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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2915_Библиотеки_им_академика_М_И_Перельмана.pdf
Melanoma
21
• ALM is relatively uncommon. Contrary to SSM, NM, and LMM, which occur
almost exclusively in fair-skinned persons, ALM can occur in any ethnic group or in
persons with any degree of skin pigmentation. Lesions occur on the palms, soles of
the feet, and nail beds. They tend to present as more locally advanced lesions and
they tend to be more aggressive in their behavior.
Figure 2. Clinicopathologic caractheristics of melanoma. A- Lentigo melanoma, B- superficial, CAcral lentigious and D- nodular.
Reference
Rigel DS et al. ABCDE: An evolving concept in the early diagnosis of melanoma. Arch
Dermatol. 2005; 141:1032.
5. Diagnostic and Evaluation
• A complete skin examination should be performed, including scalp, trunk, axillae,
genital area, interdigital webs, and oropharynx.
• Melanoma in men occurs more frequently on the trunk or head and neck, and in
women on the extremities, but it can arise from any site. Although most primary
lesions are pigmented, frequently skin metastases are not pigmented, and they may
appear as red or subcutaneous nodules.
• Some signs and symptoms are considered of warning for melanoma and they are
called ABCD rule
A: Asymmetry
B: irregular Borders
Gustavo Arruda Viani
22
Breslow
Regional lymph
node metastasis (%)
Clarck`s level
Description
<=0.75 mm
5% I Confined to epidermis
II
>=0.76 to
<=1.50 mm
10%
II
Invasion into papillary dermis
I
>=1.51 to
<=4 mm
20%
III
Tumor into papillary dermis and
pushing the reticular dermis
>= 4mm
30 – 50%
IV
Invasion of reticular dermis
V
Invasion of subcutaneous tissue
C: changes in Color; pigmentation is not uniform
D: Diameter >6 mm
E: Enlargement of the lesion
• Ulceration or bleeding usually represents deeper lesions. In-transit lesions and skin
metastases appear as skin or subcutaneous erythematous nodules between the
primary tumor site and the regional nodal basin. The nodules can be no pigmented.
• Biopsy of these lesions should be obtained. Precision of the diagnosis can be
increased by use of a dermatoscope, an instrument that magnifies pigmented lesions
about 10 times.
• Incisional biopsies may be used for large lesions or lesions on the face, palmar
surfaces of the hand, sole of the foot, ear, distal digits, genitalia, or under nails.
• Lesions, with any of signs and symptoms cited above, should be evaluated promptly
with an incisional biopsy or, if cosmetically feasible, excisional biopsy with narrow
(at least 2-mm) margins.
• Malignant melanoma is characterized on microscopic for the presence of mitoses,
invasion, and immunohistochemical staining to S100 protein and HMB-45 antibody.
The pathological analysis should include description of maximum thickness, level of
invasion, presence of ulceration, size , and microscopic margins of resection.
• Maximum thickness must be reported as per Breslow thickness (mm) as per the
Clark’s level (Levels I–V) (Table-2 and figure-3)
Table 2. breslow and clark`s level description
Figure 3. Clark`s levels.
Melanoma
23
Superficial
spreading
melanoma (SSM)
Superficial melanoma is the most common MM type with 70% of cases; it
accounts for the changing epidemiology in recent decades, usually arising from a
dysplastic naevus. Macroscopically, SSMs are pigmented lesions that are often
flator with slight elevation.
Characteristically they have an irregular border and irregular pigmentation.
Nodular melanoma
Nodular melanomas make up approximately 15% of cases; they form raised, nod-
ular lesions which may vary in colour from blue-grey to completely amelanotic,
Acral lentiginous
melanoma (ALM)
ALM occurs in approximately 10% of cases; they occur on the soles, palms,
subungual regions and mucosal surfaces.
It is probable that ALMs are genetically distinct from SSM and less related to UV
light exposure.
Mucosal lesions are often diagnosed in advanced stage.
