CPC

AMAL KURBAN

MUHAMMAD KHAWAR NAZIR

DERMATOLOGY
BMC

5/29/2009
Plz don’t do this to me……
 CASE 1

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 KOILOCYTE
FORMATION

Electron microscopic: Nuclei

of differentiated keratinocytes
is the site where replication
and assembly of human
papillomavirus takes place.
Large numbers of small
electron dense viral particles
lead to formation of crystalline
structures (arrows). The
expression of intact virions is
accompanied by cytopathic
effects, among them
margination of chromatin
(arrowheads) and perinuclear
cytoplasm devoid of organelles
and keratin filaments (P), a
combination that accounts for
the koilocytotic appearance of
keratinocytes.

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 CONDYLOMA ACCUMINATA

The designation "condyloma

acuminatum" is a contradiction
in terms. "Condyloma" means
"knobby," like a knuckle,
whereas "acuminatum" means
"pointed.“

The lesion is a type of wart, but

the projections of it more often
are knobby than digitate.

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Knobby Sport Wheel Knobby Ball

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 CONDYLOMA ACCUMINATA
• Genital warts or venereal warts

• Most commonly caused by human papillomavirus (HPV) type 6

& 11

• Genital warts are an STD. Evaluation for other STDs and

simultaneous evaluation of sexual contacts is required

• Spread through direct skin-to-skin contact during oral, genital,

or anal sex with an infected partner

• In women, and less commonly in men, genital warts are

potentially oncogenic ( e.g. cervical dysplasia )

• Genital warts in children (especially warts after 6 months of

age) require an evaluation for sexual abuse

• Atypical, flat, and pigmented condylomata may suggest the

diagnosis of Bowenoid papulosis

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 MANAGEMENT OF ANOGENITAL WARTS WITH
GRADING OF RECOMMENDATIONS

Cytotoxic or antiviral agent

• Podophyllotoxin 0.5% solution, 0.15% cream (1)
• Cidofovir 1% cream (3), intralesional injection (3)

Physical destruction
• Cryotherapy (liquid nitrogen, cryoprobe) (1)
• Trichloroacetic acid (TCA) 70–90% solution (1)
• Electrosurgery (1)
• Scissors excision (1)
• Laser vaporization (2)

Immunomodulatory
• Imiquimod 5% cream (1)
• Intralesional immunotherapy with skin test
antigens (2)

Key to evidence-based support: (1) prospective controlled trial; (2)

retrospective study or large case series; (3) small case series or
individual case reports72

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 • Criteria for diagnosis clinically:

* Well-circumscribed Plaques with a prominent

papillomatous surface
* Hues of different shades of brown

• Differential diagnosis clinically:

Seborrheic keratosis
Bowenoid Papulosis (HPV16,18)
Verrucous Carcinoma(Giant Condyloma
Acuminatum, HPV 6)

-Final differentiation by microscopy

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 • Criteria for diagnosis histopathologically:

-Hyperkeratosis, papillomatosis, Hypergranulosis

-Columns of Parakeratosis, especially over dermal
papillae
-Vacuolated superficial keratinocytes with pyknotic
raisin-like nuclei ( KOILOCYTES )
-Rete Ridges often slope inward at borders of lesion
-Dilated Capillaries in dermal pappilae
-Perivascular lymphocytes

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 Lessons

• Keratinocytes often appear as "Basaloid"

in Seborrheic Keratosis

• Condyloma is Exophytic, Seborrheic

Keratosis is mostly Endophytic

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 Misdiagnosis as Seb. K
It is not uncommon for clinicians and
histopathologists to misdiagnose lesions such as
this one as a seborrheic keratosis. In fact, in
the most recent edition of his textbook, Weedon
wrote these lines:

"Human papillomavirus (HPV) has been

detected in a small number of cases [of
seborrheic keratosis], particularly from the
genital region.“

In Berny Ackerman,s view, every so-called

seborrheic keratosis that houses papillomavirus
is a condyloma acuminatum and not a
seborrheic keratosis.
(derm101.com)

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 CASE 2

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Cystic Squamous Cell Carcinoma
• SCC 2nd most common type of skin cancer

• Red papule, nodule or plaque, often hyperkeratotic or

ulcerated, mostly on sun damaged skin

• Less often in irradiated sites, burn scars, chronically

infected sites or associated with other dermatosis

• Nonsurgical options for the treatment of cutaneous

squamous cell carcinoma (SCC) include topical
chemotherapy, topical immune response modifiers,
photodynamic therapy (PDT), radiotherapy, and
systemic chemotherapy
• Surgical care includes, Cryotherapy, Electrodesiccation
and curettage Excision with conventional margins and
MOH,s micrographic surgery.

