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264
Staging
Manipal Manual of Surgery
TNM STAGING Definition of regional lymph node (N)
N Number of tumour-involved Presence of
Category regional lymph node in-transit,
satellite, and/
or
microsatellite
metastases
Nx Regional nodes not assessed (e.g. SLN
biopsy not performed, regional nodes No
previously removed for another reason)
N0 No regional metastases detected No
N1 One tumour-involved node or in-transit,
satellite, and/or microsatellite metastases
with no tumour-involved nodes
N1a One clinically occult (i.e. detected by
SLN biopsy)
N1b One clinically detected No
N1c No regional lymph node disease Yes
N2 Two or three tumour-involved nodes
or in-transit, satellite, and/or microsatellite
metastases with one tumour-involved node
N2a Two or three clinically occult (i.e. detected
by SLN biopsy) No
N2b Two or three, at least one of which was
clinically detected No
N2c One clinically occult or clinically detected Yes
N3 Four or more tumour-involved nodes
or in-transit, satellite, and/or microsatellite
metastases with two or more tumourinvolved nodes, or any number of matted
nodes without or with in-transit, satellite,
and/or microsatellite metastases.
N3a Four or more clinically occult (i.e.
detected by SLN biopsy) No
N3b Four or more, at least one of which
was clinically detected, or presence No
of any number of matted nodes
N3c Two or more clinically occult or clinically
detected and/or presence Yes
of any number of matted nodes
TNM STAGING Definition of primary tumour (T)
T Category Thickness Ulceration Status
TX: Primary Not applicable Not applicable
tumour thickness
cannot
be assessed
(e.g. diagnosis
by curettage)
T0: No evidence Not applicable Not applicable
of primary tumour
(e.g. unknown
primary or completely regressed
melanoma)
Tis (melanoma Not applicable Not applicable
in situ)
T1 ≤1.0 mm Unknown or
unspecified
T1a <0.8 mm Without ulceration
T1b <0.8 mm With ulceration
0.8–1.0 mm With or without
ulceration
T2 >1.0–2.0 mm Unknown or
unspecified
T2a >1.0–2.0 mm Without ulceration
T2b >1.0–2.0 mm With ulceration
T3 >2.0–4.0 mm Unknown or
unspecified
T3a >2.0–4.0 mm Without ulceration
T3b >2.0–4.0 mm With ulceration
T4 >4.0 mm Unknown or
unspecified
T4a >4.0 mm Without ulceration
T4b >4.0 mm With ulceration
a = without ulceration, b = with ulceration
CLINICAL STAGING*
Stage 0 Tis N0 M0
Stage IA T1a N0 M0
Stage IB T1b N0 M0
T2a N0 M0
Stage IIA T2b N0 M0
T3a N0 M0
Stage IIB T3b N0 M0
T4a N0 M0
Stage IIC T4b N0 M0
Stage III Any T, Tis >N1 M0
Stage IV Any T Any N M1
*Clinical staging includes microstaging of the primary melanoma and clinical/radiologic evaluation for metastases. By convention, it should be
used after complete excision of the primary melanoma with clinical assessment for regional and distant metastases
Section II • General Surgery
Skin Tumours
TNM STAGING Definition of distant metastasis (M)
M Criteria
M Category Anatomic site LDH level
M0 No evidence of distant metastasis Not applicable
M1 Evidence of distant metastasis See below
M1a Distant metastasis to skin, soft tissue including muscle, Not recorded or unspecified
M1a(0) and/or nonregional lymph node Not elevated
M1a(1) Elevated
M1b Distant metastasis to lung with or without M1a sites Not recorded or unspecified
M1b(0) of disease Not elevated
M1b(1) Elevated
M1c Distant metastasis to non-CNS visceral sites with Not recorded or unspecified
M1c(0) or without M1a, M1b Not elevated
M1c(1) Elevated
M1d Distant metastasis to CNS with or without M1a, M1b, Not recorded or unspecified
M1d(0) or M1c Not elevated
M1d(1) Elevated
• Serum lactate dehydrogenase (LDH)
• Suffixes for M category: (0) LDH not elevated, (1) LDH elevated.
