The staging of melanoma has undergone tremendous revision and change since
the initial pathologic descriptions of the disease. Here, the recent AJCC
revisions are included. In addition, there is an ever burgeoning collection
of prognostic factors that may lead to improved surveillance and treatment
for this deadly disease.
| PROGNOSIS AND TREATMENT |
CHARACTERIZATION |
| PROGNOSTIC FACTORS |
|
| OVERVIEW |
These parameters have been cited as having prognostic significance:
Vertical growth phase
Thickness
Depth of invasion
Ulceration
Angiolymphatic invasion
Satellitosis
Mitotic activity
Host response
Regression
|
| GENERAL |
|
|
Lack of Relevant Information for Tumor Staging in
Pathology Reports of Primary Cutaneous Melanoma
Klaus J. Busam
|
Am J Clin Pathol 2001;115:743-746 Abstract quote
For the T classification of primary cutaneous melanoma, the current
American Joint Committee on Cancer staging (AJCC) system relies on tumor
thickness and level of invasion. A new T classification has been proposed
based on thickness and ulceration. The slides and reports of 135 departmental
pathology consultations of patients referred to a major cancer center
with a diagnosis of primary cutaneous invasive malignant melanoma were
examined. Whether the outside pathology reports contained information
on tumor thickness, level of invasion, and ulceration was recorded.
Dermatopathologists had issued 76.3% of the reports and general surgical
pathologists, 24.3%. Information provided was as follows: tumor thickness,
97.8%; Clark level, 71.9%; and presence or absence of ulceration, 28.1%.
Of the 97 melanomas with no comment on ulceration, 17 were indeed ulcerated.
Thus, the lack of a comment on ulceration cannot be equated with the
absence of ulceration.
The present study documents that many pathology reports on melanomas
lack sufficient information for AJCC staging. Therefore, review of outside
pathology material is necessary not only to confirm or revise the tumor
diagnosis but also to provide clinicians with histologic parameters
required for AJCC staging.
|
|
ADHESION MOLECULES
|
J Natl Cancer Inst 1995;87:366-371
Increasing tumor thickness associated with expression of very late
activation (VLA-4) in tumor cells increased with a concomitant decrease
in VLA-6 expression
VLA-4 correlates significantly with metastases
Intratumoral vessels staining positive for ELAM-1 (E-selectin) and
CD62 (P-selectin) and melanoma cells positive for VLA-4 correlated with
decreased disease free survival and overall survival time
|
|
CD44
|
Eur J Cancer 1997;33:926
Tumors with high levesl had significantly reduced 5 YRS compared to
those with low levels
|
| CHILDHOOD MELANOMA |
|
|
Cutaneous melanoma and atypical Spitz tumors in childhood.
Barnhill RL, Flotte TJ, Fleischli M, Perez-Atayde A.
Department of Pathology, Brigham and Women's Hospital, Children's
Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
|
Cancer 1995 Nov 15;76(10):1833-45 Abstract quote
BACKGROUND. Malignant melanoma in childhood is rare. As a result, the
biology and natural history of melanoma in this age group is still poorly
understood. Although the majority of Spitz nevi are benign regardless
of atypical features, a particular problem is the continued confusion
of Spitz nevi with atypical features with melanoma and the lack of specific
criteria for their distinction. The latter discrimination is perhaps
not so difficult when Spitz nevi are minimally atypical; however, the
greater the atypia, the more challenging is this discrimination.
METHODS. All cases of malignant melanoma referred to Children's Hospital
(Boston, MA) and to one of the authors were examined during the period
of 1959-1995. Criteria for inclusion in the study included: (1) age
up to 15 years; (2) availability of microscopic slides; and (3) availability
of demographic data.
RESULTS. There were 11 males and 12 females, ranging in age from 2
to 15 years (mean age, 9.4 years). Histopathologically, the 23 tumors
were categorized into four subgroups: (1) small cell melanoma (5); (2)
adult-like melanoma (6); (3) Spitz-like melanoma (3), and (4) atypical
Spitz tumors (9). The small cell melanomas were notable for localization
to the scalp, significant thickness, and fatal outcome. The adult-like
melanomas resembled typical tumors occurring in adults. The one fatal
Spitz-like melanoma was located on the neck of a 14-year-old male. Two
tumors in this group metastasized to regional lymph nodes, but were
not associated with further aggressive disease on follow-up despite
treatment with surgical excision only. The atypical Spitz tumors were
characterized by significant thickness and abnormal features including
prominent cellularity and mitotic activity.
CONCLUSIONS. Anatomic site and cell type may be important prognostic
factors in addition to tumor thickness for childhood melanoma, but these
tumors require further study. In addition, the biologic potential of
atypical Spitz tumors has not been characterized sufficiently.
|
|
Childhood melanoma survival.
Saenz NC, Saenz-Badillos J, Busam K, LaQuaglia MP,
Corbally M, Brady MS.
Department of Surgery, Memorial Sloan-Kettering Cancer
Center, New York, New York, USA.
|
Cancer 1999 Feb 1;85(3):750-4 Abstract quote
BACKGROUND. Melanoma in childhood is uncommon. Some believe that melanoma
among children is associated with a better prognosis than among adults.
METHODS. The authors reviewed their institutional experience with melanoma
in 40 patients younger than 18 years treated between 1950 and 1984.
All slides were reviewed by a single dermatopathologist who was blinded
to clinical outcomes. Long term follow-up was available for all but
three patients.
RESULTS. There were 26 girls and 14 boys. The median age at diagnosis
was 15 years (range, 3-17 years). Eleven patients (28%) were younger
than 12 years. Fifteen patients (38%) had melanoma arise in a congenital
nevus (2 had bathing trunk nevi. The most common site was the extremity
(n = 23), followed by the trunk (n = 10) and the head and neck (n =
7). Seventeen patients (43%) initially were considered to have benign
lesions, and 23 patients (57%) were diagnosed correctly with melanoma
at initial presentation. Only 21 of 37 evaluable patients (57%) were
alive at last follow-up with a median follow-up of 18 years (range,
2-48 years). Fifteen patients (41%) died of their disease, with a median
survival of 12 months (range, 6-60 months). One patient died of breast
carcinoma 14 years after treatment for melanoma. Disease free survival
was 57% at 5 and 10 years. Of the 15 patients who died of disease, 12
were female (P = 0.09) and 10 had melanoma arising in a congenital nevus
(P < 0.05). Five-year overall survival was 78% for patients who presented
with localized disease (n = 23) and 30% for patients who presented with
regional metastasis (n = 16, P < 0.001). There were no survivors among
those who presented with systemic disease (n = 1).
CONCLUSIONS. Children with melanoma are at significant risk of dying
of their disease. Survival is similar to that seen among adults and
depends on stage at presentation. The survival advantage observed for
adult females is not seen among children.
|
|
Prepubertal malignant melanoma: report of three cases.
Strojan P, Lamovec J.
Department of Radiotherapy, Institute of Oncology,
Ljubljana, Slovenia.
|
Pediatr Hematol Oncol 2000 Mar;17(2):163-9 Abstract quote
Prepubertal malignant melanoma (MM) is an extremely rare tumor.
In Slovenia, 13 MM cases were registered between 1968 and 1996 by the
Cancer Registry of Slovenia. The diagnosis of MM was confirmed by histology
in 3 children. In 3 other children the lesions initially diagnosed as
MM were reclassified as Spitz nevus. In the remaining cases, the slides
were not accessible for histological review, and the clinical course
of disease corroborated the diagnosis of a benign nevus.
In the present report, 3 of 13 cases with histologically confirmed
prepubertal MM are described. The difficulties encountered in the diagnosis
and management of this rare condition are discussed.
|
|
Reliability of the histopathologic diagnosis of malignant melanoma in
childhood.
Wechsler J, Bastuji-Garin S, Spatz A, Bailly C, Cribier
B, Andrac-Meyer L, Vergier B, Fraitag S, Verola O, Wolkenstein P.
Department of Dermatology, Henri-Mondor Hospital,
F-94010 Creteil CEDEX, France.
|
Arch Dermatol 2002 May;138(5):625-8 Abstract quote
OBJECTIVE: To assess interrater reliability in the diagnosis of malignant
melanoma in children.