Lentigo maligna
melanoma (LMM)
LMM occur in approximately 5% of cases, mainly, in older patients, on the face,
and related to chronic sun exposure. LMM is slow growing with a long radial
growth phase. About 5% progress to invasive LMM, which may be indicated by
localised thickening of the lesion.
• Clinical evaluation of MM should consist of physical examination (inspection and
palpation) of the involved area of skin and the regional lymph nodes. Lesions with
thicker than 1 mm are generally staged at the time of wide local excision with
sentinel lymph node biopsy.
• MM thinner than 1 mm may still be at risk of nodal disease and could benefit from
sentinel lymph node biopsy when there is an ulceratation, bleeding or satellite lesion.
• If the sentinel node is involved, CT scanning of the lungs, abdomen, and pelvis is
warranted as a baseline evaluation.
• MRI of the brain is indicated for patients with documented distant disease, clinical
symptoms of brain metastases or in patients with multiple or clinically palpable nodal
metastases.
References
Johnson TM et al: Staging workup, sentinel node biopsy, and followup tests for melanoma:
Update of current concepts, Arch Dermatol 140:107, 2004
Rigel DS et al: ABCDE: An evolving concept in the early diagnosis of melanoma. Arch
Dermatol. 2005; 141:1032.
Breslow. A Thickness, cross-sectional areas and depth of invasion in the prognosis of
cutaneous melanoma. Ann Surg ; 1970, 172:902–908;
McMasters KM, Wong SL, Edwards MJ et al. Factors that predict the presence of sentinel
lymph node metastasis in patients with melanoma. Surgery; 2001, 130:151–156;
Rousseau DL, Ross MI, Johnson MM et al. Revised AJCC staging criteria accurately predict
sentinel lymph node positivity in clinically node-negative melanoma patients. Ann Surg
Oncol; 2003, 10:569–574
6. Pathology
Basically there are four main types of MM with distinct clinic pathological characteristics, as described in table-3.
Table 3. Clinical pathologic characteristic of melanoma subtypes
Gustavo Arruda Viani
24
AJCC stage
Thickeness mm
Ulceration
Nodal disease
M 0 In situ
N/A
No
No
IA
<1
No
No
No
IB
<1
1.01-2
Yes
No
No
No
No
No
AJCC stage
Thickeness mm
Ulceration
Nodal disease
M
IIA
1.01-2
2.01-4
Yes
No
No
No
No
No
IIB
2.01-4
>4
Yes
No
No
No
No
No
IIIA
Any
No
1 node w/microscopic disease
2 2-3 nodes w/microscopic disease
No
IIIB
Any
Any
Yes
Yes
1 node w/microscopic disease
2–3 nodes w/microscopic disease
No
Reference
Liu V, Mihm MC. Pathology of malignant melanoma. Surg Clin North Am. 2003;83(1):31.
7. Routes of Spread
• The first site of metastatic disease is the skin, subcutaneous tissues and lymph nodes
and they are present up to 60% of patients.
• Melanoma can become highly invasive, penetrating into and beyond the dermis.
Initially there is a variable horizontal growth phase, followed by a vertical growth
phase invading through dermis and into surrounding structures.
• Lymphatic spread to regional nodes is the most common occurrence. In-transit
metastases or satellite nodules are defined as cutaneous or subcutaneous nodules that
are more than 2 cm from the primary tumour and not beyond the draining lymph
nodes.
• Lungs, liver, bone, brain and skin are not uncommon sites of distant metastases,
mainly, for more invasive and thicker lesions.
Reference
Johnson J TM et al. Staging workup, sentinel node biopsy, and followup tests for melanoma:
Update of current concepts, Arch Dermatol. 2004; 140:107.