• No suffix is used if LDH is not recorded or is unspecified.
265
*Each stage classified based on LDH level
Important Changes in the New AJCC Staging of
Malignant Melanoma
1. Thickness and ulceration in T-category rather than
level of invasion.
Number of metastatic nodes is more important.
2.
3. LDH (details are given later) is included in ‘M’
category (metastatic spread).
4. If there is ulceration, 3 stages are upgraded.
5. Satellite nodules and in-transit deposits are grouped
into stage III disease.
CUTANEOUS MELANOMA—AMERICAN JOINT COMMITTEE
ON CANCER (AJCC 8th
Edition)—4 STAGES
• Stage 0: In situ carcinoma.
• Stages I and II: Primary tumours confined to the skin
without regional lymph node involvement—
depending on the thickness (depth) of the tumour,
the presence or absence of ulceration of the overlying
epithelium
Stage IA: <0.8 mm thick, NO ulceration
Stage IB (T1B): <0.8 mm thick with ulceration or
0.8–10 mm thickness ± ulceration
Stage IB: T2a or Stage II: >10 mm thick with any
features
• Stage III: With clinical or pathological evidence of
regional lymph node + OR the presence of in-transit
or satellite metastases.
• Stage IV: Disease is defined by the presence of distant
metastasis—biopsy proven.
Investigations
Blood tests such as haemoglobin, total RBC, and
1.
WBC counts are done. Lactic dehydrogenase (LDH)
has been included under M (Metastasis) category.
LDH represents a strong prognostic factor in
unresectable, metastatic (stage IV) melanoma. Levels
>500–1000 U/L suggest a high tumour burden. LDH
which is present in the normal cells gets released
when the cells are destroyed by the tumour.
. A chest X-ray is taken—if it shows metastasis, it is
2
stage IV disease. However, a negative chest X-ray
does not rule out metastasis.
3. Biopsy: A full-thickness biopsy of the lesion with
a narrow (1 to 2 mm) margin of grossly normal skin
is made. The depth of excision should include the
full thickness of the dermis and, thus, should extend
into the subcutaneous tissue. Accurate measurement
of tumour thickness is important because it is critical
for the prognosis and affects surgical recommendations. Incision biopsy is indicated only in advanced
lesions. Once the specimen is removed, the following
details have to be studied—Breslow thickness,
ulceration, dermal mitotic rate, microsatellitosis, pure
desmoplasia, and deep and peripheral margin status.
In subungual melanomas, biopsy may be taken after
removal of all or a large part of the nail and one or
more punch biopsies of the base of the nailbed.
In cases of melanoma in situ, blood tests and imaging are not
required.
Section II • General Surgery
266
Manipal Manual of Surgery
4. Imaging: Ultrasound abdomen is economical and
easily available. Presence of iliac or para-aortic lymph
nodes and secondaries in the liver can easily be made
out. However, in all cases of stage III melanomas
(lymph nodes positive), contrast-enhanced CT scan
of the chest and abdomen should be done (Fig. 31.49).
5. PET with fluorodeoxyglucose (FDG): It is used for
staging patients with advanced melanoma, but its
role in earlier stages is unclear because it is expensive
and associated with substantial radiation exposure.
6. FNAC of the lymph nodes: Clinically palpable lymph
nodes may be subjected for ultrasound-guided
aspiration. In melanoma even a palpable lymph node
is enough to decide about block dissection (Figs 31.50
and 31.51).
7. Genetic: Melanocyte protein, also known as pre-
melanosome protein (PMEL), is a protein that
is encoded by the PMEL gene. This may be used as a
specific immunohistochemical marker for melanoma.
Treatment
Surgery is the main treatment modality for malignant
melanoma. All other modalities are only palliative and
supportive
. In early stages without lymph node enlargement and the tumour with good histology, it is still a
curable cancer. Surgery can be divided as treatment of
the primary lesion and of metastatic lymph nodes.
A. Treatment of the Primary
Excision biopsy-wide excision: A small lesion of
1.
