Microbiology & parasitology
Fungi
Molds
Dematiaceous molds


Topic Completed: 22 September 2020

Minor changes: 22 September 2020

Copyright: 2019-2020, PathologyOutlines.com, Inc.

PubMed Search: Dematiaceous mold[TIAB]

Alison Burkett, M.D.
Sixto M. Leal, Jr., M.D., Ph.D.
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Cite this page: Burkett A, Saitornuang S, Leal SM. Dematiaceous molds. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/microbiologydematiaceousmolds.html. Accessed October 24th, 2020.
Definition / general
  • Heterogeneous molds characterized by dark pigmentation of hyphae (Clin Microbiol Rev 2010;23:884)
  • Hundreds of species known to cause disease in humans
  • Phaeohyphomycosis: invasion of tissue by pigmented hyphae
  • Chromoblastomycosis: chronic subcutaneous infection characterized by pigmented round structures termed copper pennies
  • Mycetoma: subcutaneous collection of pigmented hyphae that expands within the tissue (tumor-like growth)
Essential features
  • Phaeohyphomycosis
    • Alternaria sp.
    • Bipolaris sp.
    • Curvularia sp.
    • Exserohilium sp. (outbreak associated with steroid injections)
    • Lomentospora prolificans (resistant to all antifungal agents)
    • Cladophialophora bantiana (neurotropic; immunocompetent)
    • Exophiala dermatitidis (neurotropic; black yeast)
    • Rhinocladiella mackenzeii (neurotropic)
    • Verruconis gallopava (neurotropic)
  • Chromoblastomycosis
    • Fonsecaea pedrosoi and other species
    • Phialophora sp.
    • Cladophialophora sp.
  • Mycetomas
    • Madurella sp.
    • Rhinocladiella
    • Exophiala jeanselmei (black yeast)
  • Allergic disease
    • Many ubiquitous black molds
  • Reference: Clin Microbiol Rev 2010;23:884
Epidemiology
  • Organisms present in soil with worldwide distribution
  • Mycetoma and chromoblastomycosis with highest incidence in tropical and subtropical zones
  • Direct subcutaneous inoculation or spore inhalation
  • CARD9 genetic deficiency associated with severe disease (Front Immunol 2018;9:1836)
    • A type of primary immunodeficiency affecting the caspase recruitment domain family member 9 regulating apoptosis and inflammation through modulation of signals from pro and anti-inflammatory cytokines
    • Individuals have increased susceptibility to fungal infections, especially phaeohyphomycetes, dermatophytes and candida
    • The condition follows an autosomal recessive mode of inheritance
Sites
Pathophysiology
  • Melanin production in hyphae scavenges free radicals and inhibits phagocytosis (Kauffman: Essentials of Clinical Mycology, 2nd Edition, 2011)
  • Acute inflammatory cells fail to clear infection, leading to pyogranulomatous inflammation
    • Characterized by neutrophils infiltrating a chronically inflamed area containing mononuclear cells
Clinical features
  • Phaeohyphomycotic cyst: well circumscribed subcutaneous nodule with pigmented hyphae
  • Phaeohyphomycosis: pigmented hyphae invading within tissue (typically skin, lung, brain)
  • Chromoblastomycosis: psoriasis-like chronic skin inflammation and hyperkeratinization with pigmented round sclerotic bodies (copper pennies) in tissue; no hyphae present (Bennett: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th Edition, 2014)
  • Mycetoma: a focal subcutaneous collection of pigmented hyphae (fungus ball)
  • All lesions are characterized by pyogranulomatous inflammation
Diagnosis
  • MALDI-TOF mass spectrometry is a standard method for speciation and antimicrobial susceptibility; while microscopic examination is widely used in most institutions, results are often limited to genus
Laboratory
  • Black pigmentation on the backside of the culture plate is due to melanin production in hyphae and is pathognomonic for dematiaceous mold (Kauffman: Essentials of Clinical Mycology, 2nd Edition, 2011)
  • Rapidly growing molds (~2 - 4 days) include:
    • Alternaria sp.
    • Bipolaris sp.
    • Curvularia sp.
    • Exserohilum sp.
    • Lomentospora prolificans
  • Most other pathogenic dematiaceous molds are slow growing
  • Black yeast colonies initially appear yeast-like, develop a fuzzy edge and convert to molds
Case reports
Treatment
  • No standardized treatment; however, itraconazole, voriconazole and posaconazole have been used successfully
  • Infection with chromoblastomycosis can be treated with combination itraconazole and terbinafine but may require surgery, chemotherapy or thermotherapy (Kauffman: Essentials of Clinical Mycology, 2nd Edition, 2011)
  • Treatment often occurs over an extended period of time; months to years
Clinical images