DESIGN, SETTING, AND PARTICIPANTS: We collected 85 slides of melanomas
diagnosed in patients younger than 17 years through a network of dermatopathologists
and dermatologists. The slides were classified into 3 categories: (1)
slides from children with metastatic melanoma; (2) slides from disease-free
children with a follow-up of less than 5 years; (3) slides from disease-free
children with a follow-up of 5 years or longer. Category 1 was considered
the gold standard. Four pairs of expert dermatopathologists reviewed
the slides and classified them into melanoma, nevus (including Spitz
nevus), or ambiguous tumors.
INTERVENTION: None.
MAIN OUTCOME MEASURE: Concordance between pairs of experts.
RESULTS: For category 1 slides (n = 20), the concordance was weak to
moderate. For category 2 slides (n = 47), the concordance was weak.
For category 3 slides (n = 18), the concordance was poor to moderate.
CONCLUSION: This study demonstrates that the reliability of diagnosis
of melanoma in childhood is poor, even when submitted to experts.
|
|
Cutaneous melanoma in childhood and adolescence: An analysis of 36 patients.
Schmid-Wendtner MH, Berking C, Baumert J, Schmidt
M, Sander CA, Plewig G, Volkenandt M.
Department of Dermatology and Allergology and Tumor
Registry, Department of Medical Informatics, Biometry and Epidemiology,
Ludwig-Maximilians-University, Munich.
|
J Am Acad Dermatol 2002 Jun;46(6):874-9 Abstract quote
Analysis of data of 6931 patients with cutaneous melanoma seen at the
Department of Dermatology and Allergology at the Ludwig-Maximilians-University
of Munich between 1977 and 1998 identified 36 patients in whom cutaneous
melanomas developed during childhood or adolescence (age <18 years).
Clinical courses of all patients and histopathologic characteristics
of the lesions were reviewed. Seventeen patients were boys and 19 patients
were girls. The median ages of the boys and girls were 15 and 16 years,
respectively (range, 2-17 years). Thirty-one patients presented with
nonmetastatic primary melanomas and 5 patients presented with metastatic
melanoma. Forty-seven percent of the primary lesions were associated
with a nevus (22% with congenital nevi and 25% with acquired nevi).
Tumor thickness ranged from 0.24 to 7.0 mm, with a median of 1.29 mm
(mean, 1.67 mm). All patients with primary melanomas received surgical
therapy; patients with metastatic disease received chemotherapy, radiation
therapy, or both. Relative 5-year survival was 87.5% for the group of
patients younger than 18 years. Similar to experience in adult patients,
survival strongly correlated with tumor thickness and clinical stage
at the time of diagnosis.
The data emphasize that a high index of suspicion for cutaneous melanoma
is needed by clinicians assessing melanocytic lesions in children and
adolescents for early diagnosis. Reduction of the melanoma mortality
rate in children and adolescents will be achieved through identification
of patients at increased risk.
|
|
Congenital and infantile melanoma: review of the literature and report
of an uncommon variant, pigment-synthesizing melanoma.
Richardson SK, Tannous ZS, Mihm MC Jr.
Dermatopathology Unit, Massachusetts General Hospital,
Harvard Medical School, 55 Fruit Street, Boston, MA 02114-2696, USA
|
J Am Acad Dermatol 2002 Jul;47(1):77-90 Abstract quote
Congenital and infantile types of melanoma are uncommon conditions
for which there are limited epidemiologic data. The number of reported
cases is small with several ascribed etiologies.
We review the literature and report the first documented case, to our
knowledge, of pigment-synthesizing melanoma in an infant. Reported cases
of congenital and infantile melanoma were identified and categorized
on the basis of disease origin. Dermatopathologic specimens from an
infant given a diagnosis of pigment-synthesizing melanoma are described.
Disease arising from medium and large/giant congenital nevi was most
common, whereas reports of de novo and transplacental disease were infrequent.
Death of approximately 40% of patients was noted within 18 months of
diagnosis. Male infants accounted for approximately 74% of cases. The
most commonly affected anatomic sites were the head and neck.
The prognosis for congenital and infantile melanoma is poor. The high
incidence of head-and-neck involvement and male predominance for disease
suggest dispositions for both anatomic disease localization and sex.
|
| c-MYC |
|
|
Extra c-myc oncogene copies in high risk cutaneous
malignant melanoma and melanoma metastases.
Kraehn GM, Utikal J, Udart M, Greulich KM, Bezold
G, Kaskel P, Leiter U, Peter RU.
Department of Dermatology, University of Ulm, Ulm,
Germany.
|
Br J Cancer 2001 Jan 5;84(1):72-9 Abstract quote
Amplification and overexpression of the c-myc gene have been associated
with neoplastic transformation in a plethora of malignant tumours.
We applied interphase fluorescence in situ hybridization (FISH) with
a locus-specific probe for the c-myc gene (8q24) in combination with
a corresponding chromosome 8 alpha-satellite probe to evaluate genetic
alterations in 8 primary melanomas and 33 advanced melanomas and compared
it to 12 melanocytic nevi, 7 safety margins and 2 cases of normal skin.
Additionally, in metaphase spreads of 7 melanoma cell lines a whole
chromosome 8 paint probe was used.
We investigated the functionality of the c-myc gene by detecting c-myc
RNA expression with RT-PCR and c-myc protein by immunohistochemistry.
4/8 primary melanomas and 11/33 melanoma metastases showed additional
c-myc signals relative to the centromere of chromosome 8 copy number.
None of the nevi, safety margins or normal skin samples demonstrated
this gain. In 2/7 melanoma cell lines (C32 and WM 266-4) isochromosome
8q formation with a relative gain of c-myc copies and a loss of 8p was
observed. The highest c-myc gene expression compared to GAPDH was found
in melanoma metastases (17.5%). Nevi (6.6%) and primary melanomas (5.0%)
expressed the c-myc gene on a lower level. 72.7% of the patients with
c-myc extra copies had visceral melanoma metastases (UICC IV), patients
without c-myc gain in 35.0% only. The collective with additional c-myc
copies also expressed the gene on a significantly higher level.
These results indicate that a c-myc gain in relation to the centromere
8 copy number might be associated with advanced cutaneous melanoma.
|
| CYCLINS |
|
|
Mitotic cyclins and cyclin-dependent kinases in melanocytic
lesions.
Tran TA, Ross JS, Carlson JA, Mihm MC Jr.
Department of Pathology and Laboratory Medicine,
Albany Medical College and Samuel S. Stratton Veterans Administration
Medical Center, NY 12208, USA.
|
Hum Pathol 1998 Oct;29(10):1085-90 Abstract quote
Recent evidence has implicated cyclins and cyclin-dependent kinases
in the evolution and progression of various malignancies.
We studied the immunohistochemical expression of cyclin A, cyclin B,
and cyclin-dependent kinase p34cdc2 in a broad spectrum of benign and
malignant melanocytic lesions. Formalin-embedded, parrafin-fixed tissue
sections from 66 malignant melanomas (MM) and 60 benign nevi were examined
for the expression of these cell-cycle proteins. The results were compared
with the standard proliferative marker Ki-67 and mitotic index. MM showed
significantly higher immunoreactivity for cyclin A, cyclin B, p34cdc2,
and Ki-67 compared with benign nevi. Cyclin A, p34cdc2, and Ki-67 displayed
strong co-expression in MM. Overexpression of cyclin A and p34cdc2 correlated
with histological type, mitotic activity, Ki-67 index, tumor thickness,
Clark's level, and clinical outcome in MM.
In invasive MM, increased immunostaining of cyclin A and Ki-67 were
associated with decreased patient survival. These findings indicate
potential roles of mitotic cyclins and cyclin-dependent kinases in the
pathogenesis and progression of malignant melanoma.
|
| ELASTIN |
|
|
Relationship of tumorigenic malignant melanomas to dermal elastin: an
expression of tumor/stromal interaction that may be related to prognosis.
Feinmesser M, Schachter JM, Tobar A, Sulkes J, Gutman H, Kruk N,
Okon E.