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 General Risk Factors
• Age older than 50 years , Male sex

• Skin that sunburns easily (Fitzpatrick skin types I and II)

• Geography (closer to the equator)

• History of prior nonmelanoma skin cancer

• Exposure to UV light (high cumulative dose of sunshine, tanning beds, or

medical UV treatments)

• Exposure to chemical carcinogens (eg, arsenic, tar)

• Exposure to ionizing radiation (medical treatments, occupational or

accidental radiation exposure)

• Chronic immunosuppression

• Chronic scarring conditions

• Certain genodermatoses

• Human papillomavirus (HPV) infection (specific subtypes)

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 Histopathlogy
• Invasions of dermis by Atypical
Keratinocytes (hyperchromatic,
pleomorphic cells often epitheliod, with
atypical mitosis

• Squamous eddies or keratin pearls some

times

• Variable perivascular, lichenoid or diffuse

lymphocytes or plsma cells

• Perineural invasion in some aggressive

forms

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 CYSTIC SCC

• Criteria for diagnosis clinically: No judgment with

certainty can be made clinically about the exact nature
of this reddish brown nodule, there being nothing
specific about it and, moreover, it not being pristine,
representing as it does persistence at this site of a
primary pathological process, the evidence for
persistence being the linear scar in continuity with it.

• Differential diagnosis clinically: This could be any

one of a host of pathologic processes, ranging from a
keloid to the squamous-cell carcinoma that it
actually turned out to be. Biopsy is requisite to
determining the precise nature of this lesion.

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 CYSTIC SCC
• Criteria for diagnosis histopathologically:
At the periphery of the epithelium-lined sac, atypical
keratinocytes whose nuclei are crowded, large, pleomorphic,
and heterochromatic, and whose cytoplasm is eosinophilic.

• The presence of a good scar positioned between the base of

surface epidermis and the summit of the cystic neoplasm
indicates that at least one surgical procedure had been
performed previously at this site.

• Differential diagnosis histopathologically:

Keratoacanthoma, is not cystic, rather a keratin filled crater in
the center. Atypia is usually mild.

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 CYSTIC SCC
• Clinico-pathologic correlation:

• The surface of the nodule is smooth because the cornified layer

is not hyperkeratotic.

• The carcinoma is cystic because it has taken the form of a sac

lined by epithelial cells and housing contents that, in this
instance, are corneocytes.

• Options for therapy predicated on knowledge of

histopathologic findings: A squamous-cell carcinoma such as
this one must be excised completely. The margin taken in this
instance may be too narrow, neoplastic cells extending to very
near one lateral margin and to very near the deep margin. In
the context of this squamous-cell carcinoma having
persisted twice following attempts to remove it, excision in
toto is mandatory now.

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 CYSTIC SCC

It is impossible to make a diagnosis clinically of

squamous-cell carcinoma here by inspection only; the
surface of the nodule is smooth, neither scaly nor
keratotic.

In short, the lesion bears no resemblance to any well-

recognized type of squamous-cell carcinoma, surely
none at all to the type known as "keratoacanthoma."

But the "cystic" malignant neoplasm pictured has been

tampered with surgically twice, and it represents
persistence of a "solid" squamous-cell carcinoma
that had been excised only in parte, not yet in toto
( as a whole, completely ).

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 CYSTIC SCC

• The "cystic" squamous-cell carcinoma illustrated

here did not begin cystic, but rather solid,
according to histopathologists who described
and diagnosed it twice before.
• That being so, the situation here is analogous to
that in a so-called epidermal inclusion cyst
where surface epidermis is carried forcibly into
the reticular dermis, for example, by a
penetrating injury such as a puncture or by a
suture placed too tightly, and there it proliferates
in a manner that eventuates in an authentic cyst.

• In the case of the squamous-cell carcinoma that

is the object of our attention here, what
originally was "solid" became "cystic." How that
happens in the case of the cyst and of the cystic
carcinoma never has been made believable in
compelling fashion.

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 CYSTIC SCC

• When a keratoacanthoma involutes, fibroplasia is seen at the

base of it. In this cystic SCC no fibroplasia is present at the
base, only at the surface of it in the form of scar from previous
surgical procedures.

• The only rational explanation is that this squamous-cell

carcinoma was never keratoacanthomatous, and that judgment
confirmed by reference to biopsy reports of findings in sections
from the two specimens produced previously.

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 CYSTIC SCC

• Conceptually, this "cystic" squamous-cell carcinoma is

very different than what is dubbed "cystic" basal-cell
carcinoma, the essential difference being consequent
to the very big differences in the essential character of
those two malignant neoplasms of epithelial cells.

