ORIGINAL ARTICLE

Diagnosis of deep cutaneous fungal infections:

Correlation between skin tissue culture
and histopathology
Tania M. Gonzalez Santiago, MD,a Bobbi Pritt, MD,b Lawrence E. Gibson, MD,a,b and Nneka I. Comfere, MDa,b
Rochester, Minnesota

Background: Deep cutaneous fungal infections (DCFIs) are responsible for significant morbidity and
mortality, particularly in immunocompromised patients. Although a direct correlation between histopath-
ologic examination and culture is expected, discordant findings may be seen, presenting a unique
diagnostic and therapeutic challenge.

Objectives: We sought to determine the correlation between skin tissue cultures and histopathologic
examination in patients with DCFI.

Methods: This is a 10-year retrospective review (2003-2012) of patients with a diagnosis of DCFI seen at a
single tertiary care institution. Tissue cultures and histopathologic findings were reviewed.

Results: In 8 of 33 cases, fungal elements were seen on routine histopathologic sections but skin cultures
were negative. Three of 8 of the discordant cases had concurrent positive noneskin tissue cultures that
correlated with the pathology interpretation, and 3 of 8 patients in the discordant group died of systemic
fungal infection.

Limitations: This was a retrospective study design and a single tertiary care institution experience.

Conclusions: The histopathologic interpretation of skin tissue specimens is critical for rapid and accurate
diagnosis of DCFI. Despite the identification of fungal organisms on histopathologic assessment of skin
tissue specimens, skin tissue culture may fail to show fungal growth. A diagnosis of a DCFI and initiation of
appropriate treatment should always be considered in spite of discordant results. ( J Am Acad Dermatol
http://dx.doi.org/10.1016/j.jaad.2014.03.042.)

D eep cutaneous fungal infections (DCFIs) are

associated with significant morbidity and
mortality, especially in immunocompro-
mised patients. Mortality rates range from 4% to
Abbreviations used:
BAL:
CSF:
DCFI:
bronchoalveolar lavage
cerebrospinal fluid
deep cutaneous fungal infection
10% in localized infections and can be as high as GMS: Grocott methenamine silver
83% to 94% in disseminated disease.1 The clinical MPA: microscopic polyangiitis
PAS: periodic acideSchiff
presentation of DCFI is variable and dependent on PBSCT: peripheral blood stem cell transplant
host-related factors, the type of fungal organism, SLE: systemic lupus erythematosus
and the mode of transmission.2,3 Because of the
nonspecificity of presenting clinical symptoms, cuta-
neous lesions may be misdiagnosed as cutaneous the skin may herald the onset of a life-threatening
neoplasms or necrotizing lesions caused by coagu- systemic mycosis.4,5 Therefore, the rapid diagnosis
lation disorders. In addition, initial presentations in and characterization of the offending fungus is

From the Departments of Dermatologya and Laboratory Medicine
and Pathology,b Mayo Clinic, College of Medicine, Rochester.
Funding sources: None.
Conflicts of interest: None declared.
Accepted for publication March 30, 2014.
Reprints not available from the authors.
Correspondence to: Nneka I. Comfere, MD, Department of
Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN
55905. E-mail: comfere.nneka@mayo.edu.
Published online May 15, 2014.
0190-9622/$36.00
Ó 2014 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2014.03.042