Department of Pathology, Rabin Medical Center, Beilinson Campus,
Petah Tiqva, Israel.
|
Am J Dermatopathol 2002 Apr;24(2):108-17 Abstract quote
Malignant melanomas, which produce a large number of substances active
in connective tissue modulation, must contend with the dermis to grow
and propagate.
We studied the morphologic interactions between tumorigenic malignant
melanomas and dermal elastin. Formalin-fixed and paraffin-embedded tissues
of 108 tumorigenic malignant melanomas were stained for elastic tissue
with the Verhoeff-van Gieson method. Various aspects of the relationship
between malignant melanoma and dermal elastin were analyzed in relation
to the histologic and clinical data using univariate and multivariate
analyses. Tumor thickness, mitotic rate, and the presence of elastin
remnants within the tumors were found to be independent negative prognostic
factors, the latter with borderline significance.
Tumors with more remnants of elastin were associated with higher stage
of disease and lymph node and distant metastases. Tumor infiltration
between the elastic fibers in the tumor depth was associated with high
Clark level, greater tumor thickness, high stage of disease, and lymph
node metastases. At least partial preservation of elastic fibers in
the tumor depth was a relatively good prognostic factor whereas complete
absence of elastin was an adverse factor. Focal or multifocal absence
of elastin in the midst of the tumors or in their depth was usually
associated with lymphocytic infiltrates.
We suggest that tumors with remnants of elastic fibers and/or invasion
between elastic fibers in their depth may be fast growing and highly
invasive. The absence of elastin within tumors and at their advancing
edge may be related to the elaboration of elastin-degrading substances
by melanoma cells or various inflammatory cells. Our findings indicate
that the relationship between malignant melanomas and dermal connective
tissue components, specifically elastin, may have prognostic significance.
|
| HISTOPATHOLOGY |
|
|
Epithelioid cell melanomas have greater DNA ploidy
abnormalities than spindle cell melanomas: cytological evidence for
a higher malignant potential of the former.
Chi HI, Uyeda Y, Umebayashi Y, Otsuka F.
Department of Dermatology, Tokyo Hitachi Hospital,
Japan.
|
Arch Dermatol Res 1993;285(7):410-4 Abstract quote
The cellular DNA ploidy of 30 cases of malignant melanoma was measured
by 4',6-diamidino-2-phenylindole-DNA (DAPI-DNA) microfluorometry.
DNA histograms and DNA index values were compared among melanomas of
different cell morphology. Epithelioid cell melanomas often showed greater
DNA aneuploidy than spindle cell melanomas in terms of histographic
pattern. DNA index values of the former (mean +/- standard error, 1.84
+/- 0.31) were significantly higher than those of the latter (1.55 +/-
0.24; P < 0.05). The DNA index values of mixed-type melanomas were
intermediate. These results indicate that the epithelioid cell melanomas
have greater DNA ploidy abnormalities which are usually correlated with
a greater malignant potential in pigmentary neoplasms.
Thus our results confirm clinical evidence that melanoma patients with
the epithelioid type of cells have a poorer prognosis than those with
the spindle type of cells.
|
| INCISIONAL BIOPSY |
|
|
Does biopsy type influence survival in clinical stage I cutaneous melanoma?
Lederman JS, Sober AJ.
|
J Am Acad Dermatol 1985 Dec;13(6):983-7 Abstract quote
A total of 472 patients with clinical Stage I cutaneous melanoma were
analyzed to determine influence of type of diagnostic biopsy on survival.
Of these patients, 119 had had an incisional biopsy (either punch or
incision) and 353 had an excisional biopsy. Patients were grouped by
thickness category and outcome compared between the biopsy types.
Within each thickness category, there is no statistically significant
difference in survival between the two groups. The observation that
none of the seventy-six patients with primary tumors less than 1.70
mm have died following incisional biopsy strongly argues against any
deleterious effect of incisional biopsy in this group. Alternatively,
if the two highest-risk groups (greater than or equal to 1.70 mm) are
analyzed as a single group, an adverse effect is seen in the incisional
biopsy group (p less than 0.05). However, when the data from these groups
are subjected to multivariate analysis, biopsy type is not a significant
factor in the model.
This study shows that either biopsy method may be used in first evaluating
patients with suspected melanoma.
|
|
Does wide excision as the initial diagnostic procedure improve prognosis
in patients with cutaneous melanoma?
Lederman JS, Sober AJ.
|
J Dermatol Surg Oncol 1986 Jul;12(7):697-9 Abstract quote
502 patients with clinical stage I cutaneous melanoma were reviewed
to determine if performing a wide excision (4-5 cm) at the time when
the diagnosis of melanoma is suspected, improves the survival.
Patients were divided into two groups based on initial biopsy type
and thickness category. Group 1, wide excision; group 2, total excision
with narrow margins, incisional, or punch biopsies. There was no evidence
that patients who had had a diagnostic and therapeutic procedure (wide
excision) as the initial approach had a better survival than those who
had had another form of biopsy before definitive surgery.
We cannot recommend excision with wide margins as the initial biopsy
procedure for a lesion suspected to be melanoma before histologic verification,
since it does not increase survival for melanoma and may result in unnecessary
aggressive surgery in the case of a misdiagnosed benign lesion.
|
|
Effect of initial biopsy procedure on prognosis in Stage 1 invasive
cutaneous malignant melanoma: review of 1086 patients.
Lees VC, Briggs JC.
Department of Plastic Surgery, Addenbrooke's Hospital, Cambridge,
UK.
|
Br J Surg 1991 Sep;78(9):1108-10 Abstract quote
After treatment for primary clinical Stage 1 invasive cutaneous malignant
melanoma, 1086 patients were followed for a minimum of 5 years from
initial operation. Patient data were retrieved from the unit's melanoma
registry; 96 (8.8 per cent) were treated initially by incisional biopsy,
292 (26.9 per cent) by narrow margin excision biopsy and 698 (64.3 per
cent) by wide margin excision.
Logistic regression analysis was performed to assess the statistical
significance of the association between the various factors. The method
of initial biopsy was related to maximal tumour thickness, age, and
sex.
Incisional biopsy rendered 38 out of 96 (40 per cent) lesions not fully
assessable on current histopathological criteria, significantly higher
than for the other biopsy techniques (P less than 0.0001). Incisional
biopsy did not adversely affect prognosis in terms of local recurrence
and mortality. Prognosis was related to tumour thickness, age and sex
of the patient, and not to biopsy technique.
We recommend that all suspicious lesions should be submitted to excisional
rather than incisional biopsy to avoid compromising the histological
assessment, given the importance of maximal tumour thickness in determining
treatment and prognosis.
|
|
Influence of biopsy on the prognosis of cutaneous melanoma of the head
and neck.
Austin JR, Byers RM, Brown WD, Wolf P.
Department of Head and Neck Surgery, University of Texas M.D. Anderson
Cancer Center, Houston, USA.
|
Head Neck 1996 Mar-Apr;18(2):107-17 Abstract quote
BACKGROUND: This study was performed to determine the effect of biopsy
type on survival rates and on local, regional, and distant metastasis
in patients with head and neck cutaneous melanoma.
METHODS: A case series of 159 patients with melanoma of the head and
neck referred to a tertiary-care center between 1983 and 1991, with
a median follow-up of 38 months, was reviewed. Information analyzed
included patient's age, sex, type of treatment, mode of biopsy, presence
of residual melanoma in reexcision, location of lesion, presence of
ulceration, Clark's level, Breslow thickness, and histologic type of
the melanoma.
RESULTS: Excisional biopsy was performed in 79 patients, incisional
biopsy in 48, and other procedures (shave, needle biopsy, cauterization,
or cryotherapy) in 32. There were no significant pretreatment differences
among the three groups in sex, thickness, histologic type, presence
of nodal disease, or type of treatment. Pretreatment location of lesion
was significantly different (p = .03) between the excisional and other
biopsy types. Association between type of biopsy and survival rate was
significant (p<.001):31.3% of patients in the incisional biopsy group
died of disease, as did 25% of the other biopsy group, versus 8.9% of
the excisional biopsy group; 31.3% of patients in the incisional biopsy
group developed distant metastases, as did 28.1% of the other biopsy
type, versus 10.1% of those in the excisional biopsy group (p = .01).
