Dermatofibroma, Dermatofibrosarcoma protuberans (DFSP), Fibromatoses -Knuckle pads

1. FIBROUS AND FIBROHISTIOCYTIC
PROLIFERATIONS OF THE SKIN P.II
WWW.FACEBOOK.COM/GROUPS/DERMATOLOGYCOURSEONLINE

2. DERMATOFIBROMA

16. It dimples inward with lateral pressure  Dimple sign

17. On applying pressure around DF  smooth, firm nodule can be
palpated under the skin (black arrows) & a dimple can be seen
in the center (blue arrow)

20. Cellular dermatofibroma

21. Polypoid nodular dermatofibroma

22. OVERVIEW
A dermatofibroma (DF) is a
COMMON SLOWLY-GROWING
BENIGN FIBROHISTIOCYTIC skin
lesion that usually has OVERLYING
HYPERPIGMENTATION on the
LOWER EXTREMITIES.
Also called BENIGN FIBROUS
HISTIOCYTOMA.
DERMATOFIBROMA

23. ETIOLOGY
The exact cause is UNKNOWN, but
the lesions are thought to arise at
sites of prior MINOR TRAUMA or as
a late dermal dendritic
HISTIOCYTIC REACTION to an
ARTHROPOD BITE.
WHETHER it is due to a NEOPLASM
or REACTIVE PROCESS is debated.
DERMATOFIBROMA

24. CLINICAL FEATURES
They appear as ROUND or OVOID
SINGLE FIRM DERMAL NODULES,
often YELLOW-BROWN in colour,
sometimes PINK (especially in fair
skinned individuals) and sometimes
quite DARK, (especially in dark
colored skin).
POLYPOID, FLAT, DOME SHAPED or
DEPRESSED.
DERMATOFIBROMA

25. CLINICAL FEATURES
If the skin over a
dermatofibroma is SQUEEZED a
DIMPLE (central depression)
FORMS  DIMPLE
SIGN or FITZPATRICK'S
SIGN indicating TETHERING of
the skin to the UNDERLYING
FIBROUS TISSUE.
DERMATOFIBROMA

26. CLINICAL FEATURES
More commonly in FEMALES.
Most commonly on the LOWER
EXTREMITIES (most common
growth below the knee in young
adults) & ARMS, but may be seen
in any location.
Once developed, they usually
PERSIST FOR YRS.
DERMATOFIBROMA

28. A white centre (blue arrows) and a peripheral pigment
network (black arrows)

30. CLINICAL VARIANTS
1. MULTIPLE ERUPTIVE
DERMATOFIBROMAS may be seen in
normal individuals but also associated
within immunosuppression or SLE.
2. CELLULAR DERMATOFIBROMA- 5%
of all dermatofibromas and is clinically
larger than more typical lesions.
3. POLYPOID NODULAR
DERMATOFIBROMA
DERMATOFIBROMA

34. Typical epidermal change of dermatofibroma-induced
hyperkeratosis, acanthosis and basal layer hyperpigmentation

36. Collagen trapping

41. Tumor cells with vacuolated cytoplasm (foam cells)

42. Proliferation of fibrohistiocytic cells. Some cells contain
brown granular hemosiderin pigment

43. Basaloid induction

44. Factor XIIIa

45. HISTOPATHOLOGY
Large BUNDLESof KELOIDAL
COLLAGEN.
proliferation of SPINDLED
FIBROBLASTS around the collagen
bundles  “COLLAGEN TRAPPING”
at the PERIPHERY.
LIPID LADEN HISTIOCYTES, and
MULTINUCLEATE GIANT CELLS
sometimes the cells contain
HEMOSIDERIN pigment.
DERMATOFIBROMA

46. HISTOPATHOLOGY
These benign dermal
proliferations can induce
overlying EPIDERMAL
PROLIFERATION.
The BASAL epidermal LAYER is
classically HYPERPIGMENTED.
May cause BASALOID
INDUCTION.
DERMATOFIBROMA

47. HISTOPATHOLOGICAL
VARIANTS
1. Fibrocollagenous (most common)
2. Cellular
3. Aneurismal
4. Epithelioid
5. Atypical
6. Lipidized
7. Palisading
8. Cholesterotic
DERMATOFIBROMA