The American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM)
staging system incorporates lesion thickness, ulceration, and nodal involvement for nonmetastatic melanoma (table-4)
8. Staging
Table 4. TNM staging for melanoma
Melanoma
25
Any
Any
Any
No
No
Any
1 node w/macroscopic disease
2–3 nodes w/macroscopic disease
in transit or satellite disease
IIIC
Any
Yes
Yes
Any
1 node w/macroscopic disease
2–3 nodes w/macroscopic disease
>=4 metastatic or matted nodes, in
transit or satellite disease
No
IV
Any
Any
Any
Yes
Factor
Description
Tumour
thickness
The principal prognostic factors for patients with early MM (stages I to III) relate
to the depth of invasion of the primary lesion. The level of invasion, or Clark
level, is strongly correlated with outcome but is not as reproducible among
pathologists.
Ulceration
The absence of an intact epidermis diagnosed histologically is associated with a
doubling of the risk associated with the depth of penetration.
Anatomical
location
Tumours on the extremities appear to have a better prognosis than those on the
trunk.
Gender
Most studies have shown a better prognosis for females than males
Lymph nodes
The prognosis worsens with the number of nodes involved. A thin lesion (Breslow
depth <0.76 mm) without lymph node involvement has a 3% risk of metastasizing
in 5 years, whereas if regional lymph nodes are macroscopically involved there is
a less than 20 to 50% chance of surviving 5 years.
Age
Older patients tend to have thicker lesions, are male with tumours on the head and
neck and have ulcerated tumours at the time of diagnosis.
Reference
American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton
CC, et al (Eds), Springer, New York 2010.
9. Prognostic factors
Several prognostic factors have been identified with local control and survival in patients
with melanoma (table-5).
Table 5. Prognostic factors for melanoma
Reference
Balch CM et al: Prognostic factors analysis of 17,600 melanoma patients:Validation of the
American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;
19:3622.
Gustavo Arruda Viani
26
Study
Description
Burmeister et al.
(2006)
234 patients with positive lymph node treated adjuvantly with 48 Gy in 20 fractions.
If involved margins, 50 Gy in 21 fractions.
47% were radiated to the axilla, 33% to head and neck, 20% to ilio-inguinal.
At 5 years, infield regional relapse was 6.8%. Five-year OS 36%, PFS 27%, and
regional control 91%.
Study
Description
Grade 3 lymphedema 9% in axillary RT patients and 19% in ilio-inguinal RT
patients.
10. Treatment
• The main objective of treatment is to detect the lesion as initially as possible and to
excise it with adequate margins without compromising the functional and esthetical
results.
• Once that the diagnosis of melanoma has been established, surgical excision with an
adequate margin of normal tissue is required. The recommended width of
surrounding local normal tissue is determined by thickness of the primary tumor.
• Melanomas with thickness <1 mm should be resected with a 1 cm margin of normal
tissue. Wider margins have not resulted in an improved survival or a decreased
incidence of local recurrence. On the other hand, margins <1 cm should not be used.
• Lesions with thickness between 1 to 4 mm, should be operated with 2 cm of margins.
More extensive resection margins have not been shown to improve survival or
decrease the frequency of local recurrence. Narrower margins have been associated
with an increased frequency of local recurrence in intermediate thickness
melanomas.
• Melanomas thicker than 4 mm should be ressected with 2 cm margins, since there is
no evidence that wider margins decrease the incidence of local recurrence or improve
overall survival. On the other hand, narrower margins have been associated with an
increased frequency of local recurrence in this setting.
• Lymphatic mapping and sentinel lymph node biopsy are indicated in the initial
management of melanomas with a thickness ≥0.76 mm, or high risk features such as
ulceration or mitoses >1/mm2 in otherwise healthy patients.
• Radiotherapy is rarely indicated as definitive treatment for initial melanoma.
However, adjuvant radiotherapy can improve local control for melanoma metastatic
to regional lymph nodes after surgical excision. Several prognostic factors increase
the rate of locoregional recurrence after regional lymphadenectomy alone such as;
presence of extracapsular lymph node extension (ECE), ≥4 involved nodes, bulky
adenopathy (≥3 cm in size), cervical lymph node location, positive sentinel lymph
node and complete node dissection not performed. Thus, adjuvant radiotherapy must
be indicated for patients with one of these factors (table-6).