There was no significant difference in local p = .37) or regional (p
= 1.00) recurrence among the three biopsy groups. Multivariate analysis
showed presence of tumor in the re-excision specimen, biopsy type, and
nodal disease to be independent prognostic factors.
CONCLUSIONS: Our study suggests that the type of biopsy of cutaneous
melanoma of the head and neck may influence the clinical outcome.
|
|
Incisional biopsy and melanoma prognosis.
Bong JL, Herd RM, Hunter JA.
Departments of Dermatology, Western Infirmary, Glasgow, and The
Royal Infirmary of Edinburgh.
|
J Am Acad Dermatol 2002 May;46(5 Pt 1):690-4 Abstract quote
BACKGROUND: There are many circumstances in clinical practice in which
it is helpful to have a definitive diagnosis of melanoma before subjecting
a patient to mutilating surgery. Previous studies on the effect of incisional
biopsy on melanoma prognosis were conflicting and lacked a matched control
group to account for the other prognostic indicators.
OBJECTIVE: We set up this study to investigate the effect of incisional
biopsy on melanoma prognosis.
METHODS: The design was of a retrospective case control. Data were
obtained from the database of the Scottish Melanoma Group; the database
was set up in 1979 to collect detailed clinical, pathologic, and follow-up
data on all patients diagnosed with melanoma in Scotland. Each incisional
case was matched against 2 excision cases controlling for age, sex,
sites, and Breslow thickness. The main outcome measures were time from
initial biopsy to recurrence and to melanoma-related death.
RESULTS: Two hundred sixty-five patients who had incisional biopsy
before definitive excision of melanoma were included in the study; these
were matched with 496 cases of excisional biopsy specimens. Cox's proportional
hazard model for survival analysis showed that biopsy type had no significant
effect on recurrence (P =.30) or melanoma-related death (P =.34).
CONCLUSIONS: This study is the largest series on the effect of incisional
biopsy on melanoma prognosis to date and the first to include matched
controls. Melanoma prognosis is not influenced by incisional biopsy,.
before definitive excision.
|
|
Ki-67 (MIB-1)
|
J Cutan Pathol 1991;18:264-72.
J Cutan Pathol 1992;19:110-5.
J Invest Dermatol 1995;105:22-6.
J Am Acad Dermatol 1996;35:416-8.
|
|
Concurrent Ki-67 and p53 immunolabeling in cutaneous
melanocytic neoplasms: an adjunct for recognition of the vertical growth
phase in malignant melanomas?
Kaleem Z, Lind AC, Humphrey PA, Sueper RH, Swanson
PE, Ritter JH, Wick MR. Lauren V.
Ackerman Laboratory of Surgical Pathology, Washington
University Medical Center, St. Louis, Missouri, USA.
|
Mod Pathol 2000 Mar;13(3):217-22 Abstract quote
Ki-67 labeling of paraffin sections has been correlated with the number
of cells in non-G(o) phases of the replicative cell cycle, and this
immunohistochemical technique has been applied to the evaluation of
a variety of human neoplasms. Similarly, immunolabeling for p53 protein
has been used to detect mutations in the corresponding gene, as a reflection
of possible cellular transformation in the same context.
Both of these techniques were applied to 253 melanocytic tumors of
the skin to assess their possible utility in the diagnosis and subcategorization
of such lesions. They included 76 banal (common) nevi (CN), 39 Spitz
nevi (SN), 62 superficial spreading malignant melanomas in radial growth
(SSMMs), 32 nodular malignant melanomas (NMMs), 21 lentigo maligna melanomas
in radial growth (LMMs), and 23 melanomas arising in association with
preexisting compound nevi (MCN). One hundred cells were counted randomly
in each tumor, and dark, exclusively nuclear reactivity was scored as
positive labeling; results were recorded as percentages.
Negligible Ki-67 and p53 labeling was seen in CN and SN, at a level
that was similar to that obtained in cases of LMM and MCN. T
he largest proportion of Ki-67-positive and p53-positive cells was
observed in NMMs, followed by SSMMs. Radial growth-phase SSMMs and LMMs
demonstrated immunoprofiles that were similar to those of melanocytic
nevi, and MCN did so as well.
The prototypical malignant melanocytic tumor representing the vertical
growth phase-nodular melanoma--demonstrated a statistically significant
difference from all other lesions in this study with respect to Ki-67
index (P = .008, chi2) and p53 reactivity (P < .000001, chi2). Subsequent
concurrent use of a Ki-67 threshold index of 10% and a p53 index of
5% correctly indicated the presence of vertical growth in 75% of NMMs,
whereas only 8% of radial growth phase melanomas of other types were
colabeled at the same levels of reactivity for the two markers (P <
.00001, chi2).
Thus, although the distinction between benign and malignant melanocytic
tumors could and should not be based on immunohistology for Ki-67 and
p53, these results suggest that the latter determinants may, in fact,
be used as an adjunct to morphology in the recognition of the vertical
growth phase in cutaneous malignant melanomas.
|
|
|
J Am Acad Dermatol 2001;44:188-92
Ki-67 reactivity in primary melanomas was evaluated as at least 5%
of positive neoplastic cells and was assessed on fresh specimens of
55 primary lesions at the time of excision
At least 4 fields of approximately 100 tumor cells each per slide were
counted at 40× magnification. The number of Ki-67-reactive cells in
each field was determined as a percentage of the total number of tumor
cells counted. A mean percentage of Ki-67 immunoreactive melanoma cells
was calculated for each lesion. The percentage of positive cells per
lesion was scored according to 3 different categories: zero to 4%, 5%
to 10%, 11% to 30%. A cut-off point of 5% stained cells was chosen to
identify positive lesions.
Reactivity was correlated with metastatic relapse of patients in a
prospective study, by means of multivariate Cox regression models (follow-up,
3-120 months)
Ki-67 immunoreactivity was associated with increasing thickness (P
= .003)
Positive correlation was found between Ki-67 reactivity and metastatic
dissemination in primary melanomas less than 1.5 mm thick (n = 23; mean
thickness, 0.75 ± 0.3 mm; P = .002)
A negative correlation was found between Ki-67 reactivity and metastatic
activity in primary melanomas thicker than 1.5 mm (n = 32; mean thickness,
4.0 ± 1.6 mm; P = .019).
Ki-67 proliferative activity appears to be a possible predictor of
metastasis in primary melanomas, in particular, an indicator of poor
prognosis in lesions less than 1.5 mm thick.
|
| |
Am J Dermatopathol 2001;22:489-495
Average number and maximal number (%) of MIB-1 positive nuclei were
determined in superficial, middle, and deep dermal zones as well as
the entire lesion
Examined:
23 compound nevi
17 dysplastic nevi
8 Spitz nevi
24 malignant melanomas
Utilizing the % MIB-1 mean and max from whole lesions had better discriminating
abilities than individual zones
Using the % Mean from all zones, all lesions except one Spitz nevus
and 3 melanomsa could be correctly classified as benign or malignant
Using the % MIB-1-max from all zones, all lesions but 2 Spitz nevi
could be correctly classified
|
|
A zonal comparison of MIB1-Ki67 immunoreactivity in
benign and malignant melanocytic lesions.
Li LX, Crotty KA, McCarthy SW, Palmer AA, Kril JJ.
Department of Pathology, University of Sydney, and
Centre for Education and Research on Ageing, Concord Hospital, New South
Wales, Australia.
|
Am J Dermatopathol 2000 Dec;22(6):489-95 Abstract quote
Differentiation between malignant melanomas and benign nevi can sometimes
be difficult by conventional histopathology, and additional diagnostic
markers may be helpful.
This study investigated the immunoreactivity of the cell proliferation
marker MIB1-Ki67 in 23 compound nevi, 17 dysplastic nevi, 8 Spitz nevi
(SN), and 24 malignant melanomas (MMs) and evaluated its ability in
separating benign nevi from MMs.