48. TREATMENT
A dermatofibroma is of COSMETIC
SIGNIFICANCE only and although it
tends to persist long term, it seldom
causes any symptoms.
Usually only REASSURANCE is
needed.
Sometimes its dark color can raise
anxiety about melanoma; if there is any
doubt about its nature, the lesion can
be excised for histology.
DERMATOFIBROMA

49. TREATMENT
TREATMENT TECHNIQUES include;
1. SURGICAL EXCISION may leaves scars
that are evident and sometimes more
noticeable than the original lesion.
2. CRYOTHERAPY - rarely completely
successful and may leave a
hypopigmentation.
3. INTRALESIONAL STEROIDS.
DERMATOFIBROMA

50. a Small reddish cutaneous nodule on the right leg, consistent
with DF. b Appearance of the scar 1.5 years after surgery.

52. DERMATOFIBROSARCOMA
PROTUBERANS

56. A broad, pink-brown, multinodular, firm plaque on the back

57. 42-year-old woman presented with a 3-cm, firm, violaceous,
multinodular mass located on the left upper abdomen

64. DFSP on lower abdomen right side

68. OVERVIEW
RARE SLOWLY GROWING
INTERMEDIATE-GRADE LOCALLY
AGGRESSIVE FIBROBLASTIC
MALIGNANT skin tumor arising
from the DERMIS &
RARELY METASTASIZES.
DFSP

69. ETIOLOGY
Most DFSPs (>90%) have
ABNORMAL CHROMOSOMES
within the tumor cells either
TRANSLOCATION OR
SUPERNUMERARY RING
CHROMOSOMES.
DFSP

70. ETIOLOGY
DFSP
CHROMOSOMAL
TRANSLOCATION EXPRESSION
NEW
FUSION
GENE
HIGH
LEVELS
OF
PDGF
PROLIFERA
-TION OF
FIBRO-
BLASTS
DFSP

71. ETIOLOGY
This chromosomal TRANSLOCATION
fuses the alpha chain type 1 of
COLLAGEN of CHROMOSOME 17 and
PLATELET-DERIVED GROWTH FACTOR
genes at CHROMOSOME 22  PDGF β-
CHAIN gene is now UNDER the CONTROL
of the COLLAGEN 1A1 PROMOTER
EXPRESSION of this FUSION GENE 
high levels of PDGF  stimulates
PROLIFERATION of FIBROBLASTS  DFSP.
DFSP

72. ETIOLOGY
—t(17;22)(q22;q13) fusion  the
fused PROTO-
ONCOGENE COL1A1-PDGFβ.
DFSP

73. CLINICAL FEATURES
Usually presents in EARLY or
MIDDLE ADULT life between 20
and 59 years of age, but all ages
can be affected.
MALES are affected slightly more
frequently than females.
DFSP

74. CLINICAL FEATURES
Usually ASYMPTOMATIC this often
leads to a DELAY in DIAGNOSIS.
Often “INFECTED KELOID”
appearance.
It usually grows VERY SLOWLY over
MONTHS to YEARS.
May range in size from 1 TO 25
CM in diameter.
DFSP

75. CLINICAL FEATURES
PAINLESS FIRM indurated RED-
BROWN or SKIN COLORED PLAQUE
and/or nodules
(CHARACTERISTICALLY
MULTINODULAR) FIXED to the
UNDERLYING TISSUE.
50-60% arise on the TRUNK often in
the SHOULDER and CHEST area.
DFSP

76. CLINICAL FEATURES
DFSP is OFTEN DIAGNOSED
LATER ON when it enters a MORE
RAPID GROWTH PHASE giving
rise to larger lesions.
May METASTASIZE (<5%),
possibly to LUNGS.
DFSP