Table 6. Clinical evidence for adjuvant radiotherapy
Melanoma
27
Ang et al. (1994)
Phase II trial of adjuvant RT in head and neck melanoma patients.
79 patients had WLE of >1.5 mm primary or Clark’s IV–V, 32 patients had WLE and
elective LND, and 63 patients had LND after neck relapse.
RT was 6 Gy/fx given biweekly to 30 Gy over 2.5 weeks.
5-year LRC 88%, OS 47%. Five-year OS by pathologic parameters: <1.5 mm-100%,
1.6–4 mm 72%, >4 mm 30%, >3 LN+ 23%, 1–3LN+ 39%.
Chang et al.
(2006):
56 patients with high-risk disease treated with hypofractionation, 30 Gy in five
fractions (41 patients) or with conventional fractionation, median 60 Gy in 30
fractions.
No difference in LRC, OS, and CSS between two fractionation schemes.
Two patients with severe late complications, osteoradionecrosis of temporal bone and
RT plexopathy, received hypofractionation.
Table 6. (Continued)
References
Burmeister BH, Mark Smithers B, Burmeister E, et al. A prospective phase II study of
adjuvant postoperative radiation therapy following nodal surgery in malignant melanoma
–Trans Tasman Radiation Oncology Group (TROG) Study 96.06. Radiother Oncol.
2006;81:136-42.
Ang KK, Peters LJ, Weber RS. Postoperative radiotherapy for cutaneous melanoma of the
head and neck region. Int J Radiat Oncol Biol Phys. 1994; 30(4):795-798.
Chang DT, Amdur RJ, Morris CG, et al. Adjuvant radiotherapy for cutaneous melanoma:
comparing hypofractionation to conventional fractionation. Int J Radiat Oncol Biol Phys.
2006;66(4):1051-1055.
11. Radiotherapy Techniques
Radiotherapy rarely is indicated to treat early stage melanoma. But, when necessary, the
melanomas may be treated with superficial or electron beam radiotherapy. The margins need
to be carefully defined, as there is often a large area of subclinical disease requiring a margin
of up to 2 cm from GTV to PTV. For adjuvant setting radiation therapy portal design should
be confined to the involved nodal area. Extended field treatment does not result in any
additional benefits but may increase adverse effects (figure-4).
Several studies have shown that larger fraction sizes can effectively overcome apparent
resistance of malignant melanoma cells. Skin or mucosal melanomas involving the oral
cavity, vagina, and anus can be treated effectively with irradiation. Doses of 60 to 70 Gy, in
2- to 3-Gy fractions, are frequently administered. The usual dose for lentigo maligna is 45 Gy
in 3-Gy fractions, or 50 to 60 Gy in 2-Gy fractions. For adjuvant treatment, the dose
fractionation varies from conventional fractionation of 2 Gy/ day to hypofractionation of 6–
7.5 Gy per fraction twice a week treatment. Total doses vary from 60 Gy with conventional
fractionation scheme to 30–48 Gy, depending on the dose per fraction. For head and neck
mealnomas have been recommended only to treat the compromised lymph node drainage,
profilatic radiotherapy treatment of uninvolved drainage is not indicated because of high risk
of long term complications (figure 5).
Gustavo Arruda Viani
28
Figure 4. Anterior beams eye view and isodose line distribution of an inguinofemoral field.
Figure 5. Anterior beams eye view of an extensive head and neck melanoma, which compromises all
oral and oropharyngeal cavity.
Conclusion
• The incidence of melanoma has increased over the last years.
• The management of melanomas evolves surgeon oncology, clinical oncology and
radiation oncology.