In each lesion, the average number (percentage) of MIB1-positive nuclei
(%MIB1-Mean) and the maximal number (percentage) of MIB1-positive nuclei
(%MIB1-Max) were determined from each of the superficial, middle, and
deep dermal zones of the lesion as well as from the entire lesion. The
%MIB1-Max was determined from subjectively selected area(s) of high
count. Malignant melanomas had a significantly greater %MIB1-Mean and
%MIB1-Max than all benign nevi in all individual zones and in the entire
lesion (p < 0.05). Discriminant analysis showed that the %MIB1-Mean
and %MIB1-Max counted from the whole lesions had better discriminating
abilities than from the individual zones. By using the %MIB1-Mean from
all zones, all lesions except 1 SN and 3 MMs could be correctly classified
as benign or malignant. When using the %MIB1-Max from all zones, all
but 2 SN could be correctly separated as benign or malignant.
Thus, MIB1-Ki67 immunoreactivity closely correlates with the benignancy
or malignancy of melanocytic lesions and may assist in the differentiation
of benign nevi from MMs.
|
|
MIB-1 monoclonal antibody to determine proliferative
activity of Ki-67 antigen as an adjunct to the histopathologic differential
diagnosis of Spitz nevi
|
J Am Acad Dermatol 2001;44:500-4 Abstract quote
Twenty-five compound SNs, 27 MMs, and 26 compound nondysplastic melanocytic
nevi (MNs) were immunostained with the MIB-1 antibody.
Results: The mean counts of MIB-1-stained tumor cells of the epidermal
and dermal components, both alone and together, were significantly lower
in SNs and MNs than in MMs (P < .0001). The dermal counts showed the
best discriminating power. In addition, the mean dermal/epidermal count
ratios for MIB-1 in SNs and MNs (0.25 and 0.23, respectively) were significantly
lower than the corresponding ratio (0.94) in MMs (P < .0001).
Conclusion: MIB-1-stained tumor cell counts, especially of the dermal
component, and dermal/epidermal MIB-1 count ratios may be helpful as
an adjunct to the histopathologic differential diagnosis of SN.
|
| MAST CELLS |
|
|
Cutaneous malignant melanoma: correlation between
neovascularization and peritumor accumulation of mast cells overexpressing
vascular endothelial growth factor.
Toth-Jakatics R, Jimi S, Takebayashi S, Kawamoto N.
Second Department of Pathology, Fukuoka University,
School of Medicine, Japan.
|
Hum Pathol 2000 Aug;31(8):955-60 Abstract quote
To investigate the possible role of mast cells (MC) in the angiogenic
process in cutaneous melanoma, we examined tissue samples from 35 adult
patients with primary malignant melanoma and compared with 20 intradermal
benign nevi.
MC were identified by anti-tryptase, microvessels by anti-CD34, and
vascular endothelial growth factor (VEGF) expression by standard immunohistochemical
methods. Tryptase-positive MC expressing VEGF were identified by double
immunostaining. The numbers of MC and microvessels around the tumor
were determined by the point counting method. MC density was significantly
greater in melanoma compared with benign nevi (197.6 +/- 19.4 v 95.7
+/- 5.0/mm2, P < .001). Vascular density was also significantly higher
in melanoma than in benign lesions (3.6-fold, P < .001). Double immunostaining
showed the presence of VEGF in the cytoplasm of tryptase-positive peritumoral
MC. The percentage of this MC-subtype was significantly higher in melanoma
than in nevus tissues (71.9 +/- 2.4% v 30.6 +/- 2.5%, P < .001). A strong
significant correlation was shown between the number of VEGF+ MC and
microvessel density (r = .811, P < .001). MC count and VEGF+ MC count,
as well as microvessel density were significantly higher in aggressive
(metastasizing) melanomas (P < .001).
Our results suggest that peritumoral accumulation of MC and the subsequent
release of potent angiogenic factor such as VEGF may thus represent
a tumor-host interaction that may favor progression of this tumor.
|
|
METALLOTHIENIN
|
Am J Dermatopathol 2001;23:29-35
Tumors of 44 patients
25/44 positive (nuclear and/or cytoplasmic staining positivity)
37.5% of level I-III positive
80% of level IV-V positive
Strong correlation between expression and level of invasion and tumor
thickness
Survival distribution function curve (Kaplan-Meier) had a better survival
rate for negative group
|
|
METASTATIN mRNA
|
Hum Pathol 2000;31:1346-1356
Inverse correlation with metastatic potential in human and murine cell
lines, this study examined archived specimens
Study utilized in situ hybridization with S35 labeled probes, mRNA
expression was analyzed in 64 cases of normal skin, benign melanocytic
nevi, primary cutaneous melanoma, and melanoma metastases
Ubiquitous expression was observed in all benign nevi (14/14) with
some nevi showing a gradient of reduced expression with increased dermal
depth
Uniform expression in 49% of primary cutaneous melanoma (18/37)
Loss of expression in 53% (19/36) of invasive melanoma
Loss of expression in 100% of melanoma metastases (11/11)
Focal aggregate or nodule of melanoma cells without detectable signal
was the most commonly observed pattern in melastatin loss of expression
|
| MGSA |
|
|
Melanoma growth stimulatory activity in primary malignant melanoma:
prognostic significance.
Middleman BR, Friedman M, Lawson DH, DeRose PB, Cohen C.
Emory University School of Medicine, Atlanta, Georgia.
|
Mod Pathol 2002 May;15(5):532-7 Abstract quote
Malignant melanoma (MM) cells do not require all exogenous growth factors
of normal melanocytes. It is hypothesized that they make their own growth
factors including melanoma growth stimulatory activity (MGSA). Cultured
melanoma cells respond to MGSA with increased growth and angiogenesis
suggesting a role for MGSA in MM proliferation, differentiation, and
progression.
We assessed the prognostic significance of MGSA expression in 37 primary
MM immunostained for MGSA. Immunostains were graded for intensity (0-3+),
percentage of cells immunostained, and location of immunostain (intraepidermal,
junctional, or dermal). In addition, 31 melanocytic and 23 dysplastic
nevi were similarly studied for MGSA expression. All MM showed the presence
of immunostain, 6 (16%) 1+, 12 (32%) 2+, and 19 (51%) 3+. Six (16%)
had immunostain in </=50% tumor cells, 31 (84%) in >50%. A significant
number of MM showed >50% tumor cells staining at the dermal-epidermal
junction compared with intraepidermal staining (P <.0001). Intensity
and amount of immunostain did not correlate with Clark's or Breslow's
level. During a mean follow-up of 60 months (range: 5-101) on 27 patients,
there were 4 local recurrences, 6 distant metastases, and 10 deaths.
MGSA expression was not of prognostic significance with regard to survival
(overall, disease free), or local recurrence or distant metastasis in
primary MM. MGSA expression was similar in benign melanocytic and dysplastic
nevi. Strong diffuse expression was noted in the junctional component
of all junctional and most compound nevi.
The dermal component consistently expressed less or no (in 45% of intradermal
nevi) MGSA. MGSA expression does not correlate with prognosis in MM.
Increased expression of MGSA at the dermal-epidermal junction in nevi
and MM may indicate a role for MGSA in early local growth, before development
of atypia.
|
| PLK1 |
|
|
Expression of polo-like kinase (PLK1) in thin melanomas: a novel marker
of metastatic disease.
Kneisel L, Strebhardt K, Bernd A, Wolter M, Binder A, Kaufmann R.
Department of Dermatology Johann Wolfgang Goethe-University, School
of Medicine, Frankfurt, Germany Department of Gynaecology, Johann Wolfgang
Goethe-University, School of Medicine, Frankfurt, Germany.
|
J Cutan Pathol 2002 Jul;29(6):354-8 Abstract
quote
Background: The maximum thickness of a primary malignant melanoma as
measured by Breslow's method is currently the most important prognostic
factor. However, some thin melanomas (</= 0.75 mm), which should
have an excellent prognosis according to Breslow, can be lethal due
to their ability to metastasize.
