeasts with a transverse septum, which are predominantly within macrophages. 

Submitted by Efrain Gutierrez-Lanz, University of Michigan, Ann Arbor, Michigan, USA.

Further Reading

  1. CA Kauffman, Clin Microbiol Rev, 20, 115 (2007). PMID: 17223625.
  2. EF Glassy, Color Atlas of Hematology: An Illustrated Field Guide Based on Proficiency Testing, 266. College of American Pathologists: 1998.
  3. J Guarner, ME Brandt ME, Clin Microbiol Rev, 24, 247 (2011). PMID: 21482725.
  4. BJ Bain et al., Bone Marrow Pathology, 5th ed. Wiley Blackwell: 2019.
  5. AL Mora Carpio, A Climaco A (2020). Available at: bit.ly/3eqxbbw.

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