1
2 Gonzalez Santiago et al J AM ACAD DERMATOL

essential for appropriate treatment, which carries defined as those with fungal organisms identified on
significant prognostic implications. histopathology and without growth of fungal
Routine histopathologic examination of lesional organisms in skin tissue culture. The discordant
skin tissue remains the primary method of confirming group was defined this way given the differences
a DCFI. It permits fast, presumptive identification of in turnaround time, with return of histopathology
fungi and can also provide some insight into the results preceding tissue culture results.
diagnostic implication of some culture isolates.
Because of the variable and
longer turnaround time on RESULTS
tissue culture results relative CAPSULE SUMMARY Patient characteristics
to routine histopathology, Twenty-six of 33 patients
the latter is often relied on
d Deep cutaneous fungal infections are were in an immunosup-
for the rapid diagnosis of responsible for significant morbidity and pressed state. Thirteen of 26
DCFI. Although direct mortality. immunosuppressed patients
correlation between these 2 d Discordant findings between were also transplant patients
diagnostic tests is expected, histopathology and culture results are (9/13 with a history of solid
discrepancies between histo- often seen and present a diagnostic and organ transplant and 4/13
pathology and culture results therapeutic challenge. with bone marrow/stem cell
are sometimes seen,6 with d Increased awareness about these transplant). Five patients had
resultant treatment delays, diagnostic pitfalls may prevent adverse an underlying lymphoproli-
morbidity, and mortality. consequences associated with delays in ferative disorder without a
Few studies have investi- diagnosis and treatment, especially in history of transplantation.
gated the correlation be- immunosuppressed patients. The remaining immuno-
tween the results of suppressed patients had
histopathologic examination an underlying malignancy
of skin tissue specimens and (10/22). Three patients had
tissue cultures. The aim of this review is to describe a history of autoimmune disorders managed with
the clinical, histopathologic, and microbiologic long-term systemic corticosteroids, including 1 case
findings in a series of patients with a diagnosis each of microscopic polyangiitis (MPA), psoriasis,
of DCFI and characterize features predictive of and systemic lupus erythematosus (SLE). Other
discordance between the lesional histopathology identified comorbid conditions included HIV,
and skin tissue culture. sarcoidosis, diabetes, and occupational exposure
(in a patient who worked at a turkey processing
METHODS plant). Seven of 33 patients were otherwise healthy.
We performed a 10-year retrospective review of Healthy individuals were immunocompetent and
all histopathologic specimens diagnosed as DCFIs had no identifiable underlying systemic predisposi-
and their corresponding skin culture results in the tion for opportunistic infections. Twenty-one of 33
Department of Dermatology, Mayo Clinic, Rochester, patients had a primary cutaneous mycosis, while 12
Minnesota between 2003 and 2012. Forty-six DCFI of 33 patients had a systemic mycosis with secondary
cases were identified by a search of our CoPath cutaneous involvement (Tables I-III).
(pathology information system) database. Thirteen
cases of DCFI without concurrent skin tissue culture Clinical findings
for fungi were excluded from analysis. Thirty-three Areas of involvement included the upper extrem-
patients with a diagnosis of DCFI were included. The ities (15/33), lower extremities (10/33), trunk (3/33),
electronic medical record for included cases was multiple sites of skin involvement (3/33), and the
reviewed and the following data were abstracted: head and neck region (2/33). Clinical presentations
patient age, sex, location of the sampled skin lesion, encompassed nodules (22/33), ulcerated nodules
underlying medical comorbidities, histopathologic (4/33), plaques (4/33), ulcers (2/33), and erythema-
interpretation, histochemical stains, skin microbi- tous macules in 1 patient. Nine of 33 patients
ology results, and antifungal therapy. The subset of presented with clinical evidence of tissue necrosis
cases with discordance between the pathology (Part A of Figs 1 to 3).
diagnosis and tissue culture results (discordant
cases) were identified, and review of the lesional Histopathologic findings
skin pathology was performed by a board-certified In all cases (33/33), fungal elements were identi-
dermatopathologist (N.C.). Discordant cases were fied on routine hematoxylineeosin (H&E) stained
J AM ACAD DERMATOL Gonzalez Santiago et al 3