Methods: In our study, thin malignant melanomas (</= 0.75 mm) from
36 patients were analyzed with immunohistochemical techniques using
monoclonal antibodies directed against PLK1 and Ki-67. The immunoreactivity
of 22 melanomas which developed metastases within 5 years of follow-up
was compared with a group of 14 non-metastasized melanomas. Two independent
investigators evaluated stained sections. Differences of PLK1 and Ki-67
indices between melanomas with and without metastases were tested statistically
using the Mann-Whitney U-test.
Results: Malignant melanomas with metastases expressed PLK1 at markedly
elevated levels compared to melanomas without metastases (median, 60.00%
vs. 37.98%; p = 0.000053). The difference of the Ki-67 index between
both groups was not significant (median, 6.35% vs. 4.53%; p = 0.150473).
Conclusions: Our results suggest that PLK1 expression in thin melanomas
is a reliable marker to identify patients at high risk for metastases.
|
|
REGRESSION
|
Histopathology 1990;17:389-395
Cancer 1978;42:2282-2292
Cancer 1986;57:545-548
Arch Surg 1983;118:41-44
Ann Surg 1988;208:150-161
Virchows Arch 1985;406:179-195
Controversial whether regression is associated with a worse prognosis
and risk of metastases
|
| |
Pathology 1975;7:91-99
This study found regressive change in 12.3% of 437 primary melanomas
with less than 10% of patients reporting regression of a pigmented lesion
|
| |
Arch Dermatol 1987;123:1326-1330
Most ominous study found that patients with thin melanomas with regression
in greater than 75% of the lesion, metastases are prone to occur
|
Lichenoid Tissue Reaction in Malignant Melanoma
A Potential Diagnostic Pitfall
CPT Scott R. Dalton, MC, USA,1,3 Capt Matt A. Baptista, USAF, MC,1,3
COL Lester F. Libow, MC, USA,2 and COL Dirk M. Elston, MC, USA2
|
Am J Clin Pathol 2002;117:766-770 Abstract quote
Lichenoid tissue reactions can occur in malignant melanoma and may cause
partial regression of the lesion. We studied a series of melanomas to
determine how frequently lichenoid tissue reaction obscures the diagnosis
of malignant melanoma.
We retrospectively reviewed 342 cases of invasive malignant melanoma
and melanoma in situ from the head, neck, chest, and back. Of the 342
cases, 23 (6.7%) had a lichenoid tissue reaction obscuring a portion
of the lesion. In 6 cases (1.8%), the lichenoid tissue reaction replaced
a major portion of the lesion.
Knowledge of this phenomenon can prevent misdiagnosis.
|
| SIZE |
|
|
Small melanomas: a clinical study on 270 consecutive
cases of cutaneous melanoma.
Bono A, Bartoli C, Moglia D, Maurichi A, Camerini
T, Grassi G, Tragni G, Cascinelli N.
Unit for Cutaneous Oncology, Istituto Nazionale Tumori,
Milan, Italy.
|
Melanoma Res 1999 Dec;9(6):583-6 Abstract quote
The ABCD (asymmetry, border, colour, dimension) criteria represent
a commonly used clinical guide for the diagnosis of early cutaneous
melanoma (CM). This guide stipulates that CMs usually are more than
6 mm in diameter.
The purpose of this retrospective study was to establish the frequency
of occurrence of small (< or =6 mm) melanomas in a clinical context.
Our series consisted of 270 consecutive CMs (39 in situ and 231 invasive)
in 267 patients. Of these 270 lesions, 47 (17%) were small lesions,
ranging from 2 to 6 mm in maximum linear extent, with a median value
of 5 mm. Of these small lesions, 14 were in situ and 33 Invasive CMs.
The median thickness of the 33 small invasive lesions was 0.31 mm.
The clinical features of CMs were sufficiently distinctive to suggest
a diagnosis of CM in half of the cases, irrespective of the invasiveness
or not of the lesions. Dermatoscopy was performed on 36 of the small
lesions and achieved a correct diagnosis in 72% of the cases. The combination
of simple visual examination with dermatoscopy allowed a higher rate
of recognition (86%) than when the two methods were considered separately.
Results of our study show that small CMs represent a considerable
clinical subset of all CMs. Clinicians must be aware of this fact in
their diagnostic activity.
|
| SOLITARY MELANOMA CONFINED TO DERMIS OR FAT |
|
|
Solitary melanoma confined to the dermal and/or
subcutaneous tissue
|
Arch Dermatol 2000;136:1397-1399
By the current AJCC staging classification, these tumors are considered
Stage IV disease, that is a metastatic melanoma with an unknown primary.
11/1800 patients were identified (0.61%) with a single focus of presumed
metastatic disease
Kaplan-Meier 8 year survival curve was 83%
Suggesting that these presumed metastatic tumors do not behave like
stage IV metastatic disease to the skin but instead behave as primary
tumors
|
| THICK MELANOMAS |
|
|
Prognostic factors in patients with thick cutaneous melanoma (> 4
mm).
Zettersten E, Sagebiel RW, Miller JR 3rd, Tallapureddy S, Leong
SP, Kashani-Sabet M.
Melanoma Center, Cutaneous Oncology Program, University of California
at San Francisco, Comprehensive Cancer Center, San Francisco, California
94115, USA.
|
Cancer 2002 Feb 15;94(4):1049-56 Abstract quote
BACKGROUND: The current study was conducted to examine the role of
multiple clinical and histologic factors in the prognostic assessment
of patients with thick primary melanoma (> 4 mm, classified as T4).
METHODS: A retrospective analysis was performed in 329 patients with
T4 cutaneous melanomas who were seen at the University of California
at San Francisco Melanoma Center between 1978 and 2000. Fourteen histopathologic
features were recorded prospectively by a single dermatopathologist.
In addition, 9 clinical factors were analyzed.
RESULTS: Several histologic factors were found to have a significant
impact on the survival of patients with T4 melanoma. On univariate analysis,
tumor thickness, ulceration, mitotic rate, microsatellites, vascular
involvement, and histogenetic type of the primary tumor all were found
to have a significant impact on the overall survival rate. Regional
lymph node involvement reduced the overall survival of T4 patients dramatically.
The 5-year overall survival of patients with lymph node-negative T4
disease was 61%, compared with 30% for those with lymph node-positive
disease. When lymph node status was taken into account, tumor thickness,
vascular involvement, and ulceration all remained independent predictors
of overall survival on multivariate Cox regression analysis. Neither
age, gender, nor anatomic location appeared to affect the recurrence-free
or overall survival rates.
CONCLUSIONS: Patients with thick primary cutaneous melanomas (>
4 mm) comprise a heterogeneous group. The presence or absence of lymph
node involvement, vascular involvement, and ulceration appears to result
in significantly divergent overall survival rates in this patient cohort.
Consideration of these factors has important implications in the management
of patients with T4 melanoma.
|
|
Nodular type and older age as the most significant associations of thick
melanoma in victoria, australia.
Chamberlain AJ, Fritschi L, Giles GG, Dowling JP, Kelly JW.
Department of Dermatology, Churchill Hospital, Oxford Radcliffe
NHS Trust, Old Road, Headington, Oxford OX3 7LJ, England.
|
Arch Dermatol 2002 May;138(5):609-14 Abstract quote
OBJECTIVES: To explore the clinical associations of thick melanoma
and to compare the clinicopathological variables of nodular and superficial
spreading types. DESIGN: Cross-sectional study of all invasive primary
melanomas recorded by the Victorian Cancer Registry for 1998 and those
reviewed by the Victorian Melanoma Service between October 1, 1994,
and April 31, 1999.
SETTING: Population-based cancer registry and public hospital-based
multidisciplinary melanoma clinic.
PATIENTS: This study included 1422 patients recorded by the Victorian
Cancer Registry and 674 patients who had attended the Victorian Melanoma
Service; unclassifiable tumor types were excluded, leaving 1144 and
645 patients, respectively, eligible for analysis.
MAIN OUTCOME MEASURES: Melanomas were categorized by thickness into
thin (</=1 mm), intermediate (>1-3 mm), and thick (>3 mm) and
compared according to patient age, sex, and tumor type and site. Superficial
spreading and nodular types were also compared in this manner. Use of
the Victorian Melanoma Service database enabled a more comprehensive
analysis of historical and phenotypic characteristics.
