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Sakda Sathirareuangchai, M.D.
Carolyn Glass, M.D., Ph.D.

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PubMed search: coccidioides [title] pulmonary pathology

Sakda Sathirareuangchai, M.D.
Carolyn Glass, M.D., Ph.D.
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Cite this page: Sathirareuangchai S, Glass C. Coccidioides. website. Accessed October 4th, 2023.
Definition / general
  • Lung infection caused by dimorphic fungi, Coccidioides spp.
Essential features
  • Highly prevalent in the endemic areas (southwest U.S., Central and South America)
  • Lower respiratory tract symptoms resembling bacterial pneumonia; mass lesion with cavity formation in chronic infection
  • Necrotizing granulomatous inflammation with characteristic spherules
  • Pulmonary coccidioidomycosis
  • San Joaquin Valley fever, valley fever
ICD coding
  • ICD-10: B38.2 - pulmonary coccidioidomycosis, unspecified
  • ICD-11: 1F25.0 - pulmonary coccidioidomycosis
  • Acquired via inhalation of aerosolized arthroconidia (3 - 5 microns) from the soil
  • A specialized structure called a spherule forms in the lung
  • Endospores are released from the ruptured spherule and develop into new spherules
  • Disseminate via hematogenous route
  • Dimorphic fungi in the genus Coccidioides, which contain 2 species
    • Coccidioides immitis (central and southern California, San Joaquin Valley)
    • Coccidioides posadasii (isolated outside California)
  • No difference in clinical course and microscopic morphology between the 2 species
Diagrams / tables

Images hosted on other servers:
Endemic areas

Endemic areas

Endemic areas

Coccidioides spp. life cycle

Clinical features
  • Most infected individuals are asymptomatic or minimally symptomatic
  • Symptoms include cough, fever, dyspnea, pleuritic chest pain
  • Can be disseminated in 1 - 5% of cases, especially immunocompromised patients (Medicine (Baltimore) 2004;83:149)
  • Desert rheumatism refers to the immunologic phenomena triad, including fever, arthralgia and erythema nodosum
  • Traveling history or residence in the endemic areas
  • Fungal organism identification by histology, culture or serology
  • Standard fungal culture: no specific plate morphology; lactophenol cotton blue stains shows septate hyphae with alternating barrel shaped arthroconidia
    • Biosafety level 3 pathogen: laboratory personnel should be aware of the diagnosis
  • Serologic testing for anticoccidioidal IgG, IgM
  • Increased serum (1→3)-β-D-glucan can be used to indicate invasive fungal disease, although not specific for coccidioidomycosis (J Clin Microbiol 2012;50:3060)
  • Complete blood count: eosinophilia found in 27% of cases (West J Med 1993;159:153)
Radiology description
  • Chest Xray and CT chest in acute infection: nonspecific, resembling acute bacterial pneumonia, including consolidation (75%), nodular opacities (20%), hilar adenopathy (20%), pleural effusion (15 - 20%); solitary pulmonary nodule may be seen (Radiographics 2014;34:912)
  • Disseminated infection: miliary nodules from hematogenous spread (Radiographics 2014;34:912)
  • Chronic cavitary lesion can be seen radiographically in 2% of cases, up to 11% by CT scan (Radiographics 2014;34:912)
  • Grape skin sign: classic finding in chronic pulmonary coccidioidomycosis (AJR Am J Roentgenol 2014;202:479)
    • Very thin walled cavitary lesion that develops in lung parenchyma previously affected by consolidation followed by central necrosis
Radiology description