Table I. Patient characteristics Table II. Comorbid conditions

Characteristic n (%) Condition n (%)
Gender Oligoastrocytoma (grade 2) 1
Male 24 (72.7) Lymphoproliferative disorders 9 (27.3)
Female 9 (27.3) Chronic myelogenous leukemia (allogeneic 1
Median age, y 54 PBSCT)
Immunologic status Follicular lymphoma (grade 3) 1
Immunosuppressed 26 (78.7) Hodgkin lymphoma (autologous PBSCT) 1
Nonimmunosuppressed 7 (21.2) Acute myelocytic leukemia (allogeneic 2
PBSCT)
Chronic lymphocytic leukemia 1
skin sections, and in 29 of 33 cases fungal Chronic lymphocytic leukemia (stem cell 1
stains (ie, Grocott methenamine silver and/or transplant)
periodic acideSchiff) were used to confirm Mantle cell lymphoma 1
B-cell acute lymphocytic leukemia 1
the diagnosis (Parts B and C of Figs 1 and 2
Organ transplant 9 (27.3)
and Parts B to D of Fig 3). Fungi identified on
Kidney, pancreas 3
H&E sections included zygomycosis, Alternaria, Heart 2
phaeohyphomycosis, blastomycosis, Coccidioides, Lung 1
hyalohyphomycosis, and Trichophyton. The pre- Liver 1
dominant histopathologic patterns were granuloma- Kidney 1
tous inflammation (18/33), pseudoepitheliomatous Kidney, liver, and heart 1
hyperplasia (2/33), perivascular and interstitial Iatrogenic immunosuppression* 3 (9)
inflammation without granulomas (1/33), small Microscopic polyangiitis 1
vessel vasculitis (1/33), and necrosis (1/33). In Psoriasis 1
10 of 33 cases, a mixture of histopathologic Systemic lupus erythematosus 1
patterns was seen (Table IV). Miscellaneousconditions and exposures 4 (12)
Occupational (turkey meateprocessing plant 1
employee)
Microbiologic findings Sarcoidosis 1
In 25 of 33 cases, the skin tissue culture revealed Diabetes 1
fungal growth, while in 8 of 33 cases skin HIV/AIDS 1
cultures were negative. Organisms identified in Total 26 (78.7)
tissue cultures included Blastomyces dermatitidis, Healthy individuals 7 (21)
Alternaria, Rhizopus, Fusarium, Acremonium,
Pseudoallescheria, Trichophyton mentagrophytes, PBSCT, Peripheral blood stem cell transplant.
*Iatrogenic immunosuppression includes long-term systemic
Coccidioides immitis, and Aspergillus. In addition, steroids.
7 of 12 patients with systemic mycosis also had a
noneskin tissue culture performed (ie, cerebrospi-
nal fluid [CSF], brain tissue, or bronchoalveolar Table III. Primary versus secondary infection
lavage [BAL]). Four of the 7 patients with noneskin according to immunologic state
tissue cultures had a concomitant positive skin tissue n (%)
culture (Table V). Primary deep cutaneous mycosis 21 (63.6)
Immunosuppressed 15
Fungal identification Nonimmunosuppressed 7
Fungal organisms were identified within routine Systemic mycosis with secondary 12 (36.4)
histologic sections in 23 of 33 cases, either of a cutaneous involvement
specific fungal species or within a fungal class. Immunosuppressed 7
Eighteen of 23 had the same identified fungus on Nonimmunosuppressed 4
histopathology and tissue culture results; however, 5
of 23 were misclassified on histopathology.
mycosis and secondary cutaneous involvement (3/6)
Discordant cases and primary cutaneous mycosis (3/6). Two of 8
In 8 of 33 cases, skin tissue cultures were negative patients were not immunosuppressed, and both
despite the identification of fungal organisms on had primary cutaneous mycosis. A noneskin tissue
histopathology. Six of 8 patients were immunosup- culture was performed in 3 of 8 cases. This was
pressed, with equal numbers of cases with systemic positive for all 3 cases with the following findings:
4 Gonzalez Santiago et al
Fig 1. A, Zygomycosis. Purpuric, indurated, plaques
(solid arrows) on the abdomen of a patient with chronic
lymphocytic leukemia, posteperipheral blood stem cell
transplantation. B and C, Hematoxylineeosin staining
revealed small, intravascular, hyaline, fungal hyphal forms
(dashed arrows). In this case, skin cultures were
negative despite the identification of intravascular hyphae.
This patient died of disease. (Original magnification: B and
C, 320.)
Aspergillus spp on CSF culture and a BAL, and
Exophiala jeanselmei in a body fluid secretion
from a skin lesion. In 2 of these 3 cases, the
fungal organisms were correctly identified on
histopathology (Table VI).
DISCUSSION
Over a 10-year period at a single tertiary care
facility, we identified 33 patients with a histopatho-
logic diagnosis of a DCFI. While the incidence of
DCFI in the general population is unknown, it is
more common in the immunocompromised
J AM ACAD DERMATOL
Fig 2. A, Disseminated aspergillosis. Purpuric plaque
(solid arrow) with associated bulla (dashed arrow) on
the chest of a patient with heart transplant. B, Hematox-
ylineeosin staining revealed multiple 458 (dashed arrow),
branching hyphae (solid arrows) associated with suppu-
rative inflammation and necrosis. C, Grocott methenamine
silver staining of lesional skin demonstrates branching
fungal hyphae and budding (blue arrows). In this case,
skin cultures were negative despite these histopathologic
findings. Diagnosis was confirmed with CSF cultures.
Patient died of disease. (Original magnification: B and
C, 340.)
population, occurring in 20% to 30% of organ
transplant recipients, with the highest rates noted
within the first 2 years posttransplantation. The
observed frequency of invasive fungal infections
has been estimated to range between 20% and 30%
in patients with acute leukemia, 10% and 15% in
patients with lymphoma, and 5% in patients with
other malignancies.7-11 In this study, the number of
identified DCFI cases is lower than estimates in the
J AM ACAD DERMATOL Gonzalez Santiago et al 5