1 mm may be excised even under local anaesthesia
with 1 cm of healthy margin around (narrow excision).
Defect may be closed by primary suturing. While
excising the tumour, it is better not to handle the
tumour. It is possible to remove the tumour by strictly
adhering to the principle of ‘No touch’ technique
(Figs 31.52 and 31.53). Wide excision is based on principle of ‘centrifugal spread of melanoma.’ One of the
causes of recurrence is inadequate excision (Fig. 3
1.54).
Fig. 31.49: Lung metastasis in CT of the chest. It was not visible
in X-ray chest
Fig. 31.50: Hugely enlarged inguinal lymph nodes—the nodes
can be firm to hard. Sometimes, they are soft due to degeneration
Tumour thickness (mm) Wide excision margin
<1 mm 1 cm
1–2 mm 2 cm
>2 mm 2 cm
– Desmoplastic melanoma: Has a high rate of recu-
rrence; hence, a wide margin of excision is required.
Fig. 31.52: Ulcerated melanoma over the heel—poor prognosis
Fig. 31.51: FNAC of the recurrent inguinal node secondaries—
bluish black aspirate
Section II • General Surgery
Fig. 31.53: Wide excision (minimum 2 cm) specimen
Skin Tumours
Fig. 31.54: Local recurrence after 2 years probably because of
inadequate local excision—you can see the previous skin graft
267
• Sentinel lymph node mapping: Isosulfan blue is
injected intradermally and the node that gets stained
is identified and sent for frozen section (haematoxylin
and eosin stains and immunohistochemical technique).
If the node is positive, regional lymphadenectomy
is done even if the nodes are clinically not palpable.
At least 20–30% of patients who are in stage I will be
identified as stage III after sentinel node biopsy
(SNBx). There is a definite survival advantage in
patients who undergo SNBx and regional lymphadenectomy when the nodes are not palpable.
Fig. 31.55: 8 cm ulcerated pigmented lesion in the foot—
malignant melanoma foot required amputation
2. Subungual malignant melanoma is treated by
amputation of the digit.
3. Amputation (advanced and large lesions) (Fig. 31.55).
4. Malignant melanoma of the choroid has good prog-
nosis. Choroid does not have lymphatic drainage.
However, metastasis may occur through the haematogenous route even after many years. It is treated by
enucleation of the eye.
B. Treatment of Lymph Nodes
1. If lymph nodes are situated adjacent to the primary
lesion, block dissection is done along with the
primary lesion in continuity to include ‘in-transit’
deposits also.
. If lymph nodes are away, radical block dissection is
2
done. Example: For a lower limb malignant melanoma,
inguinal nodes along with the iliac nodes are removed
(ilioinguinal block dissection). If these groups of
nodes are positive on frozen section, lymph node
clearance should include lymph nodes of obturator
vessels (ilio-obturator block dissection) (Figs 31.56
and 31.57), or if pelvic CT scan is positive or Cloquet
node is positive, the obturator group of lymph nodes
is removed. To get the best results if facilities are
available sentinel lymph node mapping is done.
Depending upon the results of the findings, lymph
node dissection is done. Details are given below.
Fig. 31.56: Lazy S incision is given for inguinal block dissection—
this incision decreases incidence of flap necrosis
Fig. 31.57: Observe pigmented lymph nodes
Types of lymph node dissections:
• If sentinel node biopsy is negative, prophylactic block
dissection is indicated only if the melanoma has poor
prognostic histological factors.
• If lymph nodes are positive after FNAC: TLND—
therapeutic lymph node dissection is done.
• In patients with no clinical lymph nodal metastasis
but ELND—elective or prophylactic lymph node
dissection is beneficial. In cases of 1–4 mm thick
melanoma, melanoma without ulceration, extremity
melanoma, patients <6 years of age. In these patients
only 25% of patients show occult metastasis.
Section II • General Surgery
268
Manipal Manual of Surgery
Summary of skin tumours is given in Table 31.6.
