Noduloulcerative skin

lesions
 Objectives
• By the end of this lecture you should be able to recognize
and manage the following conditions

• Leishmaniasis

• Basal cell carcinoma

• Squamous cell carcinoma

• Cutaneous tuberculosis
 leishmaniasis
• Infection caused by various species of Leishmania
protozoa, which are transmitted by bite of sandflies
(vector). Sandflies are approximately half the size of
mosquitoes.

• Leishmania life cycle begins when parasites in the

promastigote form are inoculated by a sandfly bite
into the skin of a mammalian host. Human
neutrophils first ingest the organisms → burst out →
ingested by macrophages but cannot be killed.
Clinical Presentation and Types
Cutaneous leishmaniasis (CL) – infection limited to the skin and lymphatic
system, but it may affect deeper tissues in diffuse CL or recur in the mucous
membranes of the mouth, nose, or pharynx in MCL.

Different Leishmania species cause Old World versus New World (American)
cutaneous leishmaniasis.

In the Old World (the Eastern Hemisphere), the etiologic agents include:
Leishmania tropica, L. major, and L. aethiopica, as well as L. infantum and L.
donovani.

The main species in the New World (the Western Hemisphere) are either in the L.
mexicana species complex (L. mexicana, L. amazonensis, and L. venezuelensis) or
the subgenus Viannia (L. [V.] braziliensis, L. [V.] guyanensis, L. [V.] panamensis,
and L. [V.] peruviana).

leishmaniasis recidivans- recurrence at site of an original ulcer, usually

within 2 years and often at the edge of a scar.
L. tropica: also known as L. tropica minor.(causes dry sore or
urban cutaneous leishmaniasis).
Produce chronic disease that if not treated, lasts for year or
longer.
with 2month – 3year incubation period
It is characterized by the production of dry lesions that
ulcerate only after several months
Lesions are usually single and occur primarily on the face.
It is found in urban areas, it is found in Iraq and around the
Mediterranean basin and in Asia Minor, Afghanistan, India and
Kenya.
L. major: also called L.
tropica major (causes wet
sore or rural
cutaneous leishmaniasis).
Produces an acute infection
with duration of 3-6 months.
With as little as 2 weeks
incubation period.
The lesions occur primarily
on the lower limb.
The lesions are moist and
tend to ulcerate very early.
There may be secondary or
satellite lesions.
L. major occurs in Asia
Minor, Middle East (Iran,
Syria, Palestine
and Jordan) and in north and
middle Africa.
It is primarily a disease of
rural areas.
Reservoir hosts (Rodents)
are important source of
human
infection.
Diagnosis

1-Usually made in endemic areas on clinical grounds.

2-Microscopic detection of amastigotes (L.D. bodies) within large

monocytic cells in biopsy of skin and in Giemsa stained smear obtained by
aspiration of fluid from beneath the ulcer bed, especially its active borders.
Scraping taken from the ulcer surface do not reveal the
organisms, which are destroyed in areas secondarily infected with
Bacteria

3-Culture: on NNN (Novy-MacNeal-Nicolle) media.

Culturing of material obtained by aspiration or biopsy may
demonstrate promastigote forms.

5-Leishmanin skin test (Montenegro test): involves the forearm

intradermal injection of 0.1 ml suspension of killed promasitigote,
this test is used to measure delayed hypersensitivity. Positive
result is indicated by an induration of 5mm or more in 48-72
hours. In cutaneous leishmaniasis this test is positive.
 amastigotes (L.D.
bodies) within large
monocytic cells in
biopsy of skin

Differential diagnosis of cutaneous leishmaniasis:

1. cutaneous tuberculosis, and other atypical mycobacteria.
2. syphilis.
3. Deep fungal infection.
4. cutaneous neoplasms.
5. sarcoidosis
Treatment

Aim of treatment is: (1) prevent mucosal invasion (2) accelerate

healing, and (3) prevent disfiguring scars

○ Depending on the species, anatomic location

○ Treatment encouraged for multiple lesions or large (> 4–5 cm), if
present for > 6 months or if lesions in a cosmetically sensitive
area or over a joint

– The sandfly’s biting apparatus cannot penetrate clothing and

thus clothing can be protective
– Sandflies can penetrate mosquito netting; however, one can
spray the netting with permethrin spray (available at sporting
goods stores) and this will last through a few washes and can be
effective
– Insect repellant helpful in prevention – recommend long-lasting
repellant such as Ultrathon (contains DEET)
Basal cell
carcinoma
Bcc
Most common
malignancy

Sun exposure and anatomic site appear to be important in development

Most common gene alteration = PTCH gene
Second most common gene alteration = p53 mutation
• It typically occurs
in areas of chronic
sun exposure

• BCC is usually
slow growing and
rarely
metastasizes, but it
can cause
clinically
significant local
destruction and
disfigurement if
neglected or
inadequately
treated
• Prognosis is
excellent with
proper therapy
 Clinical
Presentation and
Types

1. Nodular – most
common type
■ Papule or nodule,
translucent or
“pearly”. Skin-
colored or reddish,
smooth
surface with
telangiectasias. Well-
defined
2. Pigmented
BCC

May be brown
to blue-black.
Smooth,
glistening
surface.