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CT chest acute infection

CT chest acute infection

Case reports
  • Oral azole antifungal
  • Amphotericin B
  • Surgical resection of the cavitary lesion if (Clin Infect Dis 2016;63:e112)
    • Cavities are persistently symptomatic despite antifungal treatment
    • Cavities have been present for more than 2 years and if symptoms recur whenever antifungal treatment is stopped
Gross description
  • Mass lesion can be seen in chronic infection, usually well demarcated, often with central cavitation
  • Fungus ball (mycetoma) was found in 28% of cases with cavity lesion (Hum Pathol 2014;45:153)
Microscopic (histologic) description
  • Necrotizing, often suppurative, granulomatous inflammation
  • Large (20 - 200 microns) thick walled spherules, with or without granular basophilic endospores (2 - 4 microns)
  • Eosinophilic infiltrate is common
  • Thin, septate hyphae with arthroconidia formation may be seen, more often in diabetes mellitus patients (Eur J Clin Microbiol Infect Dis 2008;27:813)
  • Cavitary lesion features (Hum Pathol 2014;45:153)
    • Palisading fibroblasts and fibrosis with chronic inflammation
    • Granuloma not seen in the cavity wall, while multinucleated giant cells occasionally present
    • Squamous metaplasia in the lining of the cavity wall
    • Hyphal forms identified in 62% of cases
    • Blood vessel lesion: arteritis with fibrinoid necrosis and rupture, thrombus and mural chronic inflammation
  • Surrounding lung parenchyma (Hum Pathol 2014;45:153)
    • Lymphoid hyperplasia
    • Chronic bronchiolitis
    • Organizing pneumonia
Microscopic (histologic) images

Contributed by Sakda Sathirareuangchai, M.D.




Spherules GMS

Spherules GMS

Cytology description
  • Bronchoalveolar lavage (BAL) cytology (Diagn Cytopathol 2016;44:195)
    • Various forms of spherules with associated acute inflammatory response
    • Spherules can be immature (not adsorb any stains), smaller, larger, empty or fractured
  • Granulomas were rare and mostly seen in lymph nodes and extra pulmonary sites (Diagn Cytopathol 2016;44:195)
  • Mycelial form in BAL is uncommon but has been reported (Diagn Cytopathol 2007;35:535)
Cytology images

Contributed by Sakda Sathirareuangchai, M.D.
Spherule cytologic smear

Spherule cytologic smear

Positive stains
Negative stains
Molecular / cytogenetics description
  • Real time PCR assay is available for various types of specimen (e.g., bronchoalveolar lavage, sputum, lung tissue, etc.)
  • In situ hybridization for C. immitis ribosomal RNA has been described (Diagn Mol Pathol 2010;19:99)

Dimorphic fungi: coccidioidomycosis by Glenn D. Roberts, Ph.D.

Sample pathology report
  • Left lung, core needle biopsy:
    • Necrotizing granulomatous inflammation (see comment)
    • Comment: Fungal organism identified on H&E and GMS stain, consistent with Coccidioides spp.
Differential diagnosis
  • Histoplasmosis:
    • Endemic in the central and eastern U.S. (Ohio and Mississippi River valleys)
    • Small (2 - 5 microns) budding yeast within the histiocytes
  • Blastomycosis:
    • Endemic in the eastern U.S. (Ohio, Mississippi River valleys, Great Lakes region)
    • Broad based budding yeast, smaller (8 - 15 microns) than Coccidioides sp.
  • Paracoccidioidomycosis:
    • Endemic in South America
    • Large (10 - 60 microns) spherical yeast with circumferential budding, resembling mariner’s wheel
  • Cryptococcosis:
    • No specific endemic area
    • Round, medium sized (4 - 7 microns), yeast with thick mucoid capsule
  • Tuberculosis:
    • Acid fast positive bacilli
Board review style question #1

A 40 year old man presents with chronic cough, low grade fever and mild dyspnea for several months. CT scan of the chest shows a 3 cm mass lesion in the right upper lobe of the lung. The H&E image of the core needle biopsy is shown. Which one of the followings is the most likely exposure history?

  1. Cave diving in Ohio
  2. Military training in Arizona
  3. Parakeet breeder
  4. Traveling to Africa
  5. Camping in Colorado
Board review style answer #1
B. Military training in Arizona. The patient has coccidiomycosis.

Comment Here

Reference: Coccidioides immitis
Board review style question #2
What is the pathognomonic microscopic feature of coccidioidomycosis in a histologic section?

  1. Broad based budding yeast
  2. Round yeast with large mucoid capsule
  3. Acute angle, branching septate hyphae
  4. Large spherule with numerous endospores
  5. Oval yeast with pseudohyphae budding
Board review style answer #2
D. Large spherule with numerous endospores

Comment Here

Reference: Coccidioides immitis
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