Table 31.6 Summary of skin tumours
Squamous cell carcinoma Basal cell carcinoma Malignant melanoma
Incidence Common (20–30%) Most common (60–70%) Less common (10–20%)
Origin Prickle cell layer Basal layer Melanoblasts
Aetiology Chronic irritation Ultraviolet rays, fair skin Ultraviolet rays, fair skin, pre-existing mole
Site Trunk, leg, hand, oral cavity Tear cancer Head and neck, face, digits, palm and sole
Types Ulcerative or cauliflower Nodular or ulcerative Nodular or ulcerative
Edge Everted Rolled out and beaded Irregular
Induration Maximum Moderate Minimum
Scab Never occurs Occurs Never occurs
Pigmentation Absent Absent Present in 90% of cases
Spread Mainly by lymphatics. Blood spread Does not spread by lymphatics Mainly by lymphatics, also by blood
is rare and late Blood spread is very, very late spread, does not infiltrate like rodent ulcer
Spreads by local spread. Hence
the name, rodent ulcer
Cytokeratin Expression No No
STAGEWISE TREATMENT (MORE DETAILS) AND RECENT ADVANCES
Please note: Recent advances in the treatment of
melanoma are very complicated. It not only includes
surgery, radiotherapy, and chemotherapy, but also biochemotherapy, vaccines, monoclonal antibodies, kit
inhibitors, etc. Those of you who would like to get more
marks can refer these.
Surgery in the form of wide excision is the most important curative treatment in stage I and stage IIB. Other
various forms of treatment are available in Fig. 31.58.
STAGEWISE TREATMENT: CLINICAL TISN0M0, STAGE 0:
CLINICALL
Y LOCALIZED MELANOMA OR MELANOMA
IN SITU
• Melanoma in situ by definition is not invasive or
metastatic. However, metastatic melanoma to
regional nodes has been observed occasionally from
melanoma in situ with histologic evidence of
regression.
• Examine the nodes clinically.
• Radiological studies are not necessary.
• Wide excision alone in the majority of cases.
PRINCIPLES OF WIDE EXCISION
• Full-thickness excision of skin and subcutaneous
tissue to the underlying deep fascia.
• A 5 mm margin is the standard recommendation, but
melanoma in situ may extend beyond its visible
extent. Thus, if cosmetically acceptable, it is reasonable to obtain a margin of as much as 1 cm, especially
if the original biopsy was incomplete.
Section II • General Surgery
Fig. 31.58: Various treatment available for malignant melanoma
Skin Tumours
269
STAGE I: CLINICAL T1A
1. Thin Primary Melanoma
Thin melanomas, such as T1a melanomas, are those
2
<1 mm thick, with <1 mitosis per mm
, and without
ulceration. In the absence of any clinical evidence of
metastasis, these are clinical stage IA melanomas. 5-year
survival rate of 94%.
Treatment of T1A
• Wide excision with a 1 cm margin (including skin
and all underlying subcutaneous tissue to the deep
muscle fascia).
• The margin should be measured from the visible
edge of the pigmented lesion or from the biopsy scar,
whichever is larger.
• After excision, primary closure is performed.
However, if on the face, palms, or feet, skin grafts or
rotation flaps are used.
2. Melanomas of the Trunk and Proximal Extremities
• Wide local excisions should involve measuring the
appropriate margin (usually 1–2 cm) around the
entire scar from the biopsy, or
• From the visible edge of residual melanoma, and
extending the incision to make an ellipse that is
approximately three times as long as it is wide.
Incision/Excision Principles
• Extremities—ideally, the direction of the scar should be
longitudinal.
• Over the joints, on the trunk and neck—along skin
lines.
• On the upper back—it is usually best for the scar to run
transversely.
• The excision should include all skin and subcutaneous
tissue up to the deep fascia (but not including the
fascia).
• When a major cutaneous nerve runs along the deep
fascia to innervate distal cutaneous structures—
preserve the nerve.
• Wide excisions can almost always be performed under
local anaesthesia.
3. Clinical T2A, T2B Melanomas
• Melanomas 1–2 mm thick, with or without ulcera-
tion.
• History and physical examination—may suggest
metastatic disease.