77. DDx
1. KELOID
2. LARGE DERMATOFIBROMA
3. DERMATOMYOFIBROMA
4. MORPHEA
DFSP

79. Plaque stage - Characteristic multilayered pattern of
infiltration into the subcutaneous tissue

80. Storiform or cartwheel arrangement of tumor cells in a DFSP

84. Tumor cells enveloping the adnexal structures and
invading the dermal collagen, subcutaneous tissues

85. Spindle cells infiltrate SC fat in honeycomb pattern

86. Tentacles of tumor infiltrating into the underlying
subcutaneous fat.

89. HISTOPATHOLOGY
NON CIRCUMSCRIBED, HIGHLY
CELLULAR DERMAL proliferation
of SPINDLE CELLS in distinct
STORIFORM or CARTWHEEL
PATTERN.
DFSP

90. HISTOPATHOLOGY
Spindle cells are THIN
MONOMORPHIC with MINIMAL
ATYPIA and spindly with SCANT
EOSINOPHILIC CYTOPLASM and
ELONGATED HYPERCHROMATIC
NUCLEI and LITTLE or NO
PLEOMORPHISM & MITOTIC figures
are RARE but EASILY IDENTIFIED
LATER in NODULAR stage.
DFSP

91. HISTOPATHOLOGY
ADNEXAL STRUCTURES are
INFILTRATED and obliterated. The
spindle cells infiltrate into the
SUBCUTANEOUS TISSUE, very often
in a MULTILAYERED PATTERN EARLY
in PLAQUE STAGE & entraps fat
cells to form characteristic
HONEYCOMB pattern LATER in
NODULAR STAGE.
DFSP

92. HISTOPATHOLOGY
INVASION of MUSCLE may occur.
Usually NO/RARE HISTIOCYTES,
no HISTIOCYTE-LIKE cells, no
FOAM CELLS, no GIANT CELLS or
other INFLAMMATORY CELLS.
DFSP

93. HISTOPATHOLOGY
May show areas of
FIBROSARCOMATOUS
TRANSFORMATION
It is important to identify this
fibrosarcomatous DFSP, which is
MORE AGGRESSIVE tumor, that
requires MORE AGGRESSIVE
TREATMENT.
DFSP

94. CD34 immunostaining in DFSP

95. IMMUNOHISTOCHEMISTRY
STRONGLY POSITIVE STAINING
FOR CD34.
DFSP

97. Bednar tumor- dendritic cells contain melanin

98. INVESTIGATIONS
LAB
FISH
RT-PCR
RADIOGRAPHY
CT
MRI
DFSP

100. CT scan shows DFSP of the left axilla

101. TREATMENT
COMPLETE SURGICAL EXCISION,
including Mohs micrographic
surgery is considered the
STANDARD TREATMENT.
Chemotherapy is ineffective.
DFSP

102. TREATMENT
1. WIDE LOCAL EXCISION 2-3 cm margins 
Local recurrence so follow-up is important.
2. MOHS MICROGRAPHIC SURGERY
recurrence ~1%
3. POST-OPERATIVE RADIOTHERAPY may be
used as an adjunct to surgery. when resection is
incomplete.
4. IMATINIB MESYLATE an oral PDGF receptor
tyrosine kinase inhibitor. FDA-approved for
unresectable, recurrent or metastatic cases in
adults.
DFSP

103. (A) Baseline view of advanced, primary dermatofibrosarcoma
protuberans of the chest wall, (B) the partial response after 12 weeks
of imatinib therapy, and (C) 2 years after resection of the tumor.

104. DIFFERENCES BETWEEN DF & DFSP
DF DFSP
NATURE OF THE TUMOR benign Intermediate-grade malignancy
ETIOLOGY ? Minor trauma, insect bite mutations
PREVALENCE common rare
CLINICALLY
SEX female Males (slightly more)
DIMPLE SIGN + -
SITE OF
PREDILECTION
Lower extremities or arms Trunk especially shoulder or chest
SIZE generally < 1 cm 1-25 cm
MORPHOLOGY
Single Static well-defined
hyperpigmented firm nodule
Expanding keloidal plaque
characteristically multilobulated
red-blue to brown color