• During a long time, melanoma was considered a radioresistant tumor. Actually, the
evidences show, that delivering large doses by fraction, a good local control is
possible to be achieved.
• Thus, in the last decades, the role of radiotherapy has been enlarged mainly in
patients with high risk of regional failure.
• Radiotherapy is rarely indicated as primary treatment for melanomas.
Chapter 3
Soft Tissue Sarcoma
Abstract
Soft-tissue sarcoma (SFTS) is a histopathologically diverse group of tumors
The proximal lower extremity is the most common site for STS, accounting for
approximately 45% of all cases.
Core needle biopsy is preferred over fine-needle aspiration (FNA) as the diagnostic
tool of choice because the tissue specimen retrieved by core needle predicts type and
grade 90% of time.
MRI is the preferred over CT for the evaluation of soft tissue masses of the
extremities, trunk, and head and neck.
The most important prognostic factors for local control are histological grade,
surgical margins and size of tumor.
Surgical resection of the primary tumor is the pivotal component of treatment for all
patients. The surgical principle is total en bloc excision of the primary tumor without
cutting into tumor tissue associated with safety margins.
Surgery followed by adjuvant radiation therapy has resulted in a better local control
than either modality alone. The benefits of adjuvant radiotherapy in this setting are in
producing good functional outcomes, avoiding the significant morbidity with radical
resection.
Neoadjuvant chemotherapy can also be considered for large (> 8 cm) or recurrent
high-grade tumors.
The best way to integrate radiation therapy, chemotherapy, and surgery, and which is
the optimal neoadjuvant regimen, remains unknown.
Introduction
Soft-tissue sarcoma (SFTS) is a histopathologically diverse group of tumors accounting
for approximately 10,000 new malignancies in the US each year. The proximal lower
extremity is the most common site for STS, accounting for approximately one-third of all
cases. Coordinated multimodality management in the form of surgery and radiation is often
critical to local control, limb preservation, and functional outcome. Based on a review of
currently available literature, this chapter provides an overview of the treatment of SFTS of
the lower extremity.
Gustavo Arruda Viani
30
1. Epidemiology
• Soft tissue sarcomas (SFTS) constitute about 1% of all cancers. It account for about
9,220 new cases of STS and 2,370 cases of bone sarcoma in the United States.
• These will be associated with 3,560 and 1,330 deaths, respectively. STSs outnumber
bone sarcomas by a ratio of 3:1.
• In children, most STSs are rhabdomyosarcomas or undifferentiated tumors
originating in the head and neck regions. In adults, STSs occur most frequently on
the extremities or retroperitoneum and least frequently in the head and neck region.
• Bone sarcomas occur mostly between 10 and 20 years of age (osteogenic sarcoma) or
between 40 and 60 years of age (chondrosarcoma).
• Most sarcomas show no sexual predilection. Incidence peaks during childhood and
in the fifth decade.
Reference
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10.
2. Risk Factors
Certain types of sarcomas are associated with exposure to specific agents or with
underlying medical conditions.
• Lymphangiosarcoma. Prolonged postmastectomy arm edema (Stewart-Treves
syndrome)
• Angiosarcoma and other STSs. Polyvinyl chloride, thorium dioxide, dioxin, arsenic,
and androgens
• Osteosarcoma. Radium (watch dials) exposure; postmastectomy irradiation; Paget
disease of bone Fibrosarcoma.
• Postirradiation: Paget disease of bone
• Kaposi sarcoma. Cytomegalovirus and human immunodeficiency virus type 1
• Leiomyosarcoma. HIV-1 in children Genetic diseases and syndromes Li-Fraumeni
syndrome.
General risk factor for developing SFTS:
• Radiation exposure. Exposure to ionizing radiation, usually given to treat other
tumors, is a risk factor accounting for less than 5% of sarcoma diagnoses. The
average time between the exposure and diagnosis of a sarcoma is about 10 years.
However, advances in radiation therapy treatment are expected to reduce the number
of related secondary malignancies.