• In brief, SCC is constituted of abnormal spinous cells

(keratocytes) whose justification is cornification; this
cystic squamous-cell carcinoma houses abundant
corneocytes .

• In contrast, basal-cell carcinoma is made up of

follicular germinative cells (trichoblasts) that usually
undergo necrosis rather than cornification (there are
exceptions—as always!) A cystic basal-cell carcinoma
comes into being by virtue of extensive necrosis en
masse of trichoblasts in the center of solid
aggregations or due to mucin.

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 CASE 3

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DH
• Chronic, intensely pruritic disorder
• Symmetrically distributed bullae or erosions
• Deposition of IgA in the dermal papillae
• Evidence of gluten-sensitive enteropathy
• 10% of patients experience spontaneous
remission
• Therapeutic strategy is control of pruritus and
at least most of the skin lesions
• Drug of choice is Dapsone 100 mg/day
• Sulfapyridine, Colchicines - Alternative
Therapies
• Gluten-free diet

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 • Criteria for diagnosis clinically:

Papules, many of them excoriated as evidenced by

erosion covered by hemorrhagic crust, arranged in
groups on an extensor surface are characteristic of
dermatitis herpetiformis.

• Differential diagnosis clinically:

Insect "bites"
picker's papule
(usually are not grouped in herpetiform fashion)

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 • Criteria for diagnosis histopathologically:

-Neutrophilic microabscesses in dermal papillae, with few

eosinophils
-Small subepidermal vesicles
-DIF from normal appearing skin has granular deposits of IgA
in the tips of dermal papillae

• Differential diagnosis histopathologically:

-Linear IgA Dermatosis

-Lupus erythematosus
-Pemphigoid ( sometimes)
-Neutrophilic Dermatosis group (Sweet, Behcet,s syndrome,
Pyoderm Gangrenosum)

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 • Histological changes identical to those of dermatitis
herpetiformis may be seen in linear IgA dermatosis
and changes very similar to them may be encountered
early in the course of a lesion of lupus erythematosus.

• In order to be able to distinguish with certainty

among these diseases, studies by immunofluorescence
are mandatory. In the case of dermatitis
herpetiformis, direct immunofluorescence reveals
granular deposits of IgA in dermal papillae of
perilesional skin, IgM in about a third of specimens,
and C3 in about 50% of them.

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 CASE 4

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LYPHOMATOID PAPULOSIS
• Rare
• Corps of pruritic papules or nodules
• Sometimes ulcerate, appear and spontaeously
regress
• Lymphamatoid means resembling lymphoma
• Benign course in 90%
• Lymphoma in 10%
• Low-dose weekly methotrexate, PUVA
• Topical carmustine, topical nitrogen mustard,
topical MTX, topical imiquimod cream,10
intralesional interferon, low-dose
cyclophosphamide, chlorambucil, medium-dose
UVA-1 therapy, excimer laser therapy,11 and
dapsone

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 • Term Lymphomatoid Papulosis
originally was used by Macaulay1
in 1968 to describe

"a self-healing rhythmical

paradoxical eruption,
histologically malignant but
clinically benign."

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 • Criteria for diagnosis clinically:
A red, scaly papule, punctuated in its center by
a hemorrhagic crust, atop an ulcer in company
with lesions less fully developed and joined by
hyperpigmented atrophic scars is a
manifestation of lymphomatoid papulosis.

• Differential diagnosis clinically:

Mucha-Habermann (PLEVA )
Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell
Lymphoma
Cutaneous T-Cell Lymphoma

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 • Criteria for diagnosis histopathologically:
-Epidermal Necrosis often or ulceration
-Nodular infiltrate of ordinary lymphocytes,
very atypical CD30 positive activated T
lymphocytes, with epidermotropism into the
epidermis.
-Neutro and Eosin sometimes present
-Extravasated RBC,s often in epidermis

TypeA: many very large CD30+ atypical cells resemble histiocytes

TypeB: Mostly small cerebriform lympho, may not be CD30+

• Differential diagnosis histopathologically:

• Mycosis Fungoides
• Hodgken,s lymphoma
• PLEVA
• Anaplastic Large Cell Lymphoma

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 • Clinicopathologic correlation:

The papule came into being by dint of the

infiltrate of lymphocytes in the dermis

The redness is a consequence of venules in the

upper part of the dermis having been dilated
widely in vivo and there stuffed with
erythrocytes

The scale is the result of ortho- and

parakeratosis

The crust consists of a constellation of fibrin,

degenerate collagen, neoplastic lymphocytes,
and extravasated erythrocytes.

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 LyP and PLEVA

• (1) Although some lesions of LyP may not be distinguishable

clinically from some lesions of PLEVA, as a rule, the two very
different conditions
• First a process malignant (i.e., a lymphoma), and the second a
process inflammatory (i.e., an interface dermatitis often
affiliated with ballooning dermatitis)—are differentiated readily
from one another by gross inspection alone.

