J Med Cases

Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Med Cases and Elmer Press Inc

Journal website https://jmc.elmerpub.com

Case Report

Volume 16, Number 11, November 2025, pages 427-433

Histoplasmosis-Associated Hemophagocytic Lymphohistiocytosis in the Setting of Granulomatosis With Polyangiitis

Figure 1. Bone marrow core biopsy histopathology. (a) H&E staining at × 20 magnification showing hypercellular marrow (60% cellularity). (b) CD68 staining diffusely positive showing histiocytosis (right upper). (c) Wright-Giemsa staining at × 100 magnification showing erythrophagocytic forms and hemophagocytic forms with ingested leukocytes (lower left). (d) GMS staining showing narrow-based budding yeasts consistent with histoplasma capsulatum (right lower). GMS: Grocott-Gomori methenamine silver; H&E: hematoxylin and eosin.

Figure 2. Wright-Giemsa stain at × 200 (left) and × 1,000 (right) magnification showing a single histiocyte performing hemophagocytosis with ingestion of mature RBCs. RBCs: red blood cells.

Figure 3. GMS staining at × 40 (upper left, lower left) and × 100 (upper right, lower right) showing numerous extracellular small narrow-based yeast cells consistent with disseminated histoplasmosis. GMS: Grocott-Gomori methenamine silver.

**Table 1.** HLH-2004 Diagnostic Criteria and Patient Findings
Criteria	Patient finding	Criteria met?
HLH: hemophagocytic lymphohistiocytosis; NK: natural killer; sIL2R: soluble interleukin-2 receptor; WBC: white blood cell count.
Fever	Persistent fever up to 39.7 °C	Yes
Splenomegaly	Marked splenomegaly on imaging	Yes
Cytopenias in 2+ lineages	WBC 2.1 × 10⁹, Hgb 9.6 g/dL, platelets 71 × 10⁹	Yes
Hypertriglyceridemia (> 3 mmol/L) and/or hypofibrinogenemia (< 1.5 g/L)	Triglycerides 2.73 mmol/L, hypofibrinogenemia < 5 g/L	Yes (hypofibrinogenemia)
Hemophagocytosis in bone marrow, spleen, or lymph nodes	Bone marrow biopsy with hemophagocytic forms	Yes
Low or absent NK-cell activity	Not performed	No
Hyperferritinemia (> 500 µg/L)	Ferritin 12,700 µg/L	Yes
Elevated soluble CD25 (sIL2R) (> 2,400 U/mL)	sIL2R 10,324 U/mL	Yes

Table 1. HLH-2004 Diagnostic Criteria and Patient Findings

Criteria

Patient finding

Criteria met?

HLH: hemophagocytic lymphohistiocytosis; NK: natural killer; sIL2R: soluble interleukin-2 receptor; WBC: white blood cell count.

Fever

Persistent fever up to 39.7 °C

Yes

Splenomegaly

Marked splenomegaly on imaging

Yes

Cytopenias in 2+ lineages

WBC 2.1 × 10⁹, Hgb 9.6 g/dL, platelets 71 × 10⁹

Yes

Hypertriglyceridemia (> 3 mmol/L) and/or hypofibrinogenemia (< 1.5 g/L)

Triglycerides 2.73 mmol/L, hypofibrinogenemia < 5 g/L

Yes (hypofibrinogenemia)

Hemophagocytosis in bone marrow, spleen, or lymph nodes

Bone marrow biopsy with hemophagocytic forms

Yes

Low or absent NK-cell activity

Not performed

Hyperferritinemia (> 500 µg/L)

Ferritin 12,700 µg/L

Yes

Elevated soluble CD25 (sIL2R) (> 2,400 U/mL)

sIL2R 10,324 U/mL

Yes

**Table 2.** Key Laboratory Findings Over Hospital Course
Test	Result	Reference range	Hospital day
ALT: alanine transaminase; AST: aspartate aminotransferase; sIL2R: soluble interleukin-2 receptor; WBC: white blood cell count.
WBC	2.1 × 10⁹/L	4.0 - 11.00 × 10⁹/L	0
Hemoglobin	9.6 g/dL	12.0 - 16.0 g/dL	0
Platelets	71 × 10⁹/L	150 - 450 × 10⁹/L	0
AST	53 U/L	10 - 40 U/L	0
ALT	37 U/L	7 - 56 U/L	0
Ferritin	12,700 µg/L	13 - 150 µg/L	14
Triglycerides	2.73 mmol/L	< 1.7 mmol/L	14
Fibrinogen	< 5 g/L	200 - 400 mg/dL	14
sIL2R	10,324 U/mL	< 1,033 U/mL	14

Table 2. Key Laboratory Findings Over Hospital Course

Test

Result

Reference range

Hospital day

ALT: alanine transaminase; AST: aspartate aminotransferase; sIL2R: soluble interleukin-2 receptor; WBC: white blood cell count.

WBC

2.1 × 10⁹/L

4.0 - 11.00 × 10⁹/L

Hemoglobin

9.6 g/dL

12.0 - 16.0 g/dL

Platelets

71 × 10⁹/L

150 - 450 × 10⁹/L

AST

53 U/L

10 - 40 U/L

ALT

37 U/L

7 - 56 U/L

Ferritin

12,700 µg/L

13 - 150 µg/L

Triglycerides

2.73 mmol/L

< 1.7 mmol/L

Fibrinogen

< 5 g/L

200 - 400 mg/dL

sIL2R

10,324 U/mL

< 1,033 U/mL