Can mimic
melanoma or
blue nevus
3. Cystic BCC

Round, oval shape

with
depressed/umbilicated
center
 4. Superficial BCC
Pink or red, scaly, eczematous patch
5. Morpheaform and Infiltrating – aggressive BCC
subtypes; sclerotic plaques or papules
May appear as a scar
Treatment
1. Electrodessication & Curettage (ED&C)
○ Overall cure rate is 80–90%
○ Not recommended on the face and ears – high-risk areas
○ Not a good option for – aggressive subtypes of BCC, such as morpheaform,
infiltrating, and recurrent tumors, are usually not friable and therefore unlikely to be
removed by using the curette

2.Surgical Excision
○ Margins: at least 4 mm to achieve 95% cure rates (even for least aggressive
tumors)
Mohs surgery;
○ Recommended for face, ears, and for aggressive histologic subtypes
○ With the Mohs technique, almost 100% of the tissue margins are examined

3. Radiation therapy
○ For most BCCs, cure rate over 90%; if tumor recurs, tends to be more aggressive.
Limit to those patients who cannot undergo surgery
4. Cryotherapy – not for aggressive tumors
5. Imiquimod 5% cream – for superficial BCCs○ Apply 5x/week for 6 weeks
6. 5-Fluorouracil – small, superficial BCCs
○ Apply BID for at least 6 weeks; may need 10–12 weeks
Squamous Cell Carcinoma (SCC)

SCC is a malignant tumor of epidermal keratinocytes associated with p53 muta-

tions from UV-induced DNA damage

Second most common form of skin cancer and frequently arises on the sun-
exposed skin of middle-aged and elderly individuals
Some cases of SCC occur de novo (i.e., in the absence of a precursor lesion);
however, some SCCs arise from sun-induced precancerous lesions known as actinic
keratosis (AKs) and patients with multiple AKs are at increased risk for developing
SCC
SCC is capable of locally infiltrative growth, spread to regional lymph nodes, and
distant metastasis, most often to the lungs

actinic keratosis
Risk Factors
○ age>50, male sex, fair skin, geography (closer to equator), Hx of prior
NMSC, exposure to UV light (high cumulative dose), exposure to chemical
carcinogens (arsenic, tar), exposure to ionizing radiation, chronic immuno-
suppression, chronic scarring condition, genodermatoses, HPV infection (specific
subtypes)
 Clinical Variants

○ SCC in situ (Bowen’s disease) –

red, scaly patch that arises in sun-
exposed areas or in genital area
(HPV-16 or -18 typically)
 ○ Invasive SCC – Erythematous, keratotic papule or nodule
arising on background of sun-damaged skin. Often tender and
may enlarge rapidly
 ○ Marjolin ulcer – subtype of SCC appears as a new area of
induration, elevation, or ulceration at the site of a preexisting scar or
ulcer
○ Verrucous carcinoma – locally destructive, but rarely metastasizes
DDx of SCC–

• superficial basal cell carcinoma,

• verruca vulgaris, actinic keratosis,
• condyloma accuminata in genital area,
• neuroendocrine carcinoma,
• amelanotic melanoma,
• adnexal tumors,
• prurigo nodule,
• irritated seborrheic keratose,
• atypical fibroxanthoma.
Treatment

SCC in situ – Surgical excision, Mohs, Imiquimod, 5-Fluorouracil cream (5-FU),

photodynamic therapy, cryotherapy

SCC – Surgical excision (4 mm margins), Mohs, Radiation – for select patients ○

Consider radiation if multiple involved nodes or extensive extracapsular extension
is present or inoperable disease (latter +/− chemotherapy with
cisplatin)

Risk Factors for recurrence

• Large size
• Poorly defined borders,
• history of recurrence,
• immunosuppression present,
• site of prior radiation therapy,
• rapidly growing tumor,
• perineural invasion
• Cutaneous tuberculosis
Scrofuloderma
Tuberculous gumma
Tuberculosis cutis
orificialis
Tuberculous
chancre
Tuberculosis verrucosa cutis
Lupus vulgaris
Investiagations include

Biopsy The typical TB lesion is epithelioid granuloma with central caseation

necrosis
CXR
Tuberculin test
Culture is a method of high specificity and sensitivity in diagnosing TB.
Classical methods of mycobacteria culture use sample seeding in solid media:
Lowenstein-Jensen and Ogawa-Kudoh. The time to detect bacterial growth
ranges from 14 to 30 days and may extend up to eight weeks.

IMMUNOLOGICAL TESTS - IGRAS- INTERFERON-GAMMA RELEASE ASSAYS

These are immunological tests based on cellular response stimulation through

peptides that are absent from BCG and most non-tuberculous mycobacteria.
They assess sensitization to M. tuberculosis by measuring the amount of INF
gamma released by lymphocytes confronted with M. tuberculosis-specific
antigens

Treatment regimens adequate for pulmonary TB also are effective for

extrapulmonary disease.
 Melanoma

Clinical
Presentations
and Types

Superficial Spreading Melanoma

○ Accounts for 70% of all cutaneous melanomas.
○ Location (men) – trunk; Location (women) – lower extremities
○ Asymmetric patch or plaque with variations in color and border irregularity
○ Papular or nodular component suggests deeper invasion
○ Can arise from preexisting nevi
Nodular Melanoma

○ Distribution similar to superficial spreading melanoma, but onset more rapid

○ Papule or nodule with colors ranging from red to blue/black. Occasionally
ulcerated.
○ Precursor moles not usually associated
Acral Lentiginous Melanoma

○ Distribution is on palms/sole or nail apparatus

○ dark brown/black macular lesion with foci of plaque or nodule formation.
Can develop ulceration. Borders often very ill-defined.
Lentigo Maligna Melanoma

○ Usually related to cumulative sun exposure and occurs on sun-exposed areas

○ Typically has both a macular component and a papular or nodular
component
DDx – many conditions can simulate melanoma, either clinically or histologically
–
spitz nevi, dysplastic nevi, seborrheic keratoses, blue nevi, pyogenic granuloma,
etc.

spitz nevus

Treatment
If untreated, cancer will likely metastasize – spreads to draining lymph nodes →
distant sites
Surgical excision with safe margins according to depth of tumor
 45 yr old woman with 2 months
duration of painless ulcer on
leg

What is your differential diagnosis?