Fig 3. A, Primary cutaneous alternariosis and microscopic polyangiitis. Ulcerated purpuric

plaques in a sporotrichoid distribution on the leg (arrows). Patient was chronically
immunosuppressed, with a history of microscopic polyangiitis. B and C, Hematoxylineeosin
staining revealed suppurative and granulomatous inflammation (solid arrows) with focal tissue
necrosis (dashed arrows). D, Grocott methenamine silver staining revealed fungal elements
(arrows). Skin cultures were positive for Alternaria spp. This patient was treated and cured.
(Original magnification: B, 320; C and D, 340.)

literature, especially in light of notable increases in
the incidence of DCFI in parallel with the increased
use of aggressive antimicrobial, chemotherapeutic,
immunomodulatory, and transplantation-related
therapies.1
The most common comorbid condition in our
study population was an impaired immunologic
status. Half of our patients were solid organ
transplant recipients or had underlying hematologic
malignancies and had received bone marrow or stem
cell transplantation. Among immunosuppressed
patients, neutropenia (neutrophil counts \1000
cells/mL for $ 7 days) has been described as a
predisposing factor for DCFIs. Other risk factors
include diabetes mellitus, renal failure and renal
transplantation, chronic corticosteroid therapy, and
immunosuppressive therapy.6,12,13 A high index of
suspicion for a DCFI should be maintained in
immunosuppressed patients, particularly when
they present with persistent fever and unresponsive-
ness to antimicrobial agents.8
Primary cutaneous fungal infections are most
commonly attributed to traumatic inoculation of
the fungi or foreign material containing the fungi
into the skin.7 Most of our patients (21/33) had a
primary cutaneous mycosis without systemic signs or
6 Gonzalez Santiago et al J AM ACAD DERMATOL