Contributed by Sixto M. Leal, Jr., M.D., Ph.D.

Dermatiaceous (black) mold

Microscopic (histologic) description
  • Phaeohyphomycosis: pigmented septate hyphae with occasional globose swellings
  • Chromoblastomycosis: dark sclerotic bodies with thick walled septations
  • Mycetoma: black mycotic granules or grains surrounded by dense extracellular matrix
  • May exhibit Splendore-Hoeppli phenomena due to antigen / antibody protein complex deposition
    • Also known as asteroid bodies, these formations of eosinophilic material around microorganisms (fungi, parasites, bacteria) and foreign material are observed in multiple mucocutaneous and noninfectious conditions (J Cutan Pathol 2008;35:979)
  • Pigmentation may be faint; Fontana-Masson stain for melanin may prove helpful
Microscopic (histologic) images

Contributed by Sixto M. Leal, Jr., M.D., Ph.D.

Characteristic fruiting bodies

Evaluation of fungal elements with various stains

Molecular / cytogenetics description
  • 28S rDNA sequencing
Differential diagnosis
Board review style question #1
A 64 year old man with medical history significant for hypertension, atrial fibrillation and deep vein thrombosis presents to the hospital with generalized right sided weakness and right sided facial droop for 12 days. Neurological deficits are noted on physical exam but lab results are within normal limits. He is afebrile and denies nausea, vomiting or headache. Imaging reveals a 3 cm x 2 cm ring enhancing mass in the left frontal lobe. Biopsy reveals abscess formation with necrotizing granulomatous inflammation and irregular brown hyphal elements on H&E.

What is the most likely etiology?

  1. Actinomyces meyeri
  2. Cladophialophora bantiana
  3. Rhizopus oryae
  4. Toxoplasma gondii
Board review answer #1
A. Anaerobic filamentous bacteria like Actinomyces meyeri form large aggregates (sulfur granules) in tissue and are not pigmented. Rhizopus hyphae are broad and pauciseptate but not pigmented. T. gondii is a parasite and does not make hyphae. The neurotropic mold C. bantiana, like other dematiaceous molds causing phaeohyphomycosis, have hyphae with melanin that appear light to dark brown / black in tissue.

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Reference: Dematiaceous molds
Board review style question #2
A 42 year old woman from Brazil presented with a red verrucous lesion on her wrist which has been progressively increasing in size over the last 4 months. Further evaluation reveals erythematous plaques with silvery scales on the extensor surfaces of her upper extremities. Biopsy reveals pyogranulomatous inflammation and dark brown round structures but no hyphae. 4 weeks later, 5 mold colonies appear on the plate all with dark brown pigmentation on the reverse of the plate.

What is the most likely etiology?

  1. Malignancy: squamous cell carcinoma
  2. Fungal infection: phaeohyphomycosis
  3. Autoimmune: plaque psoriasis
  4. Fungal infection: chromoblastomycosis
Board review answer #2
D. Chronic skin lesions caused by chromoblastomycosis can grossly mimic squamous cell carcinoma but most closely resemble the scaly plaques of psoriasis. A diagnosis of phaeohyphomycosis requires the detection of invasive pigmented hyphae. Chromoblastomycosis is caused by slow growing dematiaceous molds such as Fonsecaea pedrosoi that elicit acute and chronic inflammation (pyogranulomatous). No hyphae are seen in the tissue and instead the mold forms darkly pigmented muriform structures termed copper pennies.

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Reference: Dematiaceous molds
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