RESULTS: Thick melanoma was predominantly nodular, occurring in older
men, mostly on the head and neck and associated with fewer nevi. Nodular
melanoma was thicker and found mostly on the lower limbs or head and
neck; it had a greater association with a history of solar keratoses
than did superficial spreading melanoma.
CONCLUSION: Nodular type and older age are the most significant associations
of thick melanoma.
|
|
THIN MELANOMAS
|
Clin Lab Med 2000;20:713-729
Controversial term but most have taken it to refer to melanomas less
than 1 mm thick although this measurement has ranged from 0.7mm to 1.5mm
If <1mm is used (as recommended by the NIH Consensus Development
Conference of 1992), patients have >90% chance of long term survival
|
|
Follow-up of patients with a thin melanoma.
Johnson RC, Fenn NJ, Horgan K, Mansel RE.
Department of Surgery, University of Wales College
of Medicine, Cardiff, UK.
|
Br J Surg 1999 May;86(5):619-21 Abstract quote
BACKGROUND: The aim of this study was to determine the value of follow-up
in two subgroups of patients with a thin melanoma less than 0.76 mm
and 0.76-1.5 mm thick.
METHODS: The study group comprised all patients presenting to the Cardiff
Melanoma Clinic from its introduction in 1976 to the end of 1994. All
patients attend follow-up according to a strict protocol, determined
by the thickness of the original melanoma (less than 0.76 mm, annually;
more than 0.76 mm, every 2 months for 2 years, 3 monthly for 2 years,
4 monthly for 1 year and then annually).
RESULTS: In total there were 306 patients with a thin melanoma: 178
with a melanoma thinner than 0.76 mm (group 1) and 128 with a melanoma
of 0.76-1.5 mm (group 2). The groups were well matched for age (mean
50.6 (range 8-87) versus 50.6 (range 19-89) years respectively) and
length of follow-up (mean 88.6 (range 4-296) versus 80.4 (range 2-296)
months). Four patients (2.2 per cent) developed recurrence in group
1 and 16 (12.5 per cent) in group 2. The mean time to recurrence was
84.5 (range 49-143) months in group 1 and 45.3 (range 2-74) months in
group 2. All patients in group 1 and 14 of 16 in group 2 died from recurrent
disease.
CONCLUSION: Follow-up of patients with a melanoma less than 0.76 mm
thick is not worthwhile. All recurrences would have been detected by
annual review for 7 years in patients with melanomas between 0.76 and
1.5 mm thick.
|
|
High proliferative activity may predict early metastasis
of thin melanomas
Sven-Olaf Frahm, MD
Christoph Schubert, MD, PhD
Reza Parwaresch, MD, PhD
Pierre Rudolph, MD, PhD
|
Hum Pathol 2002;32:1376-1381. Abstract quote
Metastasis of thin melanomas is uncommon and unpredictable.
We prospectively investigated the clinical course of 167 thin melanomas
(<1 mm thickness) over a median observation period of 4 years (18 to
87 months). In addition to Breslow thickness, Clark level, and growth
phase characteristics, we assessed cellular proliferation by counting
mitoses and immunohistochemically using the monoclonal antibody Ki-S5
(Ki-67).
Mitotic and Ki-S5 indices were correlated to tumor thickness, Clarks
level, and radial/vertical growth phase (RGP/VGP). However, 5 tumors
had proliferation indices above 25% (outside the range of a theoretical
normal distribution). Four of these tumors metastasized, and none of
the melanomas with lower proliferative activity progressed during the
observation period. The metastatic behavior was independent of tumor
thickness and Clark level and did not unconditionally coincide with
VGP or high mitotic counts.
It is concluded that the immunohistochemical proliferation index may
be a powerful predictor of early systemic progression in thin melanomas,
which may be helpful in making therapeutic decisions. Further investigations
are needed to determine the value of proliferation measurements for
the long-term prognosis of thin melanomas.
|
|
Histological characteristics of metastasizing thin melanomas: a case-control
study of 43 cases.
Guitart J, Lowe L, Piepkorn M, Prieto VG, Rabkin MS,
Ronan SG, Shea CR, Tron VA, White W, Barnhill RL.
Department of Dermatology, Northwestern University
Medical School, 675 N St Clair, Suite 19-150, Chicago, IL 60611
|
Arch Dermatol 2002 May;138(5):603-8 Abstract quote
OBJECTIVE: To study clinical and histological features associated with
metastasizing thin melanomas (MTMs).
DESIGN: Case-control study of clinicopathological features of patients
with MTMs by a panel of 10 dermatopathologists.
SETTING: Members of the North American Melanoma Pathology Study Group
selected the cases from the melanoma databases at 8 academic institutions.
PATIENTS: Forty-three patients with MTMs (<1 mm thick) and 42 control
subjects without metastasis matched for age, sex, tumor site, and Breslow
thickness.
INTERVENTION: None.
MAIN OUTCOME MEASURES: Clinical (age, sex, site of lesion, stage at
diagnosis, metastasis site, disease-free survival, and outcome) and
histological (Breslow thickness, Clark level, growth phase, regression,
and inflammatory response) features of patients with MTMs vs controls.
RESULTS: There was an overrepresentation of axial tumors among patients
with MTMs. Extensive regression was present in 18 patients (42%) with
MTM vs 2 matched control subjects (5%) (95% confidence interval, 21%-53%;
P =.001). Other histological variables were not significantly different.
Two patients had melanomas in situ with subsequent metastasis.
CONCLUSIONS: Thin melanomas with extensive regression represent a group
at higher risk for the development of metastasis. Furthermore, the risk
of metastasis cannot be dismissed in cases of melanoma in situ.
|
| TUMOR INFILTRATING LYMPHOCYTES |
|
|
Histologic Classification of Tumor-Infiltrating Lymphocytes
in Primary Cutaneous Malignant Melanoma A Study of Interobserver Agreement
Klaus J. Busam, MD, Cristina R. Antonescu, MD, Ashfaq
A. Marghoob, MD, Kishwer S. Nehal, MD, Dana L. Sachs, MD, Jinru Shia,
MD, and Marianne Berwick, PhD
|
Am J Clin Pathol 2001;115:856-860 Abstract quote
The density and distribution of lymphocytes infiltrating the vertical
growth phase of primary cutaneous melanomas has been suggested by several
studies to be of prognostic significance. However, few pathologists
comment on tumor-infiltrating lymphocytes (TILs), and there is the perception
that the assessment of TILs is subject to great interobserver variability.
We studied interobserver agreement on the categorization of TILs; 20
cases of primary cutaneous malignant melanoma with a vertical growth
phase component were circulated among 3 pathologists and 3 dermatologists.
For each case, TILs were classified as brisk, nonbrisk, or absent according
to Clark. Only 1 pathologist (a dermatopathologist) was familiar with
the classification of TILs. Observers were given written guidelines
and a brief tutorial before their examination of the slides. Our results
show that with little instruction, overall agreement among observers
was good (kappa values, 0.6 or more), especially among pathologists
(kappa values, > 0.7). Three observers had excellent agreement among
each other (kappa values, > 0.75).
These findings suggest that the categorization of TILs can be easily
taught and can be applied with an acceptable level of reproducibility
in routine diagnostic practice.
|
| VASCULAR INVOLVEMENT |
|
|
Vascular Involvement in the Prognosis of Primary Cutaneous
Melanoma
Mohammed Kashani-Sabet, MD; Richard W. Sagebiel, MD;
Carlos M. M. Ferreira, MD; Mehdi Nosrati, BS; James R. Miller III, PhD
|
Arch Dermatol. 2001;137:1169-1173 Abstract quote
Objective
To examine the role of vascular invasion as a prognostic factor in melanoma.
Design
Retrospective survival analysis.
Setting
Academic medical center.
Patients
A total of 526 patients with primary cutaneous melanoma from the University
of California, San Francisco, Melanoma Center database with 2 years
of follow-up or documented relapse. Main
Outcome Measures
(1) Presence of vascular involvement defined as vascular invasion with
tumor cells within blood or lymphatic vessels; or uncertain vascular
invasion, with melanoma cells immediately adjacent to the endothelium.