Table IV. Histopathologic features diagnostic confirmation. Necrosis is seen when the
n (%)
offending fungi have angioinvasive properties, such
as Mucorales. Although histopathology is often
Histochemical stains*
needed to confirm the specific etiologic fungal
Performed 28 (84.8)
Not performed 5 (15.2) organism, the clinical presence of necrosis should
Predominant histopathologic pattern enable clinical consideration of a DCFI in the
Granulomatous inflammation 18 (54.5) differential diagnosis.
Pseudoepitheliomatous hyperplasia 2 (6) Histopathologic findings in DCFIs can vary, and
Perivascular and interstitial inflammation 1 (3) close inspection of serial sections may be necessary
without granulomas to identify the offending organism(s). A granuloma-
Vasculitis 1 (3) tous inflammatory pattern is often described as the
Necrosis 1 (3) most common histopathologic feature.14 This was
Combination of histopathologic patterns 10 (30) confirmed in our study, where a majority of cases
*Including Grocott methenamine silver and periodic acideSchiff
(18/33) presented primarily with this pattern.
stains. Histochemical stains (ie, Grocott methenamine silver
and/or periodic acideSchiff) were used to assist with
pathologic interpretation in most cases (28/33). In
Table V. Skin culture results only 5 of 33 cases, identification of the fungal
n/N or n (%) organisms (ie, hyaline and dematiaceous fungi,
Positive skin culture (%) 25/33 (76) Zygomycetes, and Aspergillus spp) was possible
Blastomyces dermatitidis 9 (27) based solely on histopathologic review, without the
Alternaria spp 5 (15) need for adjunctive histochemical staining. High
Rhizopus spp 3 (9) rates of concordance between the pathologic
Fusarium spp 3 (9) diagnosis and skin tissue culture results are reflective
Acremonium spp 1 (3) of the relatively high diagnostic accuracy of
Pseudoallescheria 1 (3) histopathology for DCFIs in our practice. These
Trichophyton mentagrophytes 1 (3) concordance rates are supported by limited studies
Coccidioides immitis 1 (3)
on culture (skin and noneskin tissue) and pathology
Aspergillus 1 (3)
Negative skin culture 8/33 (24)
(histopathology and cytopathology) correlations
Other, noneskin tissue culture 7 (21) showing that overall diagnostic accuracy for
Positive noneskin tissue culture, 4 (57) microscopic morphologic techniques ranges from
positive skin culture 20% to 80%.6,15,16 Guarner and Brandt6 attributed
CSF culture (Alternaria spp)* 1 discordance between histopathology and tissue
BAL (Blastomyces dermatitidis)* 2 culture to the following: (1) alteration of fungal
BAL (Coccidioides immitis)* 1 characteristics because of antifungal medications or
Positive noneskin tissue culture, 3 (43) host responses; (2) lack of experience of the
negative skin culture pathologist in fungal identification; (3) differences
Brain culture (Aspergillus spp) 1 in fungal morphology caused by fragmentation
Body fluid secretion (Exophiala 1
of the fungal elements with tissue processing;
jeanselmei)
BAL (Aspergillus spp) 1
(4) inflammatory response obscuring fungal
morphology; (5) similarities among different fungal
BAL, Bronchoalveolar lavage; CSF, cerebrospinal fluid. species; and (6) only 1 fungus growing in culture in a
*Same organism for both skin and noneskin tissue cultures. dual infection where 1 is more abundant.17 It is also
important to note that not all cases of phaeohypho-
symptoms. Occupational exposures may also mycosis feature pigmented hyphae (ie, they can
represent important risk factors, because 1 of appear hyaline). It is unclear to what extent $ 1 of
our patients with a diagnosis of disseminated the above factors may have contributed to the
blastomycosis worked in a turkey meateprocessing misclassification (5/33) noted between pathology
factory. and tissue culture in our case series.
The clinical diagnosis of a DCFI can be For discordant cases, the skin tissue culture was
challenging. In most cases, while an infection may negative despite the identification of fungal elements
be suspected, a specific infectious agent cannot be in histopathologic sections. However, culture of a
implicated solely on the basis of the clinical findings. nonskin tissue in 3 of 8 discordant cases revealed
Skin lesions are nonspecific, requiring adjunctive growth of the offending fungal organism. As
pathologic examination and skin tissue cultures for expected, these patients (2/3) fared poorly and
 J AM ACAD DERMATOL
Table VI. Discordant cases
Histopathologic findings
Age (y), Other noneskin
sex Clinical findings Underlying disease(s) Description Stains Fungi tissue culture Treatment Outcome
60, M Ulcerated Diabetes Granulomatous Positive GMS Zygomycetes N/A Voriconazole and Lesion
nodules inflammation and PAS amphotericin B resolution
61, M* Erythematous Heart transplant PEH Not performed Aspergillus Aspergillus spp Voriconazole and Death
nodulesy on CSF amphotericin B
60, F Erythematous None Granulomatous Positive GMS NS N/A Excision and Lesion
nodules inflammation debridement resolution
75, M* Erythematous Lymphoproliferative Granulomatous Positive GMS NS Exophiala Itraconazole Lesion
nodules disorder inflammation jeanselmei resolution
on skin
secretion
70, M* Erythematous Lymphoproliferative Panniculitis Positive GMS Hyaline N/A Amphotericin B Death
nodulesy disorder fungus
45, M* Necrotic Lymphoproliferative Granulomatous Positive PAS Zygomycetes N/A AmBisone and Lesion
nodules disorder inflammation Voriconazole resolution
and vasculitis
44, M* Erythematous Heart, kidney, and Granulomatous Positive GMS Dematiaceous N/A Itraconazole Lesion
papules liver transplant inflammation fungus resolution
31, M* Necrotic Lymphoproliferative Vasculitis Negative Zygomycetes Aspergillus spp AmBisone Death
plaquey disorder on BAL

AmBisone is a registered trademark of Astellas Pharma (Tokyo, Japan).