• In the absence of such findings, very low yield of addi-
tional staging studies—hence, not recommended.
• No evidence of metastasis—wide excision with a
1–2 cm margin and SNBx.
4. Primary Melanomas of the Fingers and Toes
• Subungual melanomas of any finger or toe—
amputation at the interphalangeal joint of the toe or
just proximal to the distal inter-phalangeal joint of
the finger (Fig. 31.59).
• SNBx should usually be performed for melanomas
of the fingers or toes if they are at least T1b lesions.
Fig. 31.59: Ulcerated melanoma—Stage IIB
5. Sentinel Node Biopsy
• If the SNBx is negative, then the patient is patho-
logically staged as T2aN0M0 (stage IB) or T2bN0M0
(stage IIA).
• No additional surgical management is required, and
no adjuvant systemic therapy is indicated.
STAGE II: MELANOMA (T2B–T4B)
. Clinical T3A Melanomas (Clinical Stage IIA)
A
• Melanomas 2–4 mm thick without ulceration repre-
sent T3a lesions, and in the absence of metastases,
these are clinical stage IIA lesions.
• Serum LDH level: LDH is a key enzyme in the
process of energy production in cancer cells. It
catalyzes the conversion of pyruvate to lactate in
hypoxic conditions. LDH levels are increased in
response to tissue injury or during disease states.
LDH may be a marker of tumour burden for
advanced cancer patients.
• Wide excision with a 2 cm margin plus SNBx.
B. Clinical T3B Melanomas (Clinical Stage IIB)
• Wide excision with a 2 cm margin plus SNBx.
• If the nodes are negative, treat like stage IIB
(T3bN0M0).
Section II • General Surgery
270
Manipal Manual of Surgery
• No additional surgical therapy required.
• HDI (high-dose IFN-
2-b) and pegylated-interferon—
postsurgical adjuvant therapy in resected stage
IIB–III melanoma.
C. Clinical T3B Melanomas (Clinical Stage IIB)
• Melanomas 2–4 mm thick with ulceration represent
T3b lesions—clinical stage IIB (Fig. 31.60).
• If symptoms suggest metastatic disease, perform
imaging.
• Staging with CT scans of the chest, abdomen, and
pelvis (or PET/CT scan) plus MRI scan of the brain—
symptomatic cases.
D. Thick Melanomas (T4A, T4B, >4 mm Thick)
• Thick melanomas: A 50% risk of metastasis and
mortality over 5–10 years.
• Ulceration increases this risk: T4a melanomas are
clinical stage IIB, whereas T4b melanomas are clinical
stage IIC.
• CT scans of the chest, abdomen, and pelvis plus MRI
of the head.
• Wide excision with ≥2 cm margin plus SNBx.
• In patients with negative sentinel nodes, adjuvant
low dose interferon (LDI) should be considered.
• If the sentinel node biopsy is positive: These are
melanomas >10-mm thick with or without ulceration.
Subsequent management should follow recommendations given later for stage IIIA melanoma (T2a with
positive SNBx involving 1–3 nodes) or stage IIIB melanoma (T2b with positive SNBx involving 1–3 nodes).
• Low-dose interferon alfa (LDI-): Interferon-α-2a is
approved for clinically lymph node negative melanoma patients with a tumour thickness of ≥1.5 mm.
Figs 31.60 and 31.61: Loco regional recurrent melanoma
Section II • General Surgery
STAGE III: MELANOMA
egionally Metastatic Melanoma (Stage III)
R
Figures 31.61 and 31.62. They should be managed with
a curative intent.
• Primary lesion with lymph node metastasis, satellite
lesions, and in-transit metastases
• Wide excision—maximum of 2 cm margin
• Complete lymph node dissection (CLND)
• Observation or adjuvant immunotherapy with
Nivolumab or BRAF mutation gene positive—
Tremenitib or IFN-α
Indications for Adjuvant Systemic Therapy
(Stages IIb, IIc, and III)
• HDI—for 1 month followed by 1 year of intermediate
dosing IFN for 1–2 years. Interferon—at a low dose
administered for 1–3 years. Pegylated IFN administered for a target period of 5 years.