(2) Percentage with metastasis or death and relapse-free and overall
survival.
Results
The presence of either type of vascular involvement significantly increased
the risk of relapse and death and reduced the survival associated with
melanoma. The impact of vascular involvement on these outcomes was similar
to that of ulceration. In a multivariate analysis, vascular involvement
was the second most important factor (after tumor thickness) in the
primary tumor in predicting survival.
Conclusions
Vascular involvement is an important independent predictor of metastasis
and survival in melanoma. The phenomenon of uncertain vascular invasion
describes an earlier step than definite vascular invasion in tumor progression.
|
| RECURRENCE |
Cancer 1991;67:1984-1989
Of patients with a melanoma, another will develop in 1.2-8.2%
|
| |
Arch Surg 1985;120:115-1159
Ann Surg 1990;212:173-177
Among patients surviving more than 10 years after primary surger, 7-25%
develop late recurrences
|
| |
Non-familial cases 3% develop second melanomas
within 3 years
Familial cases 33% develop second melanomas within 5 years |
|
The pathogenesis of local recurrence of melanoma at
the primary excision site.
Heenan PJ, Ghaznawie M.
Department of Pathology, Hasanuddin University, Ujungpandang,
Indonesia.
|
Br J Plast Surg 1999 Apr;52(3):209-13 Abstract quote
Local recurrence of melanoma at the primary excision site may imply
that the primary excision was incomplete or 'inadequate', and that the
recurrence was due to retained primary melanoma cells or occult microsatellites
in the adjacent tissue. Pathologists frequently report these tumours
in the scar as recurrent or residual melanoma, without further qualification,
apparently without considering the possibility that they may be metastases
and manifestations of systemic disease.
In this study, 17 of 19 cases of locally recurrent melanoma at the
primary excision site showed the histological features of metastasis
rather than residual incompletely excised primary melanoma.
Because the prevention of local recurrence is the main reason given
in recommendations for wide excision of melanoma beyond complete excision
of the primary tumour itself, it is essential that surgeons and pathologists
should classify these neoplasms precisely as either persistent incompletely
excised primary melanoma or metastatic melanoma.
|
|
Outcome of patients with melanoma and histologically
negative sentinel lymph nodes.
Gadd MA, Cosimi AB, Yu J, Duncan LM, Yu L, Flotte
TJ, Souba WW, Ott MJ, Wong LS, Sober AJ, Mihm MC, Haluska FG, Tanabe
KK.
Department of Surgery, Massachusetts General Hospital,
Harvard Medical School, Boston 02114, USA.
|
Arch Surg 1999 Apr;134(4):381-7 Abstract quote
HYPOTHESIS: Patients with melanoma and histologically negative sentinel
lymph nodes identified by lymphatic mapping have a very good prognosis.
DESIGN: Cohort study with follow-up information obtained from medical
records and telephone interviews.
SETTING AND PATIENTS: Of all patients with cutaneous melanoma who underwent
intraoperative sentinel lymph node mapping between November 15, 1993,
and April 18, 1997, at the Massachusetts General Hospital, Boston, 89
were found to have no evidence of melanoma in their sentinel nodes.
Forty-six lesions (51%) were on an extremity and 44 (49%) were of axial
location. The median tumor thickness was 1.8 mm (range, 0.36-12.0 mm)
and 11 tumors (12%) were ulcerated.
INTERVENTIONS: Patients underwent intraoperative sentinel lymph node
mapping with lymphazurin and radiolabeled sulfur colloid. Sentinel lymph
nodes were analyzed by standard hematoxylin-eosin staining. Only 2 patients
received adjuvant therapy following wide excision of the primary lesion.
MAIN OUTCOME MEASURES: Site of initial recurrence and time to initial
recurrence.
RESULTS: The median follow-up for all patients was 23 months (range,
2-54 months). Eleven patients (12%) developed melanoma recurrences,
and 78 (88%) patients remain disease free. Regional lymph nodes were
the initial site of recurrence in 7 (8%) of 89 patients, and 7 (7%)
of 106 mapped basins. Four patients had recurrence without involvement
of regional lymph nodes: 2 with distant metastases and 2 with in transit
metastases. The median time to recurrence was 12 months (range, 2-35
months). Sentinel lymph nodes were reanalyzed using serial sections
and immunoperoxidase stains in 7 patients with recurrence and metastatic
melanoma was identified in 3 (43%).
CONCLUSIONS: The risk for melanoma recurrence is relatively low in
patients with histologically negative sentinel nodes identified by lymphatic
mapping. Longer follow-up will improve our understanding of the prognostic
value of this procedure.
|
| SURVIVAL |
Cutaneous melanoma. 2nd ed. Philadelphia: JB Lippincott; 1992. p. 200-12.
10YR cure rate 90% <1.5 mm in thickness
<50% survival with 3 mm in thickness
<50% to 75% of patients >4mm in thickness
Stage IV disease 5-17.9% with a median survival of 6 months
|
| |
(T1-2, N0) have 10 YRS of 85%
(T3-4, N0) have 10 YRS of 50%
Stage III have 10 YRS of <25% |
| METASTASIS |
|
|
Desmoplastic Melanomas
|
World J Surg 1992;16:186-90.
Series of 58 patients, 17 patients were noted to have local recurrence
with the primary site of involvement on the head and neck
Eleven of these patients progressed to wider dissemination
No relationship between the site and histologic pattern of the primary
lesion in those patients with lymph node metastasis
Elective lymphadenectomy was performed in 6 patients, all of whom had
negative pathology
For those who had visceral disease, the major sites of involvement were
liver, bone, brain, lung, spine, para-aortic nodes, and general dissemination
Melanomas with predominant neurotropism had a low incidence of visceral
metastasis
However, those with evidence of neural transformation (ie, tumors that
develop a neural appearance) without neurotropism appeared to have a
high incidence of local recurrence and the potential for visceral recurrence
rather than perineural and intraneural invasion
Rate of lymph node metastases of 14% appears to be lower compared with
37% for nondesmoplastic melanomas
Patients with a median tumor thickness of 6.5 mm (range, 2.15-11 mm)
had lymph node recurrence, visceral recurrence, or cranial nerve neuropathies,
whereas those without systemic recurrence had a median thickness of
3.6 mm (range, 0.45-16 mm)
|
|
Microsatellites
|
Ann Surg 1981;194:108-112
Defined as discrete nests of melanoma cells that are noncontiguous
and clearly separated from the main body of tumor by normal reticular
dermal collagen or subcutaneous fat and are detected histologically
Overall, prognosis of patients is similar to that of patients with
macrosatellites and should be categorized as stage III
|
|
Melanoma metastatic to "lipomata".
Mann BD, Finck SJ, Cohchran AJ, Morton DL.
|
J Surg Oncol 1984 Feb;25(2):98-9 Abstract quote
Three patients presented with solitary melanoma metastases that mimicked
a simple "lipomata." On further investigation each patient had a discrete
fatty tissue tumor mass surrounding a melanoma metastasis.
The presence of an enlarging mass in patients with a history of melanoma
should be viewed with suspicion and a biopsy should be performed.
|
| |
Cancer 1984;53:2183-2187
Presence of microsatellites is highly correlated with occult regional
lymph node metastases in multivariate analysis
|
| |
Arch Surg 1991;126:1461-1468
Compared with matched controls, microsatellite patients had a significantly
decreased disease-free survival (27% versus 60% at 10 years) and decreased
overall survival (37% versus 65% at 10 years)
5 YRS was 36% for patients with microsatellites versus 89% for patients
without
|
| SCREENING |
Each scheduled visit should include:
Complete history and physical examination
Complete blood count
Liver function tests
Serum lactic dehydrogenase level
If one or more tests are abnormal, additional sophisticated testing
should be performed
|
|
Stage I
|
Annually |
|
Stage II
|
Every 6 months for 2 years, then annually thereafter |
|
Stage III
|
Every 3 months for 1 year, every 4 months for the second
year, and every 6 months for years 3-5 |
|
All patients
|
Annual visits from year 6 onward |