• Lesions of LyP in some patients tend to aggregate in a locale,

such as part of an arm or of a thigh, whereas that is not the
case in PLEVA;

• Lesions of LyP do not vesiculate, but those of PLEVA often do;

• Lesions of LyP sometimes, although uncommonly, progress

from papules to nodules and rarely, to tumors, whereas that
never is the case for PLEVA.

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 • The immunohistologic hallmark of the
abnormal T-lymphocytes in lymphomatoid
papulosis is their positivity for CD30, but such
positivity is not unique to them.

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CASE 5

CASE 5

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 Miescher's Nevus
• Dome-shaped, intradermal melanocytic nevi
that are commonly expressed on the face and
the upper part of the trunk.

• A papule of Miescher's nevus or Unna's nevus

usually is uniform in color

• Miescher's nevus and Unna's nevus, for

example, fulfill certain histopathologic criteria
for a congenital nevus. Both are associated with
splaying of monomorphous melanocytes
between collagen bundles in the reticular
dermis, but neither type of nevus is present at
birth.

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 Miescher's Nevus
• Histopathologically by a wedge-shaped
infiltrate of melanocytes of the nevus that
extends throughout much, if not all, of the
dermis

• By contrast, an Unna's nevus looks

clinically like an acrochordon, and consists
of nests of melanocytes like those of
Miescher's nevus; nests of it are present
throughout the extent of the entire
exophytic portion of the lesion.

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 Miescher's Nevus
• The classification of melanocytic nevi as
"congenital" or "acquired" has serious
limitations.

• Many types of melanocytic nevi that fulfill

criteria, clinically and histopathologically, for a
congenital nevus, such as congenital speckled
lentiginous nevus (nevus spilus) are not present
at birth; some of them even appear at puberty
or later.

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 Miescher's Nevus
• The decisive discriminative feature between
Unna's and Miescher's nevi is that Unna's nevus
is an almost purely adventitial lesion confined
to expanded papillary dermis and, many times,
to the perifollicular dermis too.

• In Miescher's nevus melanocytes diffusely

infiltrate both adventitial and reticular dermis in
a wedge-shaped pattern. With these concepts
in mind, every acquired intradermal
melanocytic nevus can be easily classified as
either Unna's or Miescher's.

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 Miescher's Nevus

• Criteria for diagnosis histopathologically: A

dome-shaped and somewhat wedge-shaped
proliferation of abnormal melanocytes disposed
in nests, but also in cords and strands, as well
as solitary units in no pattern recognizable, and
affiliated with Meissner corpuscle-like structures
in all parts of it throughout the reticular dermis,
is characteristic of Miescher's nevus.

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 Miescher's Nevus
• Criteria for diagnosis clinically:

• A smooth-surfaced, dome-shaped nodule of

subtly brown hue associated with a hint of
whiteness and from which spring terminal hairs,
the lesion being situated on a face, represents
one expression of Miescher's nevus.

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 Miescher's Nevus
• Clinicopathologic correlation:

• Lesion is elevated markedly because of the mass of

abnormal melanocytes in the reticular dermis;

• white in loci because of prominent collagenous stroma

in the upper part of the dermis;

• surface is smooth because the stratum corneum is

normal.

• hairs that emanate from the nodule are produced by

terminal follicles within it.

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 Miescher's Nevus

• Early in life, such a nevus tends to be brown distinctly,

but in the course of decades ensuing, it becomes
lighter progressively and may even end up off-white
consequent to collagenization that over time becomes
an accompaniment.

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 Miescher's Nevus

• Neural Differentiation is expected in a long-standing

lesion of Miescher's nevus. That may take the form of
Meissner-like corpuscles, as is the case here, or of so-
called neural tubes and, in loci, of changes that
resemble those of neurofibroma.

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 Miescher's Nevus
• Although a Miescher's nevus, cutting the
swath that it does throughout the width of
the reticular dermis, qualifies as a lesion
congenital, it is not present at birth, but
rather makes its appearance early in
childhood.
• The dichotomy of a lesion deemed to
be congenital morphologically and yet
is acquired biologically poses a
controversery to dermatologists,
some of whom employ the term
"congenital nevus, tardive type" in an
unsatisfactory effort at resolving the
dilemma.

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 Miescher's Nevus

• On occasion rare, a melanoma may develop at the

dermoepidermal junction above a Miescher's nevus
and even more rare in the upper part of the dermal
component of the nevus itself.

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 Miescher's Nevus

• TREATMENT

• Surgical EXCISION

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THANK YOU SO MUCH