• Interferon is administered by IV infusion, 20 million
2
U/m
, for 5 consecutive days every 7 days for 4 weeks
during the “induction” phase.
• For the subsequent 48 weeks, 10 million U/m2 are
administered by subcutaneous injection on alternate
days for a total of 3 doses every 7 days in the
“maintenance” phase.
• The HDI is used for the treatment of stage III
melanoma patients (6 µg/kg/week for 8 weeks then
3 µg/kg/week for up to 5 years).
• Toxicity: Fatigue, anorexia, hepatotoxicity, flu-like
symptoms, injection site reactions and depression.
Management of Palpable Metastatic Melanoma in
R
egional Nodes: Therapeutic or Completion Lympha-
denectomy
• Inguinal block dissection has two components: Block
dissection of
A.
Superficial inguinal lymph nodes along the long
saphenous vein (vertical) and horizontal group
of lymph nodes below inguinal ligament
B. Deep inguinal node dissection: They are located
medial to the femoral vein and under the cribriform fascia. There are approximately 3–5 deep
nodes. The superior most node is located under
the inguinal ligament and is called Cloquet’s
node. This node is deep to deep fascia on the
medial side of the femoral vein. They are 1–3 in
number. One of them may lie in the femoral
canal (lymph node of Cloquet). Afferent: From
the deep lymphatics of the lower limb and the
superficial inguinal LNs. Efferent: To the
external iliac LNs. Metastasis to a regional node
represents stage III (A, B, or C) disease. It may
be curable. Hence complete lymphadenectomy
should be done.
Skin Tumours
271
• Complete lymph node dissection refers to clearing
the anatomically complete dissection of the nodal
basin, elective ilio-obturator dissection when inguinofemoral nodes are positive or >3 nodes are positive
or when pelvic CT is positive or when Cloquet node
is positive. Cloquet node is the transitional node
between the inguinal region and the iliac region.
• Lymphatic anatomy of the inguinal canal, the impor-
tance of various lymph nodes, and types of dissection
are given below (Fig. 31.62).
• An iliac node dissection involves skeletonizing the
external iliac vessels. It is generally combined with
removal of the iliac node-bearing tissue and the
obturator fat pad (obturator dissection).
Regional Metastases: Definitions
• Local recurrence: Recurrence of melanoma in the scar
from the original excision or at the edge of the skin graft
(if used for closure).
• Satellite metastases: Either occur simultaneously with
the original diagnosis or arise subsequent to original
excision. Typically, recurrences that are separate from
the scar but within 2–5 cm of it are considered
satellite metastases.
• In-transit metastases: Regional recurrences beyond
5 cm of the scar but proximal to regional nodes.
• Regional node metastases are typically in a draining
nodal basin near the lesion.
A. Intratumoral Therapies
• Intralesional BCG: Regression of uninjected and
injected lesions.
• Intralesional injection of melanoma metastases with
an oncolytic herpes virus encoding granulocyte
macrophage–colony-stimulating factor (GM-CSF).
B. Solitary In-transit Metastasis or a Localized
Cluster of In-transit Metastases
• Excision plus SNBx
• The margin of excision: 5–10 mm
C. Hyperthermic Isolated Limb Perfusion with
Melphalan Infusion
• Complete responses in 60–90% of patients
• Risk of limb loss
D. Palliative Treatment of Regional Metastasis
• Radiation therapy: After surgical resection.
• Intralesional therapy with IFN, IL-2, BCG, or oncolytic
replication competent virus injections.
• Highest response rates to intralesional therapy—
intratumoral IL-2, intratumoral electrochemotherapy
with bleomycin or cisplatin.
• Dyes like Rose Bengal or application of diphency-
prone.
• Topical treatment of superficial metastases with
imiquimod.
STAGE IV: MELANOMA
Metastatic disease: M1a: Skin, soft tissue, remote nodes;
M1b: Visceral pulmonary and M1c: Visceral nonpulmo-
Stage 4 disease with metastasis and increased LDH
nary.
is the highest risk category—Stage 1VC.