Gonzalez Santiago et al 7
BAL, Bronchoalveolar lavage; CSF, cerebrospinal fluid; GMS, Grocott methenamine silver; N/A, not available; NS, not specified; PAS, periodic acideSchiff; PEH, pseudoepitheliomatous hyperplasia.
*Immunosuppressed.
y
Systemic infection.
8 Gonzalez Santiago et al
died of systemic aspergillosis, while the remaining
patient with localized E jeanselmei infection
(identified on skin secretions but not on skin culture)
was successfully treated. In the remaining 5
discordant cases, treatment was given empirically
based on the histomorphologic description of the
fungal organism.
These findings suggest that the skin culture,
although essential for the diagnosis and accurate
identification of a DCFI, may fail to provide needed
confirmation of the histopathology when negative.
Our results found that skin cultures could be
negative despite histopathologic evidence of
fungal organisms in skin tissue sections. Possible
explanations for this phenomenon have been
described and include: (1) homogenization of tissue;
(2) nonviable fungal organisms in the tissue, such as
walled-off infections with dimorphic fungi; (3) tissue
sampling from 2 different areas6; and (4) the use of
preservative-containing local anesthesia.18
Homogenization of the tissue refers to the process
of chemically or mechanically ‘‘reducing’’ samples
into small particles. Mechanical techniques are used
for most skin cultures and include grinding,
shearing, beating, and sonification of the tissue
before implantation on culture media.19 Some fungi,
especially Mucorales and Aspergillus spp, are
particularly prone to destruction with this
technique, resulting in a negative skin culture.6
These techniques may have contributed to positive
nontissue cultures (ie, CSF, body secretion, and BAL)
in our discordant cases, because these samples are
typically directly planted onto the culture medium
without homogenization. In our discordant group, 3
cases were described as Mucorales on histologic
sections, making this a possible explanation for the
discordant skin culture result (note that the terms
zygomycosis and mucormycosis are often used
interchangeably). For this reason, planting larger
samples of tissue on fungal culture media has been
proposed.6,17 In addition, the growth pattern for
each genus varies. Organisms of the Mucorales order
should grow within 3 days, while others, such as
Histoplasma capsulatum and Paracoccidioides
brasiliensis, grow slowly in most laboratories.
Therefore, in certain cases, a longer incubation
time may be required to increase skin culture
specificity. The clinician must convey the clinical
suspicion for a DCFI to the microbiology laboratory
so that the skin tissue specimen may be processed
with caution and longer incubation times may be
allowed, if necessary.
Other possible explanations for our discordant
results include sampling error when multiple
biopsy specimens are obtained, with the skin tissue
J AM ACAD DERMATOL
containing the fungal organisms sent to pathology
while the second sample—possibly not containing
fungi or containing nonviable fungi—sent to
microbiology.6 In addition, when used inadver-
tently, the fungicidal preservative methylparaben
can directly affect the culture results.18 Clinicians
should also be aware that although tissue cultures
and histopathologic investigations are required for
an accurate diagnosis, in some cases a diagnosis
could be made immediately by staining the roof of a
bulla or examining a potassium hydroxide prepara-
tion of a biopsy specimen.6 Frozen sections for faster
results should be considered in severe cases.
Study limitations included the fact that this was
a retrospective review of a small number of cases
(n = 33) from a single institution. There is a high
likelihood that we underestimated the number of
cases given that we only included patients with