105. DIFFERENCES BETWEEN DF & DFSP
DF DFSP
HISTO-
PATHOLOGY
TUMOR CELLS Fibrohistiocytic proliferation
Spindle cells in storiform
pattern
COLLAGEN
BUNDLES
Keloidal & may be entrapped thin
SC INVOLVEMENT in a radial pattern Multilayered  Honeycomb
ATYPICALITY No minimal
HISTIOCYTES lipid laden histiocytes no/rare
GIANT CELLS present no
IMMUNO-
STAINING
S100 – or + –
CD34 – +
FXIIIA ++ –
STROMELYSIN-3 + –
Rx
REASSURANCE /Surgical/
cryotherapy/intralesional steroids
WLE/ Mohs MS/ adjuvant
radioRx/ Imatinib mesylate

106. FIBROMATOSES

107. FIBROMATOSIS
Fibromatosis is a condition
where FIBROUS OVERGROWTHS
of DERMAL and SUBCUTANEOUS
CONNECTIVE TISSUE develop
tumors called FIBROMAS. These
fibromas are usually BENIGN.

108. CLASSIFICATION OF
FIBROMATOSIS
SUPERFICIAL
FIBROMATOSES
DEEP
FIBROMATOSES
PALMAR (DUPUYTREN
CONTRACTURE)
FIBROMATOSIS
DESMOID TUMOURS
PLANTAR (LEDDERHOSE
DISEASE) FIBROMATOSIS
PENILE FIBROMATOSIS
(PEYRONIE’S DISEASE)
KNUCKLE PADS

109. OVERVIEW
Knuckle pads are WELL DEFINED
THICKENINGS over the dorsum
of FINGER OR TOE JOINTS more
likely develop from REPETITIVE
PRESSURE or FRICTION related to
SPORTS or OCCUPATION.
KNUCKLE PADS

117. ETIOLOGY
1. IDIOPATHIC
2. GENETIC as part of an inherited
syndrome e.g. epidermolytic
palmoplantar keratoderma, may
run in families together with other
forms of fibromatosis.
3. ACQUIRED as a response to
repetitive trauma, or associated
with several other acquired
conditions.
KNUCKLE PADS

118. CLINICAL FEATURES
Most commonly become
apparent after the age of 30
YEARS.
Usually ASYMPTOMATIC WELL-
DEFINED, SMOOTH, FIRM SKIN-
COLORED dome-shaped
PAPULES, NODULES, or
PLAQUES.
KNUCKLE PADS

119. CLINICAL FEATURES
More commonly located over
DORSAL ASPECTS of the PROXIMAL
INTERPHALANGEAL JOINTS than over
the KNUCKLES
(METACARPOPHALANGEAL
joint/”misnomer”) or DISTAL
INTERPHALANGEAL joints.
Over SINGLE or MULTIPLE joints.
In most cases, PERSIST INDEFINITELY
with little change.
KNUCKLE PADS

120. HISTOPATHOLOGY
HYPERKERATOSIS and mild
ACANTHOSIS of the epidermis.
THICKENING of the DERMIS and
thickened, IRREGULAR COLLAGEN
BUNDLES.
Slight PROLIFERATION of
FIBROBLASTS and capillaries in the
papillary dermis.
KNUCKLE PADS

121. HISTOPATHOLOGY
When associated with a
KERATIN 9 GENE MUTATION, as
in EPIDERMOLYTIC
PALMOPLANTAR KERATODERMA,
SUPRABASAL EPIDERMOLYSIS is
also seen.
KNUCKLE PADS

122. TREATMENT
In general TREATMENT is NOT
REQUIRED.
AVOIDANCE of a REPETITIVE
BEHAVIOR if possible may
improve the situation e.g.
CHANGING OCCUPATION or
WEARING PROTECTIVE GLOVES.
KNUCKLE PADS

123. TREATMENT
1. MOISTURIZERS & KERATOLYTICS
may be useful if the knuckle pads
are hyperkeratotic.
2. INTRALESIONAL INJECTIONS of
CORTICOSTEROIDS or
FLUOROURACIL.
3. SURGERY has been used, but may
be complicated by the
development of keloid scars,
tendon tethering or Recurrence.
KNUCKLE PADS

124. REFERENCES
BOLONGIA DERMATOLOGY ESSENTIALS
BOLONGIA 3rd ed
WEEDON’S SKIN PATHOLOGY
ESSENTIALS
GOOGLE IMAGES
DERMNETNZ.ORG
EMEDICINE.MEDSCAPE.COM
DERMIS.NET

125. THANK YOU