Fig. 31.62: Lymphatic anatomy of the groin region
1. Cytotoxic Chemotherapy and Biochemotherapy
• Biochemotherapy consisting of dacarbazine
2
800 mg/m
1–4; vinblastine 1.2 mg/m
on day 1, cisplatin 20 mg/m2 on days
2
on days 1 –4; IL-29 MU/m
per day continuous IV administration on days 1–4;
interferon 5 MU/m2 subcutaneously on days 1–4, 8,
10, and 12; and granulocyte colony stimulating
factor 5 µg/kg per day subcutaneously on days
7–16. Biochemotherapy cycles are given every 21 days
for 3 cycles (9 weeks total) (Key Box 31.15).
Key Box 31.15
Interferon-
It has stimulatory effect on natural killer cells (NK)
It has anti-angiogenic activity
It is toxic—weight loss and myelosuppression can occur
IL-2—can cause capillary leak syndrome—hypotension
and renal failure
2
Section II • General Surgery
272
Manipal Manual of Surgery
2. Cytotoxic T-lymphocyte Antigen 4 and PD-1
Blockade in Adjuvant Therapy
Ipilimumab is a fully human immunoglobulin G1
monoclonal antibody that blocks CTLA4, which has
demonstrated improvement in OS in the treatment of
metastatic melanoma in two randomized clinical trials.
3. Interleukin-2
• IV bolus infusion of 600,000 to 720,000 IU/ kg every
8 hours to tolerance using 2 cycles separated by
approximately 10 days (maximum of 15 doses/cycle).
• Significant toxicity (but reversible).
4. Chemotherapy
• Inherent resilience of melanocytes, which have to be
naturally resistant to apoptotic death when exposed
to UV radiation from the sun.
• Dacarbazine, an imidazole carboxamide, is a classic
alkylating agent. It is given intravenously at daily
2
doses of 200 mg/m
for 5 days every 3–4 weeks.
• Temozolomide is an orally available prodrug—not
superior.
• Combination chemotherapy.
• 20% response for carboplatin-paclitaxel-sorafeniband,
and 18% for carboplatin-paclitaxel.
RECIST criteria: Response Evaluation Criteria In Solid
Tumours. Response to the tumour or lymph nodes by
chemotherapy/radiotherapy or any other therapies
are measured by means of CT scan or X-rays or with
callipers. A few other lesions are non-measurable such
as pleural effusions, pericardial effusions, etc.
1
Indications to Radiotherapy
Radiation Therapy for Regional Metastasis
• Melanoma is a radioresponsive tumour and conven-
tional and high dose per fraction schedules are
equally effective clinically.
• 8.0 Gy × 4 fractions (32 Gy total) in 21 days delivered
once weekly or 2.5 Gy × 20 fractions (50 Gy total) in
26–28 days delivered 5 days a week.
Adjuvant Radiation Therapy in the Management
rimary Melanoma Lesions
of P
• Lentigo maligna: Medically inoperable, or if the
proposed resection would result in a poor cosmetic
outcome.
• Desmoplastic melanoma: High chances of recurrence.
• Neurotropic melanoma: Propensity to recur at the
skull base by tracking along cranial nerves.
• Palliation of unresectable primary disease.
5. Anti-cytotoxic T-Lymphocyte Antigen 4 Blocking
Antibodies
• Inactivated tumour vaccines, dendritic cell vaccines
or immune-stimulating cytokines like IFN and IL-2
are aimed at turning on T cells against cancer.
• Tumour responses tend to be durable (counted in
years) in most cases.
• Thus, there is interest in this mode of therapy for
advanced melanoma.
6. Adoptive Cell Transfer Therapy
• Adoptive cell transfer (ACT) therapy refers to an
immunotherapy approach for the treatment of cancer
that involves the infusion to the tumour-bearing host
of cells with antitumour activity that may recognize
cancer antigens and result in the destruction of
cancer cells.
• Although it is still experimental, ACT has emerged
among the most effective treatments for patients with
metastatic melanoma.