histopathologic evidence of a fungal infection and
excluded those in whom a concurrent skin culture
was not performed. None of our patients reported a
history of traumatic injury preceding the diagnosis of
a DCFI. This could be reflective of recall bias,
because most of our patients were evaluated on a
referral basis.
We conclude that a diagnosis of DCFI should
be considered in the differential diagnosis of
nonspecific cutaneous lesions with supportive
histopathology despite a negative skin tissue culture.
In situ hybridizationebased diagnostic tests have
been found to be useful for the diagnosis of
invasive mycosis. Although not yet widely available,
the development and implementation of these
techniques may be useful. Increased awareness
within the dermatology community about the
histopathologic and microbiologic diagnostic pitfalls
is necessary. This can prevent adverse consequences
associated with delays in diagnosis and treatment,
particularly in immunosuppressed patients.
REFERENCES
1. Skiada A, Petrikkos G. Cutaneous zygomycosis. Clin Microbiol
Infect 2009;15(suppl 5):41-5.
2. Hinshaw M, Longley JB. Fungal diseases. In: Elder DE, Elenitsas
R, Johnson BL, Murphy GF, editors. Lever’s histopathology of
the skin. 9th ed Philadelphia (PA): Lippincott Williams and
Wilkins; 2005. pp. 601-34.
3. Vera-Cabrera L, Salinas-Carmona MC, Waksman N, Messe-
guer-Perez J, Ocampo-Candiani J, Welsh O. Host defenses in
subcutaneous mycoses. Clin Dermatol 2012;30:382-8.
4. McNeil MM, Brown JM. The medically important aerobic
actinomycetes: epidemiology and microbiology. Clin Micro-
biol Rev 1994;7:357-417.
5. van Burik JA, Colven R, Spach DH. Cutaneous aspergillosis.
J Clin Microbiol 1998;36:3115-21.
6. Guarner J, Brandt M. Histopathologic diagnosis of fungal
infections in the 21st century. Clin Microbiol Rev 2011;24:
247-80.
J AM ACAD DERMATOL
7. Kim MS, Lee SM, Sung HS, Won CH, Chang S, Lee MW, et al.
Clinical analysis of deep cutaneous mycoses: a 12-year
experience at a single institution. Mycoses 2012;55:501-6.
8. Singh N. Fungal infection in the recipients of solid organ
transplantation. Infect Dis Clin North Am 2003;17:113.
9. Patterson JE. Epidemiology of fungal infections in solid organ
transplants recipients. Transpl Infect Dis 1999;1:229.
10. Gabardi S, Kubiak DW, Chandraker AK, Tullius SG. Invasive
fungal infections and antifungal therapies in solid organ
transplant recipients. Transpl Int 2007;20:993.
11. Miller J, Kappe R, Kubitza D, Fessler R, Scheidecker I. The
incidence of deep-seated mycoses in Freiburg. Mycoses 1988;
31(suppl 1):9-18.
12. Bassiri Jahromi S, Khaksar AA. Deep-seated fungal infections in
immunocompromised patients in Iran. Iran J Allergy Asthma
Immunol 2005;4:27-32.
13. Hart PD, Russell E Jr, Remington JS. The compromised
host and deep fungal infection. J Infect Dis 1969;120:
169-91.
Gonzalez Santiago et al 9
14. Pang KR, Wu JJ, Huang DB, Tyring SK. Subcutaneous fungal
infections. Dermatol Ther 2004;17:523-31.
15. Schofield CM, Murray CK, Horvath EE, Cancio LC, Kim SH, Wolf
SE, et al. Correlation of culture with histopathology in fungal
burn wound colonization and infection. Burns 2007;33:341-6.
16. Tarrand JJ, Lichterfeld M, Warraich I, Luna M, Han XY, May GS,
et al. Diagnosis of invasive septate mold infections. A corre-
lation of microbiological culture and histologic or cytologic
examination. Am J Clin Pathol 2003;119:854-8.
17. Sangoi AR, Rogers WM, Longacre TA, Montoya JG, Baron EJ,
Banaei N. Challenges and pitfalls of morphologic identification
of fungal infections in histologic and cytologic specimens: a
ten-year retrospective review at a single institution. Am J Clin
Pathol 2009;131:364-75.
18. Miller MA, Shelley WB. Antibacterial properties of lidocaine on
bacteria isolated from dermal lesions. Arch Dermatol 1985;121:
1157-9.
19. Burden DW. Guide to the homogenization of biological
samples. Random Primers 2008;7:1-14.