• 50–70% of patients with metastatic melanoma
experience objective cancer regressions as per RECIST
criteria when treated with ACT.
GENETIC TESTING AND IMMUNOTHERAPY
• BRAF mutation test may be performed using the
mutation-specific PCR tests for the use of
vemurafenib, dabrafenib, or trametinib.
Melanoma Antigen Gene as
in Cancer Immunotherapy
• Immunization against antigenic tumour epitopes is
achieved by injecting recombinant tumour antigen
protein along with an immunostimulant to induce
both humoral and cellular immune responses.
• Patients receiving recombinant MAGE-A3-based
vaccine will develop MAGE-A3-specific antibodies
and have more clinical benefits.
Melanoma Antigen Gene (MAGE)
• Modern immunotherapies mainly aim to activate
immune responses by either stimulating the activities
of specific components of the immune system or by
counteracting signals produced by cancer cells, such
as immune checkpoint modulators and immune cell
therapy.
1
Section II • General Surgery
European Journal of Cancer 45 (2009) 228–247.
Skin Tumours
273
OTHER MALIGNANT SKIN TUMOURS
Dermatofibrosarcoma Protuberans
• This is a locally malignant tumour arising from the
dermis.
• Common sites are the trunk and flexor region of
limbs. It presents as a nodular (bosselated) ulcerative
lesion of many years duration (Figs 31.63 and 31.64).
• Regional lymph node involvement is uncommon.
• It is less aggressive and, therefore, curable.
• Treatment is by local wide excision, followed by
primary closure or skin grafting.
Fig. 31.63: Dermatofibrosarcoma over the nape of the neck
Key Box 31.16
Diseases Associated with Kaposi’s Sarcoma
Diabetes mellitus
Lymphoma
Following renal transplantation
Acute and chronic immunosuppression (HIV)
Key Box 31.17
Types of Kaposi’s Sarcoma
European : Elderly males
African : Young and children
Transplant : Due to immunosuppression
AIDS : Homosexuals
OTHER SKIN LESIONS
They arise from sebaceous glands, sweat glands, hair follicles, etc. Key Box 31.18 describes types of exocrine glands.
• A few examples are syringoma, hidradenoma, tricho-
epithelioma, and sebaceous carcinoma.
• They present as a localised swelling and are treated
by excision.
• They have to be kept in mind as a differential
diagnosis for malignant skin tumours. Details of a
few skin lesions are given in this chapter.
Fig. 31.64: Dermatofibroma protuberans upper limb
Kaposi’s Angiosarcoma (Key Boxes 31.16 and 31.17)
• Common among the Black population
• It arises from proliferating capillary vessels and
perivascular connective tissue cells.
• Multiple, purplish nodules appear in the limb, which
ulcerate and bleed. This is its characteristic feature.
• Regional lymph node involvement may occur.
• Increasing incidence due to AIDS.
Differential Diagnoses
1. Malignant melanoma
. Soft tissue sarcoma
2
3. Multiple cutaneous metastases
4. T cell lymphoma
Keratoacanthoma: Molluscum Sebaceum,
Molluscum P
seudocarcinomatosum
• Self-limiting benign neoplasm of viral origin (probably).
• Arises due to overgrowth of the hair follicle.
• Subsequent spontaneous regression is characteristic.
• It is a painless swelling in the skin with a central dark-
brown core. After an initial rapid growth of 2–4 weeks,
spontaneous regression occurs within 24 hours. After
separation of the central core, the lump diminishes
in size, leaving a deep indrawn scar.
• Usually single—face is the most common site.
• Like sebaceous cyst, it presents as a hemispherical
swelling.
• It is treated by excision.
Key Box 31.18
Types of Exocrine Glands
Holocrine: Entire cell dies or disintegrates to liberate
secretion, e.g. sebaceous gland.
Apocrine: Only the luminal part of the cell disinte-
grates, cell regeneration takes place from the nucleus
and basal portion, e.g. mammary gland.
Merocrine: Secretion is discharged without destruction
of the cells. Most of the glands belong to this type.
Section II • General Surgery